Continuing evidence for poorer treatment outcomes for single male patients: retreatment data from RTOG 97-14.

PubMed

Konski, Andre; Desilvio, Michelle; Hartsell, William; Watkins-Bruner, Deborah; Coyne, James; Scarantino, Charles; Janjan, Nora

2006-09-01

The specific aim of this study was to evaluate outcome differences by gender and partner status for patients treated on Radiation Therapy Oncology Group (RTOG) protocol 97-14. RTOG 97-14 randomized patients with metastatic breast or prostate cancer to bone to receive 8 Gy in 1 fraction or 30 Gy in 10 fractions. Retreatment rates and overall survival were made based upon gender, marital status, and Karnofsky Performance Status (KPS). The cumulative incidence method was used to estimate retreatment time at 36 months from enrollment, and Gray's test was used to test for treatment differences within the same groupings. Marital status, gender, KPS, and treatment were variables tested in a univariate Cox model evaluating the time to retreatment. Married men and women and single women receiving 30 Gy had significantly longer time to retreatment, p = 0.0067, p = 0.0052, and p = 0.0009 respectively. We failed to show a difference in retreatment rates over time in single men receiving either 30 Gy or 8 Gy. Univariate analysis of the entire group determined patients receiving 30 Gy in 10 fractions significantly less likely to receive retreatment, p < 0.0001, with a trend toward single patients less likely to be re-treated, p = 0.07. Non-disease-related variables, such as social support, might influence the results of clinical trials with subjective endpoints such as retreatment rates. The statistically nonsignificant difference in the 36-month retreatment rates observed in single male patients receiving 8 Gy may be a result of inadequate social support systems in place to facilitate additional care. Patients receiving 8 Gy in a single fraction had significantly higher retreatment rates compared with patients receiving 30 Gy in 10 fractions.

Mometasone Furoate Cream Reduces Acute Radiation Dermatitis in Patients Receiving Breast Radiation Therapy: Results of a Randomized Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hindley, Andrew, E-mail: andrew.hindley@lthtr.nhs.uk; Zain, Zakiyah; Wood, Lisa

Purpose: We wanted to confirm the benefit of mometasone furoate (MF) in preventing acute radiation reactions, as shown in a previous study (Boström et al, Radiother Oncol 2001;59:257-265). Methods and Materials: The study was a double-blind comparison of MF with D (Diprobase), administered daily from the start of radiation therapy for 5 weeks in patients receiving breast radiation therapy, 40 Gy in 2.67-Gy fractions daily over 3 weeks. The primary endpoint was mean modified Radiation Therapy Oncology Group (RTOG) score. Results: Mean RTOG scores were significantly less for MF than for D (P=.046). Maximum RTOG and mean erythema scores were significantly less for MFmore » than for D (P=.018 and P=.012, respectively). The Dermatology Life Quality Index (DLQI) score was significantly less for MF than for D at weeks 4 and 5 when corrected for Hospital Anxiety and Depression (HAD) questionnaire scores. Conclusions: MF cream significantly reduces radiation dermatitis when applied to the breast during and after radiation therapy. For the first time, we have shown a significantly beneficial effect on quality of life using a validated instrument (DLQI), for a topical steroid cream. We believe that application of this cream should be the standard of care where radiation dermatitis is expected.« less

Institutional Clinical Trial Accrual Volume and Survival of Patients With Head and Neck Cancer

PubMed Central

Wuthrick, Evan J.; Zhang, Qiang; Machtay, Mitchell; Rosenthal, David I.; Nguyen-Tan, Phuc Felix; Fortin, André; Silverman, Craig L.; Raben, Adam; Kim, Harold E.; Horwitz, Eric M.; Read, Nancy E.; Harris, Jonathan; Wu, Qian; Le, Quynh-Thu; Gillison, Maura L.

2015-01-01

Purpose National Comprehensive Cancer Network guidelines recommend patients with head and neck cancer (HNC) receive treatment at centers with expertise, but whether provider experience affects survival is unknown. Patients and Methods The effect of institutional experience on overall survival (OS) in patients with stage III or IV HNC was investigated within a randomized trial of the Radiation Therapy Oncology Group (RTOG 0129), which compared cisplatin concurrent with standard versus accelerated fractionation radiotherapy. As a surrogate for experience, institutions were classified as historically low- (HLACs) or high-accruing centers (HHACs) based on accrual to 21 RTOG HNC trials (1997 to 2002). The effect of accrual volume on OS was estimated by Cox proportional hazards models. Results Median RTOG accrual (1997 to 2002) at HLACs was four versus 65 patients at HHACs. Analysis included 471 patients in RTOG 0129 (2002 to 2005) with known human papillomavirus and smoking status. Patients at HLACs versus HHACs had better performance status (0: 62% v 52%; P = .04) and lower T stage (T4: 26.5% v 35.3%; P = .002) but were otherwise similar. Radiotherapy protocol deviations were higher at HLACs versus HHACs (18% v 6%; P < .001). When compared with HHACs, patients at HLACs had worse OS (5 years: 51.0% v 69.1%; P = .002). Treatment at HLACs was associated with increased death risk of 91% (hazard ratio [HR], 1.91; 95% CI, 1.37 to 2.65) after adjustment for prognostic factors and 72% (HR, 1.72; 95% CI, 1.23 to 2.40) after radiotherapy compliance adjustment. Conclusion OS is worse for patients with HNC treated at HLACs versus HHACs to cooperative group trials after accounting for radiotherapy protocol deviations. Institutional experience substantially influences survival in locally advanced HNC. PMID:25488965

Institutional clinical trial accrual volume and survival of patients with head and neck cancer.

PubMed

Wuthrick, Evan J; Zhang, Qiang; Machtay, Mitchell; Rosenthal, David I; Nguyen-Tan, Phuc Felix; Fortin, André; Silverman, Craig L; Raben, Adam; Kim, Harold E; Horwitz, Eric M; Read, Nancy E; Harris, Jonathan; Wu, Qian; Le, Quynh-Thu; Gillison, Maura L

2015-01-10

National Comprehensive Cancer Network guidelines recommend patients with head and neck cancer (HNC) receive treatment at centers with expertise, but whether provider experience affects survival is unknown. The effect of institutional experience on overall survival (OS) in patients with stage III or IV HNC was investigated within a randomized trial of the Radiation Therapy Oncology Group (RTOG 0129), which compared cisplatin concurrent with standard versus accelerated fractionation radiotherapy. As a surrogate for experience, institutions were classified as historically low- (HLACs) or high-accruing centers (HHACs) based on accrual to 21 RTOG HNC trials (1997 to 2002). The effect of accrual volume on OS was estimated by Cox proportional hazards models. Median RTOG accrual (1997 to 2002) at HLACs was four versus 65 patients at HHACs. Analysis included 471 patients in RTOG 0129 (2002 to 2005) with known human papillomavirus and smoking status. Patients at HLACs versus HHACs had better performance status (0: 62% v 52%; P = .04) and lower T stage (T4: 26.5% v 35.3%; P = .002) but were otherwise similar. Radiotherapy protocol deviations were higher at HLACs versus HHACs (18% v 6%; P < .001). When compared with HHACs, patients at HLACs had worse OS (5 years: 51.0% v 69.1%; P = .002). Treatment at HLACs was associated with increased death risk of 91% (hazard ratio [HR], 1.91; 95% CI, 1.37 to 2.65) after adjustment for prognostic factors and 72% (HR, 1.72; 95% CI, 1.23 to 2.40) after radiotherapy compliance adjustment. OS is worse for patients with HNC treated at HLACs versus HHACs to cooperative group trials after accounting for radiotherapy protocol deviations. Institutional experience substantially influences survival in locally advanced HNC. © 2014 by American Society of Clinical Oncology.

The Influence of Total Nodes Examined, Number of Positive Nodes, and Lymph Node Ratio on Survival After Surgical Resection and Adjuvant Chemoradiation for Pancreatic Cancer: A Secondary Analysis of RTOG 9704

DOE Office of Scientific and Technical Information (OSTI.GOV)

Showalter, Timothy N.; Winter, Kathryn A.; Berger, Adam C., E-mail: adam.berger@jefferson.edu

2011-12-01

Purpose: Lymph node status is an important predictor of survival in pancreatic cancer. We performed a secondary analysis of Radiation Therapy Oncology Group (RTOG) 9704, an adjuvant chemotherapy and chemoradiation trial, to determine the influence of lymph node factors-number of positive nodes (NPN), total nodes examined (TNE), and lymph node ratio (LNR ratio of NPN to TNE)-on OS and disease-free survival (DFS). Patient and Methods: Eligible patients from RTOG 9704 form the basis of this secondary analysis of lymph node parameters. Actuarial estimates for OS and DFS were calculated using Kaplan-Meier methods. Cox proportional hazards models were performed to evaluatemore » associations of NPN, TNE, and LNR with OS and DFS. Multivariate Cox proportional hazards models were also performed. Results: There were 538 patients enrolled in the RTOG 9704 trial. Of these, 445 patients were eligible with lymph nodes removed. Overall median NPN was 1 (min-max, 0-18). Increased NPN was associated with worse OS (HR = 1.06, p = 0.001) and DFS (HR = 1.05, p = 0.01). In multivariate analyses, both NPN and TNE were associated with OS and DFS. TNE > 12, and >15 were associated with increased OS for all patients, but not for node-negative patients (n = 142). Increased LNR was associated with worse OS (HR = 1.01, p < 0.0001) and DFS (HR = 1.006, p = 0.002). Conclusion: In patients who undergo surgical resection followed by adjuvant chemoradiation, TNE, NPN, and LNR are associated with OS and DFS. This secondary analysis of a prospective, cooperative group trial supports the influence of these lymph node parameters on outcomes after surgery and adjuvant therapy using contemporary techniques.« less

Elective Clinical Target Volumes for Conformal Therapy in Anorectal Cancer: A Radiation Therapy Oncology Group Consensus Panel Contouring Atlas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Myerson, Robert J.; Garofalo, Michael C.; El Naqa, Issam

2009-07-01

Purpose: To develop a Radiation Therapy Oncology Group (RTOG) atlas of the elective clinical target volume (CTV) definitions to be used for planning pelvic intensity-modulated radiotherapy (IMRT) for anal and rectal cancers. Methods and Materials: The Gastrointestinal Committee of the RTOG established a task group (the nine physician co-authors) to develop this atlas. They responded to a questionnaire concerning three elective CTVs (CTVA: internal iliac, presacral, and perirectal nodal regions for both anal and rectal case planning; CTVB: external iliac nodal region for anal case planning and for selected rectal cases; CTVC: inguinal nodal region for anal case planning andmore » for select rectal cases), and to outline these areas on individual computed tomographic images. The imaging files were shared via the Advanced Technology Consortium. A program developed by one of the co-authors (I.E.N.) used binomial maximum-likelihood estimates to generate a 95% group consensus contour. The computer-estimated consensus contours were then reviewed by the group and modified to provide a final contouring consensus atlas. Results: The panel achieved consensus CTV definitions to be used as guidelines for the adjuvant therapy of rectal cancer and definitive therapy for anal cancer. The most important difference from similar atlases for gynecologic or genitourinary cancer is mesorectal coverage. Detailed target volume contouring guidelines and images are discussed. Conclusion: This report serves as a template for the definition of the elective CTVs to be used in IMRT planning for anal and rectal cancers, as part of prospective RTOG trials.« less

Valproic Acid Use During Radiation Therapy for Glioblastoma Associated With Improved Survival

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barker, Christopher A., E-mail: barkerc@mskcc.org; Bishop, Andrew J.; Chang, Maria

2013-07-01

Purpose: Valproic acid (VA) is an antiepileptic drug (AED) and histone deacetylase (HDAC) inhibitor taken by patients with glioblastoma (GB) to manage seizures, and it can modulate the biologic effects of radiation therapy (RT). We investigated whether VA use during RT for GB was associated with overall survival (OS). Methods and Materials: Medical records of 544 adults with GB were retrospectively reviewed. Analyses were performed to determine the association of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) class, seizure history, and concurrent temozolomide (TMZ) and AED use during RT with OS. Results: Seizures before the end of RTmore » were noted in 217 (40%) patients, and 403 (74%) were taking an AED during RT; 29 (7%) were taking VA. Median OS in patients taking VA was 16.9 months (vs 13.6 months taking another AED, P=.16). Among patients taking an AED during RT, OS was associated with VA (P=.047; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.27-1.07), and RTOG RPA class (P<.0001; HR, 1.49; 95% CI, 1.37-1.61). Of the 5 most common AEDs, only VA was associated with OS. Median OS of patients receiving VA and TMZ during RT was 23.9 months (vs 15.2 months for patients taking another AED, P=.26). When the analysis was restricted to patients who received concurrent TMZ, VA use was marginally associated with OS (P=.057; HR, 0.54; 95% CI, −0.09 to 1.17), independently of RTOG RPA class and seizure history. Conclusions: VA use during RT for GB was associated with improved OS, independently of RTOG RPA, seizure history, and concurrent TMZ use. Further studies of treatment that combines HDAC inhibitors and RT are warranted.« less

HDR-192Ir intraluminal brachytherapy in treatment of malignant obstructive jaundice

PubMed Central

Chen, Yi; Wang, Xiao-Lin; Yan, Zhi-Ping; Cheng, Jie-Min; Wang, Jian-Hua; Gong, Gao-Quan; Qian, Sheng; Luo, Jian-Jun; Liu, Qing-Xin

2004-01-01

AIM: To determine the feasibility and safety of intraluminal brachytherapy in treatment of malignant obstructive jaundice (MOJ) and to evaluate the clinical effect of intraluminal brachytherapy on stent patency and patient survival. METHODS: Thirty-four patients with MOJ were included in this study. Having biliary stent placed, all patients were classified into intraluminal brachytherapy group (group A, n = 14) and control group (group B, n = 20) according to their own choice. Intraluminal brachytherapy regimen included: HDR-192Ir was used in the therapy, fractional doses of 4-7 Gy were given every 3-6 d for 3-4 times, and standard points were established at 0.5-1.0 cm. Some patients of both groups received transcatheter arterial chemoembolization (TACE) after stent placement. RESULTS: In group A, the success rate of intraluminal brachytherapy was 98.0%, RTOG grade 1 acute radiation morbidity occurred in 3 patients, RTOG/EORTC grade 1 late radiation morbidity occurred in 1 patient. Mean stent patency of group A (12.6 mo) was significantly longer than that of group B (8.3 mo) (P < 0.05). There was no significant difference in the mean survival (9.4 mo vs 6.0 mo) between the two groups. CONCLUSION: HDR-192Ir intraluminal brachytherapy is a safe palliative therapy in treating MOJ, and it may prolong stent patency and has the potentiality of extending survival of patients with MOJ. PMID:15526374

Effect of Long-Term Hormonal Therapy (vs Short-Term Hormonal Therapy): A Secondary Analysis of Intermediate-Risk Prostate Cancer Patients Treated on NRG Oncology RTOG 9202

PubMed Central

Mirhadi, Amin J.; Zhang, Qiang; Hanks, Gerald E.; Lepor, Herbert; Grignon, David J.; Peters, Christopher A.; Rosenthal, Seth A.; Zeitzer, Kenneth; Radwan, John S.; Lawton, Colleen; Parliament, Matthew B.; Reznik, Robert S.; Sandler, Howard M.

2017-01-01

Purpose NRG Oncology RTOG 9202 was a randomized trial testing long-term adjuvant androgen deprivation (LTAD) versus initial androgen deprivation only (STAD) with external beam radiation therapy (RT) in mostly high-risk and some intermediate-risk prostate cancer patients. RTOG 9408 found an overall survival (OS) advantage in patients with cT1b-T2b disease and prostate-specific antigen (PSA) <20 ng/mL, with benefit observed mostly among intermediate-risk patients. It was still unknown whether intermediate-risk patients would experience an additional survival benefit with LTAD; thus, we performed a secondary analysis to explore whether LTAD had any incremental benefit beyond STAD among the intermediate-risk subset of RTOG 9202. The study endpoints were OS, disease-specific survival (DSS), and PSA failure (PSAF). Methods and Materials An analysis was performed for all patients enrolled in RTOG 9202 defined as intermediate-risk (cT2 disease, PSA<10 ng/mL, and Gleason score = 7 or cT2 disease, PSA 10-20 ng/mL, and Gleason score <7). This review yielded 133 patients: 74 (STAD) and 59 (LTAD). The Kaplan-Meier method was used to estimate OS; the cumulative incidence approach was used to estimate DSS and PSAF. A 2-sided test was used, with significance level defined to be .05. Results With over 11 years of median follow-up, 39 STAD patients were alive and 33 LTAD patients were alive. There was no difference in OS (10-year estimates, 61% STAD vs 65% LTAD; P=.53), DSS (10-year DSS, 96% vs 97%; P=.72), or PSAF (10-year PSAF, 53% vs 55%; P=.99) between groups. Conclusion LTAD did not confer a benefit in terms of OS, DSS, or PSAF rates in the intermediate-risk subset in this study. Whereas the subset was relatively small, treatment assignment was randomly applied, and a trend in favor of LTAD would have been of interest. Given the small number of disease-specific deaths observed and lack of benefit with respect to our endpoints, this secondary analysis does not suggest that exploration of longer hormonal therapy is worth testing in the intermediate-risk prostate cancer subset. PMID:28126300

A Phase II Study of a Paclitaxel-Based Chemoradiation Regimen With Selective Surgical Salvage for Resectable Locoregionally Advanced Esophageal Cancer: Initial Reporting of RTOG 0246

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swisher, Stephen G., E-mail: sswisher@mdanderson.org; Winter, Kathryn A.; Komaki, Ritsuko U.

2012-04-01

Purpose: The strategy of definitive chemoradiation with selective surgical salvage in locoregionally advanced esophageal cancer was evaluated in a Phase II trial in Radiation Therapy Oncology Group (RTOG)-affiliated sites. Methods and Materials: The study was designed to detect an improvement in 1-year survival from 60% to 77.5% ({alpha} = 0.05; power = 80%). Definitive chemoradiation involved induction chemotherapy with 5-fluorouracil (5-FU) (650 mg/mg{sup 2}/day), cisplatin (15 mg/mg{sup 2}/day), and paclitaxel (200 mg/mg{sup 2}/day) for two cycles, followed by concurrent chemoradiation with 50.4 Gy (1.8 Gy/fraction) and daily 5-FU (300 mg/mg{sup 2}/day) with cisplatin (15 mg/mg{sup 2}/day) over the first 5more » days. Salvage surgical resection was considered for patients with residual or recurrent esophageal cancer who did not have systemic disease. Results: Forty-three patients with nonmetastatic resectable esophageal cancer were entered from Sept 2003 to March 2006. Forty-one patients were eligible for analysis. Clinical stage was {>=}T3 in 31 patients (76%) and N1 in 29 patients (71%), with adenocarcinoma histology in 30 patients (73%). Thirty-seven patients (90%) completed induction chemotherapy followed by concurrent chemoradiation. Twenty-eight patients (68%) experienced Grade 3+ nonhematologic toxicity. Four treatment-related deaths were noted. Twenty-one patients underwent surgery following definitive chemoradiation because of residual (17 patients) or recurrent (3 patients) esophageal cancer,and 1 patient because of choice. Median follow-up of live patients was 22 months, with an estimated 1-year survival of 71%. Conclusions: In this Phase II trial (RTOG 0246) evaluating selective surgical salvage after definitive chemoradiation in locoregionally advanced esophageal cancer, the hypothesized 1-year RTOG survival rate (77.5%) was not achieved (1 year, 71%; 95% confidence interval< 54%-82%).« less

Dose specification and quality assurance of RTOG protocol 95-17; a cooperative group study of 192Ir breast implants as sole therapy

PubMed Central

Ibbott, Geoffrey S.; Hanson, W.F.; Martin, Elizabeth; Kuske, Robert R.; Arthur, Douglas; Rabinovitch, Rachel; White, Julia; Wilenzick, Raymond M.; Harris, Irene; Tailor, Ramesh C.

2007-01-01

Purpose RTOG protocol 95-17 was a phase I/II trial to evaluate multi-catheter brachytherapy as the sole method of adjuvant breast radiotherapy for stage I/II breast carcinoma following breast conserving surgery. Low or high dose rate sources were allowed. Dose prescription and treatment evaluation were based on recommendations in ICRU Report 58, and included the parameters mean central dose (MCD), average peripheral dose, dose homogeneity index (DHI), and the dimensions of the low and high dose regions. Methods and Materials Three levels of quality assurance were implemented: (1) Credentialing of institutions was required prior to entering patients onto the study. (2) Rapid review of each treatment plan was conducted prior to treatment, and (3) Retrospective review was performed by the Radiological Physics Center in conjunction with the study chairman and RTOG dosimetry staff. Results Credentialing focused on the accuracy of dose calculation algorithm and compliance with protocol guidelines. Rapid review was designed to identify and correct deviations from the protocol prior to treatment. The retrospective review involved recalculation of dosimetry parameters and review of dose distributions to evaluate the treatment. Specifying both central and peripheral doses resulted in uniform dose distributions, with a mean dose homogeneity index of 0.83 ±0.06. Conclusions Vigorous quality assurance resulted in a high-quality study with few deviations; only 4 of 100 patients were judged as minor variations from protocol and no patient was judged a major deviation. This study should be considered a model for quality assurance of future trials. PMID:18035213

Low Interrater Reliability in Grading of Rectal Bleeding Using National Cancer Institute Common Toxicity Criteria and Radiation Therapy Oncology Group Toxicity Scales: A Survey of Radiation Oncologists

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huynh-Le, Minh-Phuong; Zhang, Zhe; Tran, Phuoc T.

2014-12-01

Purpose: To measure concordance among genitourinary radiation oncologists in using the National Cancer Institute Common Toxicity Criteria (NCI CTC) and Radiation Therapy Oncology Group (RTOG) grading scales to grade rectal bleeding. Methods and Materials: From June 2013 to January 2014, a Web-based survey was sent to 250 American and Canadian academic radiation oncologists who treat prostate cancer. Participants were provided 4 case vignettes in which patients received radiation therapy and developed rectal bleeding and were asked for management plans and to rate the bleeding according to NCI CTC v.4 and RTOG late toxicity grading (scales provided). In 2 cases, participantsmore » were also asked whether they would send the patient for colonoscopy. A multilevel, random intercept modeling approach was used to assess sources of variation (case, respondent) in toxicity grading to calculate the intraclass correlation coefficient (ICC). Agreement on a dichotomous grading scale (low grades 1-2 vs high grades 3-4) was also assessed, using the κ statistic for multiple respondents. Results: Seventy-two radiation oncologists (28%) completed the survey. Forty-seven (65%) reported having either written or been principal investigator on a study using these scales. Agreement between respondents was moderate (ICC 0.52, 95% confidence interval [CI] 0.47-0.58) when using NCI CTC and fair using the RTOG scale (ICC 0.28, 95% CI 0.20-0.40). Respondents who chose an invasive management were more likely to select a higher toxicity grade (P<.0001). Using the dichotomous scale, we observed moderate agreement (κ = 0.42, 95% CI 0.40-0.44) with the NCI CTC scale, but only slight agreement with the RTOG scale (κ = 0.19, 95% CI 0.17-0.21). Conclusion: Low interrater reliability was observed among radiation oncologists grading rectal bleeding using 2 common scales. Clearer definitions of late rectal bleeding toxicity should be constructed to reduce this variability and avoid ambiguity in both reporting and interpretation.« less

Pelvic Normal Tissue Contouring Guidelines for Radiation Therapy: A Radiation Therapy Oncology Group Consensus Panel Atlas

PubMed Central

Gay, Hiram A.; Barthold, H. Joseph; O’Meara, Elizabeth; Bosch, Walter R.; El Naqa, Issam; Al-Lozi, Rawan; Rosenthal, Seth A.; Lawton, Colleen; Lee, W. Robert; Sandler, Howard; Zietman, Anthony; Myerson, Robert; Dawson, Laura A.; Willett, Christopher; Kachnic, Lisa A.; Jhingran, Anuja; Portelance, Lorraine; Ryu, Janice; Small, William; Gaffney, David; Viswanathan, Akila N.; Michalski, Jeff M.

2012-01-01

Purpose To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology Group (RTOG) trials. Methods and Materials One male pelvis computed tomography (CT) data set and one female pelvis CT data set were shared via the Image-Guided Therapy QA Center. A total of 16 radiation oncologists participated. The following organs at risk were contoured in both CT sets: anus, anorectum, rectum (gastrointestinal and genitourinary definitions), bowel NOS (not otherwise specified), small bowel, large bowel, and proximal femurs. The following were contoured in the male set only: bladder, prostate, seminal vesicles, and penile bulb. The following were contoured in the female set only: uterus, cervix, and ovaries. A computer program used the binomial distribution to generate 95% group consensus contours. These contours and definitions were then reviewed by the group and modified. Results The panel achieved consensus definitions for pelvic normal tissue contouring in RTOG trials with these standardized names: Rectum, AnoRectum, SmallBowel, Colon, BowelBag, Bladder, UteroCervix, Adnexa_R, Adnexa_L, Prostate, SeminalVesc, PenileBulb, Femur_R, and Femur_L. Two additional normal structures whose purpose is to serve as targets in anal and rectal cancer were defined: AnoRectumSig and Mesorectum. Detailed target volume contouring guidelines and images are discussed. Conclusions Consensus guidelines for pelvic normal tissue contouring were reached and are available as a CT image atlas on the RTOG Web site. This will allow uniformity in defining normal tissues for clinical trials delivering pelvic radiation and will facilitate future normal tissue complication research. PMID:22483697

Breast cancer brain metastases: differences in survival depending on biological subtype, RPA RTOG prognostic class and systemic treatment after whole-brain radiotherapy (WBRT).

PubMed

Niwińska, A; Murawska, M; Pogoda, K

2010-05-01

Patients with breast cancer brain metastasis are a heterogeneous group in relation to tumor biology and outcome. The group of 222 breast cancer patients with brain metastasis was divided into three biological subgroups. The propensity of biological subtypes for metastases to the brain and survivals depending on biological subtype, recursive partitioning analysis of Radiation Therapy Oncology Group (RPA RTOG) prognostic class and the use of systemic treatment after whole-brain radiotherapy were assessed. The rate of patients with triple-negative, human epidermal growth factor receptor 2 (HER2)-positive and luminal breast cancer with brain metastases was 28%, 53% and 19%, respectively. Median survival from brain metastases in triple-negative, HER2-positive and luminal subtype was 3.7, 9 and 15 months, respectively. Median survival from brain metastases in RPA RTOG prognostic class I, II and III was 15, 11 and 3 months, respectively. In the luminal and in the triple-negative subtype, systemic therapy prolonged survival from 3 to 14 months and from 3 to 4 months, respectively. In HER2-positive subtype, median survival without further treatment, after chemotherapy and after chemotherapy with targeted therapy were 3, 8 and 11 months, respectively. HER2-positive and triple-negative breast cancers have special predilection for metastases to the brain. Survival from brain metastases depended on performance status and the use of systemic treatment.

Evolving management of low grade glioma: No consensus amongst treating clinicians.

PubMed

Field, K M; Rosenthal, M A; Khasraw, M; Sawkins, K; Nowak, A K

2016-01-01

Following the widely publicized presentation of the Radiation Therapy Oncology Group (RTOG) 9802 data, we sought to understand how these data had been translated to the management of low grade gliomas (LGG) by Australian neuro-oncology clinicians. The de novo management of LGG is transitioning to include postoperative radiotherapy and chemotherapy after the RTOG 9802 study results demonstrated a survival benefit in this setting. In 2014, neurosurgeons, radiation oncologists and neuro-oncologists who were members of the Australian Cooperative Trials Group for Neuro-oncology (COGNO), as well as additional attendants of the COGNO annual scientific meeting, were surveyed. The survey presented six LGG clinical scenarios and asked respondents to select their preferred management strategy. Some additional questions included the respondents' approach to 1p/19q testing and chemotherapy preferences. The response rate was 30.2% (61/202), with the majority (77%) working in tertiary referral neuro-oncology centers. There was no consensus regarding the management approach for each scenario, with postsurgery observation alone remaining a popular strategy. Only 25% of respondents reported that their institution routinely tests for 1p/19q status in LGG, although 69% were of the opinion that all LGG patients should be tested. The majority (81%) preferred to use temozolomide rather than the procarbazine, lomustine, and vincristine combination as the first line chemotherapy for LGG, but only 44% would actually use it in this setting. Up front chemotherapy, prior to radiotherapy, would be considered by 52% of respondents for certain LGG patients. This survey assessed the management strategies for LGG since the updated RTOG 9802 data were presented. It demonstrates no consensus in the postoperative treatment approaches for LGG. Copyright © 2015 Elsevier Ltd. All rights reserved.

Secondary Analysis of RTOG 9508, a Phase 3 Randomized Trial of Whole-Brain Radiation Therapy Versus WBRT Plus Stereotactic Radiosurgery in Patients With 1-3 Brain Metastases; Poststratified by the Graded Prognostic Assessment (GPA)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sperduto, Paul W., E-mail: psperduto@mropa.com; Shanley, Ryan; Luo, Xianghua

2014-11-01

Purpose: Radiation Therapy Oncology Group (RTOG) 9508 showed a survival advantage for patients with 1 but not 2 or 3 brain metastasis (BM) treated with whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) versus WBRT alone. An improved prognostic index, the graded prognostic assessment (GPA) has been developed. Our hypothesis was that if the data from RTOG 9508 were poststratified by the GPA, the conclusions may vary. Methods and Materials: In this analysis, 252 of the 331 patients were evaluable by GPA. Of those, 211 had lung cancer. Breast cancer patients were excluded because the components of the breast GPAmore » are not in the RTOG database. Multiple Cox regression was used to compare survival between treatment groups, adjusting for GPA. Treatment comparisons within subgroups were performed with the log-rank test. A free online tool ( (brainmetgpa.com)) simplified GPA use. Results: The fundamental conclusions of the primary analysis were confirmed in that there was no survival benefit overall for patients with 1 to 3 metastases; however, there was a benefit for the subset of patients with GPA 3.5 to 4.0 (median survival time [MST] for WBRT + SRS vs WBRT alone was 21.0 versus 10.3 months, P=.05) regardless of the number of metastases. Among patients with GPA 3.5 to 4.0 treated with WBRT and SRS, the MST for patients with 1 versus 2 to 3 metastases was 21 and 14.1 months, respectively. Conclusions: This secondary analysis of predominantly lung cancer patients, consistent with the original analysis, shows no survival advantage for the group overall when treated with WBRT and SRS; however, in patients with high GPA (3.5-4), there is a survival advantage regardless of whether they have 1, 2, or 3 BM. This benefit did not extend to patients with lower GPA. Prospective validation of this survival benefit for patients with multiple BM and high GPA when treated with WBRT and SRS is warranted.« less

Secondary Analysis of RTOG 9508, a Phase 3 Randomized Trial of Whole-Brain Radiation Therapy Versus WBRT Plus Stereotactic Radiosurgery in Patients With 1-3 Brain Metastases; Poststratified by the Graded Prognostic Assessment (GPA)

PubMed Central

Sperduto, Paul W.; Shanley, Ryan; Luo, Xianghua; Andrews, David; Werner-Wasik, Maria; Valicenti, Richard; Bahary, Jean-Paul; Souhami, Luis; Won, Minhee; Mehta, Minesh

2015-01-01

Purpose Radiation Therapy Oncology Group (RTOG) 9508 showed a survival advantage for patients with 1 but not 2 or 3 brain metastasis (BM) treated with whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) versus WBRT alone. An improved prognostic index, the graded prognostic assessment (GPA) has been developed. Our hypothesis was that if the data from RTOG 9508 were poststratified by the GPA, the conclusions may vary. Methods and Materials In this analysis, 252 of the 331 patients were evaluable by GPA. Of those, 211 had lung cancer. Breast cancer patients were excluded because the components of the breast GPA are not in the RTOG database. Multiple Cox regression was used to compare survival between treatment groups, adjusting for GPA. Treatment comparisons within subgroups were performed with the log-rank test. A free online tool (brainmetgpa.com) simplified GPA use. Results The fundamental conclusions of the primary analysis were confirmed in that there was no survival benefit overall for patients with 1 to 3 metastases; however, there was a benefit for the subset of patients with GPA 3.5 to 4.0 (median survival time [MST] for WBRT + SRS vs WBRT alone was 21.0 versus 10.3 months, P = .05) regardless of the number of metastases. Among patients with GPA 3.5 to 4.0 treated with WBRT and SRS, the MST for patients with 1 versus 2 to 3 metastases was 21 and 14.1 months, respectively. Conclusions This secondary analysis of predominantly lung cancer patients, consistent with the original analysis, shows no survival advantage for the group overall when treated with WBRT and SRS; however, in patients with high GPA (3.5-4), there is a survival advantage regardless of whether they have 1, 2, or 3 BM. This benefit did not extend to patients with lower GPA. Prospective validation of this survival benefit for patients with multiple BM and high GPA when treated with WBRT and SRS is warranted. PMID:25304947

Secondary analysis of RTOG 9508, a phase 3 randomized trial of whole-brain radiation therapy versus WBRT plus stereotactic radiosurgery in patients with 1-3 brain metastases; poststratified by the graded prognostic assessment (GPA).

PubMed

Sperduto, Paul W; Shanley, Ryan; Luo, Xianghua; Andrews, David; Werner-Wasik, Maria; Valicenti, Richard; Bahary, Jean-Paul; Souhami, Luis; Won, Minhee; Mehta, Minesh

2014-11-01

Radiation Therapy Oncology Group (RTOG) 9508 showed a survival advantage for patients with 1 but not 2 or 3 brain metastasis (BM) treated with whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) versus WBRT alone. An improved prognostic index, the graded prognostic assessment (GPA) has been developed. Our hypothesis was that if the data from RTOG 9508 were poststratified by the GPA, the conclusions may vary. In this analysis, 252 of the 331 patients were evaluable by GPA. Of those, 211 had lung cancer. Breast cancer patients were excluded because the components of the breast GPA are not in the RTOG database. Multiple Cox regression was used to compare survival between treatment groups, adjusting for GPA. Treatment comparisons within subgroups were performed with the log-rank test. A free online tool (brainmetgpa.com) simplified GPA use. The fundamental conclusions of the primary analysis were confirmed in that there was no survival benefit overall for patients with 1 to 3 metastases; however, there was a benefit for the subset of patients with GPA 3.5 to 4.0 (median survival time [MST] for WBRT + SRS vs WBRT alone was 21.0 versus 10.3 months, P=.05) regardless of the number of metastases. Among patients with GPA 3.5 to 4.0 treated with WBRT and SRS, the MST for patients with 1 versus 2 to 3 metastases was 21 and 14.1 months, respectively. This secondary analysis of predominantly lung cancer patients, consistent with the original analysis, shows no survival advantage for the group overall when treated with WBRT and SRS; however, in patients with high GPA (3.5-4), there is a survival advantage regardless of whether they have 1, 2, or 3 BM. This benefit did not extend to patients with lower GPA. Prospective validation of this survival benefit for patients with multiple BM and high GPA when treated with WBRT and SRS is warranted. Copyright © 2014 Elsevier Inc. All rights reserved.

Prognostic value of the Glasgow Prognostic Score for glioblastoma multiforme patients treated with radiotherapy and temozolomide.

PubMed

Topkan, Erkan; Selek, Ugur; Ozdemir, Yurday; Yildirim, Berna A; Guler, Ozan C; Ciner, Fuat; Mertsoylu, Huseyin; Tufan, Kadir

2018-04-25

To evaluate the prognostic value of the Glasgow Prognostic Score (GPS), the combination of C-reactive protein (CRP) and albumin, in glioblastoma multiforme (GBM) patients treated with radiotherapy (RT) and concurrent plus adjuvant temozolomide (GPS). Data of newly diagnosed GBM patients treated with partial brain RT and concurrent and adjuvant TMZ were retrospectively analyzed. The patients were grouped into three according to the GPS criteria: GPS-0: CRP < 10 mg/L and albumin > 35 g/L; GPS-1: CRP < 10 mg/L and albumin < 35 g/L or CRP > 10 mg/L and albumin > 35 g/L; and GPS-2: CRP > 10 mg/L and albumin < 35 g/L. Primary end-point was the association between the GPS groups and the overall survival (OS) outcomes. A total of 142 patients were analyzed (median age: 58 years, 66.2% male). There were 64 (45.1%), 40 (28.2%), and 38 (26.7%) patients in GPS-0, GPS-1, and GPS-2 groups, respectively. At median 15.7 months follow-up, the respective median and 5-year OS rates for the whole cohort were 16.2 months (95% CI 12.7-19.7) and 9.5%. In multivariate analyses GPS grouping emerged independently associated with the median OS (P < 0.001) in addition to the extent of surgery (P = 0.032), Karnofsky performance status (P = 0.009), and the Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) classification (P < 0.001). The GPS grouping and the RTOG RPA classification were found to be strongly correlated in prognostic stratification of GBM patients (correlation coefficient: 0.42; P < 0.001). The GPS appeared to be useful in prognostic stratification of GBM patients into three groups with significantly different survival durations resembling the RTOG RPA classification.

Pelvic Normal Tissue Contouring Guidelines for Radiation Therapy: A Radiation Therapy Oncology Group Consensus Panel Atlas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gay, Hiram A., E-mail: hgay@radonc.wustl.edu; Barthold, H. Joseph; Beth Israel Deaconess Medical Center, Boston, MA

2012-07-01

Purpose: To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology Group (RTOG) trials. Methods and Materials: One male pelvis computed tomography (CT) data set and one female pelvis CT data set were shared via the Image-Guided Therapy QA Center. A total of 16 radiation oncologists participated. The following organs at risk were contoured in both CT sets: anus, anorectum, rectum (gastrointestinal and genitourinary definitions), bowel NOS (not otherwise specified), small bowel, large bowel, and proximal femurs. The following were contoured in the male set only: bladder, prostate, seminal vesicles, and penile bulb. The followingmore » were contoured in the female set only: uterus, cervix, and ovaries. A computer program used the binomial distribution to generate 95% group consensus contours. These contours and definitions were then reviewed by the group and modified. Results: The panel achieved consensus definitions for pelvic normal tissue contouring in RTOG trials with these standardized names: Rectum, AnoRectum, SmallBowel, Colon, BowelBag, Bladder, UteroCervix, Adnexa{sub R}, Adnexa{sub L}, Prostate, SeminalVesc, PenileBulb, Femur{sub R}, and Femur{sub L}. Two additional normal structures whose purpose is to serve as targets in anal and rectal cancer were defined: AnoRectumSig and Mesorectum. Detailed target volume contouring guidelines and images are discussed. Conclusions: Consensus guidelines for pelvic normal tissue contouring were reached and are available as a CT image atlas on the RTOG Web site. This will allow uniformity in defining normal tissues for clinical trials delivering pelvic radiation and will facilitate future normal tissue complication research.« less

Combination of external-beam radiotherapy with intraoperative electron-beam therapy is effective in incompletely resected pediatric malignancies.

PubMed

Oertel, Susanne; Niethammer, Andreas G; Krempien, Robert; Roeder, Falk; Eble, Michael J; Baer, Claudia; Huber, Peter E; Kulozik, Andreas; Waag, Karl-Ludwig; Treiber, Martina; Debus, Juergen

2006-01-01

Intraoperative electron-beam radiotherapy (IOERT) has been applied for local dose escalation in over 1,400 patients in Heidelberg since 1991. Among these were 30 children, in 18 of whom IOERT was employed in radiation treatment with external-beam radiotherapy (EBRT) on account of incomplete resection. We address the question whether IOERT is able to compensate for microscopic or macroscopic tumor residue if employed in the overall radiation regimen. The data of the aforementioned 18 children were analyzed with regard to local recurrence, overall survival, and complication rates. All children suffered from either sarcomas or neuroblastomas. In all children, IOERT was employed for local dose escalation after or before EBRT. After a median follow-up of 60.5 months, 15 of the treated children are alive. One local failure has been observed. Six children show clinically significant late morbidity, including the loss of a treated limb (Radiation Therapy Oncology Group Grade 4 [RTOG 4]), a severe nerve lesion (RTOG 3), an orthopedic complication (RTOG 2), a ureteral stenosis (not clinically significant), and a kidney hypotrophy (not clinically significant). In 1 child a fracture due to radionecrosis (RTOG 4) was diagnosed; however, in the follow-up, local tumor relapse was diagnosed as another possible reason for the fracture. Regarding the low incidence of local failure, IOERT seems to be able to compensate incomplete tumor resection in childhood sarcoma and neuroblastoma patients. The incidence of late morbidity is low enough to justify the employment of IOERT as part of the radiation treatment regimen for pediatric patients.

A phase II comparative study of gross tumor volume definition with or without PET/CT fusion in dosimetric planning for non-small-cell lung cancer (NSCLC): primary analysis of Radiation Therapy Oncology Group (RTOG) 0515.

PubMed

Bradley, Jeffrey; Bae, Kyounghwa; Choi, Noah; Forster, Ken; Siegel, Barry A; Brunetti, Jacqueline; Purdy, James; Faria, Sergio; Vu, Toni; Thorstad, Wade; Choy, Hak

2012-01-01

Radiation Therapy Oncology Group (RTOG) 0515 is a Phase II prospective trial designed to quantify the impact of positron emission tomography (PET)/computed tomography (CT) compared with CT alone on radiation treatment plans (RTPs) and to determine the rate of elective nodal failure for PET/CT-derived volumes. Each enrolled patient underwent definitive radiation therapy for non-small-cell lung cancer (≥ 60 Gy) and had two RTP datasets generated: gross tumor volume (GTV) derived with CT alone and with PET/CT. Patients received treatment using the PET/CT-derived plan. The primary end point, the impact of PET/CT fusion on treatment plans was measured by differences of the following variables for each patient: GTV, number of involved nodes, nodal station, mean lung dose (MLD), volume of lung exceeding 20 Gy (V20), and mean esophageal dose (MED). Regional failure rate was a secondary end point. The nonparametric Wilcoxon matched-pairs signed-ranks test was used with Bonferroni adjustment for an overall significance level of 0.05. RTOG 0515 accrued 52 patients, 47 of whom are evaluable. The follow-up time for all patients is 12.9 months (2.7-22.2). Tumor staging was as follows: II = 6%; IIIA = 40%; and IIIB = 54%. The GTV was statistically significantly smaller for PET/CT-derived volumes (98.7 vs. 86.2 mL; p < 0.0001). MLDs for PET/CT plans were slightly lower (19 vs. 17.8 Gy; p = 0.06). There was no significant difference in the number of involved nodes (2.1 vs. 2.4), V20 (32% vs. 30.8%), or MED (28.7 vs. 27.1 Gy). Nodal contours were altered by PET/CT for 51% of patients. One patient (2%) has developed an elective nodal failure. PET/CT-derived tumor volumes were smaller than those derived by CT alone. PET/CT changed nodal GTV contours in 51% of patients. The elective nodal failure rate for GTVs derived by PET/CT is quite low, supporting the RTOG standard of limiting the target volume to the primary tumor and involved nodes. Copyright © 2012 Elsevier Inc. All rights reserved.

Feasibility of magnetic resonance imaging-guided liver stereotactic body radiation therapy: A comparison between modulated tri-cobalt-60 teletherapy and linear accelerator-based intensity modulated radiation therapy.

PubMed

Kishan, Amar U; Cao, Minsong; Wang, Pin-Chieh; Mikaeilian, Argin G; Tenn, Stephen; Rwigema, Jean-Claude M; Sheng, Ke; Low, Daniel A; Kupelian, Patrick A; Steinberg, Michael L; Lee, Percy

2015-01-01

The purpose of this study was to investigate the dosimetric feasibility of liver stereotactic body radiation therapy (SBRT) using a teletherapy system equipped with 3 rotating (60)Co sources (tri-(60)Co system) and a built-in magnetic resonance imager (MRI). We hypothesized tumor size and location would be predictive of favorable dosimetry with tri-(60)Co SBRT. The primary study population consisted of 11 patients treated with SBRT for malignant hepatic lesions whose linear accelerator (LINAC)-based SBRT plans met all mandatory Radiation Therapy Oncology Group (RTOG) 1112 organ-at-risk (OAR) constraints. The secondary study population included 5 additional patients whose plans did not meet the mandatory constraints. Patients received 36 to 60 Gy in 3 to 5 fractions. Tri-(60)Co system SBRT plans were planned with ViewRay system software. All patients in the primary study population had tri-(60)Co SBRT plans that passed all RTOG constraints, with similar planning target volume coverage and OAR doses to LINAC plans. Mean liver doses and V10Gy to the liver, although easily meeting RTOG 1112 guidelines, were significantly higher with tri-(60)Co plans. When the 5 additional patients were included in a univariate analysis, the tri-(60)Co SBRT plans were still equally able to pass RTOG constraints, although they did have inferior ability to pass more stringent liver and kidney constraints (P < .05). A multivariate analysis found the ability of a tri-(60)Co SBRT plan to meet these constraints depended on lesion location and size. Patients with smaller or more peripheral lesions (as defined by distance from the aorta, chest wall, liver dome, and relative lesion volume) were significantly more likely to have tri-(60)Co plans that spared the liver and kidney as well as LINAC plans did (P < .05). It is dosimetrically feasible to perform liver SBRT with a tri-(60)Co system with a built-in MRI. Patients with smaller or more peripheral lesions are more likely to have optimal liver and kidney sparing, with the added benefit of MRI guidance, when receiving tri-(60)Co-based SBRT. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Metabolic Tumor Volume as a Prognostic Imaging-Based Biomarker for Head-and-Neck Cancer: Pilot Results From Radiation Therapy Oncology Group Protocol 0522

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwartz, David L., E-mail: david.schwartz@utsw.edu; Harris, Jonathan; Yao, Min

2015-03-15

Purpose: To evaluate candidate fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging biomarkers for head-and-neck chemoradiotherapy outcomes in the cooperative group trial setting. Methods and Materials: Radiation Therapy Oncology Group (RTOG) protocol 0522 patients consenting to a secondary FDG-PET/CT substudy were serially imaged at baseline and 8 weeks after radiation. Maximum standardized uptake value (SUVmax), SUV peak (mean SUV within a 1-cm sphere centered on SUVmax), and metabolic tumor volume (MTV) using 40% of SUVmax as threshold were obtained from primary tumor and involved nodes. Results: Of 940 patients entered onto RTOG 0522, 74 were analyzable for this substudy. Neither high baselinemore » SUVmax nor SUVpeak from primary or nodal disease were associated with poor treatment outcomes. However, primary tumor MTV above the cohort median was associated with worse local-regional control (hazard ratio 4.01, 95% confidence interval 1.28-12.52, P=.02) and progression-free survival (hazard ratio 2.34, 95% confidence interval 1.02-5.37, P=.05). Although MTV and T stage seemed to correlate (mean MTV 6.4, 13.2, and 26.8 for T2, T3, and T4 tumors, respectively), MTV remained a strong independent prognostic factor for progression-free survival in bivariate analysis that included T stage. Primary MTV remained prognostic in p16-associated oropharyngeal cancer cases, although sample size was limited. Conclusion: High baseline primary tumor MTV was associated with worse treatment outcomes in this limited patient subset of RTOG 0522. Additional confirmatory work will be required to validate primary tumor MTV as a prognostic imaging biomarker for patient stratification in future trials.« less

Feasibility of Economic Analysis of Radiation Therapy Oncology Group (RTOG) 91-11 Using Medicare Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Konski, Andre, E-mail: akonski@med.wayne.ed; Bhargavan, Mythreyi; Owen, Jean

Purpose: The specific aim of this analysis was to evaluate the feasibility of performing a cost-effectiveness analysis using Medicare data from patients treated on a randomized Phase III clinical trial. Methods and Materials: Cost data included Medicare Part A and Part B costs from all providers-inpatient, outpatient, skilled nursing facility, home health, hospice, and physicians-and were obtained from the Centers for Medicare and Medicaid Services for patients eligible for Medicare, treated on Radiation Therapy Oncology Group (RTOG) 9111 between 1992 and 1996. The 47-month expected discounted (annual discount rate of 3%) cost for each arm of the trial was calculatedmore » in 1996 dollars, with Kaplan-Meier sampling average estimates of survival probabilities for each month and mean monthly costs. Overall and disease-free survival was also discounted 3%/year. The analysis was performed from a payer's perspective. Incremental cost-effectiveness ratios were calculated comparing the chemotherapy arms to the radiation alone arm. Results: Of the 547 patients entered, Medicare cost data and clinical outcomes were available for 66 patients. Reasons for exclusion included no RTOG follow-up, Medicare HMO enrollment, no Medicare claims since trial entry, and trial entry after 1996. Differences existed between groups in tumor characteristics, toxicity, and survival, all which could affect resource utilization. Conclusions: Although we were able to test the methodology of economic analysis alongside a clinical trial using Medicare data, the results may be difficult to translate to the entire trial population because of non-random missing data. Methods to improve Medicare data capture and matching to clinical trial samples are required.« less

RTOG GU Radiation Oncology Specialists Reach Consensus on Pelvic Lymph Node Volumes for High-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lawton, Colleen A.F.; Michalski, Jeff; El-Naqa, Issam

2009-06-01

Purpose: Radiation therapy to the pelvic lymph nodes in high-risk prostate cancer is required on several Radiation Therapy Oncology Group (RTOG) clinical trials. Based on a prior lymph node contouring project, we have shown significant disagreement in the definition of pelvic lymph node volumes among genitourinary radiation oncology specialists involved in developing and executing current RTOG trials. Materials and Methods: A consensus meeting was held on October 3, 2007, to reach agreement on pelvic lymph node volumes. Data were presented to address the lymph node drainage of the prostate. Extensive discussion ensued to develop clinical target volume (CTV) pelvic lymphmore » node consensus. Results: Consensus was obtained resulting in computed tomography image-based pelvic lymph node CTVs. Based on this consensus, the pelvic lymph node volumes to be irradiated include: distal common iliac, presacral lymph nodes (S{sub 1}-S{sub 3}), external iliac lymph nodes, internal iliac lymph nodes, and obturator lymph nodes. Lymph node CTVs include the vessels (artery and vein) and a 7-mm radial margin being careful to 'carve out' bowel, bladder, bone, and muscle. Volumes begin at the L5/S1 interspace and end at the superior aspect of the pubic bone. Consensus on dose-volume histogram constraints for OARs was also attained. Conclusions: Consensus on pelvic lymph node CTVs for radiation therapy to address high-risk prostate cancer was attained and is available as web-based computed tomography images as well as a descriptive format through the RTOG. This will allow for uniformity in evaluating the benefit and risk of such treatment.« less

Vitamin D Deficiency Is Associated With the Severity of Radiation-Induced Proctitis in Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghorbanzadeh-Moghaddam, Amir; Gholamrezaei, Ali, E-mail: Gholamrezaei@med.mui.ac.ir; Poursina Hakim Research Institution, Isfahan

Purpose: Radiation-induced injury to normal tissues is a common complication of radiation therapy in cancer patients. Considering the role of vitamin D in mucosal barrier hemostasis and inflammatory responses, we investigated whether vitamin D deficiency is associated with the severity of radiation-induced acute proctitis in cancer patients. Methods and Materials: This prospective observational study was conducted in cancer patients referred for pelvic radiation therapy. Serum concentration of 25-hydroxyvitamin D was measured before radiation therapy. Vitamin D deficiency was defined as 25-hydroxyvitamin D concentrations of <35 nmol/L and <40 nmol/L in male and female patients, respectively, based on available normative data.more » Acute proctitis was assessed after 5 weeks of radiation therapy (total received radiation dose of 50 Gy) and graded from 0 to 4 using Radiation Therapy Oncology Group (RTOG) criteria. Results: Ninety-eight patients (57.1% male) with a mean age of 62.8 ± 9.1 years were studied. Vitamin D deficiency was found in 57 patients (58.1%). Symptoms of acute proctitis occurred in 72 patients (73.4%) after radiation therapy. RTOG grade was significantly higher in patients with vitamin D deficiency than in normal cases (median [interquartile range] of 2 [0.5-3] vs 1 [0-2], P=.037). Vitamin D deficiency was associated with RTOG grade of ≥2, independent of possible confounding factors; odds ratio (95% confidence interval) = 3.07 (1.27-7.50), P=.013. Conclusions: Vitamin D deficiency is associated with increased severity of radiation-induced acute proctitis. Investigating the underlying mechanisms of this association and evaluating the effectiveness of vitamin D therapy in preventing radiation-induced acute proctitis is warranted.« less

Implementation of Remote 3-Dimensional Image Guided Radiation Therapy Quality Assurance for Radiation Therapy Oncology Group Clinical Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cui Yunfeng; Galvin, James M.; Radiation Therapy Oncology Group, American College of Radiology, Philadelphia, Pennsylvania

2013-01-01

Purpose: To report the process and initial experience of remote credentialing of three-dimensional (3D) image guided radiation therapy (IGRT) as part of the quality assurance (QA) of submitted data for Radiation Therapy Oncology Group (RTOG) clinical trials; and to identify major issues resulting from this process and analyze the review results on patient positioning shifts. Methods and Materials: Image guided radiation therapy datasets including in-room positioning CT scans and daily shifts applied were submitted through the Image Guided Therapy QA Center from institutions for the IGRT credentialing process, as required by various RTOG trials. A centralized virtual environment is establishedmore » at the RTOG Core Laboratory, containing analysis tools and database infrastructure for remote review by the Physics Principal Investigators of each protocol. The appropriateness of IGRT technique and volumetric image registration accuracy were evaluated. Registration accuracy was verified by repeat registration with a third-party registration software system. With the accumulated review results, registration differences between those obtained by the Physics Principal Investigators and from the institutions were analyzed for different imaging sites, shift directions, and imaging modalities. Results: The remote review process was successfully carried out for 87 3D cases (out of 137 total cases, including 2-dimensional and 3D) during 2010. Frequent errors in submitted IGRT data and challenges in the review of image registration for some special cases were identified. Workarounds for these issues were developed. The average differences of registration results between reviewers and institutions ranged between 2 mm and 3 mm. Large discrepancies in the superior-inferior direction were found for megavoltage CT cases, owing to low spatial resolution in this direction for most megavoltage CT cases. Conclusion: This first experience indicated that remote review for 3D IGRT as part of QA for RTOG clinical trials is feasible and effective. The magnitude of registration discrepancy between institution and reviewer was presented, and the major issues were investigated to further improve this remote evaluation process.« less

Decline in Tested and Self-Reported Cognitive Functioning After Prophylactic Cranial Irradiation for Lung Cancer: Pooled Secondary Analysis of Radiation Therapy Oncology Group Randomized Trials 0212 and 0214

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gondi, Vinai, E-mail: vgondi@chicagocancer.org; University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin; Paulus, Rebecca

Purpose: To assess the impact of prophylactic cranial irradiation (PCI) on self-reported cognitive functioning (SRCF), a functional scale on the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). Methods and Materials: Radiation Therapy Oncology Group (RTOG) protocol 0214 randomized patients with locally advanced non-small cell lung cancer to PCI or observation; RTOG 0212 randomized patients with limited-disease small cell lung cancer to high- or standard-dose PCI. In both trials, Hopkins Verbal Learning Test (HVLT)-Recall and -Delayed Recall and SRCF were assessed at baseline (after locoregional therapy but before PCI or observation) and atmore » 6 and 12 months. Patients developing brain relapse before follow-up evaluation were excluded. Decline was defined using the reliable change index method and correlated with receipt of PCI versus observation using logistic regression modeling. Fisher's exact test correlated decline in SRCF with HVLT decline. Results: Of the eligible patients pooled from RTOG 0212 and RTOG 0214, 410 (93%) receiving PCI and 173 (96%) undergoing observation completed baseline HVLT or EORTC QLQ-C30 testing and were included in this analysis. Prophylactic cranial irradiation was associated with a higher risk of decline in SRCF at 6 months (odds ratio 3.60, 95% confidence interval 2.34-6.37, P<.0001) and 12 months (odds ratio 3.44, 95% confidence interval 1.84-6.44, P<.0001). Decline on HVLT-Recall at 6 and 12 months was also associated with PCI (P=.002 and P=.002, respectively) but was not closely correlated with decline in SRCF at the same time points (P=.05 and P=.86, respectively). Conclusions: In lung cancer patients who do not develop brain relapse, PCI is associated with decline in HVLT-tested and self-reported cognitive functioning. Decline in HVLT and decline in SRCF are not closely correlated, suggesting that they may represent distinct elements of the cognitive spectrum.« less

Evaluating which plan quality metrics are appropriate for use in lung SBRT.

PubMed

Yaparpalvi, Ravindra; Garg, Madhur K; Shen, Jin; Bodner, William R; Mynampati, Dinesh K; Gafar, Aleiya; Kuo, Hsiang-Chi; Basavatia, Amar K; Ohri, Nitin; Hong, Linda X; Kalnicki, Shalom; Tome, Wolfgang A

2018-02-01

Several dose metrics in the categories-homogeneity, coverage, conformity and gradient have been proposed in literature for evaluating treatment plan quality. In this study, we applied these metrics to characterize and identify the plan quality metrics that would merit plan quality assessment in lung stereotactic body radiation therapy (SBRT) dose distributions. Treatment plans of 90 lung SBRT patients, comprising 91 targets, treated in our institution were retrospectively reviewed. Dose calculations were performed using anisotropic analytical algorithm (AAA) with heterogeneity correction. A literature review on published plan quality metrics in the categories-coverage, homogeneity, conformity and gradient was performed. For each patient, using dose-volume histogram data, plan quality metric values were quantified and analysed. For the study, the radiation therapy oncology group (RTOG) defined plan quality metrics were: coverage (0.90 ± 0.08); homogeneity (1.27 ± 0.07); conformity (1.03 ± 0.07) and gradient (4.40 ± 0.80). Geometric conformity strongly correlated with conformity index (p < 0.0001). Gradient measures strongly correlated with target volume (p < 0.0001). The RTOG lung SBRT protocol advocated conformity guidelines for prescribed dose in all categories were met in ≥94% of cases. The proportion of total lung volume receiving doses of 20 Gy and 5 Gy (V 20 and V 5 ) were mean 4.8% (±3.2) and 16.4% (±9.2), respectively. Based on our study analyses, we recommend the following metrics as appropriate surrogates for establishing SBRT lung plan quality guidelines-coverage % (ICRU 62), conformity (CN or CI Paddick ) and gradient (R 50% ). Furthermore, we strongly recommend that RTOG lung SBRT protocols adopt either CN or CI Padddick in place of prescription isodose to target volume ratio for conformity index evaluation. Advances in knowledge: Our study metrics are valuable tools for establishing lung SBRT plan quality guidelines.

Radiotherapy induced dermatitis is a strong predictor for late fibrosis in head and neck cancer. The development of a predictive model for late fibrosis.

PubMed

Nevens, Daan; Duprez, Fréderic; Daisne, Jean Francois; Laenen, Annouschka; De Neve, Wilfried; Nuyts, Sandra

2017-02-01

To determine if the severity of radiodermatitis at the end of radio(chemo)therapy (R(C)T) for head and neck cancer (HNC) is a predictive factor for late fibrosis of the neck and to find a model to predict neck fibrosis grade⩾2 (fibrosis RTOG 2-4 ) at 6months following R(C)T for HNC. 161 patients were prospectively included. We correlated radiodermatitis at the end of RCT, age, sex, T/N stage, tumor site, concomitant chemotherapy, upfront neck dissection, neo-adjuvant chemotherapy, accelerated RT, smoking, alcohol consumption, HPV status and the dose prescribed to the elective neck with fibrosis RTOG 2-4 6months after the end of treatment. Radiodermatitis at the end of R(C)T ⩾grade 3 proved to be associated with the incidence of fibrosis RTOG 2-4 at 6months (p<0.01). Furthermore, upfront neck dissection (p<0.01), increasing N stage (p<0.01) and tumor site (p=0.02) are significantly associated in univariate analysis with fibrosis RTOG 2-4 at 6months of follow-up. Upfront neck dissection and radiodermatitis grade⩾3 at the end of R(C)T were identified by our multivariate model. Additionally, increasing N stage was selected as an independent predictor variable. The AUC for this model was 0.92. A model for the prediction of fibrosis RTOG 2-4 following R(C)T for head and neck cancer is presented with an AUC of 0.92. Interestingly, radiodermatitis grade⩾3 at the end of R(C)T is associated with RTOG 2-4 fibrosis at 6months. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Xerostomia health-related quality of life: NRG oncology RTOG 0537.

PubMed

Wyatt, Gwen; Pugh, Stephanie L; Wong, Raimond K W; Sagar, Stephen; Singh, Anurag K; Koyfman, Shlomo A; Nguyen-Tân, Phuc F; Yom, Sue S; Cardinale, Francis S; Sultanem, Khalil; Hodson, Ian; Krempl, Greg A; Lukaszczyk, Barbara; Yeh, Alexander M; Berk, Lawrence

2016-09-01

The purpose of this secondary analysis was to determine change in overall health-related quality of life (HRQOL) based on patient data obtained from NRG Oncology RTOG 0537 as measured by the RTOG-modified University of Washington Head and Neck Symptom Score (RM-UWHNSS). A multi-site prospective randomized clinical trial design stratified 137 patients with post-radiation therapy xerostomia according to prior pilocarpine (PC) treatment and time after radiation therapy and/or chemotherapy and randomized patients into two groups. Patients were assigned to acupuncture or PC. Twenty-four sessions of acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) were administered over 12 weeks, or oral PC (5 mg) three times daily over the same 12 weeks. The RM-UWHNSS was administered at baseline and at 4, 6, 9, and 15 months after the date of randomization. There were no between-arm differences in change scores on the RM-UWHNSS in the individual items, total score, or factor scores. For statistical modeling, race and time were significant for all outcomes (total and factor scores), while treatment arm was not significant. The ALTENS arm showed greater yet nonsignificant improvement in outcomes compared to the PC arm. Although no significant treatment differences were seen in this trial, patients receiving ALTENS consistently had lower scores, indicating better function, as compared to those receiving PC. Radiation-induced xerostomia improved over time for all patients.

Conventional and conformal technique of external beam radiotherapy in locally advanced cervical cancer: Dose distribution, tumor response, and side effects

NASA Astrophysics Data System (ADS)

Mutrikah, N.; Winarno, H.; Amalia, T.; Djakaria, M.

2017-08-01

The objective of this study was to compare conventional and conformal techniques of external beam radiotherapy (EBRT) in terms of the dose distribution, tumor response, and side effects in the treatment of locally advanced cervical cancer patients. A retrospective cohort study was conducted on cervical cancer patients who underwent EBRT before brachytherapy in the Radiotherapy Department of Cipto Mangunkusumo Hospital. The prescribed dose distribution, tumor response, and acute side effects of EBRT using conventional and conformal techniques were investigated. In total, 51 patients who underwent EBRT using conventional techniques (25 cases using Cobalt-60 and 26 cases using a linear accelerator (LINAC)) and 29 patients who underwent EBRT using conformal techniques were included in the study. The distribution of the prescribed dose in the target had an impact on the patient’s final response to EBRT. The complete response rate of patients to conformal techniques was significantly greater (58%) than that of patients to conventional techniques (42%). No severe acute local side effects were seen in any of the patients (Radiation Therapy Oncology Group (RTOG) grades 3-4). The distribution of the dose and volume to the gastrointestinal tract affected the proportion of mild acute side effects (RTOG grades 1-2). The urinary bladder was significantly greater using conventional techniques (Cobalt-60/LINAC) than using conformal techniques at 72% and 78% compared to 28% and 22%, respectively. The use of conformal techniques in pelvic radiation therapy is suggested in radiotherapy centers with CT simulators and 3D Radiotherapy Treatment Planning Systems (RTPSs) to decrease some uncertainties in radiotherapy planning. The use of AP/PA pelvic radiation techniques with Cobalt-60 should be limited in body thicknesses equal to or less than 18 cm. When using conformal techniques, delineation should be applied in the small bowel, as it is considered a critical organ according to RTOG consensus guidelines.

Optimal treatment for localized esophageal cancer still uncertain.

PubMed

Lord, R V

2000-01-01

These articles both report the results of multi-institutional, randomized, phase 3 trials for the treatment of patients with localized (T1-3 N0-1 M0) esophageal squamous cell carcinoma (SCC) or esophageal adenocarcinoma. Both studies were initiated and coordinated by the Radiation Therapy Oncology Group (RTOG) but included patients enrolled by other study groups as well. Cooper et al. report late follow-up results for the RTOG 85-01 trial that was conducted between 1986 and 1990. This trial randomized patients to either radiation therapy (RT) alone (RT, 64 Gy in 32 fractions over 6.4 wk, n = 62) or combined RT and chemotherapy (50 Gy in 25 fractions over 5 wk, plus cisplatin 75 mg/m2 i.v. on first day of wk 1, 5, 8, and 11, and continuous infusion fluorouracil (5FU) 1 g/m2 per day on the first 4 days of the same weeks, n = 61). Most (82%) of the patients had SCC. Eight percent of the cohort randomly assigned to combined modality therapy experienced acute life-threatening toxic effects, and an additional 2% died as a direct consequence of treatment. The randomized trial was halted in 1990 when an interim analysis found a highly significant difference in survival favoring the combined therapy group, after which 73 consecutive patients were enrolled into a nonrandomized study offering only the combined therapy regimen. At 5-yr of follow-up, the overall survival rate for the combined therapy group in the randomized study was 26% (95% CI, 15-37%) compared with 0% for RT alone. In the nonrandomized study, the 5-yr overall survival rate was 14% (95% CI, 6-23%). The histopathological type of tumor did not significantly influence survival. Cooper et al. now report that 22% of the randomized combined modality group survived at least 8 yr after treatment, and that there were no deaths caused by esophageal cancer after 5 yr post-treatment. The study reported by Kelsen et al. included 440 patients with esophageal adenocarcinoma (n = 236) or SCC (n = 204) randomized to either preoperative chemotherapy plus esophagectomy or to esophagectomy alone. The chemotherapy regimen consisted of three cycles of preoperative cisplatin and 5FU and two cycles after operation for responding patients. Doses were higher than those used in the RTOG 85-01 trial. Although radiation therapy was not part of the treatment plan, it could be given in some circumstances. There was no significant difference in median survival (14.9 months for chemotherapy plus surgery compared with 16.1 months for surgery alone), and there were also no significant differences in 1-yr, 2-yr, 3-yr, or disease-free survival rates. There were no significant differences in survival between patients with adenocarcinoma and those with SCC. A clinical response to chemotherapy, as assessed by barium contrast radiography, was found in 19% of patients who received chemotherapy. A complete pathological response was found in 2.5% of patients. There was no significant increase in operative complications in the chemotherapy treated group.

Local control of brain metastases by stereotactic radiosurgery in relation to dose to the tumor margin.

PubMed

Vogelbaum, Michael A; Angelov, Lilyana; Lee, Shih-Yuan; Li, Liang; Barnett, Gene H; Suh, John H

2006-06-01

The maximal tolerated dose (MTD) for stereotactic radiosurgery (SRS) for brain tumors was established by the Radiation Therapy Oncology Group (RTOG) in protocol 90-05, which defined three dose groups based on the maximal tumor diameter. The goal in this retrospective study was to determine whether differences in doses to the margins of brain metastases affect the ability of SRS to achieve local control. Between 1997 and 2003, 202 patients harboring 375 tumors that met study entry criteria underwent SRS for treatment of one or multiple brain metastases. The median overall follow-up duration was 10.7 months (range 3-83 months). A dose of 24 Gy to the tumor margin had a significantly lower risk of local failure than 15 or 18 Gy (p = 0.0005; hazard ratio 0.277, confidence interval [CI] 0.134-0.573), whereas the 15- and 18-Gy groups were not significantly different from each other (p = 0.82) in this regard. The 1-year local control rate was 85% (95% CI 78-92%) in tumors treated with 24 Gy, compared with 49% (CI 30-68%) in tumors treated with 18 Gy and 45% (CI 23-67%) in tumors treated with 15 Gy. Overall patient survival was independent of dose to the tumor margin. Use of the RTOG 90-05 dosing scheme for brain metastases is associated with a variable local control rate. Tumors larger than 2 cm are less effectively controlled than smaller lesions, which can be safely treated with 24 Gy. Prospective evaluations of the relationship between dose to the tumor margin and local control should be performed to confirm these observations.

Evaluation of acute and late radiation morbidity in patients with gynaecologic malignancy using the RTOG criteria and Franco-Italian glossary.

PubMed

Yildirim, G; Ozsaran, Z; Yalman, D; Kamer, S; Aras, A

2008-01-01

The purpose of this study was to evaluate acute and late radiation morbidity in patients with gynaecologic malignancy using the RTOG criteria and Franco-Italian glossary, and to compare the usefulness and disadvantages of each system. Between February 2001 and February 2003, 107 patients with gynaecologic malignancy who received either radical or djuvant external radiotherapy +/- intracavitary brachytherapy or radiochemotherapy were enrolled in this study. The patients were evaluated before radiotherapy and weekly during radiotherapy for acute morbidity using the RTOG grading system and Franco-Italian glossary. Postradiotherapy evaluation was done one month after radiotherapy and at 3-month intervals thereafter. Median follow-up duration was 17 months. Morbidity was graded and recorded according to each scoring system. Median age was 46 years (range 37-82). Sixty-four patients (59.8%) had endometrial cancer. Radical radiotherapy was applied to 26 patients because of inoperability and 81 patients received postoperative radiotherapy. Biologically effective doses for the bladder, rectum and vagina were 98.39, 103.54 and 121.81, respectively, for late morbidity (BED3); 70.88, 72.84 and 80.92, respectively, for acute morbidity (BED10). According to the RTOG grading system acute morbidity rate for the genitourinary and gastrointestinal systems, and skin were 52.3%, 83.2% and 63.5%, respectively. Late morbidity rate for the bladder, colon-rectum, skin and vagina were 16.8%, 20.6%, 47.7% and 51.4%, respectively. The morbidity rate for the bladder, nonspecific abdominal, hematopoietic system, uterus-vulva-vagina, skin and rectum were 35.4%, 29.9%, 5.6%, 60.8%, 40.1% and 32.7%, respectively using the Franco-Italian glossary. In patients with carcinoma of the vulva--whose treatment fields were wider--acute morbidity rate according to RTOG criteria was higher (p = 0.057); photon energy (6 Mv rather than 1.25 MV) (p = 0.01) and treatment interruption of more than eight days (p = 0.019) were correlated with decreased long-term morbidity. According to the Franco-Italian glossary morbidity rates were higher in patients who received chemotherapy (p = 0.047), both external radiotherapy and brachytherapy (p = 0.022) and treatment interruption of less than eight days (p = 0.019). There is no common language between the RTOG grading system and Franco-Italian glossary for defining and scoring radiation morbidity. Up to date no standard and well-defined system has been developed for recording and reporting acute and late radiation morbidity in gynaecologic malignancy, but rather it depends on the subjective evaluation and experience of a radiation oncologist and subjective complaints of the patient, and sometimes on clinical findings. A standard and well-defined user friendly objective scoring system is needed to define and predict the morbidity rate more properly.

The impact of RTOG 0614 and RTOG 0933 trials in routine clinical practice: The US Survey of Utilization of Memantine and IMRT planning for hippocampus sparing in patients receiving whole brain radiotherapy for brain metastases.

PubMed

Slade, Alexander N; Stanic, Sinisa

2016-03-01

Two recent clinical trials, phase III RTOG 0614 and phase II RTOG 0933, showed some effectiveness of Memantine and IMRT planning for hippocampus sparing, among patients receiving whole brain radiotherapy (WBRT) for brain metastases; however, their use in routine clinical practice is unknown. A survey was sent to 1933 radiation oncologists in the US. Data collected included utilization of Memantine and hippocampus sparing, reasons for adoption and non-adoption, and demographic variables. A total of 196 radiation oncologists responded to the survey, with 64% reporting using Memantine in almost none of the patients receiving WBRT for brain metastases, and only 11% considering Memantine for <10% of their patients. The most common reason for not using Memantine was a poor patient performance status, and limited life expectancy. Likewise, 56% of radiation oncologists would not change their clinical practice to include hippocampus sparing IMRT in patients receiving WBRT based on the results of RTOG 0933. Further validation of hippocampus sparing in a phase III trial was supported by 71% of radiation oncologists, whereas further exploration of Memantine for this purpose in a phase III trial was supported by 42%. At this time, the majority of surveyed radiation oncologists in the US do not use Memantine, or IMRT planning for hippocampus sparing in patients receiving WBRT. Further validation of the hippocampus sparing concept in a phase III trial was supported, before adopting it in routine clinical practice. Copyright © 2015 Elsevier Inc. All rights reserved.

Racial Differences in CYP3A4 Genotype and Survival Among Men Treated on Radiation Therapy Oncology Group (RTOG) 9202: A Phase III Randomized Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roach, Mack; Silvio, Michelle de; Rebbick, Timothy

2007-09-01

Purpose: Inherited genotypes may explain the inferior outcomes of African American (AA) men with prostate cancer. To understand how variation in CYP3A4 correlated with outcomes, a retrospective examination of the CYP3A4*1B genotype was performed on men treated with Radiation Therapy Oncology Group (RTOG) 92-02. Methods and Materials: From 1,514 cases, we evaluated 56 (28.4%) of 197 AA and 54 (4.3%) of 1,274 European American (EA) patients. All patients received goserelin and flutamide for 2 months before and during RT (STAD-RT) {+-} 24 months of goserelin (long-term androgen deprivation plus radiation [LTAD-RT]). Events studied included overall survival and biochemical progression usingmore » American Society for Therapeutic Radiology and Oncology consensus guidelines. Results: There were no differences in outcome in patients in with or without CYP3A4 data. There was an association between race and CYP3A4 polymorphisms with 75% of EAs having the Wild Type compared to only 25% of AA men (p <0.0001). There was no association between CYP3A4 classification or race and survival or progression. Conclusions: The samples analyzed support previously reported observations about the distribution of CYP3A4*1B genotype by race, but race was not associated with poorer outcome. However, patient numbers were limited, and selection bias cannot be completely ruled out.« less

High Occurrence of Aberrant Lymph Node Spread on Magnetic Resonance Lymphography in Prostate Cancer Patients With a Biochemical Recurrence After Radical Prostatectomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meijer, Hanneke J.M., E-mail: H.Meijer@rther.umcn.nl; Lin, Emile N. van; Debats, Oscar A.

2012-03-15

Purpose: To investigate the pattern of lymph node spread in prostate cancer patients with a biochemical recurrence after radical prostatectomy, eligible for salvage radiotherapy; and to determine whether the clinical target volume (CTV) for elective pelvic irradiation in the primary setting can be applied in the salvage setting for patients with (a high risk of) lymph node metastases. Methods and Materials: The charts of 47 prostate cancer patients with PSA recurrence after prostatectomy who had positive lymph nodes on magnetic resonance lymphography (MRL) were reviewed. Positive lymph nodes were assigned to a lymph node region according to the guidelines ofmore » the Radiation Therapy Oncology Group (RTOG) for delineation of the CTV for pelvic irradiation (RTOG-CTV). We defined four lymph node regions for positive nodes outside this RTOG-CTV: the para-aortal, proximal common iliac, pararectal, and paravesical regions. They were referred to as aberrant lymph node regions. For each patient, clinical and pathologic features were recorded, and their association with aberrant lymph drainage was investigated. The distribution of positive lymph nodes was analyzed separately for patients with a prostate-specific antigen (PSA) <1.0 ng/mL. Results: MRL detected positive aberrant lymph nodes in 37 patients (79%). In 20 patients (43%) a positive lymph node was found in the pararectal region. Higher PSA at the time of MRL was associated with the presence of positive lymph nodes in the para-aortic region (2.49 vs. 0.82 ng/mL; p = 0.007) and in the proximal common iliac region (1.95 vs. 0.59 ng/mL; p = 0.009). There were 18 patients with a PSA <1.0 ng/mL. Ten of these patients (61%) had at least one aberrant positive lymph node. Conclusion: Seventy-nine percent of the PSA-recurrent patients had at least one aberrant positive lymph node. Application of the standard RTOG-CTV for pelvic irradiation in the salvage setting therefore seems to be inappropriate.« less

Clonal Evaluation of Prostate Cancer by ERG/SPINK1 Status to Improve Prognosis Prediction

DTIC Science & Technology

2016-10-01

clinical oncology , cancer genetics, genomic science/bioinformatics, clinical pathology, social and behavioral sciences, and bioethics in order to...Interpret and translate sequence variants into clinical oncology setting; 5) Assess and evaluate costs associated with clinical sequencing. Role...Lethal Prostate Cancer Goal(s): Radiation Therapy Oncology Group (RTOG) 96-01 represents a phase III trial of of salvage radiation therapy (RT) alone

Mapping Patterns of Ipsilateral Supraclavicular Nodal Metastases in Breast Cancer: Rethinking the Clinical Target Volume for High-risk Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jing, Hao; Wang, Shu-Lian, E-mail: wsl20040118@yahoo.com; Li, Jing

2015-10-01

Purpose: To map the location of metastatic supraclavicular (SCV) lymph nodes (LNMs) in breast cancer patients with SCV node involvement and determine whether and where the radiation therapy clinical target volume (CTV) of this region could be modified in high-risk subsets. Methods and Materials: Fifty-five patients with metastatic SCV LNMs were eligible for geographic mapping and atlas coverage analysis. All LNMs and their epicenters were registered proportionally by referencing the surrounding landmarks onto simulation computed tomography images of a standard patient. CTVs based on selected SCV atlases, including the one by the Radiation Therapy Oncology Group (RTOG) were contoured. Amore » modified SCV CTV was tried and shown to have better involved-node coverage and thus theoretically improved prophylaxis in this setting. Results: A total of 50 (91%) and 45 (81.8%) patients had LNMs in the medial and lateral SCV subregions, respectively. Also, 36 patients (65.5%) had LNMs located at the junction of the jugular-subclavian veins. All nodes were covered in only 25.5% to 41.8% of patients by different atlases. The RTOG atlas covered all nodes in 25.5% of patients. Stratified by the nodes in all the patients as a whole, 49.2% to 81.3% were covered, and the RTOG atlas covered 62.6%. The lateral and posterior borders were the most overlooked locations. Modification by extending the borders to natural anatomic barriers allowed the new CTV to cover all the nodes in 81.8% of patients and encompass 96.1% of all the nodes. Conclusions: According to the distribution of SCV LNMs, the extent of existing atlases might not be adequate for potential metastatic sites in certain groups of patients. The extension of the lateral and posterior CTV borders in high-risk or recurrent patients might be a reasonable approach for increasing coverage. However, additional data in more homogeneous populations with localized disease are needed before routine application.« less

Acute skin toxicity associated with a 1-week schedule of whole breast radiotherapy compared with a standard 3-week regimen delivered in the UK FAST-Forward Trial.

PubMed

Brunt, A Murray; Wheatley, Duncan; Yarnold, John; Somaiah, Navita; Kelly, Stephen; Harnett, Adrian; Coles, Charlotte; Goodman, Andrew; Bahl, Amit; Churn, Mark; Zotova, Rada; Sydenham, Mark; Griffin, Clare L; Morden, James P; Bliss, Judith M

2016-07-01

FAST-Forward is a phase 3 clinical trial testing a 1-week course of whole breast radiotherapy against the UK standard 3-week regimen after primary surgery for early breast cancer. Two acute skin toxicity substudies were undertaken to test the safety of the test schedules with respect to early skin reactions. Patients were randomly allocated to 40Gy/15 fractions (F)/3-weeks, 27Gy/5F/1-week or 26Gy/5F/1-week. Acute breast skin reactions were graded using RTOG (first substudy) and CTCAE criteria v4.03 (second substudy) weekly during treatment and for 4weeks after treatment ended. Primary endpoint was the proportion of patients within each treatment group with grade ⩾3 toxicity (RTOG and CTCAE, respectively) at any time from the start of radiotherapy to 4weeks after completion. 190 and 162 patients were recruited. In the first substudy, evaluable patients with grade 3 RTOG toxicity were: 40Gy/15F 6/44 (13.6%); 27Gy/5F 5/51 (9.8%); 26Gy/5F 3/52 (5.8%). In the second substudy, evaluable patients with grade 3 CTCAE toxicity were: 40Gy/15F 0/43; 27Gy/5F 1/41 (2.4%); 26Gy/5F 0/53. Acute breast skin reactions with two 1-week schedules of whole breast radiotherapy under test in FAST-Forward were mild. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Localized volume effects for late rectal and anal toxicity after radiotherapy for prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peeters, Stephanie T.H.; Lebesque, Joos V.; Heemsbergen, Wilma D.

2006-03-15

Purpose: To identify dosimetric parameters derived from anorectal, rectal, and anal wall dose distributions that correlate with different late gastrointestinal (GI) complications after three-dimensional conformal radiotherapy for prostate cancer. Methods and Materials: In this analysis, 641 patients from a randomized trial (68 Gy vs. 78 Gy) were included. Toxicity was scored with adapted Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer (RTOG/EORTC) criteria and five specific complications. The variables derived from dose-volume histogram of anorectal, rectal, and anal wall were as follows: % receiving {>=}5-70 Gy (V5-V70), maximum dose (D{sub max}), and mean dose (D{sub mean}).more » The anus was defined as the most caudal 3 cm of the anorectum. Statistics were done with multivariate Cox regression models. Median follow-up was 44 months. Results: Anal dosimetric variables were associated with RTOG/EORTC Grade {>=}2 (V5-V40, D{sub mean}) and incontinence (V5-V70, D{sub mean}). Bleeding correlated most strongly with anorectal V55-V65, and stool frequency with anorectal V40 and D{sub mean}. Use of steroids was weakly related to anal variables. No volume effect was seen for RTOG/EORTC Grade {>=}3 and pain/cramps/tenesmus. Conclusion: Different volume effects were found for various late GI complications. Therefore, to evaluate the risk of late GI toxicity, not only intermediate and high doses to the anorectal wall volume should be taken into account, but also the dose to the anal wall.« less

No Clinically Significant Changes in Pulmonary Function Following Stereotactic Body Radiation Therapy for Early- Stage Peripheral Non-Small Cell Lung Cancer: An Analysis of RTOG 0236

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stanic, Sinisa, E-mail: sinisa.stanic@carle.com; Paulus, Rebecca; Timmerman, Robert D.

2014-04-01

Purpose: To investigate pulmonary function test (PFT) results and arterial blood gas changes (complete PFT) following stereotactic body radiation therapy (SBRT) and to see whether baseline PFT correlates with lung toxicity and overall survival in medically inoperable patients receiving SBRT for early stage, peripheral, non-small cell lung cancer (NSCLC). Methods and Materials: During the 2-year follow-up, PFT data were collected for patients with T1-T2N0M0 peripheral NSCLC who received effectively 18 Gy × 3 in a phase 2 North American multicenter study (Radiation Therapy Oncology Group [RTOG] protocol 0236). Pulmonary toxicity was graded by using the RTOG SBRT pulmonary toxicity scale. Paired Wilcoxon signedmore » rank test, logistic regression model, and Kaplan-Meier method were used for statistical analysis. Results: At 2 years, mean percentage predicted forced expiratory volume in the first second and diffusing capacity for carbon monoxide declines were 5.8% and 6.3%, respectively, with minimal changes in arterial blood gases and no significant decline in oxygen saturation. Baseline PFT was not predictive of any pulmonary toxicity following SBRT. Whole-lung V5 (the percentage of normal lung tissue receiving 5 Gy), V10, V20, and mean dose to the whole lung were almost identical between patients who developed pneumonitis and patients who were pneumonitis-free. Poor baseline PFT did not predict decreased overall survival. Patients with poor baseline PFT as the reason for medical inoperability had higher median and overall survival rates than patients with normal baseline PFT values but with cardiac morbidity. Conclusions: Poor baseline PFT did not appear to predict pulmonary toxicity or decreased overall survival after SBRT in this medically inoperable population. Poor baseline PFT alone should not be used to exclude patients with early stage lung cancer from treatment with SBRT.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Machtay, Mitchell, E-mail: mitchell.machtay@uhhospitals.org; Moughan, Jennifer; Farach, Andrew

Purpose: Concurrent chemoradiation therapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN) increases local tumor control but at the expense of increased toxicity. We recently showed that several clinical/pretreatment factors were associated with the occurrence of severe late toxicity. This study evaluated the potential relationship between radiation dose delivered to the pharyngeal wall and toxicity. Methods and Materials: This was an analysis of long-term survivors from 3 previously reported Radiation Therapy Oncology Group (RTOG) trials of CCRT for locally advanced SCCHN (RTOG trials 91-11, 97-03, and 99-14). Severe late toxicity was defined in this secondary analysis asmore » chronic grade 3-4 pharyngeal/laryngeal toxicity and/or requirement for a feeding tube {>=}2 years after registration and/or potential treatment-related death (eg, pneumonia) within 3 years. Radiation dosimetry (2-dimensional) analysis was performed centrally at RTOG headquarters to estimate doses to 4 regions of interest along the pharyngeal wall (superior oropharynx, inferior oropharynx, superior hypopharynx, and inferior hypopharynx). Case-control analysis was performed with a multivariate logistic regression model that included pretreatment and treatment potential factors. Results: A total of 154 patients were evaluable for this analysis, 71 cases (patients with severe late toxicities) and 83 controls; thus, 46% of evaluable patients had a severe late toxicity. On multivariate analysis, significant variables correlated with the development of severe late toxicity, including older age (odds ratio, 1.062 per year; P=.0021) and radiation dose received by the inferior hypopharynx (odds ratio, 1.023 per Gy; P=.016). The subgroup of patients receiving {<=}60 Gy to the inferior hypopharynx had a 40% rate of severe late toxicity compared with 56% for patients receiving >60 Gy. Oropharyngeal dose was not associated with this outcome. Conclusions: Severe late toxicity following CCRT is common in long-term survivors. Age is the most significant factor, but hypopharyngeal dose also was associated.« less

Successful Treatment of Acute Radiation Proctitis with Aloe Vera: A Preliminary Randomized Controlled Clinical Trial.

PubMed

Sahebnasagh, Adeleh; Ghasemi, Arash; Akbari, Jafar; Alipour, Abbas; Lashkardoost, Hossein; Ala, Shahram; Salehifar, Ebrahim

2017-11-01

Acute radiation proctitis (ARP) is a common side-effect that affects up to 50% of patients receiving radiotherapy. The aim of this study was to evaluate the role of a topical preparation of Aloe vera in the treatment of ARP induced by radiotherapy of pelvic area. In this double-blind placebo-controlled trial, 20 consecutive patients with ARP after external-beam radiation therapy (46-72 Gy) of pelvic malignancies were randomized to receive either Aloe vera 3% or placebo ointment, 1 g twice daily for 4 weeks. These patients presented with at least two of the following symptoms: rectal bleeding, abdominal/rectal pain, diarrhea, or fecal urgency. These symptoms were rated by the patients in terms of their severity (grade 0-4) for each of the symptoms mentioned earlier at baseline and then weekly for 4 weeks. A symptom index was calculated by the addition of the scores (16 most symptomatic). Radiation Therapy Oncology Group (RTOG) acute toxicity criteria and psychosocial status of the patients were also recorded weekly. The lifestyle impact of the symptoms was assessed by questionnaire grading from 0 (no effect on daily activity) to 4 (afraid to leave home). There was a significant (p < 0.05) improvement in the symptom index (before treatment vs. after treatment with Aloe vera) for diarrhea (median score: 0.67 vs. 0.11), fecal urgency (median score: 0.89 vs. 0.11), clinical presentation total (median score: 4.33 vs. 1.22), RTOG total (median score: 2.89 vs. 0.89), and lifestyle (median score: 1.1 vs. 0.33). Hemorrhage and abdominal/rectal pain did not improve significantly. The odds ratios for advantage of Aloe vera over placebo for "clinical presentation total" and "RTOG total" were 3.97 (1.3-11.9) and 5.9 (1.6-21.6), respectively. A substantial number of patients with radiation proctitis seem to benefit from therapy with Aloe vera 3% ointment.

A randomized placebo-controlled trial of manuka honey for radiation-induced oral mucositis.

PubMed

Hawley, Philippa; Hovan, Allan; McGahan, Colleen E; Saunders, Deborah

2014-03-01

Few treatments have the potential to reduce the severity of radiation-induced mucositis in head and neck cancer patients. Some small studies have suggested that organic honey may be a useful preventive treatment. This investigator-initiated double-blind randomized placebo-controlled trial investigated whether honey reduced the severity of radiation-induced oral mucositis (ROM). One hundred six head and neck cancer patients from the Vancouver and Sudbury Cancer Centers in Canada were randomized to swish, hold, and swallow either 5 ml of irradiated organic manuka honey or a placebo gel, four times a day throughout radiation treatment, plus seven more days. Severity of oral mucositis according to the Radiation Therapy Oncology Group (RTOG), World Health Organization (WHO), and Oral Mucositis Assessment Scale scales, weight, and subjects' symptom severity and quality of life were assessed weekly. Sialometry was performed at baseline and at the last study visit. One hundred six patients were recruited. Twenty-four did not attend any mucositis assessments. One was removed from the study because of off-study consumption of store-bought manuka honey. The remaining 81 patients had at least one mucositis assessment and were included in the analysis. Sixty-two percent of subjects received concurrent chemotherapy; 81 % were male. The groups were well-matched, and blinding was excellent. Dropouts were mostly due to nausea and were similar in both arms, with 78 % being able to tolerate the study products for more than 1 week. The dropout rate was 57 % in those who received honey and 52 % in those who received placebo gel. The dropout rate in those who had concurrent chemotherapy was 59 % and in those who only received radiation was 47 %. There was no statistically significant difference between the honey and placebo arms in any of the outcome indicators. Those who completed the study in both treatment arms had low rates of RTOG greater than or equal to grade 3 mucositis; 35 % in the honey group and 43 % in the placebo group. Despite promising earlier reports, manuka honey was not tolerated well by our patients and, even when used as directed, did not have a significant impact on the severity of ROM.

No differences between Calendula cream and aqueous cream in the prevention of acute radiation skin reactions--results from a randomised blinded trial.

PubMed

Sharp, Lena; Finnilä, Kristina; Johansson, Hemming; Abrahamsson, Marie; Hatschek, Thomas; Bergenmar, Mia

2013-08-01

The purpose of this blinded, randomized clinical trial was to compare two topical agents (Calendula Weleda cream vs. Essex cream) in reducing the risk of severe acute radiation skin reactions (ARSR) in relation to adjuvant radiotherapy (RT) for breast cancer. The primary endpoint was the difference in proportion of patients with ARSR, assessed with the Radiation Therapy Oncology Group/The Organization for Research and Treatment of Cancer Acute Radiation Morbidity Scoring Criteria (RTOG/EORTC scale) at follow-up. The secondary endpoints included patient reported outcome measures; Quality of Life Questionnaire (QLQ-C30), Sleep disturbances (MOS-sleep questionnaire) and symptoms from the irradiated area (visual analogue scale). Patients' experiences and adherence to the topical agents were also evaluated. A total of 420 patients were randomised and 411 were analysed. With the exception of previous chemotherapy, the treatment groups were well balanced, both regarding treatment- and patient-related factors. The incidence of severe ARSR (RTOG/EORTC grade ≤2) at the follow-up visit was 23% (n = 45) in the Calendula group and 19% (n = 38) in the Essex group. We found no difference in severe ARSR between the groups at any point of assessment. The patients reported low levels of skin related symptoms and no statistically significant differences between the groups were found. No differences in ARSR between patients randomised to Calendula or Essex cream was found. ARSR seem to be a relatively limited problem, probably more influenced by treatment related factors than by choice of skin care products in this patient group. Copyright © 2012 Elsevier Ltd. All rights reserved.

Feasibility of Patient Reporting of Symptomatic Adverse Events via the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in a Chemoradiotherapy Cooperative Group Multicenter Clinical Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Basch, Ethan, E-mail: ebasch@med.unc.edu; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; Pugh, Stephanie L.

Purpose: To assess the feasibility of measuring symptomatic adverse events (AEs) in a multicenter clinical trial using the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Methods and Materials: Patients enrolled in NRG Oncology's RTOG 1012 (Prophylactic Manuka Honey for Reduction of Chemoradiation Induced Esophagitis-Related Pain during Treatment of Lung Cancer) were asked to self-report 53 PRO-CTCAE items representing 30 symptomatic AEs at 6 time points (baseline; weekly ×4 during treatment; 12 weeks after treatment). Reporting was conducted via wireless tablet computers in clinic waiting areas. Compliance was defined as the proportion of visitsmore » when an expected PRO-CTCAE assessment was completed. Results: Among 226 study sites participating in RTOG 1012, 100% completed 35-minute PRO-CTCAE training for clinical research associates (CRAs); 80 sites enrolled patients, of which 34 (43%) required tablet computers to be provided. All 152 patients in RTOG 1012 agreed to self-report using the PRO-CTCAE (median age 66 years; 47% female; 84% white). Median time for CRAs to learn the system was 60 minutes (range, 30-240 minutes), and median time for CRAs to teach a patient to self-report was 10 minutes (range, 2-60 minutes). Compliance was high, particularly during active treatment, when patients self-reported at 86% of expected time points, although compliance was lower after treatment (72%). Common reasons for noncompliance were institutional errors, such as forgetting to provide computers to participants; patients missing clinic visits; Internet connectivity; and patients feeling “too sick.” Conclusions: Most patients enrolled in a multicenter chemoradiotherapy trial were willing and able to self-report symptomatic AEs at visits using tablet computers. Minimal effort was required by local site staff to support this system. The observed causes of missing data may be obviated by allowing patients to self-report electronically between visits, and by using central compliance monitoring. These approaches are being incorporated into ongoing studies.« less

Feasibility of Patient Reporting of Symptomatic Adverse Events via the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in a Chemoradiotherapy Cooperative Group Multicenter Clinical Trial.

PubMed

Basch, Ethan; Pugh, Stephanie L; Dueck, Amylou C; Mitchell, Sandra A; Berk, Lawrence; Fogh, Shannon; Rogak, Lauren J; Gatewood, Marcha; Reeve, Bryce B; Mendoza, Tito R; O'Mara, Ann M; Denicoff, Andrea M; Minasian, Lori M; Bennett, Antonia V; Setser, Ann; Schrag, Deborah; Roof, Kevin; Moore, Joan K; Gergel, Thomas; Stephans, Kevin; Rimner, Andreas; DeNittis, Albert; Bruner, Deborah Watkins

2017-06-01

To assess the feasibility of measuring symptomatic adverse events (AEs) in a multicenter clinical trial using the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Patients enrolled in NRG Oncology's RTOG 1012 (Prophylactic Manuka Honey for Reduction of Chemoradiation Induced Esophagitis-Related Pain during Treatment of Lung Cancer) were asked to self-report 53 PRO-CTCAE items representing 30 symptomatic AEs at 6 time points (baseline; weekly ×4 during treatment; 12 weeks after treatment). Reporting was conducted via wireless tablet computers in clinic waiting areas. Compliance was defined as the proportion of visits when an expected PRO-CTCAE assessment was completed. Among 226 study sites participating in RTOG 1012, 100% completed 35-minute PRO-CTCAE training for clinical research associates (CRAs); 80 sites enrolled patients, of which 34 (43%) required tablet computers to be provided. All 152 patients in RTOG 1012 agreed to self-report using the PRO-CTCAE (median age 66 years; 47% female; 84% white). Median time for CRAs to learn the system was 60 minutes (range, 30-240 minutes), and median time for CRAs to teach a patient to self-report was 10 minutes (range, 2-60 minutes). Compliance was high, particularly during active treatment, when patients self-reported at 86% of expected time points, although compliance was lower after treatment (72%). Common reasons for noncompliance were institutional errors, such as forgetting to provide computers to participants; patients missing clinic visits; Internet connectivity; and patients feeling "too sick." Most patients enrolled in a multicenter chemoradiotherapy trial were willing and able to self-report symptomatic AEs at visits using tablet computers. Minimal effort was required by local site staff to support this system. The observed causes of missing data may be obviated by allowing patients to self-report electronically between visits, and by using central compliance monitoring. These approaches are being incorporated into ongoing studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Three-dimensional conformal radiation therapy for squamous cell carcinoma of the esophagus: a prospective phase I/II study.

PubMed

Wu, Kai-Liang; Chen, Guei-Yuan; Xu, Zhi-Yong; Fu, Xiao-Long; Qian, Hao; Jiang, Guo-Liang

2009-12-01

A prospective phase I-II study was conducted to determine the tolerance and local control rate of three-dimensional conformal radiotherapy (3-DCRT) for esophageal squamous cell carcinoma (SCC). Thirty patients underwent 3-DCRT for thoracic esophageal SCC. PTV1 composed of a 1.2-1.5 cm margin lateral around GTV and 3.0 cm margin superior/inferior of GTV. PTV2 encompassed GTV with a margin of 0.5-0.7 cm. The dose for PTV1 was 50 Gy in 2 Gy daily fractions; PTV2 received a boost of 16 Gy in 2 Gy daily fractions to a total dose of 66 Gy. Median follow-up time was 18 months. The most common acute toxicity was esophagitis in 63% of patients with RTOG grades 1-2, and in 3% with grade 3. RTOG grades 1-2 radiation pneumonitis developed in 27% of patients. One patient developed pulmonary fibrosis RTOG grade 2 and another patient experienced grade 3 pulmonary fibrosis. Two patients developed mild esophageal stricture requiring dilatation. Two-year overall survival, local disease progression-free rate, and distant metastasis-free rate were 69%, 36% and 56%, respectively. Although 3-DCRT to 66 Gy for esophageal SCC was well tolerated, the local control was disappointing. The result supports the use of chemoradiation as the standard care for esophageal SCC.

Cartographic Mapping and Travel Burden to Assess and Develop Strategies to Improve Minority Access to National Cancer Clinical Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bruner, Deborah Watkins, E-mail: deborah.w.bruner@emory.edu; Pugh, Stephanie L.; Yeager, Katherine A.

Purpose: To assess how accrual to clinical trials is related to US minority population density relative to clinical trial site location and distance traveled to Radiation Therapy Oncology Group (RTOG) clinical trial sites. Methods and Materials: Data included member site address and ZIP codes, patient accrual, and patient race or ethnicity and ZIP code. Geographic Information System maps were developed for overall, Latino, and African American accrual to trials by population density. The Kruskal-Wallis test was used to assess differences in distance traveled by site, type of trial, and race or ethnicity. Results: From 2006 to 2009, 6168 patients enrolledmore » on RTOG trials. The RTOG US site distribution is generally concordant with overall population density. Sites with highest accrual are located throughout the United States and parts of Canada and do not cluster, nor does highest minority accrual cluster in areas of highest US minority population density. Of the 4913 US patients with complete data, patients traveled a median of 11.6 miles to participate in clinical trials. Whites traveled statistically longer distances (12.9 miles; P<.0001) to participate, followed by Latinos (8.22 miles) and African Americans (5.85 miles). Patients were willing to drive longer distances to academic sites than community sites, and there was a trend toward significantly longer median travel for therapeutic versus cancer control or metastatic trials. Conclusions: Location matters, but only to a degree, for minority compared with nonminority participation in clinical trials. Geographic Information System tools help identify gaps in geographic access and travel burden for clinical trials participation. Strategies that emerged using these tools are discussed.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hong, Linda X., E-mail: lhong0812@gmail.com; Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY; Shankar, Viswanathan

We report our experience of establishing planning objectives to achieve dose coverage, conformity, and dose falloff for spine stereotactic body radiation therapy (SBRT) plans. Patients with spine lesions were treated using SBRT in our institution since September 2009. Since September 2011, we established the following planning objectives for our SBRT spine plans in addition to the cord dose constraints: (1) dose coverage—prescription dose (PD) to cover at least 95% planning target volume (PTV) and 90% PD to cover at least 99% PTV; (2) conformity index (CI)—ratio of prescription isodose volume (PIV) to the PTV < 1.2; (3) dose falloff—ratio ofmore » 50% PIV to the PTV (R{sub 50%}); (4) and maximum dose in percentage of PD at 2 cm from PTV in any direction (D{sub 2cm}) to follow Radiation Therapy Oncology Group (RTOG) 0915. We have retrospectively reviewed 66 separate spine lesions treated between September 2009 and December 2012 (31 treated before September 2011 [group 1] and 35 treated after [group 2]). The χ{sup 2} test was used to examine the difference in parameters between groups. The PTV V{sub 100%} {sub PD} ≥ 95% objective was met in 29.0% of group 1 vs 91.4% of group 2 (p < 0.01) plans. The PTV V{sub 90%} {sub PD} ≥ 99% objective was met in 38.7% of group 1 vs 88.6% of group 2 (p < 0.01) plans. Overall, 4 plans in group 1 had CI > 1.2 vs none in group 2 (p = 0.04). For D{sub 2cm}, 48.3% plans yielded a minor violation of the objectives and 16.1% a major violation for group 1, whereas 17.1% exhibited a minor violation and 2.9% a major violation for group 2 (p < 0.01). Spine SBRT plans can be improved on dose coverage, conformity, and dose falloff employing a combination of RTOG spine and lung SBRT protocol planning objectives.« less

Transformation of Physical DVHs to Radiobiologically Equivalent Ones in Hypofractionated Radiotherapy Analyzing Dosimetric and Clinical Parameters: A Practical Approach for Routine Clinical Practice in Radiation Oncology

PubMed Central

Thrapsanioti, Zoi; Karanasiou, Irene; Platoni, Kalliopi; Efstathopoulos, Efstathios P.; Matsopoulos, George; Dilvoi, Maria; Patatoukas, George; Chaldeopoulos, Demetrios; Kelekis, Nikolaos; Kouloulias, Vassilis

2013-01-01

Purpose. The purpose of this study was to transform DVHs from physical to radiobiological ones as well as to evaluate their reliability by correlations of dosimetric and clinical parameters for 50 patients with prostate cancer and 50 patients with breast cancer, who were submitted to Hypofractionated Radiotherapy. Methods and Materials. To achieve this transformation, we used both the linear-quadratic model (LQ model) and the Niemierko model. The outcome of radiobiological DVHs was correlated with acute toxicity score according to EORTC/RTOG criteria. Results. Concerning the prostate radiotherapy, there was a significant correlation between RTOG acute rectal toxicity and D 50 (P < 0.001) and V 60 (P = 0.001) dosimetric parameters, calculated for α/β = 10 Gy. Moreover, concerning the breast radiotherapy there was a significant correlation between RTOG skin toxicity and V ≥60 dosimetric parameter, calculated for both α/β = 2.3 Gy (P < 0.001) and α/β = 10 Gy (P < 0.001). The new tool seems reliable and user-friendly. Conclusions. Our proposed model seems user-friendly. Its reliability in terms of agreement with the presented acute radiation induced toxicity was satisfactory. However, more patients are needed to extract safe conclusions. PMID:24348743

Acupuncture-Like Transcutaneous Electrical Nerve Stimulation Versus Pilocarpine in Treating Radiation-Induced Xerostomia: Results of RTOG 0537 Phase 3 Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wong, Raimond K.W., E-mail: wongrai@hhsc.ca; Deshmukh, Snehal; Wyatt, Gwen

Purpose and Objectives: This report presents the analysis of the RTOG 0537 multicenter randomized study that compared acupuncture-like transcutaneous stimulation (ALTENS) with pilocarpine (PC) for relieving radiation-induced xerostomia. Methods and Materials: Eligible patients were randomized to twice-weekly 20-minute ALTENS sessions for 24 sessions during 12 weeks or PC (5 mg 3 times daily for 12 weeks). The primary endpoint was the change in the University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS) scores from baseline to 9 months from randomization (MFR). Secondary endpoints included basal and citric acid primed whole salivary production (WSP), ratios of positive responders (defined as patients with ≥20% reductionmore » in overall radiation-induced xerostomia symptom burden), and the presence of adverse events based on the Common Terminology Criteria for Adverse Events version 3. An intention-to-treat analysis was conducted. Results: One hundred forty-eight patients were randomized. Only 96 patients completed the required XeQOLS and were evaluable at 9 MFR (representing merely 68.6% statistical power). Seventy-six patients were evaluable at 15 MFR. The median change in the overall XeQOLS in ALTENS and PC groups at 9 and 15 MFR were −0.53 and −0.27 (P=.45) and −0.6 and −0.47 (P=.21). The corresponding percentages of positive responders were 81% and 72% (P=.34) and 83% and 63% (P=.04). Changes in WSP were not significantly different between the groups. Grade 3 or less adverse events, mostly consisting of grade 1, developed in 20.8% of patients in the ALTENS group and in 61.6% of the PC group. Conclusions: The observed effect size was smaller than hypothesized, and statistical power was limited because only 96 of the recruited 148 patients were evaluable. The primary endpoint—the change in radiation-induced xerostomia symptom burden at 9 MFR—was not significantly different between the ALTENS and PC groups. There was significantly less toxicity in patients receiving ALTENS.« less

Acupuncture-Like Transcutaneous Electrical Nerve Stimulation Versus Pilocarpine in Treating Radiation-Induced Xerostomia: Results of RTOG 0537 Phase 3 Study.

PubMed

Wong, Raimond K W; Deshmukh, Snehal; Wyatt, Gwen; Sagar, Stephen; Singh, Anurag K; Sultanem, Khalil; Nguyen-Tân, Phuc F; Yom, Sue S; Cardinale, Joseph; Yao, Min; Hodson, Ian; Matthiesen, Chance L; Suh, John; Thakrar, Harish; Pugh, Stephanie L; Berk, Lawrence

2015-06-01

This report presents the analysis of the RTOG 0537 multicenter randomized study that compared acupuncture-like transcutaneous stimulation (ALTENS) with pilocarpine (PC) for relieving radiation-induced xerostomia. Eligible patients were randomized to twice-weekly 20-minute ALTENS sessions for 24 sessions during 12 weeks or PC (5 mg 3 times daily for 12 weeks). The primary endpoint was the change in the University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS) scores from baseline to 9 months from randomization (MFR). Secondary endpoints included basal and citric acid primed whole salivary production (WSP), ratios of positive responders (defined as patients with ≥20% reduction in overall radiation-induced xerostomia symptom burden), and the presence of adverse events based on the Common Terminology Criteria for Adverse Events version 3. An intention-to-treat analysis was conducted. One hundred forty-eight patients were randomized. Only 96 patients completed the required XeQOLS and were evaluable at 9 MFR (representing merely 68.6% statistical power). Seventy-six patients were evaluable at 15 MFR. The median change in the overall XeQOLS in ALTENS and PC groups at 9 and 15 MFR were -0.53 and -0.27 (P=.45) and -0.6 and -0.47 (P=.21). The corresponding percentages of positive responders were 81% and 72% (P=.34) and 83% and 63% (P=.04). Changes in WSP were not significantly different between the groups. Grade 3 or less adverse events, mostly consisting of grade 1, developed in 20.8% of patients in the ALTENS group and in 61.6% of the PC group. The observed effect size was smaller than hypothesized, and statistical power was limited because only 96 of the recruited 148 patients were evaluable. The primary endpoint-the change in radiation-induced xerostomia symptom burden at 9 MFR-was not significantly different between the ALTENS and PC groups. There was significantly less toxicity in patients receiving ALTENS. Copyright © 2015 Elsevier Inc. All rights reserved.

Quantifying Unnecessary Normal Tissue Complication Risks due to Suboptimal Planning: A Secondary Study of RTOG 0126.

PubMed

Moore, Kevin L; Schmidt, Rachel; Moiseenko, Vitali; Olsen, Lindsey A; Tan, Jun; Xiao, Ying; Galvin, James; Pugh, Stephanie; Seider, Michael J; Dicker, Adam P; Bosch, Walter; Michalski, Jeff; Mutic, Sasa

2015-06-01

The purpose of this study was to quantify the frequency and clinical severity of quality deficiencies in intensity modulated radiation therapy (IMRT) planning in the Radiation Therapy Oncology Group 0126 protocol. A total of 219 IMRT patients from the high-dose arm (79.2 Gy) of RTOG 0126 were analyzed. To quantify plan quality, we used established knowledge-based methods for patient-specific dose-volume histogram (DVH) prediction of organs at risk and a Lyman-Kutcher-Burman (LKB) model for grade ≥2 rectal complications to convert DVHs into normal tissue complication probabilities (NTCPs). The LKB model was validated by fitting dose-response parameters relative to observed toxicities. The 90th percentile (22 of 219) of plans with the lowest excess risk (difference between clinical and model-predicted NTCP) were used to create a model for the presumed best practices in the protocol (pDVH0126,top10%). Applying the resultant model to the entire sample enabled comparisons between DVHs that patients could have received to DVHs they actually received. Excess risk quantified the clinical impact of suboptimal planning. Accuracy of pDVH predictions was validated by replanning 30 of 219 patients (13.7%), including equal numbers of presumed "high-quality," "low-quality," and randomly sampled plans. NTCP-predicted toxicities were compared to adverse events on protocol. Existing models showed that bladder-sparing variations were less prevalent than rectum quality variations and that increased rectal sparing was not correlated with target metrics (dose received by 98% and 2% of the PTV, respectively). Observed toxicities were consistent with current LKB parameters. Converting DVH and pDVH0126,top10% to rectal NTCPs, we observed 94 of 219 patients (42.9%) with ≥5% excess risk, 20 of 219 patients (9.1%) with ≥10% excess risk, and 2 of 219 patients (0.9%) with ≥15% excess risk. Replanning demonstrated the predicted NTCP reductions while maintaining the volume of the PTV receiving prescription dose. An equivalent sample of high-quality plans showed fewer toxicities than low-quality plans, 6 of 73 versus 10 of 73 respectively, although these differences were not significant (P=.21) due to insufficient statistical power in this retrospective study. Plan quality deficiencies in RTOG 0126 exposed patients to substantial excess risk for rectal complications. Copyright © 2015 Elsevier Inc. All rights reserved.

Phase 2 Study of Temozolomide-Based Chemoradiation Therapy for High-Risk Low-Grade Gliomas: Preliminary Results of Radiation Therapy Oncology Group 0424

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fisher, Barbara J., E-mail: barbara.fisher@lhsc.on.ca; Hu, Chen; Macdonald, David R.

2015-03-01

Purpose: Radiation Therapy Oncology Group (RTOG) 0424 was a phase 2 study of a high-risk low-grade glioma (LGG) population who were treated with temozolomide (TMZ) and radiation therapy (RT), and outcomes were compared to those of historical controls. This study was designed to detect a 43% increase in median survival time (MST) from 40.5 to 57.9 months and a 20% improvement in 3-year overall survival (OS) rate from 54% to 65% at a 10% significance level (1-sided) and 96% power. Methods and Materials: Patients with LGGs with 3 or more risk factors for recurrence (age ≥40 years, astrocytoma histology, bihemispherical tumor, preoperativemore » tumor diameter of ≥6 cm, or a preoperative neurological function status of >1) were treated with RT (54 Gy in 30 fractions) and concurrent and adjuvant TMZ. Results: From 2005 to 2009, 129 evaluable patients (75 males and 54 females) were accrued. Median age was 49 years; 91% had a Zubrod score of 0 or 1; and 69%, 25%, and 6% of patients had 3, 4, and 5 risk factors, respectively. Patients had median and minimum follow-up examinations of 4.1 years and 3 years, respectively. The 3-year OS rate was 73.1% (95% confidence interval: 65.3%-80.8%), which was significantly improved compared to that of prespecified historical control values (P<.001). Median survival time has not yet been reached. Three-year progression-free survival was 59.2%. Grades 3 and 4 adverse events occurred in 43% and 10% of patients, respectively. One patient died of herpes encephalitis. Conclusions: The 3-year OS rate of 73.1% for RTOG 0424 high-risk LGG patients is higher than that reported for historical controls (P<.001) and the study-hypothesized rate of 65%.« less

Is heterogeneity in stage 3 non-small cell lung cancer obscuring the potential benefits of dose-escalated concurrent chemo-radiotherapy in clinical trials?

PubMed

Hudson, Andrew; Chan, Clara; Woolf, David; McWilliam, Alan; Hiley, Crispin; O'Connor, James; Bayman, Neil; Blackhall, Fiona; Faivre-Finn, Corinne

2018-04-01

The current standard of care for the management of inoperable stage 3 non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy (cCRT) using radiotherapy dose-fractionation and chemotherapy regimens that were established 3 decades ago. In an attempt to improve the chances of long-term control from cCRT, dose-escalation of the radiotherapy dose was assessed in the RTOG 0617 randomised control study comparing the standard 60 Gy in 30 fractions with a high-dose arm receiving 74 Gy in 37 fractions. Following the publication of this trial the thoracic oncology community were surprised to learn that there was worse survival in the dose-escalated arm and that for now the standard of care must remain with the lower dose. In this article we review the RTOG 0617 paper with subsequent analyses and studies to explore why the use of dose-escalated cCRT in stage 3 NSCLC has not shown the benefits that were expected. The overarching theme of this opinion piece is how heterogeneity between stage 3 NSCLC cases in terms of patient, tumour, and clinical factors may obscure the potential benefits of dose-escalation by causing imbalances in the arms of studies such as RTOG 0617. We also examine recent advances in the staging, management, and technological delivery of radiotherapy in NSCLC and how these may be employed to optimise cCRT trials in the future and ensure that any potential benefits of dose-escalation can be detected. Copyright © 2018 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gentile, Michelle S.; Usman, Asad A.; Neuschler, Erin I.

Purpose: The purpose of this study was to identify the axillary lymph nodes on pretreatment diagnostic computed tomography (CT) of the chest to determine their position relative to the anatomic axillary borders as defined by the Radiation Therapy Oncology Group (RTOG) breast cancer atlas for radiation therapy planning. Methods and Materials: Pretreatment diagnostic CT chest scans available for 30 breast cancer patients with clinically involved lymph nodes were fused with simulation CT. Contouring of axillary levels I, II, and III according to the RTOG guidelines was performed. Measurements were made from the area of distal tumor to the anatomic bordersmore » in 6 dimensions for each level. Results: Of the 30 patients, 100%, 93%, and 37% had clinical involvement of levels I, II, and III, respectively. The mean number of lymph nodes dissected was 13.6. The mean size of the largest lymph node was 2.4 cm. Extracapsular extension was seen in 23% of patients. In 97% of patients, an aspect of the involved lymph node lay outside of the anatomic border of a level. In 80% and 83% of patients, tumor extension was seen outside the cranial (1.78 ± 1.0 cm; range, 0.28-3.58 cm) and anterior (1.27 ± 0.92 cm; range, 0.24-3.58 cm) borders of level I, respectively. In 80% of patients, tumor extension was seen outside the caudal border of level II (1.36 ± 1.0 cm, range, 0.27-3.86 cm), and 0% to 33% of patients had tumor extension outside the remaining borders of all levels. Conclusions: To cover 95% of lymph nodes at the cranial and anterior borders of level I, an additional clinical target volume margin of 3.78 cm and 3.11 cm, respectively, is necessary. The RTOG guidelines may be insufficient for coverage of axillary disease in patients with clinical nodal involvement who are undergoing neoadjuvant chemotherapy, incomplete axillary dissection, or treatment with intensity modulated radiation therapy. In patients with pretreatment diagnostic CT chest scans, fusion with simulation CT should be considered for tumor delineation.« less

Impact of Intensity-Modulated Radiation Therapy Technique for Locally Advanced Non-Small-Cell Lung Cancer: A Secondary Analysis of the NRG Oncology RTOG 0617 Randomized Clinical Trial.

PubMed

Chun, Stephen G; Hu, Chen; Choy, Hak; Komaki, Ritsuko U; Timmerman, Robert D; Schild, Steven E; Bogart, Jeffrey A; Dobelbower, Michael C; Bosch, Walter; Galvin, James M; Kavadi, Vivek S; Narayan, Samir; Iyengar, Puneeth; Robinson, Clifford G; Wynn, Raymond B; Raben, Adam; Augspurger, Mark E; MacRae, Robert M; Paulus, Rebecca; Bradley, Jeffrey D

2017-01-01

Purpose Although intensity-modulated radiation therapy (IMRT) is increasingly used to treat locally advanced non-small-cell lung cancer (NSCLC), IMRT and three-dimensional conformal external beam radiation therapy (3D-CRT) have not been compared prospectively. This study compares 3D-CRT and IMRT outcomes for locally advanced NSCLC in a large prospective clinical trial. Patients and Methods A secondary analysis was performed to compare IMRT with 3D-CRT in NRG Oncology clinical trial RTOG 0617, in which patients received concurrent chemotherapy of carboplatin and paclitaxel with or without cetuximab, and 60- versus 74-Gy radiation doses. Comparisons included 2-year overall survival (OS), progression-free survival, local failure, distant metastasis, and selected Common Terminology Criteria for Adverse Events (version 3) ≥ grade 3 toxicities. Results The median follow-up was 21.3 months. Of 482 patients, 53% were treated with 3D-CRT and 47% with IMRT. The IMRT group had larger planning treatment volumes (median, 427 v 486 mL; P = .005); a larger planning treatment volume/volume of lung ratio (median, 0.13 v 0.15; P = .013); and more stage IIIB disease (30.3% v 38.6%, P = .056). Two-year OS, progression-free survival, local failure, and distant metastasis-free survival were not different between IMRT and 3D-CRT. IMRT was associated with less ≥ grade 3 pneumonitis (7.9% v 3.5%, P = .039) and a reduced risk in adjusted analyses (odds ratio, 0.41; 95% CI, 0.171 to 0.986; P = .046). IMRT also produced lower heart doses ( P < .05), and the volume of heart receiving 40 Gy (V40) was significantly associated with OS on adjusted analysis ( P < .05). The lung V5 was not associated with any ≥ grade 3 toxicity, whereas the lung V20 was associated with increased ≥ grade 3 pneumonitis risk on multivariable analysis ( P = .026). Conclusion IMRT was associated with lower rates of severe pneumonitis and cardiac doses in NRG Oncology clinical trial RTOG 0617, which supports routine use of IMRT for locally advanced NSCLC.

Changes in skin microcirculation during radiation therapy for breast cancer.

PubMed

Tesselaar, Erik; Flejmer, Anna M; Farnebo, Simon; Dasu, Alexandru

2017-08-01

The majority of breast cancer patients who receive radiation treatment are affected by acute radiation-induced skin changes. The assessment of these changes is usually done by subjective methods, which complicates the comparison between different treatments or patient groups. This study investigates the feasibility of new robust methods for monitoring skin microcirculation to objectively assess and quantify acute skin reactions during radiation treatment. Laser Doppler flowmetry, laser speckle contrast imaging, and polarized light spectroscopy imaging were used to measure radiation-induced changes in microvascular perfusion and red blood cell concentration (RBC) in the skin of 15 patients undergoing adjuvant radiation therapy for breast cancer. Measurements were made before treatment, once a week during treatment, and directly after the last fraction. In the treated breast, perfusion and RBC concentration were increased after 1-5 fractions (2.66-13.3 Gy) compared to baseline. The largest effects were seen in the areola and the medial area. No changes in perfusion and RBC concentration were seen in the untreated breast. In contrast, Radiation Therapy Oncology Group (RTOG) scores were increased only after 2 weeks of treatment, which demonstrates the potential of the proposed methods for early assessment of skin changes. Also, there was a moderate to good correlation between the perfusion (r = 0.52) and RBC concentration (r = 0.59) and the RTOG score given a week later. We conclude that radiation-induced microvascular changes in the skin can be objectively measured using novel camera-based techniques before visual changes in the skin are apparent. Objective measurement of microvascular changes in the skin may be valuable in the comparison of skin reactions between different radiation treatments and possibly in predicting acute skin effects at an earlier stage.

Comparison of toxicity associated with early morning versus late afternoon radiotherapy in patients with head-and-neck cancer: a prospective randomized trial of the National Cancer Institute of Canada Clinical Trials Group (HN3).

PubMed

Bjarnason, Georg A; Mackenzie, Robert G; Nabid, Abdenour; Hodson, Ian D; El-Sayed, Samy; Grimard, Laval; Brundage, Michael; Wright, James; Hay, John; Ganguly, Pradip; Leong, Carson; Wilson, Jane; Jordan, Richard C K; Walker, Melanie; Tu, Dongsheng; Parulekar, Wendy

2009-01-01

Based on our demonstration of a circadian rhythm in the human oral mucosa cell cycle, with most cells in the G(1) phase in the morning and M phase at night, we hypothesized that morning radiotherapy (RT) would lead to less oral mucositis than afternoon RT. A total of 216 patients were randomized to morning (8-10 AM) vs. afternoon (4-6 PM) RT and stratified by radiation dose, smoking status, and center. Patients receiving primary or postoperative RT alone were eligible. Oral mucositis was scored using the Radiation Therapy Oncology Group (RTOG) criteria and a validated scoring system. Of 205 evaluable patients, 52.9% vs. 62.4% developed RTOG Grade 3 or greater mucositis after morning vs. afternoon RT, respectively (p = 0.17). Morning RT was also associated with significantly less weight loss after 5 months (p = 0.024). In a subgroup of 111 patients treated to a dose of 66-70 Gy in 33-35 fractions, exploratory analyses revealed a significant reduction in Grade 3 or greater mucositis with morning RT (44.6% vs. 67.3%, p = 0.022) and a longer interval to the development of Grade 3 or greater mucositis (median, >7.9 vs. 5.6 weeks, p = 0.033). In 53 patients, who smoked during therapy, a significant reduction was found in Grade 3 or greater mucositis with morning RT (42.9% vs. 76%, p = 0.025). In this proof of principle study, morning RT was associated with significantly less weight loss after 5 months and an apparent reduction in oral mucositis in a subset of patients receiving >/=66 Gy and in patients who smoked during therapy.

Late effect of multiple daily fraction palliation schedule for advanced pelvic malignancies (RTOG 8502)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spanos, W.J. Jr.; Clery, M.; Perez, C.A.

1994-07-30

The purpose was to determine late complication incidence for pelvic palliation using accelerated multiple daily fraction radiation [Radiation Therapy Oncology Group (RTOG) 8502]. None of the patients with < 30 Gy (less than three courses) developed late toxicity. A total of 11/193 (6%) developed Grade 3+ late toxicity (nine Grade 3, on Grade 4, one Grade 5). Actuarial analysis of complication rate by survival time for Grades 3, 4, and 5 shows a cumulative incidence for complications after 6 months that plateaus at 6.9% by 18 months. The cumulative incidence for Grades 4 and 5 is 2.0% by 12 months.more » The difference in late effect for the 2-week rest vs. 4-week rest was not statistically different (p = .47). Patient factors evaluated for increased risk of late complications included prior surgeries, age, sex, KPS and primary. None were found to have significant statistical correlations with late effects. The crude late complications rate is 6%. Actuarial analysis using cumulative incidence shows 6.9% by 18 months. This represents a significant decrease in late complications from 49% seen with higher dose per fraction (10 Gy {times} 3) piloted by Radiation Therapy Oncology Group (7905) for a similar group of patients. Long-term analysis of late complication indicates this schedule can be used in the pelvis with relatively low incidence of complication. This schedule has significant logistic benefits and has been shown to produce good tumor regression and excellent palliation of symptoms. 14 refs., 4 figs., 4 tabs.« less

Modeling the Risk of Radiation-Induced Acute Esophagitis for Combined Washington University and RTOG Trial 93-11 Lung Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Ellen X.; Bradley, Jeffrey D.; El Naqa, Issam

2012-04-01

Purpose: To construct a maximally predictive model of the risk of severe acute esophagitis (AE) for patients who receive definitive radiation therapy (RT) for non-small-cell lung cancer. Methods and Materials: The dataset includes Washington University and RTOG 93-11 clinical trial data (events/patients: 120/374, WUSTL = 101/237, RTOG9311 = 19/137). Statistical model building was performed based on dosimetric and clinical parameters (patient age, sex, weight loss, pretreatment chemotherapy, concurrent chemotherapy, fraction size). A wide range of dose-volume parameters were extracted from dearchived treatment plans, including Dx, Vx, MOHx (mean of hottest x% volume), MOCx (mean of coldest x% volume), and gEUDmore » (generalized equivalent uniform dose) values. Results: The most significant single parameters for predicting acute esophagitis (RTOG Grade 2 or greater) were MOH85, mean esophagus dose (MED), and V30. A superior-inferior weighted dose-center position was derived but not found to be significant. Fraction size was found to be significant on univariate logistic analysis (Spearman R = 0.421, p < 0.00001) but not multivariate logistic modeling. Cross-validation model building was used to determine that an optimal model size needed only two parameters (MOH85 and concurrent chemotherapy, robustly selected on bootstrap model-rebuilding). Mean esophagus dose (MED) is preferred instead of MOH85, as it gives nearly the same statistical performance and is easier to compute. AE risk is given as a logistic function of (0.0688 Asterisk-Operator MED+1.50 Asterisk-Operator ConChemo-3.13), where MED is in Gy and ConChemo is either 1 (yes) if concurrent chemotherapy was given, or 0 (no). This model correlates to the observed risk of AE with a Spearman coefficient of 0.629 (p < 0.000001). Conclusions: Multivariate statistical model building with cross-validation suggests that a two-variable logistic model based on mean dose and the use of concurrent chemotherapy robustly predicts acute esophagitis risk in combined-data WUSTL and RTOG 93-11 trial datasets.« less

A planning comparison of 7 irradiation options allowed in RTOG 1005 for early-stage breast cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Guang-Pei, E-mail: gpchen@mcw.edu; Liu, Feng; White, Julia

2015-04-01

This study compared the 7 treatment plan options in achieving the dose-volume criteria required by the Radiation Therapy Oncology Group (RTOG) 1005 protocol. Dosimetry plans were generated for 15 representative patients with early-stage breast cancer (ESBC) based on the protocol-required dose-volume criteria for each of the following 7 treatment options: 3D conformal radiotherapy (3DCRT), whole-breast irradiation (WBI) plus 3DCRT lumpectomy boost, 3DCRT WBI plus electron boost, 3DCRT WBI plus intensity-modulated radiation therapy (IMRT) boost, IMRT WBI plus 3DCRT boost, IMRT WBI plus electron boost, IMRT WBI plus IMRT boost, and simultaneous integrated boost (SIB) with IMRT. A variety of dose-volumemore » parameters, including target dose conformity and uniformity and normal tissue sparing, were compared for these plans. For the patients studied, all plans met the required acceptable dose-volume criteria, with most of them meeting the ideal criteria. When averaged over patients, most dose-volume goals for all plan options can be achieved with a positive gap of at least a few tenths of standard deviations. The plans for all 7 options are generally comparable. The dose-volume goals required by the protocol can in general be easily achieved. IMRT WBI provides better whole-breast dose uniformity than 3DCRT WBI does, but it causes no significant difference for the dose conformity. All plan options are comparable for lumpectomy dose uniformity and conformity. Patient anatomy is always an important factor when whole-breast dose uniformity and conformity and lumpectomy dose conformity are considered.« less

Five-year follow-up using a prostate stent as fiducial in image-guided radiotherapy of prostate cancer.

PubMed

Carl, Jesper; Sander, Lotte

2015-06-01

To report results from the five-year follow-up on a previously reported study using image-guided radiotherapy (IGRT) of localized or locally advanced prostate cancer (PC) and a removable prostate stent as fiducial. Patients with local or locally advanced PC were treated using five-field 3D conformal radiotherapy (3DRT). The clinical target volumes (CTV) were treated to 78 Gy in 39 fractions using daily on-line image guidance (IG). Late genito-urinary (GU) and gastro-intestinal (GI) toxicities were scored using the radiotherapy oncology group (RTOG) score and the common toxicity score of adverse events (CTC) score. Urinary symptoms were also scored using the international prostate symptom score (IPSS). Median observation time was 5.4 year. Sixty-two of the 90 patients from the original study cohort were eligible for toxicity assessment. Overall survival, cancer-specific survival and biochemical freedom from failure were 85%, 96% and 80%, respectively at five years after radiotherapy. Late toxicity GU and GI RTOG scores≥2 were 5% and 0%. Comparing pre- and post-radiotherapy IPSS scores indicate that development in urinary symptoms after radiotherapy may be complex. Prostate image-guided radiotherapy using a prostate stent demonstrated survival data comparable with recently published data. GU and GI toxicities at five-year follow-up were low and comparable to the lowest toxicity rates reported. These findings support that the precision of the prostate stent technique is at least as good as other techniques. IPSS revealed a complex development in urinary symptoms after radiotherapy.

Functional Interference Clusters in Cancer Patients With Bone Metastases: A Secondary Analysis of RTOG 9714

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chow, Edward, E-mail: Edward.Chow@sunnybrook.c; James, Jennifer; Barsevick, Andrea

Purpose: To explore the relationships (clusters) among the functional interference items in the Brief Pain Inventory (BPI) in patients with bone metastases. Methods: Patients enrolled in the Radiation Therapy Oncology Group (RTOG) 9714 bone metastases study were eligible. Patients were assessed at baseline and 4, 8, and 12 weeks after randomization for the palliative radiotherapy with the BPI, which consists of seven functional items: general activity, mood, walking ability, normal work, relations with others, sleep, and enjoyment of life. Principal component analysis with varimax rotation was used to determine the clusters between the functional items at baseline and the follow-up.more » Cronbach's alpha was used to determine the consistency and reliability of each cluster at baseline and follow-up. Results: There were 448 male and 461 female patients, with a median age of 67 years. There were two functional interference clusters at baseline, which accounted for 71% of the total variance. The first cluster (physical interference) included normal work and walking ability, which accounted for 58% of the total variance. The second cluster (psychosocial interference) included relations with others and sleep, which accounted for 13% of the total variance. The Cronbach's alpha statistics were 0.83 and 0.80, respectively. The functional clusters changed at week 12 in responders but persisted through week 12 in nonresponders. Conclusion: Palliative radiotherapy is effective in reducing bone pain. Functional interference component clusters exist in patients treated for bone metastases. These clusters changed over time in this study, possibly attributable to treatment. Further research is needed to examine these effects.« less

Significant Reduction of Late Toxicities in Patients With Extremity Sarcoma Treated With Image-Guided Radiation Therapy to a Reduced Target Volume: Results of Radiation Therapy Oncology Group RTOG-0630 Trial.

PubMed

Wang, Dian; Zhang, Qiang; Eisenberg, Burton L; Kane, John M; Li, X Allen; Lucas, David; Petersen, Ivy A; DeLaney, Thomas F; Freeman, Carolyn R; Finkelstein, Steven E; Hitchcock, Ying J; Bedi, Manpreet; Singh, Anurag K; Dundas, George; Kirsch, David G

2015-07-10

We performed a multi-institutional prospective phase II trial to assess late toxicities in patients with extremity soft tissue sarcoma (STS) treated with preoperative image-guided radiation therapy (IGRT) to a reduced target volume. Patients with extremity STS received IGRT with (cohort A) or without (cohort B) chemotherapy followed by limb-sparing resection. Daily pretreatment images were coregistered with digitally reconstructed radiographs so that the patient position could be adjusted before each treatment. All patients received IGRT to reduced tumor volumes according to strict protocol guidelines. Late toxicities were assessed at 2 years. In all, 98 patients were accrued (cohort A, 12; cohort B, 86). Cohort A was closed prematurely because of poor accrual and is not reported. Seventy-nine eligible patients from cohort B form the basis of this report. At a median follow-up of 3.6 years, five patients did not have surgery because of disease progression. There were five local treatment failures, all of which were in field. Of the 57 patients assessed for late toxicities at 2 years, 10.5% experienced at least one grade ≥ 2 toxicity as compared with 37% of patients in the National Cancer Institute of Canada SR2 (CAN-NCIC-SR2: Phase III Randomized Study of Pre- vs Postoperative Radiotherapy in Curable Extremity Soft Tissue Sarcoma) trial receiving preoperative radiation therapy without IGRT (P < .001). The significant reduction of late toxicities in patients with extremity STS who were treated with preoperative IGRT and absence of marginal-field recurrences suggest that the target volumes used in the Radiation Therapy Oncology Group RTOG-0630 (A Phase II Trial of Image-Guided Preoperative Radiotherapy for Primary Soft Tissue Sarcomas of the Extremity) study are appropriate for preoperative IGRT for extremity STS. © 2015 by American Society of Clinical Oncology.

SU-F-T-629: Effect of Multi-Leaf Collimator (MLC) Width On Plan Quality of Single-Isocenter VMAT Intracranial Stereotactic Radiosurgery for Multiple Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kraus, J; Thomas, E; Wu, X

2016-06-15

Purpose: Single-isocenter VMAT has been shown able to create high quality plans for complex intracranial multiple metastasis SRS cases. Linacs capable of the technique are typically outfitted with an MLC that consists of a combination of 5 mm and 10 mm leaves (standard) or 2.5 mm and 5 mm leaves (high-definition). In this study, we test the hypothesis that thinner collimator leaves are associated with improved plan quality. Methods: Ten multiple metastasis cases were identified and planned for VMAT SRS using a 10 MV flattening filter free beam. Plans were created for a standard (std) and a high-definition (HD) MLC.more » Published values for leaf transmission factor and dosimetric leaf gap were utilized. All other parameters were invariant. Conformity (plan and individual target), moderate isodose spill (V50%), and low isodose spill (mean brain dose) were selected for analysis. Results: Compared to standard MLC, HD-MLC improved overall plan conformity (median: Paddick CI-HD = 0.83, Paddick CI-std = 0.79; p = 0.004 and median: RTOG CI-HD =1.18, RTOG CI-std =1.24; p = 0.01 ), improved individual lesion conformity (median: Paddick CI-HD,i =0.77, Paddick CI-std,i =0.72; p < 0.001 and median: RTOG CI-HD,i = 1.28, RTOG CI-std,i =1.35; p < 0.001), improved moderate isodose spill (median: V50%-HD = 37.0 cc, V50%-std = 45.7 cc; p = 0.002), and improved low dose spill (median: dmean-HD = 2.90 Gy, dmean-std = 3.19 Gy; p = 0.002). Conclusion: For the single-isocenter VMAT SRS of multiple metastasis plans examined, use of HD-MLC modestly improved conformity, moderate isodose, and low isodose spill compared to standard MLC. However, in all cases we were able to generate clinically acceptable plans with the standard MLC. More work is need to further quantify the difference in cases with higher numbers of small targets and to better understand any potential clinical significance. This research was supported in part by Varian Medical Systems.« less

SU-E-T-321: Dosimetric Evaluation of Non-Coplanar Arcs in VMAT Planning for SBRT Lung Cases: A Planning Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, S; Gardner, S; Doemer, A

Purpose: Investigate use of standardized non-coplanar arcs to improve plan quality in lung Stereotactic Body Radiation Therapy(SBRT) VMAT planning. Methods: VMAT planning was performed for 9 patients previously treated with SBRT for peripheral lung tumors (tumor size:12.7cc to 32.5cc). For each patient, 7 VMAT plans (couch rotation values:0,5,10,15,20,25,and 30 deg) were generated; the coplanar plans were pushed to meet the RTOG0915 constraints and each non-coplanar plans utilized the same optimization constraints. The following plan dose metrics were used (taken from RTOG 0915): D-2cm: the maximum dose at 2 cm from the PTV, conformality index (CI), gradient index (GI), lung volumemore » receiving 5 Gy (V5) and lung volume receiving 20 Gy (V20). The couch collision clearance was checked for each plan through a dry run using the couch position from the patient’s treatment. Results: Of the 9 cases, one coplanar plan failed to meet two protocol guidelines (both gradient index and D-2cm parameter), and an additional plan failed the D-2cm parameter. When introducing at least 5 degree couch rotation, all plans met the protocol guidelines. The largest feasible couch angle available was 15 to 20 degrees due to gantry collision issues. Non-coplanar plans resulted in the average (standard deviation) reduction of the following metrics: GI by 7.3% (3.7%); lung V20 by 11.1% (3.2%); D-2cm by 12.7% (3.9%). The CI was unchanged (−0.3%±0.6%), and lung V5 increased (3.8%±8.2%). Conclusion: The use of couch rotations as little as 5 degrees allows for plan quality that will meet RTOG0915 constraints while reducing D-2cm, GI, and lung V20. Using default couch rotations while planning SBRT cases will allow for more efficient planning with the stated goal of meeting RTOG0915 criteria for all clinical cases. Gantry clearance checks in the treatment room may be necessary to ensure safe treatments for larger couch rotation values.« less

Quantifying Unnecessary Normal Tissue Complication Risks due to Suboptimal Planning: A Secondary Study of RTOG 0126

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moore, Kevin L., E-mail: kevinmoore@ucsd.edu; Schmidt, Rachel; Moiseenko, Vitali

Purpose: The purpose of this study was to quantify the frequency and clinical severity of quality deficiencies in intensity modulated radiation therapy (IMRT) planning in the Radiation Therapy Oncology Group 0126 protocol. Methods and Materials: A total of 219 IMRT patients from the high-dose arm (79.2 Gy) of RTOG 0126 were analyzed. To quantify plan quality, we used established knowledge-based methods for patient-specific dose-volume histogram (DVH) prediction of organs at risk and a Lyman-Kutcher-Burman (LKB) model for grade ≥2 rectal complications to convert DVHs into normal tissue complication probabilities (NTCPs). The LKB model was validated by fitting dose-response parameters relative tomore » observed toxicities. The 90th percentile (22 of 219) of plans with the lowest excess risk (difference between clinical and model-predicted NTCP) were used to create a model for the presumed best practices in the protocol (pDVH{sub 0126,top10%}). Applying the resultant model to the entire sample enabled comparisons between DVHs that patients could have received to DVHs they actually received. Excess risk quantified the clinical impact of suboptimal planning. Accuracy of pDVH predictions was validated by replanning 30 of 219 patients (13.7%), including equal numbers of presumed “high-quality,” “low-quality,” and randomly sampled plans. NTCP-predicted toxicities were compared to adverse events on protocol. Results: Existing models showed that bladder-sparing variations were less prevalent than rectum quality variations and that increased rectal sparing was not correlated with target metrics (dose received by 98% and 2% of the PTV, respectively). Observed toxicities were consistent with current LKB parameters. Converting DVH and pDVH{sub 0126,top10%} to rectal NTCPs, we observed 94 of 219 patients (42.9%) with ≥5% excess risk, 20 of 219 patients (9.1%) with ≥10% excess risk, and 2 of 219 patients (0.9%) with ≥15% excess risk. Replanning demonstrated the predicted NTCP reductions while maintaining the volume of the PTV receiving prescription dose. An equivalent sample of high-quality plans showed fewer toxicities than low-quality plans, 6 of 73 versus 10 of 73 respectively, although these differences were not significant (P=.21) due to insufficient statistical power in this retrospective study. Conclusions: Plan quality deficiencies in RTOG 0126 exposed patients to substantial excess risk for rectal complications.« less

Hematologic Toxicity in RTOG 0418: A Phase 2 Study of Postoperative IMRT for Gynecologic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klopp, Ann H., E-mail: aklopp@mdanderson.org; Moughan, Jennifer; Portelance, Lorraine

2013-05-01

Purpose: Intensity modulated radiation therapy (IMRT), compared with conventional 4-field treatment, can reduce the volume of bone marrow irradiated. Pelvic bone marrow sparing has produced a clinically significant reduction in hematologic toxicity (HT). This analysis investigated HT in Radiation Therapy Oncology Group (RTOG) 0418, a prospective study to test the feasibility of delivering postoperative IMRT for cervical and endometrial cancer in a multiinstitutional setting. Methods and Materials: Patients in the RTOG 0418 study were treated with postoperative IMRT to 50.4 Gy to the pelvic lymphatics and vagina. Endometrial cancer patients received IMRT alone, whereas patients with cervical cancer received IMRTmore » and weekly cisplatin (40 mg/m{sup 2}). Pelvic bone marrow was defined within the treatment field by using a computed tomography density-based autocontouring algorithm. The volume of bone marrow receiving 10, 20, 30, and 40 Gy and the median dose to bone marrow were correlated with HT, graded by Common Terminology Criteria for Adverse Events, version 3.0, criteria. Results: Eighty-three patients were eligible for analysis (43 with endometrial cancer and 40 with cervical cancer). Patients with cervical cancer treated with weekly cisplatin and pelvic IMRT had grades 1-5 HT (23%, 33%, 25%, 0%, and 0% of patients, respectively). Among patients with cervical cancer, 83% received 5 or more cycles of cisplatin, and 90% received at least 4 cycles of cisplatin. The median percentage volume of bone marrow receiving 10, 20, 30, and 40 Gy in all 83 patients, respectively, was 96%, 84%, 61%, and 37%. Among cervical cancer patients with a V40 >37%, 75% had grade 2 or higher HT compared with 40% of patients with a V40 less than or equal to 37% (P =.025). Cervical cancer patients with a median bone marrow dose of >34.2 Gy also had higher rates of grade ≥2 HT than did those with a dose of ≤34.2 Gy (74% vs 43%, P=.049). Conclusions: Pelvic IMRT with weekly cisplatin is associated with low rates of HT and high rates of weekly cisplatin use. The volume of bone marrow receiving 40 Gy and the median dose to bone marrow correlated with higher rates of grade ≥2 toxicity among patients receiving weekly cisplatin (cervical cancer patients). Evaluation and limitation of the volume of bone marrow treated with pelvic IMRT is warranted in patients receiving concurrent chemotherapy.« less

Development of a Set of Nomograms to Predict Acute Lower Gastrointestinal Toxicity for Prostate Cancer 3D-CRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valdagni, Riccardo; Rancati, Tiziana; Fiorino, Claudio

2008-07-15

Purpose: To predict acute Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) and Subjective Objective Signs Management and Analysis/Late Effect of Normal Tissue (SOMA/LENT) toxicities of the lower gastrointestinal (LGI) syndrome in patients with prostate cancer undergoing three-dimensional conformal radiotherapy using a tool (nomogram) that takes into account clinical and dosimetric variables that proved to be significant in the Italian Association for Radiation Oncology (AIRO) Group on Prostate Cancer (AIROPROS) 0102 trial. Methods and Materials: Acute rectal toxicity was scored in 1,132 patients by using both the RTOG/EORTC scoring system and a 10-item self-assessed questionnaire.more » Correlation between clinical variables/dose-volume histogram constraints and rectal toxicity was investigated by means of multivariate logistic analyses. Multivariate logistic analyses results were used to create nomograms predicting the symptoms of acute LGI syndrome. Results: Mean rectal dose was a strong predictor of Grade 2-3 RTOG/EORTC acute LGI toxicity (p 0.0004; odds ratio (OR) = 1.035), together with hemorrhoids (p = 0.02; OR 1.51), use of anticoagulants/antiaggregants (p = 0.02; OR = 0.63), and androgen deprivation (AD) (p = 0.04; OR = 0.65). Diabetes (p = 0.34; OR 1.28) and pelvic node irradiation (p = 0.11; OR = 1.56) were significant variables to adjust toxicity prediction. Bleeding was related to hemorrhoids (p = 0.02; OR = 173), AD (p = 0.17; OR = 0.67), and mean rectal dose (p 0.009; OR = 1.024). Stool frequency was related to seminal vesicle irradiation (p = 0.07; OR = 6.46), AD administered for more than 3 months (p = 0.002; OR = 0.32), and the percent volume of rectum receiving more than 60 Gy (V60Gy) V60 (p = 0.02; OR = 1.02). Severe fecal incontinence depended on seminal vesicle irradiation (p = 0.14; OR = 4.5) and V70 (p = 0.033; OR 1.029). Conclusions: To the best of our knowledge, this work presents the first set of nomograms available in the literature specific to symptoms of LGI syndrome and provides clinicians with a tailored probability of the specific outcome. Validation of the tool is in progress.« less

Recursive partitioning analysis of 1999 Radiation Therapy Oncology Group (RTOG) patients with locally-advanced non-small-cell lung cancer (LA-NSCLC): identification of five groups with different survival.

PubMed

Werner-Wasik, M; Scott, C; Cox, J D; Sause, W T; Byhardt, R W; Asbell, S; Russell, A; Komaki, R; Lee, J S

2000-12-01

Survival of patients with locally-advanced non-small-cell lung cancer (LA-NSCLC) is predicted by the stage of the disease and other characteristics. This analysis was undertaken to identify these characteristics in a large cooperative group patient population, as well as to define subgroups of the population with differing outcomes. Analysis included 1,999 patients treated in 9 RTOG trials between 1983 and 1994 with thoracic irradiation (RT) with (n = 355) or without chemotherapy (CT). In univariate analysis, the following characteristics were significantly associated with an improved survival: use of CT, CT delivered without major deviation, abnormal pulmonary function tests, normal hemoglobin, protein, LDH and BUN, presence of dyspnea, hemoptysis, cough or hoarseness, uninvolved lymph nodes, T1 or T2 stage, no malignant pleural effusion (PE), weight loss of < 8%, Karnofsky performance status (KPS) of at least 90, adenocarcinoma histology, female gender, and age less than 70 years. Recursive partitioning analysis (RPA) was subsequently applied to identify 5 patient subgroups with significantly different median survival times (MST): Group I, KPS of > or = 90, who received chemotherapy (MST 16.2 months); Group II, KPS of > or = 90, who received no CT, but had no PE (MST 11.9 months); Group III, KPS < 90, younger than 70 years, with non-large cell histology (MST 9.6 months); Group IV, KPS > or = 90, but with PE, or KPS < 90, younger than 70 years, and with large cell histology, or older than 70 years, but without PE (MST 5.6-6.4 months); Group V, older than 70, with PE (MST 2.9 months). Cisplatinum-based CT improves survival, for excellent prognosis of LA-NSCLC patients, over RT alone. The presence of a malignant pleural effusion is a major negative prognostic factor for survival. The identification of RPA prognostic groups among patients with LA-NSCLC provides prognostic information and may serve as a basis of stratification in future trials.

A planning comparison of 7 irradiation options allowed in RTOG 1005 for early-stage breast cancer.

PubMed

Chen, Guang-Pei; Liu, Feng; White, Julia; Vicini, Frank A; Freedman, Gary M; Arthur, Douglas W; Li, X Allen

2015-01-01

This study compared the 7 treatment plan options in achieving the dose-volume criteria required by the Radiation Therapy Oncology Group (RTOG) 1005 protocol. Dosimetry plans were generated for 15 representative patients with early-stage breast cancer (ESBC) based on the protocol-required dose-volume criteria for each of the following 7 treatment options: 3D conformal radiotherapy (3DCRT), whole-breast irradiation (WBI) plus 3DCRT lumpectomy boost, 3DCRT WBI plus electron boost, 3DCRT WBI plus intensity-modulated radiation therapy (IMRT) boost, IMRT WBI plus 3DCRT boost, IMRT WBI plus electron boost, IMRT WBI plus IMRT boost, and simultaneous integrated boost (SIB) with IMRT. A variety of dose-volume parameters, including target dose conformity and uniformity and normal tissue sparing, were compared for these plans. For the patients studied, all plans met the required acceptable dose-volume criteria, with most of them meeting the ideal criteria. When averaged over patients, most dose-volume goals for all plan options can be achieved with a positive gap of at least a few tenths of standard deviations. The plans for all 7 options are generally comparable. The dose-volume goals required by the protocol can in general be easily achieved. IMRT WBI provides better whole-breast dose uniformity than 3DCRT WBI does, but it causes no significant difference for the dose conformity. All plan options are comparable for lumpectomy dose uniformity and conformity. Patient anatomy is always an important factor when whole-breast dose uniformity and conformity and lumpectomy dose conformity are considered. Copyright © 2015 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

A Phase III Study of Conventional Radiation Therapy Plus Thalidomide Versus Conventional Radiation Therapy for Multiple Brain Metastases (RTOG 0118)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Knisely, Jonathan P.S.; Berkey, Brian; Chakravarti, Arnab

2008-05-01

Purpose: To compare whole-brain radiation therapy (WBRT) with WBRT combined with thalidomide for patients with brain metastases not amenable to resection or radiosurgery. Patients and Methods: Patients with Zubrod performance status 0-1, MRI-documented multiple (>3), large (>4 cm), or midbrain brain metastases arising from a histopathologically confirmed extracranial primary tumor, and an anticipated survival of >8 weeks were randomized to receive WBRT to a dose of 37.5 Gy in 15 fractions with or without thalidomide during and after WBRT. Prerandomization stratification used Radiation Therapy Oncology Group (RTOG) Recursive Partitioning Analysis (RPA) Class and whether post-WBRT chemotherapy was planned. Endpoints includedmore » overall survival, progression-free survival, time to neurocognitive progression, the cause of death, toxicities, and quality of life. A protocol-planned interim analysis documented that the trial had an extremely low probability of ever showing a significant difference favoring the thalidomide arm given the results at the time of the analysis, and it was therefore closed on the basis of predefined statistical guidelines. Results: Enrolled in the study were 332 patients. Of 183 accrued patients, 93 were randomized to receive WBRT alone and 90 to WBRT and thalidomide. Median survival was 3.9 months for both arms. No novel toxicities were seen, but thalidomide was not well tolerated in this population. Forty-eight percent of patients discontinued thalidomide because of side effects. Conclusion: Thalidomide provided no survival benefit for patients with multiple, large, or midbrain metastases when combined with WBRT; nearly half the patients discontinued thalidomide due to side effects.« less

Impact of Gender, Partner Status, and Race on Locoregional Failure and Overall Survival in Head and Neck Cancer Patients in Three Radiation Therapy Oncology Group Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dilling, Thomas J., E-mail: Thomas.Dilling@moffitt.org; Bae, Kyounghwa; Paulus, Rebecca

Purpose: We investigated the impact of race, in conjunction with gender and partner status, on locoregional control (LRC) and overall survival (OS) in three head and neck trials conducted by the Radiation Therapy Oncology Group (RTOG). Methods and Materials: Patients from RTOG studies 9003, 9111, and 9703 were included. Patients were stratified by treatment arms. Covariates of interest were partner status (partnered vs. non-partnered), race (white vs. non-white), and sex (female vs. male). Chi-square testing demonstrated homogeneity across treatment arms. Hazards ratio (HR) was used to estimate time to event outcome. Unadjusted and adjusted HRs were calculated for all covariatesmore » with associated 95% confidence intervals (CIs) and p values. Results: A total of 1,736 patients were analyzed. Unpartnered males had inferior OS rates compared to partnered females (adjusted HR = 1.22, 95% CI, 1.09-1.36), partnered males (adjusted HR = 1.20, 95% CI, 1.09-1.28), and unpartnered females (adjusted HR = 1.20, 95% CI, 1.09-1.32). White females had superior OS compared with white males, non-white females, and non-white males. Non-white males had inferior OS compared to white males. Partnered whites had improved OS relative to partnered non-white, unpartnered white, and unpartnered non-white patients. Unpartnered males had inferior LRC compared to partnered males (adjusted HR = 1.26, 95% CI, 1.09-1.46) and unpartnered females (adjusted HR = 1.30, 95% CI, 1.05-1.62). White females had LRC superior to non-white males and females. White males had improved LRC compared to non-white males. Partnered whites had improved LRC compared to partnered and unpartnered non-white patients. Unpartnered whites had improved LRC compared to unpartnered non-whites. Conclusions: Race, gender, and partner status had impacts on both OS and locoregional failure, both singly and in combination.« less

Five Year Results of US Intergroup/RTOG 9704 With Postoperative CA 19-9 {<=}90 U/mL and Comparison to the CONKO-001 Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berger, Adam C., E-mail: adam.berger@jefferson.edu; Winter, Kathryn; Hoffman, John P.

2012-11-01

Purpose: Radiation Therapy Oncology Group (RTOG) trial 9704 was the largest randomized trial to use adjuvant chemoradiation therapy for patients with pancreatic cancer. This report analyzes 5-year survival by serum level of tumor marker CA 19-9 of {<=}90 vs >90 U/mL and compares results to the those of the CONKO-001 trial. Methods and Materials: CA 19-9 expression was analyzed as a dichotomized variable ({<=}90 vs >90 U/mL). Cox proportional hazard models were used to identify the impact of the CA 19-9 value on overall survival (OS). Actuarial estimates of OS were calculated using the Kaplan-Meier method. Results: Both univariate (hazardmore » ratio [HR] = 3.2; 95% confidence interval [CI], 2.3-4.3, P<.0001) and multivariate (HR = 3.1; 95% CI, 2.2-4.2, P<.0001) analyses demonstrated a statistically significant decrease in OS for CA 19-9 serum level of {>=}90 U/mL. For patients in the gemcitabine (Gem) treatment arm with CA 19-9 <90 U/mL, median survival was 21 months. For patients with CA 19-9 {>=}90 U/mL, this number dropped to 10 months. In patients with pancreatic head tumors in the Gem treatment arm with RT quality assurance per protocol and CA 19-9 of <90 U/mL, median survival and 5-year rate were 24 months and 34%. In comparison, the median survival and 5-year OS rate for patients in the Gem arm of the CONKO trial were 22 months and 21%. Conclusions: This analysis demonstrates that patients with postresection CA 19-9 values {>=}90 U/mL had a significantly worse survival. Patients with pancreatic head tumors treated with Gem with CA 19-9 serum level of <90 U/mL and per protocol RT had favorable survival compared to that seen in the CONKO trial. CA 19-9 is a stratification factor for the current RTOG adjuvant pancreas trial (0848).« less

SU-F-T-112: Long-Term Follow-Up of NSCLC Patients Treated with Lung SBRT Using the Modified Conformal Arc (MDCA) Planning Technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ku, E; Desai, A; Fang, D

2016-06-15

Purpose: To assess long-term toxicity and primary tumor changes for Stage I/II non-small cell lung carcinoma (NSCLC) patients after treatment with lung SBRT using the modified dynamic conformal arc (MDCA) planning technique. Methods: Clinical and radiograph data from electronic health records of 15 NSCLC patients treated with lung SBRT utilizing the MDCA technique between October 2011 and July 2014 were retrospectively reviewed. MDCA uses a coplanar beam arrangement, patient body center for the beam isocenter, and six partial rotation conformal arcs to target the tumor. Radiation Therapy Oncology Group (RTOG) guidelines for treatment parameters were followed. Most patients received 5more » radiation fractions (Range: 3 to 7 fractions) with 48 hours between each fraction. Median total dose was 60 Gy (range: 45 to 70 Gy). Results: Median follow-up was 18 months (range: 6–51 months). Median age was 72.5 years (range: 48–90 years). Post-treatment findings included fatigue (n = 5) and chronic chest wall pain (n=1). Seven patients reported respiratory symptoms, which included: cough (n = 4), dyspnea (n = 5), and hemoptysis (n = 1). No patients deaths or grade ≥4 toxicity were recorded. Radiographic scarring was seen on computed tomography (CT) imaging in 6 patients. Local control rate was 93.3% (n = 14) and 1 patient had local recurrence. Conclusion: Our results were very similar to RTOG 0236 findings reported by Timmerman et al. – our local control rate was 93.3% compared to their 3-year primary tumor control rate of 97.6%. Toxicity rates were also similar – RTOG 0236 constitutional symptoms and pulmonary/upper respiratory symptoms rates were 36.4% and 60.0%, respectively, while ours were 33.3% and 46.7%, respectively. We were limited by a small sample size and relatively short follow-up but our findings support the use of the MDCA technique for lung SBRT treatment of Stage I/II NSCLC.« less

Real-Time Pretreatment Review Limits Unacceptable Deviations on a Cooperative Group Radiation Therapy Technique Trial: Quality Assurance Results of RTOG 0933

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gondi, Vinai, E-mail: vgondi@chicagocancer.org; University of Wisconsin School of Medicine & Public Health, Madison, Wisconsin; Cui, Yunfeng

2015-03-01

Purpose: RTOG 0933 was a phase II trial of hippocampal avoidance during whole brain radiation therapy for patients with brain metastases. The results demonstrated improvement in short-term memory decline, as compared with historical control individuals, and preservation of quality of life. Integral to the conduct of this trial were quality assurance processes inclusive of pre-enrollment credentialing and pretreatment centralized review of enrolled patients. Methods and Materials: Before enrolling patients, all treating physicians and sites were required to successfully complete a “dry-run” credentialing test. The treating physicians were credentialed based on accuracy of magnetic resonance imaging–computed tomography image fusion and hippocampal andmore » normal tissue contouring, and the sites were credentialed based on protocol-specified dosimetric criteria. Using the same criteria, pretreatment centralized review of enrolled patients was conducted. Physicians enrolling 3 consecutive patients without unacceptable deviations were permitted to enroll further patients without pretreatment review, although their cases were reviewed after treatment. Results: In all, 113 physicians and 84 sites were credentialed. Eight physicians (6.8%) failed hippocampal contouring on the first attempt; 3 were approved on the second attempt. Eight sites (9.5%) failed intensity modulated radiation therapy planning on the first attempt; all were approved on the second attempt. One hundred thirteen patients were enrolled in RTOG 0933; 100 were analyzable. Eighty-seven cases were reviewed before treatment; 5 (5.7%) violated the eligibility criteria, and 21 (24%) had unacceptable deviations. With feedback, 18 cases were approved on the second attempt and 2 cases on the third attempt. One patient was treated off protocol. Twenty-two cases were reviewed after treatment; 1 (4.5%) violated the eligibility criteria, and 5 (23%) had unacceptable deviations. Conclusions: Although >95% of the cases passed the pre-enrollment credentialing, the pretreatment centralized review disqualified 5.7% of reviewed cases, prevented unacceptable deviations in 24% of reviewed cases, and limited the final unacceptable deviation rate to 5%. Thus, pretreatment review is deemed necessary in future hippocampal avoidance trials and is potentially useful in other similarly challenging radiation therapy technique trials.« less

Dosimetric effect of multileaf collimator leaf width on volumetric modulated arc stereotactic radiotherapy for spine tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amoush, Ahmad, E-mail: aamoush@augusta.edu; Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195; Long, Huang

This work aimed to study the dosimetric effect of multileaf collimator (MLC) leaf widths in treatment plans for patients receiving volumetric modulated arc therapy (VMAT) for spine stereotactic body radiation therapy (SBRT). Thirteen patients treated with spine SBRT were retrospectively selected for this study. The patients were treated following the protocol of the Radiation Therapy Oncology Group 0631 (RTOG 0631) for spine metastasis. The prescription dose was 16 Gy in 1 fraction to 90% of the target volume (V16 > 90%). The maximum spinal cord dose of 14 Gy and 10% of the spinal cord receiving < 10 Gy (V10) were the acceptable tolerance doses. For themore » purpose of this study, 2 dual-arc VMAT plans were created for each patient using 3 different MLC leaf widths: 2.5 mm, 4 mm, and 5 mm. The compliance with the RTOG 0631 protocol, conformity index (CI), dose gradient index (DGI), and number of monitor units (MUs) were compared. The average V16Gy of the targets was 91.8 ± 1.2%, 92.2 ± 2.1%, and 91.7 ± 2.3% for 2.5-mm, 4-mm, and 5-mm leaf widths, respectively (p = 0.78). Accordingly, the average CI was 1.45 ± 0.4, 1.47 ± 0.29, and 1.47 ± 0.31 (p = 0.98), respectively. The average DGI was 0.22 ± 0.04, 0.20 ± 0.06, and 0.22 ± 0.05, respectively (p = 0.77). The average maximum dose to the spinal cord was 12.45 ± 1.0 Gy, 12.80 ± 1.0 Gy, and 12.48 ± 1.1 (p = 0.62) and V10% of the spinal cord was 3.6 ± 2.1%, 5.6 ± 2.8%, and 5.5 ± 3.0% (p = 0.11) for 2.5-mm, 4-mm, and 5-mm leaf widths, respectively. Accordingly, the average number of MUs was 4341 ± 500 MU, 5019 ± 834 MU, and 4606 ± 691 MU, respectively (p = 0.053). The use of 2.5-mm, 4-mm, and 5-mm MLCs achieved similar VMAT plan quality as recommended by the RTOG 0631. The dosimetric parameters were also comparable for the 3 MLCs. In general, any of these leaf widths can be used for spine SBRT using VMAT.« less

Late Gastrointestinal Toxicity After Dose-Escalated Conformal Radiotherapy for Early Prostate Cancer: Results From the UK Medical Research Council RT01 Trial (ISRCTN47772397)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Syndikus, Isabel; Morgan, Rachel C.; Sydes, Matthew R., E-mail: ms@ctu.mrc.ac.u

2010-07-01

Purpose: In men with localized prostate cancer, dose-escalated conformal radiotherapy (CFRT) improves efficacy outcomes at the cost of increased toxicity. We present a detailed analysis to provide further information about the incidence and prevalence of late gastrointestinal side effects. Methods and Materials: The UK Medical Research Council RT01 trial included 843 men with localized prostate cancer, who were treated for 6 months with neoadjuvant radiotherapy and were randomly assigned to either 64-Gy or 74-Gy CFRT. Toxicity was evaluated before CFRT and during long-term follow-up using Radiation Therapy Oncology Group (RTOG) grading, the Late Effects on Normal Tissue: Subjective, Objective, Managementmore » (LENT/SOM) scale, and Royal Marsden Hospital assessment scores. Patients regularly completed Functional Assessment of Cancer Therapy--Prostate (FACT-P) and University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) questionnaires. Results: In the dose-escalated group, the hazard ratio (HR) for rectal bleeding (LENT/SOM grade {>=}2) was 1.55 (95% CI, 1.17-2.04); for diarrhea (LENT/SOM grade {>=}2), the HR was 1.79 (95% CI, 1.10-2.94); and for proctitis (RTOG grade {>=}2), the HR was 1.64 (95% CI, 1.20-2.25). Compared to baseline scores, the prevalence of moderate and severe toxicities generally increased up to 3 years and than lessened. At 5 years, the cumulative incidence of patient-reported severe bowel problems was 6% vs. 8% (standard vs. escalated, respectively) and severe distress was 4% vs. 5%, respectively. Conclusions: There is a statistically significant increased risk of various adverse gastrointestinal events with dose-escalated CFRT. This remains at clinically acceptable levels, and overall prevalence ultimately decreases with duration of follow-up.« less

Predicting radiotherapy outcomes using statistical learning techniques

NASA Astrophysics Data System (ADS)

El Naqa, Issam; Bradley, Jeffrey D.; Lindsay, Patricia E.; Hope, Andrew J.; Deasy, Joseph O.

2009-09-01

Radiotherapy outcomes are determined by complex interactions between treatment, anatomical and patient-related variables. A common obstacle to building maximally predictive outcome models for clinical practice is the failure to capture potential complexity of heterogeneous variable interactions and applicability beyond institutional data. We describe a statistical learning methodology that can automatically screen for nonlinear relations among prognostic variables and generalize to unseen data before. In this work, several types of linear and nonlinear kernels to generate interaction terms and approximate the treatment-response function are evaluated. Examples of institutional datasets of esophagitis, pneumonitis and xerostomia endpoints were used. Furthermore, an independent RTOG dataset was used for 'generalizabilty' validation. We formulated the discrimination between risk groups as a supervised learning problem. The distribution of patient groups was initially analyzed using principle components analysis (PCA) to uncover potential nonlinear behavior. The performance of the different methods was evaluated using bivariate correlations and actuarial analysis. Over-fitting was controlled via cross-validation resampling. Our results suggest that a modified support vector machine (SVM) kernel method provided superior performance on leave-one-out testing compared to logistic regression and neural networks in cases where the data exhibited nonlinear behavior on PCA. For instance, in prediction of esophagitis and pneumonitis endpoints, which exhibited nonlinear behavior on PCA, the method provided 21% and 60% improvements, respectively. Furthermore, evaluation on the independent pneumonitis RTOG dataset demonstrated good generalizabilty beyond institutional data in contrast with other models. This indicates that the prediction of treatment response can be improved by utilizing nonlinear kernel methods for discovering important nonlinear interactions among model variables. These models have the capacity to predict on unseen data. Part of this work was first presented at the Seventh International Conference on Machine Learning and Applications, San Diego, CA, USA, 11-13 December 2008.

Future directions in treatment of brain metastases

PubMed Central

Barani, Igor J.; Larson, David A.; Berger, Mitchel S.

2013-01-01

Background: Brain metastases affect up to 30% of patients with cancer. Management of brain metastases continues to evolve with ever increasing focus on cognitive preservation and quality of life. This manuscript reviews current state of brain metastases management and discusses various treatment controversies with focus on future clinical trials. Stereotactic radiosurgery (SRS) and whole-brain radiotherapy (WBRT) are discussed in context of multiple (4+ brain metastases) as well as new approaches combining radiation and targeted agents. A brief discussion of modified WBRT approaches, including hippocampal-avoidance WBRT (HA-WBRT) is included as well as a section on recently presented results of Radiation Therapy Oncology Group (RTOG) 0614, a randomized, double-blind, placebo-controlled trial of menantine for prevention of neurocognitive injury after WBRT. Methods: A search of selected studies relevant to management of brain metastases was performed in PubMed as well as in various published meeting abstracts. This data was collated and analyzed in context of contemporary management and future clinical trial plans. This data is presented in tabular form and discussed extensively in the text. Results: The published data demonstrate continued evolution of clinical trials and management strategies designed to minimize and/or prevent cognitive decline following radiation therapy management of brain metastases. Hippocampal avoidance whole-brain radiation therapy (HA-WBRT) and radiosurgery treatments for multiple brain metastases are discussed along with preliminary results of RTOG 0614, a trial of memantine therapy to prevent cognitive decline following WBRT. Trial results appear to support the use of memantine for prevention of cognitive decline. Conclusions: Different management strategies for multiple brain metastases (>4 brain metastases) are currently being evaluated in prospective clinical trials to minimize the likelihood of cognitive decline following WBRT. PMID:23717793

Future directions in treatment of brain metastases.

PubMed

Barani, Igor J; Larson, David A; Berger, Mitchel S

2013-01-01

Brain metastases affect up to 30% of patients with cancer. Management of brain metastases continues to evolve with ever increasing focus on cognitive preservation and quality of life. This manuscript reviews current state of brain metastases management and discusses various treatment controversies with focus on future clinical trials. Stereotactic radiosurgery (SRS) and whole-brain radiotherapy (WBRT) are discussed in context of multiple (4+ brain metastases) as well as new approaches combining radiation and targeted agents. A brief discussion of modified WBRT approaches, including hippocampal-avoidance WBRT (HA-WBRT) is included as well as a section on recently presented results of Radiation Therapy Oncology Group (RTOG) 0614, a randomized, double-blind, placebo-controlled trial of menantine for prevention of neurocognitive injury after WBRT. A search of selected studies relevant to management of brain metastases was performed in PubMed as well as in various published meeting abstracts. This data was collated and analyzed in context of contemporary management and future clinical trial plans. This data is presented in tabular form and discussed extensively in the text. The published data demonstrate continued evolution of clinical trials and management strategies designed to minimize and/or prevent cognitive decline following radiation therapy management of brain metastases. Hippocampal avoidance whole-brain radiation therapy (HA-WBRT) and radiosurgery treatments for multiple brain metastases are discussed along with preliminary results of RTOG 0614, a trial of memantine therapy to prevent cognitive decline following WBRT. Trial results appear to support the use of memantine for prevention of cognitive decline. Different management strategies for multiple brain metastases (>4 brain metastases) are currently being evaluated in prospective clinical trials to minimize the likelihood of cognitive decline following WBRT.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Acar, H; Cebe, M; Mabhouti, H

Purpose: Stereotactic body radiosurgery (SBRT) for spine metastases involves irradiation using a single high dose fraction. The purpose of this study was to investigate a Hybrid VMAT/IMRT technique which combines volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) for spine SBRT in terms of its dosimetric quality and treatment efficiency using Radiation Therapy Oncology Group (RTOG) 0631 guidelines. Methods: 7 fields IMRT, 2 full arcs VMAT and Hybrid VMAT/IMRT were created for ten previously treated patients. The Hybrid VMAT/IMRT technique consisted of 1 full VMAT arc and 5 IMRT fields. Hybrid VMAT/IMRT plans were compared with IMRTmore » and VMAT plans in terms of the dose distribution, spinal cord sparing, homogeneity, conformity and gradient indexies, monitor unit (MU) and beam on time (BOT). RTOG 0631 recommendations were applied for treatment planning. All plans were normalized and prescribed to deliver 18.0 Gy in a single fraction to 90% of the target volume. Results: The Hybrid VMAT/IMRT technique significantly improved target dose homogeneity and conformity compared with IMRT and VMAT techniques. Providing sharp dose gradient Hybrid VMAT/IMRT plans spare the spinal cord and healthy tissue more effectively. Although, both MU and BOT slightly increased in Hybrid VMAT/IMRT plans there is no statistically meaningful difference between VMAT and Hybrid VMAT/IMRT plans. Conclusion: In IMRT, a smaller volume of healthy tissue can be irradiated in the low dose region, VMAT plans provide better target volume coverage, favorable dose gradient, conformity and better OAR sparing and also they require a much smaller number of MUs and thus a shorter treatment time than IMRT plans. Hybrid plan offers a sinergy through combination of these two techniques with slightly increased number of MU and thus more treatment time.« less

Reirradiation on recurrent cervical cancer case: Treatment response and side effects

NASA Astrophysics Data System (ADS)

Siregar, M. F.; Supriana, N.; Nuranna, L.; Prihartono, J.

2017-08-01

Management of recurrent cervical cancer by reirradiation after radiation treatment remains controversial. In Indonesia, there is currently no data about reirradiation tumor response and side effects. This study aims to assess the tumor response to and side effects of reirradiation, the effect of time interval between first radiation treatment and cancer recurrence on the tumor response and side effects, and the effect of tumor size on tumor response. A cohort retrospective study with no comparison was done with the Radiotherapy Department at Cipto Mangunkusumo General Hospital, Jakarta. Participants were recurrent cervical cancer patients undergoing reirradiation. Data was collected from patients’ medical records and follow-up phone calls. Twenty-two patients participated in this study. Nine patients (40.9%) had complete responses, 10 patients (45.5%) had partial responses, 1 patient (4.5%) had a stable response, and 2 patients (9.1%) had tumor progressions. In general, 15 patients (68.2%) had no to light side effects (grade 0-2 RTOG) and 7 patients (31.8%) had severe side effects (grade 3-4 RTOG). Four patients (18.1%) had severe gastrointestinal acute side effects, 6 patients (27.3%) had severe gastrointestinal late side effects, 2 patients (9.1%) had severe urogenital side effects, and there were no patients had severe urogenital late side effects. There was no significant difference in tumor response between patients with time interval between first radiation treatment and recurrence of <12 months vs. ≥12 months. There was no significant difference in tumor response between patients with tumor size ≤4 cm vs. >4 cm. Reirradiation can be considered as a modality in recurrent cervical cancer management since good tumor response was achieved and the majority of patients had no to light side effects (grade 0-2 RTOG). This study found no correlation between tumor response, side effects, and time gap between first radiation treatment and recurrence of <12 months vs. ≥12 months. There was also no correlation between tumor response and tumor size of ≤4 cm vs. > 4 cm.

Comparison of different contouring definitions of the rectum as organ at risk (OAR) and dose-volume parameters predicting rectal inflammation in radiotherapy of prostate cancer: which definition to use?

PubMed

Nitsche, Mirko; Brannath, Werner; Brückner, Matthias; Wagner, Dirk; Kaltenborn, Alexander; Temme, Nils; Hermann, Robert M

2017-02-01

The objective of this retrospective planning study was to find a contouring definition for the rectum as an organ at risk (OAR) in curative three-dimensional external beam radiotherapy (EBRT) for prostate cancer (PCa) with a predictive correlation between the dose-volume histogram (DVH) and rectal toxicity. In a pre-study, the planning CT scans of 23 patients with PCa receiving definitive EBRT were analyzed. The rectum was contoured according to 13 different definitions, and the dose distribution was correlated with the respective rectal volumes by generating DVH curves. Three definitions were identified to represent the most distinct differences in the shapes of the DVH curves: one anatomical definition recommended by the Radiation Therapy Oncology Group (RTOG) and two functional definitions based on the target volume. In the main study, the correlation between different relative DVH parameters derived from these three contouring definitions and the occurrence of rectal toxicity during and after EBRT was studied in two consecutive collectives. The first cohort consisted of 97 patients receiving primary curative EBRT and the second cohort consisted of 66 patients treated for biochemical recurrence after prostatectomy. Rectal toxicity was investigated by clinical investigation and scored according to the Common Terminology Criteria for Adverse Events. Candidate parameters were the volume of the rectum, mean dose, maximal dose, volume receiving at least 60 Gy (V 60 ), area under the DVH curve up to 25 Gy and area under the DVH curve up to 75 Gy in dependence of each chosen rectum definition. Multivariable logistic regression considered other clinical factors such as pelvine lymphatics vs local target volume, diabetes, prior rectal surgery, anticoagulation or haemorrhoids too. In Cohort 1 (primary EBRT), the mean rectal volumes for definitions "RTOG", planning target volume "(PTV)-based" and "PTV-linked" were 100 cm 3 [standard deviation (SD) 43 cm 3 ], 60 cm 3 (SD 26 cm 3 ) and 74 cm 3 (SD 31 cm 3 ), respectively (p < 0.01; analysis of variance). The mean rectal doses according to these definitions were 35 Gy (SD 8 Gy), 48 Gy (SD 4 Gy) and 44 Gy (SD 5 Gy) (p < 0.01). In Cohort 2 (salvage EBRT), the mean rectal volumes were 114 cm 3 (SD 47 cm 3 ), 64 cm 3 (SD 26 cm 3 ) and 81 cm 3 (SD 30 cm 3 ) (p < 0.01) and the mean doses received by the rectum were 36 Gy (SD 8 Gy), 49 Gy (SD 5 Gy) and 44 Gy (SD 5 Gy) (p < 0.01). Acute or subacute rectal inflammation occurred in 69 (71.9%) patients in Cohort 1 and in 43 (70.5%) in Cohort 2. We did not find a correlation between all investigated DVH parameters and rectal toxicity, irrespective of the investigated definition. By adding additional variables in multivariate analysis, the predictive ability was substantially improved. Still, there was essentially no difference in the probability of predicting rectal inflammation occurrence between the tested contouring definitions. The RTOG anatomy-based recommendations are questionable in comparison with functional definitions, as they result in higher variances in several relative DVH parameters. Moreover, the anatomy-based definition is no better and no worse in the predictive value concerning clinical end points. Advances in knowledge: Functional definitions for the rectum as OAR are easier to apply, faster to contour, have smaller variances and do not offer less information than the anatomy-based RTOG definition.

The Significance of Co-Expression of Epidermal Growth Factor Receptor (EGFR) and Ki67 on Clinical Outcome in Patients with Anal Cancer Treated with Chemoradiotherapy: An Analysis of NRG Oncology RTOG 9811

PubMed Central

Doll, Corinne M.; Moughan, Jennifer; Klimowicz, Alexander; Ho, Clement K.; Kornaga, Elizabeth N.; Lees-Miller, Susan P.; Ajani, Jaffer A.; Crane, Christopher H.; Kachnic, Lisa A.; Okawara, Gordon S.; Berk, Lawrence B.; Roof, Kevin S.; Becker, Mark J.; Grisell, David L.; Ellis, Robert J; Sperduto, Paul; Marsa, Gerald; Guha, Chandan; Magliocco, Anthony

2017-01-01

Purpose To measure co-expression of EGFR and Ki67 proteins in pre-treatment tumor biopsies of anal cancer patients enrolled on NRG Oncology RTOG 9811, a phase III trial comparing 5FU/MMC/RT (Arm A) vs. 5FU/cisplatin/RT (Arm B), and to correlate expression with clinical outcome. Materials/Methods EGFR and Ki67 co-expression was measured after constructing a tissue microarray using fluorescence immunohistochemistry and automated quantitative image analysis (AQUA). Ki67 score within EGFR high vs. low areas (Ki67ratio in EGFRhigh:low) in each tumor core was analyzed at the median, quartiles and as a continuous variable. Associations between the tumor markers and clinical endpoints [overall and disease-free survival (OS, DFS), locoregional and colostomy failure (LRF, CF), and distant metastases (DM] were explored. Results 282 pre-treatment tumors were analyzed from NRG Oncology RTOG 9811. Of evaluated specimens, 183 (65%, n=89, Arm A; n=94, Arm B) were eligible and analyzable. There were no significant differences in baseline characteristics or outcomes between analyzable and unanalyzable patient cases. Median follow-up was 6.0 years. On multivariate analysis, after adjusting for gender, patients with Ki67ratio in EGFRhigh:low ≥ median had worse OS (HR=2.41, 95% C.I. = [1.38, 4.19], p=0.0019). After adjusting for N stage and largest tumor dimension, patients with Ki67ratio in EGFRhigh:low ≥ median had a higher risk of a disease-free failure (HR=1.85, 95% C.I. = [1.18, 2.92], p=0.0078). Technical validation with an independent anal cancer patient cohort was performed and shows a very similar biomarker score distribution. Conclusions High Ki67ratio in EGFRhigh:low is associated with worse clinical outcome in this subset of patients with anal cancer treated with chemoradiation on NRG Oncology RTOG 9811. Evaluation within a clinical trial will be required to determine whether patients with these tumor characteristics may specifically benefit from an EGFR targeted therapeutic agent. PMID:28126304

Does an Algorithmic Approach to Using Brachytherapy and External Beam Radiation Result in Good Function, Local Control Rates, and Low Morbidity in Patients With Extremity Soft Tissue Sarcoma?

PubMed

Klein, Jason; Ghasem, Alex; Huntley, Samuel; Donaldson, Nathan; Keisch, Martin; Conway, Sheila

2018-03-01

High-dose-rate brachytherapy (HDR-BT) and external-beam radiation therapy (EBRT) are two modalities used in the treatment of soft tissue sarcoma. Previous work at our institution showed early complications and outcomes for patients treated with HDR-BT, EBRT, or a combination of both radiation therapy modalities. As the general indications for each of these approaches to radiation therapy differ, it is important to evaluate the use of each in an algorithmic way, reflecting how they are used in contemporary practice at sites that use these treatments. QUESTION/PURPOSES: (1) To determine the proportions of intermediate- and long-term complications associated with the use of brachytherapy in the treatment of primary high-grade extremity soft tissue sarcomas; (2), to characterize the long-term morbidity of the three radiation treatment groups using the Radiation Therapy Oncology Group/ European Organization for Research and Treatment of Cancer (RTOG/EORTC) Late Radiation Morbidity Scoring Scheme; (3) to determine whether treatment with HDR-BT, EBRT, and HDR-BT+EBRT therapy, in combination with limb-salvage surgery, results in acceptable local control in this high-risk group of sarcomas. We retrospectively studied data from 171 patients with a diagnosis of high-grade extremity soft tissue sarcoma treated with limb-sparing surgery and radiation therapy between 1990 and 2012 at our institution, with a mean followup of 72 months. Of the 171 patients, 33 (20%) were treated with HDR-BT, 128 (75%) with EBRT, and 10 (6%) with HDR-BT+EBRT. We excluded 265 patients with soft tissue sarcomas owing to axial tumor location, previous radiation to the affected extremity, incomplete patient records, patients receiving primary amputation, recurrent tumors, pediatric patients, low- and intermediate-grade tumors, and rhabdoid histology. Fifteen patients (9%) were lost to followup for any reason including died of disease or other causes during the first 12 months postoperatively. This included four patients who received HDR-BT (12%), 11 who received EBRT (9%), and none who received HDR-BT+EBRT (0%) with less than 12 months followup. Determination of radiation therapy technique for each patient was individualized in a multidisciplinary forum of sarcoma specialists. Anticipated close or positive surgical margins and a low likelihood of complex soft tissue procedures were factors that encouraged use of brachytherapy, whereas the anticipated need for secondary procedures and/or soft tissue coverage encouraged use of EBRT alone. Combination therapy was used when the treatment volume exceeded the treatment field of the brachytherapy catheters or when the catheters were used to boost a close or positive surgical margin. Local recurrence, complications, and morbidity outcomes scores (RTOG) were calculated based on chart review. Between-group comparisons pertaining to the proportion of patients experiencing complications, morbidity outcomes scores, and local recurrence rates were not performed because of dissimilarities among the patients in each group at baseline. The HDR-BT treatment group showed a high incidence of intermediate-term complications, with the three most common being: deep infection (33%, 11 of 33); dehiscence and delayed wound healing (24%, eight of 33); and seroma and hematoma (21%, seven of 33). The EBRT group showed a high incidence of intermediate- and long-term complications with the three most common being: chronic radiation dermatitis (35%, 45 of 128); fibrosis (27%, 35 of 128); and chronic pain and neuritis (13%, 16 of 128). The RTOG scores for each treatment group were: HDR-BT 0.8 ± SD 1.2; EBRT 1.9 ± 2.0; and HDR-BT+EBRT 1.7 ± 1.7. Overall, 142 of 169 (84%) patients were free from local recurrence: 27 (82%) in the HDR-BT group, 108 (86%) in the EBRT group, and seven (70%) in the combination therapy group. In this single-institution study, an algorithmic approach to using HDR-BT and EBRT in the treatment of patients with high-grade soft tissue sarcomas can yield acceptable complication rates, good morbidity outcome scores, and a high degree of local control. Based on these results, we believe HDR-BT is best for patients with an anticipated close margin, a positive surgical margin, and for patients who are unlikely to receive a complex soft tissue procedure. Conversely, if a secondary procedure and/or soft tissue coverage are likely to be used, EBRT alone may be reasonable. Finally, combination therapy might be considered when the treatment volume exceeded the treatment field capacity for HDR-BT or when the catheters were used to boost a close or positive surgical margin. Level IV, therapeutic study.

Intensity-modulated radiotherapy as primary treatment for prostate cancer: acute toxicity in 114 patients.

PubMed

De Meerleer, Gert; Vakaet, Luc; Meersschout, Sabine; Villeirs, Geert; Verbaeys, Antony; Oosterlinck, Wim; De Neve, Wilfried

2004-11-01

Dose escalation improves local control in prostate cancer. At Ghent University Hospital, intensity-modulated radiotherapy (IMRT) is used to increase the dose to the prostate and/or seminal vesicles. We report on acute toxicity in 114 patients who received IMRT for prostate cancer. Intensity-modulated radiotherapy was initiated after approval of our ethics committee. A class solution was used to plan all cases. Three beams (gantry 0 degrees , 116 degrees , and 244 degrees ) and anatomy-based segmentation were used to create an intensity-modulated dose distribution. Maximal rectal dose was set at 2 Gy per fraction. Detailed dose-volume histograms for all relevant structures were present. For all patients, we determined the pretreatment morbidity by a detailed preradiotherapy, in-house developed symptom scale. All patients were treated with 18 MV photons of an Elekta linear accelerator. Patients were seen on a weekly basis during treatment, and 1 month (M1) and 3 months (M3) thereafter. The registration of acute toxicity was standardized by a fixed questionnaire. The Radiation Therapy Oncology Group (RTOG) toxicity scale served as a basis, but additional symptoms, such as rectal blood loss, urgency, and incontinence, were scored as well. All 114 IMRT plans were delivered successfully without any interruption or technical problem. Daily treatment time was always less than 8 min and less than 6 min in 90% of the cases. Grade 1 and Grade 2 gastrointestinal (GI) toxicities were observed in 44% and 29% of the patients, respectively, during the whole period. If only the RTOG scale was used, Grade 1 and Grade 2 GI toxicities were noted in 39% and 27% of the patients, respectively, leaving 34% free of acute RTOG-scaled toxicity. Grade 3 genitourinary (GU) toxicity was seen in 8 patients (7%), all but 1 during treatment. Grade 2 and Grade 1 GU toxicities were seen in 36% and 47% of the patients, respectively, leaving only 10% free of acute GU toxicity. Anatomy-based IMRT to treat prostate cancer is incorporated into our daily routine without any problem. Acute toxicity is very low. Most of the recorded symptoms decrease over time, except for GI urgency and incontinence. The incorporation of additional symptoms makes the scoring more detailed.

Predictors of Radiation Pneumonitis in Patients Receiving Intensity Modulated Radiation Therapy for Hodgkin and Non-Hodgkin Lymphoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pinnix, Chelsea C., E-mail: ccpinnix@mdanderson.org; Smith, Grace L.; Milgrom, Sarah

Purpose: Few studies to date have evaluated factors associated with the development of radiation pneumonitis (RP) in patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), especially in patients treated with contemporary radiation techniques. These patients represent a unique group owing to the often large radiation target volumes within the mediastinum and to the potential to receive several lines of chemotherapy that add to pulmonary toxicity for relapsed or refractory disease. Our objective was to determine the incidence and clinical and dosimetric risk factors associated with RP in lymphoma patients treated with intensity modulated radiation therapy (IMRT) at a singlemore » institution. Methods and Materials: We retrospectively reviewed clinical charts and radiation records of 150 consecutive patients who received mediastinal IMRT for HL and NHL from 2009 through 2013. Clinical and dosimetric predictors associated with RP according to Radiation Therapy Oncology Group (RTOG) acute toxicity criteria were identified in univariate analysis using the Pearson χ{sup 2} test and logistic multivariate regression. Results: Mediastinal radiation was administered as consolidation therapy in 110 patients with newly diagnosed HL or NHL and in 40 patients with relapsed or refractory disease. The overall incidence of RP (RTOG grades 1-3) was 14% in the entire cohort. Risk of RP was increased for patients who received radiation for relapsed or refractory disease (25%) versus those who received consolidation therapy (10%, P=.019). Several dosimetric parameters predicted RP, including mean lung dose of >13.5 Gy, V{sub 20} of >30%, V{sub 15} of >35%, V{sub 10} of >40%, and V{sub 5} of >55%. The likelihood ratio χ{sup 2} value was highest for V{sub 5} >55% (χ{sup 2} = 19.37). Conclusions: In using IMRT to treat mediastinal lymphoma, all dosimetric parameters predicted RP, although small doses to large volumes of lung had the greatest influence. Patients with relapsed or refractory lymphoma who received salvage chemotherapy and hematopoietic stem cell transplantation were at higher risk for symptomatic RP.« less

Pretreatment 18F-FDG PET Textural Features in Locally Advanced Non-Small Cell Lung Cancer: Secondary Analysis of ACRIN 6668/RTOG 0235.

PubMed

Ohri, Nitin; Duan, Fenghai; Snyder, Bradley S; Wei, Bo; Machtay, Mitchell; Alavi, Abass; Siegel, Barry A; Johnson, Douglas W; Bradley, Jeffrey D; DeNittis, Albert; Werner-Wasik, Maria; El Naqa, Issam

2016-06-01

In a secondary analysis of American College of Radiology Imaging Network (ACRIN) 6668/RTOG 0235, high pretreatment metabolic tumor volume (MTV) on (18)F-FDG PET was found to be a poor prognostic factor for patients treated with chemoradiotherapy for locally advanced non-small cell lung cancer (NSCLC). Here we utilize the same dataset to explore whether heterogeneity metrics based on PET textural features can provide additional prognostic information. Patients with locally advanced NSCLC underwent (18)F-FDG PET prior to treatment. A gradient-based segmentation tool was used to contour each patient's primary tumor. MTV, maximum SUV, and 43 textural features were extracted for each tumor. To address overfitting and high collinearity among PET features, the least absolute shrinkage and selection operator (LASSO) method was applied to identify features that were independent predictors of overall survival (OS) after adjusting for MTV. Recursive binary partitioning in a conditional inference framework was utilized to identify optimal thresholds. Kaplan-Meier curves and log-rank testing were used to compare outcomes among patient groups. Two hundred one patients met inclusion criteria. The LASSO procedure identified 1 textural feature (SumMean) as an independent predictor of OS. The optimal cutpoint for MTV was 93.3 cm(3), and the optimal SumMean cutpoint for tumors above 93.3 cm(3) was 0.018. This grouped patients into three categories: low tumor MTV (n = 155; median OS, 22.6 mo), high tumor MTV and high SumMean (n = 23; median OS, 20.0 mo), and high tumor MTV and low SumMean (n = 23; median OS, 6.2 mo; log-rank P < 0.001). We have described an appropriate methodology to evaluate the prognostic value of textural PET features in the context of established prognostic factors. We have also identified a promising feature that may have prognostic value in locally advanced NSCLC patients with large tumors who are treated with chemoradiotherapy. Validation studies are warranted. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Pretreatment 18F-FDG PET Textural Features in Locally Advanced Non–Small Cell Lung Cancer: Secondary Analysis of ACRIN 6668/RTOG 0235

PubMed Central

Ohri, Nitin; Duan, Fenghai; Snyder, Bradley S.; Wei, Bo; Machtay, Mitchell; Alavi, Abass; Siegel, Barry A.; Johnson, Douglas W.; Bradley, Jeffrey D.; DeNittis, Albert; Werner-Wasik, Maria; El Naqa, Issam

2016-01-01

In a secondary analysis of American College of Radiology Imaging Network (ACRIN) 6668/RTOG 0235, high pretreatment metabolic tumor volume (MTV) on 18F-FDG PET was found to be a poor prognostic factor for patients treated with chemoradiotherapy for locally advanced non–small cell lung cancer (NSCLC). Here we utilize the same dataset to explore whether heterogeneity metrics based on PET textural features can provide additional prognostic information. Methods Patients with locally advanced NSCLC underwent 18F-FDG PET prior to treatment. A gradient-based segmentation tool was used to contour each patient’s primary tumor. MTV, maximum SUV, and 43 textural features were extracted for each tumor. To address over-fitting and high collinearity among PET features, the least absolute shrinkage and selection operator (LASSO) method was applied to identify features that were independent predictors of overall survival (OS) after adjusting for MTV. Recursive binary partitioning in a conditional inference framework was utilized to identify optimal thresholds. Kaplan–Meier curves and log-rank testing were used to compare outcomes among patient groups. Results Two hundred one patients met inclusion criteria. The LASSO procedure identified 1 textural feature (SumMean) as an independent predictor of OS. The optimal cutpoint for MTV was 93.3 cm3, and the optimal Sum-Mean cutpoint for tumors above 93.3 cm3 was 0.018. This grouped patients into three categories: low tumor MTV (n = 155; median OS, 22.6 mo), high tumor MTV and high SumMean (n = 23; median OS, 20.0 mo), and high tumor MTV and low SumMean (n = 23; median OS, 6.2 mo; log-rank P < 0.001). Conclusion We have described an appropriate methodology to evaluate the prognostic value of textural PET features in the context of established prognostic factors. We have also identified a promising feature that may have prognostic value in locally advanced NSCLC patients with large tumors who are treated with chemoradiotherapy. Validation studies are warranted. PMID:26912429

Dosimetric equivalence of nonstandard HDR brachytherapy catheter patterns

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cunha, J. A. M.; Hsu, I-C.; Pouliot, J.

2009-01-15

Purpose: To determine whether alternative high dose rate prostate brachytherapy catheter patterns can result in similar or improved dose distributions while providing better access and reducing trauma. Materials and Methods: Standard prostate cancer high dose rate brachytherapy uses a regular grid of parallel needle positions to guide the catheter insertion. This geometry does not easily allow the physician to avoid piercing the critical structures near the penile bulb nor does it provide position flexibility in the case of pubic arch interference. This study used CT datasets with 3 mm slice spacing from ten previously treated patients and digitized new cathetersmore » following three hypothetical catheter patterns: conical, bi-conical, and fireworks. The conical patterns were used to accommodate a robotic delivery using a single entry point. The bi-conical and fireworks patterns were specifically designed to avoid the critical structures near the penile bulb. For each catheter distribution, a plan was optimized with the inverse planning algorithm, IPSA, and compared with the plan used for treatment. Irrelevant of catheter geometry, a plan must fulfill the RTOG-0321 dose criteria for target dose coverage (V{sub 100}{sup Prostate}>90%) and organ-at-risk dose sparing (V{sub 75}{sup Bladder}<1 cc, V{sub 75}{sup Rectum}<1 cc, V{sub 125}{sup Urethra}<<1 cc). Results: The three nonstandard catheter patterns used 16 nonparallel, straight divergent catheters, with entry points in the perineum. Thirty plans from ten patients with prostate sizes ranging from 26 to 89 cc were optimized. All nonstandard patterns fulfilled the RTOG criteria when the clinical plan did. In some cases, the dose distribution was improved by better sparing the organs-at-risk. Conclusion: Alternative catheter patterns can provide the physician with additional ways to treat patients previously considered unsuited for brachytherapy treatment (pubic arch interference) and facilitate robotic guidance of catheter insertion. In addition, alternative catheter patterns may decrease toxicity by avoidance of the critical structures near the penile bulb while still fulfilling the RTOG criteria.« less

Clinical Outcomes With Dose-Escalated Adaptive Radiation Therapy for Urinary Bladder Cancer: A Prospective Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murthy, Vedang, E-mail: vmurthy@actrec.gov.in; Masodkar, Renuka; Kalyani, Nikhil

Purpose: The purpose of this study was to assess feasibility, clinical outcomes, and toxicity in patients with bladder cancer treated with adaptive, image guided radiation therapy (IGRT) for bladder preservation as a part of trimodality treatment. The role of dose escalation was also studied. Methods and Materials: Forty-four patients with localized bladder cancer were enrolled in a prospective study. They underwent maximal safe resection of bladder tumor and concurrent platinum-based chemotherapy. Patients with large tumors were offered induction chemotherapy. Radiation therapy planning was done using either 3 (n=34) or 6 (n=10) concentrically grown planning target volumes (PTV). Patients received 64 Gymore » in 32 fractions to the whole bladder and 55 Gy to the pelvic nodes and, if appropriate, a simultaneous integrated boost to the tumor bed to 68 Gy (equivalent dose for 2-Gy fractions assuming α/β of 10 [EQD2]{sub 10} = 68.7 Gy). Daily megavoltage (MV) imaging helped to choose the most appropriate PTV encompassing bladder for the particular day (using plan-of-the-day approach). Results: Most patients (88%) had T2 disease. Sixteen patients (36%) received neoadjuvant chemotherapy. A majority of the patients (73%) received prophylactic nodal irradiation, whereas 55% of the patients received escalated dose to the tumor bed. With a median follow-up of 30 months, the 3-year locoregional control (LRC), disease-free survival, and overall survival (OS) were 78%, 66%, and 67%, respectively. The bladder preservation rate was 83%. LRC (87% vs 68%, respectively, P=.748) and OS (74% vs 60%, respectively, P=.36) rates were better in patients receiving dose escalation. Instances of acute and late Radiation Therapy Oncology Group (RTOG) grade 3 genitourinary toxicity was seen in 5 (11%) and 2 (4%) patients, respectively. There was no acute or late RTOG grade 3 or higher gastrointestinal toxicity. Conclusions: Adaptive IGRT using plan-of-the-day approach for bladder preservation is clinically feasible, with good oncological outcomes and low rates of acute and late toxicities. Dose escalation is safe and possibly improves outcomes in bladder preservation.« less

The impact of concurrent granulocyte-macrophage colony-stimulating factor on quality of life in head and neck cancer patients: results of the randomized, placebo-controlled Radiation Therapy Oncology Group 9901 trial.

PubMed

Hoffman, Karen E; Pugh, Stephanie L; James, Jennifer L; Scarantino, Charles; Movsas, Benjamin; Valicenti, Richard K; Fortin, Andre; Pollock, JonDavid; Kim, Harold; Brachman, David G; Berk, Lawrence B; Bruner, Deborah Watkins; Kachnic, Lisa A

2014-08-01

The Radiation Therapy Oncology Group (RTOG) conducted a randomized, placebo-controlled trial evaluating the efficacy of GM-CSF in reducing mucosal injury and symptom burden from curative radiotherapy for head and neck (H&N) cancer. Eligible patients with H&N cancer receiving radiation encompassing ≥50 % of the oral cavity or oropharynx received subcutaneous GM-CSF or placebo. Quality of life (QoL) was assessed using the RTOG-modified University of Washington H&N Symptom Questionnaire at baseline 4, 13, 26, and 48 weeks from radiation initiation. Of 125 eligible patients, 114 were evaluable for QoL (58 GM-CSF, 56 placebo). Patient demographics, clinical characteristics, and baseline symptom scores were well balanced between the treatment arms. At the end of the acute period (13 weeks), patients in both arms reported negative change in total symptom score indicating increase in symptom burden relative to baseline (mean -18.4 GM-CSF, -20.8 placebo). There was no difference in change in total symptom score (p > 0.05) or change in mucous, pain, eating, or activity domain scores (p > 0.01) between patients in the GM-CSF and placebo arms. Analysis limited to patients treated per protocol or with an acceptable protocol deviation also found no difference in change in total symptom score (p > 0.05) or change in domain scores (p > 0.01) between treatment arms. Provider assessment of acute mucositis during treatment did not correlate with patient-reported mucous domain and total symptom scores (p > 0.05). GM-CSF administered concurrently during head and neck radiation does not appear to significantly improve patient-reported QoL symptom burden.

Distribution of prostate nodes: a PET/CT-derived anatomic atlas of prostate cancer patients before and after surgical treatment.

PubMed

Hegemann, Nina-Sophie; Wenter, Vera; Spath, Sonja; Kusumo, Nadia; Li, Minglun; Bartenstein, Peter; Fendler, Wolfgang P; Stief, Christian; Belka, Claus; Ganswindt, Ute

2016-03-11

In order to define adequate radiation portals in nodal positive prostate cancer a detailed knowledge of the anatomic lymph-node distribution is mandatory. We therefore systematically analyzed the localization of Choline PET/CT positive lymph nodes and compared it to the RTOG recommendation of pelvic CTV, as well as to previous work, the SPECT sentinel lymph node atlas. Thirty-two patients being mostly high risk patients with a PSA of 12.5 ng/ml (median) received PET/CT before any treatment. Eighty-seven patients received PET/CT for staging due to biochemical failure with a median PSA of 3.12 ng/ml. Each single PET-positive lymph node was manually contoured in a "virtual" patient dataset to achieve a 3-D visualization, resulting in an atlas of the cumulative PET positive lymph node distribution. Further the PET-positive lymph node location in each patient was assessed with regard to the existence of a potential geographic miss (i.e. PET-positive lymph nodes that would not have been treated adequately by the RTOG consensus on CTV definition of pelvic lymph nodes). Seventy-eight and 209 PET positive lymph nodes were detected in patients with no prior treatment and in postoperative patients, respectively. The most common sites of PET positive lymph nodes in patients with no prior treatment were external iliac (32.1 %), followed by common iliac (23.1 %) and para-aortic (19.2 %). In postoperative patients the most common sites of PET positive lymph nodes were common iliac (24.9 %), followed by external iliac (23.0 %) and para-aortic (20.1 %). In patients with no prior treatment there were 34 (43.6 %) and in postoperative patients there were 77 (36.8 %) of all detected lymph nodes that would not have been treated adequately using the RTOG CTV. We compared the distribution of lymph nodes gained by Choline PET/CT to the preexisting SPECT sentinel lymph node atlas and saw an overall good congruence. Choline PET/CT and SPECT sentinel lymph node atlas are comparable to each other. More than one-third of the PET positive lymph nodes in patients with no prior treatment and in postoperative patients would not have been treated adequately using the RTOG CTV. To reduce geographical miss, image based definition of an individual target volume is necessary.

SU-E-CAMPUS-J-04: Image Guided Radiation Therapy (IGRT): Review of Technical Standards and Credentialing in Radiotherapy Clinical Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giaddui, T; Chen, W; Yu, J

2014-06-15

Purpose: To review IGRT credentialing experience and unexpected technical issues encountered in connection with advanced radiotherapy technologies as implemented in RTOG clinical trials. To update IGRT credentialing procedures with the aim of improving the quality of the process, and to increase the proportion of IGRT credentialing compliance. To develop a living disease site-specific IGRT encyclopedia. Methods: Numerous technical issues were encountered during the IGRT credentialing process. The criteria used for credentialing review were based on: image quality; anatomy included in fused data sets and shift results. Credentialing requirements have been updated according to the AAPM task group reports for IGRTmore » to ensure that all required technical items are included in the quality review process. Implementation instructions have been updated and expanded for recent protocols. Results: Technical issues observed during the credentialing review process include, but are not limited to: poor quality images; inadequate image acquisition region; poor data quality; shifts larger than acceptable; no soft tissue surrogate. The updated IGRT credentialing process will address these issues and will also include the technical items required from AAPM: TG 104; TG 142 and TG 179 reports. An instruction manual has been developed describing a remote credentialing method for reviewers. Submission requirements are updated, including images/documents as well as facility questionnaire. The review report now includes summary of the review process and the parameters that reviewers check. We have reached consensus on the minimum IGRT technical requirement for a number of disease sites. RTOG 1311(NRG-BR002A Phase 1 Study of Stereotactic Body Radiotherapy (SBRT) for the Treatment of Multiple Metastases) is an example, here; the protocol specified the minimum requirement for each anatomical sites (with/without fiducials). Conclusion: Technical issues are identified and reported. IGRT guidelines are updated, with the corresponding credentialing requirements. An IGRT encyclopedia describing site-specific implementation issues is currently in development.« less

Regional Lymph Node Uptake of [{sup 18}F]Fluorodeoxyglucose After Definitive Chemoradiation Therapy Predicts Local-Regional Failure of Locally Advanced Non-Small Cell Lung Cancer: Results of ACRIN 6668/RTOG 0235

DOE Office of Scientific and Technical Information (OSTI.GOV)

Markovina, Stephanie; Duan, Fenghai; Snyder, Bradley S.

2015-11-01

Purpose: The American College of Radiology Imaging Network (ACRIN) 6668/Radiation Therapy Oncology Group (RTOG) 0235 study demonstrated that standardized uptake values (SUV) on post-treatment [{sup 18}F]fluorodeoxyglucose-positron emission tomography (FDG-PET) correlated with survival in locally advanced non-small cell lung cancer (NSCLC). This secondary analysis determined whether SUV of regional lymph nodes (RLNs) on post-treatment FDG-PET correlated with patient outcomes. Methods and Materials: Included for analysis were patients treated with concurrent chemoradiation therapy, using radiation doses ≥60 Gy, with identifiable FDG-avid RLNs (distinct from primary tumor) on pretreatment FDG-PET, and post-treatment FDG-PET data. ACRIN core laboratory SUV measurements were used. Event time was calculatedmore » from the date of post-treatment FDG-PET. Local-regional failure was defined as failure within the treated RT volume and reported by the treating institution. Statistical analyses included Wilcoxon signed rank test, Kaplan-Meier curves (log rank test), and Cox proportional hazards regression modeling. Results: Of 234 trial-eligible patients, 139 (59%) had uptake in both primary tumor and RLNs on pretreatment FDG-PET and had SUV data from post-treatment FDG-PET. Maximum SUV was greater for primary tumor than for RLNs before treatment (P<.001) but not different post-treatment (P=.320). Post-treatment SUV of RLNs was not associated with overall survival. However, elevated post-treatment SUV of RLNs, both the absolute value and the percentage of residual activity compared to the pretreatment SUV were associated with inferior local-regional control (P<.001). Conclusions: High residual metabolic activity in RLNs on post-treatment FDG-PET is associated with worse local-regional control. Based on these data, future trials evaluating a radiation therapy boost should consider inclusion of both primary tumor and FDG-avid RLNs in the boost volume to maximize local-regional control.« less

A class solution for volumetric-modulated arc therapy planning in postprostatectomy radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Forde, Elizabeth, E-mail: eforde@tcd.ie; Bromley, Regina; Institute of Medical Physics, School of Physics, University of Sydney, New South Wales

This study is aimed to test a postprostatectomy volumetric-modulated arc therapy (VMAT) planning class solution. The solution applies to both the progressive resolution optimizer algorithm version 2 (PRO 2) and the algorithm version 3 (PRO 3), addressing the effect of an upgraded algorithm. A total of 10 radical postprostatectomy patients received 68 Gy to 95% of the planning target volume (PTV), which was planned using VMAT. Each case followed a set of planning instructions; including contouring, field setup, and predetermined optimization parameters. Each case was run through both algorithms only once, with no user interaction. Results were averaged and comparedmore » against Radiation Therapy Oncology Group (RTOG) 0534 end points. In addition, the clinical target volume (CTV) D{sub 100}, PTV D{sub 99}, and PTV mean doses were recorded, along with conformity indices (CIs) (95% and 98%) and the homogeneity index. All cases satisfied PTV D{sub 95} of 68 Gy and a maximum dose < 74.8 Gy. The average result for the PTV D{sub 99} was 64.1 Gy for PRO 2 and 62.1 Gy for PRO 3. The average PTV mean dose for PRO 2 was 71.4 Gy and 71.5 Gy for PRO 3. The CTV D{sub 100} average dose was 67.7 and 68.0 Gy for PRO 2 and PRO 3, respectively. The mean homogeneity index for both algorithms was 0.08. The average 95% CI was 1.17 for PRO 2 and 1.19 for PRO 3. For 98%, the average results were 1.08 and 1.12 for PRO 2 and PRO 3, respectively. All cases for each algorithm met the RTOG organs at risk dose constraints. A successful class solution has been established for prostate bed VMAT radiotherapy regardless of the algorithm used.« less

Rebamipide gargle in preventive management of chemo-radiotherapy induced oral mucositis.

PubMed

Chaitanya, B; Pai, Keerthilatha M; Yathiraj, Prahlad H; Fernandes, Donald; Chhaparwal, Yogesh

2017-09-01

Oral mucositis is inflammation of mucosa of oral cavity which is an inevitable and acute side effect in patients undergoing chemoradiotherapy for head & neck cancer. Though many agents have been tried in prevention & treatment of oral mucositis, until date no single agent exists that is universally established to be effective. 60 Patients diagnosed with Head & Neck cancer recruited for concurrent chemo-radiotherapy were assigned in a double blind fashion into 2 groups using computer based 1:1 ratio randomization. Subjects in Group 1 were given Rebamipide gargle while subjects in Group 2 were given Placebo gargle in similar colour coded bottles to gargle 6 times/day. Subjective assessment of oral mucositis was done by Numeric Rating Scale (NRS) and objective scoring according to RTOG system. All subjects in the Group 1 reported good treatment compliance but 4 subjects in Group 2 developed burning sensation to gargle and were excluded. Onset of oral mucositis was 3.5days earlier in Group 2 (mean=11.17) as compared to Group 1 (mean=14.63). At the end of chemo-radiotherapy, severity of oral mucositis was significantly lower in Group 1 (mean=1.97) than in Group 2 (mean=2.81). Findings of this study revealed that Rebamipide gargle may be an effective means to prolong the onset of oral mucositis and may reduce the severity of oral mucositis in undergoing chemo-radiotherapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

SU-E-T-534: Dosimetric Effect of Multileaf Collimator Leaf Width On Volumetric Modulated Arc Stereotactic Radiotherapy for Spine Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amoush, A; Djemil, T; Subedi, L

2014-06-01

Purpose: To study the dosimetric impact of MLC leaf width in patients treated with Volumetric Modulated Arc Therapy (VMAT) for spine Stereotactic Body radiation Therapy (SBRT). Methods: Twelve spine SBRT patients were retrospectively selected for this study. The patients were treated with IMRT following the RTOG-0631 of spine metastasis. The prescription dose was 16 Gy in one fraction to 90% of the target volume (V16 > 90%). The maximum spinal cord dose of 14 Gy and 10% of the cord receiving < 10 Gy (V10) were set as dose constraints. For purpose of this study, three dual arc VMAT plansmore » were created for each patient using three different MLC leaf widths: 2.5 mm, 4mm, and 5mm. The compliance to RTOG 0631, conformal index (CI), dose gradient index (DGI), and number of monitor units (MUs) were compared. Results: The average V16 of the target was 91.91±1.36%, 93.73±2.38%, and 92.25±2.49% for 2.5 mm, 4 mm, and 5 mm leaf widths, respectively (p=0.39). Accordingly, the average CI was 1.36±0.39, 1.36±0.34, and 1.41±0.3 (0.96), respectively. The average DGI was 0.24 ± 0.05, 0.22 ± 0.05, and 0.23 ± 0.04, respectively (p=0.86). The average spinal cord maximum dose was 12.10 ± 0.88 Gy, 12.52 ± 1.15 Gy, and 12.05 ± 1.12 (p=0.75) and V10 was 2.69 ± 1.71 cc, 5.43 ± 2.16 cc, and 3.71 ± 2.34 cc (p=0.15) for 2.5 mm, 4 mm, and 5 mm leaf widths, respectively. According, the average number of MUs was 4255 ± 431 MU, 5049 ± 1036 MU, and 4231 ± 580 MU respectively (p=0.17). Conclusion: The use of 2.5 mm, 4 mm, and 5 mm MLCs achieved similar VMAT plan quality as recommended by RTOG-0631. The dosimetric parameters were also comparable for the three MLCs.« less

SU-E-T-129: Dosimetric Evaluation of the Impact of Density Correction On Dose Calculation of Breast Cancer Treatment: A Study Based On RTOG 1005 Cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, J; Yu, Y

Purpose: RTOG 1005 requires density correction in the dose calculation of breast cancer radiation treatment. The aim of the study was to evaluate the impact of density correction on the dose calculation. Methods: Eight cases were studied, which were planned on an XiO treatment planning system with pixel-by-pixel density correction using a superposition algorithm, following RTOG 1005 protocol requirements. Four were protocol Arm 1 (standard whole breast irradiation with sequential boost) cases and four were Arm 2 (hypofractionated whole breast irradiation with concurrent boost) cases. The plans were recalculated with the same monitor units without density correction. Dose calculations withmore » and without density correction were compared. Results: Results of Arm 1 and Arm 2 cases showed similar trends in the comparison. The average differences between the calculations with and without density correction (difference = Without - With) among all the cases were: -0.82 Gy (range: -2.65∼−0.18 Gy) in breast PTV Eval D95, −0.75 Gy (range: −1.23∼0.26 Gy) in breast PTV Eval D90, −1.00 Gy (range: −2.46∼−0.29 Gy) in lumpectomy PTV Eval D95, −0.78 Gy (range: −1.30∼0.11 Gy) in lumpectomy PTV Eval D90, −0.43% (range: −0.95∼−0.14%) in ipsilateral lung V20, −0.81% (range: −1.62∼−0.26%) in V16, −1.95% (range: −4.13∼−0.84%) in V10, −2.64% (−5.55∼−1.04%) in V8, −4.19% (range: −6.92∼−1.81%) in V5, and −4.95% (range: −7.49∼−2.01%) in V4, respectively. The differences in other normal tissues were minimal. Conclusion: The effect of density correction was observed in breast target doses (an average increase of ∼1 Gy in D95 and D90, compared to the calculation without density correction) and exposed ipsilateral lung volumes in low dose region (average increases of ∼4% and ∼5% in V5 and V4, respectively)« less

SU-F-BRD-05: Dosimetric Comparison of Protocol-Based SBRT Lung Treatment Modalities: Statistically Significant VMAT Advantages Over Fixed- Beam IMRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Best, R; Harrell, A; Geesey, C

2014-06-15

Purpose: The purpose of this study is to inter-compare and find statistically significant differences between flattened field fixed-beam (FB) IMRT with flattening-filter free (FFF) volumetric modulated arc therapy (VMAT) for stereotactic body radiation therapy SBRT. Methods: SBRT plans using FB IMRT and FFF VMAT were generated for fifteen SBRT lung patients using 6 MV beams. For each patient, both IMRT and VMAT plans were created for comparison. Plans were generated utilizing RTOG 0915 (peripheral, 10 patients) and RTOG 0813 (medial, 5 patients) lung protocols. Target dose, critical structure dose, and treatment time were compared and tested for statistical significance. Parametersmore » of interest included prescription isodose surface coverage, target dose heterogeneity, high dose spillage (location and volume), low dose spillage (location and volume), lung dose spillage, and critical structure maximum- and volumetric-dose limits. Results: For all criteria, we found equivalent or higher conformality with VMAT plans as well as reduced critical structure doses. Several differences passed a Student's t-test of significance: VMAT reduced the high dose spillage, evaluated with conformality index (CI), by an average of 9.4%±15.1% (p=0.030) compared to IMRT. VMAT plans reduced the lung volume receiving 20 Gy by 16.2%±15.0% (p=0.016) compared with IMRT. For the RTOG 0915 peripheral lesions, the volumes of lung receiving 12.4 Gy and 11.6 Gy were reduced by 27.0%±13.8% and 27.5%±12.6% (for both, p<0.001) in VMAT plans. Of the 26 protocol pass/fail criteria, VMAT plans were able to achieve an average of 0.2±0.7 (p=0.026) more constraints than the IMRT plans. Conclusions: FFF VMAT has dosimetric advantages over fixed beam IMRT for lung SBRT. Significant advantages included increased dose conformity, and reduced organs-at-risk doses. The overall improvements in terms of protocol pass/fail criteria were more modest and will require more patient data to establish difference trends of more statistical significance.« less

Automatic planning on hippocampal avoidance whole-brain radiotherapy.

PubMed

Wang, Shuo; Zheng, Dandan; Zhang, Chi; Ma, Rongtao; Bennion, Nathan R; Lei, Yu; Zhu, Xiaofeng; Enke, Charles A; Zhou, Sumin

2017-01-01

Mounting evidence suggests that radiation-induced damage to the hippocampus plays a role in neurocognitive decline for patients receiving whole-brain radiotherapy (WBRT). Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) has been proposed to reduce the putative neurocognitive deficits by limiting the dose to the hippocampus. However, urgency of palliation for patients as well as the complexities of the treatment planning may be barriers to protocol enrollment to accumulate further clinical evidence. This warrants expedited quality planning of HA-WBRT. Pinnacle 3 Automatic treatment planning was designed to increase planning efficiency while maintaining or improving plan quality and consistency. The aim of the present study is to evaluate the performance of the Pinnacle 3 Auto-Planning on HA-WBRT treatment planning. Ten patients previously treated for brain metastases were selected. Hippocampal volumes were contoured on T1 magnetic resonance (MR) images, and planning target volumes (PTVs) were generated based on RTOG0933. The following 2 types of plans were generated by Pinnacle 3 Auto-Planning: the one with 2 coplanar volumetric modulated arc therapy (VMAT) arcs and the other with 9-field noncoplanar intensity-modulated radiation therapy (IMRT). D 2% and D 98% of PTV were used to calculate homogeneity index (HI). HI and Paddick Conformity index (CI) of PTV as well as D 100% and D max of the hippocampus were used to evaluate the plan quality. All the auto-plans met the dose coverage and constraint objectives based on RTOG0933. The auto-plans eliminated the necessity of generating pseudostructures by the planners, and it required little manual intervention which expedited the planning process. IMRT quality assurance (QA) results also suggest that all the auto-plans are practically acceptable on delivery. Pinnacle 3 Auto-Planning generates acceptable plans by RTOG0933 criteria without time-consuming planning process. The expedited quality planning achieved by Auto-Planning (AP) may facilitate protocol enrollment of patients to further investigate the hippocampal-sparing effect and be used to ensure timely start of palliative treatment in future clinical practice. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Predictors of Radiation Therapy–Related Gastrointestinal Toxicity From Anal Cancer Dose-Painted Intensity Modulated Radiation Therapy: Secondary Analysis of NRG Oncology RTOG 0529

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olsen, Jeffrey R., E-mail: Jeffrey.R.Olsen@ucdenver.edu; Moughan, Jennifer; Myerson, Robert

Purpose: NRG Oncology RTOG 0529 assessed the feasibility of dose-painted intensity modulated radiation therapy (DP-IMRT) to reduce the acute morbidity of chemoradiation with 5-fluorouracil (5FU) and mitomycin-C (MMC) for T2-4N0-3M0 anal cancer. This secondary analysis was performed to identify patient and treatment factors associated with acute and late gastrointestinal (GI) adverse events (AEs). Methods and Materials: NRG Oncology RTOG 0529 treatment plans were reviewed to extract dose-volume data for tightly contoured small bowel, loosely contoured anterior pelvic contents (APC), and uninvolved colon outside the target volume (UC). Univariate logistic regression was performed to evaluate association between volumes of each structuremore » receiving doses ≥5 to 60 Gy (V5-V60) in 5-Gy increments between patients with and without grade ≥2 acute and late GI AEs, and grade ≥3 acute GI AEs. Additional patient and treatment factors were evaluated in multivariate logistic regression (acute AEs) or Cox proportional hazards models (late AEs). Results: Among 52 evaluable patients, grade ≥2 acute, grade ≥2 late, and grade ≥3 acute GI AEs were observed in 35, 17, and 10 patients, respectively. Trends (P<.05) toward statistically significant associations were observed between grade ≥2 acute GI AEs and small bowel dose (V20-V40), grade ≥2 late GI AEs and APC dose (V60), grade ≥3 acute GI AEs and APC dose (V5-V25), increasing age, tumor size >4 cm, and worse Zubrod performance status. Small bowel volumes of 186.0 cc, 155.0 cc, 41.0 cc, and 30.4 cc receiving doses greater than 25, 30, 35, and 40 Gy, respectively, correlated with increased risk of acute grade ≥2 GI AEs. Conclusions: Acute and late GI AEs from 5FU/MMC chemoradiation using DP-IMRT correlate with radiation dose to the small bowel and APC. Such associations will be incorporated in the dose-volume normal tissue constraint design for future NRG oncology anal cancer studies.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guida, K; Qamar, K; Thompson, M

Purpose: The RTOG 1005 trial offered a hypofractionated arm in delivering WBRT+SIB. Traditionally, treatments were planned at our institution using field-in-field (FiF) tangents with a concurrent 3D conformal boost. With the availability of VMAT, it is possible that a hybrid VMAT-3D planning technique could provide another avenue in treating WBRT+SIB. Methods: A retrospective study of nine patients previously treated using RTOG 1005 guidelines was performed to compare FiF+3D plans with the hybrid technique. A combination of static tangents and partial VMAT arcs were used in base-dose optimization. The hybrid plans were optimized to deliver 4005cGy to the breast PTVeval andmore » 4800cGy to the lumpectomy PTVeval over 15 fractions. Plans were optimized to meet the planning goals dictated by RTOG 1005. Results: Hybrid plans yielded similar coverage of breast and lumpectomy PTVs (average D95 of 4013cGy compared to 3990cGy for conventional), while reducing the volume of high dose within the breast; the average D30 and D50 for the hybrid technique were 4517cGy and 4288cGy, compared to 4704cGy and 4377cGy for conventional planning. Hybrid plans increased conformity as well, yielding CI95% values of 1.22 and 1.54 for breast and lumpectomy PTVeval volumes; in contrast, conventional plans averaged 1.49 and 2.27, respectively. The nearby organs at risk (OARs) received more low dose with the hybrid plans due to low dose spray from the partial arcs, but all hybrid plans did meet the acceptable constraints, at a minimum, from the protocol. Treatment planning time was also reduced, as plans were inversely optimized (VMAT) rather than forward optimized. Conclusion: Hybrid-VMAT could be a solution in delivering WB+SIB, as plans yield very conformal treatment plans and maintain clinical standards in OAR sparing. For treating breast cancer patients with a simultaneously-integrated boost, Hybrid-VMAT offers superiority in dosimetric conformity and planning time as compared to FIF techniques.« less

Margin reduction from image guided radiation therapy for soft tissue sarcoma: Secondary analysis of Radiation Therapy Oncology Group 0630 results.

PubMed

Li, X Allen; Chen, Xiaojian; Zhang, Qiang; Kirsch, David G; Petersen, Ivy; DeLaney, Thomas F; Freeman, Carolyn R; Trotti, Andy; Hitchcock, Ying; Bedi, Meena; Haddock, Michael; Salerno, Kilian; Dundas, George; Wang, Dian

2016-01-01

Six imaging modalities were used in Radiation Therapy Oncology Group (RTOG) 0630, a study of image guided radiation therapy (IGRT) for primary soft tissue sarcomas of the extremity. We analyzed all daily patient-repositioning data collected in this trial to determine the impact of daily IGRT on clinical target volume-to-planning target volume (CTV-to-PTV) margin. Daily repositioning data, including shifts in right-left (RL), superior-inferior (SI), and anterior-posterior (AP) directions and rotations for 98 patients enrolled in RTOG 0630 from 18 institutions were analyzed. Patients were repositioned daily on the basis of bone anatomy by using pretreatment images, including kilovoltage orthogonal images (KVorth), megavoltage orthogonal images (MVorth), KV fan-beam computed tomography (KVCT), KV cone beam CT (KVCB), MV fan-beam CT (MVCT), and MV cone beam CT (MVCB). Means and standard deviations (SDs) for each shift and rotation were calculated for each patient and for each IGRT modality. The Student's t tests and F-tests were performed to analyze the differences in the means and SDs. Necessary CTV-to-PTV margins were estimated. The repositioning shifts and day-to-day variations were large and generally similar for the 6 imaging modalities. Of the 2 most commonly used modalities, MVCT and KVorth, there were no statistically significant differences in the shifts and rotations (P = .15 and .59 for the RL and SI shifts, respectively; and P = .22 for rotation), except for shifts in AP direction (P = .002). The estimated CTV-to-PTV margins in the RL, SI, and AP directions would be 13.0, 10.4, and 11.7 mm from MVCT data, respectively, and 13.1, 8.6, and 10.8 mm from KVorth data, respectively, indicating that margins substantially larger than 5 mm used with daily IGRT would be required in the absence of IGRT. The observed large daily repositioning errors and the large variations among institutions imply that daily IGRT is necessary for this tumor site, particularly in multi-institutional trials. Otherwise, a CTV-to-PTV margin of 1.5 cm is required to account for daily setup variations. Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

A pilot study using dynamic contrast enhanced-MRI as a response biomarker of the radioprotective effect of memantine in patients receiving whole brain radiotherapy

PubMed Central

Wong, Philip; Leppert, Ilana R.; Roberge, David; Boudam, Karim; Brown, Paul D.; Muanza, Thierry; Pike, G. Bruce; Chankowsky, Jeffrey; Mihalcioiu, Catalin

2016-01-01

Purpose This pilot prospective study sought to determine whether dynamic contrast enhanced MRI (DCE-MRI) could be used as a clinical imaging biomarker of tissue toxicity from whole brain radiotherapy (WBRT). Method 14 patients who received WBRT were imaged using dynamic contrast enhanced DCE-MRI prior to and at 8-weeks, 16-weeks and 24-weeks after the initiation of WBRT. Twelve of the patients were also enrolled in the RTOG 0614 trial, which randomized patients to the use of placebo or memantine. After the unblinding of the treatments received by RTOG 0614 patients, DCE-MRI measures of tumor tissue and normal appearing white matter (NAWM) vascular permeability (Initial Area Under the Curve (AUC) Blood Adjusted) was analyzed. Cognitive, quality-of-life (QOL) assessment and blood samples were collected according to the patient's ability to tolerate the exams. Circulating endothelial cells (CEC) were measured using flow cytometry. Results Following WBRT, there was an increasing trend in the vascular permeability of tumors (p=0.09) and NAWM (p=0.06) with time. Memantine significantly (p=0.01) reduced NAWM AUC changes following radiotherapy. Patients on memantine retained (COWA p= 0.03) better cognitive functions than those on placebo. No association was observed between the level of CEC and DCE-MRI changes, time from radiotherapy or memantine use. Conclusions DCE-MRI can detect vascular damage secondary to WBRT. Our data suggests that memantine reduces WBRT-induced brain vasculature damages. PMID:27248467

A pilot study using dynamic contrast enhanced-MRI as a response biomarker of the radioprotective effect of memantine in patients receiving whole brain radiotherapy.

PubMed

Wong, Philip; Leppert, Ilana R; Roberge, David; Boudam, Karim; Brown, Paul D; Muanza, Thierry; Pike, G Bruce; Chankowsky, Jeffrey; Mihalcioiu, Catalin

2016-08-09

This pilot prospective study sought to determine whether dynamic contrast enhanced MRI (DCE-MRI) could be used as a clinical imaging biomarker of tissue toxicity from whole brain radiotherapy (WBRT). 14 patients who received WBRT were imaged using dynamic contrast enhanced DCE-MRI prior to and at 8-weeks, 16-weeks and 24-weeks after the initiation of WBRT. Twelve of the patients were also enrolled in the RTOG 0614 trial, which randomized patients to the use of placebo or memantine. After the unblinding of the treatments received by RTOG 0614 patients, DCE-MRI measures of tumor tissue and normal appearing white matter (NAWM) vascular permeability (Initial Area Under the Curve (AUC) Blood Adjusted) was analyzed. Cognitive, quality-of-life (QOL) assessment and blood samples were collected according to the patient's ability to tolerate the exams. Circulating endothelial cells (CEC) were measured using flow cytometry. Following WBRT, there was an increasing trend in the vascular permeability of tumors (p=0.09) and NAWM (p=0.06) with time. Memantine significantly (p=0.01) reduced NAWM AUC changes following radiotherapy. Patients on memantine retained (COWA p= 0.03) better cognitive functions than those on placebo. No association was observed between the level of CEC and DCE-MRI changes, time from radiotherapy or memantine use. DCE-MRI can detect vascular damage secondary to WBRT. Our data suggests that memantine reduces WBRT-induced brain vasculature damages.

Multi-criteria optimization achieves superior normal tissue sparing in a planning study of intensity-modulated radiation therapy for RTOG 1308-eligible non-small cell lung cancer patients.

PubMed

Kamran, Sophia C; Mueller, Birgit S; Paetzold, Peter; Dunlap, Joseph; Niemierko, Andrzej; Bortfeld, Thomas; Willers, Henning; Craft, David

2016-03-01

In this planning study, we studied the benefit of intensity-modulated radiation therapy (IMRT) with multi-criteria optimization (MCO) in locally advanced non-small cell lung carcinoma (NSCLC). We selected 10 consecutive patients with gross tumor within 1cm of the esophagus eligible for RTOG 1308, randomized phase II trial of 70 Gy protons vs photons. Planning was performed per protocol. In addition, a novel approach for esophagus sparing was applied by making the contralateral esophagus (CE) an avoidance structure. MCO and non-MCO plans underwent double-blinded review. Plan differences in dose-volume histogram parameters were analyzed. Median plan differences were mean lung dose=0.8 Gy (p=0.01), lung V20=1.1% (p=0.06), heart V30=1.0% (p=0.03), heart V45=0.6% (p=0.03), esophagus V60=1.2% (p=0.04), and CE V45=3.2% (p=0.01), all favoring MCO over non-MCO. PTV coverage with 95% dose was ⩾98.0% for both plans. There were 5 minor protocol deviations with non-MCO plans and 2 with MCO. Median improvement of active planning time with MCO was 88 min (p<0.01). Physicians preferred 8 MCO and 2 non-MCO plans (p=0.04). MCO plans yielded significant improvements in organ-at-risk sparing without compromising target coverage, consumed less dosimetrist time, and were preferred by physicians. We suggest incorporating MCO into prospective clinical trials. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Quality of Life and Performance Status From a Substudy Conducted Within a Prospective Phase 3 Randomized Trial of Concurrent Standard Radiation Versus Accelerated Radiation Plus Cisplatin for Locally Advanced Head and Neck Carcinoma: NRG Oncology RTOG 0129.

PubMed

Xiao, Canhua; Zhang, Qiang; Nguyen-Tân, Phuc Felix; List, Marcie; Weber, Randal S; Ang, K Kian; Rosenthal, David; Filion, Edith J; Kim, Harold; Silverman, Craig; Raben, Adam; Galloway, Thomas; Fortin, Andre; Gore, Elizabeth; Winquist, Eric; Jones, Christopher U; Robinson, William; Raben, David; Le, Quynh-Thu; Bruner, Deborah

2017-03-15

To analyze quality of life (QOL) and performance status (PS) for head and neck cancer (HNC) patients treated on NRG Oncology RTOG 0129 by treatment (secondary outcome) and p16 status, and to examine the association between QOL/PS and survival. Eligible patients were randomized into either an accelerated-fractionation arm or a standard-fractionation arm, and completed the Performance Status Scale for the Head and Neck (PSS-HN), the Head and Neck Radiotherapy Questionnaire (HNRQ), and the Spitzer Quality of Life Index (SQLI) at 8 time points from before treatment to 5 years after treatment. The results from the analysis of area under the curve showed that QOL/PS was not significantly different between the 2 arms from baseline to year after treatment (P ranged from .39 to .98). The results from general linear mixed models further supported the nonsignificant treatment effects until 5 years after treatment (P=.95, .90, and .84 for PSS-HN Diet, Eating, and Speech, respectively). Before treatment and after 1 year after treatment, p16-positive oropharyngeal cancer (OPC) patients had better QOL than did p16-negative patients (P ranged from .0283 to <.0001 for all questionnaires). However, QOL/PS decreased more significantly from pretreatment to the last 2 weeks of treatment in the p16-positive group than in the p16-negative group (P ranged from .0002 to <.0001). Pretreatment QOL/PS was a significant independent predictor of overall survival, progression-free survival, and local-regional failure but not of distant metastasis (P ranged from .0063 to <.0001). The results indicated that patients in both arms may have experienced similar QOL/PS. p16-positive patients had better QOL/PS at baseline and after 1 year of follow-up. Patients presenting with better baseline QOL/PS scores had better survival. Copyright © 2016 Elsevier Inc. All rights reserved.

Quality of Life and Performance Status From a Substudy Conducted Within a Prospective Phase 3 Randomized Trial of Concurrent Standard Radiation Versus Accelerated Radiation Plus Cisplatin for Locally Advanced Head and Neck Carcinoma: NRG Oncology RTOG 0129

PubMed Central

Xiao, Canhua; Zhang, Qiang; Nguyen-Tân, Phuc Felix; List, Marcie; Weber, Randal S.; Ang, K. Kian; Rosenthal, David; Filion, Edith J.; Kim, Harold; Silverman, Craig; Raben, Adam; Galloway, Thomas; Fortin, Andre; Gore, Elizabeth; Winquist, Eric; Jones, Christopher U.; Robinson, William; Raben, David; Le, Quynh-Thu; Bruner, Deborah

2016-01-01

Purpose/Objective(s) To analyze quality of life (QOL) and performance status (PS) for head and neck cancer (HNC) patients treated on NRG Oncology RTOG 0129 by treatment (secondary outcome) and p16 status, and to examine the association between QOL/PS and survival. Methods and Materials Eligible patients were randomized into either an accelerated-fractionation arm or a standard-fractionation arm, and completed the Performance Status Scale for the Head and Neck (PSS-HN), the Head and Neck Radiotherapy Questionnaire (HNRQ), and the Spitzer Quality of Life Index (SQLI) at 8 time points from before treatment to 5 years after treatment. Results The results from the analysis of area under the curve showed that QOL/PS was not significantly different between the 2 arms from baseline to year after treatment (P ranged from .39 to .98). The results from general linear mixed models further supported the nonsignificant treatment effects until 5 years after treatment (P=.95, .90, and .84 for PSS-HN Diet, Eating, and Speech, respectively). Before treatment and after 1 year after treatment, p16-positive oropharyngeal cancer (OPC) patients had better QOL than did p16-negative patients (P ranged from .0283 to <.0001 for all questionnaires). However, QOL/PS decreased more significantly from pretreatment to the last 2 weeks of treatment in the p16-positive group than in the p16-negative group (P ranged from .0002 to <.0001). Pretreatment QOL/PS was a significant independent predictor of overall survival, progression-free survival, and local-regional failure but not of distant metastasis (P ranged from .0063 to <.0001). Conclusions The results indicated that patients in both arms may have experienced similar QOL/PS. p16-positive patients had better QOL/PS at baseline and after 1 year of follow-up. Patients presenting with better baseline QOL/PS scores had better survival. PMID:27727063

Long-Term Results of a Phase II Trial of Ultrasound-Guided Radioactive Implantation of the Prostate for Definitive Management of Localized Adenocarcinoma of the Prostate (RTOG 98-05)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lawton, Colleen A., E-mail: clawton@mcw.edu; Hunt, Daniel; Lee, W. Robert

2011-09-01

Purpose: To evaluate the long-term effectiveness of transrectal ultrasound-guided permanent radioactive I{sup 125} implantation of the prostate for organ confined adenocarcinoma of the prostate compared with historical data of prostatectomy and external beam radiotherapy within a cooperative group setting. Methods and Materials: Patients accrued to this study had histologically confirmed, locally confined adenocarcinoma of the prostate clinical stage T1b, T1c, or T2a; no nodal or metastatic disease; prostate-specific antigen level of {<=}10 ng/ml; and a Gleason score of {<=}6. All patients underwent transrectal ultrasound-guided radioactive I{sup 125} seed implantation into the prostate. The prescribed dose was 145 Gy to themore » prostate planning target volume. Results: A total of 101 patients from 27 institutions were accrued to this protocol; by design, no single institution accrued more than 8 patients. There were 94 eligible patients. The median follow up was 8.1 years (range, 0.1-9.2 years). After 8 years, 8 patients had protocol-defined biochemical (prostate-specific antigen) failure (cumulative incidence, 8.0%); 5 patients had local failure (cumulative incidence, 5.5%); and 1 patient had distant failure (cumulative incidence, 1.1%; this patient also had biochemical failure and died of causes not related to prostate cancer). The 8-year overall survival rate was 88%. At last follow-up, no patient had died of prostate cancer or related toxicities. Three patients had maximum late toxicities of Grade 3, all of which were genitourinary. No Grade 4 or 5 toxicities were observed. Conclusions: The long-term results of this clinical trial have demonstrated that this kind of trial can be successfully completed through the RTOG and that results in terms of biochemical failure and toxicity compare very favorably with other brachytherapy published series as well as surgical and external beam radiotherapy series. In addition, the prospective, multicenter design highlights the probable generalizability of the outcomes.« less

Acute Toxicity After Image-Guided Intensity Modulated Radiation Therapy Compared to 3D Conformal Radiation Therapy in Prostate Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wortel, Ruud C.; Incrocci, Luca; Pos, Floris J.

Purpose: Image-guided intensity modulated radiation therapy (IG-IMRT) allows significant dose reductions to organs at risk in prostate cancer patients. However, clinical data identifying the benefits of IG-IMRT in daily practice are scarce. The purpose of this study was to compare dose distributions to organs at risk and acute gastrointestinal (GI) and genitourinary (GU) toxicity levels of patients treated to 78 Gy with either IG-IMRT or 3D-CRT. Methods and Materials: Patients treated with 3D-CRT (n=215) and IG-IMRT (n=260) receiving 78 Gy in 39 fractions within 2 randomized trials were selected. Dose surface histograms of anorectum, anal canal, and bladder were calculated. Identical toxicitymore » questionnaires were distributed at baseline, prior to fraction 20 and 30 and at 90 days after treatment. Radiation Therapy Oncology Group (RTOG) grade ≥1, ≥2, and ≥3 endpoints were derived directly from questionnaires. Univariate and multivariate binary logistic regression analyses were applied. Results: The median volumes receiving 5 to 75 Gy were significantly lower (all P<.001) with IG-IMRT for anorectum, anal canal, and bladder. The mean dose to the anorectum was 34.4 Gy versus 47.3 Gy (P<.001), 23.6 Gy versus 44.6 Gy for the anal canal (P<.001), and 33.1 Gy versus 43.2 Gy for the bladder (P<.001). Significantly lower grade ≥2 toxicity was observed for proctitis, stool frequency ≥6/day, and urinary frequency ≥12/day. IG-IMRT resulted in significantly lower overall RTOG grade ≥2 GI toxicity (29% vs 49%, respectively, P=.002) and overall GU grade ≥2 toxicity (38% vs 48%, respectively, P=.009). Conclusions: A clinically meaningful reduction in dose to organs at risk and acute toxicity levels was observed in IG-IMRT patients, as a result of improved technique and tighter margins. Therefore reduced late toxicity levels can be expected as well; additional research is needed to quantify such reductions.« less

Late Toxicity and Patient Self-Assessment of Breast Appearance/Satisfaction on RTOG 0319: A Phase 2 Trial of 3-Dimensional Conformal Radiation Therapy-Accelerated Partial Breast Irradiation Following Lumpectomy for Stages I and II Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chafe, Susan, E-mail: susan.chafe@albertahealthservices.ca; Moughan, Jennifer; McCormick, Beryl

2013-08-01

Purpose: Late toxicities and cosmetic analyses of patients treated with accelerated partial breast irradiation (APBI) on RTOG 0319 are presented. Methods and Materials: Patients with stages I to II breast cancer ≤3 cm, negative margins, and ≤3 positive nodes were eligible. Patients received three-dimensional conformal external beam radiation therapy (3D-CRT; 38.5 Gy in 10 fractions twice daily over 5 days). Toxicity and cosmesis were assessed by the patient (P), the radiation oncologist (RO), and the surgical oncologist (SO) at 3, 6, and 12 months from the completion of treatment and then annually. National Cancer Institute Common Terminology Criteria for Adversemore » Events, version 3.0, was used to grade toxicity. Results: Fifty-two patients were evaluable. Median follow-up was 5.3 years (range, 1.7-6.4 years). Eighty-two percent of patients rated their cosmesis as good/excellent at 1 year, with rates of 64% at 3 years. At 3 years, 31 patients were satisfied with the treatment, 5 were not satisfied but would choose 3D-CRT again, and none would choose standard radiation therapy. The worst adverse event (AE) per patient reported as definitely, probably, or possibly related to radiation therapy was 36.5% grade 1, 50% grade 2, and 5.8% grade 3 events. Grade 3 AEs were all skin or musculoskeletal-related. Treatment-related factors were evaluated to potentially establish an association with observed toxicity. Surgical bed volume, target volume, the number of beams used, and the use of bolus were not associated with late cosmesis. Conclusions: Most patients enrolled in RTOG 0319 were satisfied with their treatment, and all would choose to have the 3D-CRT APBI again.« less

Late toxicity and patient self-assessment of breast appearance/satisfaction on RTOG 0319: a phase 2 trial of 3-dimensional conformal radiation therapy-accelerated partial breast irradiation following lumpectomy for stages I and II breast cancer.

PubMed

Chafe, Susan; Moughan, Jennifer; McCormick, Beryl; Wong, John; Pass, Helen; Rabinovitch, Rachel; Arthur, Douglas W; Petersen, Ivy; White, Julia; Vicini, Frank A

2013-08-01

Late toxicities and cosmetic analyses of patients treated with accelerated partial breast irradiation (APBI) on RTOG 0319 are presented. Patients with stages I to II breast cancer ≤3 cm, negative margins, and ≤3 positive nodes were eligible. Patients received three-dimensional conformal external beam radiation therapy (3D-CRT; 38.5 Gy in 10 fractions twice daily over 5 days). Toxicity and cosmesis were assessed by the patient (P), the radiation oncologist (RO), and the surgical oncologist (SO) at 3, 6, and 12 months from the completion of treatment and then annually. National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, was used to grade toxicity. Fifty-two patients were evaluable. Median follow-up was 5.3 years (range, 1.7-6.4 years). Eighty-two percent of patients rated their cosmesis as good/excellent at 1 year, with rates of 64% at 3 years. At 3 years, 31 patients were satisfied with the treatment, 5 were not satisfied but would choose 3D-CRT again, and none would choose standard radiation therapy. The worst adverse event (AE) per patient reported as definitely, probably, or possibly related to radiation therapy was 36.5% grade 1, 50% grade 2, and 5.8% grade 3 events. Grade 3 AEs were all skin or musculoskeletal-related. Treatment-related factors were evaluated to potentially establish an association with observed toxicity. Surgical bed volume, target volume, the number of beams used, and the use of bolus were not associated with late cosmesis. Most patients enrolled in RTOG 0319 were satisfied with their treatment, and all would choose to have the 3D-CRT APBI again. Copyright © 2013. Published by Elsevier Inc.

Experience of micromultileaf collimator linear accelerator based single fraction stereotactic radiosurgery: Tumor dose inhomogeneity, conformity, and dose fall off

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hong, Linda X.; Garg, Madhur; Lasala, Patrick

2011-03-15

Purpose: Sharp dose fall off outside a tumor is essential for high dose single fraction stereotactic radiosurgery (SRS) plans. This study explores the relationship among tumor dose inhomogeneity, conformity, and dose fall off in normal tissues for micromultileaf collimator (mMLC) linear accelerator (LINAC) based cranial SRS plans. Methods: Between January 2007 and July 2009, 65 patients with single cranial lesions were treated with LINAC-based SRS. Among them, tumors had maximum diameters {<=}20 mm: 31; between 20 and 30 mm: 21; and >30 mm: 13. All patients were treated with 6 MV photons on a Trilogy linear accelerator (Varian Medical Systems,more » Palo Alto, CA) with a tertiary m3 high-resolution mMLC (Brainlab, Feldkirchen, Germany), using either noncoplanar conformal fixed fields or dynamic conformal arcs. The authors also created retrospective study plans with identical beam arrangement as the treated plan but with different tumor dose inhomogeneity by varying the beam margins around the planning target volume (PTV). All retrospective study plans were normalized so that the minimum PTV dose was the prescription dose (PD). Isocenter dose, mean PTV dose, RTOG conformity index (CI), RTOG homogeneity index (HI), dose gradient index R{sub 50}-R{sub 100} (defined as the difference between equivalent sphere radius of 50% isodose volume and prescription isodose volume), and normal tissue volume (as a ratio to PTV volume) receiving 50% prescription dose (NTV{sub 50}) were calculated. Results: HI was inversely related to the beam margins around the PTV. CI had a ''V'' shaped relationship with HI, reaching a minimum when HI was approximately 1.3. Isocenter dose and mean PTV dose (as percentage of PD) increased linearly with HI. R{sub 50}-R{sub 100} and NTV{sub 50} initially declined with HI and then reached a plateau when HI was approximately 1.3. These trends also held when tumors were grouped according to their maximum diameters. The smallest tumor group (maximum diameters {<=}20 mm) had the most HI dependence for dose fall off. For treated plans, CI averaged 2.55{+-}0.79 with HI 1.23{+-}0.06; the average R{sub 50}-R{sub 100} was 0.41{+-}0.08, 0.55{+-}0.10, and 0.65{+-}0.09 cm, respectively, for tumors {<=}20 mm, between 20 and 30 mm, and >30 mm. Conclusions: Tumor dose inhomogeneity can be used as an important and convenient parameter to evaluate mMLC LINAC-based SRS plans. Sharp dose fall off in the normal tissue is achieved with sufficiently high tumor dose inhomogeneity. By adjusting beam margins, a homogeneity index of approximately 1.3 would provide best conformity for the authors' SRS system.« less

Left hippocampus sparing whole brain radiotherapy (WBRT): A planning study.

PubMed

Kazda, Tomas; Vrzal, Miroslav; Prochazka, Tomas; Dvoracek, Petr; Burkon, Petr; Pospisil, Petr; Dziacky, Adam; Nikl, Tomas; Jancalek, Radim; Slampa, Pavel; Lakomy, Radek

2017-12-01

Unilateral sparing of the dominant (left) hippocampus during whole brain radiotherapy (WBRT) could mitigate cognitive decline, especially verbal memory, similar to the widely investigated bilateral hippocampus avoidance (HA-WBRT). The aim of this planning study is dosimetrical comparison of HA-WBRT with only left hippocampus sparing (LHA-WBRT) plans. HA-WBRT plans for 10 patients were prepared in accordance with RTOG 0933 trial and served as baseline for comparisons with several LHA-WBRT plans prepared with an effort: 1) to maintain the same left hippocampus dosimetry ("BEST PTV") and 2) to maintain same dosimetry in planning target volume as in HA-WBRT ("BEST LH"). All HA-WBRT plans met RTOG 0933 protocol criteria with a mean Conformity index 1.09 and mean Homogeneity index (HI) 0.21. Mean right and left hippocampal D100% was 7.8 Gy and 8.5 Gy and mean Dmax 14.0 Gy and 13.8 Gy, respectively. "BEST PTV" plans reduced HI by 31.2% (P=0.005) which is mirrored by lower PTV_D2% (-0.8 Gy, P=0.005) and higher PTV_D98% (+1.3 Gy, P=0.005) as well as decreased optic pathway's Dmax by 1 Gy. In "BEST LH", mean D100% and Dmax for the left hippocampus were significantly reduced by 11.2% (P=0.005) and 10.9% (P=0.005) respectively. LHA-WBRT could improve target coverage and/or further decrease in dose to spared hippocampus. Future clinical trials must confirm whether statistically significant reduction in left hippocampal dose is also clinically significant.

Volumetric-modulated arc therapy (VMAT) for whole brain radiotherapy: not only for hippocampal sparing, but also for reduction of dose to organs at risk.

PubMed

Sood, Sumit; Pokhrel, Damodar; McClinton, Christopher; Lominska, Christopher; Badkul, Rajeev; Jiang, Hongyu; Wang, Fen

2017-01-01

A prospective clinical trial, Radiation Therapy Oncology Group (RTOG) 0933, has demonstrated that whole brain radiotherapy (WBRT) using conformal radiation delivery technique with hippocampal avoidance is associated with less memory complications. Further sparing of other organs at risk (OARs) including the scalp, ear canals, cochleae, and parotid glands could be associated with reductions in additional toxicities for patients treated with WBRT. We investigated the feasibility of WBRT using volumetric-modulated arc therapy (VMAT) to spare the hippocampi and the aforementioned OARs. Ten patients previously treated with nonconformal WBRT (NC-WBRT) using opposed lateral beams were retrospectively re-planned using VMAT with hippocampal sparing according to the RTOG 0933 protocol. The OARs (scalp, auditory canals, cochleae, and parotid glands) were considered as dose-constrained structures. VMAT plans were generated for a prescription dose of 30 Gy in 10 fractions. Comparison of the dosimetric parameters achieved by VMAT and NC-WBRT plans was performed using paired t-tests using upper bound p-value of < 0.001. Average beam on time and monitor units (MUs) delivered to the patients on VMAT were compared with those obtained with NC-WBRT. All VMAT plans met RTOG 0933 dosimetric criteria including the dose to hippocampi of 100% of the volume (D 100% ) of 8.4 ± 0.3 Gy and maximum dose of 15.6 ± 0.4 Gy, respectively. A statistically significant dose reduction (p < 0.001) to all OARs was achieved. The mean and maximum scalp doses were reduced by an average of 9 Gy (32%) and 2 Gy (6%), respectively. The mean and maximum doses to the auditory canals were reduced from 29.5 ± 0.5 Gy and 31.0 ± 0.4 Gy with NC-WBRT, to 21.8 ± 1.6 Gy (26%) and 27.4 ± 1.4 Gy (12%) with VMAT. VMAT also reduced mean and maximum doses to the cochlea by an average of 4 Gy (13%) and 2 Gy (6%), respectively. The parotid glands mean and maximum doses with VMAT were 4.4 ± 1.9 Gy and 15.7 ± 5.0 Gy, compared to 12.8 ± 4.9 Gy and 30.6 ± 0.5 Gy with NC-WBRT, respectively. The average dose reduction of mean and maximum of parotid glands from VMAT were 65% and 50%, respectively. The average beam on time and MUs were 2.3minutes and 719 on VMAT, and 0.7 minutes and 350 on NC-WBRT. This study demonstrated the feasibility of WBRT using VMAT to not only spare the hippocampi, but also significantly reduce dose to OARs. These advantages of VMAT could potentially decrease the toxicities associated with NC-WBRT and improve patients' quality of life, especially for patients with favorable prognosis receiving WBRT or patients receiving prophylactic cranial irradiation (PCI). Published by Elsevier Inc.

An Aloe Vera-Based Cosmeceutical Cream Delays and Mitigates Ionizing Radiation-Induced Dermatitis in Head and Neck Cancer Patients Undergoing Curative Radiotherapy: A Clinical Study.

PubMed

Rao, Suresh; Hegde, Sanath Kumar; Baliga-Rao, Manjeshwar Poonam; Palatty, Princy Louis; George, Thomas; Baliga, Manjeshwar Shrinath

2017-06-24

Background: This study was planned to evaluate the efficacy of topical application of an Aloe vera -based cream (AVC) for the prevention of ionizing radiation (X ray)-induced dermatitis in head and neck cancer patients requiring therapeutic radiation treatment (>62 Gy). Methods: From July 2012 to December 2012, a total of 60 head and neck cancer patients requiring curative radiotherapy (RT) of more than 66 Gy were prospectively enrolled and treated with AVC or a comparator Johnson's Baby Oil (JBO). Acute skin reaction was monitored and classified according to the Radiation Therapy Oncology Group (RTOG) four-point rating scale on a weekly basis. Results: The results indicate that there was a statistically significant delay in the incidence ( p = 0.04) of dermatitis at week three in the AVC application group. Application of AVC reduced the incidence of Grade 1, 2, and 3 dermatitis at subsequent time points, while Grade 4 dermatitis was not seen in either cohort. The other most important observation was that the continued application of AVC two weeks after the completion of RT was effective in reducing the average grade of dermatitis and was statistically significant ( p < 0.02). Conclusions : Prophylactic use of an AVC-based cream is thus effective in delaying radiation dermatitis in head and neck cancer.

An Aloe Vera-Based Cosmeceutical Cream Delays and Mitigates Ionizing Radiation-Induced Dermatitis in Head and Neck Cancer Patients Undergoing Curative Radiotherapy: A Clinical Study

PubMed Central

Rao, Suresh; Hegde, Sanath Kumar; Baliga-Rao, Manjeshwar Poonam; Palatty, Princy Louis; George, Thomas; Baliga, Manjeshwar Shrinath

2017-01-01

Background: This study was planned to evaluate the efficacy of topical application of an Aloe vera-based cream (AVC) for the prevention of ionizing radiation (X ray)-induced dermatitis in head and neck cancer patients requiring therapeutic radiation treatment (>62 Gy). Methods: From July 2012 to December 2012, a total of 60 head and neck cancer patients requiring curative radiotherapy (RT) of more than 66 Gy were prospectively enrolled and treated with AVC or a comparator Johnson’s Baby Oil (JBO). Acute skin reaction was monitored and classified according to the Radiation Therapy Oncology Group (RTOG) four-point rating scale on a weekly basis. Results: The results indicate that there was a statistically significant delay in the incidence (p = 0.04) of dermatitis at week three in the AVC application group. Application of AVC reduced the incidence of Grade 1, 2, and 3 dermatitis at subsequent time points, while Grade 4 dermatitis was not seen in either cohort. The other most important observation was that the continued application of AVC two weeks after the completion of RT was effective in reducing the average grade of dermatitis and was statistically significant (p < 0.02). Conclusions: Prophylactic use of an AVC-based cream is thus effective in delaying radiation dermatitis in head and neck cancer. PMID:28930258

The influence of parotid gland sparing on radiation damages of dental hard tissues.

PubMed

Hey, Jeremias; Seidel, Johannes; Schweyen, Ramona; Paelecke-Habermann, Yvonne; Vordermark, Dirk; Gernhardt, Christian; Kuhnt, Thomas

2013-07-01

The aim of the present study was to evaluate whether radiation damage on dental hard tissue depends on the mean irradiation dose the spared parotid gland is subjected to or on stimulated whole salivary flow rate. Between June 2002 and October 2008, 70 patients with neck and cancer curatively irradiated were included in this study. All patients underwent dental treatment referring to the guidelines and recommendations of the German Society of Dental, Oral and Craniomandibular Sciences prior, during, and after radiotherapy (RT). During the follow-up period of 24 months, damages on dental hard tissues were classified according to the RTOG/EORTC guidelines. The mean doses (D(mean)) during spared parotid gland RT were determined. Stimulated whole saliva secretion flow rates (SFR) were measured before RT and 1, 6, 12, 24 months after RT. Thirty patients showed no carious lesions (group A), 18 patients developed sporadic carious lesions (group B), and 22 patients developed general carious lesions (group C). Group A patients received a D mean of 21.2 ± 11.04 Gy. Group B patients received a D(mean) of 26.5 ± 11.59 Gy and group C patients received a D(mean) of 33.9 ± 9.93 Gy, respectively. The D(mean) of group A was significantly lower than the D(mean) of group C (p < 0.001). Additionally, the mean SFR 6 months after RT of group A was significantly higher than the mean SFR of group C (p < 0.01). Irradiation damage on dental hard tissue correlates with increased mean irradiation doses as well as decreased salivary flow rates. Parotid gland sparing resulting in a dose below 20 Gy reduces radiation damage on dental hard tissues, and therefore, the dose may act as a predictor for the damage to be expected.

Spectrophotometer and ultrasound evaluation of late toxicity following breast-cancer radiotherapy.

PubMed

Yoshida, E J; Chen, H; Torres, M A; Curran, W J; Liu, T

2011-10-01

Radiation-induced normal-tissue toxicities are common, complex, and distressing side effects that affect 90% of patients receiving breast-cancer radiotherapy and 40% of patients post radiotherapy. In this study, the authors investigated the use of spectrophotometry and ultrasound to quantitatively measure radiation-induced skin discoloration and subcutaneous-tissue fibrosis. The study's purpose is to determine whether skin discoloration correlates with the development of fibrosis in breast-cancer radiotherapy. Eighteen breast-cancer patients were enrolled in our initial study. All patients were previously treated with a standard course of radiation, and the median follow-up time was 22 months. The treated and untreated breasts were scanned with a spectrophotometer and an ultrasound. Two spectrophotometer parameters-melanin and erythema indices-were used to quantitatively assess skin discoloration. Two ultrasound parameters-skin thickness and Pearson coefficient of the hypodermis-were used to quantitatively assess severity of fibrosis. These measurements were correlated with clinical assessments (RTOG late morbidity scores). Significant measurement differences between the treated and contralateral breasts were observed among all patients: 27.3% mean increase in skin thickness (p < 0.001), 34.1% mean decrease in Pearson coefficient (p < 0.001), 27.3% mean increase in melanin (p < 0.001), and 22.6% mean increase in erythema (p < 0.001). All parameters except skin thickness correlated with RTOG scores. A moderate correlation exists between melanin and erythema; however, spectrophotometer parameters do not correlate with ultrasound parameters. Spectrophotometry and quantitative ultrasound are objective tools that assess radiation-induced tissue injury. Spectrophotometer parameters did not correlate with those of quantitative ultrasound suggesting that skin discoloration cannot be used as a marker for subcutaneous fibrosis. These tools may prove useful for the reduction of radiation morbidities and improvement of patient quality of life.

A Phase 3 Trial of 2 Years of Androgen Suppression and Radiation Therapy With or Without Adjuvant Chemotherapy for High-Risk Prostate Cancer: Final Results of Radiation Therapy Oncology Group Phase 3 Randomized Trial NRG Oncology RTOG 9902

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosenthal, Seth A., E-mail: rosents@sutterhealth.org; Hunt, Daniel; Sartor, A. Oliver

Purpose: Long-term (LT) androgen suppression (AS) with radiation therapy (RT) is a standard treatment of high-risk, localized prostate cancer (PCa). Radiation Therapy Oncology Group 9902 was a randomized trial testing the hypothesis that adjuvant combination chemotherapy (CT) with paclitaxel, estramustine, and oral etoposide plus LT AS plus RT would improve overall survival (OS). Methods and Materials: Patients with high-risk PCa (prostate-specific antigen 20-100 ng/mL and Gleason score [GS] ≥7 or clinical stage ≥T2 and GS ≥8) were randomized to RT and AS (AS + RT) alone or with adjuvant CT (AS + RT + CT). CT was given as four 21-day cycles, delivered beginning 28 days after 70.2 Gy of RT.more » AS was given as luteinizing hormone-releasing hormone for 24 months, beginning 2 months before RT plus an oral antiandrogen for 4 months before and during RT. The study was designed based on a 6% improvement in OS from 79% to 85% at 5 years, with 90% power and a 2-sided alpha of 0.05. Results: A total of 397 patients (380 eligible) were randomized. The patients had high-risk PCa, 68% with GS 8 to 10 and 34% T3 to T4 tumors, and median prostate-specific antigen of 22.6 ng/mL. The median follow-up period was 9.2 years. The trial closed early because of excess thromboembolic toxicity in the CT arm. The 10-year results for all randomized patients revealed no significant difference between the AS + RT and AS + RT + CT arms in OS (65% vs 63%; P=.81), biochemical failure (58% vs 54%; P=.82), local progression (11% vs 7%; P=.09), distant metastases (16% vs 14%; P=.42), or disease-free survival (22% vs 26%; P=.61). Conclusions: NRG Oncology RTOG 9902 showed no significant differences in OS, biochemical failure, local progression, distant metastases, or disease-free survival with the addition of adjuvant CT to LT AS + RT. The trial results provide valuable data regarding the natural history of high-risk PCa treated with LT AS + RT and have implications for the feasibility of clinical trial accrual and tolerability using CT for PCa.« less

Localized Unresectable Pancreatic Cancer Treated with High Energy Neutrons and Chemotherapy at Fermilab - Preliminary Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saroja, K. R.; Cohen, Lionel; Hendrickson, Frank R.

1990-01-01

Between January 1985 and July 1989 a total of thirty-eight patients with locally advanced pancreatic cancer were treated with high energy neutrons at Fermilab. Twenty-one patients received only neutrons and seventeen were given chemotherapy in addition, either concurrently or subsequently following the completion of neutron irradiation. This is a retrospective study. Data were analyzed for tolerance, complications and survival. Three of the twenty-one (14%) patients who received only neutron beam therapy developed Grade ID or greater complications in the RTOG/EORTC scale. The median survival was 6.4 months. One of these patients is alive 10 months post treatment. Of seventeen patientsmore » who also received chemotherapy, five (29%) had severe complications. However, median survival was 13.5 months. Four of these seventeen patients are still alive at the time of this analysis. The preliminary results show that there is improvement in the survival of patients treated with combined neutron irradiation and chemotherapy. A pilot study to further evaluate these results in a larger group of patients is underway. Details of complications and chemotherapy regimen will be preseqted.« less

Ultrasonic Nakagami-parameter characterization of parotid-gland injury following head-and-neck radiotherapy: A feasibility study of late toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Xiaofeng; Wu, Ning; Wang, Yuefeng

Purpose: The study aims to investigate whether Nakagami parameters—estimated from the statistical distribution of the backscattered ultrasound radio-frequency (RF) signals—could provide a means for quantitative characterization of parotid-gland injury resulting from head-and-neck radiotherapy. Methods: A preliminary clinical study was conducted with 12 postradiotherapy patients and 12 healthy volunteers. Each participant underwent one ultrasound study in which ultrasound scans were performed in the longitudinal, i.e., vertical orientation on the bilateral parotids. For the 12 patients, the mean radiation dose to the parotid glands was 37.7 ± 9.5 Gy, and the mean follow-up time was 16.3 ± 4.8 months. All enrolled patientsmore » experienced grade 1 or 2 late salivary-gland toxicity (RTOG/EORTC morbidity scale). The normal parotid glands served as the control group. The Nakagami-scaling and Nakagami-shape parameters were computed from the RF data to quantify radiation-induced parotid-gland changes. Results: Significant differences in Nakagami parameters were observed between the normal and postradiotherapy parotid glands. Compared with the control group, the Nakagami-scaling parameter of the postradiotherapy group decreased by 25.8% (p < 0.001), and the Nakagami-shape parameter decreased by 31.3% (p < 0.001). The area under the receiver operating characteristic curve was 0.85 for the Nakagami-scaling parameter and was 0.95 for the Nakagami-shape parameter, which further demonstrated the diagnostic efficiency of the Nakagami parameters. Conclusions: Nakagami parameters could be used to quantitatively measure parotid-gland injury following head-and-neck radiotherapy. Moreover, the clinical feasibility was demonstrated and this study provides meaningful preliminary data for future clinical investigation.« less

Ultrasonic Nakagami-parameter characterization of parotid-gland injury following head-and-neck radiotherapy: A feasibility study of late toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Xiaofeng; Wu, Ning; Wang, Yuefeng

2014-02-15

Purpose: The study aims to investigate whether Nakagami parameters—estimated from the statistical distribution of the backscattered ultrasound radio-frequency (RF) signals—could provide a means for quantitative characterization of parotid-gland injury resulting from head-and-neck radiotherapy. Methods: A preliminary clinical study was conducted with 12 postradiotherapy patients and 12 healthy volunteers. Each participant underwent one ultrasound study in which ultrasound scans were performed in the longitudinal, i.e., vertical orientation on the bilateral parotids. For the 12 patients, the mean radiation dose to the parotid glands was 37.7 ± 9.5 Gy, and the mean follow-up time was 16.3 ± 4.8 months. All enrolled patientsmore » experienced grade 1 or 2 late salivary-gland toxicity (RTOG/EORTC morbidity scale). The normal parotid glands served as the control group. The Nakagami-scaling and Nakagami-shape parameters were computed from the RF data to quantify radiation-induced parotid-gland changes. Results: Significant differences in Nakagami parameters were observed between the normal and postradiotherapy parotid glands. Compared with the control group, the Nakagami-scaling parameter of the postradiotherapy group decreased by 25.8% (p < 0.001), and the Nakagami-shape parameter decreased by 31.3% (p < 0.001). The area under the receiver operating characteristic curve was 0.85 for the Nakagami-scaling parameter and was 0.95 for the Nakagami-shape parameter, which further demonstrated the diagnostic efficiency of the Nakagami parameters. Conclusions: Nakagami parameters could be used to quantitatively measure parotid-gland injury following head-and-neck radiotherapy. Moreover, the clinical feasibility was demonstrated and this study provides meaningful preliminary data for future clinical investigation.« less

The allegheny general modification of the Harvard Breast Cosmesis Scale for the retreated breast.

PubMed

Trombetta, Mark; Julian, Thomas B; Kim, Yongbok; Werts, E Day; Parda, David

2009-10-01

The use of brachytherapy--and to a lesser extent, external-beam radiotherapy--in the management of locally recurrent breast cancer following ipsilateral breast tumor recurrence (IBTR) followed by repeat breast-conservation surgery and irradiation is currently an area of intense study. The current cosmetic scoring system is inadequate to score the outcome resulting from retreatment because it does not account for the cosmetic effect of the initial treatment. We propose a modification of the scale for patients who undergo retreatment--the Allegheny General Modification of the Harvard/NSABP/RTOG scoring scale.

Benefit From Procarbazine, Lomustine, and Vincristine in Oligodendroglial Tumors Is Associated With Mutation of IDH

PubMed Central

Cairncross, J. Gregory; Wang, Meihua; Jenkins, Robert B.; Shaw, Edward G.; Giannini, Caterina; Brachman, David G.; Buckner, Jan C.; Fink, Karen L.; Souhami, Luis; Laperriere, Normand J.; Huse, Jason T.; Mehta, Minesh P.; Curran, Walter J.

2014-01-01

Purpose Patients with 1p/19q codeleted anaplastic oligodendroglial tumors who participated in RTOG (Radiation Therapy Oncology Group) 9402 lived much longer after chemoradiotherapy (CRT) than radiation therapy (RT) alone. However, some patients with noncodeleted tumors also benefited from CRT; survival curves separated after the median had been reached, and significantly more patients lived ≥ 10 years after CRT than RT. Thus, 1p/19q status may not identify all responders to CRT. Patients and Methods Using trial data, we inquired whether an IDH mutation or germ-line polymorphism associated with IDH-mutant gliomas identified the patients in RTOG 9402 who benefited from CRT. Results IDH status was evaluable in 210 of 291 patients; 156 (74%) had mutations. rs55705857 was evaluable in 245 patients; 76 (31%) carried the G risk allele. Both were associated with longer progression-free survival after CRT, and mutant IDH was associated with longer overall survival (9.4 v 5.7 years; hazard ratio [HR], 0.59; 95% CI, 0.40 to 0.86; P = .006). For those with wild-type tumors, CRT did not prolong median survival (1.3 v 1.8 years; HR, 1.14; 95% CI, 0.63 to 2.04; P = .67) or 10-year survival rate (CRT, 6% v RT, 4%). Patients with codeleted mutated tumors (14.7 v 6.8 years; HR, 0.49; 95% CI, 0.28 to 0.85; P = .01) and noncodeleted mutated tumors (5.5 v 3.3 years; HR, 0.56; 95% CI, 0.32 to 0.99; P < .05) lived longer after CRT than RT. Conclusion IDH mutational status identified patients with oligodendroglial tumors who did (and did not) benefit from alkylating-agent chemotherapy with RT. Although patients with codeleted tumors lived longest, patients with noncodeleted IDH-mutated tumors also lived longer after CRT. PMID:24516018

Potential for reduced radiation‐induced toxicity using intensity‐modulated arc therapy for whole‐brain radiotherapy with hippocampal sparing

PubMed Central

Sood, Sumit; Lominska, Christopher; Kumar, Parvesh; Badkul, Rajeev; Jiang, Hongyu; Wang, Fen

2015-01-01

The purpose of this study was to retrospectively investigate the accuracy, plan quality, and efficiency of using intensity‐modulated arc therapy (IMAT) for whole brain radiotherapy (WBRT) patients with sparing not only the hippocampus (following RTOG 0933 compliance criteria) but also other organs at risk (OARs). A total of 10 patients previously treated with nonconformal opposed laterals whole‐brain radiotherapy (NC‐WBRT) were retrospectively replanned for hippocampal sparing using IMAT treatment planning. The hippocampus was volumetrically contoured on fused diagnostic T1‐weighted MRI with planning CT images and hippocampus avoidance zone (HAZ) was generated using a 5 mm uniform margin around the hippocampus. Both hippocampi were defined as one paired organ. Whole brain tissue minus HAZ was defined as the whole‐brain planning target volume (WB‐PTV). Highly conformal IMAT plans were generated in the Eclipse treatment planning system for Novalis TX linear accelerator consisting of high‐definition multileaf collimators (HD‐MLCs: 2.5 mm leaf width at isocenter) and 6 MV beam for a prescription dose of 30 Gy in 10 fractions following RTOG 0933 dosimetric criteria. Two full coplanar arcs with orbits avoidance sectors were used. In addition to RTOG criteria, doses to other organs at risk (OARs), such as parotid glands, cochlea, external/middle ear canals, skin, scalp, optic pathways, brainstem, and eyes/lens, were also evaluated. Subsequently, dose delivery efficiency and accuracy of each IMAT plan was assessed by delivering quality assurance (QA) plans with a MapCHECK device, recording actual beam‐on time and measuring planed vs. measured dose agreement using a gamma index. On IMAT plans, following RTOG 0933 dosimetric criteria, the maximum dose to WB‐PTV, mean WB‐PTV D2%, and mean WB‐PTV D98% were 34.9±0.3 Gy,33.2±0.4 Gy, and 26.0±0.4 Gy, respectively. Accordingly, WB‐PTV received the prescription dose of 30 Gy and mean V30 was 90.5%±0.5%. The D100%, and mean and maximum doses to hippocampus were 8.4±0.3 Gy,11.2±0.3 Gy, and 15.6±0.4 Gy, on average, respectively. The mean values of homogeneity index (HI) and conformity index (CI) were 0.23×0.02 and 0.96×0.02, respectively. The maximum point dose to WB‐PTV was 35.3 Gy, well below the optic pathway tolerance of 37.5 Gy. In addition, compared to NC‐WBRT, dose reduction of mean and maximum of parotid glands from IMAT were 65% and 50%, respectively. Ear canals mean and maximum doses were reduced by 26% and 12%, and mean and maximum scalp doses were reduced by 9 Gy (32%) and 2 Gy (6%), on average, respectively. The mean dose to skin was 9.7 Gy with IMAT plans compared to 16 Gy with conventional NC‐WBRT, demonstrating that absolute reduction of skin dose by a factor of 2. The mean values of the total number of monitor units (MUs) and actual beam on time were 719×44 and 2.34×0.14 min, respectively. The accuracy of IMAT QA plan delivery was (98.1±0.8) %, on average, with a 3%/3 mm gamma index passing rate criteria. All of these plans were considered clinically acceptable per RTOG 0933 criteria. IMAT planning provided highly conformal and homogenous plan with a fast and effective treatment option for WBRT patients, sparing not only hippocampi but also other OARs, which could potentially result in an additional improvement of the quality life (QoL). In the future, we plan to evaluate the clinical potential of IMAT planning and treatment option with hippocampal and other OARs avoidance in our patient's cohort and asses the QoL of the WBRT patients, as well as simultaneous integrated boost (SIB) for the brain metastases diseases. PACS number: 87 PMID:26699321

Quality of Life Analysis of a Radiation Dose-Escalation Study of Patients With Non-Small-Cell Lung Cancer: A Secondary Analysis of the Radiation Therapy Oncology Group 0617 Randomized Clinical Trial.

PubMed

Movsas, Benjamin; Hu, Chen; Sloan, Jeffrey; Bradley, Jeffrey; Komaki, Ritsuko; Masters, Gregory; Kavadi, Vivek; Narayan, Samir; Michalski, Jeff; Johnson, Douglas W; Koprowski, Christopher; Curran, Walter J; Garces, Yolanda I; Gaur, Rakesh; Wynn, Raymond B; Schallenkamp, John; Gelblum, Daphna Y; MacRae, Robert M; Paulus, Rebecca; Choy, Hak

2016-03-01

A recent randomized radiation dose-escalation trial in unresectable stage III non-small-cell lung cancer (NSCLC) (Radiation Therapy Oncology Group [RTOG] 0617) showed a lower survival rate in the high-dose radiation therapy (RT) arm (74 Gy) than in the low-dose arm (60 Gy) with concurrent chemotherapy. The primary QOL hypothesis predicted a clinically meaningful decline in quality of life (QOL) via the Functional Assessment of Cancer Therapy (FACT)-Lung Cancer Subscale (LCS) in the high-dose RT arm at 3 months. The RTOG 0617 trial was a randomized phase 3 study (conducted from November 2007 to November 2011) in stage III NSCLC using a 2 × 2 factorial design and stratified by histology, positron emission tomography staging, performance status, and irradiation technique (3-dimensional conformal RT [3D-CRT] vs intensity-modulated RT [IMRT]). A total of 185 institutions in the United States and Canada took part. Of 424 eligible patients with stage III NSCLC randomized, 360 (85%) consented to QOL evaluation, of whom 313 (88%) completed baseline QOL assessments. Treatment with 74-Gy vs 60-Gy RT with concurrent and consolidation carboplatin/paclitaxel with or without cetuximab. The QOL data were collected prospectively via FACT Trial Outcome Index (FACT-TOI), calculated as the sum of the following measures: Physical Well Being (PWB), Functional Well Being (FWB), and the LCS. Data are presented at baseline and 3 and 12 months via minimal clinically meaningful changes of 2 points or more for PWB, FWB, and LCS or 5 points or more for TOI. Of the 313 patients who completed baseline QOL assessments, 219 patients (70%) completed the 3-month QOL assessments, and 137 of the living patients (57%) completed the 12-month assessment. Patient demographics and baseline QOL scores were comparable between the 74-Gy and 60-Gy arms. Significantly more patients in the 74-Gy arm than in the 60-Gy arm had clinically meaningful decline in FACT-LCS at 3 months (45% vs 30%; P = .02). At 12 months, fewer patients who received IMRT (vs 3D-CRT) had clinically meaningful decline in FACT-LCS (21% vs 46%; P = .003). Baseline FACT-TOI was associated with overall survival in multivariate analysis. Despite few differences in clinician-reported toxic effects between treatment arms, QOL analysis demonstrated a clinically meaningful decline in QOL in the 74-Gy arm at 3 months, confirming the primary QOL hypothesis. Baseline QOL was an independent prognostic factor for survival. clinicaltrials.gov Identifier: NCT00533949.

A multi-institutional study to assess adherence to lung stereotactic body radiotherapy planning goals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woerner, Andrew; Roeske, John C.; Harkenrider, Matthew M.

2015-08-15

Purpose: A multi-institutional planning study was performed to evaluate the frequency that current guidelines established by Radiation Therapy Oncology Group (RTOG) protocols and other literature for lung stereotactic body radiotherapy (SBRT) treatments are followed. Methods: A total of 300 patients receiving lung SBRT treatments in four different institutions were retrospectively reviewed. The treatments were delivered using Linac based SBRT (160 patients) or image guided robotic radiosurgery (140). Most tumors were located peripherally (250/300). Median fractional doses and ranges were 18 Gy (8–20 Gy), 12 Gy (6–15 Gy), and 10 Gy (5–12 Gy) for three, four, and five fraction treatments, respectively.more » The following planning criteria derived from RTOG trials and the literature were used to evaluate the treatment plans: planning target volumes, PTV{sub V} {sub 100} ≥ 95% and PTV{sub V} {sub 95} ≥ 99%; conformality indices, CI{sub 100%} < 1.2 and CI{sub 50%} range of 2.9–5.9 dependent on PTV; total lung-ITV: V{sub 20Gy} < 10%, V{sub 12.5Gy} < 15%, and V{sub 5Gy} < 37%; contralateral lung V{sub 5Gy} < 26%; and maximum doses for spinal cord, esophagus, trachea/bronchus, and heart and great vessels. Populations were grouped by number of fractions, and dosimetric criteria satisfaction rates (CSRs) were reported. Results: Five fraction regimens were the most common lung SBRT fractionation (46%). The median PTV was 27.2 cm{sup 3} (range: 3.8–419.5 cm{sup 3}). For all plans: mean PTV{sub V} {sub 100} was 94.5% (±5.6%, planning CSR: 69.8%), mean PTV{sub V} {sub 95} was 98.1% (±4.1%, CSR: 69.5%), mean CI{sub 100%} was 1.14 (±0.21, CSR: 79.1%, and 16.5% within minor deviation), and mean CI{sub 50%} was 5.63 (±2.8, CSR: 33.0%, and 28.0% within minor deviation). When comparing plans based on location, peripherally located tumors displayed higher PTV{sub V} {sub 100} and PTV{sub V} {sub 95} CSR (71.5% and 71.9%, respectively) than centrally located tumors (61.2% and 57.1%, respectively). Overall, the planning criteria were met for all the critical structure such as lung, heart, spinal cord, esophagus, and trachea/bronchus for at least 85% of the patients. Conclusions: Among the various parameters that were used to evaluate the SBRT plans, the CI{sub 100%} and CI{sub 50%} were the most challenging criteria to meet. Although the CSRs of organs at risk were higher among all cases, their proximity to the PTV was a significant factor.« less

Fast Neutron Radiotherapy for Locally Advanced Prostate Cancer: Update of a Past Trial and Future Research Directions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krieger, John N.; Krall, John M.; Laramore, George E.

1987-01-01

Between June, 1977 and April, 1983 the Radiation Therapy Oncology Group (RTOG) sponsored a Phase III study comparing fast neutron radiotherapy as part of a mixed beam (neutron/photon) regimen with conventional photon (x-ray) radiotherapy for patients with locally advanced (stages C and o1 ) adenocarcinoma of the prostate. A total of 91 analyzable patients were entered into the study with -the two treatment groups being balanced in regard to all major prognostic variables. The current analysis is for a median follow-up of 6.7 years (range 3.4-9.0). Actuarial curves are presented for local/regional control, overall survival and "determinantal" survival. The resultsmore » are statistically significant in favor of the mixed beam group for all of the above parameters. At 5 years the local control rate is 81% on the mixed beam arm compared to 60% on the photon arm. Histologic evidence of residual prostatic carcinoma was documented in six patients with no clinical evidence of disease on both treatment arms. The actuarial overall survival rate at S years is 70% on the mixed beam compared to 56% on the photon arm. The determinantal survival at 5 years was 82%. on the mixed beam arm compared to 61% on the photon arm. The type of therapy appeared to be the most important predictor of both local tumor control and patient survival in a step-wise Cox analysis. There was no difference in the treatment related morbidity for the two patient groups. Mixed beam therapy may be superior to standard photon radiotherapy for treatment of locally advanced prostate cancer.« less

CogState computerized memory tests in patients with brain metastases: secondary endpoint results of NRG Oncology RTOG 0933.

PubMed

Caine, Chip; Deshmukh, Snehal; Gondi, Vinai; Mehta, Minesh; Tomé, Wolfgang; Corn, Benjamin W; Kanner, Andrew; Rowley, Howard; Kundapur, Vijayananda; DeNittis, Albert; Greenspoon, Jeffrey Noah; Konski, Andre A; Bauman, Glenn S; Raben, Adam; Shi, Wenyin; Wendland, Merideth; Kachnic, Lisa

2016-01-01

Whole brain radiotherapy (WBRT) is associated with memory dysfunction. As part of NRG Oncology RTOG 0933, a phase II study of WBRT for brain metastases that conformally avoided the hippocampal stem cell compartment (HA-WBRT), memory was assessed pre- and post-HA-WBRT using both traditional and computerized memory tests. We examined whether the computerized tests yielded similar findings and might serve as possible alternatives for assessment of memory in multi-institution clinical trials. Adult patients with brain metastases received HA-WBRT to 30 Gy in ten fractions and completed Hopkins Verbal Learning Test-Revised (HVLT-R), CogState International Shopping List Test (ISLT) and One Card Learning Test (OCLT), at baseline, 2 and 4 months. Tests' completion rates were 52-53 % at 2 months and 34-42 % at 4 months. All baseline correlations between HVLT-R and CogState tests were significant (p ≤ 0.003). At baseline, both CogState tests and one component of HVLT-R differentiated those who were alive at 6 months and those who had died (p ≤ 0.01). At 4 months, mean relative decline was 7.0 % for HVLT-R Delayed Recall and 18.0 % for ISLT Delayed Recall. OCLT showed an 8.0 % increase. A reliable change index found no significant changes from baseline to 2 and 4 months for ISLT Delayed Recall (z = -0.40, p = 0.34; z = -0.68, p = 0.25) or OCLT (z = 0.15, p = 0.56; z = 0.41, p = 0.66). Study findings support the possibility that hippocampal avoidance may be associated with preservation of memory test performance, and that these computerized tests also may be useful and valid memory assessments in multi-institution adult brain tumor trials.

Spectrophotometer and ultrasound evaluation of late toxicity following breast-cancer radiotherapy

PubMed Central

Yoshida, E. J.; Chen, H.; Torres, M. A.; Curran, W. J.; Liu, T.

2011-01-01

Purpose: Radiation-induced normal-tissue toxicities are common, complex, and distressing side effects that affect 90% of patients receiving breast-cancer radiotherapy and 40% of patients post radiotherapy. In this study, the authors investigated the use of spectrophotometry and ultrasound to quantitatively measure radiation-induced skin discoloration and subcutaneous-tissue fibrosis. The study’s purpose is to determine whether skin discoloration correlates with the development of fibrosis in breast-cancer radiotherapy.Methods : Eighteen breast-cancer patients were enrolled in our initial study. All patients were previously treated with a standard course of radiation, and the median follow-up time was 22 months. The treated and untreated breasts were scanned with a spectrophotometer and an ultrasound. Two spectrophotometer parameters—melanin and erythema indices—were used to quantitatively assess skin discoloration. Two ultrasound parameters—skin thickness and Pearson coefficient of the hypodermis—were used to quantitatively assess severity of fibrosis. These measurements were correlated with clinical assessments (RTOG late morbidity scores).Results: Significant measurement differences between the treated and contralateral breasts were observed among all patients: 27.3% mean increase in skin thickness (p < 0.001), 34.1% mean decrease in Pearson coefficient (p < 0.001), 27.3% mean increase in melanin (p < 0.001), and 22.6% mean increase in erythema (p < 0.001). All parameters except skin thickness correlated with RTOG scores. A moderate correlation exists between melanin and erythema; however, spectrophotometer parameters do not correlate with ultrasound parameters.Conclusions: Spectrophotometry and quantitative ultrasound are objective tools that assess radiation-induced tissue injury. Spectrophotometer parameters did not correlate with those of quantitative ultrasound suggesting that skin discoloration cannot be used as a marker for subcutaneous fibrosis. These tools may prove useful for the reduction of radiation morbidities and improvement of patient quality of life. PMID:21992389

Prognostic Value of p16 Status on the Development of a Complete Response in Involved Oropharynx Cancer Neck Nodes After Cisplatin-Based Chemoradiation: A Secondary Analysis of NRG Oncology RTOG 0129

DOE Office of Scientific and Technical Information (OSTI.GOV)

Galloway, Thomas J., E-mail: thomas.galloway@fccc.edu; Zhang, Qiang; Nguyen-Tan, Phuc Felix

Purpose: To determine the relationship between p16 status and the regional response of patients with node-positive oropharynx cancer treated on NRG Oncology RTOG 0129. Methods and Materials: Patients with N1-N3 oropharynx cancer and known p16 status who underwent treatment on RTOG 0129 were analyzed. Pathologic complete response (pCR) rates in patients treated with a postchemoradiation neck dissection (with p16-positive or p16-negative cancer) were compared by Fisher exact test. Patients managed expectantly were compared with those treated with a neck dissection. Results: Ninety-nine (34%) of 292 patients with node-positive oropharynx cancer and known p16 status underwent a posttreatment neck dissection (p16-positive:more » n=69; p16-negative: n=30). The remaining 193 patients with malignant lymphadenopathy at diagnosis were observed. Neck dissection was performed a median of 70 (range, 17-169) days after completion of chemoradiation. Neither the pretreatment nodal stage (P=.71) nor the postradiation, pre-neck dissection clinical/radiographic neck assessment (P=.42) differed by p16 status. A pCR was more common among p16-positive patients (78%) than p16-negative patients (53%, P=.02) and was associated with a reduced incidence of local–regional failure (hazard ratio 0.33, P=.003). On multivariate analysis of local–regional failure, a test for interaction between pCR and p16 status was not significant (P=.37). One-hundred ninety-three (66%) of 292 of initially node-positive patients were managed without a posttreatment neck dissection. Development of a clinical (cCR) was not significantly influenced by p16-status (P=.42). Observed patients with a clinical nodal CR had disease control outcomes similar to those in patients with a pCR neck dissection. Conclusions: Patients with p16-positive tumors had significantly higher pCR and locoregional control rates than those with p16-negative tumors.« less

Prognostic Value of p16 Status on the Development of a Complete Response in Involved Oropharynx Cancer Neck Nodes After Cisplatin-Based Chemoradiation: A Secondary Analysis of NRG Oncology RTOG 0129.

PubMed

Galloway, Thomas J; Zhang, Qiang Ed; Nguyen-Tan, Phuc Felix; Rosenthal, David I; Soulieres, Denis; Fortin, André; Silverman, Craig L; Daly, Megan E; Ridge, John A; Hammond, J Alexander; Le, Quynh-Thu

2016-10-01

To determine the relationship between p16 status and the regional response of patients with node-positive oropharynx cancer treated on NRG Oncology RTOG 0129. Patients with N1-N3 oropharynx cancer and known p16 status who underwent treatment on RTOG 0129 were analyzed. Pathologic complete response (pCR) rates in patients treated with a postchemoradiation neck dissection (with p16-positive or p16-negative cancer) were compared by Fisher exact test. Patients managed expectantly were compared with those treated with a neck dissection. Ninety-nine (34%) of 292 patients with node-positive oropharynx cancer and known p16 status underwent a posttreatment neck dissection (p16-positive: n=69; p16-negative: n=30). The remaining 193 patients with malignant lymphadenopathy at diagnosis were observed. Neck dissection was performed a median of 70 (range, 17-169) days after completion of chemoradiation. Neither the pretreatment nodal stage (P=.71) nor the postradiation, pre-neck dissection clinical/radiographic neck assessment (P=.42) differed by p16 status. A pCR was more common among p16-positive patients (78%) than p16-negative patients (53%, P=.02) and was associated with a reduced incidence of local-regional failure (hazard ratio 0.33, P=.003). On multivariate analysis of local-regional failure, a test for interaction between pCR and p16 status was not significant (P=.37). One-hundred ninety-three (66%) of 292 of initially node-positive patients were managed without a posttreatment neck dissection. Development of a clinical (cCR) was not significantly influenced by p16-status (P=.42). Observed patients with a clinical nodal CR had disease control outcomes similar to those in patients with a pCR neck dissection. Patients with p16-positive tumors had significantly higher pCR and locoregional control rates than those with p16-negative tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

SU-E-T-581: Planning Evaluation of Step-And-Shoot IMRT, RapidArc and Helical TomoTherapy for Hippocampal-Avoidance Whole Brain Radiotherapy (HA-WBRT).

PubMed

Evans, J; Chen, Q; Wuthrick, E; Weldon, M; Rong, Y

2012-06-01

Several planning strategies are available for hippocampal- avoidance whole-brain radiotherapy (HA-WBRT) following RTOG protocol 0933, but have yet to be compared on a common set of patient data. In this inter-institutional investigation, we evaluate three modalities likely to be employed by protocol participants; step-and-shoot IMRT, volumetric modulated arc therapy, and helical tomotherapy. A common set of patients is used for comparison, including credentialing and successfully accrued patients. Eight patient datasets were selected and de-identified prior to planning. Structures were contoured by physicians per protocol using fused MRI datasets. Three plans were generated for each dataset: Philips Pinnacle 9-field non-coplanar IMRT using protocol recommended beam parameters, Varian's RapidArc using two coplanar arcs, and Accuray's TomoTherapy using a 1cm jaw width. With the goal of meeting the compliance criteria outlined in RTOG 0933 (target coverage and dose limits to the hippocampus and optic structures), three planners independently planned each modality without prior knowledge of the patient's other plans to reduce bias. The three plans for each patient were compared according to the protocol's dosimetric compliance criteria. A homogeneity index was also computed to compare target dose uniformity. All plans achieved the protocol dose criteria, except for one RapidArc plan with slightly inferior dose to the optic chiasm. TomoTherapy offered superior dose homogeneity for all patients. For the two linac based methods, RapidArc was found to provide dose homogeneity at least as good as, and in most cases superior to, 9-field step-and-shoot IMRT. Helical TomoTherapy offers superior dose homogeneity for HA-WBRT following RTOG 0933. Compared to step-and-shoot IMRT, volumetric modulated arc techniques, such as RapidArc, can offer improved homogeneity for HA- WBRT and are generally more efficient/expeditious to deliver than the noncoplanar 9-field arrangement recommended by the protocol, which uses 7 separate couch angles. © 2012 American Association of Physicists in Medicine.

Automatic planning on hippocampal avoidance whole-brain radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Shuo, E-mail: shuo0220@gmail.com; Zheng, Dandan; Zhang, Chi

Mounting evidence suggests that radiation-induced damage to the hippocampus plays a role in neurocognitive decline for patients receiving whole-brain radiotherapy (WBRT). Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) has been proposed to reduce the putative neurocognitive deficits by limiting the dose to the hippocampus. However, urgency of palliation for patients as well as the complexities of the treatment planning may be barriers to protocol enrollment to accumulate further clinical evidence. This warrants expedited quality planning of HA-WBRT. Pinnacle{sup 3} Automatic treatment planning was designed to increase planning efficiency while maintaining or improving plan quality and consistency. The aim of the present studymore » is to evaluate the performance of the Pinnacle{sup 3} Auto-Planning on HA-WBRT treatment planning. Ten patients previously treated for brain metastases were selected. Hippocampal volumes were contoured on T1 magnetic resonance (MR) images, and planning target volumes (PTVs) were generated based on RTOG0933. The following 2 types of plans were generated by Pinnacle{sup 3} Auto-Planning: the one with 2 coplanar volumetric modulated arc therapy (VMAT) arcs and the other with 9-field noncoplanar intensity-modulated radiation therapy (IMRT). D{sub 2%} and D{sub 98%} of PTV were used to calculate homogeneity index (HI). HI and Paddick Conformity index (CI) of PTV as well as D{sub 100%} and D{sub max} of the hippocampus were used to evaluate the plan quality. All the auto-plans met the dose coverage and constraint objectives based on RTOG0933. The auto-plans eliminated the necessity of generating pseudostructures by the planners, and it required little manual intervention which expedited the planning process. IMRT quality assurance (QA) results also suggest that all the auto-plans are practically acceptable on delivery. Pinnacle{sup 3} Auto-Planning generates acceptable plans by RTOG0933 criteria without time-consuming planning process. The expedited quality planning achieved by Auto-Planning (AP) may facilitate protocol enrollment of patients to further investigate the hippocampal-sparing effect and be used to ensure timely start of palliative treatment in future clinical practice.« less

A Phase 1/2 Trial of a Combination of Paclitaxel and Trastuzumab With Daily Irradiation or Paclitaxel Alone With Daily Irradiation After Transurethral Surgery for Noncystectomy Candidates With Muscle-Invasive Bladder Cancer (Trial NRG Oncology RTOG 0524)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Michaelson, M. Dror, E-mail: dmichaelson1@partners.org; Hu, Chen; Sydney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland

Purpose: Bladder preservation therapy is an effective treatment for muscle-invasive urothelial carcinoma (UC). In this study we treated noncystectomy candidates with daily radiation and weekly paclitaxel for 7 weeks. Patients whose tumors showed her2/neu overexpression were additionally treated with weekly trastuzumab. Methods and Materials: Sixty-eight evaluable patients were treated with radiation therapy and either paclitaxel + trastuzumab (group 1) or paclitaxel alone (group 2). Groups were assigned on the basis of her2/neu immunohistochemistry results. Patients received 1.8-Gy fractions to a total dose of 64.8 Gy. The primary endpoint of the study was treatment-related toxicity, and secondary endpoints included complete response (CR) rate, protocol completionmore » rate, and survival. Results: A total of 20 evaluable patients were treated in group 1 and 46 patients in group 2. Acute treatment-related adverse events (AEs) were observed in 7 of 20 patients in group 1 (35%) and 14 of 46 patients in group 2 (30.4%). Protocol therapy was completed by 60% (group 1) and 74% (group 2) of patients. Most incompletions were due to toxicity, and the majority of AEs were gastrointestinal, including 1 grade 5 AE (group 1). Two other deaths (both in group 2) were unrelated to protocol therapy. No unexpected cardiac, hematologic, or other toxicities were observed. The CR rate at 1 year was 72% for group 1 and 68% for group 2. Conclusions: In patients with muscle-invasive UC who are not candidates for cystectomy, daily radiation combined with paclitaxel is an effective treatment strategy with a high completion rate and moderate toxicity. In patients with her2/neu-positive tumors, a group generally considered to have worse outcomes, the addition of trastuzumab appears to result in comparable efficacy and toxicity. Further biomarker-driven trials should be undertaken in advancing treatment of this challenging disease.« less

Clinical study of concurrent chemoradiotherapy or radiotherapy alone for esophageal cancer patients with positive lymph node metastasis.

PubMed

Han, Jihua; Zhu, Weiguo; Yu, Changhua; Zhou, Xilei; Li, Tao; Zhang, Xiaoye

2012-01-01

Esophageal cancer patients with pathologic lymph node involvement generally have a poor prognosis. Many randomized controlled trials have not achieved consistent results similar to those of the RTOG8501 trial, and the long-term survival rate has not increased. The present study aimed to compare the efficacy and toxic side effects of concurrent chemoradiotherapy and radiotherapy alone to treat N1 esophageal carcinoma. A total of 130 N1 esophageal carcinoma patients were enrolled and randomly divided into two groups: concurrent chemoradiotherapy group (n = 65) and radiotherapy group (n = 65). Both groups received three-dimensional conformal radiotherapy with a total dose of 64-66 Gy. Meanwhile, to the concurrent chemoradiotherapy group, an additional chemotherapy protocol (nedaplatin, 20 mg/m²/d, 5-FU, 500 mg/m²/d for four days) was given from day 1, and such treatment was repeated until day 29. From day 21 after radiotherapy, two cycles of a consolidated chemotherapy protocol were given at an interval of 28 days. The survival rates at one, two, and three years were 72.3%, 55.3%, and 40% in the concurrent chemoradiotherapy group, respectively, and 75.3%, 38.5%, and 18.5% in the radiotheray group (P = 0.007), respectively. The survival rates of the patients in the concurrent chemoradiotherapy group who completed one to two cycles and three to four cycles at one, two, and three years were 70%, 53.3%, and 30%, and 74.2%, 57.1%, 48.6% (P = 0.128), respectively. Three-year distant metastasis rates were 10.7% in the concurrent chemoradiotherapy group and 16.9% in the radiotherapy group. Acute toxicity in the concurrent chemoradiotherapy group was higher than in the radiotherapy group. Late toxic side effects were similar in the two groups. Compared with radiotherapy alone, concurrent chemoradiotherapy in the treatment of esophageal carcinoma with local lymph node enlargement can improve the three-year survival rate. Moreover, completion of three to four cycles of chemotherapy may have better efficacy than one to two cycles.

Hyperfractionated accelerated radiotherapy with concomitant integrated boost of 70-75 Gy in 5 weeks for advanced head and neck cancer. A phase I dose escalation study.

PubMed

Cvek, J; Kubes, J; Skacelikova, E; Otahal, B; Kominek, P; Halamka, M; Feltl, D

2012-08-01

The present study was performed to evaluate the feasibility of a new, 5-week regimen of 70-75 Gy hyperfractionated accelerated radiotherapy with concomitant integrated boost (HARTCIB) for locally advanced, inoperable head and neck cancer. A total of 39 patients with very advanced, stage IV nonmetastatic head and neck squamous cell carcinoma (median gross tumor volume 72 ml) were included in this phase I dose escalation study. A total of 50 fractions intensity-modulated radiotherapy (IMRT) were administered twice daily over 5 weeks. Prescribed total dose/dose per fraction for planning target volume (PTV(tumor)) were 70 Gy in 1.4 Gy fractions, 72.5 Gy in 1.45 Gy fractions, and 75 Gy in 1.5 Gy fractions for 10, 13, and 16 patients, respectively. Uninvolved lymphatic nodes (PTV(uninvolved)) were irradiated with 55 Gy in 1.1 Gy fractions using the concomitant integrated boost. Acute toxicity was evaluated according to the RTOG/EORTC scale; the incidence of grade 3 mucositis was 51% in the oral cavity/pharynx and 0% in skin and the recovery time was ≤ 9 weeks for all patients. Late toxicity was evaluated in patients in complete remission according to the RTOG/EORTC scale. No grade 3/4 late toxicity was observed. The 1-year locoregional progression-free survival was 50% and overall survival was 55%. HARTCIB (75 Gy in 5 weeks) is feasible for patients deemed unsuitable for chemoradiation. Acute toxicity was lower than predicted from radiobiological models; duration of dysphagia and confluent mucositis were particularly short. Better conformity of radiotherapy allows the use of more intensive altered fractionation schedules compared with older studies. These results suggest that further dose escalation might be possible when highly conformal techniques (e.g., stereotactic radiotherapy) are used.

Cure modeling in real-time prediction: How much does it help?

PubMed

Ying, Gui-Shuang; Zhang, Qiang; Lan, Yu; Li, Yimei; Heitjan, Daniel F

2017-08-01

Various parametric and nonparametric modeling approaches exist for real-time prediction in time-to-event clinical trials. Recently, Chen (2016 BMC Biomedical Research Methodology 16) proposed a prediction method based on parametric cure-mixture modeling, intending to cover those situations where it appears that a non-negligible fraction of subjects is cured. In this article we apply a Weibull cure-mixture model to create predictions, demonstrating the approach in RTOG 0129, a randomized trial in head-and-neck cancer. We compare the ultimate realized data in RTOG 0129 to interim predictions from a Weibull cure-mixture model, a standard Weibull model without a cure component, and a nonparametric model based on the Bayesian bootstrap. The standard Weibull model predicted that events would occur earlier than the Weibull cure-mixture model, but the difference was unremarkable until late in the trial when evidence for a cure became clear. Nonparametric predictions often gave undefined predictions or infinite prediction intervals, particularly at early stages of the trial. Simulations suggest that cure modeling can yield better-calibrated prediction intervals when there is a cured component, or the appearance of a cured component, but at a substantial cost in the average width of the intervals. Copyright © 2017 Elsevier Inc. All rights reserved.

Reirradiation of head and neck cancer: Long-term disease control and toxicity.

PubMed

Bots, Wouter T C; van den Bosch, Sven; Zwijnenburg, Ellen M; Dijkema, Tim; van den Broek, Guido B; Weijs, Willem L J; Verhoef, Lia C G; Kaanders, Johannes H A M

2017-06-01

The purpose of this study was to report long-term disease control and late radiation toxicity for patients reirradiated for head and neck cancer. We conducted a retrospective analysis of 137 patients reirradiated with a prescribed dose ≥45 Gy between 1986 and 2013 for a recurrent or second primary malignancy. Endpoints were locoregional control, overall survival (OS), and grade ≥4 late complications according to European Organization for Research and Treatment of Cancer (EORTC)/Radiation Therapy Oncology Group (RTOG) criteria. Five-year locoregional control rates were 46% for patients reirradiated postoperatively versus 20% for patients who underwent reirradiation as the primary treatment (p < .05). Sixteen cases of serious (grade ≥4) late toxicity were seen in 11 patients (actuarial 28% at 5 years). In patients reirradiated with intensity-modulated radiotherapy (IMRT), a borderline improved locoregional control was observed (49% vs 36%; p = .07), whereas late complication rates did not differ. Reirradiation should be considered for patients with a recurrent or second primary head and neck cancer, especially postoperatively, if indicated. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1122-1130, 2017. © 2017 The Authors Head & Neck Published by Wiley Periodicals, Inc.

A double-blind, placebo-controlled, randomised trial of active manuka honey and standard oral care for radiation-induced oral mucositis.

PubMed

Bardy, Joy; Molassiotis, Alex; Ryder, W David; Mais, Kathleen; Sykes, Andrew; Yap, Beng; Lee, Lip; Kaczmarski, Ed; Slevin, Nicholas

2012-04-01

Our aim was to investigate the effect of active manuka honey on radiation-induced mucositis. A total of 131 patients diagnosed with head and neck cancer who were having radiotherapy to the oral cavity or oropharyngeal area were recruited into the study, and were randomly allocated to take either manuka honey or placebo (golden syrup) 20 ml 4 times daily for 6 weeks. Mucositis was assessed according to the Radiation Therapy Oncology Group (RTOG) scale at baseline, weekly during radiotherapy, and twice weekly thereafter until the mucositis resolved. The patient's weight was recorded at the same time as the mucositis was assessed. Throat swabs to identify bacterial or fungal infections were taken at baseline, and during and after radiotherapy. There was no significant difference between honey and golden syrup in their effects on mucositis. Active manuka honey did not improve mucositis, but both the honey and the syrup seemed to be associated with a reduction in bacterial infections. Compliance was a problem after the onset of mucositis, which may have affected the findings. Copyright © 2011 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Radiation-induced complications in prostate cancer patients treated with radiotherapy

NASA Astrophysics Data System (ADS)

Azuddin, A. Yusof; Rahman, I. Abdul; Siah, N. J.; Mohamed, F.; Saadc, M.; Ismail, F.

2014-09-01

The purpose of the study is to determine the relationship between radiation-induced complications with dosimetric and radiobiological parameters for prostate cancer patients that underwent the conformal radiotherapy treatment. 17 prostate cancer patients that have been treated with conformal radiotherapy were retrospectively analysed. The dosimetric data was retrieved in the form of dose-volume histogram (DVH) from Radiotherapy Treatment Planning System. The DVH was utilised to derived Normal Tissue Complication Probability (NTCP) in radiobiological data. Follow-up data from medical records were used to grade the occurrence of acute gastrointestinal (GI) and genitourinary (GU) complications using Radiation Therapy Oncology Group (RTOG) scoring system. The chi-square test was used to determine the relationship between radiation-induced complication with dosimetric and radiobiological parameters. 8 (47%) and 7 (41%) patients were having acute GI and GU complications respectively. The acute GI complication can be associated with V60rectum, rectal mean dose and NTCPrectum with p-value of 0.016, 0.038 and 0.049 respectively. There are no significant relationships of acute GU complication with dosimetric and radiobiological variables. Further study can be done by increase the sample size and follow up duration for deeper understanding of the factors that effecting the GU and GI complication in prostate cancer radiotherapy.

WE-E-BRB-11: Riview a Web-Based Viewer for Radiotherapy.

PubMed

Apte, A; Wang, Y; Deasy, J

2012-06-01

Collaborations involving radiotherapy data collection, such as the recently proposed international radiogenomics consortium, require robust, web-based tools to facilitate reviewing treatment planning information. We present the architecture and prototype characteristics for a web-based radiotherapy viewer. The web-based environment developed in this work consists of the following components: 1) Import of DICOM/RTOG data: CERR was leveraged to import DICOM/RTOG data and to convert to database friendly RT objects. 2) Extraction and Storage of RT objects: The scan and dose distributions were stored as .png files per slice and view plane. The file locations were written to the MySQL database. Structure contours and DVH curves were written to the database as numeric data. 3) Web interfaces to query, retrieve and visualize the RT objects: The Web application was developed using HTML 5 and Ruby on Rails (RoR) technology following the MVC philosophy. The open source ImageMagick library was utilized to overlay scan, dose and structures. The application allows users to (i) QA the treatment plans associated with a study, (ii) Query and Retrieve patients matching anonymized ID and study, (iii) Review up to 4 plans simultaneously in 4 window panes (iv) Plot DVH curves for the selected structures and dose distributions. A subset of data for lung cancer patients was used to prototype the system. Five user accounts were created to have access to this study. The scans, doses, structures and DVHs for 10 patients were made available via the web application. A web-based system to facilitate QA, and support Query, Retrieve and the Visualization of RT data was prototyped. The RIVIEW system was developed using open source and free technology like MySQL and RoR. We plan to extend the RIVIEW system further to be useful in clinical trial data collection, outcomes research, cohort plan review and evaluation. © 2012 American Association of Physicists in Medicine.

American Association of Physicists in Medicine Task Group 263: Standardizing Nomenclatures in Radiation Oncology.

PubMed

Mayo, Charles S; Moran, Jean M; Bosch, Walter; Xiao, Ying; McNutt, Todd; Popple, Richard; Michalski, Jeff; Feng, Mary; Marks, Lawrence B; Fuller, Clifton D; Yorke, Ellen; Palta, Jatinder; Gabriel, Peter E; Molineu, Andrea; Matuszak, Martha M; Covington, Elizabeth; Masi, Kathryn; Richardson, Susan L; Ritter, Timothy; Morgas, Tomasz; Flampouri, Stella; Santanam, Lakshmi; Moore, Joseph A; Purdie, Thomas G; Miller, Robert C; Hurkmans, Coen; Adams, Judy; Jackie Wu, Qing-Rong; Fox, Colleen J; Siochi, Ramon Alfredo; Brown, Norman L; Verbakel, Wilko; Archambault, Yves; Chmura, Steven J; Dekker, Andre L; Eagle, Don G; Fitzgerald, Thomas J; Hong, Theodore; Kapoor, Rishabh; Lansing, Beth; Jolly, Shruti; Napolitano, Mary E; Percy, James; Rose, Mark S; Siddiqui, Salim; Schadt, Christof; Simon, William E; Straube, William L; St James, Sara T; Ulin, Kenneth; Yom, Sue S; Yock, Torunn I

2018-03-15

A substantial barrier to the single- and multi-institutional aggregation of data to supporting clinical trials, practice quality improvement efforts, and development of big data analytics resource systems is the lack of standardized nomenclatures for expressing dosimetric data. To address this issue, the American Association of Physicists in Medicine (AAPM) Task Group 263 was charged with providing nomenclature guidelines and values in radiation oncology for use in clinical trials, data-pooling initiatives, population-based studies, and routine clinical care by standardizing: (1) structure names across image processing and treatment planning system platforms; (2) nomenclature for dosimetric data (eg, dose-volume histogram [DVH]-based metrics); (3) templates for clinical trial groups and users of an initial subset of software platforms to facilitate adoption of the standards; (4) formalism for nomenclature schema, which can accommodate the addition of other structures defined in the future. A multisociety, multidisciplinary, multinational group of 57 members representing stake holders ranging from large academic centers to community clinics and vendors was assembled, including physicists, physicians, dosimetrists, and vendors. The stakeholder groups represented in the membership included the AAPM, American Society for Radiation Oncology (ASTRO), NRG Oncology, European Society for Radiation Oncology (ESTRO), Radiation Therapy Oncology Group (RTOG), Children's Oncology Group (COG), Integrating Healthcare Enterprise in Radiation Oncology (IHE-RO), and Digital Imaging and Communications in Medicine working group (DICOM WG); A nomenclature system for target and organ at risk volumes and DVH nomenclature was developed and piloted to demonstrate viability across a range of clinics and within the framework of clinical trials. The final report was approved by AAPM in October 2017. The approval process included review by 8 AAPM committees, with additional review by ASTRO, European Society for Radiation Oncology (ESTRO), and American Association of Medical Dosimetrists (AAMD). This Executive Summary of the report highlights the key recommendations for clinical practice, research, and trials. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herrington, J; Price, M; Brindle, J

Purpose: To evaluate the equivalence of spine SBRT treatment plans created in Eclipse for the TrueBeam STx (Varian Medical System, Palo Alto, CA) compared to plans using CyberKnife and MultiPlan (Accuray, Sunnyvale, CA). Methods: CT data and contours for 23 spine SBRT patients previously treated using CyberKnife (CK) were exported from MultiPlan treatment planning system into Eclipse where they were planned using static IMRT 6MV coplanar beams. Plans were created according to the original prescription dose and fractionation schedule while limiting spinal dose according to the RTOG 0631 protocol and maintaining target coverage comparable to the original CK plans. Plansmore » were evaluated using new conformity index (nCI), homogeneity index (HI), dose-volume histogram data, number of MU, and estimated treatment time. To ensure all Eclipse plans were deliverable, standard clinical IMRT QA was performed. The plan results were matched with their complimentary CK plans for paired statistical analysis. Results: Plans generated in Eclipse demonstrated statistically significant (p<0.01) improvements compared to complimentary CK plans in median values of maximum spinal cord dose (17.39 vs. 18.12 Gy), RTOG spinal cord constraint dose (14.50 vs. 16.93 Gy), nCI (1.28 vs. 1.54), HI (1.13 vs. 1.27), MU (3918 vs. 36416), and estimated treatment time (8 vs. 48 min). All Eclipse generated plans passed our clinically used protocols for IMRT QA. Conclusion: CK spine SBRT replanned utilizing Eclipse for LINAC delivery demonstrated dosimetric advantages. We propose improvements in plan quality metrics reviewed in this study may be attributed to dynamic MLCs that facilitate treatment of complicated geometries as well as posterior beams ideal for centrally located and/or posterior targets afforded by gantry-based RT delivery.« less

Salvage brachytherapy for local recurrences of prostate cancer treated previously with radiotherapy.

PubMed

Gawkowska-Suwinska, Marzena; Fijałkowski, Marek; Białas, Brygida; Szlag, Marta; Kellas-Ślęczka, Sylwia; Nowicka, Elżbieta; Behrendt, Katarzyna; Plewicki, Grzegorz; Smolska-Ciszewska, Beata; Giglok, Monika; Zajusz, Aleksander; Owczarek, Grzegorz

2009-12-01

The aim of the study was to analyze early effects and toxicity of salvage high dose rate brachytherapy for local recurrences of adenocarcinoma of the prostate after external beam radiotherapy (EBRT). In MCS Memorial Institute of Oncology in Gliwice a research programme on salvage HDR brachytherapy for local recurrences of prostate cancer treated previously with EBRT has been ongoing since February 2008. The treatment consisted of 3 fractions of 10 Gy each given every 14 days. Maximal urethral doses were constrained to be ≤ 120% of the prescribed dose. Maximal bladder and rectum doses were constrained to be ≤ 70% of the prescribed dose. Fifteen eligible patients were treated and analyzed from February 2008. All patients completed the treatment without major complications. The most common early complications were: macroscopic haematuria, pain in lower part of the abdomen, and transient dysuria. During the first week after the procedure a transient increase in IPSS score was noticed. The Foley catheter was removed on day 2 to 5. No complications after spinal anaesthesia were observed. Acute toxicity according to EORTC/RTOG was low. For bladder EORTC/RTOG score ranged from 0 to 2. Only in two patients grade 1 toxicity for rectum was observed. The follow-up ranged from 3 to 9 months. In one patient grade 2 rectal toxicity was observed, and one had urethral stricture. Other patients did not have any other significant late toxicity of the treatment. Two patients developed bone metastases. Salvage brachytherapy for localized prostate cancer (3 × 10 Gy every 14 days) seems to be a safe and well tolerated procedure. A significant decline in prostate-specific antigen (PSA) level is seen in patients with hormone-responsive cancer. Long-term efficiency and toxicity of the procedure are yet to be established.

Institutional Enrollment and Survival Among NSCLC Patients Receiving Chemoradiation: NRG Oncology Radiation Therapy Oncology Group (RTOG) 0617.

PubMed

Eaton, Bree R; Pugh, Stephanie L; Bradley, Jeffrey D; Masters, Greg; Kavadi, Vivek S; Narayan, Samir; Nedzi, Lucien; Robinson, Cliff; Wynn, Raymond B; Koprowski, Christopher; Johnson, Douglas W; Meng, Joanne; Curran, Walter J

2016-09-01

The purpose of this analysis is to evaluate the effect of institutional accrual volume on clinical outcomes among patients receiving chemoradiation for locally advanced non-small cell lung cancer (LA-NSCLC) on a phase III trial. Patients with LA-NSCLC were randomly assigned to 60 Gy or 74 Gy radiotherapy (RT) with concurrent carboplatin/paclitaxel +/- cetuximab on NRG Oncology RTOG 0617. Participating institutions were categorized as low-volume centers (LVCs) or high-volume centers (HVCs) according to the number of patients accrued (≤3 vs > 3). All statistical tests were two-sided. Range of accrual for LVCs (n = 195) vs HVCs (n = 300) was 1 to 3 vs 4 to 18 patients. Baseline characteristics were similar between the two cohorts. Treatment at a HVC was associated with statistically significantly longer overall survival (OS) and progression-free survival (PFS) compared with treatment at a LVC (median OS = 26.2 vs 19.8 months; HR = 0.70, 95% CI = 0.56 to 0.88, P = .002; median PFS: 11.4 vs 9.7 months, HR = 0.80, 95% CI = 0.65-0.99, P = .04). Patients treated at HVCs were more often treated with intensity-modulated RT (54.0% vs 39.5%, P = .002), had a lower esophageal dose (mean = 26.1 vs 28.0 Gy, P = .03), and had a lower heart dose (median = V5 Gy 38.2% vs 54.1%, P = .006; V50 Gy 3.6% vs 7.3%, P < .001). Grade 5 adverse events (AEs) (5.3% vs 9.2%, P = .09) and RT termination because of AEs (1.3% vs 4.1%, P = .07) were less common among patients treated at HVCs. HVC remained independently associated with longer OS (P = .03) when accounting for other factors. Treatment at institutions with higher clinical trial accrual volume is associated with longer OS among patients with LA-NSCLC participating in a phase III trial. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Anal Carcinoma: Impact of TN Category of Disease on Survival, Disease Relapse, and Colostomy Failure in US Gastrointestinal Intergroup RTOG 98-11 Phase 3 Trial

PubMed Central

Gunderson, Leonard L.; Moughan, Jennifer; Ajani, Jaffer A.; Pedersen, John E.; Winter, Kathryn A.; Benson, Al B.; Thomas, Charles R.; Mayer, Robert J.; Haddock, Michael G.; Rich, Tyvin A.; Willett, Christopher G.

2013-01-01

Purpose The long-term update of US GI Intergroup RTOG 98-11 anal cancer trial found that concurrent chemoradiation (CCRT) with fluorouracil (5-FU) plus mitomycin had a significant impact on disease-free survival (DFS) and overall survival (OS) compared with induction plus concurrent 5-FU plus cisplatin. The intent of the current analysis was to determine the impact of tumor node (TN) category of disease on survival (DFS and OS), colostomy failure (CF), and relapse (local-regional failure [LRF] and distant metastases [DM]) in this patient group. Methods and Materials DFS and OS were estimated univariately by using the Kaplan-Meier method, and 6 TN categories were compared by the log–rank test (T2N0, T3N0, T4N0, T2N1-3, T3N1-3, and T4N1-3). Time to relapse and colostomy were estimated by the cumulative incidence method, and TN categories were compared using Gray’s test. Results Of 682 patients, 620 were analyzable for outcomes by TN category. All endpoints showed statistically significant differences among the TN categories of disease (OS, P<.0001; DFS, P<.0001; LRF, P<.0001; DM, P=.0011; CF, P=.01). Patients with the poorest OS, DFS, and LRF outcomes were those with T3-4N-positive (+) disease. CF was lowest for T2N0 and T2N+ (11%, 11%, respectively) and worst for the T4N0, T3N+, and T4N+ categories (26%, 27%, 24%, respectively). Conclusions TN category of disease has a statistically significant impact on OS, DFS, LRF, DM, and CF in patients treated with CCRT and provides excellent prognostic information for outcomes in patients with anal carcinoma. Significant challenges remain for patients with T4N0 and T3-4N+ categories of disease with regard to survival, relapse, and CF and lesser challenges for T2-3N0/T2N+ categories. PMID:24035327

A Contralateral Esophagus-Sparing Technique to Limit Severe Esophagitis Associated With Concurrent High-Dose Radiation and Chemotherapy in Patients With Thoracic Malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Halabi, Hani; Paetzold, Peter; Sharp, Gregory C.

2015-07-15

Purpose: Severe (Radiation Therapy Oncology Group [RTOG] grade 3 or greater) esophagitis generally occurs in 15% to 25% of non–small cell lung cancer (NSCLC) patients undergoing concurrent chemotherapy and radiation therapy (CCRT), which may result in treatment breaks that compromise local tumor control and pose a barrier to dose escalation. Here, we report a novel contralateral esophagus-sparing technique (CEST) that uses intensity modulated radiation therapy (IMRT) to reduce the incidence of severe esophagitis. Methods and Materials: We reviewed consecutive patients with thoracic malignancies undergoing curative CCRT in whom CEST was used. The esophageal wall contralateral (CE) to the tumor wasmore » contoured as an avoidance structure, and IMRT was used to guide a rapid dose falloff gradient beyond the target volume in close proximity to the esophagus. Esophagitis was recorded based on the RTOG acute toxicity grading system. Results: We identified 20 consecutive patients treated with CCRT of at least 63 Gy in whom there was gross tumor within 1 cm of the esophagus. The median radiation dose was 70.2 Gy (range, 63-72.15 Gy). In all patients, ≥99% of the planning and internal target volumes was covered by ≥90% and 100% of prescription dose, respectively. Strikingly, no patient experienced grade ≥3 esophagitis (95% confidence limits, 0%-16%) despite the high total doses delivered. The median maximum dose, V45, and V55 of the CE were 60.7 Gy, 2.1 cc, and 0.4 cc, respectively, indicating effective esophagus cross-section sparing by CEST. Conclusion: We report a simple yet effective method to avoid exposing the entire esophagus cross-section to high doses. By using proposed CE dose constraints of V45 <2.5 cc and V55 <0.5 cc, CEST may improve the esophagus toxicity profile in thoracic cancer patients receiving CCRT even at doses above the standard 60- to 63-Gy levels. Prospective testing of CEST is warranted.« less

SU-E-J-134: Optimizing Technical Parameters for Using Atlas Based Automatic Segmentation for Evaluation of Contour Accuracy Experience with Cardiac Structures From NRG Oncology/RTOG 0617

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, J; Gong, Y; Bar-Ad, V

Purpose: Accurate contour delineation is crucial for radiotherapy. Atlas based automatic segmentation tools can be used to increase the efficiency of contour accuracy evaluation. This study aims to optimize technical parameters utilized in the tool by exploring the impact of library size and atlas number on the accuracy of cardiac contour evaluation. Methods: Patient CT DICOMs from RTOG 0617 were used for this study. Five experienced physicians delineated the cardiac structures including pericardium, atria and ventricles following an atlas guideline. The consistency of cardiac structured delineation using the atlas guideline was verified by a study with four observers and seventeenmore » patients. The CT and cardiac structure DICOM files were then used for the ABAS technique.To study the impact of library size (LS) and atlas number (AN) on automatic contour accuracy, automatic contours were generated with varied technique parameters for five randomly selected patients. Three LS (20, 60, and 100) were studied using commercially available software. The AN was four, recommended by the manufacturer. Using the manual contour as the gold standard, Dice Similarity Coefficient (DSC) was calculated between the manual and automatic contours. Five-patient averaged DSCs were calculated for comparison for each cardiac structure.In order to study the impact of AN, the LS was set 100, and AN was tested from one to five. The five-patient averaged DSCs were also calculated for each cardiac structure. Results: DSC values are highest when LS is 100 and AN is four. The DSC is 0.90±0.02 for pericardium, 0.75±0.06 for atria, and 0.86±0.02 for ventricles. Conclusion: By comparing DSC values, the combination AN=4 and LS=100 gives the best performance. This project was supported by NCI grants U24CA12014, U24CA180803, U10CA180868, U10CA180822, PA CURE grant and Bristol-Myers Squibb and Eli Lilly.« less

SU-F-T-455: Is Contouring the Whole Breast Necessary for Two-Field 3D Breast Planning?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Desai, A; Ku, Eric; Fang, D

Purpose: To investigate the effect of contouring the whole breast on reducing the radiation dose to the heart and affected lung in tangential field-in-field 3D breast planning. We hypothesize that contouring the whole breast will simplify the plan normalization process, reduce dose to critical structures, while maintaining treatment plan quality and consistency. Methods: Twenty previously treated breast cancer patients using tangential field-in-field 3D planning technique were randomly selected. The affected breast was contoured following the RTOG breast atlas guideline. Breast PTV was created by shrinking 5 mm from the breast contour. The same plan has been pasted to the newmore » contour and normalized to 95% of the Breast PTV receiving the prescribed isodose line. Lung V20 Gy% and Heart V25 Gy% were the primary study endpoints. Homogeneity Index (HI) and Conformity Index (CI) were calculated based on the following equations. HI= Dmax/ D95 and Nakamura’s Conformity Index= PIV/TVPIV × TV/TVPIV. Results: The average CI for previous plans was 1.68 vs. 1.66 for the new hybrid plan: both plans were conformal to the breast with similar quality. The HI for both the previous and the new hybrid plan was 1.24. Lung V 20% slightly increased from 4.27% to 4.82%. Heart V 25% for LT breast patients slightly decreased from 0.38% to 0.29%. Heart V 25% for RT breast patients was close to zero in both cases. Conclusion: With similar conformal and homogeneity indices for the plan quality, by contouring the whole breast following RTOG breast atlas guideline will simplify the planning process. The study showed that contouring the whole breast for patients with left-sided breast cancer reduced the heart V 25%, although not significantly, while maintaining the CI and HI. There was no measurable gain seen with whole breast contour for right-sided breast cancer patients.« less

Dose-surface analysis for prediction of severe acute radio-induced skin toxicity in breast cancer patients.

PubMed

Pastore, Francesco; Conson, Manuel; D'Avino, Vittoria; Palma, Giuseppe; Liuzzi, Raffaele; Solla, Raffaele; Farella, Antonio; Salvatore, Marco; Cella, Laura; Pacelli, Roberto

2016-01-01

Severe acute radiation-induced skin toxicity (RIST) after breast irradiation is a side effect impacting the quality of life in breast cancer (BC) patients. The aim of the present study was to develop normal tissue complication probability (NTCP) models of severe acute RIST in BC patients. We evaluated 140 consecutive BC patients undergoing conventional three-dimensional conformal radiotherapy (3D-CRT) after breast conserving surgery in a prospective study assessing acute RIST. The acute RIST was classified according to the RTOG scoring system. Dose-surface histograms (DSHs) of the body structure in the breast region were extracted as representative of skin irradiation. Patient, disease, and treatment-related characteristics were analyzed along with DSHs. NTCP modeling by Lyman-Kutcher-Burman (LKB) and by multivariate logistic regression using bootstrap resampling techniques was performed. Models were evaluated by Spearman's Rs coefficient and ROC area. By the end of radiotherapy, 139 (99%) patients developed any degree of acute RIST. G3 RIST was found in 11 of 140 (8%) patients. Mild-moderate (G1-G2) RIST was still present at 40 days after treatment in six (4%) patients. Using DSHs for LKB modeling of acute RIST severity (RTOG G3 vs. G0-2), parameter estimates were TD50=39 Gy, n=0.38 and m=0.14 [Rs = 0.25, area under the curve (AUC) = 0.77, p = 0.003]. On multivariate analysis, the most predictive model of acute RIST severity was a two-variable model including the skin receiving ≥30 Gy (S30) and psoriasis [Rs = 0.32, AUC = 0.84, p < 0.001]. Using body DSH as representative of skin dose, the LKB n parameter was consistent with a surface effect for the skin. A good prediction performance was obtained using a data-driven multivariate model including S30 and a pre-existing skin disease (psoriasis) as a clinical factor.

Patient-Reported Outcomes and Survivorship in Radiation Oncology: Overcoming the Cons

PubMed Central

Siddiqui, Farzan; Liu, Arthur K.; Watkins-Bruner, Deborah; Movsas, Benjamin

2014-01-01

Purpose Although patient-reported outcomes (PROs) have become a key component of clinical oncology trials, many challenges exist regarding their optimal application. The goal of this article is to methodically review these barriers and suggest strategies to overcome them. This review will primarily focus on radiation oncology examples, will address issues regarding the “why, how, and what” of PROs, and will provide strategies for difficult problems such as methods for reducing missing data. This review will also address cancer survivorship because it closely relates to PROs. Methods Key articles focusing on PROs, quality of life, and survivorship issues in oncology trials are highlighted, with an emphasis on radiation oncology clinical trials. Publications and Web sites of various governmental and regulatory agencies are also reviewed. Results The study of PROs in clinical oncology trials has become well established. There are guidelines provided by organizations such as the US Food and Drug Administration that clearly indicate the importance of and methodology for studying PROs. Clinical trials in oncology have repeatedly demonstrated the value of studying PROs and suggested ways to overcome some of the key challenges. The Radiation Therapy Oncology Group (RTOG) has led some of these efforts, and their contributions are highlighted. The current state of cancer survivorship guidelines is also discussed. Conclusion The study of PROs presents significant benefits in understanding and treating toxicities and enhancing quality of life; however, challenges remain. Strategies are presented to overcome these hurdles, which will ultimately improve cancer survivorship. PMID:25113760

Correlation of High-Risk Soft Tissue Sarcoma Biomarker Expression Patterns with Outcome following Neoadjuvant Chemoradiation

PubMed Central

Magliocco, Anthony; Zhang, Qiang; Wang, Dian; Klimowicz, Alex; Harris, Jonathan; Simko, Jeff; DeLaney, Thomas; Kraybill, William; Kirsch, David G.

2018-01-01

Background Sarcoma mortality remains high despite adjuvant chemotherapy. Biomarker predictors of treatment response and outcome could improve treatment selection. Methods Tissue microarrays (TMAs) were created using pre- and posttreatment tumor from two prospective trials (MGH pilot and RTOG 9514) of neoadjuvant/adjuvant MAID chemotherapy and preoperative radiation. Biomarkers were measured using automated computerized imaging (AQUA or ACIS). Expression was correlated with disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS). Results Specimens from 60 patients included 23 pretreatment (PRE), 40 posttreatment (POST), and 12 matched pairs (MPs). In the MP set, CAIX, GLUT1, and PARP1 expression significantly decreased following neoadjuvant therapy, but p53 nuclear/cytoplasmic (N/C) ratio increased. In the PRE set, no biomarker expression was associated with DFS, DDFS, or OS. In the POST set, increased p53 N/C ratio was associated with a significantly decreased DFS and DDFS (HR 4.13, p=0.017; HR 4.16, p=0.016), while increased ERCC1 and XPF expression were associated with an improved DFS and DDFS. No POST biomarkers were associated with OS. Conclusions PRE biomarker expression did not predict survival outcomes. Expression pattern changes after neoadjuvant chemoradiation supports the concepts of tumor reoxygenation, altered HIF-1α signaling, and a p53 nuclear accumulation DNA damage response. Clinical Trial Registration NRG Oncology RTOG 9514 is registered with ClinicalTrials.gov. The ClinicalTrials.gov Identifier is NCT00002791. PMID:29681762

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pokhrel, D; Sood, S; Badkul, R

Purpose: To evaluate XVMC computed rib doses for peripherally located non-small-cell-lung tumors treated with SBRT following RTOG-0915 guidelines. Methods: Twenty patients with solitary peripherally located non-small-cell-lung tumors were treated using XVMC-based SBRT to 50–54Gy in 5−3 fractions, respectively, for PTV(V100%)=95%. Based on 4D-CT, ITV was delineated on MaximumIP images and organs-at-risk(OARs) including ribs were contoured on MeanIP images. Mean PTV(ITV+5mm uniform margin) was 46.1±38.7cc (range, 11.1–163.0cc). XVMC SBRT treatment plans were generated with a combination of non-coplanar 3D-conformal arcs/beams, and were delivered by Novalis-TX consisting of HD-MLCs and a 6MV-SRS(1000MU/min) beam, following RTOG-0915 criteria. XVMC rib maximum dose and dosemore » to <1cc, <5cc, <10cc were evaluated as a function of PTV, prescription dose and 3D-distance from tumor isocenter to the most proximal rib contour. Plans were re-computed using heterogeneity-corrected pencil-beam (PB-hete) algorithm utilizing identical beam geometry/MLC positions and MUs and subsequently compared to XVMC. Results: XVMC average maximum rib dose was 50.9±6.4Gy (range, 35.1–59.3Gy). XVMC mean rib dose to <1cc was 41.6±5.6Gy (range, 27.9–47.9Gy), <5cc was 31.2±7.3Gy (range, 10.6–43.1Gy), and <10cc was 21.2±8.7Gy (range, 1.1–36Gy), respectively. For the given prescription, correlation between PTV and rib doses to <5cc (p=0.005) and <10cc (p=0.018) was observed. 3D-distance from the tumor isocenter to the proximal rib contour strongly correlated with maximum rib dose (p=0.0001). PB-hete algorithm overestimated maximum rib dose and dose to <1cc, <5cc, and <10cc of ribs by 5%, 3%, 3%, and 3%, respectively. Conclusion: PB-hete overestimates ribs dose relative to XVMC. Since all the clinical XVMC plans were generated without compromising the target coverage (per RTOG-0915), almost all patient’s ribs doses were higher than the protocol guidelines. As expected, larger tumor size and proximity to ribs received higher absolute dose to ribs. Prospective observation is needed to determine if XVMC delivered rib doses correlates with patient symptoms including chest wall pain and/or rib fractures.« less

A geometrically based method for automated radiosurgery planning.

PubMed

Wagner, T H; Yi, T; Meeks, S L; Bova, F J; Brechner, B L; Chen, Y; Buatti, J M; Friedman, W A; Foote, K D; Bouchet, L G

2000-12-01

A geometrically based method of multiple isocenter linear accelerator radiosurgery treatment planning optimization was developed, based on a target's solid shape. Our method uses an edge detection process to determine the optimal sphere packing arrangement with which to cover the planning target. The sphere packing arrangement is converted into a radiosurgery treatment plan by substituting the isocenter locations and collimator sizes for the spheres. This method is demonstrated on a set of 5 irregularly shaped phantom targets, as well as a set of 10 clinical example cases ranging from simple to very complex in planning difficulty. Using a prototype implementation of the method and standard dosimetric radiosurgery treatment planning tools, feasible treatment plans were developed for each target. The treatment plans generated for the phantom targets showed excellent dose conformity and acceptable dose homogeneity within the target volume. The algorithm was able to generate a radiosurgery plan conforming to the Radiation Therapy Oncology Group (RTOG) guidelines on radiosurgery for every clinical and phantom target examined. This automated planning method can serve as a valuable tool to assist treatment planners in rapidly and consistently designing conformal multiple isocenter radiosurgery treatment plans.

TH-E-BRF-09: Gaussian Mixture Model Analysis of Radiation-Induced Parotid-Gland Injury: An Ultrasound Study of Acute and Late Xerostomia in Head-And-Neck Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, T; Yu, D; Beitler, J

Purpose: Xerostomia (dry mouth), secondary to parotid-gland injury, is a distressing side-effect in head-and-neck radiotherapy (RT). This study's purpose is to develop a novel ultrasound technique to quantitatively evaluate post-RT parotid-gland injury. Methods: Recent ultrasound studies have shown that healthy parotid glands exhibit homogeneous echotexture, whereas post-RT parotid glands are often heterogeneous, with multiple hypoechoic (inflammation) or hyperechoic (fibrosis) regions. We propose to use a Gaussian mixture model to analyze the ultrasonic echo-histogram of the parotid glands. An IRB-approved clinical study was conducted: (1) control-group: 13 healthy-volunteers, served as the control; (2) acutetoxicity group − 20 patients (mean age: 62.5more » ± 8.9 years, follow-up: 2.0±0.8 months); and (3) late-toxicity group − 18 patients (mean age: 60.7 ± 7.3 years, follow-up: 20.1±10.4 months). All patients experienced RTOG grade 1 or 2 salivary-gland toxicity. Each participant underwent an ultrasound scan (10 MHz) of the bilateral parotid glands. An echo-intensity histogram was derived for each parotid and a Gaussian mixture model was used to fit the histogram using expectation maximization (EM) algorithm. The quality of the fitting was evaluated with the R-squared value. Results: (1) Controlgroup: all parotid glands fitted well with one Gaussian component, with a mean intensity of 79.8±4.9 (R-squared>0.96). (2) Acute-toxicity group: 37 of the 40 post-RT parotid glands fitted well with two Gaussian components, with a mean intensity of 42.9±7.4, 73.3±12.2 (R-squared>0.95). (3) Latetoxicity group: 32 of the 36 post-RT parotid fitted well with 3 Gaussian components, with mean intensities of 49.7±7.6, 77.2±8.7, and 118.6±11.8 (R-squared>0.98). Conclusion: RT-associated parotid-gland injury is common in head-and-neck RT, but challenging to assess. This work has demonstrated that the Gaussian mixture model of the echo-histogram could quantify acute and late toxicity of the parotid glands. This study provides meaningful preliminary data from future observational and interventional clinical research.« less

Final Results of NRG Oncology RTOG 0246: An Organ-Preserving Selective Resection Strategy in Esophageal Cancer Patients Treated with Definitive Chemoradiation.

PubMed

Swisher, Stephen G; Moughan, Jennifer; Komaki, Ritsuko U; Ajani, Jaffer A; Wu, Tsung T; Hofstetter, Wayne L; Konski, Andre A; Willett, Christopher G

2017-02-01

The impact of selective surgical resection for patients with esophageal cancer treated with definitive chemoradiation has not been clearly evaluated long-term. NRG (National Surgical Adjuvant Breast and Bowel Project, Radiation Therapy Oncology Group, Gynecologic Oncology Group) Oncology Radiation Therapy Oncology Group 0246 was a multi-institutional, single-arm, open-label, nonrandomized phase II study that enrolled 43 patients from September 2003 to March 2008 with clinical stage T1-4N0-1M0 squamous cell or adenocarcinoma of the esophagus or gastroesophageal junction from 19 sites. Patients received induction chemotherapy with fluorouracil (650 mg/m 2 /d), cisplatin (15 mg/m 2 /d), and paclitaxel (200 mg/m 2 /d) for two cycles followed by concurrent chemoradiation consisting of 50.4 Gy of radiation (1.8 Gy per fraction) and daily fluorouracil (300 mg/m 2 /d) with cisplatin (15 mg/m 2 /d) over the first 5 days. After definitive chemoradiation, patients were evaluated for residual disease. Selective esophagectomy was considered only for patients with residual disease after chemoradiation (clinical incomplete response) or recurrent disease on surveillance. This report looks at the long-term outcome of this selective surgical strategy. With a median follow-up of 8.1 years (minimum to maximum for 12 alive patients 7.2-9.8 years), the estimated 5- and 7-year survival rates are 36.6% (95% confidence interval [CI]: 22.3-51.0) and 31.7% (95% CI: 18.3-46.0). Clinical complete response was achieved in 15 patients (37%), with 5- and 7-yearr survival rates of 53.3% (95% CI: 26.3-74.4) and 46.7% (95% CI: 21.2-68.7). Esophageal resection was not required in 20 of 41 patients (49%) on this trial. The long-term results of NRG Oncology Radiation Therapy Oncology Group 0246 demonstrate promising efficacy of a selective surgical resection strategy and suggest the need for larger randomized studies to further evaluate this organ-preserving approach. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

ATM Heterozygosity and the Development of Radiation-Induced Erectile Dysfunction and Urinary Morbidity Following Radiotherapy for Prostate Cancer

DTIC Science & Technology

2005-02-01

such as diabetes or collagen vascular diseases. However, there exists an important subset of patients with no clear explanation for excessive post...Reformed smoker 9(24) Tic 25 (68) Diabetes 3 (8) T2a 8 (22) Pretreatment American Urologic T2b 4(11) Association urinary function score Good (0-7) 28 (76...No 18 No 1 197 43 37 IVS22-6T>G No 22 No 3 210 29 Abbreviations: CAD = coronary artery disease; DM = diabetes mellitus; RTOG = Radiation Therapy

SU-E-T-578: On Definition of Minimum and Maximum Dose for Target Volume

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gong, Y; Yu, J; Xiao, Y

Purpose: This study aims to investigate the impact of different minimum and maximum dose definitions in radiotherapy treatment plan quality evaluation criteria by using tumor control probability (TCP) models. Methods: Dosimetric criteria used in RTOG 1308 protocol are used in the investigation. RTOG 1308 is a phase III randomized trial comparing overall survival after photon versus proton chemoradiotherapy for inoperable stage II-IIIB NSCLC. The prescription dose for planning target volume (PTV) is 70Gy. Maximum dose (Dmax) should not exceed 84Gy and minimum dose (Dmin) should not go below 59.5Gy in order for the plan to be “per protocol” (satisfactory).A mathematicalmore » model that simulates the characteristics of PTV dose volume histogram (DVH) curve with normalized volume is built. The Dmax and Dmin are noted as percentage volumes Dη% and D(100-δ)%, with η and d ranging from 0 to 3.5. The model includes three straight line sections and goes through four points: D95%= 70Gy, Dη%= 84Gy, D(100-δ)%= 59.5 Gy, and D100%= 0Gy. For each set of η and δ, the TCP value is calculated using the inhomogeneously irradiated tumor logistic model with D50= 74.5Gy and γ50=3.52. Results: TCP varies within 0.9% with η; and δ values between 0 and 1. With η and η varies between 0 and 2, TCP change was up to 2.4%. With η and δ variations from 0 to 3.5, maximum of 8.3% TCP difference is seen. Conclusion: When defined maximum and minimum volume varied more than 2%, significant TCP variations were seen. It is recommended less than 2% volume used in definition of Dmax or Dmin for target dosimetric evaluation criteria. This project was supported by NIH grants U10CA180868, U10CA180822, U24CA180803, U24CA12014 and PA CURE Grant.« less

An ultrasonographic evaluation of skin thickness in breast cancer patients after postmastectomy radiation therapy

PubMed Central

2011-01-01

Background To determine the usefulness of ultrasonography in the assessment of post radiotherapy skin changes in postmastectomy breast cancer patients. Methods Patients treated for postmastectomy radiotherapy in National University Hospital (NUH) and Tan Tock Seng Hospital (TTSH), Singapore between January 2004- December 2005 was recruited retrospectively. Ultrasound scan was performed on these Asian patients who had been treated to a total dose of 46-50 Gy with 1 cm bolus placed on the skin. The ultrasound scans were performed blinded to the RTOG scores, and the skin thickness of the individually marked points on the irradiated chest wall was compared to the corresponding points on the non-irradiated breast. Results The mean total skin thickness inclusive of the epidermis and the dermis of the right irradiated chest wall was 0.1712 mm (± 0.03392 mm) compared with the contra-lateral non-irradiated breast which was 0.1845 mm (± 0.04089 mm; p = 0.007). The left irradiated chest wall had a mean skin thickness of 0.1764 mm (± 0.03184 mm) compared with the right non-irradiated breast which was 0.1835 mm (± 0.02584 mm; p = 0.025). These independent t-tests produced a significant difference of reduced skin thickness on the right irradiated chest wall, p = 0.007 (p < 0.05) and left irradiated chest wall p = 0.025 (p < 0.025) in comparison to the non-irradiated skin thickness investigating chronic skin reactions. Patients with grade 2 acute skin toxicity presented with thinner skin as compared to patients with grade 1 (p = 0.006). Conclusions This study has shown that there is a statistically significant difference between the skin thicknesses of the irradiated chest wall and the contra-lateral non-irradiated breast and a predisposition to chronic reactions was found in patients with acute RTOG scoring of grade1 and grade 2. PMID:21261940

Whole-pelvis, 'mini-pelvis,' or prostate-only external beam radiotherapy after neoadjuvant and concurrent hormonal therapy in patients treated in Radiation Therapy Oncology Group 9413 trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roach, Mack; De Silvio, Michelle; Valicenti, Richard

2006-11-01

Purpose: Radiation Therapy Oncology Group (RTOG) 9413 trial demonstrated a better progression-free survival (PFS) with whole-pelvis (WP) radiotherapy (RT) compared with prostate-only (PO) RT. This secondary analysis was undertaken to determine whether 'mini-pelvis' (MP; defined as {>=}10 x 11 cm but <11 x 11 cm) RT resulted in progression-free survival (PFS) comparable to that of WP RT. To avoid a timing bias, this analysis was limited to patients receiving neoadjuvant and concurrent hormonal therapy (N and CHT) in Arms 1 and 2 of the study. Methods and Materials: Eligible patients had a risk of lymph node (LN) involvement >15%. Neoadjuvantmore » and concurrent hormonal therapy (N and CHT) was administered 2 months before and during RT for 4 months. From April 1, 1995, to June 1, 1999, a group of 325 patients were randomized to WP RT + N and CHT and another group of 324 patients were randomized to receive PO RT + N and CHT. Patients randomized to PO RT were dichotomized by median field size (10 x 11 cm), with the larger field considered an 'MP' field and the smaller a PO field. Results: The median PFS was 5.2, 3.7, and 2.9 years for WP, MP, and PO fields, respectively (p = 0.02). The 7-year PFS was 40%, 35%, and 27% for patients treated to WP, MP, and PO fields, respectively. There was no association between field size and late Grade 3+ genitourinary toxicity but late Grade 3+ gastrointestinal RT complications correlated with increasing field size. Conclusions: This subset analysis demonstrates that RT field size has a major impact on PFS, and the findings support comprehensive nodal treatment in patients with a risk of LN involvement of >15%.« less

Impact of geometric uncertainties on dose calculations for intensity modulated radiation therapy of prostate cancer

NASA Astrophysics Data System (ADS)

Jiang, Runqing

Intensity-modulated radiation therapy (IMRT) uses non-uniform beam intensities within a radiation field to provide patient-specific dose shaping, resulting in a dose distribution that conforms tightly to the planning target volume (PTV). Unavoidable geometric uncertainty arising from patient repositioning and internal organ motion can lead to lower conformality index (CI) during treatment delivery, a decrease in tumor control probability (TCP) and an increase in normal tissue complication probability (NTCP). The CI of the IMRT plan depends heavily on steep dose gradients between the PTV and organ at risk (OAR). Geometric uncertainties reduce the planned dose gradients and result in a less steep or "blurred" dose gradient. The blurred dose gradients can be maximized by constraining the dose objective function in the static IMRT plan or by reducing geometric uncertainty during treatment with corrective verification imaging. Internal organ motion and setup error were evaluated simultaneously for 118 individual patients with implanted fiducials and MV electronic portal imaging (EPI). A Gaussian probability density function (PDF) is reasonable for modeling geometric uncertainties as indicated by the 118 patients group. The Gaussian PDF is patient specific and group standard deviation (SD) should not be used for accurate treatment planning for individual patients. In addition, individual SD should not be determined or predicted from small imaging samples because of random nature of the fluctuations. Frequent verification imaging should be employed in situations where geometric uncertainties are expected. Cumulative PDF data can be used for re-planning to assess accuracy of delivered dose. Group data is useful for determining worst case discrepancy between planned and delivered dose. The margins for the PTV should ideally represent true geometric uncertainties. The measured geometric uncertainties were used in this thesis to assess PTV coverage, dose to OAR, equivalent uniform dose per fraction (EUDf) and NTCP. The dose distribution including geometric uncertainties was determined from integration of the convolution of the static dose gradient with the PDF. Integration of the convolution of the static dose and derivative of the PDF can also be used to determine the dose including geometric uncertainties although this method was not investigated in detail. Local maximum dose gradient (LMDG) was determined via optimization of dose objective function by manually adjusting DVH control points or selecting beam numbers and directions during IMRT treatment planning. Minimum SD (SDmin) is used when geometric uncertainty is corrected with verification imaging. Maximum SD (SDmax) is used when the geometric uncertainty is known to be large and difficult to manage. SDmax was 4.38 mm in anterior-posterior (AP) direction, 2.70 mm in left-right (LR) direction and 4.35 mm in superior-inferior (SI) direction; SDmin was 1.1 mm in all three directions if less than 2 mm threshold was used for uncorrected fractions in every direction. EUDf is a useful QA parameter for interpreting the biological impact of geometric uncertainties on the static dose distribution. The EUD f has been used as the basis for the time-course NTCP evaluation in the thesis. Relative NTCP values are useful for comparative QA checking by normalizing known complications (e.g. reported in the RTOG studies) to specific DVH control points. For prostate cancer patients, rectal complications were evaluated from specific RTOG clinical trials and detailed evaluation of the treatment techniques (e.g. dose prescription, DVH, number of beams, bean angles). Treatment plans that did not meet DVH constraints represented additional complication risk. Geometric uncertainties improved or worsened rectal NTCP depending on individual internal organ motion within patient.

[Effect of intensity modulated radiation therapy on oral mucosa and immune function in patients with nasopharyngeal carcinoma].

PubMed

Liang, Shaoqiang; Zhang, Ning; Chen, Lusi; Zhang, Yang; Zheng, Zhenhe; Luo, Weijun; Xu, Tao; Lü, Zhiqian; Li, Shao'en

2018-05-28

To study the potential effects of intensity modulated radiation therapy (IMRT) on clinical efficacy, oral mucosa reaction and immunological foundation; and to explore the effect of immunological changes on clinical efficacy and oral mucosa reaction in patients with nasopharyngeal carcinoma.
 Methods: A total of 200 patients with nasopharyngeal carcinoma, who came from First Department of Nasopharyngeal Radiotherapy, the First People's Hospital of Foshan from October 2008 to November 2011, were selected. The patients were treated with nasopharyngeal radiotherapy, and divided into an observation group and a control group (n=100 in each group). The control group underwent common conventional two-dimensional radiotherapy treatment, while the observation group underwent IMRT. The 5-year survival rates and recurrence rates were recorded at follow-up. After the radiotherapy, the oral mucosa in the patients were evaluated by the classification standard of acute radioactive mucositis by American Radiotherapy Oncology Group (RTOG), and the number of T lymphocyte subsets before and after treatment was detected.
 Results: There were significant difference in non-regional-recurrence survival rate, disease-free survival rate, local recurrence rate between the above 2 groups (all P<0.05), but no significant difference in the distant metastasis-free survival rate (P>0.05). The acute oral mucosa reactions of grade 1, 2, 3, 4 in the control group were 8.00%, 20.00%, 12.00%, 7.00%, respectively, and those were 7.00%, 22.00%, 15.00%, 1.00% respectively. There was no significant difference in the acute response of oral mucosa in grade 1, 2 and 3 in the 2 groups (all P>0.05), but there was significant difference in the grade 4 (P<0.05). There were significantly difference in CD8+, CD4+/ CD8+ and CD4+ T lymphocyte subsets before and after treatment in the above 2 groups (all P<0.01); there were also significantly difference after treatment between the observation group and the control group (all P<0.01).
 Conclusion: In the process of treatment in patients with nasopharyngeal carcinoma, the use of IMRT on the basis of chemotherapy is more effective than the conventional two-dimensional radiotherapy, which can reduce the proportion of grade 4 (severe) acute oral mucosa reaction. It may be related to the protective effect of IMRT on immune function in the patients.

Evaluation of the Dosimetric Feasibility of Hippocampal Sparing Intensity-Modulated Radiotherapy in Patients with Locally Advanced Nasopharyngeal Carcinoma

PubMed Central

Gan, Hua; Denniston, Kyle A.; Li, Sicong; Tan, Wenyong; Wang, Zhaohua

2014-01-01

Purpose The objective of this study was to evaluate the dosimetric feasibility of using hippocampus (HPC) sparing intensity-modulated radiotherapy (IMRT) in patients with locally advanced nasopharyngeal carcinoma (NPC). Materials/Methods Eight cases of either T3 or T4 NPC were selected for this study. Standard IMRT treatment plans were constructed using the volume and dose constraints for the targets and organs at risk (OAR) per Radiation Therapy Oncology Group (RTOG) 0615 protocol. Experimental plans were constructed using the same criteria, with the addition of the HPC as an OAR. The two dose-volume histograms for each case were compared for the targets and OARs. Results All plans achieved the protocol dose criteria. The homogeneity index, conformity index, and coverage index for the planning target volumes (PTVs) were not significantly compromised by the avoidance of the HPC. The doses to all OARs, excluding the HPC, were similar. Both the dose (Dmax, D2%, D40%, Dmean, Dmedian, D98% and Dmin) and volume (V5, V10, V15, V20, V30, V40 and V50) parameters for the HPC were significantly lower in the HPC sparing plans (p<0.05), except for Dmin (P = 0.06) and V5 (P = 0.12). Conclusions IMRT for patients with locally advanced NPC exposes the HPC to a significant radiation dose. HPC sparing IMRT planning significantly decreases this dose, with minimal impact on the therapeutic targets and other OARs. PMID:24587184

Patterns of failure after radical prostatectomy in prostate cancer - implications for radiation therapy planning after 68Ga-PSMA-PET imaging.

PubMed

Schiller, Kilian; Sauter, K; Dewes, S; Eiber, M; Maurer, T; Gschwend, J; Combs, S E; Habl, G

2017-09-01

Salvage radiotherapy (SRT) after radical prostatectomy (RPE) and lymphadenectomy (LAE) is the appropriate radiotherapy option for patients with persistent/ recurrent prostate cancer (PC). 68 Ga-PSMA-PET imaging has been shown to accurately detect PC lesions in a primary setting as well as for local recurrence or for lymph node (LN) metastases. In this study we evaluated the patterns of recurrence after RPE in patients with PC, putting a highlight on the differentiation between sites that would have been covered by a standard radiation therapy (RT) field in consensus after the RTOG consensus and others that would have not. Thirty-one out of 83 patients (37%) with high-risk PC were the subject of our study. Information from 68 Ga-PSMA-PET imaging was used to individualize treatment plans to include suspicious lesions as well as possibly boost sites with tracer uptake in LN or the prostate bed. For evaluation, 68 Ga-PSMA-PET-positive LN were contoured in a patient dataset with a standard lymph drainage (RTOG consensus on CTV definition of pelvic lymph nodes) radiation field depicting color-coded nodes that would have been infield or outfield of that standard lymph drainage field and thereby visualizing typical patterns of failure of a "blind" radiation therapy after RPE and LAE. Compared to negative conventional imaging (CT/MRI), lesions suspicious for PC were detected in 27/31 cases (87.1%) by 68 Ga-PSMA-PET imaging, which resulted in changes to the radiation concept. There were 16/31 patients (51.6%) that received a simultaneous integrated boost (SIB) to a subarea of the prostate bed (in only three cases this dose escalation would have been planned without the additional knowledge of 68 Ga-PSMA-PET imaging) and 18/31 (58.1%) to uncommon (namely presacral, paravesical, pararectal, preacetabular and obturatoric) LN sites. Furthermore, 14 patients (45.2%) had a changed TNM staging result by means of 68 Ga-PSMA-PET imaging. Compared to conventional CT or MRI staging, 68 Ga-PSMA-PET imaging detects more PC lesions and, thus, significantly influences radiation planning in recurrent prostate cancer patients enabling individually tailored treatment.

Analysis of acute radiation-induced esophagitis in non-small-cell lung cancer patients using the Lyman NTCP model.

PubMed

Zhu, Jian; Zhang, Zi-Cheng; Li, Bao-Sheng; Liu, Min; Yin, Yong; Yu, Jin-Ming; Luo, Li-Min; Shu, Hua-Zhong; De Crevoisier, Renaud

2010-12-01

To analyze acute esophagitis (AE) in a Chinese population receiving 3D conformal radiotherapy (3DCRT) for non-small cell lung cancer (NSCLC), combined or not with chemotherapy (CT), using the Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model. 157 Chinese patients (pts) presented with NSCLC received 3DCRT: alone (34 pts) or combined with sequential CT (59 pts) (group 1) or with concomitant CT (64 pts) (group 2). Parameters (TD(50), n, and m) of the LKB NTCP model predicting for>grade 2 AE (RTOG grading) were identified using maximum likelihood analysis. Univariate and multivariate analyses using a binary regression logistic model were performed to identify patient, tumor and dosimetric predictors of AE. Grade 2 or 3 AE occurred in 24% and 52% of pts in group 1 and 2, respectively (p<0.001). For the 93 group 1 pts, the fitted LKB model parameters were: m=0.15, n=0.29 and TD(50)=46 Gy. For the 64 group 2 pts, the parameters were: m=0.42, n=0.09 and TD(50)=36 Gy. In multivariate analysis, the only significant predictors of AE were: NTCP (p<0.001) and V(50), as continuous variable (RR=1.03, p=0.03) or being more than a threshold value of 11% (RR=3.6, p=0.009). A LKB NTCP model has been established to predict AE in a Chinese population, receiving thoracic RT, alone or combined with CT. The parameters of the models appear slightly different than the previous one described in Western countries, with a lower volume effect for Chinese patients. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Sandalwood Oil and Turmeric-Based Cream Prevents Ionizing Radiation-Induced Dermatitis in Breast Cancer Patients: Clinical Study.

PubMed

Rao, Suresh; Hegde, Sanath Kumar; Baliga-Rao, Manjeshwar Poonam; Lobo, Jyothi; Palatty, Princy Louis; George, Thomas; Baliga, Manjeshwar Shrinath

2017-06-24

Background : The primary objective of this study was to ascertain the benefit of Vicco turmeric Ayurvedic cream (VTC; Vicco Laboratories, Mumbai, India) sandalwood oil and turmeric-based cream in preventing radiodermatitis in women undergoing curative radiotherapy for their breast cancer. Methods and Materials : The study was an investigator-blinded randomized study with Johnsons Baby Oil (JBO; Johnson & Johnson Ltd., Baddi, India) as a comparator, administered daily from the start of radiation therapy for 5 weeks in women receiving breast radiation therapy, 50 Gy in 2 Gy fractions daily for 5 weeks. The endpoints were to ascertain the delay in the appearance and the degree of severity of dermatitis throughout the study period in accordance to the Therapy Oncology Group (RTOG) score. Results : The results indicated that the topical application of VTC delayed and mitigated the radiodermatitis. When compared to the Johnson's Baby Oil, a significant decrease ( p = 0.025) in the incidence of grade 1 was seen at week two, and also in grade 2 and 3 at week 3 ( p = 0.003) and week 4 ( p = 0.02), respectively, in the VTC cohort. A concomitant decrease in the average severity was also observed at week 2 ( p = 0.02), week 3 ( p = 0.05) and week 4 ( p = 0.03). The results indicate that VTC cream significantly reduces radiation dermatitis when applied to the breast during and after radiation therapy. The result of this study indicates the beneficial effects. Double blind randomized control studies are required to further confirm the beneficial effects of VTC in mitigating radiodermatitis is people undergoing radiation treatment for their cancer.

Sandalwood Oil and Turmeric-Based Cream Prevents Ionizing Radiation-Induced Dermatitis in Breast Cancer Patients: Clinical Study

PubMed Central

Rao, Suresh; Hegde, Sanath Kumar; Baliga-Rao, Manjeshwar Poonam; Lobo, Jyothi; Palatty, Princy Louis; George, Thomas; Baliga, Manjeshwar Shrinath

2017-01-01

Background: The primary objective of this study was to ascertain the benefit of Vicco turmeric Ayurvedic cream (VTC; Vicco Laboratories, Mumbai, India) sandalwood oil and turmeric-based cream in preventing radiodermatitis in women undergoing curative radiotherapy for their breast cancer. Methods and Materials: The study was an investigator-blinded randomized study with Johnsons Baby Oil (JBO; Johnson & Johnson Ltd., Baddi, India) as a comparator, administered daily from the start of radiation therapy for 5 weeks in women receiving breast radiation therapy, 50 Gy in 2 Gy fractions daily for 5 weeks. The endpoints were to ascertain the delay in the appearance and the degree of severity of dermatitis throughout the study period in accordance to the Therapy Oncology Group (RTOG) score. Results: The results indicated that the topical application of VTC delayed and mitigated the radiodermatitis. When compared to the Johnson’s Baby Oil, a significant decrease (p = 0.025) in the incidence of grade 1 was seen at week two, and also in grade 2 and 3 at week 3 (p = 0.003) and week 4 (p = 0.02), respectively, in the VTC cohort. A concomitant decrease in the average severity was also observed at week 2 (p = 0.02), week 3 (p = 0.05) and week 4 (p = 0.03). Conclusions: The results indicate that VTC cream significantly reduces radiation dermatitis when applied to the breast during and after radiation therapy. The result of this study indicates the beneficial effects. Double blind randomized control studies are required to further confirm the beneficial effects of VTC in mitigating radiodermatitis is people undergoing radiation treatment for their cancer. PMID:28930259

Whole-brain hippocampal sparing radiation therapy: Volume-modulated arc therapy vs intensity-modulated radiation therapy case study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Katrina, E-mail: Trinabena23@gmail.com; Lenards, Nishele; Holson, Janice

The hippocampus is responsible for memory and cognitive function. An ongoing phase II clinical trial suggests that sparing dose to the hippocampus during whole-brain radiation therapy can help preserve a patient's neurocognitive function. Progressive research and advancements in treatment techniques have made treatment planning more sophisticated but beneficial for patients undergoing treatment. The aim of this study is to evaluate and compare hippocampal sparing whole-brain (HS-WB) radiation therapy treatment planning techniques using volume-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT). We randomly selected 3 patients to compare different treatment techniques that could be used for reducing dose to themore » hippocampal region. We created 2 treatment plans, a VMAT and an IMRT, from each patient's data set and planned on the Eclipse 11.0 treatment planning system (TPS). A total of 6 plans (3 IMRT and 3 VMAT) were created and evaluated for this case study. The physician contoured the hippocampus as per the Radiation Therapy Oncology Group (RTOG) 0933 protocol atlas. The organs at risk (OR) were contoured and evaluated for the plan comparison, which included the spinal cord, optic chiasm, the right and left eyes, lenses, and optic nerves. Both treatment plans produced adequate coverage on the planning target volume (PTV) while significantly reducing dose to the hippocampal region. The VMAT treatment plans produced a more homogenous dose distribution throughout the PTV while decreasing the maximum point dose to the target. However, both treatment techniques demonstrated hippocampal sparing when irradiating the whole brain.« less

Early and late skin reactions to radiotherapy for breast cancer and their correlation with radiation-induced DNA damage in lymphocytes.

PubMed

López, Escarlata; Guerrero, Rosario; Núñez, Maria Isabel; del Moral, Rosario; Villalobos, Mercedes; Martínez-Galán, Joaquina; Valenzuela, Maria Teresa; Muñoz-Gámez, José Antonio; Oliver, Francisco Javier; Martín-Oliva, David; Ruiz de Almodóvar, José Mariano

2005-01-01

Radiotherapy outcomes might be further improved by a greater understanding of the individual variations in normal tissue reactions that determine tolerance. Most published studies on radiation toxicity have been performed retrospectively. Our prospective study was launched in 1996 to measure the in vitro radiosensitivity of peripheral blood lymphocytes before treatment with radical radiotherapy in patients with breast cancer, and to assess the early and the late radiation skin side effects in the same group of patients. We prospectively recruited consecutive breast cancer patients receiving radiation therapy after breast surgery. To evaluate whether early and late side effects of radiotherapy can be predicted by the assay, a study was conducted of the association between the results of in vitro radiosensitivity tests and acute and late adverse radiation effects. Intrinsic molecular radiosensitivity was measured by using an initial radiation-induced DNA damage assay on lymphocytes obtained from breast cancer patients before radiotherapy. Acute reactions were assessed in 108 of these patients on the last treatment day. Late morbidity was assessed after 7 years of follow-up in some of these patients. The Radiation Therapy Oncology Group (RTOG) morbidity score system was used for both assessments. Radiosensitivity values obtained using the in vitro test showed no relation with the acute or late adverse skin reactions observed. There was no evidence of a relation between acute and late normal tissue reactions assessed in the same patients. A positive relation was found between the treatment volume and both early and late side effects. After radiation treatment, a number of cells containing major changes can have a long survival and disappear very slowly, becoming a chronic focus of immunological system stimulation. This stimulation can produce, in a stochastic manner, late radiation-related adverse effects of varying severity. Further research is warranted to identify the major determinants of normal tissue radiation response to make it possible to individualize treatments and improve the outcome of radiotherapy in cancer patients.

A Phase 3 Trial of Whole Brain Radiation Therapy and Stereotactic Radiosurgery Alone Versus WBRT and SRS With Temozolomide or Erlotinib for Non-Small Cell Lung Cancer and 1 to 3 Brain Metastases: Radiation Therapy Oncology Group 0320

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sperduto, Paul W., E-mail: psperduto@mropa.com; Wang, Meihua; Robins, H. Ian

2013-04-01

Background: A phase 3 Radiation Therapy Oncology Group (RTOG) study subset analysis demonstrated improved overall survival (OS) with the addition of stereotactic radiosurgery (SRS) to whole brain radiation therapy (WBRT) in non-small cell lung cancer (NSCLC) patients with 1 to 3 brain metastases. Because temozolomide (TMZ) and erlotinib (ETN) cross the blood-brain barrier and have documented activity in NSCLC, a phase 3 study was designed to test whether these drugs would improve the OS associated with WBRT + SRS. Methods and Materials: NSCLC patients with 1 to 3 brain metastases were randomized to receive WBRT (2.5 Gy × 15 tomore » 37.5 Gy) and SRS alone, versus WBRT + SRS + TMZ (75 mg/m{sup 2}/day × 21 days) or ETN (150 mg/day). ETN (150 mg/day) or TMZ (150-200 mg/m{sup 2}/day × 5 days/month) could be continued for as long as 6 months after WBRT + SRS. The primary endpoint was OS. Results: After 126 patients were enrolled, the study closed because of accrual limitations. The median survival times (MST) for WBRT + SRS, WBRT + SRS + TMZ, and WBRT + SRS + ETN were qualitatively different (13.4, 6.3, and 6.1 months, respectively), although the differences were not statistically significant. Time to central nervous system progression and performance status at 6 months were better in the WBRT + SRS arm. Grade 3 to 5 toxicity was 11%, 41%, and 49% in arms 1, 2, and 3, respectively (P<.001). Conclusion: The addition of TMZ or ETN to WBRT + SRS in NSCLC patients with 1 to 3 brain metastases did not improve survival and possibly had a deleterious effect. Because the analysis is underpowered, these data suggest but do not prove that increased toxicity was the cause of inferior survival in the drug arms.« less

A Phase 3 Trial of Whole Brain Radiation Therapy and Stereotactic Radiosurgery Alone Versus WBRT and SRS With Temozolomide or Erlotinib for Non-Small Cell Lung Cancer and 1 to 3 Brain Metastases: Radiation Therapy Oncology Group 0320.

PubMed Central

Sperduto, Paul W.; Wang, Meihua; Robins, H. Ian; Schell, Michael C.; Werner-Wasik, Maria; Komaki, Ritsuko; Souhami, Luis; Buyyounouski, Mark K.; Khuntia, Deepak; Demas, William; Shah, Sunjay A.; Nedzi, Lucien A.; Perry, Gad; Suh, John H.; Mehta, Minesh P.

2013-01-01

Background A phase 3 Radiation Therapy Oncology Group (RTOG) study subset analysis demonstrated improved overall survival (OS) with the addition of stereotactic radiosurgery (SRS) to whole brain radiation therapy (WBRT) in non-small cell lung cancer (NSCLC) patients with 1 to 3 brain metastases. Because temozolomide (TMZ) and erlotinib (ETN) cross the bloodbrain barrier and have documented activity in NSCLC, a phase 3 study was designed to test whether these drugs would improve the OS associated with WBRT + SRS. Methods and Materials NSCLC patients with 1 to 3 brain metastases were randomized to receive WBRT (2.5 Gy×15 to 37.5 Gy) and SRS alone, versus WBRT + SRS + TMZ (75 mg/m2/day× 21 days) or ETN (150 mg/day). ETN (150 mg/day) or TMZ (150–200 mg/m2/day ×5 days/month) could be continued for as long as 6 months after WBRT þ SRS. The primary endpoint was OS. Results After 126 patients were enrolled, the study closed because of accrual limitations. The median survival times (MST) for WBRT + SRS, WBRT + SRS + TMZ, and WBRT + SRS + ETN were qualitatively different (13.4, 6.3, and 6.1 months, respectively), although the differences were not statistically significant. Time to central nervous system progression and performance status at 6 months were better in the WBRT þ SRS arm. Grade 3 to 5 toxicity was 11%, 41%, and 49% in arms 1, 2, and 3, respectively (P<.001). Conclusion The addition of TMZ or ETN to WBRT + SRS in NSCLC patients with 1 to 3 brain metastases did not improve survival and possibly had a deleterious effect. Because the analysis is underpowered, these data suggest but do not prove that increased toxicity was the cause of inferior survival in the drug arms. PMID:23391814

A phase 3 trial of whole brain radiation therapy and stereotactic radiosurgery alone versus WBRT and SRS with temozolomide or erlotinib for non-small cell lung cancer and 1 to 3 brain metastases: Radiation Therapy Oncology Group 0320.

PubMed

Sperduto, Paul W; Wang, Meihua; Robins, H Ian; Schell, Michael C; Werner-Wasik, Maria; Komaki, Ritsuko; Souhami, Luis; Buyyounouski, Mark K; Khuntia, Deepak; Demas, William; Shah, Sunjay A; Nedzi, Lucien A; Perry, Gad; Suh, John H; Mehta, Minesh P

2013-04-01

A phase 3 Radiation Therapy Oncology Group (RTOG) study subset analysis demonstrated improved overall survival (OS) with the addition of stereotactic radiosurgery (SRS) to whole brain radiation therapy (WBRT) in non-small cell lung cancer (NSCLC) patients with 1 to 3 brain metastases. Because temozolomide (TMZ) and erlotinib (ETN) cross the blood-brain barrier and have documented activity in NSCLC, a phase 3 study was designed to test whether these drugs would improve the OS associated with WBRT + SRS. NSCLC patients with 1 to 3 brain metastases were randomized to receive WBRT (2.5 Gy × 15 to 37.5 Gy) and SRS alone, versus WBRT + SRS + TMZ (75 mg/m(2)/day × 21 days) or ETN (150 mg/day). ETN (150 mg/day) or TMZ (150-200 mg/m(2)/day × 5 days/month) could be continued for as long as 6 months after WBRT + SRS. The primary endpoint was OS. After 126 patients were enrolled, the study closed because of accrual limitations. The median survival times (MST) for WBRT + SRS, WBRT + SRS + TMZ, and WBRT + SRS + ETN were qualitatively different (13.4, 6.3, and 6.1 months, respectively), although the differences were not statistically significant. Time to central nervous system progression and performance status at 6 months were better in the WBRT + SRS arm. Grade 3 to 5 toxicity was 11%, 41%, and 49% in arms 1, 2, and 3, respectively (P<.001). The addition of TMZ or ETN to WBRT + SRS in NSCLC patients with 1 to 3 brain metastases did not improve survival and possibly had a deleterious effect. Because the analysis is underpowered, these data suggest but do not prove that increased toxicity was the cause of inferior survival in the drug arms. Copyright © 2013 Elsevier Inc. All rights reserved.

Utility of the ACE Inhibitor Captopril in Mitigating Radiation-associated Pulmonary Toxicity in Lung Cancer: Results From NRG Oncology RTOG 0123.

PubMed

Small, William; James, Jennifer L; Moore, Timothy D; Fintel, Dan J; Lutz, Stephen T; Movsas, Benjamin; Suntharalingam, Mohan; Garces, Yolanda I; Ivker, Robert; Moulder, John; Pugh, Stephanie; Berk, Lawrence B

2018-04-01

The primary objective of NRG Oncology Radiation Therapy Oncology Group 0123 was to test the ability of the angiotensin-converting enzyme inhibitor captopril to alter the incidence of pulmonary damage after radiation therapy for lung cancer; secondary objectives included analyzing pulmonary cytokine expression, quality of life, and the long-term effects of captopril. Eligible patients included stage II-IIIB non-small cell lung cancer, stage I central non-small cell lung cancer, or limited-stage small cell. Patients who met eligibility for randomization at the end of radiotherapy received either captopril or standard care for 1 year. The captopril was to be escalated to 50 mg three times a day. Primary endpoint was incidence of grade 2+ radiation-induced pulmonary toxicity in the first year. Eighty-one patients were accrued between June 2003 and August 2007. Given the low accrual rate, the study was closed early. No significant safety issues were encountered. Eight patients were ineligible for registration or withdrew consent before randomization and 40 patients were not randomized postradiation. Major reasons for nonrandomization included patients' refusal and physician preference. Of the 33 randomized patients, 20 were analyzable (13 observation, 7 captopril). The incidence of grade 2+ pulmonary toxicity attributable to radiation therapy was 23% (3/13) in the observation arm and 14% (1/7) in the captopril arm. Despite significant resources and multiple amendments, NRG Oncology Radiation Therapy Oncology Group 0123 was unable to test the hypothesis that captopril mitigates radiation-induced pulmonary toxicity. It did show the safety of such an approach and the use of newer angiotensin-converting enzyme inhibitors started during radiotherapy may solve the accrual problems.

Predictors for long-term survival free from whole brain radiation therapy in patients treated with radiosurgery for limited brain metastases.

PubMed

Gorovets, Daniel; Rava, Paul; Ebner, Daniel K; Tybor, David J; Cielo, Deus; Puthawala, Yakub; Kinsella, Timothy J; DiPetrillo, Thomas A; Wazer, David E; Hepel, Jaroslaw T

2015-01-01

To identify predictors for prolonged survival free from salvage whole brain radiation therapy (WBRT) in patients with brain metastases treated with stereotactic radiosurgery (SRS) as their initial radiotherapy approach. Patients with brain metastases treated with SRS from 2001 to 2013 at our institution were identified. SRS without WBRT was typically offered to patients with 1-4 brain metastases, Karnofsky performance status ≥70, and life expectancy ≥3 months. Three hundred and eight patients met inclusion criteria for analysis. Medical records were reviewed for patient, disease, and treatment information. Two comparison groups were identified: those with ≥1-year WBRT-free survival (N = 104), and those who died or required salvage WBRT within 3 months of SRS (N = 56). Differences between these groups were assessed by univariate and multivariate analyses. Median survival for all patients was 11 months. Among patients with ≥1-year WBRT-free survival, median survival was 33 months (12-107 months) with only 21% requiring salvage WBRT. Factors significantly associated with prolonged WBRT-free survival on univariate analysis (p < 0.05) included younger age, asymptomatic presentation, RTOG RPA class I, fewer brain metastases, surgical resection, breast primary, new or controlled primary, absence of extracranial metastatic disease, and oligometastatic disease burden (≤5 metastatic lesions). After controlling for covariates, asymptomatic presentation, breast primary, single brain metastasis, absence of extracranial metastases, and oligometastatic disease burden remained independent predictors for favorable WBRT-free survival. A subset of patients with brain metastases can achieve long-term survival after upfront SRS without the need for salvage WBRT. Predictors identified in this study can help select patients that might benefit most from a treatment strategy of SRS alone.

Spot-scanning proton therapy for malignant soft tissue tumors in childhood: First experiences at the Paul Scherrer Institute

DOE Office of Scientific and Technical Information (OSTI.GOV)

Timmermann, Beate; Schuck, Andreas; Niggli, Felix

2007-02-01

Purpose: Radiotherapy plays a major role in the treatment strategy of childhood sarcomas. Consequences of treatment are likely to affect the survivor's quality of life significantly. We investigated the feasibility of spot-scanning proton therapy (PT) for soft tissue tumors in childhood. Methods and Materials: Sixteen children with soft tissue sarcomas were included. Median age at PT was 3.3 years. In 10 children the tumor histology was embryonal rhabdomyosarcoma. All tumors were located in the head or neck, parameningeal, or paraspinal, or pelvic region. In the majority of children, the tumor was initially unresectable (Intergroup Rhabdomyosarcoma Study [IRS] Group III inmore » 75%). In 50% of children the tumors exceeded 5 cm. Fourteen children had chemotherapy before and during PT. Median total dose of radiotherapy was 50 cobalt Gray equivalent (CGE). All 16 children were treated with spot-scanning proton therapy at the Paul Scherrer Institute, and in 3 children the PT was intensity-modulated (IMPT). Results: After median follow-up of 1.5 years, local control was achieved in 12 children. Four children failed locally, 1 at the border of the radiation field and 3 within the field. All 4 children died of tumor recurrence. All 4 showed unfavorable characteristic either of site or histopathology of the tumor. Acute toxicity was low, with Grade 3 or 4 side effects according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria occurring in the bone marrow only. Conclusions: Proton therapy was feasible and well tolerated. Early local control rates are comparable to those being achieved after conventional radiotherapy. For investigations on late effect, longer follow-up is needed.« less

Australasian Gastrointestinal Trials Group (AGITG) Contouring Atlas and Planning Guidelines for Intensity-Modulated Radiotherapy in Anal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ng, Michael, E-mail: mng@radoncvic.com.au; Leong, Trevor; University of Melbourne

2012-08-01

Purpose: To develop a high-resolution target volume atlas with intensity-modulated radiotherapy (IMRT) planning guidelines for the conformal treatment of anal cancer. Methods and Materials: A draft contouring atlas and planning guidelines for anal cancer IMRT were prepared at the Australasian Gastrointestinal Trials Group (AGITG) annual meeting in September 2010. An expert panel of radiation oncologists contoured an anal cancer case to generate discussion on recommendations regarding target definition for gross disease, elective nodal volumes, and organs at risk (OARs). Clinical target volume (CTV) and planning target volume (PTV) margins, dose fractionation, and other IMRT-specific issues were also addressed. A steeringmore » committee produced the final consensus guidelines. Results: Detailed contouring and planning guidelines and a high-resolution atlas are provided. Gross tumor and elective target volumes are described and pictorially depicted. All elective regions should be routinely contoured for all disease stages, with the possible exception of the inguinal and high pelvic nodes for select, early-stage T1N0. A 20-mm CTV margin for the primary, 10- to 20-mm CTV margin for involved nodes and a 7-mm CTV margin for the elective pelvic nodal groups are recommended, while respecting anatomical boundaries. A 5- to 10-mm PTV margin is suggested. When using a simultaneous integrated boost technique, a dose of 54 Gy in 30 fractions to gross disease and 45 Gy to elective nodes with chemotherapy is appropriate. Guidelines are provided for OAR delineation. Conclusion: These consensus planning guidelines and high-resolution atlas complement the existing Radiation Therapy Oncology Group (RTOG) elective nodal ano-rectal atlas and provide additional anatomic, clinical, and technical instructions to guide radiation oncologists in the planning and delivery of IMRT for anal cancer.« less

Skin dose for head and neck cancer patients treated with intensity-modulated radiation therapy(IMRT)

NASA Astrophysics Data System (ADS)

Fu, Hsiao-Ju; Li, Chi-Wei; Tsai, Wei-Ta; Chang, Chih-Chia; Tsang, Yuk-Wah

2017-11-01

The reliability of thermoluminescent dosimeters (ultrathin TLD) and ISP Gafchromic EBT2 film to measure the surface dose in phantom and the skin dose in head-and-neck patients treated with intensity-modulated radiation therapy technique(IMRT) is the research focus. Seven-field treatment plans with prescribed dose of 180 cGy were performed on Eclipse treatment planning system which utilized pencil beam calculation algorithm(PBC). In calibration tests, the variance coefficient of the ultrathin TLDs were within 3%. The points on the calibration curve of the Gafchromic film was within 1% variation. Five measurements were taken on phantom using ultrathin TLD and EBT2 film respectively. The measured mean surface doses between ultrathin TLD or EBT2 film were within 5% deviation. Skin doses of 6 patients were measured for initial 5 fractions and the mean dose per-fraction was calculated. If the extrapolated doses for 30 fractions were below 4000 cGy, the skin reaction grading observed according to Radiation Therapy Oncology Group (RTOG) was either grade 1 or grade 2. If surface dose exceeded 5000 cGy in 32 fractions, then grade 3 skin reactions were observed.

Prognostic impact of HPV-associated p16-expression and smoking status on outcomes following radiotherapy for oropharyngeal cancer: The MARCH-HPV project.

PubMed

Lassen, Pernille; Lacas, Benjamin; Pignon, Jean-Pierre; Trotti, Andy; Zackrisson, Bjorn; Zhang, Qiang; Overgaard, Jens; Blanchard, Pierre

2018-01-01

Evaluate the prognostic and predictive impact of HPV-associated p16-expression and assess the combined prognostic impact of p16 and smoking on altered fractionated radiotherapy (AFRT) for oropharyngeal cancer (OPC) within the frames of the update of the Meta-Analysis of Radiotherapy in Carcinomas of Head and neck (MARCH). Patients with OPC, known tumor p16-status and smoking history were identified from the MARCH update, resulting in a dataset of 815 patients from four randomized trials (RTOG9003, DAHANCA6&7, RTOG0129, ARTSCAN). Analysis was performed using a Cox model stratified by trial and adjusted on gender, age, T-stage, N-stage, type of radiotherapy fractionation, p16, smoking. Primary endpoint was progression-free survival (PFS). In total, 465 patients (57%) had p16-positive tumors and 350 (43%) p16-negative. Compared to p16-negative, p16-positive patients had significantly better PFS (HR = 0.42 [95% CI: 0.34-0.51], 28.9% absolute increase at 10 years) and OS (HR = 0.40 [0.32-0.49], 32.1% absolute increase at 10 years). No interaction between p16-status and fractionation schedule was detected. Smoking negatively impacted outcome; in the p16-positive subgroup, never smokers had significantly better PFS than former/current smokers (HR = 0.49 [0.33-0.75], 24.2% survival benefit at 10 years). No predictive impact of p16-status on response to AFRT could be detected but the strong prognostic impact of p16-status was confirmed and especially p16-positive never smoking patients have superior outcome after RT. Copyright © 2017 Elsevier B.V. All rights reserved.

MDM2 and Ki-67 predict for distant metastasis and mortality in men treated with radiotherapy and androgen deprivation for prostate cancer: RTOG 92-02.

PubMed

Khor, Li-Yan; Bae, Kyounghwa; Paulus, Rebecca; Al-Saleem, Tahseen; Hammond, M Elizabeth; Grignon, David J; Che, Mingxin; Venkatesan, Varagur; Byhardt, Roger W; Rotman, Marvin; Hanks, Gerald E; Sandler, Howard M; Pollack, Alan

2009-07-01

PURPOSE MDM2 regulates p53, which controls cell cycle arrest and apoptosis. Both proteins, along with Ki-67, which is an established strong determinant of metastasis, have shown promise in predicting the outcome of men treated with radiation therapy (RT) with or without short-term androgen deprivation (STAD). This report compares the utility of abnormal expression of these biomarkers in estimating progression in a cohort of men treated on RTOG 92-02. PATIENTS AND METHODS Adequate tissue for immunohistochemistry was available for p53, Ki-67, and MDM2 analyses in 478 patient cases. The percentage of tumor nuclei staining positive (PSP) was quantified manually or by image analysis, and the per-sample mean intensity score (MIS) was quantified by image analysis. Cox regression models were used to estimate overall mortality (OM), and Fine and Gray's regressions were applied to the end points of distant metastasis (DM) and cause-specific mortality (CSM). Results In multivariate analyses that adjusted for all markers and treatment covariates, MDM2 overexpression was significantly related to DM (P = .02) and OM (P = .003), and Ki-67 overexpression was significantly related to DM (P < .0001), CSM (P = .0007), and OM (P = .01). P53 overexpression was significantly related to OM (P = .02). When considered in combination, the overexpression of both Ki-67 and MDM2 at high levels was associated with significantly increased failure rates for all end points (P < .001 for DM, CSM, and OM). CONCLUSION Combined MDM2 and Ki-67 expression levels were independently related to distant metastasis and mortality and, if validated, could be considered for risk stratification of patients with prostate cancer in clinical trials.

Long-Term Update of NRG Oncology RTOG 0319: A Phase 1 and 2 Trial to Evaluate 3-Dimensional Conformal Radiation Therapy Confined to the Region of the Lumpectomy Cavity for Stage I and II Breast Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rabinovitch, Rachel, E-mail: rachel.rabinovitch@ucdenver.edu; Moughan, Jennifer; Vicini, Frank

Purpose: NRG Oncology RTOG 0319 was the first cooperative group trial in the United States to evaluate 3-dimensional conformal radiation therapy (3D-CRT) accelerated partial breast irradiation (APBI). This report updates secondary endpoints of toxicity and efficacy. Methods and Materials: Patients with stage I or II invasive breast cancer (tumor size ≤3 cm, ≤3 positive lymph nodes, negative margins) were eligible for 3D-CRT APBI: 38.5 Gy in 10 twice-daily fractions. Patient characteristics and treatment details have previously been reported. Adverse events were graded with CTCAE v3.0 (National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0). This analysis updates the rates of ipsilateral breastmore » recurrence (IBR), contralateral breast recurrence, ipsilateral node recurrence (INR), metastatic sites (distant metastases [DM]), mastectomy, disease-free survival, mastectomy-free survival, and overall survival. Results: Of 58 enrolled patients, 52 were eligible, with a median age of 61 years; 94% had stage I cancer and 83% had estrogen receptor positive disease. The median follow-up period was 8 years (minimum-maximum, 1.7-9.0 years). The 7-year estimate of isolated IBR (no DM) was 5.9%. The 7-year estimates of all IBRs, INR, mastectomy rate, and DM were 7.7%, 5.8%, 7.7%, and 7.7%, respectively. All 4 IBRs were invasive, of which 3 had a component within the planning target volume. The patterns of failure were as follows: 3 IBRs, 1 INR, 2 DM, 1 INR plus DM, and 1 IBR plus INR plus DM. The 7-year estimates of mastectomy-free survival, disease-free survival, and overall survival were 71.2%, 71.2%, and 78.8%, respectively. Thirteen patients died: 3 of breast cancer and 10 of other causes. Grade 3 (G3) treatment-related adverse events were reported by 4 patients (7.7%). No G3 pain or pulmonary or cardiac toxicities were reported. Conclusions: This phase 1 and 2 trial of 3D-CRT APBI continues to show durable tumor control and minimal G3 toxicity, comparable to other APBI techniques. Mature phase 3 results will determine the appropriateness and limitations of this noninvasive APBI technique.« less

Spine Radiosurgery: A Dosimetric Analysis in 124 Patients Who Received 18 Gy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schipani, Stefano; Wen, Winston; Jin, Jain-Yue

2012-12-01

Purpose: To define the safely tolerated doses to organs at risk (OARs) adjacent to the target volume (TV) of spine radiosurgery (SRS) with 18-Gy in a single fraction. Methods and Materials: A total of 124 patient cases with 165 spine metastases were reviewed. An 18-Gy single-fraction regimen was prescribed to the 90% isodose line encompassing the TV. A constraint of 10 Gy to 10% of the spinal cord outlined 6 mm above and below the TV was used. Dosimetric data to OARs were analyzed. Results: A total of 124 patients (100%) were followed-up, and median follow-up time was 7 monthsmore » (1-50 months). Symptoms and local control were achieved in 114 patients (92%). Acute Radiation Therapy Oncology Group (RTOG) grade 1 oral mucositis occurred in 11 of 11 (100%) patients at risk for oropharyngeal toxicity after cervical spine treatment. There were no RTOG grade 2-4 acute or late complications. Median TV was 43.2 cc (5.3-175.4 cc) and 90% of the TV received median dose of 19 Gy (17-19.8 Gy). Median (range) of spinal cord maximum dose (Dmax), dose to spinal cord 0.35 cc (Dsc0.35), and cord volume receiving 10 Gy (Vsc10) were 13.8 Gy (5.4-21 Gy), 8.9 Gy (2.6-11.4 Gy) and 0.33 cc (0-1.6 cc), respectively. Other OARs were evaluated when in proximity to the TV. Esophagus (n=58), trachea (n=28), oropharynx (n=11), and kidneys (n=34) received median (range) V10 and V15 of 3.1 cc (0-5.8 cc) and 1.2 cc (0-2.9 cc), 2.8 cc (0-4.9 cc), and 0.8 cc (0-2.1 cc), 3.4 cc (0-6.2 cc) and 1.6 cc (0-3.2 cc), 0.3 cc (0-0.8 cc) and 0.08 cc (0-0.1 cc), respectively. Conclusions: Cord Dmax of 14 Gy and D0.35 of 10 Gy are safe dose constraints for 18-Gy single-fraction SRS. Esophagus V10 of 3 cc and V15 of 1 cc, trachea V10 of 3 cc, and V15 of 1 cc, oropharynx V10 of 3.5 cc and V15 of 1.5 cc, kidney V10 of 0.3 cc, and V15 of 0.1 cc are planning guidelines when these OARs are in proximity to the TV.« less

Long-Term Update of NRG Oncology RTOG 0319: A Phase 1 and 2 Trial to Evaluate 3-Dimensional Conformal Radiation Therapy Confined to the Region of the Lumpectomy Cavity for Stage I and II Breast Carcinoma.

PubMed

Rabinovitch, Rachel; Moughan, Jennifer; Vicini, Frank; Pass, Helen; Wong, John; Chafe, Susan; Petersen, Ivy; Arthur, Douglas W; White, Julia

2016-12-01

NRG Oncology RTOG 0319 was the first cooperative group trial in the United States to evaluate 3-dimensional conformal radiation therapy (3D-CRT) accelerated partial breast irradiation (APBI). This report updates secondary endpoints of toxicity and efficacy. Patients with stage I or II invasive breast cancer (tumor size ≤3 cm, ≤3 positive lymph nodes, negative margins) were eligible for 3D-CRT APBI: 38.5 Gy in 10 twice-daily fractions. Patient characteristics and treatment details have previously been reported. Adverse events were graded with CTCAE v3.0 (National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0). This analysis updates the rates of ipsilateral breast recurrence (IBR), contralateral breast recurrence, ipsilateral node recurrence (INR), metastatic sites (distant metastases [DM]), mastectomy, disease-free survival, mastectomy-free survival, and overall survival. Of 58 enrolled patients, 52 were eligible, with a median age of 61 years; 94% had stage I cancer and 83% had estrogen receptor positive disease. The median follow-up period was 8 years (minimum-maximum, 1.7-9.0 years). The 7-year estimate of isolated IBR (no DM) was 5.9%. The 7-year estimates of all IBRs, INR, mastectomy rate, and DM were 7.7%, 5.8%, 7.7%, and 7.7%, respectively. All 4 IBRs were invasive, of which 3 had a component within the planning target volume. The patterns of failure were as follows: 3 IBRs, 1 INR, 2 DM, 1 INR plus DM, and 1 IBR plus INR plus DM. The 7-year estimates of mastectomy-free survival, disease-free survival, and overall survival were 71.2%, 71.2%, and 78.8%, respectively. Thirteen patients died: 3 of breast cancer and 10 of other causes. Grade 3 (G3) treatment-related adverse events were reported by 4 patients (7.7%). No G3 pain or pulmonary or cardiac toxicities were reported. This phase 1 and 2 trial of 3D-CRT APBI continues to show durable tumor control and minimal G3 toxicity, comparable to other APBI techniques. Mature phase 3 results will determine the appropriateness and limitations of this noninvasive APBI technique. Copyright © 2016. Published by Elsevier Inc.

TU-C-9A-01: IROC Organization and Clinical Trial Credentialing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Followill, D; Molineu, A; Xiao, Y

2014-06-15

As a response to recommendations from a report from the Institute of Medicine, NCI is reorganizing it clinical trial groups into a National Clinical Trial Network (NCTN) that consists of four adult groups (Alliance, ECOGACRIN, NRG, and SWOG) and one children’s group (COG). NRG will house CIRO, a center to promote innovative radiation therapy research and intergroup collaboration in radiation. The quality assurance groups that support clinical trials have also been restructured. ITC, OSU Imaging corelab, Philadelphia Imaging core-lab, QARC, RPC, and RTOGQA have joined together to create the Imaging and Radiation Oncology Core (IROC) Group. IROC’s mission is tomore » provide integrated radiation oncology and diagnostic imaging quality control programs in support of the NCI’s NCTN thereby assuring high quality data for clinical trials designed to improve the clinical outcomes for cancer patients worldwide. This will be accomplished through five core services: site qualification, trial design support, credentialing, data management, case review.These changes are important for physicist participating in NCI clinical trials to understand. We will describe in detail the IROC’s activities and five core services so that as a user, the medical physicist can learn how to efficiently utilize this group. We will describe common pitfalls encountered in credentialing for current protocols and present methods to avoid them. These may include the which benchmarks are required for NSABP B-51/RTOG 1304 and how to plan them as well as tips for phantom planning. We will explain how to submit patient and phantom cases in the TRIAD system used by IROC. Learning Objectives: To understand the basic organization of IROC, its mission and five core services To learn how to use TRIAD for patient and phantom data submission To learn how to avoid common pitfalls in credentialing for current trials.« less

Chromosomal Radiosensitivity in Lymphocytes of Cervix Cancer Patients—Correlation with Side Effect after Radiotherapy

NASA Astrophysics Data System (ADS)

Wegierek-Ciuk, Aneta; Lankoff, Anna; Lisowska, Halina; Banasik-Nowak, Anna; Arabski, Michał; Kedzierawski, Piotr; Florek, Agnieszka; Wojcik, Andrzej

2010-01-01

It is well known that cancer patients receiving similar radiotherapy treatments differ widely in normal tissue reactions ranging from undetectable to unacceptably severe levels. Therefore, an important goal of radiobiological research is to establish a test which would allow identifying individual radiosensitivity of patients prior to radiotherapy. The aim of the presented study is to assess the relationship between lymphocyte intrinsic radiosensitivity in vitro and early reaction of normal tissue in cervix cancer patients treated by radiotherapy. The following endpoints are analyzed in vitro: frequency of micronuclei, the kinetics of DNA repair and apoptosis. Acute normal tissue reaction to radiotherapy in the skin, bladder and rectum are scored according to the EORTC/RTOG scale. Our results show a wide inter-individual variability in chromosomal radiosensitivity in vitro. The majority of patients show a Grade 0, 1 or 2 reaction for all organs studied. No statistically significant correlation has been observed between the in vitro results in lymphocytes and the degree of early normal tissue and organ reaction.

[Comparation study of incidental irradiation dose to the internal mammary chain during postmastectomy radiotherapy for patients treated with different irradiation techniques].

PubMed

Wang, W; Meng, Y T; Song, Y F; Sun, T; Xu, M; Shao, Q; Zhang, Y J; Li, J B

2018-05-23

Objective: To evaluated the unplanned coverage dose to the internal mammary chain (IMC) in patient treated with postmastectomy radiotherapy (PMRT). Methods: One hundred and thirty eight patients with breast cancer receiving radiotherapy (RT) in our hospital were retrospectively analyzed. Patients were divided into three groups: three-dimensional conformal radiotherapy (3D-CRT) group, forward intensity-modulated radiotherapy (F-IMRT) group and inverse IMRT (I-IMRT) group. The IMC were contoured according to Radiation Therapy Oncology Group (RTOG) consensus, and were not include into the planning target volume (PTV). The incidental irradiation dose to IMC among the three groups and the first three intercostal spaces IMC (ICS-IMC 1-3) were all compared, and explored the relationship between the mean doses (Dmean) of IMC and the OARs (ipsilateral lung and heart). Results: The dose delivered to IMC showed no difference in CRT, F-IMRT and I-IMRT(33.80 Gy, 29.65 Gy and 32.95 Gy). And 10.42%, 2.04%, and 9.76% patients achieved ≥45 Gy when treated with CRT, F-IMRT and I-IMRT. For the IMC dose in the first three intercostal spaces (ICS1-3), there was no difference to the three treatment plannings. The Dmean, V(20), V(30), V(40) and V(50) of the ICS-IMC2 and ICS-IMC3 were all obviously superior than ICS-IMC1 for all these three plannings. Moderate positive correlation was founded between Dmean for IMC and Dmean for heart for left breast cancer patients underwent CRT ( r =0.338, P =0.01). Whereas for F-IMRT and I-IMRT groups, positive correlation were founded between Dmean for IMC and Dmean and V(20) for ipsilateral lung for all patients (F-IMRT: r =0.366, P =0.010; r =0.318, P =0.026; I-IMRT: r =0.427, P =0.005; r =0.411, P =0.008). Conclusions: In 3D-CRT, F-IMRT and I-IMRT planning methods, partial patients get IMC irradiated doses that could achieve therapeutic doses. Compared with 3D-CRT, F-IMRT and I-IMRT further reduced the dose of irradiated organs. However, there is no difference in the dose coverage of IMC for the three planned approaches when the IMC made an unplanned target.

SU-E-T-508: End to End Testing of a Prototype Eclipse Module for Planning Modulated Arc Therapy On the Siemens Platform

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, L; Sarkar, V; Spiessens, S

2014-06-01

Purpose: The latest clinical implementation of the Siemens Artiste linac allows for delivery of modulated arcs (mARC) using full-field flattening filter free (FFF) photon beams. The maximum doserate of 2000 MU/min is well suited for high dose treatments such as SBRT. We tested and report on the performance of a prototype Eclipse TPS module supporting mARC capability on the Artiste platform. Method: our spine SBRT patients originally treated with 12/13 field static-gantry IMRT (SGIMRT) were chosen for this study. These plans were designed to satisfy RTOG0631 guidelines with a prescription of 16Gy in a single fraction. The cases were re-plannedmore » as mARC plans in the prototype Eclipse module using the 7MV FFF beam and required to satisfy RTOG0631 requirements. All plans were transferred from Eclipse, delivered on a Siemens Artiste linac and dose-validated using the Delta4 system. Results: All treatment plans were straightforwardly developed, in timely fashion, without challenge or inefficiency using the prototype module. Due to the limited number of segments in a single arc, mARC plans required 2-3 full arcs to yield plan quality comparable to SGIMRT plans containing over 250 total segments. The average (3%/3mm) gamma pass-rate for all arcs was 98.5±1.1%, thus demonstrating both excellent dose prediction by the AAA dose algorithm and excellent delivery fidelity. Mean delivery times for the mARC plans(10.5±1.7min) were 50-70% lower than the SGIMRT plans(26±2min), with both delivered at 2000 MU/min. Conclusion: A prototype Eclipse module capable of planning for Burst Mode modulated arc delivery on the Artiste platform has been tested and found to perform efficiently and accurately for treatment plan development and delivered-dose prediction. Further investigation of more treatment sites is being carried out and data will be presented.« less

SU-E-T-486: Effect of the Normalized Prescription Isodose Line On Target Dose Deficiency in Lung SBRT Based On Monte Carlo Calculation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, D; Zhang, Q; Zhou, S

Purpose: To investigate the impact of normalized prescription isodose line on target dose deficiency calculated with Monte Carlo (MC) vs. pencil Beam (PB) in lung SBRT. RTOG guidelines recommend prescription lines between 60% and 90% for lung SBRT. How this affects the magnitude of MC-calculated target dose deficiency has never been studied. Methods: Under an IRB-approved protocol, four lung SBRT patients were replanned following RTOG0813 by a single physicist. For each patient, four alternative plans were generated based on PB calculation prescribing to 60–90% isodose lines, respectively. Each plan consisted of 360o coplanar dynamic conformal arcs with beam apertures manuallymore » optimized to achieve similar dose coverage and conformity for all plans of the same patient. Dose distribution was calculated with MC and compared to that with PB. PTV dose-volume endpoints were compared, including Dmin, D5, Dmean, D95, and Dmax. PTV V100 coverage, conformity index (CI), and heterogeneity index (HI) were also evaluated. Results: For all 16 plans, median (range) PTV V100 and CI were 99.7% (97.5–100%) and 1.27 (1.20–1.41), respectively. As expected, lower prescription line resulted in higher target dose heterogeneity, yielding median (range) HI of 1.26 (1.05–1.51) for all plans. Comparing MC to PB, median (range) D95, Dmean, D5 PTV dose deficiency were 18.9% (11.2–23.2%), 15.6% (10.0–22.7%), and 9.4%(5.5–13.6%) of the prescription dose, respectively. The Dmean, D5, and Dmax deficiency was found to monotonically increase with decreasing prescription line from 90% to 60%, while the Dmin deficiency monotonically decreased. D95 deficiency exhibited more complex trend, reaching the largest deficiency at 80% for all patients. Conclusion: Dependence on prescription isodose line was found for MC-calculated PTV dose deficiency of lung SBRT. When comparing reported MC dose deficiency values from different institutions, their individual selections of prescription line should be considered in addition to other factors affecting the deficiency magnitude.« less

Hypofractionated intensity modulated irradiation for localized prostate cancer, results from a phase I/II feasibility study

PubMed Central

Junius, Sara; Haustermans, Karin; Bussels, Barbara; Oyen, Raymond; Vanstraelen, Bianca; Depuydt, Tom; Verstraete, Jan; Joniau, Steven; Van Poppel, Hendrik

2007-01-01

Background To assess acute (primary endpoint) and late toxicity, quality of life (QOL), biochemical or clinical failure (secondary endpoints) of a hypofractionated IMRT schedule for prostate cancer (PC). Methods 38 men with localized PC received 66 Gy (2.64 Gy) to prostate,2 Gy to seminal vesicles (50 Gy total) using IMRT. Acute toxicity was evaluated weekly during radiotherapy (RT), at 1–3 months afterwards using RTOG acute scoring system. Late side effects were scored at 6, 9, 12, 16, 20, 24 and 36 months after RT using RTOG/EORTC criteria. Quality of life was assessed by EORTC-C30 questionnaire and PR25 prostate module. Biochemical failure was defined using ASTRO consensus and nadir+2 definition, clinical failure as local, regional or distant relapse. Results None experienced grade III-IV toxicity. 10% had no acute genito-urinary (GU) toxicity, 63% grade I; 26% grade II. Maximum acute gastrointestinal (GI) scores 0, I, II were 37%, 47% and 16%. Maximal acute toxicity was reached weeks 4–5 and resolved within 4 weeks after RT in 82%. Grade II rectal bleeding needing coagulation had a peak incidence of 18% at 16 months after RT but is 0% at 24–36 months. One developed a urethral stricture at 2 years (grade II late GU toxicity) successfully dilated until now. QOL urinary symptom scores reached a peak incidence 1 month after RT but normalized 6 months later. Bowel symptom scores before, at 1–6 months showed similar values but rose slowly 2–3 years after RT. Nadir of sexual symptom scores was reached 1–6 months after RT but improved 2–3 years later as well as physical, cognitive and role functional scales. Emotional, social functional scales were lowest before RT when diagnosis was given but improved later. Two years after RT global health status normalized. Conclusion This hypofractionated IMRT schedule for PC using 25 fractions of 2.64 Gy did not result in severe acute side effects. Until now late urethral, rectal toxicities seemed acceptable as well as failure rates. Detailed analysis of QOL questionnaires resulted in the same conclusion. PMID:17686162

A Phase II Study of Bevacizumab in Combination With Definitive Radiotherapy and Cisplatin Chemotherapy in Untreated Patients With Locally Advanced Cervical Carcinoma: Preliminary Results of RTOG 0417

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schefter, Tracey E., E-mail: tracey.schefter@ucdenver.edu; Winter, Kathryn; Kwon, Janice S.

Purpose: Concurrent cisplatin-based chemoradiotherapy (CRT) is the standard treatment for locally advanced cervical cancer. RTOG 0417 was a Phase II study exploring the safety and efficacy of the addition of bevacizumab to standard CRT. Methods and Materials: Eligible patients with bulky tumors (Stage IB-IIIB) were treated with once-weekly cisplatin (40 mg/m{sup 2}) chemotherapy and standard pelvic radiotherapy and brachytherapy. Bevacizumab was administered at 10 mg/kg intravenously every 2 weeks for three cycles. Treatment-related serious adverse event (SAE) and other adverse event (AE) rates within the first 90 days from treatment start were determined. Treatment-related SAEs were defined as any Grademore » {>=}4 vaginal bleeding or thrombotic event or Grade {>=}3 arterial event, gastrointestinal (GI) bleeding, or bowel/bladder perforation, or any Grade 5 treatment-related death. Treatment-related AEs included all SAEs and Grade 3 or 4 GI toxicity persisting for >2 weeks despite medical intervention, Grade 4 neutropenia or leukopenia persisting for >7 days, febrile neutropenia, Grade 3 or 4 other hematologic toxicity, and Grade 3 or 4 GI, renal, cardiac, pulmonary, hepatic, or neurologic AEs. All AEs were scored using the National Cancer Institute Common Terminology Criteria (CTCAE) v 3.0 (MedDRA version 6.0). Results: A total of 60 patients from 28 institutions were enrolled between 2006 and 2009, and of these, 49 patients were evaluable. The median follow-up was 12.4 months (range, 4.6-31.4 months).The median age was 45 years (range, 22-80 years). Most patients had FIGO Stage IIB (63%) and were of Zubrod performance status of 0 (67%). 80% of cases were squamous. There were no treatment-related SAEs. There were 15 (31%) protocol-specified treatment-related AEs within 90 days of treatment start; the most common were hematologic (12/15; 80%). 18 (37%) occurred during treatment or follow-up at any time. 37 of the 49 patients (76%) had cisplatin and bevacizumab administered per protocol, and 46 of the 49 (94%) had both external beam and brachytherapy administered per protocol or with acceptable variation. Conclusion: Bevacizumab in addition to standard pelvic chemoradiotherapy for locally advanced cervical cancer is feasible and safe with respect to the protocol-specified treatment-related SAEs and AEs.« less

Whole-brain hippocampal sparing radiation therapy: Volume-modulated arc therapy vs intensity-modulated radiation therapy case study.

PubMed

Lee, Katrina; Lenards, Nishele; Holson, Janice

2016-01-01

The hippocampus is responsible for memory and cognitive function. An ongoing phase II clinical trial suggests that sparing dose to the hippocampus during whole-brain radiation therapy can help preserve a patient׳s neurocognitive function. Progressive research and advancements in treatment techniques have made treatment planning more sophisticated but beneficial for patients undergoing treatment. The aim of this study is to evaluate and compare hippocampal sparing whole-brain (HS-WB) radiation therapy treatment planning techniques using volume-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT). We randomly selected 3 patients to compare different treatment techniques that could be used for reducing dose to the hippocampal region. We created 2 treatment plans, a VMAT and an IMRT, from each patient׳s data set and planned on the Eclipse 11.0 treatment planning system (TPS). A total of 6 plans (3 IMRT and 3 VMAT) were created and evaluated for this case study. The physician contoured the hippocampus as per the Radiation Therapy Oncology Group (RTOG) 0933 protocol atlas. The organs at risk (OR) were contoured and evaluated for the plan comparison, which included the spinal cord, optic chiasm, the right and left eyes, lenses, and optic nerves. Both treatment plans produced adequate coverage on the planning target volume (PTV) while significantly reducing dose to the hippocampal region. The VMAT treatment plans produced a more homogenous dose distribution throughout the PTV while decreasing the maximum point dose to the target. However, both treatment techniques demonstrated hippocampal sparing when irradiating the whole brain. Copyright © 2016 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Rectal balloon use limits vaginal displacement, rectal dose, and rectal toxicity in patients receiving IMRT for postoperative gynecological malignancies.

PubMed

Wu, Cheng-Chia; Wuu, Yen-Ruh; Yanagihara, Theodore; Jani, Ashish; Xanthopoulos, Eric P; Tiwari, Akhil; Wright, Jason D; Burke, William M; Hou, June Y; Tergas, Ana I; Deutsch, Israel

2018-01-01

Pelvic radiotherapy for gynecologic malignancies traditionally used a 4-field box technique. Later trials have shown the feasibility of using intensity-modulated radiotherapy (IMRT) instead. But vaginal movement between fractions is concerning when using IMRT due to greater conformality of the isodose curves to the target and the resulting possibility of missing the target while the vagina is displaced. In this study, we showed that the use of a rectal balloon during treatment can decrease vaginal displacement, limit rectal dose, and limit acute and late toxicities. Little is known regarding the use of a rectal balloon (RB) in treating patients with IMRT in the posthysterectomy setting. We hypothesize that the use of an RB during treatment can limit rectal dose and acute and long-term toxicities, as well as decrease vaginal cuff displacement between fractions. We performed a retrospective review of patients with gynecological malignancies who received postoperative IMRT with the use of an RB from January 1, 2012 to January 1, 2015. Rectal dose constraint was examined as per Radiation Therapy Oncology Group (RTOG) 1203 and 0418. Daily cone beam computed tomography (CT) was performed, and the average (avg) displacement, avg magnitude, and avg magnitude of vector were calculated. Toxicity was reported according to RTOG acute radiation morbidity scoring criteria. Acute toxicity was defined as less than 90 days from the end of radiation treatment. Late toxicity was defined as at least 90 days after completing radiation. Twenty-eight patients with postoperative IMRT with the use of an RB were examined and 23 treatment plans were reviewed. The avg rectal V40 was 39.3% ± 9.0%. V30 was65.1% ± 10.0%. V50 was 0%. Separate cone beam computed tomography (CBCT) images (n = 663) were reviewed. The avg displacement was as follows: superior 0.4 + 2.99 mm, left 0.23 ± 4.97 mm, and anterior 0.16 ± 5.18 mm. The avg magnitude of displacement was superior/inferior 2.22 ± 2.04 mm, laterally 3.41 ± 3.62 mm, and anterior/posterior 3.86 ± 3.45 mm. The avg vector magnitude was 6.60 ± 4.14 mm. For acute gastrointestinal (GI) toxicities, 50% experienced grade 1 toxicities and 18% grade 2 GI toxicities. For acute genitourinary (GU) toxicities, 21% had grade 1 and 18% had grade 2 toxicities. For late GU toxicities, 7% had grade 1 and 4% had grade 2 toxicities. RB for gynecological patients receiving IMRT in the postoperative setting can limit V40 rectal dose and vaginal displacement. Although V30 constraints were not met, patients had limited acute and late toxicities. Further studies are needed to validate these findings. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Long-term results of RTOG trial 8911 (USA Intergroup 113): a random assignment trial comparison of chemotherapy followed by surgery compared with surgery alone for esophageal cancer.

PubMed

Kelsen, David P; Winter, Katryn A; Gunderson, Leonard L; Mortimer, Joanne; Estes, Norman C; Haller, Daniel G; Ajani, Jaffer A; Kocha, Walter; Minsky, Bruce D; Roth, Jack A; Willett, Christopher G

2007-08-20

We update Radiation Therapy Oncology Group trial 8911 (USA Intergroup 113), a comparison of chemotherapy plus surgery versus surgery alone for patients with localized esophageal cancer. The relationship between resection type and between tumor response and outcome were also analyzed. The chemotherapy group received preoperative cisplatin plus fluorouracil. Outcome based on the type of resection (R0, R1, R2, or no resection) was evaluated. The main end point was overall survival. Disease-free survival, relapse pattern, the influence of postoperative treatment, and the relationship between response to preoperative chemotherapy and outcome were also evaluated. Two hundred sixteen patients received preoperative chemotherapy, 227 underwent immediate surgery. Fifty-nine percent of surgery only and 63% of chemotherapy plus surgery patients underwent R0 resections (P = .5137). Patients undergoing less than an R0 resection had an ominous prognosis; 32% of patients with R0 resections were alive and free of disease at 5 years, only 5% of patients undergoing an R1 resection survived for longer than 5 years. The median survival rates for patients with R1, R2, or no resections were not significantly different. While, as initially reported, there was no difference in overall survival for patients receiving perioperative chemotherapy compared with the surgery only group, patients with objective tumor regression after preoperative chemotherapy had improved survival. For patients with localized esophageal cancer, whether or not preoperative chemotherapy is administered, only an R0 resection results in substantial long-term survival. Even microscopically positive margins are an ominous prognostic factor. After a R1 resection, postoperative chemoradiotherapy therapy offers the possibility of long-term disease-free survival to a small percentage of patients.

Changes in Gene Expression Predicting Local Control in Cervical Cancer: Results from Radiation Therapy Oncology Group 0128

PubMed Central

Weidhaas, Joanne B.; Li, Shu-Xia; Winter, Kathryn; Ryu, Janice; Jhingran, Anuja; Miller, Bridgette; Dicker, Adam P.; Gaffney, David

2009-01-01

Purpose To evaluate the potential of gene expression signatures to predict response to treatment in locally advanced cervical cancer treated with definitive chemotherapy and radiation. Experimental Design Tissue biopsies were collected from patients participating in Radiation Therapy Oncology Group (RTOG) 0128, a phase II trial evaluating the benefit of celecoxib in addition to cisplatin chemotherapy and radiation for locally advanced cervical cancer. Gene expression profiling was done and signatures of pretreatment, mid-treatment (before the first implant), and “changed” gene expression patterns between pre- and mid-treatment samples were determined. The ability of the gene signatures to predict local control versus local failure was evaluated. Two-group t test was done to identify the initial gene set separating these end points. Supervised classification methods were used to enrich the gene sets. The results were further validated by leave-one-out and 2-fold cross-validation. Results Twenty-two patients had suitable material from pretreatment samples for analysis, and 13 paired pre- and mid-treatment samples were obtained. The changed gene expression signatures between the pre- and mid-treatment biopsies predicted response to treatment, separating patients with local failures from those who achieved local control with a seven-gene signature. The in-sample prediction rate, leave-one-out prediction rate, and 2-fold prediction rate are 100% for this seven-gene signature. This signature was enriched for cell cycle genes. Conclusions Changed gene expression signatures during therapy in cervical cancer can predict outcome as measured by local control. After further validation, such findings could be applied to direct additional therapy for cervical cancer patients treated with chemotherapy and radiation. PMID:19509178

Skin toxicity from external beam radiation therapy in breast cancer patients: protective effects of Resveratrol, Lycopene, Vitamin C and anthocianin (Ixor®).

PubMed

Di Franco, Rossella; Calvanese, MariaGrazia; Murino, Paola; Manzo, Roberto; Guida, Cesare; Di Gennaro, Davide; Anania, Caterina; Ravo, Vincenzo

2012-01-30

This is an observational study and the aim is to evaluate the effect of dietary supplements based on Resveratrol, Lycopene, Vitamin C and Anthocyanins (Ixor®) in reducing skin toxicity due to external beam radiotherapy in patients affected by breast cancer. 71 patients were enrolled and they were divided in two different groups: a control group (CG) of 41 patients treated with prophylactic topical therapy based on hyaluronic acid and topical steroid therapy in case of occurrence of radiodermatitis, and a Ixor-Group (IG) of 30 patients treated also with an oral therapy based on Resveratrol, Lycopene, Vitamin C and Anthocyanin (Ixor®) at a dose of 2 tablets/day, starting from 10 days before the radiation treatment until 10 days after the end of treatment. Skin toxicity has been related to PTV, to breast volume that received a radiation dose equal or lower than 107%, included between 107% and 110%, or greater than 110% of the prescribed dose. Moreover it's been studied the relationship between skin toxicity and the chemotherapy schedule used before treatment. We calculated in both groups the percentage of patients who had a skin toxicity of grade 2 or 3 (according to RTOG scale). Absolute risk reduction (ARR), relative risk (RR) and odds ratio (OR) have been calculated for each relationship. Control Group (CG) patients with a PTV > 500 ml presented skin toxicity G2 + G3 in 30% of cases, versus 25% of Ixor-Group (IG) [OR 0.77]. In patients with a PTV < 500 ml G2 + G3 toxicity was 0% in the IG compared to 18% in CG (OR 0.23). When Dmax was less than or equal to 107% of the prescribed dose skin toxicity was G2 + G3 in 12.5% in CG, versus 0% in IG (OR 0.73), instead when Dmax was included between 107 and 110% of the prescribed dose, G2 + G3 skin toxicity was 35% in CG and 21% in IG (OR 0.50). In patients undergoing chemotherapy with anthracyclines and taxanes, G2 + G3 toxicity was 27% in CG, against 20% in IG (OR 0.68). The protective effect of Resveratrol, Lycopene, Vitamin C and Anthocyanin (Ixor®) is more detected in patients with PTV < 500 ml, when Dmax reaches values lower or equal to 107%, but not exceeding 110% of the prescribed dose, and in patients undergoing adjuvant chemotherapy with anthracyclines and taxanes.

Cytoreductive prostate radiotherapy in oligometastatic prostate cancer: a single centre analysis of toxicity and clinical outcome.

PubMed

Riva, Giulia; Marvaso, Giulia; Augugliaro, Matteo; Zerini, Dario; Fodor, Cristiana; Musi, Gennaro; De Cobelli, Ottavio; Orecchia, Roberto; Jereczek-Fossa, Barbara Alicja

2017-01-01

The current standard of care for patients with metastatic prostate cancer (mPCa) at diagnosis is androgen deprivation therapy (ADT) with or without anti-androgen and chemotherapy. The aim of this study was to define the role of a local radiotherapy (RT) treatment in the mPCa setting. We retrospectively reviewed data of patients with PCa and bone oligometastases at diagnosis treated in our institution with ADT followed by cytoreductive prostate-RT with or without RT on metastases. Biochemical and clinical failure (BF, CF), overall survival (OS) and RT-toxicity were assessed. We identified 22 patients treated with ADT and external-beam RT on primary between June 2008 and March 2016. All of them but four were also treated for bone metastases. RT on primary with moderately and extremely hypofractionated regimes started after 10.3 months (3.9-51.7) from ADT. After a median follow-up of 26.4 months (10.3-55.5), 20 patients are alive. Twelve patients showed BF after a median time of 23 months (14.5-104) and CF after a median of 23.6 months (15.3-106.1) from the start of ADT. Three patients became castration resistant, starting a new therapy; median time to castration resistance was 31.03 months (range: 29.9-31.5 months). According to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC), only one patient developed acute grade 3 genitourinary toxicity. No late grade >2 adverse events were observed. Prostate RT in oligometastatic patients is safe and offers long-lasting local control. When compared to ADT alone, RT on primary seems to improve biochemical control and long-term survival; however, this hypothesis should be investigated in prospective studies. Further research is warranted.

Polymorphism of regulatory region of GHRL gene (-2531C>T) as a promising predictive factor for radiotherapy-induced oral mucositis in patients with head neck cancer.

PubMed

Brzozowska, Anna; Homa-Mlak, Iwona; Mlak, Radosław; Gołębiowski, Paweł; Mazurek, Marcin; Ciesielka, Marzanna; Małecka-Massalska, Teresa

2018-03-22

The purpose of this study was to investigate the relationship between single nucleotide polymorphisms (SNP; rs1629816) in the regulatory region (c.-2531C>T) of the ghrelin (GHRL) gene and the occurrence and severity of oral mucositis caused by radiotherapy (RT) in patients with head and neck cancer. Oral mucositis in 65 patients with head and neck cancer who underwent irradiation were assessed according to Radiation Therapy Oncology Group (RTOG)/European Organisation for Research and Treatment of Cancer (EORTC) scale. The DNA from patients with head and neck cancer was isolated from whole blood. The genotypes were determined using the minisequencing method (SNaPshot PCR). The frequency of occurrence of the GHRL gene (c.-2531C>T, rs1629816) genotypes were as follows: AA = 21.5%; GA = 40%; and GG = 38.5%. In case of AA genotype, there was a 7-fold decrease of the risk of occurrence of oral mucositis (of grades 2 and 3) in the sixth week of RT (AA vs GA or GG, respectively: 17.9% vs 82.1% patients; odds ratio [OR] 0.14; 95% confidence interval [CI] 0.02-0.98; P = .0481). No statistically significant differences were observed between the volume of oral cavity contours (V30, V40, and V50) depending on the GHRL genotype in patients with head and neck cancer. The study results have demonstrated an association between the AA genotype of the GHRL gene and the risk of more severe oral mucositis attributed to RT in patients with head and neck cancer. © 2018 Wiley Periodicals, Inc.

Clinically Meaningful Differences in Patient-Reported Outcomes With Amifostine in Combination With Chemoradiation for Locally Advanced Non-Small-Cell Lung Cancer: An Analysis of RTOG 9801

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarna, Linda; Swann, Suzanne; Langer, Corey

2008-12-01

Purpose: The purpose of this study is to analyze changes in quality of life (QOL) and symptoms from pretreatment to 6 weeks posttreatment in a Phase III randomized study (Radiation Therapy Oncology Group 9801) of amifostine (AM) vs. no AM in patients with Stages II-III non-small-cell lung cancer receiving paclitaxel and carboplatin as induction and then concurrently with hyperfractionated radiation therapy (RT). Methods and Materials: One hundred thirty-eight patients with baseline and 6-week posttreatment QOL data were analyzed. There were no significant differences in baseline demographics between those who did and did not have QOL data. The QOL and symptomsmore » were assessed by using the European Organization for Research and Treatment of Cancer (EORTC) Global QOL and Pain subscales and the EORTC-Lung Cancer-13 symptom tool. Clinically relevant changes in QOL were characterized by 10-point differences in individual scores pre/post treatment. A daily diary of patient-rated difficulty swallowing and a weekly physician-rated dysphagia log (using National Cancer Institute Common Toxicity Criteria) were completed during treatment. Weight loss was monitored. Differences in outcomes were examined according to smoking status, alcohol use, and sex. Results: Patients receiving AM reported significantly greater pain reduction after chemoradiation (34% vs. no AM, 21%), less difficulty swallowing during chemoradiation, and less weight loss than patients not receiving AM. However, physician-rated assessments of dysphagia were not significantly different by treatment arm. There were no other significant changes in QOL or symptoms according to treatment arm, smoking status, alcohol use, or sex. Conclusions: Patient evaluations of difficulty swallowing and pain suggest benefits from AM use that are distinct from clinician-rated assessments.« less

Early and late skin reactions to radiotherapy for breast cancer and their correlation with radiation-induced DNA damage in lymphocytes

PubMed Central

López, Escarlata; Guerrero, Rosario; Núñez, Maria Isabel; del Moral, Rosario; Villalobos, Mercedes; Martínez-Galán, Joaquina; Valenzuela, Maria Teresa; Muñoz-Gámez, José Antonio; Oliver, Francisco Javier; Martín-Oliva, David; de Almodóvar, José Mariano Ruiz

2005-01-01

Introduction Radiotherapy outcomes might be further improved by a greater understanding of the individual variations in normal tissue reactions that determine tolerance. Most published studies on radiation toxicity have been performed retrospectively. Our prospective study was launched in 1996 to measure the in vitro radiosensitivity of peripheral blood lymphocytes before treatment with radical radiotherapy in patients with breast cancer, and to assess the early and the late radiation skin side effects in the same group of patients. We prospectively recruited consecutive breast cancer patients receiving radiation therapy after breast surgery. To evaluate whether early and late side effects of radiotherapy can be predicted by the assay, a study was conducted of the association between the results of in vitro radiosensitivity tests and acute and late adverse radiation effects. Methods Intrinsic molecular radiosensitivity was measured by using an initial radiation-induced DNA damage assay on lymphocytes obtained from breast cancer patients before radiotherapy. Acute reactions were assessed in 108 of these patients on the last treatment day. Late morbidity was assessed after 7 years of follow-up in some of these patients. The Radiation Therapy Oncology Group (RTOG) morbidity score system was used for both assessments. Results Radiosensitivity values obtained using the in vitro test showed no relation with the acute or late adverse skin reactions observed. There was no evidence of a relation between acute and late normal tissue reactions assessed in the same patients. A positive relation was found between the treatment volume and both early and late side effects. Conclusion After radiation treatment, a number of cells containing major changes can have a long survival and disappear very slowly, becoming a chronic focus of immunological system stimulation. This stimulation can produce, in a stochastic manner, late radiation-related adverse effects of varying severity. Further research is warranted to identify the major determinants of normal tissue radiation response to make it possible to individualize treatments and improve the outcome of radiotherapy in cancer patients. PMID:16168114

Clinical results from first use of prostate stent as fiducial for radiotherapy of prostate cancer.

PubMed

Carl, Jesper; Nielsen, Jane; Holmberg, Mats; Larsen, Erik Hoejkjaer; Fabrin, Knud; Fisker, Rune V

2011-05-01

A clinical feasibility study using a removable prostate stent as fiducial for image-guided radiotherapy (IGRT) of localized prostate cancer (PC). The study included patients with local or locally advanced PC. The clinical target volume (CTV) was outlined on magnetic resonance (MR) images co-registered to planning computer tomography (CT) images. Daily online IGRT was delivered using the stent as fiducial. Risk of migration was estimated using multiple MR. Acute urinary toxicity was scored using the international prostate symptom score (IPSS). Late gastro-intestinal (GI) and genito-urinary (GU) toxicity was scored using the Radio Therapy Oncology Group (RTOG) score, biochemical failure (BF) was defined as an elevation of prostate specific antigen (PSA) above nadir plus 2 ng/ml after radiotherapy. One hundred men were enrolled in the study. Ninety completed radiotherapy with the stent as fiducial. No migration of the stent was seen, but three cases of dislocation of the stent to the bladder were observed. Acute urinary toxicity based on IPSS was comparable to toxicity in patients who had gold markers (GM) as fiducials. Removal of the stent was associated with a high frequency of urinary retention. Late GI and GU toxicity and BF were comparable to those of other studies, but longer observation time is needed. This study reports the first clinical results of using a prostate stent as fiducial. No migration of the stent observed. Dislocation of the stent to the urinary bladder was observed in three cases, requiring removal of the stent and insertion of a new fiducial. Acute toxicity during radiotherapy evaluated from IPSS was comparable to toxicity in patients with GM. Removal of the stent was associated with a high frequency of post procedural urinary retention. Late toxicity and BF were comparable to those of other studies, though longer observation time is needed.

RTOG 0529: A Phase 2 Evaluation of Dose-Painted Intensity Modulated Radiation Therapy in Combination With 5-Fluorouracil and Mitomycin-C for the Reduction of Acute Morbidity in Carcinoma of the Anal Canal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kachnic, Lisa A., E-mail: lisa.kachnic@bmc.org; Winter, Kathryn; Myerson, Robert J.

2013-05-01

Purpose: A multi-institutional phase 2 trial assessed the utility of dose-painted intensity modulated radiation therapy (DP-IMRT) in reducing grade 2+ combined acute gastrointestinal and genitourinary adverse events (AEs) of 5-fluorouracil (5FU) and mitomycin-C (MMC) chemoradiation for anal cancer by at least 15% compared with the conventional radiation/5FU/MMC arm from RTOG 9811. Methods and Materials: T2-4N0-3M0 anal cancer patients received 5FU and MMC on days 1 and 29 of DP-IMRT, prescribed per stage: T2N0, 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes (PTVs) in 28 fractions; T3-4N0-3, 45 Gy elective nodal, 50.4 Gy ≤3 cm or 54more » Gy >3 cm metastatic nodal and 54 Gy anal tumor PTVs in 30 fractions. The primary endpoint is described above. Planned secondary endpoints assessed all AEs and the investigator’s ability to perform DP-IMRT. Results: Of 63 accrued patients, 52 were evaluable. Tumor stage included 54% II, 25% IIIA, and 21% IIIB. In primary endpoint analysis, 77% experienced grade 2+ gastrointestinal/genitourinary acute AEs (9811 77%). There was, however, a significant reduction in acute grade 2+ hematologic, 73% (9811 85%, P=.032), grade 3+ gastrointestinal, 21% (9811 36%, P=.0082), and grade 3+ dermatologic AEs 23% (9811 49%, P<.0001) with DP-IMRT. On initial pretreatment review, 81% required DP-IMRT replanning, and final review revealed only 3 cases with normal tissue major deviations. Conclusions: Although the primary endpoint was not met, DP-IMRT was associated with significant sparing of acute grade 2+ hematologic and grade 3+ dermatologic and gastrointestinal toxicity. Although DP-IMRT proved feasible, the high pretreatment planning revision rate emphasizes the importance of real-time radiation quality assurance for IMRT trials.« less

SU-F-T-537: Prone Breast Accelerated Partial Breast Irradiation Using Non-Coplanar Volumetric Arc Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beninati, G; Barbiere, J; Godfrey, L

2016-06-15

Purpose: To demonstrate that Volumetric Modulated Arc Therapy (VMAT) can be an alternative technique to Brachytherapy Accelerated Partial Breast Irradiation (APBI) for treating large breasted women. The non-coplanar VMAT technique uses a commercially available couch and a small number of angles. This technique with the patient in the prone position can reduce high skin and critical structure doses in large breasted women, which are usually associated with Brachytherapy APBI. Methods: Philips Pinnacle treatment planning system with Smart Arc was used to plan a left sided laterally located excision cavity on a standard prone breast patient setup. Three thirty-degree arcs enteredmore » from the lateral side at respective couch angles of 345, 0, and 15 degrees. A fourth thirty degree arc beam entered from the medial side at a couch angle of 0 degrees. The arcs were selected to avoid critical structures as much as possible. A test run was then performed to verify that the beams did not collide with the patient nor support structures. NSABP B-39/RTOG 0413 protocol guidelines were used for dose prescription, normal tissue, and target definition. Results: Dose Volume Histogram analysis indicated that all parameters were equal or better than RTOG recommendations. Of particular note regarding the plan quality:1.(a) For a prescribed dose of 3850cGy the PTV-EVAL target volume receiving 100 percent of the dose(V100) was 93; protocol recommendation is V90 > 90 percent. (b) Maximum dose was 110 percent versus the allowed 120 percent .2. Uninvolved percentage of normal breast V100 and V50 were 17 and 47 versus allowed 35 and 60 percent respectively.3. For the skin, V100 was 5.7cc and the max dose to 0.1 cc was 4190cGy. Conclusion: Prone Breast non-coplanar VMAT APBI can achieve better skin cosmesis and lower critical structure doses than Brachytherapy APBI.« less

WE-FG-202-01: Early Prediction of Radiotherapy Induced Skin Reactions Using Dynamic Infrared Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Biswal, N; Cifter, G; Sun, J

Purpose: To predict radiotherapy induced skin reactions using dynamic infrared imaging. Methods: Thermal images were captured by our homebuilt system consisting of two flash lamps and an infrared (IR) camera. The surface temperature of the skin was first raised by ∼ 6 oC from ∼1 ms flashes. The camera then captured a series of IR images for 10 seconds. For each image, a baseline skin temperature was recorded for 0.5sec before heat impulse. The temporal temperature gradients were calculated between a reference point (immediately after the flash) and at a time point 9sec after that. Thermal effusivity, an intrinsic thermalmore » property of a material, was calculated from the surface temperature decay of skin. We present experimental data in five patients undergoing radiation therapy, of which 2 were Head & Neck, 1 was Sarcoma and 2 were Breast cancer patients. The prescribed doses were 45 – 60 Gy in 25 – 30 fractions. Each patient was imaged before treatment and after every fifth fraction until end of the treatment course. An area on the skin, outside the radiation field, was imaged as control region. During imaging, each patient’s irradiated skins were scored based on RTOG skin morbidity scoring criteria. Results: Temperature gradient, which is the temperature recovery rate, depends on the thermal properties of underlying tissue. It was observed that, the skin temperature and temporal temperature gradient increases with delivered radiation dose and skin RTOG score. The treatment does not change effusivity of superficial skin layer, however there was a significant difference in effusivity between treated and control areas at depth of ∼ 1.5 – 1.8 mm, increases with dose. Conclusion: The higher temporal temperature gradient and effusivity from irradiated areas suggest that there is more fluid under the irradiated skin, which causes faster temperature recovery. The mentioned effects may be predictors of Moist Desquamation.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valery, Charles A., E-mail: charles.valery@psl.aphp.f; Boskos, Christos; Boisserie, Gilbert

Purpose: Treatment of cerebral metastases located inside the brainstem remains a challenge, as the brainstem is considered to be a neurological organ at risk, whatever the treatment strategy. We report a retrospective study of 30 consecutive patients treated in our institution between 2005 and 2007 with micromultileaf linear accelerator (LINAC) -radiosurgery for brainstem metastases, with reduced doses compared to those usually reported in the literature. Methods and Materials: Mean follow-up was 311 days (range, 41-1351). Median age was 57 years (range, 37-82), Mean Karnofsky Index (KI) was 80. Primary tumor site was lung (n = 13), breast (n = 4),more » kidney (n = 4), skin (melanoma; n = 3), and others (n = 6). Primary tumor was controlled in 17 cases; extracranial metastases were controlled in 12 cases. Mean number of metastases was 1.46 (one to three); median volume was 2.82 cc (0.06-18). Dose was delivered by a micromultileaf collimator 6-MV LINAC . Results: Dose administered at the 70% isodose was 13.4 Gy (range, 8.2-15). Median survival was 10 months. Local control rates at 3, 6, and 12 months were 100%, 100%, and 79% respectively. Median neurological control duration was 5 months. Neurological control rates at 3, 6, and 12 months were 73%, 42%, and 25%, respectively. No parameter was found to significantly correlate with survival, local, or cerebral control. No patients had severe side effects (Grade III-IV), according to the Radiation Therapy Oncology Group (RTOG) scale. Conclusion: Lower doses than previously reported can achieve the same local control and survival rates in brain metastases, with minimal side effects.« less

Validity and reliability of the Greek version of the xerostomia questionnaire in head and neck cancer patients.

PubMed

Memtsa, Pinelopi Theopisti; Tolia, Maria; Tzitzikas, Ioannis; Bizakis, Ioannis; Pistevou-Gombaki, Kyriaki; Charalambidou, Martha; Iliopoulou, Chrysoula; Kyrgias, George

2017-03-01

Xerostomia after radiation therapy for head and neck (H&N) cancer has serious effects on patients' quality of life. The purpose of this study was to validate the Greek version of the self-reported eight-item xerostomia questionnaire (XQ) in patients treated with radiotherapy for H&N cancer. The XQ was translated into Greek and administered to 100 XQ patients. An exploratory factor analysis was performed. Reliability measures were calculated. Several types of validity were evaluated. The observer-rated scoring system was also used. The mean XQ value was 41.92 (SD 22.71). Factor analysis revealed the unidimensional nature of the questionnaire. High reliability measures (ICC, Cronbach's α, Pearson coefficients) were obtained. Patients differed statistically significantly in terms of XQ score, depending on the RTOG/EORTC classification. The Greek version of XQ is valid and reliable. Its score is well related to observer's findings and it can be used to evaluate the impact of radiation therapy on the subjective feeling of xerostomia.

Primary Analysis of a Phase II Randomized Trial Radiation Therapy Oncology Group (RTOG) 0212: Impact of Different Total Doses and Schedules of Prophylactic Cranial Irradiation on Chronic Neurotoxicity and Quality of Life for Patients With Limited-Disease Small-Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolfson, Aaron H., E-mail: awolfson@med.miami.edu; Bae, Kyounghwa; Komaki, Ritsuko

2011-09-01

Purpose: To determine the effect of dose and fractionation schedule of prophylactic cranial irradiation (PCI) on the incidence of chronic neurotoxicity (CNt) and changes in quality of life for selected patients with limited-disease small-cell lung cancer (LD SCLC). Methods and Materials: Patients with LD SCLC who achieved a complete response after chemotherapy and thoracic irradiation were eligible for randomization to undergo PCI to a total dose of 25 Gy in 10 daily fractions (Arm 1) vs. the experimental cohort of 36 Gy. Those receiving 36 Gy underwent a secondary randomization between daily 18 fractions (Arm 2) and twice-daily 24 fractionsmore » (Arm 3). Enrolled patients participated in baseline and follow-up neuropsychological test batteries along with quality-of-life assessments. Results: A total of 265 patients were accrued, with 131 in Arm 1, 67 in Arm 2, and 66 in Arm 3 being eligible. There are 112 patients (42.2%) alive with 25.3 months of median follow-up. There were no significant baseline differences among groups regarding quality-of-life measures and one of the neuropsychological tests, namely the Hopkins Verbal Learning Test. However, at 12 months after PCI there was a significant increase in the occurrence of CNt in the 36-Gy cohort (p = 0.02). Logistic regression analysis revealed increasing age to be the most significant predictor of CNt (p = 0.005). Conclusions: Because of the increased risk of developing CNt in study patients with 36 Gy, a total PCI dose of 25 Gy remains the standard of care for patients with LD SCLC attaining a complete response to initial chemoradiation.« less

SU-E-J-81: Adaptive Radiotherapy for IMRT Head & Neck Patient in AKUH

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yousuf, A; Qureshi, B; Qadir, A

2015-06-15

Purpose: In this study we proposed Adaptive radiotherapy for IMRT patients which will brought an additional dimension to the management of patients with H&N cancer in Aga Khan University Hospital. Methods: In this study 5 Head and Neck (H&N) patients plan where selected, who’s Re-CT were done during the course of their treatment, they were simulated with IMRT technique to learn the consequence of anatomical changes that may occur during the treatment, as they are more dramatic changes can occur as compare to conventional treatment. All the organ at risk were drawn according RTOG guidelines and doses were checked asmore » per NCCN guidelines. Results: The reduction in size of Planning target volume (PTV) is more than 20% in all the cases which leads to 3 to 5 % overdose to normal tissues and Organ at Risk. Conclusion: Through this study we would like to emphasis the importance of Adaptive Radiotherapy practice in all IMRT (H&N) patients, although prospective studies are required with larger sample sizes to address the safety and the clinical effect of such approaches on patient outcome, also one need to develop protocols before implementation of this technique in practice.« less

SU-F-T-204: A Preliminary Approach of Reducing Contralateral Breast and Heart Dose in Left Sided Whole Breast Cancer Patients Utilizing Proton Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Islam, M; Algan, O; Jin, H

Purpose: To investigate the plan quality and feasibility of a hybrid plan utilizing proton and photon fields for superior coverage in the internal mammary (IM) and supraclavicular (S/C) regions while minimizing heart and contralateral breast dose for the left-sided whole breast cancer patient treatment. Methods: This preliminary study carried out on single left-sided intact breast patient involved IM and S/C nodes. The IM and S/C node fields of the 5-Field 3DCRT photon-electron base plan were replaced by two proton fields. These two along with two Field-in-Field tangential photon fields were optimized for comparable dose coverage. The treatment plans were donemore » using Eclipse TPS for the total dose of 46Gy in 23 fractions with 95% of the prescription dose covering 95% of the RTOG PTV. The 3DCRT photon-electron and 4-Field photon-proton hybrid plans were compared for the PTV dose coverage as well as dose to OARs. Results: The overall RTOG PTV coverage for proton-hybrid and 3DCRT plan was comparable (95% of prescription dose covers 95% PTV volume). In proton-hybrid plan, 99% of IM volume received 100% dose whereas in 3DCRT only 77% received 100% dose. For S/C regions, 97% and 77% volume received 100% prescription dose in proton-hybrid and 3DCRT plans, respectively. The heart mean dose, V3Gy(%), and V5Gy(%) was 2.2Gy, 14.4%, 9.8% for proton-hybrid vs. 4.20 Gy, 21.5%, and 39% for 3DCRT plan, respectively. The maximum dose to the contralateral breast was 39.75Gy for proton-hybrid while 56.87Gy for 3DCRT plan. The mean total lung dose, V20Gy(%), and V30Gy(%) was 5.68Gy, 11.3%, 10.5% for proton-hybrid vs. 5.90Gy, 9.8%, 7.2% for 3DCRT, respectively. Conclusion: The protonhybrid plan can offer better dose coverage to the involved lymphatic tissues while lower doses to the heart and contralateral breast. More treatment plans are currently in progress before being implemented clinically.« less

First results of a phase I/II dose escalation trial in non-small cell lung cancer using three-dimensional conformal radiotherapy.

PubMed

Belderbos, José S A; De Jaeger, Katrien; Heemsbergen, Wilma D; Seppenwoolde, Yvette; Baas, Paul; Boersma, Liesbeth J; Lebesque, Joos V

2003-02-01

To evaluate the feasibility of dose escalation in non-small cell lung cancer (NSCLC) using three-dimensional conformal radiation therapy. The main eligibility criteria of the trial were: pathologically proven inoperable NSCLC, ECOG performance status or=grade 3 (SWOG), grade 3 early and grade 2 late esophageal toxicity or any other (RTOG) grade 3 or 4 complications). Fifty-five patients were included. Tumor stage was I/II in 47%, IIIA in 33% and IIIB in 20%. The majority of the patients received a dose of 74.3 Gy (n=17) or 81.0 Gy (n=23). Radiation pneumonitis occurred in seven patients: four patients developed a grade 2, two patients grade 3 and one patient a grade 4. Esophageal toxicity was mild. In 50 patients tumor response at 3 months follow-up was evaluable. In six patients a complete response was recorded, in 38 a partial response, five patients had stable disease and one patient experienced progressive disease. Only one patient developed an isolated failure in an uninvolved nodal area. So far the radiation dose was safely escalated to 87.8 Gy in group 1 (lowest rMLD), 81.0 Gy in groups 2 and 3 and 74.3 Gy in group 4. Three-dimensional conformal radiotherapy enables significant dose escalation in NSCLC. The maximum tolerable dose has not yet been reached in any risk group.

Phase III Comparison of Prophylactic Cranial Irradiation Versus Observation in Patients With Locally Advanced Non–Small-Cell Lung Cancer: Primary Analysis of Radiation Therapy Oncology Group Study RTOG 0214

PubMed Central

Gore, Elizabeth M.; Bae, Kyounghwa; Wong, Stuart J.; Sun, Alexander; Bonner, James A.; Schild, Steven E.; Gaspar, Laurie E.; Bogart, Jeffery A.; Werner-Wasik, Maria; Choy, Hak

2011-01-01

Purpose This study was conducted to determine if prophylactic cranial irradiation (PCI) improves survival in locally advanced non–small-cell lung cancer (LA-NSCLC). Patients and Methods Patients with stage III NSCLC without disease progression after treatment with surgery and/or radiation therapy (RT) with or without chemotherapy were eligible. Participants were stratified by stage (IIIA v IIIB), histology (nonsquamous v squamous), and therapy (surgery v none) and were randomly assigned to PCI or observation. PCI was delivered to 30 Gy in 15 fractions. The primary end point of the study was overall survival (OS). Secondary end points were disease-free survival (DFS), neurocognitive function (NCF), and quality of life. Kaplan-Meier and log-rank analyses were used for OS and DFS. The incidence of brain metastasis (BM) was evaluated with the logistic regression model. Results Overall, 356 patients were accrued of the targeted 1,058. The study was closed early because of slow accrual; 340 of the 356 patients were eligible. The 1-year OS (P = .86; 75.6% v 76.9% for PCI v observation) and 1-year DFS (P = .11; 56.4% v 51.2% for PCI v observation) were not significantly different. The hazard ratio for observation versus PCI was 1.03 (95% CI, 0.77 to 1.36). The 1-year rates of BM were significantly different (P = .004; 7.7% v 18.0% for PCI v observation). Patients in the observation arm were 2.52 times more likely to develop BM than those in the PCI arm (unadjusted odds ratio, 2.52; 95% CI, 1.32 to 4.80). Conclusion In patients with stage III disease without progression of disease after therapy, PCI decreased the rate of BM but did not improve OS or DFS. PMID:21135270

Radiation with or without Antiandrogen Therapy in Recurrent Prostate Cancer

PubMed Central

Shipley, W.U.; Seiferheld, W.; Lukka, H.R.; Major, P.P.; Heney, N.M.; Grignon, D.J.; Sartor, O.; Patel, M.P.; Bahary, J.-P.; Zietman, A.L.; Pisansky, T.M.; Zeitzer, K.L.; Lawton, C.A.F.; Feng, F.Y.; Lovett, R.D.; Balogh, A.G.; Souhami, L.; Rosenthal, S.A.; Kerlin, K.J.; Dignam, J.J.; Pugh, S.L.; Sandler, H.M.

2017-01-01

BACKGROUND Salvage radiation therapy is often necessary in men who have undergone radical pros-tatectomy and have evidence of prostate-cancer recurrence signaled by a persistently or recurrently elevated prostate-specific antigen (PSA) level. Whether antiandrogen therapy with radiation therapy will further improve cancer control and prolong overall survival is unknown. METHODS In a double-blind, placebo-controlled trial conducted from 1998 through 2003, we assigned 760 eligible patients who had undergone prostatectomy with a lymphadenectomy and had disease, as assessed on pathological testing, with a tumor stage of T2 (confined to the prostate but with a positive surgical margin) or T3 (with histologic extension beyond the prostatic capsule), no nodal involvement, and a detectable PSA level of 0.2 to 4.0 ng per milliliter to undergo radiation therapy and receive either antiandrogen therapy (24 months of bicalutamide at a dose of 150 mg daily) or daily placebo tablets during and after radiation therapy. The primary end point was the rate of overall survival. RESULTS The median follow-up among the surviving patients was 13 years. The actuarial rate of overall survival at 12 years was 76.3% in the bicalutamide group, as compared with 71.3% in the placebo group (hazard ratio for death, 0.77; 95% confidence interval, 0.59 to 0.99; P=0.04). The 12-year incidence of death from prostate cancer, as assessed by means of central review, was 5.8% in the bicalutamide group, as compared with 13.4% in the placebo group (P<0.001). The cumulative incidence of metastatic prostate cancer at 12 years was 14.5% in the bicalutamide group, as compared with 23.0% in the placebo group (P=0.005). The incidence of late adverse events associated with radiation therapy was similar in the two groups. Gynecomastia was recorded in 69.7% of the patients in the bicalutamide group, as compared with 10.9% of those in the placebo group (P<0.001). CONCLUSIONS The addition of 24 months of antiandrogen therapy with daily bicalutamide to salvage radiation therapy resulted in significantly higher rates of long-term overall survival and lower incidences of metastatic prostate cancer and death from prostate cancer than radiation therapy plus placebo. (Funded by the National Cancer Institute and AstraZeneca; RTOG 9601 ClinicalTrials.gov number, NCT00002874.) PMID:28146658

SU-E-T-370: Evaluating Plan Quality and Dose Delivery Accuracy of Tomotherapy SBRT Treatments for Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blake, S; Thwaites, D; Hansen, C

2015-06-15

Purpose: This study evaluated the plan quality and dose delivery accuracy of stereotactic body radiotherapy (SBRT) helical Tomotherapy (HT) treatments for lung cancer. Results were compared with those previously reported by our group for flattening filter (FF) and flattening filter free (FFF) VMAT treatments. This work forms part of an ongoing multicentre and multisystem planning and dosimetry audit on FFF beams for lung SBRT. Methods: CT datasets and DICOM RT structures delineating the target volume and organs at risk for 6 lung cancer patients were selected. Treatment plans were generated using the HT treatment planning system. Tumour locations were classifiedmore » as near rib, near bronchial tree or in free lung with prescribed doses of 48Gy/4fr, 50Gy/5fr and 54Gy/3fr respectively. Dose constraints were specified by a modified RTOG0915 protocol used for an Australian SBRT phase II trial. Plan quality was evaluated using mean PTV dose, PTV volume receiving 100% of the prescribed dose (V100%), target conformity (CI=VD100%/VPTV) and low dose spillage (LDS=VD50%/VPTV). Planned dose distributions were compared to those measured using an ArcCheck phantom. Delivery accuracy was evaluated using a gamma-index pass rate of 95% with 3% (of max dose) and 3mm criteria. Results: Treatment plans for all patients were clinically acceptable in terms of quality and accuracy of dose delivery. The following DVH metrics are reported as averages (SD) of all plans investigated: mean PTV dose was 115.3(2.4)% of prescription, V100% was 98.8(0.9)%, CI was 1.14(0.03) and LDS was 5.02(0.37). The plans had an average gamma-index passing rate of 99.3(1.3)%. Conclusion: The results reported in this study for HT agree within 1 SD to those previously published by our group for VMAT FF and FFF lung SBRT treatments. This suggests that HT delivers lung SBRT treatments of comparable quality and delivery accuracy as VMAT using both FF and FFF beams.« less

MO-D-BRC-01: Memorial Lecture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fraass, B.

Treatment planning is a central part of radiation therapy, including delineation in tumor volumes and critical organs, setting treatment goals of prescription doses to the tumor targets and tolerance doses to the critical organs, and finally generation of treatment plans to meet the treatment goals. National groups like RTOG have led the effort to standardize treatment goals of the prescription doses to the tumor targets and tolerance doses to the critical organs based on accumulated knowledge from decades of abundant clinical trial experience. The challenge for each clinical department is how to achieve or surpass these set goals within themore » time constraints of clinical practice. Using fifteen testing cases from different treatment sites such as head and neck, prostate with and without pelvic lymph nodes, SBRT spine, we will present clinically utility of advanced planning tools, including knowledge based, automatic based, and multiple criteria based tools that are clinically implemented. The objectives of this session are: Understand differences among these three advanced planning tools Provide clinical assessments on the utility of the advanced planning tools Discuss clinical challenges of treatment planning with large variations in tumor volumes and their relationships with adjacent critical organs. Ping Xia received research grant from Philips. Jackie Wu received research grant from Varian; P. Xia, Research support by Philips and Varian; Q. Wu, NIH, Varian Medical.« less

MO-D-BRC-03: Knowledge-Based Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Q.

Treatment planning is a central part of radiation therapy, including delineation in tumor volumes and critical organs, setting treatment goals of prescription doses to the tumor targets and tolerance doses to the critical organs, and finally generation of treatment plans to meet the treatment goals. National groups like RTOG have led the effort to standardize treatment goals of the prescription doses to the tumor targets and tolerance doses to the critical organs based on accumulated knowledge from decades of abundant clinical trial experience. The challenge for each clinical department is how to achieve or surpass these set goals within themore » time constraints of clinical practice. Using fifteen testing cases from different treatment sites such as head and neck, prostate with and without pelvic lymph nodes, SBRT spine, we will present clinically utility of advanced planning tools, including knowledge based, automatic based, and multiple criteria based tools that are clinically implemented. The objectives of this session are: Understand differences among these three advanced planning tools Provide clinical assessments on the utility of the advanced planning tools Discuss clinical challenges of treatment planning with large variations in tumor volumes and their relationships with adjacent critical organs. Ping Xia received research grant from Philips. Jackie Wu received research grant from Varian; P. Xia, Research support by Philips and Varian; Q. Wu, NIH, Varian Medical.« less

MO-D-BRC-04: Multiple-Criteria Optimization Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Donaghue, J.

Treatment planning is a central part of radiation therapy, including delineation in tumor volumes and critical organs, setting treatment goals of prescription doses to the tumor targets and tolerance doses to the critical organs, and finally generation of treatment plans to meet the treatment goals. National groups like RTOG have led the effort to standardize treatment goals of the prescription doses to the tumor targets and tolerance doses to the critical organs based on accumulated knowledge from decades of abundant clinical trial experience. The challenge for each clinical department is how to achieve or surpass these set goals within themore » time constraints of clinical practice. Using fifteen testing cases from different treatment sites such as head and neck, prostate with and without pelvic lymph nodes, SBRT spine, we will present clinically utility of advanced planning tools, including knowledge based, automatic based, and multiple criteria based tools that are clinically implemented. The objectives of this session are: Understand differences among these three advanced planning tools Provide clinical assessments on the utility of the advanced planning tools Discuss clinical challenges of treatment planning with large variations in tumor volumes and their relationships with adjacent critical organs. Ping Xia received research grant from Philips. Jackie Wu received research grant from Varian; P. Xia, Research support by Philips and Varian; Q. Wu, NIH, Varian Medical.« less

MO-D-BRC-00: In Memoriam of Jan Van De Geijn: Knowledge-Based Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

Treatment planning is a central part of radiation therapy, including delineation in tumor volumes and critical organs, setting treatment goals of prescription doses to the tumor targets and tolerance doses to the critical organs, and finally generation of treatment plans to meet the treatment goals. National groups like RTOG have led the effort to standardize treatment goals of the prescription doses to the tumor targets and tolerance doses to the critical organs based on accumulated knowledge from decades of abundant clinical trial experience. The challenge for each clinical department is how to achieve or surpass these set goals within themore » time constraints of clinical practice. Using fifteen testing cases from different treatment sites such as head and neck, prostate with and without pelvic lymph nodes, SBRT spine, we will present clinically utility of advanced planning tools, including knowledge based, automatic based, and multiple criteria based tools that are clinically implemented. The objectives of this session are: Understand differences among these three advanced planning tools Provide clinical assessments on the utility of the advanced planning tools Discuss clinical challenges of treatment planning with large variations in tumor volumes and their relationships with adjacent critical organs. Ping Xia received research grant from Philips. Jackie Wu received research grant from Varian; P. Xia, Research support by Philips and Varian; Q. Wu, NIH, Varian Medical.« less

MO-D-BRC-02: Auto-Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xia, P.

Treatment planning is a central part of radiation therapy, including delineation in tumor volumes and critical organs, setting treatment goals of prescription doses to the tumor targets and tolerance doses to the critical organs, and finally generation of treatment plans to meet the treatment goals. National groups like RTOG have led the effort to standardize treatment goals of the prescription doses to the tumor targets and tolerance doses to the critical organs based on accumulated knowledge from decades of abundant clinical trial experience. The challenge for each clinical department is how to achieve or surpass these set goals within themore » time constraints of clinical practice. Using fifteen testing cases from different treatment sites such as head and neck, prostate with and without pelvic lymph nodes, SBRT spine, we will present clinically utility of advanced planning tools, including knowledge based, automatic based, and multiple criteria based tools that are clinically implemented. The objectives of this session are: Understand differences among these three advanced planning tools Provide clinical assessments on the utility of the advanced planning tools Discuss clinical challenges of treatment planning with large variations in tumor volumes and their relationships with adjacent critical organs. Ping Xia received research grant from Philips. Jackie Wu received research grant from Varian; P. Xia, Research support by Philips and Varian; Q. Wu, NIH, Varian Medical.« less

On the use of volumetric-modulated arc therapy for single-fraction thoracic vertebral metastases stereotactic body radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pokhrel, Damodar, E-mail: damodar.pokhrel@uky.edu; Sood, Sumit; McClinton, Christopher

To retrospectively evaluate quality, efficiency, and delivery accuracy of volumetric-modulated arc therapy (VMAT) plans for single-fraction treatment of thoracic vertebral metastases using image-guided stereotactic body radiosurgery (SBRS) after RTOG 0631 dosimetric compliance criteria. After obtaining credentialing for MD Anderson spine phantom irradiation validation, 10 previously treated patients with thoracic vertebral metastases with noncoplanar hybrid arcs using 1 to 2 3D-conformal partial arcs plus 7 to 9 intensity-modulated radiation therapy beams were retrospectively re-optimized with VMAT using 3 full coplanar arcs. Tumors were located between T2 and T12. Contrast-enhanced T1/T2-weighted magnetic resonance images were coregistered with planning computed tomography and planningmore » target volumes (PTV) were between 14.4 and 230.1 cc (median = 38.0 cc). Prescription dose was 16 Gy in 1 fraction with 6 MV beams at Novalis-TX linear accelerator consisting of micro multileaf collimators. Each plan was assessed for target coverage using conformality index, the conformation number, the ratio of the volume receiving 50% of the prescription dose over PTV, R50%, homogeneity index (HI), and PTV-1600 coverage per RTOG 0631 requirements. Organs-at-risk doses were evaluated for maximum doses to spinal cord (D{sub 0.03} {sub cc}, D{sub 0.35} {sub cc}), partial spinal cord (D{sub 10%}), esophagus (D{sub 0.03} {sub cc} and D{sub 5} {sub cc}), heart (D{sub 0.03} {sub cc} and D{sub 15} {sub cc}), and lung (V{sub 5}, V{sub 10}, and maximum dose to 1000 cc of lung). Dose delivery efficiency and accuracy of each VMAT-SBRS plan were assessed using quality assurance (QA) plan on MapCHECK device. Total beam-on time was recorded during QA procedure, and a clinical gamma index (2%/2 mm and 3%/3 mm) was used to compare agreement between planned and measured doses. All 10 VMAT-SBRS plans met RTOG 0631 dosimetric requirements for PTV coverage. The plans demonstrated highly conformal and homogenous coverage of the vertebral PTV with mean HI, conformality index, conformation number, and R{sub 50%} values of 0.13 ± 0.03 (range: 0.09 to 0.18), 1.03 ± 0.04 (range: 0.98 to 1.09), 0.81 ± 0.06 (range: 0.72 to 0.89), and 4.2 ± 0.94 (range: 2.7 to 5.4), respectively. All 10 patients met protocol guidelines with maximum dose to spinal cord (average: 8.83 ± 1.9 Gy, range: 5.9 to 10.9 Gy); dose to 0.35 cc of spinal cord (average: 7.62 ± 1.7 Gy, range: 5.4 to 9.6 Gy); and dose to 10% of partial spinal cord (average 6.31 ± 1.5 Gy, range: 3.5 to 8.5 Gy) less than 14, 10, and 10 Gy, respectively. For all 10 patients, the maximum dose to esophagus (average: 9.41 ± 4.3 Gy, range: 1.5 to 14.9 Gy) and dose to 5 cc of esophagus (average: 7.43 ± 3.8 Gy, range: 1.1 to 11.8 Gy) were kept less than protocol requirements 16 Gy and 11.9 Gy, respectively. In a similar manner, all 10 patients met protocol compliance criteria with maximum dose to heart (average: 4.62 ± 3.5 Gy, range: 1.3 to 10.2 Gy) and dose to 15 cc of heart (average: 2.23 ± 1.8 Gy, range: 0.3 to 5.6 Gy) less than 22 and 16 Gy, respectively. The dose to the lung was retained much lower than protocol guidelines for all 10 patients. The total number of monitor units was, on average, 6919 ± 1187. The average beam-on time was 11.5 ± 2.0 minutes. The VMAT plans demonstrated dose delivery accuracy of 95.8 ± 0.7%, on average, for clinical gamma passing rate with 2%/2 mm criteria and 98.3 ± 0.8%, on average, with 3%/3 mm criteria. All VMAT-SBRS plans were considered clinically acceptable per RTOG 0631 dosimetric compliance criteria. VMAT planning provided highly conformal and homogenous dose distributions for the lower-dose vertebral PTV and the spinal cord as well as organs-at-risk such as esophagus, heart, and lung. Higher QA pass rates and shorter beam-on time suggest that VMAT-SBRS is a clinically feasible, fast, and effective treatment option for patients with thoracic vertebral metastases.« less

Single‐fraction spine SBRT end‐to‐end testing on TomoTherapy, Vero, TrueBeam, and CyberKnife treatment platforms using a novel anthropomorphic phantom

PubMed Central

Kaufman, Isaac; Powell, Rachel; Pandya, Shalini; Somnay, Archana; Bossenberger, Todd; Ramirez, Ezequiel; Reynolds, Robert; Solberg, Timothy; Burmeister, Jay

2015-01-01

Spine SBRT involves the delivery of very high doses of radiation to targets adjacent to the spinal cord and is most commonly delivered in a single fraction. Highly conformal planning and accurate delivery of such plans is imperative for successful treatment without catastrophic adverse effects. End–to‐end testing is an important practice for evaluating the entire treatment process from simulation through treatment delivery. We performed end‐to‐end testing for a set of representative spine targets planned and delivered using four different treatment planning systems (TPSs) and delivery systems to evaluate the various capabilities of each. An anthropomorphic E2E SBRT phantom was simulated and treated on each system to evaluate agreement between measured and calculated doses. The phantom accepts ion chambers in the thoracic region and radiochromic film in the lumbar region. Four representative targets were developed within each region (thoracic and lumbar) to represent different presentations of spinal metastases and planned according to RTOG 0631 constraints. Plans were created using the TomoTherapy TPS for delivery using the Hi·Art system, the iPlan TPS for delivery using the Vero system, the Eclipse TPS for delivery using the TrueBeam system in both flattened and flattening filter free (FFF), and the MultiPlan TPS for delivery using the CyberKnife system. Delivered doses were measured using a 0.007 cm3 ion chamber in the thoracic region and EBT3 GAFCHROMIC film in the lumbar region. Films were scanned and analyzed using an Epson Expression 10000XL flatbed scanner in conjunction with FilmQAPro2013. All treatment platforms met all dose constraints required by RTOG 0631. Ion chamber measurements in the thoracic targets delivered an overall average difference of 1.5%. Specifically, measurements agreed with the TPS to within 2.2%, 3.2%, 1.4%, 3.1%, and 3.0% for all three measureable cases on TomoTherapy, Vero, TrueBeam (FFF), TrueBeam (flattened), and CyberKnife, respectively. Film measurements for the lumbar targets resulted in average global gamma index passing rates of 100% at 3%/3 mm, 96.9% at 2%/2 mm, and 61.8% at 1%/1 mm, with a 10% minimum threshold for all plans on all platforms. Local gamma analysis was also performed with similar results. While gamma passing rates were consistently accurate across all platforms through 2%/2 mm, treatment beam‐on delivery times varied greatly between each platform with TrueBeam FFF being shortest, averaging 4.4 min, TrueBeam using flattened beam at 9.5 min, TomoTherapy at 30.5 min, Vero at 19 min, and CyberKnife at 46.0 min. In spite of the complexity of the representative targets and their proximity to the spinal cord, all treatment platforms were able to create plans meeting all RTOG 0631 dose constraints and produced exceptional agreement between calculated and measured doses. However, there were differences in the plan characteristics and significant differences in the beam‐on delivery time between platforms. Thus, clinical judgment is required for each particular case to determine most appropriate treatment planning/delivery platform. PACS number: 87.53.Ly PMID:25679169

Introduction of hypermatrix and operator notation into a discrete mathematics simulation model of malignant tumour response to therapeutic schemes in vivo. Some operator properties.

PubMed

Stamatakos, Georgios S; Dionysiou, Dimitra D

2009-10-21

The tremendous rate of accumulation of experimental and clinical knowledge pertaining to cancer dictates the development of a theoretical framework for the meaningful integration of such knowledge at all levels of biocomplexity. In this context our research group has developed and partly validated a number of spatiotemporal simulation models of in vivo tumour growth and in particular tumour response to several therapeutic schemes. Most of the modeling modules have been based on discrete mathematics and therefore have been formulated in terms of rather complex algorithms (e.g. in pseudocode and actual computer code). However, such lengthy algorithmic descriptions, although sufficient from the mathematical point of view, may render it difficult for an interested reader to readily identify the sequence of the very basic simulation operations that lie at the heart of the entire model. In order to both alleviate this problem and at the same time provide a bridge to symbolic mathematics, we propose the introduction of the notion of hypermatrix in conjunction with that of a discrete operator into the already developed models. Using a radiotherapy response simulation example we demonstrate how the entire model can be considered as the sequential application of a number of discrete operators to a hypermatrix corresponding to the dynamics of the anatomic area of interest. Subsequently, we investigate the operators' commutativity and outline the "summarize and jump" strategy aiming at efficiently and realistically address multilevel biological problems such as cancer. In order to clarify the actual effect of the composite discrete operator we present further simulation results which are in agreement with the outcome of the clinical study RTOG 83-02, thus strengthening the reliability of the model developed.

Clinical and dosimetric factors of radiation-induced esophageal injury: radiation-induced esophageal toxicity.

PubMed

Qiao, Wen-Bo; Zhao, Yan-Hui; Zhao, Yan-Bin; Wang, Rui-Zhi

2005-05-07

To analyze the clinical and dosimetric predictive factors for radiation-induced esophageal injury in patients with non-small-cell lung cancer (NSCLC) during three-dimensional conformal radiotherapy (3D-CRT). We retrospectively analyzed 208 consecutive patients (146 men and 62 women) with NSCLC treated with 3D-CRT. The median age of the patients was 64 years (range 35-87 years). The clinical and treatment parameters including gender, age, performance status, sequential chemotherapy, concurrent chemotherapy, presence of carinal or subcarinal lymph nodes, pretreatment weight loss, mean dose to the entire esophagus, maximal point dose to the esophagus, and percentage of volume of esophagus receiving >55 Gy were studied. Clinical and dosimetric factors for radiation-induced acute and late grade 3-5 esophageal injury were analyzed according to Radiation Therapy Oncology Group (RTOG) criteria. Twenty-five (12%) of the two hundred and eight patients developed acute or late grade 3-5 esophageal injury. Among them, nine patients had both acute and late grade 3-5 esophageal injury, two died of late esophageal perforation. Concurrent chemotherapy and maximal point dose to the esophagus > or =60 Gy were significantly associated with the risk of grade 3-5 esophageal injury. Fifty-four (26%) of the two hundred and eight patients received concurrent chemotherapy. Among them, 25 (46%) developed grade 3-5 esophageal injury (P = 0.0001<0.01). However, no grade 3-5 esophageal injury occurred in patients who received a maximal point dose to the esophagus <60 Gy (P = 0.0001<0.01). Concurrent chemotherapy and the maximal esophageal point dose > or =60 Gy are significantly associated with the risk of grade 3-5 esophageal injury in patients with NSCLC treated with 3D-CRT.

Immunotherapy for high-grade glioma.

PubMed

Dixit, Sanjay

2014-05-01

4th Quadrennial Meeting of the World Federation of Neuro-Oncology in conjunction with the 18th Annual Meeting of the Society for Neuro-Oncology, San Francisco, CA, USA, 21-24 November 2013. Aside from temozolomide, there has been no major breakthrough for decades to improve outcome for high-grade glioma. Bevacizumab failed to show a survival advantage in two large studies - AVaglio and RTOG-0825 - and no other novel chemotherapy agents seem to be appearing on the horizon for this universally fatal disease. Consequently, the neuro-oncology fraternity is turning to immunotherapy. This became apparent in this meeting, considering a number of delegates focused their attention to presentations on immunotherapy. The ReACT study demonstrated the safety and efficacy of the combination of a promising peptide vaccine, rindopepimut, and bevacizumab with longer survival seen in patients with a higher antibody titer. Several presentations reassured that dendritic cell-based immunotherapy is safe and can generate a lasting immune response. Employing gene therapy, increased intratumor 5-fluorouracil chemotherapy concentration can be achieved using TOCA 511, and temozolomide-resistant transgenic lymphocytes could be produced through retroviral coding. Blocking immune checkpoints PDL-01, CTLA-4 and indoleamine 2,3-dioxygenase through monoclonal antibodies appears promising.

68Ga-PSMA-11 PET/CT Mapping of Prostate Cancer Biochemical Recurrence After Radical Prostatectomy in 270 Patients with a PSA Level of Less Than 1.0 ng/mL: Impact on Salvage Radiotherapy Planning.

PubMed

Calais, Jeremie; Czernin, Johannes; Cao, Minsong; Kishan, Amar U; Hegde, John V; Shaverdian, Narek; Sandler, Kiri; Chu, Fang-I; King, Chris R; Steinberg, Michael L; Rauscher, Isabel; Schmidt-Hegemann, Nina-Sophie; Poeppel, Thorsten; Hetkamp, Philipp; Ceci, Francesco; Herrmann, Ken; Fendler, Wolfgang P; Eiber, Matthias; Nickols, Nicholas G

2018-02-01

Target volume delineations for prostate cancer (PCa) salvage radiotherapy (SRT) after radical prostatectomy are usually drawn in the absence of visibly recurrent disease. 68 Ga-labeled prostate-specific membrane antigen (PSMA-11) PET/CT detects recurrent PCa with sensitivity superior to standard-of-care imaging at serum prostate-specific antigen (PSA) values low enough to affect target volume delineations for routine SRT. Our objective was to map the recurrence pattern of PCa early biochemical recurrence (BCR) after radical prostatectomy with 68 Ga-PSMA-11 PET/CT in patients with serum PSA levels of less than 1 ng/mL, determine how often consensus clinical target volumes (CTVs) based on the Radiation Therapy Oncology Group (RTOG) guidelines cover 68 Ga-PSMA-11 PET/CT-defined disease, and assess the potential impact of 68 Ga-PSMA-11 PET/CT on SRT. Methods: This was a post hoc analysis of an intention-to-treat population of 270 patients who underwent 68 Ga-PSMA-11 PET/CT at 4 institutions for BCR after prostatectomy without prior radiotherapy at a PSA level of less than 1 ng/mL. RTOG consensus CTVs that included both the prostate bed and the pelvic lymph nodes were contoured on the CT dataset of the PET/CT image by a radiation oncologist masked to the PET component. 68 Ga-PSMA-11 PET/CT images were analyzed by a nuclear medicine physician. 68 Ga-PSMA-11-positive lesions not covered by planning volumes based on the consensus CTVs were considered to have a potential major impact on treatment planning. Results: The median PSA level at the time of 68 Ga-PSMA-11 PET/CT was 0.48 ng/mL (range, 0.03-1 ng/mL). One hundred thirty-two of 270 patients (49%) had a positive 68 Ga-PSMA-11 PET/CT result. Fifty-two of 270 (19%) had at least one PSMA-11-positive lesion not covered by the consensus CTVs. Thirty-three of 270 (12%) had extrapelvic PSMA-11-positive lesions, and 19 of 270 (7%) had PSMA-11-positive lesions within the pelvis but not covered by the consensus CTVs. The 2 most common 68 Ga-PSMA-11-positive lesion locations outside the consensus CTVs were bone (23/52, 44%) and perirectal lymph nodes (16/52, 31%). Conclusion: Post hoc analysis of 68 Ga-PSMA-11 PET/CT implied a major impact on SRT planning in 52 of 270 patients (19%) with PCa early BCR (PSA < 1.0 ng/mL). This finding justifies a randomized imaging trial of SRT with or without 68 Ga-PSMA-11 PET/CT investigating its potential benefit on clinical outcome. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

PSA Response After Short-Term Hormonal Therapy Plus External Beam Radiotherapy and Outcome in Patients Treated on RTOG 9413

PubMed Central

Cury, Fabio L.; Hunt, Daniel; Roach, Mack; Shipley, William; Gore, Elizabeht; Hsu, I-Chow; Krisch, Robert E.; Seider, Michael J.; Sandler, Howard; Lawton, Colleen

2013-01-01

Purpose Assess the impact of PSA-complete response (PSA-CR), measured at the end of external beam radiotherapy (EBRT) and short-term hormonal therapy (STHT), on treatment outcomes. Design The Phase III RTOG-9413 trial had as part of its original protocol the assessment of PSA-CR, i.e. PSA≤0.3ng/ml, at the end of STHT as a secondary endpoint. STHT consisted of flutamide plus an LHRH-agonist for 4 months. Kaplan-Meier method was used to estimate overall survival (OS) and disease-free survival (DFS). Cumulative incidence was used to estimate biochemical failure (BF), distant metastasis (DM), and disease-specific survival (DSS). Univariate and multivariate analyses were performed to correlate PSA-CR after STHT with all endpoints, and the following variables were considered for analysis: PSA at baseline, Gleason score, treatment arm, age, and baseline testosterone. Phoenix-consensus was used to define PSA failure. Results For 1070 evaluable patients, the median PSA at the end of STHT was 0.2ng/mL. A total of 744 patients (70%) had PSA-CR. With median follow-up of 7.2 years, failure to obtain PSA-CR was significantly associated with worse DSS (p=0.0003; hazard ratio, 2.03[95%CI, 1.38–2.97]) and DFS (p=0.003; 1.28[1.09–1.50]), as well as with a higher incidence of DM (p=0.0002; 1.92[1.37–2.69]) and BF (p<0.0001; 1.57[1.29–1.91]). The other factors associated with worse DSS were Gleason score 8–10 (p=0.0002; 3.06[1.71–5.47]) and PSA>20ng/mL (p=0.04; 1.55[1.02–2.30]). Conclusion Failure to obtain a post STHT and EBRT PSA-CR (≤0.3ng/mL) appears to be an independent predictor of unfavorable outcomes, and may help identify patients who could benefit from the addition of long-term androgen ablation. PMID:23504930

Accelerated partial breast irradiation using 3D conformal radiotherapy: toxicity and cosmetic outcome.

PubMed

Gatti, M; Ponzone, R; Bresciani, S; Panaia, R; Kubatzki, F; Maggiorotto, F; Di Virgilio, M R; Salatino, A; Baiotto, B; Montemurro, F; Stasi, M; Gabriele, P

2013-12-01

The aim of this paper is to analyze the incidence of acute and late toxicity and cosmetic outcome in breast cancer patients submitted to breast conserving surgery and three-dimensional conformal radiotherapy (3D-CRT) to deliver accelerated partial breast irradiation (APBI). 84 patients were treated with 3D-CRT for APBI. This technique was assessed in patients with low risk stage I breast cancer enrolled from September 2005 to July 2011. The prescribed dose was 34/38.5 Gy delivered in 10 fractions twice daily over 5 consecutive days. Four to five no-coplanar 6 MV beams were used. In all CT scans Gross Tumor Volume (GTV) was defined around the surgical clips. A 1.5 cm margin was added by defining a Clinical Target Volume (CTV). A margin of 1 cm was added to CTV to define the planning target volume (PTV). The dose-volume constraints were followed in accordance with the NSABP/RTOG protocol. Late toxicity was evaluated according to the RTOG grading schema. The cosmetic assessment was performed using the Harvard scale. Median patient age was 66 years (range 51-87). Median follow-up was 36.5 months (range 13-83). The overall incidence of acute skin toxicities was 46.4% for grade 1 and 1% for grade 2. The incidence of late toxicity was 16.7% for grade 1, 2.4% for grade 2 and 3.6% for grade 3. No grade 4 toxicity was observed. The most pronounced grade 2 late toxicity was telangiectasia, developed in three patients. Cosmetics results were excellent for 52%, good for 42%, fair for 5% and poor for 1% of the patients. There was no statistical correlation between toxicity rates and prescribed doses (p = 0.33) or irradiated volume (p = 0.45). APBI using 3D-CRT is technically feasible with very low acute and late toxicity. Long-term results are needed to assess its efficacy in reducing the incidence of breast relapse. Copyright © 2013 Elsevier Ltd. All rights reserved.

Does Response to Induction Chemotherapy Predict Survival for Locally Advanced Non-Small-Cell Lung Cancer? Secondary Analysis of RTOG 8804/8808

DOE Office of Scientific and Technical Information (OSTI.GOV)

McAleer, Mary Frances, E-mail: mfmcalee@mdanderson.or; Moughan, Jennifer M.S.; Byhardt, Roger W.

2010-03-01

Purpose: Induction chemotherapy (ICT) improves survival compared with radiotherapy (RT) alone in locally advanced non-small-cell lung cancer (LANSCLC) patients with good prognostic factors. Concurrent chemoradiotherapy (CCRT) is superior to ICT followed by RT. The question arises whether ICT response predicts the outcome of patients subsequently treated with CCRT or RT. Methods and Materials: Between 1988 and 1992, 194 LANSCLC patients were treated prospectively with ICT (two cycles of vinblastine and cisplatin) and then CCRT (cisplatin plus 63 Gy for 7 weeks) in the Radiation Therapy Oncology Group 8804 trial (n = 30) or ICT and then RT (60 Gy/6 wk)more » on Radiation Therapy Oncology Group 8808 trial (n = 164). Of the 194 patients, 183 were evaluable and 141 had undergone a postinduction assessment. The overall survival (OS) of those with complete remission (CR) or partial remission (PR) was compared with that of patients with stable disease (SD) or progressive disease (PD) after ICT. Results: Of the 141 patients, 6, 30, 99, and 6 had CR, PR, SD, and PD, respectively. The log-rank test showed a significant difference (p <0.0001) in OS when the response groups were compared (CR/PR vs. SD/PD). On univariate and multivariate analyses, a trend was seen toward a response to ICT with OS (p = 0.097 and p = 0.06, respectively). A squamous histologic type was associated with worse OS on univariate and multivariate analyses (p = 0.031 and p = 0.018, respectively). SD/PD plus a squamous histologic type had a hazard ratio of 2.25 vs. CR/PR plus a nonsquamous histologic type (p = 0.007) on covariate analysis. Conclusion: The response to ICT was associated with a significant survival difference when the response groups were compared. A response to ICT showed a trend toward, but was not predictive of, improved OS in LANSCLC patients. Patients with SD/PD after ICT and a squamous histologic type had the poorest OS. These data suggest that patients with squamous LANSCLC might benefit from immediate RT or CCRT.« less

Prognostic Value of Abnormal p53 Expression in Locally Advanced Prostate Cancer Treated With Androgen Deprivation and Radiotherapy: A Study Based on RTOG 9202

DOE Office of Scientific and Technical Information (OSTI.GOV)

Che Mingxin; DeSilvio, Michelle; Pollack, Alan

2007-11-15

Purpose: The goal of this study was to verify the significance of p53 as a prognostic factor in Radiation Therapy Oncology Group 9202, which compared short-term androgen deprivation (STAD) with radiation therapy (RT) to long-term androgen deprivation + RT in men with locally advanced prostate cancer (Pca). Methods and Materials: Tumor tissue was sufficient for p53 analysis in 777 cases. p53 status was determined by immunohistochemistry. Abnormal p53 expression was defined as 20% or more tumor cells with positive nuclei. Univariate and multivariate Cox proportional hazards models were used to evaluate the relationships of p53 status to patient outcomes. Results:more » Abnormal p53 was detected in 168 of 777 (21.6%) cases, and was significantly associated with cause-specific mortality (adjusted hazard ratio [HR] = 1.89; 95% confidence interval (CI) 1.14 - 3.14; p = 0.014) and distant metastasis (adjusted HR = 1.72; 95% CI 1.13-2.62; p = 0.013). When patients were divided into subgroups according to assigned treatment, only the subgroup of patients who underwent STAD + RT showed significant correlation between p53 status and cause-specific mortality (adjusted HR = 2.43; 95% CI = 1.32-4.49; p = 0.0044). When patients were divided into subgroups according to p53 status, only the subgroup of patients with abnormal p53 showed significant association between assigned treatment and cause-specific mortality (adjusted HR = 3.81; 95% CI 1.40-10.37; p = 0.0087). Conclusions: Abnormal p53 is a significant prognostic factor for patients with prostate cancer who undergo short-term androgen deprivation and radiotherapy. Long-term androgen deprivation may significantly improve the cause-specific survival for those with abnormal p53.« less

Dosimetric comparison of peripheral NSCLC SBRT using Acuros XB and AAA calculation algorithms.

PubMed

Ong, Chloe C H; Ang, Khong Wei; Soh, Roger C X; Tin, Kah Ming; Yap, Jerome H H; Lee, James C L; Bragg, Christopher M

2017-01-01

There is a concern for dose calculation in highly heterogenous environments such as the thorax region. This study compares the quality of treatment plans of peripheral non-small cell lung cancer (NSCLC) stereotactic body radiation therapy (SBRT) using 2 calculation algorithms, namely, Eclipse Anisotropic Analytical Algorithm (AAA) and Acuros External Beam (AXB), for 3-dimensional conformal radiation therapy (3DCRT) and volumetric-modulated arc therapy (VMAT). Four-dimensional computed tomography (4DCT) data from 20 anonymized patients were studied using Varian Eclipse planning system, AXB, and AAA version 10.0.28. A 3DCRT plan and a VMAT plan were generated using AAA and AXB with constant plan parameters for each patient. The prescription and dose constraints were benchmarked against Radiation Therapy Oncology Group (RTOG) 0915 protocol. Planning parameters of the plan were compared statistically using Mann-Whitney U tests. Results showed that 3DCRT and VMAT plans have a lower target coverage up to 8% when calculated using AXB as compared with AAA. The conformity index (CI) for AXB plans was 4.7% lower than AAA plans, but was closer to unity, which indicated better target conformity. AXB produced plans with global maximum doses which were, on average, 2% hotter than AAA plans. Both 3DCRT and VMAT plans were able to achieve D95%. VMAT plans were shown to be more conformal (CI = 1.01) and were at least 3.2% and 1.5% lower in terms of PTV maximum and mean dose, respectively. There was no statistically significant difference for doses received by organs at risk (OARs) regardless of calculation algorithms and treatment techniques. In general, the difference in tissue modeling for AXB and AAA algorithm is responsible for the dose distribution between the AXB and the AAA algorithms. The AXB VMAT plans could be used to benefit patients receiving peripheral NSCLC SBRT. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Genetic landscape of extreme responders with anaplastic oligodendroglioma.

PubMed

Holdhoff, Matthias; Cairncross, Gregory J; Kollmeyer, Thomas M; Zhang, Ming; Zhang, Peixin; Mehta, Minesh P; Werner-Wasik, Maria; Souhami, Luis; Bahary, Jean-Paul; Kwok, Young; Hartford, Alan C; Chakravarti, Arnab; Yegnasubramanian, Srinivasan; Vogelstein, Bert; Papadopoulos, Nickolas; Kinzler, Kenneth; Jenkins, Robert B; Bettegowda, Chetan

2017-05-30

The NRG Oncology RTOG 9402 trial showed significant survival benefit in patients with 1p/19q co-deleted anaplastic oligodendrogliomas (AO) who received both radiation (RT) and chemotherapy (PCV regimen) versus RT alone. Substantial separation of the survival curves was only seen after 7.3 years. We aimed to determine whether there are specific genetic alterations that distinguish co-deleted AO patients who benefit from the addition of PCV from those who do not. We performed whole exome sequencing on matched tumor and normal DNA from all available short-term (STS) and long-term survivors (LTS) who received RT+PCV. hTERT status and rs55705857 genotypes (G-allele) were analyzed in both cohorts. Six STS (survival of <7.3y) and 7 LTS (survival of ≥7.3y and no progression) had sufficient material for analysis. There was no significant difference between the groups regarding age, performance status and extent of resection. On average, STS had 7 and LTS 4 mutations. Most common mutations in STS vs. LTS were: IDH1 (67 vs. 86%), CIC (50 vs. 71%) and FUBP1 (17 vs. 71%). The hTERT promoter was mutated in 83% STS and 86% LTS. Genotyping of rs55705857 showed a higher prevalence of G allele carriers in LTS than STS (43 vs. 17%). These findings confirm that IDH, CIC, FUBP1 mutations and rs55705857 genotype are common in AO. No distinct genetic signature was identified to differentiate STS and LTS.

NCI–RTOG Translational Program Strategic Guidelines for the Early-Stage Development of Radiosensitizers

PubMed Central

2013-01-01

The addition of chemotherapeutic agents to ionizing radiation has improved survival in many malignancies. Cure rates may be further improved by adding novel targeted agents to current radiotherapy or radiochemotherapy regimens. Despite promising laboratory data, progress in the clinical development of new drugs with radiation has been limited. To define and address the problems involved, a collaborative effort between individuals within the translational research program of the Radiation Oncology Therapy Group and the National Cancer Institute was established. We discerned challenges to drug development with radiation including: 1) the limited relevance of preclinical work, 2) the pharmaceutical industry’s diminished interest, and 3) the important individual skills and institutional commitments required to ensure a successful program. The differences between early-phase trial designs with and without radiation are noted as substantial. The traditional endpoints for early-phase clinical trials—acute toxicity and maximum-tolerated dose—are of limited value when combining targeted agents with radiation. Furthermore, response rate is not a useful surrogate marker of activity in radiation combination trials.Consequently, a risk-stratified model for drug-dose escalation with radiation is proposed, based upon the known and estimated adverse effects. The guidelines discuss new clinical trial designs, such as the time-to-event continual reassessment method design for phase I trials, randomized phase II “screening” trials, and the use of surrogate endpoints, such as pathological response. It is hoped that by providing a clear pathway, this article will accelerate the rate of drug development with radiation. PMID:23231975

Older Age Predicts Decreased Metastasis and Prostate Cancer-Specific Death for Men Treated With Radiation Therapy: Meta-Analysis of Radiation Therapy Oncology Group Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamstra, Daniel A., E-mail: dhamm@umich.edu; Bae, Kyounghwa; Pilepich, Miljenko V.

2011-12-01

Purpose: The impact of age on prostate cancer (PCa) outcome has been controversial; therefore, we analyzed the effect of age on overall survival (OS), distant metastasis, prostate cancer-specific death (PCSD), and nonprostate cancer death (NPCD) on patients with locally advanced PCa. Methods and Materials: Patients who participated in four Radiation Therapy Oncology Group (RTOG) phase III trials, 8531, 8610, 9202, and 9413, were studied. Cox proportional hazards regression was used for OS analysis, and cumulative events analysis with Fine and Gray's regression was used for analyses of metastasis, PCSD, and NPCD. Results: Median follow-up of 4,128 patients with median agemore » of 70 (range, 43-88 years) was 7.3 years. Most patients had high-risk disease: cT3 to cT4 (54%) and Gleason scores (GS) of 7 (45%) and 8 to 10 (27%). Older age ({<=}70 vs. >70 years) predicted for decreased OS (10-year rate, 55% vs. 41%, respectively; p < 0.0001) and increased NPCD (10-year rate, 28% vs. 46%, respectively; p < 0.0001) but decreased metastasis (10-year rate, 27% vs. 20%, respectively; p < 0.0001) and PCSD (10-year rate, 18% vs. 14%, respectively; p < 0.0001). To account for competing risks, outcomes were analyzed in 2-year intervals, and age-dependent differences in metastasis and PCSD persisted, even in the earliest time periods. When adjusted for other covariates, an age of >70 years remained associated with decreased OS (hazard ratio [HR], 1.56 [95% confidence interval [CI], 1.43-1.70] p < 0.0001) but with decreased metastasis (HR, 0.72 [95% CI, 0.63-0.83] p < 0.0001) and PCSD (HR, 0.78 [95% CI, 0.66-0.92] p < 0.0001). Finally, the impact of the duration of androgen deprivation therapy as a function of age was evaluated. Conclusions: These data support less aggressive PCa in older men, independent of other clinical features. While the biological underpinning of this finding remains unknown, stratification by age in future trials appears to be warranted.« less

SU-E-T-466: Dosimetric Assessment of the Salivary Glands in Head and Neck Tumour Patients Treated with Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peixoto, Xavier C; Costa, Ferreira B; Khouri, L

2014-06-01

Purpose: To estimate the correlation between different dosimetric indices and the clinical outcome, which was recorded at different time points after the treatment, regarding the structure of salivary glands in head and neck cancer radiotherapy. Methods: 218 salivary glands from patients with head and neck tumours treated at IPOCFG from 2007 to 2013 were included in this study. The follow up of those patients consisted on weekly medical visits during the treatment that take about seven weeks. After that the patients had consults every three months. Treatment complications were graded using the RTOG/EORTC guidelines. The response of the salivary glandsmore » (both parotids, oral cavity and both submandibular glands) was analyzed for six time periods: 7th week, 3rd, 7th, 12th, 18th and 24th months after the start of the radiotherapy. The total dose distributions, converted to a fractionation scheme of 2Gy fractional doses, were used to calculate the DVHs and dose-response plots of salivary glands. Results: The small differences obtained between the mean DVHs showed that patients should be grouped into: with complications (G1+G2) and without complications (G0). The mean dose/2Gy was 22.2±13.2 Gy (G0) and 33.2±8.0 Gy (G1+G2) for the 7th week, 31.9±9.6 Gy (G0) and 34.6±6.8 Gy (G1+G2) for the 12th month and, 32.9±9.3 Gy (G0) and 37.2±8.5 Gy (G1+G2) for the 24th month. The dose-response plots for the 7th week and 24th month were similar to the dose-response curves published in the literature. Conclusion: In some cases, there were not major differences between the mean DVHs of the groups with and without complications in the salivary glands, when comparing them at different time periods. More radiobiological analysis should thus be made to estimate the clinical impact of those differences.« less

SU-E-T-467: Definition of the Proper Tolerances for Beam-Position Accuracy and Beam Width for Quality Assurance in Active Proton Pencil Beam Scanning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Safai, S

2014-06-01

Purpose: To estimate the correlation between different dosimetric indices and the clinical outcome, which was recorded at different time points after the treatment, regarding the structure of salivary glands in head and neck cancer radiotherapy. Methods: 218 salivary glands from patients with head and neck tumours treated at IPOCFG from 2007 to 2013 were included in this study. The follow up of those patients consisted on weekly medical visits during the treatment that take about seven weeks. After that the patients had consults every three months. Treatment complications were graded using the RTOG/EORTC guidelines. The response of the salivary glandsmore » (both parotids, oral cavity and both submandibular glands) was analyzed for six time periods: 7th week, 3rd, 7th, 12th, 18th and 24th months after the start of the radiotherapy. The total dose distributions, converted to a fractionation scheme of 2Gy fractional doses, were used to calculate the DVHs and dose-response plots of salivary glands. Results: The small differences obtained between the mean DVHs showed that patients should be grouped into: with complications (G1+G2) and without complications (G0). The mean dose/2Gy was 22.2±13.2 Gy (G0) and 33.2±8.0 Gy (G1+G2) for the 7th week, 31.9±9.6 Gy (G0) and 34.6±6.8 Gy (G1+G2) for the 12th month and, 32.9±9.3 Gy (G0) and 37.2±8.5 Gy (G1+G2) for the 24th month. The dose-response plots for the 7th week and 24th month were similar to the dose-response curves published in the literature. Conclusion: In some cases, there were not major differences between the mean DVHs of the groups with and without complications in the salivary glands, when comparing them at different time periods. More radiobiological analysis should thus be made to estimate the clinical impact of those differences.« less

Long-Term Cancer Outcomes From Study NRG Oncology/RTOG 9517: A Phase 2 Study of Accelerated Partial Breast Irradiation With Multicatheter Brachytherapy After Lumpectomy for Early-Stage Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

White, Julia, E-mail: Julia.White@osumc.edu; Winter, Kathryn; Kuske, Robert R.

Purpose: To examine 10-year rates of local, regional, and distant recurrences, patterns of recurrence, and survival rates for breast cancer patients enrolled on Study NRG Oncology/Radiation Therapy Oncology Group 9517, a multi-institutional prospective trial that studied one of the earliest methods of accelerated partial breast irradiation (APBI), multicatheter brachytherapy (MCT). Methods and Materials: Eligibility included stage I/II unifocal breast cancer <3 cm in size after lumpectomy with negative surgical margins and 0 to 3 positive axillary nodes without extracapsular extension. The APBI dose delivered was 34 Gy in 10 twice-daily fractions over 5 days for high-dose-rate (HDR); and 45 Gy in 3.5 to 5 days formore » low-dose-rate (LDR) brachytherapy. The primary endpoint was HDR and LDR MCT reproducibility. This analysis focuses on long-term ipsilateral breast recurrence (IBR), contralateral breast cancer events (CBE), regional recurrence (RR), and distant metastases (DM), disease-free, and overall survival. Results: The median follow-up was 12.1 years. One hundred patients were accrued from 1997 to 2000; 98 were evaluable; 65 underwent HDR and 33 LDR MCT. Median age was 62 years; 88% had T1 tumors; 81% were pN0. Seventy-seven percent were estrogen receptor and/or progesterone receptor positive; 33% received adjuvant chemotherapy and 64% antiendocrine therapy. There have been 4 isolated IBRs and 1 IBR with RR, for 5.2% 10-year IBR without DM. There was 1 isolated RR, 1 with IBR, and 1 with a CBE, for 3.1% 10-year RR without DM. The 10-year CBE rate was 4.2%, with 5 total events. Eleven patients have developed DM, 8 have died of breast cancer, and 22 have died from other causes. The 10-year DFS and OS rates are 69.8% and 78.0%, respectively. Conclusion: This multi-institutional, phase 2 trial studying MCT-APBI continues to report durable in-breast cancer control rates with long-term follow-up.« less

Long-Term Cancer Outcomes From Study NRG Oncology/RTOG 9517: A Phase 2 Study of Accelerated Partial Breast Irradiation With Multicatheter Brachytherapy After Lumpectomy for Early-Stage Breast Cancer.

PubMed

White, Julia; Winter, Kathryn; Kuske, Robert R; Bolton, John S; Arthur, Douglas W; Scroggins, Troy; Rabinovitch, Rachel A; Kelly, Tracy; Toonkel, Leonard M; Vicini, Frank A; McCormick, Beryl

2016-08-01

To examine 10-year rates of local, regional, and distant recurrences, patterns of recurrence, and survival rates for breast cancer patients enrolled on Study NRG Oncology/Radiation Therapy Oncology Group 9517, a multi-institutional prospective trial that studied one of the earliest methods of accelerated partial breast irradiation (APBI), multicatheter brachytherapy (MCT). Eligibility included stage I/II unifocal breast cancer <3 cm in size after lumpectomy with negative surgical margins and 0 to 3 positive axillary nodes without extracapsular extension. The APBI dose delivered was 34 Gy in 10 twice-daily fractions over 5 days for high-dose-rate (HDR); and 45 Gy in 3.5 to 5 days for low-dose-rate (LDR) brachytherapy. The primary endpoint was HDR and LDR MCT reproducibility. This analysis focuses on long-term ipsilateral breast recurrence (IBR), contralateral breast cancer events (CBE), regional recurrence (RR), and distant metastases (DM), disease-free, and overall survival. The median follow-up was 12.1 years. One hundred patients were accrued from 1997 to 2000; 98 were evaluable; 65 underwent HDR and 33 LDR MCT. Median age was 62 years; 88% had T1 tumors; 81% were pN0. Seventy-seven percent were estrogen receptor and/or progesterone receptor positive; 33% received adjuvant chemotherapy and 64% antiendocrine therapy. There have been 4 isolated IBRs and 1 IBR with RR, for 5.2% 10-year IBR without DM. There was 1 isolated RR, 1 with IBR, and 1 with a CBE, for 3.1% 10-year RR without DM. The 10-year CBE rate was 4.2%, with 5 total events. Eleven patients have developed DM, 8 have died of breast cancer, and 22 have died from other causes. The 10-year DFS and OS rates are 69.8% and 78.0%, respectively. This multi-institutional, phase 2 trial studying MCT-APBI continues to report durable in-breast cancer control rates with long-term follow-up. Copyright © 2016 Elsevier Inc. All rights reserved.

Expression of the DNA repair gene MLH1 correlates with survival in patients who have resected pancreatic cancer and have received adjuvant chemoradiation: NRG Oncology RTOG Study 9704.

PubMed

Lawrence, Yaacov R; Moughan, Jennifer; Magliocco, Anthony M; Klimowicz, Alexander C; Regine, William F; Mowat, Rex B; DiPetrillo, Thomas A; Small, William; Simko, Jeffry P; Golan, Talia; Winter, Kathryn A; Guha, Chandan; Crane, Christopher H; Dicker, Adam P

2018-02-01

The majority of patients with pancreatic cancer who undergo curative resection experience rapid disease recurrence. In previous small studies, high expression of the mismatch-repair protein mutL protein homolog 1 (MLH1) in pancreatic cancers was associated with better outcomes. The objective of this study was to validate the association between MLH1 expression and survival in patients who underwent resection of pancreatic cancer and received adjuvant chemoradiation. Samples were obtained from the NRG Oncology Radiation Therapy Oncology Group 9704 prospective, randomized trial (clinicaltrials.gov identifier NCT00003216), which compared 2 adjuvant protocols in patients with pancreatic cancer who underwent resection. Tissue microarrays were prepared from formalin-fixed, paraffin-embedded, resected tumor tissues. MLH1 expression was quantified using fluorescence immunohistochemistry and automated quantitative analysis, and expression was dichotomized above and below the median value. Immunohistochemical staining was successfully performed on 117 patients for MLH1 (60 and 57 patients from the 2 arms). The characteristics of the participants who had tissue samples available were similar to those of the trial population as a whole. At the time of analysis, 84% of participants had died, with a median survival of 17 months. Elevated MLH1 expression levels in tumor nuclei were significantly correlated with longer disease-free and overall survival in each arm individually and in both arms combined. Two-year overall survival was 16% in patients who had low MLH1 expression levels and 53% in those who had high MLH1 expression levels (P < .0001 for both arms combined). This association remained true on a multivariate analysis that allowed for lymph node status (hazard ratio, 0.41; 95% confidence interval, 0.27-0.63; P < .0001). In the current sample, MLH1 expression was correlated with long-term survival. Further studies should assess whether MLH1 expression predicts which patients with localized pancreatic cancer may benefit most from aggressive, multimodality treatment. Cancer 2018;124:491-8. © 2017 American Cancer Society. © 2017 American Cancer Society.

Cost-effectiveness of stereotactic radiosurgery versus whole-brain radiation therapy for up to 10 brain metastases.

PubMed

Lester-Coll, Nataniel H; Dosoretz, Arie P; Magnuson, William J; Laurans, Maxwell S; Chiang, Veronica L; Yu, James B

2016-12-01

OBJECTIVE The JLGK0901 study found that stereotactic radiosurgery (SRS) is a safe and effective treatment option for treating up to 10 brain metastases. The purpose of this study is to determine the cost-effectiveness of treating up to 10 brain metastases with SRS, whole-brain radiation therapy (WBRT), or SRS and immediate WBRT (SRS+WBRT). METHODS A Markov model was developed to evaluate the cost effectiveness of SRS, WBRT, and SRS+WBRT in patients with 1 or 2-10 brain metastases. Transition probabilities were derived from the JLGK0901 study and modified according to the recurrence rates observed in the Radiation Therapy Oncology Group (RTOG) 9508 and European Organization for Research and Treatment of Cancer (EORTC) 22952-26001 studies to simulate the outcomes for patients who receive WBRT. Costs are based on 2015 Medicare reimbursements. Health state utilities were prospectively collected using the Standard Gamble method. End points included cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). The willingness-to-pay (WTP) threshold was $100,000 per QALY. One-way and probabilistic sensitivity analyses explored uncertainty with regard to the model assumptions. RESULTS In patients with 1 brain metastasis, the ICERs for SRS versus WBRT, SRS versus SRS+WBRT, and SRS+WBRT versus WBRT were $117,418, $51,348, and $746,997 per QALY gained, respectively. In patients with 2-10 brain metastases, the ICERs were $123,256, $58,903, and $821,042 per QALY gained, respectively. On the sensitivity analyses, the model was sensitive to the cost of SRS and the utilities associated with stable post-SRS and post-WBRT states. In patients with 2-10 brain metastases, SRS versus WBRT becomes cost-effective if the cost of SRS is reduced by $3512. SRS versus WBRT was also cost effective at a WTP of $200,000 per QALY on the probabilistic sensitivity analysis. CONCLUSIONS The most cost-effective strategy for patients with up to 10 brain metastases is SRS alone relative to SRS+WBRT. SRS alone may also be cost-effective relative to WBRT alone, but this depends on WTP, the cost of SRS, and patient preferences.

Is Intermediate Radiation Dose Escalation With Concurrent Chemotherapy for Stage III Non–Small-Cell Lung Cancer Beneficial? A Multi-Institutional Propensity Score Matched Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodrigues, George, E-mail: george.rodrigues@lhsc.on.ca; Oberije, Cary; Senan, Suresh

2015-01-01

Purpose: The clinical benefits and risks of dose escalation (DE) for stage III non–small-cell lung cancer (NSCLC) remain uncertain despite the results from Radiation Therapy Oncology Group (RTOG) protocol 0617. There is significant heterogeneity of practice, with many clinicians prescribing intermediate dose levels between the 0617 study arms of 60 and 74 Gy. This study investigated whether this strategy is associated with any survival benefits/risks by analyzing a large multi-institutional database. Methods and Materials: An individual patient database of stage III NSCLC patients treated with radical intent concurrent chemoradiation therapy was created (13 institutions, n=1274 patients). Patients were divided into 2more » groups based on tumor Biological Effective Dose at 10 Gy (BED 10): those receiving standard dose (SD; n=552), consisting of 72Gy ≤ BED 10 ≤ 76.8 Gy (eg 60-64 Gy/30-32 fractions [fr]), and those receiving intermediate dose (ID; n=497), consisting of 76.8Gy < BED 10 < 100.8 Gy (eg >64 Gy/32 fr and <74 Gy/37 fr), with lower-dose patients (n=225) excluded from consideration. Patients were then matched using propensity scores, leading to 2 matched groups of 196 patients. Outcomes were compared using various statistics including interquartile range (IQR), Kaplan-Meier curves, and adjusted Cox regression analysis. Results: Matched groups were found to be balanced except for N stage (more N3 disease in SD), median treatment year (SD in 2003; ID in 2007), platinum and taxane chemotherapy (SD in 28%; ID in 39%), and median follow-up (SD were 89 months; ID were 40 months). Median dose fractionation was 60 Gy/30 fr in SD (BED 10 IQR: 72.0-75.5 Gy) and 66 Gy/33 fr (BED 10 IQR: 78.6-79.2 Gy) in ID. Survival curves for SD and ID matched cohorts were statistically similar (P=.27); however, a nonstatistically significant trend toward better survival for ID was observed after 15 months (median survival SD: 19.3 months; ID: 21.0 months). There was an increase in grades III to V lung toxicity associated with ID (13.0% vs 4.9%, respectively). Conclusions: No significant overall survival benefits were found with intermediate DE; however, more grade III or greater lung toxicity was observed. The separation of survival curves after 15 months of follow-up suggests that a small overall survival improvement associated with intermediate DE cannot be excluded.« less

Analysis of outcomes in radiation oncology: An integrated computational platform

PubMed Central

Liu, Dezhi; Ajlouni, Munther; Jin, Jian-Yue; Ryu, Samuel; Siddiqui, Farzan; Patel, Anushka; Movsas, Benjamin; Chetty, Indrin J.

2009-01-01

Radiotherapy research and outcome analyses are essential for evaluating new methods of radiation delivery and for assessing the benefits of a given technology on locoregional control and overall survival. In this article, a computational platform is presented to facilitate radiotherapy research and outcome studies in radiation oncology. This computational platform consists of (1) an infrastructural database that stores patient diagnosis, IMRT treatment details, and follow-up information, (2) an interface tool that is used to import and export IMRT plans in DICOM RT and AAPM/RTOG formats from a wide range of planning systems to facilitate reproducible research, (3) a graphical data analysis and programming tool that visualizes all aspects of an IMRT plan including dose, contour, and image data to aid the analysis of treatment plans, and (4) a software package that calculates radiobiological models to evaluate IMRT treatment plans. Given the limited number of general-purpose computational environments for radiotherapy research and outcome studies, this computational platform represents a powerful and convenient tool that is well suited for analyzing dose distributions biologically and correlating them with the delivered radiation dose distributions and other patient-related clinical factors. In addition the database is web-based and accessible by multiple users, facilitating its convenient application and use. PMID:19544785

Application of modified dynamic conformal arc (MDCA) technique on liver stereotactic body radiation therapy (SBRT) planning following RTOG 0438 guideline

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shi, Chengyu, E-mail: shicy1974@yahoo.com; Chen, Yong; Fang, Deborah

2015-04-01

Liver stereotactic body radiation therapy (SBRT) is a feasible treatment method for the nonoperable, patient with early-stage liver cancer. Treatment planning for the SBRT is very important and has to consider the simulation accuracy, planning time, treatment efficiency effects etc. The modified dynamic conformal arc (MDCA) technique is a 3-dimensional conformal arc planning method, which has been proposed for liver SBRT planning at our center. In this study, we compared the MDCA technique with the RapidArc technique in terms of planning target volume (PTV) coverage and sparing of organs at risk (OARs). The results show that the MDCA technique hasmore » comparable plan quality to RapidArc considering PTV coverage, hot spots, heterogeneity index, and effective liver volume. For the 5 PTVs studied among 4 patients, the MDCA plan, when compared with the RapidArc plan, showed 9% more hot spots, more heterogeneity effect, more sparing of OARs, and lower liver effective volume. The monitor unit (MU) number for the MDCA plan is much lower than for the RapidArc plans. The MDCA plan has the advantages of less planning time, no-collision treatment, and a lower MU number.« less

Impact of marital status and race on outcomes of patients enrolled in Radiation Therapy Oncology Group prostate cancer trials.

PubMed

Du, Kevin Lee; Bae, Kyounghwa; Movsas, Benjamin; Yan, Yan; Bryan, Charlene; Bruner, Deborah Watkins

2012-06-01

Previous studies by our group and others have demonstrated the importance of sociodemographic factors in cancer-related outcomes. The identification of these factors has led to novel approaches to the care of the high-risk cancer patient, specifically in the adoption of clinical interventions that convey similar benefits as favorable sociodemographic characteristics. This study examined the importance of marital status and race as prognostic indicators in men with prostate cancer. This report is a meta-analysis of 3,570 patients with prostate cancer treated in three prospective RTOG clinical trials. The Kaplan-Meier method was used to estimate the survival rate and the cumulative incidence method was used to analyze biochemical failure rate. Hazard ratios were calculated for all covariates using either the Cox or Fine and Gray's proportional hazards model or logistic regression model with associated 95% confidence intervals and p values. Hazard ratio (HR) for overall survival (OS) for single status compared to married status was 1.36 (95% CI, 1.2 to 1.53). OS HR for non-White compared to White patients was 1.05 (CI 0.92 to 1.21). In contrast, the disease-free survival (DFS) HR and biochemical failure (BF) HR were both not significantly different neither between single and married patients nor between White patients and non-White patients. Median time to death for married men was 5.68 years and for single men was 4.73 years. Median time for DFS for married men was 7.25 years and for single men was 6.56 years. Median time for BF for married men was 7.81 years and for single men was 7.05 years. Race was not associated with statistically significant differences in this analysis. Congruent with our previous work in other cancer sites, marital status predicted improved prostate cancer outcomes including overall survival. Prostate cancer is the most common visceral cancer in men in the USA. The stratification of prostate cancer risk is currently modeled solely on pathologic prognostic factors including PSA and Gleason Score. Independent of these pathologic prognostic factors, our paper describes the central sociodemographic factor of being single as a negative prognostic indicator. Single men are at high risk of poorer outcomes after prostate cancer treatment. Intriguingly, in our group of patients, race was not a significant prognostic factor. The findings in this paper add to the body of work that describes important sociodemographic prognostic factors that are currently underappreciated in patients with cancer. Future steps will include the validation of these findings in prospective studies, and the incorporation of clinical strategies that identify and compensate for sociodemographic factors that predict for poorer cancer outcomes.

Long-Term Outcomes Among Patients Who Achieve Complete or Near-Complete Responses After the Induction Phase of Bladder-Preserving Combined-Modality Therapy for Muscle-Invasive Bladder Cancer: A Pooled Analysis of NRG Oncology/RTOG 9906 and 0233

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mitin, Timur, E-mail: mitin@ohsu.edu; George, Asha; Zietman, Anthony L.

Purpose: To investigate the differences in outcomes among patients with muscle-invasive bladder cancer on NRG Oncology Radiation Therapy Oncology Group protocols 9906 and 0233 who achieved complete response and near-complete response after induction chemoradiation and then completed bladder-preserving therapy with chemoradiation therapy (chemo-RT) to full dose (60-64 Gy). Patients and Methods: A pooled analysis was performed on 119 eligible patients with muscle-invasive bladder cancer enrolled on NRG Oncology Radiation Therapy Oncology Group trials 9906 and 0233, who were classified as having a complete (T0) or near-complete (Ta or Tis) response after induction chemo-RT and completed consolidation with a total RT dose ofmore » at least 60 Gy. Bladder recurrence, salvage cystectomy rates, and disease-specific survival were estimated by the cumulative incidence method and bladder-intact and overall survivals by the Kaplan-Meier method. Results: Among the 119 eligible patients, 101 (85%) achieved T0, and 18 (15%) achieved Ta or Tis after induction chemo-RT and proceeded to consolidation. After a median follow-up of 5.9 years, 36 of 101 T0 patients (36%) versus 5 of 18 Ta or Tis patients (28%) experienced bladder recurrence (P=.52). Thirteen patients among complete responders eventually required late salvage cystectomy for tumor recurrence, compared with 1 patient among near-complete responders (P=.63). Disease-specific, bladder-intact, and overall survivals were not significantly different between T0 and Ta/Tis cases. Conclusions: The bladder recurrence and salvage cystectomy rates of the complete and the near-complete responders were similar. Therefore it is reasonable to recommend that patients with Ta or Tis after induction chemo-RT continue with bladder-sparing therapy with consolidation chemo-RT to full dose (60-64 Gy).« less

Results of a randomized comparison of radiotherapy and bromodeoxyuridine with radiotherapy alone for brain metastases: Report of RTOG trial 89-05

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phillips, T.L.; Scott, C.B.; Leibel, S.A.

1995-09-30

The purpose of this trial was to determine if the addition of bromodeoxyuridine (BrdUrd) to radiotherapy prolongs survival when compared to radiotherapy alone in patients with brain metastases. Seventy-two patients with brain metastases were randomized to 37.5 Gy in 15 fractions of 2.5 Gy or to the same dose with BrdUrd 0.8 g/m{sup 2} per day for 4 days of each of 3 weeks. Patients were stratified by primary site (breast, lung or other), number of metastases (single or multiple) and age (<60 vs. >60). There was no significant difference between the two treatment arms (p = 0.904). The studymore » was open from October 1989 to March 1993 and accrued 72 patients. Only one patient in the RT only arm remains alive. The two treatment arms were balanced with respect to all stratification variables. Toxicity due to radiotherapy was similar in both arms. BrdUrd caused significant Grade 4 and 5 hematologic and skin toxicity in five patients. Two patients died due to hematologic toxicity and one from a Stevens-Johnson type skin reaction. Phenytoin played a role in the skin reactions and ranitidine was associated with the hematologic deaths. Ranitidine was eliminated, BrdUrd was discontinued after any hematologic toxicity, and no further Grade 4 or 5 toxicities were seen. The median survival was 6.12 months in the radiotherapy group and 4.3 in the BrdUrd group (p = 0.904). Patients with solitary brain metastases had significantly better survival (p = 0.031). BrdUrd did not enhance the efficacy of the radiotherapy regiment tested, in spite of the fact that brain metastases have shown high labeling indices. The toxicity of this schedule of BrdUrd administration was apparently increased by ranitidine and phenytoin. 16 refs., 4 figs., 13 tabs.« less

Long-Term Outcomes From a Prospective Trial of Stereotactic Body Radiotherapy for Low-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

King, Christopher R., E-mail: crking@mednet.ucla.edu; Brooks, James D.; Gill, Harcharan

2012-02-01

Purpose: Hypofractionated radiotherapy has an intrinsically different normal tissue and tumor radiobiology. The results of a prospective trial of stereotactic body radiotherapy (SBRT) for prostate cancer with long-term patient-reported toxicity and tumor control rates are presented. Methods and Materials: From 2003 through 2009, 67 patients with clinically localized low-risk prostate cancer were enrolled. Treatment consisted of 36.25 Gy in 5 fractions using SBRT with the CyberKnife as the delivery technology. No patient received hormone therapy. Patient self-reported bladder and rectal toxicities were graded on the Radiation Therapy Oncology Group scale (RTOG). Results: Median follow-up was 2.7 years. There were nomore » grade 4 toxicities. Radiation Therapy Oncology Group Grade 3, 2, and 1 bladder toxicities were seen in 3% (2 patients), 5% (3 patients), and 23% (13 patients) respectively. Dysuria exacerbated by urologic instrumentation accounted for both patients with Grade 3 toxicity. Urinary incontinence, complete obstruction, or persistent hematuria was not observed. Rectal Grade 3, 2, and 1 toxicities were seen in 0, 2% (1 patient), and 12.5% (7 patients), respectively. Persistent rectal bleeding was not observed. Low-grade toxicities were substantially less frequent with QOD vs. QD dose regimen (p = 0.001 for gastrointestinal and p = 0.007 for genitourinary). There were two prostate-specific antigen (PSA), biopsy-proven failures with negative metastatic workup. Median PSA at follow-up was 0.5 {+-} 0.72 ng/mL. The 4-year Kaplan-Meier PSA relapse-free survival was 94% (95% confidence interval, 85%-102%). Conclusion: Significant late bladder and rectal toxicities from SBRT for prostate cancer are infrequent. PSA relapse-free survival compares favorably with other definitive treatments. The current evidence supports consideration of stereotactic body radiotherapy among the therapeutic options for localized prostate cancer.« less

[Dynamic observation on the short-term change of xerostomia after intensity-modulated radiotherapy for patients with nasopharyngeal carcinoma].

PubMed

Li, Yanjie; Zhao, Changqing

2015-01-01

To dynamically analyze the change of xerostomia in patients with nasopharyngeal carcinoma after radiotherapy by DW MRI. Twenty-three nasopharyngeal carcinoma patients confirmed by pathology were enrolled. Male/Female: 19/4. The age was from 37 to 69 years. The patients were divided into two groups: G1, Dmean<26 Gy, G2, Dmean ≥ 26 Gy. All patients underwent salivary glands examination by DW MRI before IMRT, at the end of IMRT, 6 months and 12 months after IMRT, at the same time the ADC value of salivary glands were calculated. According to the RTOG/EORTC salivary gland injury grading standard and referring the subjective index, the degree of xerostomia was assessed. SPSS 13.0 and SAS 8.2 software were used to analyze the data. At the end of IMRT, the change tendency of ADC in parotid and submandibular glands value was different in patients with different degree of xerostomia (F = 11.52, P < 0.01). At the end of IMRT, a significant difference for degree of xerostomia could be found in patients within different irradiation dose groups (Z = -3.622, P < 0.01). Clinical stage, treatment mode and age had no significant effect on the degree of xerostomia for patients at the end of IMRT (Z value was -0.791, -0.949, 2.488, all P > 0.05). A significant difference of xerostomia degree in patients was found at the various follow-up time after IMRT (χ(2) = 19.59, P < 0.01). There is good correlation between the function of salivary gland and subjective rating of xerostomia in patients with nasopharyngeal carcinoma after radiotherapy. The degrees of salivary gland function and dry mouth in patients with nasopharyngeal carcinoma damage evaluate with illuminated dose increases. The function of salivary gland gradually restored and the degree of dry mouth gradually reduce with the extension of time after radiotherapy.

Minimal Rectal Toxicity in the Setting of Comorbid Crohn's Disease Following Prostate Cancer Radiotherapy with a Hydrogel Rectal Spacer.

PubMed

Singh, Raj; Jackson, Philip S; Blake, Mollie; Cutlip, James; Sharma, Sanjeev

2017-08-01

We present one of the first cases of a prostate cancer (PCa) patient with inflammatory bowel disease (IBD) treated with intensity-modulated radiotherapy (IMRT) and a hydrogel rectal spacer. A 73-year-old male with a past medical history significant for Crohn's disease (CD) and the recent diagnosis of T1cN0M0 high-risk PCa was referred for definitive radiotherapy. Given the patient's history of CD and the possible increased risk of gastrointestinal (GI) toxicity and disease exacerbation, prior to IMRT, a hydrogel spacer was placed between the prostate and the anterior rectal wall to further minimize irradiation to the rectum. The patient then received IMRT (78 Gy/2 Gy fractions at a 100 percent isodose line). Over the course of treatment, Radiation Therapy Oncology Group (RTOG) Grade 1 GI toxicities of mild diarrhea were noted during the fifth and sixth weeks of treatment as well as an RTOG Grade 1 genitourinary (GU) toxicity of a decrease in the urinary stream that resolved with tamsulosin. At the 3, 6, 9, and 12-month follow-ups, bowel movements and urinary stream were reported to be at baseline with prostate-specific antigen (PSA) levels of 0.18 ng/mL and 0.03 ng/mL at the three and nine-month follow-ups, respectively. As such, this case report suggests that IBD patients with localized PCa may be viable candidates for radiotherapy given the promising results of hydrogel spacers in combination with IMRT in limiting rectal toxicity.

Dosimetric considerations and early clinical experience of accelerated partial breast irradiation using multi-lumen applicators in the setting of breast augmentation.

PubMed

Akhtari, Mani; Pino, Ramiro; Scarboro, Sarah B; Bass, Barbara L; Miltenburg, Darlene M; Butler, E Brian; Teh, Bin S

2015-12-01

Accelerated partial breast irradiation (APBI) is an accepted treatment option in breast-conserving therapy for early stage breast cancer. However, data regarding outcomes of patients treated with multi-lumen catheter systems who have existing breast implants is limited. The purpose of this study was to report treatment parameters, outcomes, and possible dosimetric correlation with cosmetic outcome for this population of patients at our institution. We report the treatment and outcome of seven consecutive patients with existing breast implants and early stage breast cancer who were treated between 2009 and 2013 using APBI following lumpectomy. All patients were treated twice per day for five days to a total dose of 34 Gy using a high-dose-rate (192)Ir source. Cosmetic outcomes were evaluated using the Harvard breast cosmesis scale, and late toxicities were reported using the Radiation Therapy Oncology Group (RTOG) late radiation morbidity schema. After a mean follow-up of 32 months, all patients have remained cancer free. Six out of seven patients had an excellent or good cosmetic outcome. There were no grade 3 or 4 late toxicities. The average total breast implant volume was 279.3 cc, received an average mean dose of 12.1 Gy, and a maximum dose of 234.1 Gy. The average percentage of breast implant volume receiving 50%, 75%, 100%, 150%, and 200% of the prescribed dose was 15.6%, 7.03%, 4.6%, 1.58%, and 0.46%, respectively. Absolute volume of breast implants receiving more than 50% of prescribed dose correlated with worse cosmetic outcomes. Accelerated partial breast irradiation using a multi-lumen applicator in patients with existing breast implants can safely be performed with promising early clinical results. The presence of the implant did not compromise the ability to achieve dosimetric criteria; however, dose to the implant and the irradiated implant volume may be related with worse cosmetic outcomes.

Management of acute skin toxicity with Hypericum perforatum and neem oil during platinum-based concurrent chemo-radiation in head and neck cancer patients.

PubMed

Franco, Pierfrancesco; Rampino, Monica; Ostellino, Oliviero; Schena, Marina; Pecorari, Giancarlo; Garzino Demo, Paolo; Fasolis, Massimo; Arcadipane, Francesca; Martini, Stefania; Cavallin, Chiara; Airoldi, Mario; Ricardi, Umberto

2017-02-01

Acute skin toxicity is a frequent finding during combined radiotherapy and chemotherapy in head and neck cancer patients. Its timely and appropriate management is crucial for both oncological results and patient's global quality of life. We herein report clinical data on the use of Hypericum perforatum and neem oil in the treatment of acute skin toxicity during concurrent chemo-radiation for head and neck cancer. A consecutive series of 50 head and neck cancer patients undergoing concomitant radio-chemotherapy with weekly cisplatin was analyzed. Treatment with Hypericum perforatum and neem oil was started in case of G2 acute skin toxicity according to the RTOG/EORTC scoring scale and continued during the whole treatment course and thereafter until complete recovery. The maximum detected acute skin toxicity included Grade 2 events in 62% of cases and G3 in 32% during treatment and G2 and G3 scores in 52 and 8%, respectively, at the end of chemo-radiation. Grade 2 toxicity was mainly observed during weeks 4-5, while G3 during weeks 5-6. Median times spent with G2 or G3 toxicity were 23.5 and 14 days. Patients with G3 toxicity were reconverted to a G2 profile in 80% of cases, while those with a G2 score had a decrease to G1 in 58% of cases. Time between maximum acute skin toxicity and complete skin recovery was 30 days. Mean worst pain score evaluated with the Numerical Rating Scale-11 was 6.9 during treatment and 4.5 at the end of chemo-radiotherapy. Hypericum perforatum and neem oil proved to be a safe and effective option in the management of acute skin toxicity in head and neck cancer patients submitted to chemo-radiation with weekly cisplatin. Further studies with a control group and patient-reported outcomes are needed to confirm this hypothesis.

RTOG 0913: A Phase 1 Study of Daily Everolimus (RAD001) in Combination With Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chinnaiyan, Prakash, E-mail: prakash.chinnaiyan@moffitt.org; Won, Minhee; Wen, Patrick Y.

Purpose: To determine the safety of the mammalian target of rapamycin inhibitor everolimus (RAD001) administered daily with concurrent radiation and temozolomide in newly diagnosed glioblastoma patients. Methods and Materials: Everolimus was administered daily with concurrent radiation (60 Gy in 30 fractions) and temozolomide (75 mg/m{sup 2} per day). Everolimus was escalated from 2.5 mg/d (dose level 1) to 5 mg/d (dose level 2) to 10 mg/d (dose level 3). Adjuvant temozolomide was delivered at 150 to 200 mg/m{sup 2} on days 1 to 5, every 28 days, for up to 12 cycles, with concurrent everolimus at the previously established dailymore » dose of 10 mg/d. Dose escalation continued if a dose level produced dose-limiting toxicities (DLTs) in fewer than 3 of the first 6 evaluable patients. Results: Between October 28, 2010, and July 2, 2012, the Radiation Therapy Oncology Group 0913 protocol initially registered a total of 35 patients, with 25 patients successfully meeting enrollment criteria receiving the drug and evaluable for toxicity. Everolimus was successfully escalated to the predetermined maximum tolerated dose of 10 mg/d. Two of the first 6 eligible patients had a DLT at each dose level. DLTs included gait disturbance, febrile neutropenia, rash, fatigue, thrombocytopenia, hypoxia, ear pain, headache, and mucositis. Other common toxicities were grade 1 or 2 hypercholesterolemia and hypertriglyceridemia. At the time of analysis, there was 1 death reported, which was attributed to tumor progression. Conclusions: Daily oral everolimus (10 mg) combined with both concurrent radiation and temozolomide followed by adjuvant temozolomide is well tolerated, with an acceptable toxicity profile. A randomized phase 2 clinical trial with mandatory correlative biomarker analysis is currently under way, designed to both determine the efficacy of this regimen and identify molecular determinants of response.« less

Initial Efficacy Results of RTOG 0319: Three-Dimensional Conformal Radiation Therapy (3D-CRT) Confined to the Region of the Lumpectomy Cavity for Stage I/ II Breast Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vicini, Frank, E-mail: fvicini@beaumont.ed; Winter, Kathryn; Wong, John

2010-07-15

Purpose: This prospective study (Radiation Therapy Oncology Group 0319) examines the use of three-dimensional conformal external beam radiotherapy (3D-CRT) to deliver accelerated partial breast irradiation (APBI). Initial data on efficacy and toxicity are presented. Methods and Materials: Patients with Stage I or II breast cancer with lesions {<=}3 cm, negative margins and with {<=}3 positive nodes were eligible. The 3D-CRT was 38.5 Gy in 3.85 Gy/fraction delivered 2x/day. Ipsilateral breast, ipsilateral nodal, contralateral breast, and distant failure (IBF, INF, CBF, DF) were estimated using the cumulative incidence method. Mastectomy-free, disease-free, and overall survival (MFS, DFS, OS) were recorded. The Nationalmore » Cancer Institute Common Terminology Criteria for Adverse Events, version 3, was used to grade acute and late toxicity. Results: Fifty-eight patients were entered and 52 patients are eligible and evaluable for efficacy. The median age of patients was 61 years with the following characteristics: 46% tumor size <1 cm; 87% invasive ductal histology; 94% American Joint Committee on Cancer Stage I; 65% postmenopausal; 83% no chemotherapy; and 71% with no hormone therapy. Median follow-up is 4.5 years (1.7-4.8). Four-year estimates (95% CI) of efficacy are: IBF 6% (0-12%) [4% within field (0-9%)]; INF 2% (0-6%); CBF 0%; DF 8% (0-15%); MFS 90% (78-96%); DFS 84% (71-92%); and OS 96% (85-99%). Only two (4%) Grade 3 toxicities were observed. Conclusions: Initial efficacy and toxicity using 3D-CRT to deliver APBI appears comparable to other experiences with similar follow-up. However, additional patients, further follow-up, and mature Phase III data are needed to evaluate the extent of application, limitations, and value of this particular form of APBI.« less

Comparing a volume based template approach and ultrasound guided freehand approach in multicatheter interstitial accelerated partial breast irradiation.

PubMed

Koh, Vicky Y; Buhari, Shaik A; Tan, Poh Wee; Tan, Yun Inn; Leong, Yuh Fun; Earnest, Arul; Tang, Johann I

2014-06-01

Currently, there are two described methods of catheter insertion for women undergoing multicatheter interstitial accelerated partial breast irradiation (APBI). These are a volume based template approach (template) and a non-template ultrasound guidance freehand approach (non-template). We aim to compare dosimetric endpoints between the template and non-template approach. Twenty patients, who received adjuvant multicatheter interstitial APBI between August 2008 to March 2010 formed the study cohort. Dosimetric planning was based on the RTOG 04-13 protocol. For standardization, the planning target volume evaluation (PTV-Eval) and organs at risk were contoured with the assistance of the attending surgeon. Dosimetric endpoints include D90 of the PTV-Eval, Dose Homogeneity Index (DHI), V200, maximum skin dose (MSD), and maximum chest wall dose (MCD). A median of 18 catheters was used per patient. The dose prescribed was 34 Gy in 10 fractions BID over 5 days. The average breast volume was 846 cm(3) (526-1384) for the entire cohort and there was no difference between the two groups (p = 0.6). Insertion time was significantly longer for the non-template approach (mean 150 minutes) compared to the template approach (mean: 90 minutes) (p = 0.02). The planning time was also significantly longer for the non-template approach (mean: 240 minutes) compared to the template approach (mean: 150 minutes) (p < 0.01). The template approach yielded a higher D90 (mean: 95%) compared to the non-template approach (mean: 92%) (p < 0.01). There were no differences in DHI (p = 0.14), V200 (p = 0.21), MSD (p = 0.7), and MCD (p = 0.8). Compared to the non-template approach, the template approach offered significant shorter insertion and planning times with significantly improved dosimetric PTV-Eval coverage without significantly compromising organs at risk dosimetrically.

Dosimetric considerations and early clinical experience of accelerated partial breast irradiation using multi-lumen applicators in the setting of breast augmentation

PubMed Central

Akhtari, Mani; Pino, Ramiro; Scarboro, Sarah B.; Bass, Barbara L.; Miltenburg, Darlene M.; Butler, E. Brian

2015-01-01

Purpose Accelerated partial breast irradiation (APBI) is an accepted treatment option in breast-conserving therapy for early stage breast cancer. However, data regarding outcomes of patients treated with multi-lumen catheter systems who have existing breast implants is limited. The purpose of this study was to report treatment parameters, outcomes, and possible dosimetric correlation with cosmetic outcome for this population of patients at our institution. Material and methods We report the treatment and outcome of seven consecutive patients with existing breast implants and early stage breast cancer who were treated between 2009 and 2013 using APBI following lumpectomy. All patients were treated twice per day for five days to a total dose of 34 Gy using a high-dose-rate 192Ir source. Cosmetic outcomes were evaluated using the Harvard breast cosmesis scale, and late toxicities were reported using the Radiation Therapy Oncology Group (RTOG) late radiation morbidity schema. Results After a mean follow-up of 32 months, all patients have remained cancer free. Six out of seven patients had an excellent or good cosmetic outcome. There were no grade 3 or 4 late toxicities. The average total breast implant volume was 279.3 cc, received an average mean dose of 12.1 Gy, and a maximum dose of 234.1 Gy. The average percentage of breast implant volume receiving 50%, 75%, 100%, 150%, and 200% of the prescribed dose was 15.6%, 7.03%, 4.6%, 1.58%, and 0.46%, respectively. Absolute volume of breast implants receiving more than 50% of prescribed dose correlated with worse cosmetic outcomes. Conclusions Accelerated partial breast irradiation using a multi-lumen applicator in patients with existing breast implants can safely be performed with promising early clinical results. The presence of the implant did not compromise the ability to achieve dosimetric criteria; however, dose to the implant and the irradiated implant volume may be related with worse cosmetic outcomes. PMID:26816499

A planning comparison of 3-dimensional conformal multiple static field, conformal arc, and volumetric modulated arc therapy for the delivery of stereotactic body radiotherapy for early stage lung cancer.

PubMed

Dickey, Mike; Roa, Wilson; Drodge, Suzanne; Ghosh, Sunita; Murray, Brad; Scrimger, Rufus; Gabos, Zsolt

2015-01-01

The primary objective of this study was to compare dosimetric variables as well as treatment times of multiple static fields (MSFs), conformal arcs (CAs), and volumetric modulated arc therapy (VMAT) techniques for the treatment of early stage lung cancer using stereotactic body radiotherapy (SBRT). Treatments of 23 patients previously treated with MSF of 48Gy to 95% of the planning target volume (PTV) in 4 fractions were replanned using CA and VMAT techniques. Dosimetric parameters of the Radiation Therapy Oncology Group (RTOG) 0915 trial were evaluated, along with the van׳t Riet conformation number (CN), monitor units (MUs), and actual and calculated treatment times. Paired t-tests for noninferiority were used to compare the 3 techniques. CA had significant dosimetric improvements over MSF for the ratio of the prescription isodose volume to PTV (R100%, p < 0.0001), the maximum dose 2cm away from the PTV (D2cm, p = 0.005), and van׳t Riet CN (p < 0.0001). CA was not statistically inferior to MSF for the 50% prescription isodose volume to PTV (R50%, p = 0.05). VMAT was significantly better than CA for R100% (p < 0.0001), R50% (p < 0.0001), D2cm (p = 0.006), and CN (p < 0.0001). CA plans had significantly shorter treatment times than those of VMAT (p < 0.0001). Both CA and VMAT planning showed significant dosimetric improvements and shorter treatment times over those of MSF. VMAT showed the most favorable dosimetry of all 3 techniques; however, the dosimetric effect of tumor motion was not evaluated. CA plans were significantly faster to treat, and minimize the interplay of tumor motion and dynamic multileaf collimator (MLC) motion effects. Given these results, CA has become the treatment technique of choice at our facility. Copyright © 2015 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Toxicity and outcome results of RTOG 9311: a phase I-II dose-escalation study using three-dimensional conformal radiotherapy in patients with inoperable non-small-cell lung carcinoma.

PubMed

Bradley, Jeffrey; Graham, Mary V; Winter, Kathryn; Purdy, James A; Komaki, Ritsuko; Roa, Wilson H; Ryu, Janice K; Bosch, Walter; Emami, Bahman

2005-02-01

To evaluate prospectively the acute and late morbidities from a multiinstitutional three-dimensional radiotherapy dose-escalation study for inoperable non-small-cell lung cancer. A total of 179 patients were enrolled in a Phase I-II three-dimensional radiotherapy dose-escalation trial. Of the 179 patients, 177 were eligible. The use of concurrent chemotherapy was not allowed. Twenty-five patients received neoadjuvant chemotherapy. Patients were stratified at escalating radiation dose levels depending on the percentage of the total lung volume that received >20 Gy with the treatment plan (V(20)). Patients with a V(20) <25% (Group 1) received 70.9 Gy in 33 fractions, 77.4 Gy in 36 fractions, 83.8 Gy in 39 fractions, and 90.3 Gy in 42 fractions, successively. Patients with a V(20) of 25-36% (Group 2) received doses of 70.9 Gy and 77.4 Gy, successively. The treatment arm for patients with a V(20) > or =37% (Group 3) closed early secondary to poor accrual (2 patients) and the perception of excessive risk for the development of pneumonitis. Toxicities occurring or persisting beyond 90 days after the start of radiotherapy were scored as late toxicities. The estimated toxicity rates were calculated on the basis of the cumulative incidence method. The following acute Grade 3 or worse toxicities were observed for Group 1: 70.9 Gy (1 case of weight loss), 77.4 Gy (nausea and hematologic toxicity in 1 case each), 83.8 Gy (1 case of hematologic toxicity), and 90.3 Gy (3 cases of lung toxicity). The following acute Grade 3 or worse toxicities were observed for Group 2: none at 70.9 Gy and 2 cases of lung toxicity at 77.4 Gy. No patients developed acute Grade 3 or worse esophageal toxicity. The estimated rate of Grade 3 or worse late lung toxicity at 18 months was 7%, 16%, 0%, and 13% for Group 1 patients receiving 70.9, 77.4, 83.8, or 90.3 Gy, respectively. Group 2 patients had an estimated late lung toxicity rate of 15% at 18 months for both 70.9 and 77.4 Gy. The prognostic factors for late pneumonitis in multivariate analysis were the mean lung dose and V(20). The estimated rate of late Grade 3 or worse esophageal toxicity at 18 months was 8%, 0%, 4%, and 6%, for Group 1 patients receiving 70.9, 77.4, 83.8, 90.3 Gy, respectively, and 0% and 5%, respectively, for Group 2 patients receiving 70.9 and 77.4 Gy. The dyspnea index scoring at baseline and after therapy for functional impairment, magnitude of task, and magnitude of effort revealed no change in 63%, functional pulmonary loss in 23%, and pulmonary improvement in 14% of patients. The observed locoregional control and overall survival rates were each similar among the study arms within each dose level of Groups 1 and 2. Locoregional control was achieved in 50-78% of patients. Thirty-one patients developed regional nodal failure. The location of nodal failure in relationship to the RT volume was documented in 28 of these 31 patients. Twelve patients had isolated elective nodal failures. Fourteen patients had regional failure in irradiated nodal volumes. Two patients had both elective nodal and irradiated nodal failure. The radiation dose was safely escalated using three-dimensional conformal techniques to 83.8 Gy for patients with V(20) values of <25% (Group 1) and to 77.4 Gy for patients with V(20) values between 25% and 36% (Group 2), using fraction sizes of 2.15 Gy. The 90.3-Gy dose level was too toxic, resulting in dose-related deaths in 2 patients. Elective nodal failure occurred in <10% of patients.

Stereotactic Body Radiation Therapy Delivery in a Genetically Engineered Mouse Model of Lung Cancer.

PubMed

Du, Shisuo; Lockamy, Virginia; Zhou, Lin; Xue, Christine; LeBlanc, Justin; Glenn, Shonna; Shukla, Gaurav; Yu, Yan; Dicker, Adam P; Leeper, Dennis B; Lu, You; Lu, Bo

2016-11-01

To implement clinical stereotactic body radiation therapy (SBRT) using a small animal radiation research platform (SARRP) in a genetically engineered mouse model of lung cancer. A murine model of multinodular Kras-driven spontaneous lung tumors was used for this study. High-resolution cone beam computed tomography (CBCT) imaging was used to identify and target peripheral tumor nodules, whereas off-target lung nodules in the contralateral lung were used as a nonirradiated control. CBCT imaging helps localize tumors, facilitate high-precision irradiation, and monitor tumor growth. SBRT planning, prescription dose, and dose limits to normal tissue followed the guidelines set by RTOG protocols. Pathologic changes in the irradiated tumors were investigated using immunohistochemistry. The image guided radiation delivery using the SARRP system effectively localized and treated lung cancer with precision in a genetically engineered mouse model of lung cancer. Immunohistochemical data confirmed the precise delivery of SBRT to the targeted lung nodules. The 60 Gy delivered in 3 weekly fractions markedly reduced the proliferation index, Ki-67, and increased apoptosis per staining for cleaved caspase-3 in irradiated lung nodules. It is feasible to use the SARRP platform to perform dosimetric planning and delivery of SBRT in mice with lung cancer. This allows for preclinical studies that provide a rationale for clinical trials involving SBRT, especially when combined with immunotherapeutics. Copyright © 2016. Published by Elsevier Inc.

Importance of Local Control in Early-Stage Prostate Cancer: Outcomes of Patients With Positive Post-Radiation Therapy Biopsy Results Treated in RTOG 9408

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krauss, Daniel J., E-mail: dkrauss@beaumont.edu; Hu, Chen; Bahary, Jean-Paul

Purpose: The purpose of this study was to assess the association between positive post-radiation therapy (RT) biopsy results and subsequent clinical outcomes in males with localized prostate cancer. Methods and Materials: Radiation Therapy Oncology Group study 94-08 analyzed 1979 males with prostate cancer, stage T1b-T2b and prostate-specific antigen concentrations of ≤20 ng/dL, to investigate whether 4 months of total androgen suppression (TAS) added to RT improved survival compared to RT alone. Patients randomized to receive TAS received flutamide with luteinizing hormone releasing hormone (LHRH) agonist. According to protocol, patients without evidence of clinical recurrence or initiation of additional endocrine therapy underwent repeatmore » prostate biopsy 2 years after RT completion. Statistical analysis was performed to evaluate the impact of positive post-RT biopsy results on clinical outcomes. Results: A total of 831 patients underwent post-RT biopsy, 398 were treated with RT alone and 433 with RT plus TAS. Patients with positive post-RT biopsy results had higher rates of biochemical failure (hazard ratio [HR] = 1.7; 95% confidence interval [CI] = 1.3-2.1) and distant metastasis (HR = 2.4; 95% CI = 1.3-4.4) and inferior disease-specific survival (HR = 3.8; 95% CI = 1.9-7.5). Positive biopsy results remained predictive of such outcomes after correction for potential confounders such as Gleason score, tumor stage, and TAS administration. Prior TAS therapy did not prevent elevated risk of adverse outcome in the setting of post-RT positive biopsy results. Patients with Gleason score ≥7 with a positive biopsy result additionally had inferior overall survival compared to those with a negative biopsy result (HR = 1.56; 95% CI = 1.04-2.35). Conclusions: Positive post-RT biopsy is associated with increased rates of distant metastases and inferior disease-specific survival in patients treated with definitive RT and was associated with inferior overall survival in patients with high-grade tumors.« less

Hypofractionated whole breast radiation and partial breast radiation for early-stage breast cancers: an update on progress.

PubMed

McCormick, Beryl

2012-09-01

This article provides an update of recent progress using partial breast irradiation (PBI) for the treatment of early-stage breast cancer, rather than whole breast radiotherapy (WBRT), which is the standard of care. Several large, prospective, randomized trials are nearing target accrual or have been completed, including the NSABP/RTOG trial, the Milan-based intraoperative radiation trial, and the international TARGIT trial, and the status of each is discussed. The American Society for Radiation Oncology has also published a consensus statement to guide the use of PBI until some of the phase III trials are more mature. Finally, several articles have appeared recently, reporting unexpected adverse effects of PBI in small series, and this information is reviewed. Several recent prospective trials of WBRT are also discussed, with the theme of comparing the standard 25 fractions to a shortened, hypofractionated trial arm delivering equivalent doses of WBRT in approximately 15 treatments, another radiation strategy for a shortened course of treatment after breast-conserving surgery.

[Initial experience of proton beam therapy at the new facility of the University of Tsukuba].

PubMed

Kagei, Kenji; Tokuuye, Koichi; Sugahara, Shinji; Hata, Masaharu; Igaki, Hiroshi; Hashimoto, Takayuki; Ohara, Kiyoshi; Akine, Yasuyuki

2004-05-01

To present the initial experience with proton beam therapy at the new Proton Medical Research Center (PMRC) of the University of Tsukuba. The new facility has a synchrotron with maximum energy of 250MeV and two rotational gantries. We treated 105 patients with 120 lesions with proton beams in the first year, beginning in September 2001. The most common lesion treated was primary liver cancer (40 lesions) followed by lung cancer, head and neck cancers, and prostate cancer. Concurrent X-ray radiotherapy was given for 38 of the 120 lesions. The median follow-up period was 11 months (range, 1-19 months). Of the 105 patients, 97% had Grade 0-2 RTOG/EORTC acute morbidities, while the remaining 3% had Grade 3. Tumor response after irradiation was CR for 35% of the lesions, PR for 25%, SD for 22%, PD for 9%, and not evaluated for 9%. The proton beam therapy conducted at the new facility of the University of Tsukuba was safe and effective.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stillwagon, G.B.; Order, S.E.; Klein, J.L.

Thirty-seven patients with primary nonresectable intrahepatic cholangiocarcinoma (57% with prior treatment and/or metastasis) were prospectively treated with external radiation, chemotherapy, and /sup 131/I labelled anti-CEA. Therapy began in all trials with whole liver irradiation (21.0 Gy, 3.0 Gy/Fx, 4 days/week, 10 MV photons) with alternate treatment day chemotherapy (Adriamycin, 15 mg + 5-FU, 500 mg). One month after external beam therapy, chemotherapy was given (Adriamycin, 15 mg + 5-FU, 500 mg) followed the next day by the first administration of /sup 131/I anti-CEA. The treatment schedule used was 20 mCi day 0; 10 mCi day 5 as an outpatient. Thismore » schedule was derived from tumor dose estimates which indicated that 20 mCi (8-10 mCi/mg IgG) was sufficient to achieve tumor saturation with a tumor effective half-life of 3 to 5 days, depending upon the species of animal from which the antibody was obtained. The median tumor dose for the 20 mCi + 10 mCi regimen was 6.2 Gy. Antibody therapy was delivered in 2-month cycles using antibody generated in different species of animals; rabbit, pig, monkey, and bovine. Toxicity was limited to hematologic toxicity and was manifested as thrombocytopenia and leukocytopenia (3.2% Grade IV for each according to RTOG toxicity criteria). Tumor remission evaluated by CT scan digitized tumor volume analysis indicated a 26.6% partial response (PR). Tumor remission by physical examination indicated a 33.3% remission rate (25.9% PR and 7.4% complete remission (CR). The median survival for patients who responded was 15.2 months. The actuarial median survival for the entire group of patients (metastases and previous treatment) was 6.5 months. The longest partial remission is presently more than 4 years.« less

Current role of radiation therapy for multiple myeloma.

PubMed

Talamo, Giampaolo; Dimaio, Christopher; Abbi, Kamal K S; Pandey, Manoj K; Malysz, Jozef; Creer, Michael H; Zhu, Junjia; Mir, Muhammad A; Varlotto, John M

2015-01-01

Radiation therapy (RT) is a treatment modality traditionally used in patients with multiple myeloma (MM), but little is known regarding the role and effectiveness of RT in the era of novel agents, i.e., immunomodulatory drugs and proteasome inhibitors. We retrospectively reviewed data from 449 consecutive MM patients seen at our institute in 2010-2012 to assess indications for RT as well as its effectiveness. Pain response was scored similarly to RTOG 0631 and used the Numerical Rating Pain Scale. Among 442 evaluable patients, 149 (34%) patients and 262 sites received RT. The most common indication for RT was palliation of bone pain (n = 109, 42%), followed by prevention/treatment of pathological fractures (n = 73, 28%), spinal cord compression (n = 26, 10%), and involvement of vital organs/extramedullary disease (n = 25, 10%). Of the 55 patients evaluable for pain relief, complete and partial responses were obtained in 76.4 and 7.2%, respectively. Prior RT did not significantly decrease the median number of peripheral blood stem cells collected for autologous transplant, even when prior RT was given to both the spine and pelvis. Inadequacy of stem cell collection for autologous stem cell transplant (ASCT) was not significantly different and it occurred in 9 and 15% of patients receiving no RT and spine/pelvic RT, respectively. None of the three cases of therapy-induced acute myelogenous leukemia/MDS occurred in the RT group. Despite the introduction of novel effective agents in the treatment of MM, RT remains a major therapeutic component for the management in 34% of patients, and it effectively provides pain relief while not interfering with successful peripheral blood stem cell collection for ASCT.

Current Role of Radiation Therapy for Multiple Myeloma

PubMed Central

Talamo, Giampaolo; Dimaio, Christopher; Abbi, Kamal K. S.; Pandey, Manoj K.; Malysz, Jozef; Creer, Michael H.; Zhu, Junjia; Mir, Muhammad A.; Varlotto, John M.

2015-01-01

Background: Radiation therapy (RT) is a treatment modality traditionally used in patients with multiple myeloma (MM), but little is known regarding the role and effectiveness of RT in the era of novel agents, i.e., immunomodulatory drugs and proteasome inhibitors. Methods: We retrospectively reviewed data from 449 consecutive MM patients seen at our institute in 2010–2012 to assess indications for RT as well as its effectiveness. Pain response was scored similarly to RTOG 0631 and used the Numerical Rating Pain Scale. Results: Among 442 evaluable patients, 149 (34%) patients and 262 sites received RT. The most common indication for RT was palliation of bone pain (n = 109, 42%), followed by prevention/treatment of pathological fractures (n = 73, 28%), spinal cord compression (n = 26, 10%), and involvement of vital organs/extramedullary disease (n = 25, 10%). Of the 55 patients evaluable for pain relief, complete and partial responses were obtained in 76.4 and 7.2%, respectively. Prior RT did not significantly decrease the median number of peripheral blood stem cells collected for autologous transplant, even when prior RT was given to both the spine and pelvis. Inadequacy of stem cell collection for autologous stem cell transplant (ASCT) was not significantly different and it occurred in 9 and 15% of patients receiving no RT and spine/pelvic RT, respectively. None of the three cases of therapy-induced acute myelogenous leukemia/MDS occurred in the RT group. Conclusion: Despite the introduction of novel effective agents in the treatment of MM, RT remains a major therapeutic component for the management in 34% of patients, and it effectively provides pain relief while not interfering with successful peripheral blood stem cell collection for ASCT. PMID:25741475

US Intergroup Anal Carcinoma Trial: Tumor Diameter Predicts for Colostomy

PubMed Central

Ajani, Jaffer A.; Winter, Kathryn A.; Gunderson, Leonard L.; Pedersen, John; Benson, Al B.; Thomas, Charles R.; Mayer, Robert J.; Haddock, Michael G.; Rich, Tyvin A.; Willett, Christopher G.

2009-01-01

Purpose The US Gastrointestinal Intergroup Radiation Therapy Oncology Group 98-11 anal carcinoma trial showed that cisplatin-based concurrent chemoradiotherapy resulted in a significantly higher rate of colostomy compared with mitomycin-based therapy. Established prognostic variables for patients with anal carcinoma include tumor diameter, clinical nodal status, and sex, but pretreatment variables that would predict the likelihood of colostomy are unknown. Methods A secondary analysis was performed by combining patients in the two treatment arms to evaluate whether new predictive and prognostic variables would emerge. Univariate and multivariate analyses were carried out to correlate overall survival (OS), disease-free survival, and time to colostomy (TTC) with pretreatment and treatment variables. Results Of 682 patients enrolled, 644 patients were assessable and analyzed. In the multivariate analysis, tumor-related prognosticators for poorer OS included node-positive cancer (P ≤ .0001), large (> 5 cm) tumor diameter (P = .01), and male sex (P = .016). In the treatment-related categories, cisplatin-based therapy was statistically significantly associated with a higher rate of colostomy (P = .03) than was mitomycin-based therapy. In the pretreatment variables category, only large tumor diameter independently predicted for TTC (P = .008). Similarly, the cumulative 5-year colostomy rate was statistically significantly higher for large tumor diameter than for small tumor diameter (Gray's test; P = .0074). Clinical nodal status and sex were not predictive of TTC. Conclusion The combined analysis of the two arms of RTOG 98-11, representing the largest prospective database, reveals that tumor diameter (irrespective of the nodal status) is the only independent pretreatment variable that predicts TTC and 5-year colostomy rate in patients with anal carcinoma. PMID:19139424

Long-Term Results of Concomitant Boost Radiation Plus Concurrent Cisplatin for Advanced Head and Neck Carcinomas: A Phase II Trial of the Radiation Therapy Oncology Group (RTOG 99-14)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garden, Adam S.; Harris, Jonathan M.S.; Trotti, Andy

2008-08-01

Purpose: The feasibility of combining concomitant boost-accelerated radiation regimen (AFX-C) with cisplatin was previously demonstrated in this Phase II trial. This article reports the long-term toxicity, relapse patterns, and survival in patients with advanced head and neck carcinoma. Methods and Materials: Between April and November 2000, 84 patients with Stage III-IV HNC were enrolled, and 76 patients were analyzable. Radiation consisted of 72 Gy over 6 weeks. Cisplatin dose was 100 mg/m{sup 2} on Days 1 and 22. Tumor and clinical status were assessed, and acute-late toxicities were graded. Results: The median follow-up for surviving patients is 4.3 years. Themore » 2- and 4-year locoregional failure rates were 33% and 36%, respectively, and the 2- and 4-year survival rates were 70% and 54%, respectively. The worst overall late Grade 3 or 4 toxicity rate was 42%. The prevalence rates of a gastrostomy at any time during follow-up, at 12 months, and at 48 months were 83%, 41%, and 17%, respectively. Five of 36 patients (14%) alive and without disease at last follow-up were gastrostomy-tube dependent. Conclusion: These data of long-term follow-up of patients treated with AFX-C with cisplatin show encouraging results with regard to locoregional disease control and survival, with few recurrences after 2 years. The late toxicity rates are relatively high. However, although prolonged dysphagia was noted in our preliminary report, its prevalence does decreased over time. A Phase III trial comparing AFX-C plus cisplatin against standard radiation plus cisplatin has completed accrual.« less

Long-Term Outcome and Morbidity After Treatment With Accelerated Radiotherapy and Weekly Cisplatin for Locally Advanced Head-and-Neck Cancer: Results of a Multidisciplinary Late Morbidity Clinic

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ruetten, Heidi, E-mail: h.rutten@rther.umcn.nl; Pop, Lucas A.M.; Janssens, Geert O.R.J.

2011-11-15

Purpose: To evaluate the long-term outcome and morbidity after intensified treatment for locally advanced head-and-neck cancer. Methods and Materials: Between May 2003 and December 2007, 77 patients with Stage III to IV head-and-neck cancer were treated with curative intent. Treatment consisted of accelerated radiotherapy to a dose of 68 Gy and concurrent cisplatin. Long-term survivors were invited to a multidisciplinary outpatient clinic for a comprehensive assessment of late morbidity with special emphasis on dysphagia, including radiological evaluation of swallowing function in all patients. Results: Compliance with the treatment protocol was high, with 87% of the patients receiving at least fivemore » cycles of cisplatin and all but 1 patient completing the radiotherapy as planned. The 5-year actuarial disease-free survival and overall survival rates were 40% and 47%, respectively. Locoregional recurrence-free survival at 5 years was 61%. The 5-year actuarial rates of overall late Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) Grade 3 and Grade 4 toxicity were 52% and 25% respectively. Radiologic evaluation after a median follow-up of 44 months demonstrated impaired swallowing in 57% of the patients, including 23% with silent aspiration. Subjective assessment using a systematic scoring system indicated normalcy of diet in only 15.6% of the patients. Conclusion: This regimen of accelerated radiotherapy with weekly cisplatin produced favorable tumor control rates and survival rates while compliance was high. However, comprehensive assessment by a multidisciplinary team of medical and paramedical specialists revealed significant long-term morbidity in the majority of the patients, with dysphagia being a major concern.« less

Patients With Proneural Glioblastoma May Derive Overall Survival Benefit From the Addition of Bevacizumab to First-Line Radiotherapy and Temozolomide: Retrospective Analysis of the AVAglio Trial.

PubMed

Sandmann, Thomas; Bourgon, Richard; Garcia, Josep; Li, Congfen; Cloughesy, Timothy; Chinot, Olivier L; Wick, Wolfgang; Nishikawa, Ryo; Mason, Warren; Henriksson, Roger; Saran, Frank; Lai, Albert; Moore, Nicola; Kharbanda, Samir; Peale, Franklin; Hegde, Priti; Abrey, Lauren E; Phillips, Heidi S; Bais, Carlos

2015-09-01

The AVAglio (Avastin in Glioblastoma) and RTOG-0825 randomized, placebo-controlled phase III trials in newly diagnosed glioblastoma reported prolonged progression-free survival (PFS), but not overall survival (OS), with the addition of bevacizumab to radiotherapy plus temozolomide. To establish whether certain patient subgroups derived an OS benefit from the addition of bevacizumab to first-line standard-of-care therapy, AVAglio patients were retrospectively evaluated for molecular subtype, and bevacizumab efficacy was assessed for each patient subgroup. A total of 349 pretreatment specimens (bevacizumab arm, n = 171; placebo arm, n = 178) from AVAglio patients (total, N = 921) were available for biomarker analysis. Samples were profiled for gene expression and isocitrate dehydrogenase 1 (IDH1) mutation status and classified into previously identified molecular subtypes. PFS and OS were assessed within each subtype. A multivariable analysis accounting for prognostic covariates revealed that bevacizumab conferred a significant OS advantage versus placebo for patients with proneural IDH1 wild-type tumors (17.1 v 12.8 months, respectively; hazard ratio, 0.43; 95% CI, 0.26 to 0.73; P = .002). This analysis also revealed an interaction between the proneural subtype biomarker and treatment arm (P = .023). The group of patients with mesenchymal and proneural tumors derived a PFS benefit from bevacizumab compared with placebo; however, this translated to an OS benefit in the proneural subset only. Retrospective analysis of AVAglio data suggests that patients with IDH1 wild-type proneural glioblastoma may derive an OS benefit from first-line bevacizumab treatment. The predictive value of the proneural subtype observed in AVAglio should be validated in an independent data set. © 2015 by American Society of Clinical Oncology.

Superficial ocular malignancies treated with strontium-90 brachytherapy: long term outcomes.

PubMed

Laskar, Siddhartha; Gurram, Lavanya; Laskar, Sarbani Ghosh; Chaudhari, Suresh; Khanna, Nehal; Upreti, Rituraj

2015-10-01

The incidence of conjunctival malignancies is less than 1%. Though surgical excision remains the mainstay of treatment, the incidence of positive surgical margins and local recurrence rates are high, which is approximately up to 33% in negative margins and 56% in positive margins. Radiotherapy reduces the risk of recurrence in these cases. Brachytherapy using β emitters such as strontium-90 ((90)Sr) is an ideal treatment technique for these tumors with the advantage of treating only a few millimeters of tissue while sparing the underlying normal eye. We report the long term outcomes in the form of local control and late sequelae of patients with conjunctival malignancies treated with (90)Sr applicator brachytherapy. During 1999-2013, 13 patients with conjunctival tumors, treated using (90)Sr brachytherapy were analyzed. Brachytherapy was either in a post-operative adjuvant or in a recurrent setting. Local control (LC), disease free survival (DFS), overall survival (OS), and late sequelae were evaluated. The median age at presentation was 47 years (range: 11-71 years). Thirteen patients with 15 tumors were treated. The commonest histology was squamous cell carcinoma. The median dose was 44 Gy over 11 fractions. The median follow up of all the patients was 51 months (range: 3-139 months). The median follow up of patients with carcinoma only was 64 months with a LC and DFS of 90.9% at 5 years. None of the patients developed ≥ grade II Radiation Therapy Oncology Group (RTOG) acute toxicities. One patient developed a focal scar and another developed corneal opacification at the limbus. Vision was not impaired in any of the patients. Strontium-90 brachytherapy used in early invasive conjunctival malignancies as an adjunct to surgery in primary and recurrent settings, results in optimal disease control and ocular functional outcomes.

WE-AB-BRA-07: Quantitative Evaluation of 2D-2D and 2D-3D Image Guided Radiation Therapy for Clinical Trial Credentialing, NRG Oncology/RTOG

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giaddui, T; Yu, J; Xiao, Y

Purpose: 2D-2D kV image guided radiation therapy (IGRT) credentialing evaluation for clinical trial qualification was historically qualitative through submitting screen captures of the fusion process. However, as quantitative DICOM 2D-2D and 2D-3D image registration tools are implemented in clinical practice for better precision, especially in centers that treat patients with protons, better IGRT credentialing techniques are needed. The aim of this work is to establish methodologies for quantitatively reviewing IGRT submissions based on DICOM 2D-2D and 2D-3D image registration and to test the methodologies in reviewing 2D-2D and 2D-3D IGRT submissions for RTOG/NRG Oncology clinical trials qualifications. Methods: DICOM 2D-2Dmore » and 2D-3D automated and manual image registration have been tested using the Harmony tool in MIM software. 2D kV orthogonal portal images are fused with the reference digital reconstructed radiographs (DRR) in the 2D-2D registration while the 2D portal images are fused with DICOM planning CT image in the 2D-3D registration. The Harmony tool allows alignment of the two images used in the registration process and also calculates the required shifts. Shifts calculated using MIM are compared with those submitted by institutions for IGRT credentialing. Reported shifts are considered to be acceptable if differences are less than 3mm. Results: Several tests have been performed on the 2D-2D and 2D-3D registration. The results indicated good agreement between submitted and calculated shifts. A workflow for reviewing these IGRT submissions has been developed and will eventually be used to review IGRT submissions. Conclusion: The IROC Philadelphia RTQA center has developed and tested a new workflow for reviewing DICOM 2D-2D and 2D-3D IGRT credentialing submissions made by different cancer clinical centers, especially proton centers. NRG Center for Innovation in Radiation Oncology (CIRO) and IROC RTQA center continue their collaborative efforts to enhance quality assurance services and to be consistently adaptive to the new advances in radiation therapy. This project was supported by NCI grants U10CA180868, U10CA180822, U24CA180803, U24CA12014 and PA CURE Grant.« less

Intensity modulated radiation therapy (IMRT): differences in target volumes and improvement in clinically relevant doses to small bowel in rectal carcinoma.

PubMed

Mok, Henry; Crane, Christopher H; Palmer, Matthew B; Briere, Tina M; Beddar, Sam; Delclos, Marc E; Krishnan, Sunil; Das, Prajnan

2011-06-08

A strong dose-volume relationship exists between the amount of small bowel receiving low- to intermediate-doses of radiation and the rates of acute, severe gastrointestinal toxicity, principally diarrhea. There is considerable interest in the application of highly conformal treatment approaches, such as intensity-modulated radiation therapy (IMRT), to reduce dose to adjacent organs-at-risk in the treatment of carcinoma of the rectum. Therefore, we performed a comprehensive dosimetric evaluation of IMRT compared to 3-dimensional conformal radiation therapy (3DCRT) in standard, preoperative treatment for rectal cancer. Using RTOG consensus anorectal contouring guidelines, treatment volumes were generated for ten patients treated preoperatively at our institution for rectal carcinoma, with IMRT plans compared to plans derived from classic anatomic landmarks, as well as 3DCRT plans treating the RTOG consensus volume. The patients were all T3, were node-negative (N = 1) or node-positive (N = 9), and were planned to a total dose of 45-Gy. Pairwise comparisons were made between IMRT and 3DCRT plans with respect to dose-volume histogram parameters. IMRT plans had superior PTV coverage, dose homogeneity, and conformality in treatment of the gross disease and at-risk nodal volume, in comparison to 3DCRT. Additionally, in comparison to the 3DCRT plans, IMRT achieved a concomitant reduction in doses to the bowel (small bowel mean dose: 18.6-Gy IMRT versus 25.2-Gy 3DCRT; p = 0.005), bladder (V40Gy: 56.8% IMRT versus 75.4% 3DCRT; p = 0.005), pelvic bones (V40Gy: 47.0% IMRT versus 56.9% 3DCRT; p = 0.005), and femoral heads (V40Gy: 3.4% IMRT versus 9.1% 3DCRT; p = 0.005), with an improvement in absolute volumes of small bowel receiving dose levels known to induce clinically-relevant acute toxicity (small bowel V15Gy: 138-cc IMRT versus 157-cc 3DCRT; p = 0.005). We found that the IMRT treatment volumes were typically larger than that covered by classic bony landmark-derived fields, without incurring penalty with respect to adjacent organs-at-risk. For rectal carcinoma, IMRT, compared to 3DCRT, yielded plans superior with respect to target coverage, homogeneity, and conformality, while lowering dose to adjacent organs-at-risk. This is achieved despite treating larger volumes, raising the possibility of a clinically-relevant improvement in the therapeutic ratio through the use of IMRT with a belly-board apparatus.

Phase I-II study of multiple daily fractions for palliation of advanced head and neck malignancies.

PubMed

Paris, K J; Spanos, W J; Lindberg, R D; Jose, B; Albrink, F

1993-03-15

To assess palliation of advance head and neck malignancies with the use of rapid hyper fractionation studies similar to the RTOG 85-02. 37 patients with 39 lesions were entered into the non-randomized Phase I-II protocol, between 1984 and 1991. Previously untreated malignancies were present in 24 lesions, primary recurrent diseases in six patients, metastasis to the head and neck in five patients and skin primaries in the remaining two cases. At presentation 15 of 37 patients (or 17 of 39 lesions) were in operable due to poor medical status, eight patients were considered technically in operable due to extent of disease, 10 patients had distant metastasis and four patients refused surgery. The protocol uses twice a day fraction (370 cGy per fraction) for 2 consecutive days totalling 1,480 cGy per course. Three courses were given at 3-week intervals for a final tumor dose of 4,440 cGy in twelve fraction over 8-9 weeks. Eleven of 39 lesions had complete response; 19 lesions had partial response; 4 lesions had no response; 3 lesions progressed under treatment. Response could not be assessed in two patients. The average survival after completion of therapy was 4.5 months ranging from 2 weeks to 31 months. Palliation was achieved in 33 of 39 lesions. The acute reactions were minimal and no late or long term complications were noted. The absence of significant complications with reasonable response in the high rate of palliation suggests that this rapid hyper fractionation palliation study should be studied for further evaluation.

TU-F-12A-09: GLCM Texture Analysis for Normal-Tissue Toxicity: A Prospective Ultrasound Study of Acute Toxicity in Breast-Cancer Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, T; Yang, X; Curran, W

2014-06-15

Purpose: To evaluate the morphologic and structural integrity of the breast glands using sonographic textural analysis, and identify potential early imaging signatures for radiation toxicity following breast-cancer radiotherapy (RT). Methods: Thirty-eight patients receiving breast RT participated in a prospective ultrasound imaging study. Each participant received 3 ultrasound scans: 1 week before RT (baseline), and at 6-week and 3-month follow-ups. Patients were imaged with a 10-MHz ultrasound on the four quadrant of the breast. A second order statistical method of texture analysis, called gray level co-occurrence matrix (GLCM), was employed to assess RT-induced breast-tissue toxicity. The region of interest (ROI) wasmore » 28 mm × 10 mm in size at a 10 mm depth under the skin. Twenty GLCM sonographic features, ratios of the irradiated breast and the contralateral breast, were used to quantify breast-tissue toxicity. Clinical assessment of acute toxicity was conducted using the RTOG toxicity scheme. Results: Ninety-seven ultrasound studies (776 images) were analyzed; and 5 out of 20 sonographic features showed significant differences (p < 0.05) among the baseline scans, the acute toxicity grade 1 and 2 groups. These sonographic features quantified the degree of tissue damage through homogeneity, heterogeneity, randomness, and symmetry. Energy ratio value decreased from 108±0.05 (normal) to 0.99±0.05 (Grade 1) and 0.84±0.04 (Grade 2); Entropy ratio value increased from 1.01±0.01 to 1.02±0.01 and 1.04±0.01; Contrast ratio value increased from 1.03±0.03 to 1.07±0.06 and 1.21±0.09; Variance ratio value increased from 1.06±0.03 to 1.20±0.04 and 1.42±0.10; Cluster Prominence ratio value increased from 0.98±0.02 to 1.01±0.04 and 1.25±0.07. Conclusion: This work has demonstrated that the sonographic features may serve as imaging signatures to assess radiation-induced normal tissue damage. While these findings need to be validated in a larger cohort, they suggest that ultrasound imaging may be used to improve early detection of normal-tissue toxicity in breast-cancer RT.« less

Improving the consistency in cervical esophageal target volume definition by special training.

PubMed

Tai, Patricia; Van Dyk, Jake; Battista, Jerry; Yu, Edward; Stitt, Larry; Tonita, Jon; Agboola, Olusegun; Brierley, James; Dar, Rashid; Leighton, Christopher; Malone, Shawn; Strang, Barbara; Truong, Pauline; Videtic, Gregory; Wong, C Shun; Wong, Rebecca; Youssef, Youssef

2002-07-01

Three-dimensional conformal radiation therapy requires the precise definition of the target volume. Its potential benefits could be offset by the inconsistency in target definition by radiation oncologists. In a previous survey of radiation oncologists, a large degree of variation in target volume definition of cervical esophageal cancer was noted for the boost phase of radiotherapy. The present study evaluated whether special training could improve the consistency in target volume definitions. A pre-training survey was performed to establish baseline values. This was followed by a special one-on-one training session on treatment planning based on the RTOG 94-05 protocol to 12 radiation oncologists. Target volumes were redrawn immediately and at 1-2 months later. Post-training vs. pre-training target volumes were compared. There was less variability in the longitudinal positions of the target volumes post-training compared to pre-training (p < 0.05 in 5 of 6 comparisons). One case had more variability due to the lack of a visible gross tumor on CT scans. Transverse contours of target volumes did not show any significant difference pre- or post-training. For cervical esophageal cancer, this study suggests that special training on protocol guidelines may improve consistency in target volume definition. Explicit protocol directions are required for situations where the gross tumor is not easily visible on CT scans. This may be particularly important for multicenter clinical trials, to reduce the occurrences of protocol violations.

Randomized phase II trial evaluating two paclitaxel and cisplatin-containing chemoradiation regimens as adjuvant therapy in resected gastric cancer (RTOG-0114).

PubMed

Schwartz, Gary K; Winter, Kathryn; Minsky, Bruce D; Crane, Christopher; Thomson, P John; Anne, Pramila; Gross, Howard; Willett, Christopher; Kelsen, David

2009-04-20

The investigational arm of INT0116, a fluorouracil (FU) and leucovorin-containing chemoradiotherapy regimen, is a standard treatment for patients with resected gastric cancer with a 2-year disease-free survival rate (DFS) of 52%. Toxicity is also significant. More beneficial and safer regimens are needed. We performed a randomized phase II study among 39 cancer centers to evaluate two paclitaxel and cisplatin-containing regimens, one with FU (PCF) and the other without (PC) in patients with resected gastric cancer. Patients received two cycles of postoperative chemotherapy followed by 45 Gy of radiation with either concurrent FU and paclitaxel or paclitaxel and cisplatin. The primary objective was to show an improvement in 2-year DFS to 67% as compared with INT 0116. From May 2001 to February 2004 (study closure), 78 patients entered this study, and 73 were evaluable. At the planned interim analysis of 22 patients on PCF, grade 3 or higher GI toxicity was 59%. This was significantly worse than INT0116, and this arm was closed. Accrual continued on PC. The median DFS was 14.6 months for PCF and has not been reached for PC. For PC the 2-year DFS is 52% (95% CI, 36% to 68%). Though PC appears to be safe and the median DFS favorable, the DFS failed to exceed the lower bound of 52.9% for the targeted 67% DFS at 2 years and can not be recommended as the adjuvant arm for future randomized trials.

Randomized Phase II Trial Evaluating Two Paclitaxel and Cisplatin–Containing Chemoradiation Regimens As Adjuvant Therapy in Resected Gastric Cancer (RTOG-0114)

PubMed Central

Schwartz, Gary K.; Winter, Kathryn; Minsky, Bruce D.; Crane, Christopher; Thomson, P. John; Anne, Pramila; Gross, Howard; Willett, Christopher; Kelsen, David

2009-01-01

Purpose The investigational arm of INT0116, a fluorouracil (FU) and leucovorin–containing chemoradiotherapy regimen, is a standard treatment for patients with resected gastric cancer with a 2-year disease-free survival rate (DFS) of 52%. Toxicity is also significant. More beneficial and safer regimens are needed. Patients and Methods We performed a randomized phase II study among 39 cancer centers to evaluate two paclitaxel and cisplatin–containing regimens, one with FU (PCF) and the other without (PC) in patients with resected gastric cancer. Patients received two cycles of postoperative chemotherapy followed by 45 Gy of radiation with either concurrent FU and paclitaxel or paclitaxel and cisplatin. The primary objective was to show an improvement in 2-year DFS to 67% as compared with INT 0116. Results From May 2001 to February 2004 (study closure), 78 patients entered this study, and 73 were evaluable. At the planned interim analysis of 22 patients on PCF, grade 3 or higher GI toxicity was 59%. This was significantly worse than INT0116, and this arm was closed. Accrual continued on PC. The median DFS was 14.6 months for PCF and has not been reached for PC. For PC the 2-year DFS is 52% (95% CI, 36% to 68%). Conclusion Though PC appears to be safe and the median DFS favorable, the DFS failed to exceed the lower bound of 52.9% for the targeted 67% DFS at 2 years and can not be recommended as the adjuvant arm for future randomized trials. PMID:19273696

Urinary adverse effects of pelvic radiotherapy

PubMed Central

Liberman, Daniel; Mehus, Brian

2014-01-01

Objective Radiation is an integral part of the treatment of many pelvic tumors. The cellular death induced by radiotherapy (RT) benefits cancer control but can also result in adverse effects (AEs) on the organ being treated or those adjacent to it. RT for cancers of the pelvis (bladder, prostate, rectum, uterus or cervix) can result in AEs in the urinary tract. While the acute urinary AEs of pelvic RT are well described, late AEs are less well characterized. The burden of treatment for late AEs may be large given the prevalence of tumors in the pelvis and the high utilization of RT to treat them. Review For prostate cancer, grade 1 and 2 urinary AEs following external beam radiation therapy (EBRT) are reported to occur in 20-43% and 7-19%, respectively, with a follow up of 10 years. Three-year cumulative risk for grade ≥2 urinary AEs is 28-30%. Following brachytherapy (BT), rates of urinary AEs at 5 years are reported to be 36%, 24%, 6.2% and 0.1% for Radiation Therapy Oncology Group (RTOG) grade 1, 2, 3, and 4, respectively. For bladder cancer, with a median follow-up of 5 years, 7-12% of patients who receive RT experience urinary AEs of grade 3 or more. For cervical cancer, there remains a 0.25% per year risk of severe AEs for at least 25 years following RT, and ureteral stricture is a well-described AE. For endometrial cancer, severe urinary AEs are rare, but at 13 years of follow up, patients report a significantly worse quality of life with respect to urinary function. In rectal cancer, preoperative RT has a lower risk of AEs than postoperative RT, and few urinary AEs are reported in the literature. Conclusions Urinary AEs can manifest long after RT, and there is a paucity of studies describing rates of these long-term AEs. It is important that the possible complications of RT are recognized by providers and properly communicated to patients so that they are able to make informed decisions about their cancer treatment. PMID:26813159

Assessment of target dose delivery in anal cancer using in vivo thermoluminescent dosimetry.

PubMed

Weber, D C; Nouet, P; Kurtz, J M; Allal, A S

2001-04-01

To measure anal dose during external beam radiotherapy (EBRT) using in vivo dosimetry, to study the difference of measured from prescribed dose values, and to evaluate possible associations of such differences with acute and late skin/mucosal toxicity and anorectal function. Thirty-one patients with localized anal carcinoma underwent in vivo measurements during the first EBRT session. Themoluminescent dosimeters (TLD) were placed at the center of the anal verge according to a localization protocol. No bolus was used. Patients received a median dose of 39.6 Gy (range: 36-45 Gy) by anteroposterior opposed AP/PA pelvic fields with 6 or 18 MV photons, followed by a median boost dose of 20 Gy (range: 13-24 Gy). Concomitant chemotherapy (CCT), consisting of 1-2 cycles of continuous infusion 5-fluorouracil (5-FU) and bolus mitomycin-C (MMC), was usually administered during the first weeks of the pelvic and boost EBRT courses. Acute and late skin/mucosal reactions were recorded according to the Radiation Therapy Oncology Group (RTOG) toxicity scale. Anal sphincter function was assessed using the Memorial Sloan Kettering Cancer Center (MSKCC) scale. TLD anal doses differed by a mean of 5.8% (SD: 5.8) in comparison to the central axis prescribed dose. Differences of at least 10% and at least 15% were observed in eight (26%) and three (9.7%) patients, respectively. TLD doses did not significantly correlate with acute or late grade 2-3 skin or mucosal toxicity. However, patients having good-fair MSKCC anal function had a significantly greater mean difference in anal TLD dose (10.5%, SD: 5.9) than patients having excellent function (3.8%, SD: 4.6) (P = 0.004). Prescribed dose values, length of follow-up, and age at diagnosis did not correlate with late sphincter function. These data show that AP/PA fields using megavoltage photons deliver adequate dose to the anal verge. However, in about one quarter of patients treated with this technique the anal dose varied from the prescribed dose by at least 10%. The observed correlation of TLD values and late sphincter function suggests that direct measurement of the dose delivered to the anal verge might be clinically relevant.

Multi-system verification of registrations for image-guided radiotherapy in clinical trials.

PubMed

Cui, Yunfeng; Galvin, James M; Straube, William L; Bosch, Walter R; Purdy, James A; Li, X Allen; Xiao, Ying

2011-09-01

To provide quantitative information on the image registration differences from multiple systems for image-guided radiotherapy (IGRT) credentialing and margin reduction in clinical trials. Images and IGRT shift results from three different treatment systems (Tomotherapy Hi-Art, Elekta Synergy, Varian Trilogy) have been sent from various institutions to the Image-Guided Therapy QA Center (ITC) for evaluation for the Radiation Therapy Oncology Group (RTOG) trials. Nine patient datasets (five head-and-neck and four prostate) were included in the comparison, with each patient having 1-4 daily individual IGRT studies. In all cases, daily shifts were re-calculated by re-registration of the planning CT with the daily IGRT data using three independent software systems (MIMvista, FocalSim, VelocityAI). Automatic fusion was used in all calculations. The results were compared with those submitted from institutions. Similar regions of interest (ROIs) and same initial positions were used in registrations for inter-system comparison. Different slice spacings for CBCT sampling and different ROIs for registration were used in some cases to observe the variation of registration due to these factors. For the 54 comparisons with head-and-neck datasets, the absolute values of differences of the registration results between different systems were 2.6±2.1 mm (mean±SD; range 0.1-8.6 mm, left-right [LR]), 1.7±1.3 mm (0.0-4.9 mm, superior-inferior [SI]), and 1.8±1.1 mm (0.1-4.0 mm, anterior-posterior [AP]). For the 66 comparisons in prostate cases, the differences were 1.1±1.0 mm (0.0-4.6 mm, LR), 2.1±1.7 mm (0.0-6.6 mm, SI), and 2.0±1.8 mm (0.1-6.9 mm, AP). The differences caused by the slice spacing variation were relatively small, and the different ROI selections in FocalSim and MIMvista also had limited impact. The extent of differences was reported when different systems were used for image registration. Careful examination and quality assurance of the image registration process are crucial before considering margin reduction using IGRT in clinical trials. Copyright © 2011 Elsevier Inc. All rights reserved.

Pancreatic cancer planning: Complex conformal vs modulated therapies.

PubMed

Chapman, Katherine L; Witek, Matthew E; Chen, Hongyu; Showalter, Timothy N; Bar-Ad, Voichita; Harrison, Amy S

2016-01-01

To compare the roles of intensity-modulated radiation therapy (IMRT) and volumetric- modulated arc therapy (VMAT) therapy as compared to simple and complex 3-dimensional chemoradiotherpy (3DCRT) planning for resectable and borderline resectable pancreatic cancer. In all, 12 patients who received postoperative radiotherapy (8) or neoadjuvant concurrent chemoradiotherapy (4) were evaluated retrospectively. Radiotherapy planning was performed for 4 treatment techniques: simple 4-field box, complex 5-field 3DCRT, 5 to 6-field IMRT, and single-arc VMAT. All volumes were approved by a single observer in accordance with Radiation Therapy Oncology Group (RTOG) Pancreas Contouring Atlas. Plans included tumor/tumor bed and regional lymph nodes to 45Gy; with tumor/tumor bed boosted to 50.4Gy, at least 95% of planning target volume (PTV) received the prescription dose. Dose-volume histograms (DVH) for multiple end points, treatment planning, and delivery time were assessed. Complex 3DCRT, IMRT, and VMAT plans significantly (p < 0.05) decreased mean kidney dose, mean liver dose, liver (V30, V35), stomach (D10%), stomach (V45), mean right kidney dose, and right kidney (V15) as compared with the simple 4-field plans that are most commonly reported in the literature. IMRT plans resulted in decreased mean liver dose, liver (V35), and left kidney (V15, V18, V20). VMAT plans decreased small bowel (D10%, D15%), small bowel (V35, V45), stomach (D10%, D15%), stomach (V35, V45), mean liver dose, liver (V35), left kidney (V15, V18, V20), and right kidney (V18, V20). VMAT plans significantly decreased small bowel (D10%, D15%), left kidney (V20), and stomach (V45) as compared with IMRT plans. Treatment planning and delivery times were most efficient for simple 4-field box and VMAT. Excluding patient setup and imaging, average treatment delivery was within 10minutes for simple and complex 3DCRT, IMRT, and VMAT treatments. This article shows significant improvements in 3D plan performance with complex planning over the more frequently compared 3- or 4-field simple 3D planning techniques. VMAT plans continue to demonstrate potential for the most organ sparing. However, further studies are required to identify if dosimetric benefits associated with inverse optimized planning can be translated into clinical benefits and if these treatment techniques are value-added therapies for this group of patients with cancer. Published by Elsevier Inc.

A Phase II Study of Submandibular Gland Transfer Prior to Radiation for Prevention of Radiation-induced Xerostomia in Head-and-Neck Cancer (RTOG 0244)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jha, Naresh, E-mail: naresh.jha@albertahealthservices.ca; Harris, Jonathan; Seikaly, Hadi

Purpose: We report the results of a phase II study to determine the reproducibility of a submandibular salivary gland transfer (SGT) surgical technique for prevention of radiation (XRT)-induced xerostomia in a multi-institutional setting and to assess severity of xerostomia. Methods and Materials: Eligible patients had surgery for primary, neck dissection, and SGT, followed by XRT, during which the transferred salivary gland was shielded. Intensity modulated radiation therapy, amifostine, and pilocarpine were not allowed, but postoperative chemotherapy was allowed. Each operation was reviewed by 2 reviewers and radiation by 1 reviewer. If 13 or more (of 43) were 'not per protocol,'more » then the technique would be considered not reproducible as per study design. The secondary endpoint was the rate of acute xerostomia, grade 2 or higher, and a rate of {<=}51% was acceptable. Results: Forty-four of the total 49 patients were analyzable: male (81.8%), oropharynx (63.6%), stage IV (61.4%), median age 56.5 years. SGT was 'per protocol' or within acceptable variation in 34 patients (77.3%) and XRT in 79.5%. Nine patients (20.9%) developed grade 2 acute xerostomia; 2 had grade 0-1 xerostomia (4.7%) but started on amifostine/pilocarpine. Treatment for these 11 patients (25.6%) was considered a failure for the xerostomia endpoint. Thirteen patients died; median follow-up for 31 surviving patients was 2.9 years. Two-year overall and disease-free survival rates were 76.4% and 71.7%, respectively. Conclusions: The technique of submandibular SGT is reproducible in a multicenter setting. Seventy-four percent of patients were prevented from XRT-induced acute xerostomia.« less

A phase II study of submandibular gland transfer prior to radiation for prevention of radiation-induced xerostomia in head-and-neck cancer (RTOG 0244).

PubMed

Jha, Naresh; Harris, Jonathan; Seikaly, Hadi; Jacobs, John R; McEwan, A J B; Robbins, K Thomas; Grecula, John; Sharma, Anand K; Ang, K Kian

2012-10-01

We report the results of a phase II study to determine the reproducibility of a submandibular salivary gland transfer (SGT) surgical technique for prevention of radiation (XRT)-induced xerostomia in a multi-institutional setting and to assess severity of xerostomia. Eligible patients had surgery for primary, neck dissection, and SGT, followed by XRT, during which the transferred salivary gland was shielded. Intensity modulated radiation therapy, amifostine, and pilocarpine were not allowed, but postoperative chemotherapy was allowed. Each operation was reviewed by 2 reviewers and radiation by 1 reviewer. If 13 or more (of 43) were "not per protocol," then the technique would be considered not reproducible as per study design. The secondary endpoint was the rate of acute xerostomia, grade 2 or higher, and a rate of ≤ 51% was acceptable. Forty-four of the total 49 patients were analyzable: male (81.8%), oropharynx (63.6%), stage IV (61.4%), median age 56.5 years. SGT was "per protocol" or within acceptable variation in 34 patients (77.3%) and XRT in 79.5%. Nine patients (20.9%) developed grade 2 acute xerostomia; 2 had grade 0-1 xerostomia (4.7%) but started on amifostine/pilocarpine. Treatment for these 11 patients (25.6%) was considered a failure for the xerostomia endpoint. Thirteen patients died; median follow-up for 31 surviving patients was 2.9 years. Two-year overall and disease-free survival rates were 76.4% and 71.7%, respectively. The technique of submandibular SGT is reproducible in a multicenter setting. Seventy-four percent of patients were prevented from XRT-induced acute xerostomia. Copyright © 2012 Elsevier Inc. All rights reserved.

A Phase II Study of Submandibular Gland Transfer Prior to Radiation for Prevention of Radiation-Induced Xerostomia in Head and Neck Cancer (Rtog 0244)s

PubMed Central

Jha, Naresh; Harris, Jonathan; Seikaly, Hadi; Jacobs, John R.; McEwan, AJB.; Thomas Robbins, K.; Grecula, John; Sharma, Anand K.; Ang, K. Kian

2012-01-01

Purpose We report the results of a phase II study to determine reproducibility of surgical technique of submandibular salivary gland transfer (SGT) for prevention of radiation (XRT) induced xerostomia in a multi-institutional setting and to assess severity of xerostomia. Methods and Materials Eligible patients had surgery for primary, neck dissection, and SGT followed by XRT during which the transferred salivary gland was shielded. IMRT, amifostine, and pilocarpine were not allowed, but postoperative chemotherapy was allowed. Each operation was reviewed by two and radiation by one reviewer. If 13 or more (out of 43) were “not per protocol”, then technique would be considered not reproducible as per study design. The secondary endpoint was the rate of acute xerostomia, Grade 2 or higher and a rate of ≤ 51% was acceptable. Results 44 of the total 49 patients were analyzable: male (81.8%), oropharynx (63.6%), stage IV (61.4%), median age 56.5 years. SGT was “per protocol” or with acceptable variation in 34 patients (77.3%) and XRT in 79.5%. 9 patients (20.9%) developed grade II acute xerostomia; 2 had grade 0 -1 xerostomia (4.7%) but started on amifostine/pilocarpine. These 11 patients (25.6%) were considered failures for the xerostomia endpoint. 13 patients have died; median follow-up for 31 surviving patients is 2.9 years. Two-year overall and disease-free survival rates are 76.4% and 71.7%, respectively. Conclusions the technique of submandibular salivary gland transfer procedure is reproducible in a multicenter setting. Seventy-four percent of patients had prevention of XRT induced acute xerostomia. PMID:22541957

SU-E-T-797: Variations of Cardiac Dose at Different Respiratory Status in CyberKnife M6â„¢ Treatment Plans for Accelerated Partial Breast Irradiation (APBI)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Long, S; Shang, C; Evans, G

2015-06-15

Purpose: Cyberknife robotic assisted radiation delivery has become a choice for accelerated breast RT, while a slightly increased cardiac dose has been reported. The dose dynamics throughout the respiration cycle has scarcely been explored. This study was designed to investigate the dose changes at each respiratory phase or status during respiration cycle. Methods: Six patients with 4DCT studies and six patients with a pair of free-breathing and deep breath-hold CT sets were used for dosimetry comparisons. 4DCT sets were obtained by Siemens™ CT and its respiratory gating system, comprising of 8 phases. Standard APBI plan at 340 cGy was donemore » per fraction per NSABP B-39/RTOG 0413 and modulated with Cyberknife M6™ on MultiPlan™5.1.2. For the purpose of this study, the tumor volume was outlined in the media-lower quadrant of the left breast. Results: Except for D5cc in plans with 4DCT, cardiac doses are significantly different between respiratory phases in well inhaled breathing phases, and more significantly in plans with BH CT. Mean cardiac doses in 100% inhalation phase were often found to be 5–15% (p< 0.02) less than those in other phases. Conclusion: Although ineligible cardiac doses are noted in APBI plans using 4D free-breathing CT and instantaneous free breathing CT series, a reduction in cardiac dose was seen for the well-inhaled phases. This provides practical guidance for cardiac dose reduction applicable with CK M6 APBR.« less

[Low dose volume histogram analysis of the lungs in prediction of acute radiation pneumonitis in patients with esophageal cancer treated with three-dimensional conformal radiotherapy].

PubMed

Shen, Wen-bin; Zhu, Shu-chai; Gao, Hong-mei; Li, You-mei; Liu, Zhi-kun; Li, Juan; Su, Jing-wei; Wan, Jun

2013-01-01

To investigate the predictive value of low dose volume of the lung on acute radiation pneumonitis (RP) in patients with esophageal cancer treated with three-dimensional conformal radiotherapy (3D-CRT) only, and to analyze the relation of comprehensive parameters of the dose-volume V5, V20 and mean lung dose (MLD) with acute RP. Two hundred and twenty-two patients with esophageal cancer treated by 3D-CRT have been followed up. The V5-V30 and MLD were calculated from the dose-volume histogram system. The clinical factors and treatment parameters were collected and analyzed. The acute RP was evaluated according to the RTOG toxicity criteria. The acute RP of grade 1, 2, 3 and 4 were observed in 68 (30.6%), 40 (18.0%), 8 (3.6%) and 1 (0.5%) cases, respectively. The univariate analysis of measurement data:The primary tumor length, radiation fields, MLD and lung V5-V30 had a significant relationship with the acute RP. The magnitude of the number of radiation fields, the volume of GTV, MLD and Lung V5-V30 had a significant difference in whether the ≥ grade 1 and ≥ grade 2 acute RP developed or not. Binary logistic regression analysis showed that MLD, Lung V5, V20 and V25 were independent risk factors of ≥ grade 1 acute RP, and the radiation fields, MLD and Lung V5 were independent risk factors of ≥ grade 2 acute RP. The ≥ grade 1 and ≥ grade 2 acute RP were significantly decreased when MLD less than 14 Gy, V5 and V20 were less than 60% and 28%,respectively. When the V20 ≤ 28%, the acute RP was significantly decreased in V5 ≤ 60% group. When the MLD was ≤ 14 Gy, the ≥ 1 grade acute RP was significantly decreased in the V5 ≤ 60% group. When the MLD was >14 Gy, the ≥ grade 2 acute RP was significantly decreased in the V5 ≤ 60% group. The low dose volume of the lung is effective in predicting radiation pneumonitis in patients with esophageal cancer treated with 3D-CRT only. The comprehensive parameters combined with V5, V20 and MLD may increase the effect in predicting radiation pneumonitis.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gunderson, Leonard L., E-mail: gunderson.leonard@mayo.edu; Moughan, Jennifer; Ajani, Jaffer A.

Purpose: The long-term update of US GI Intergroup RTOG 98-11 anal cancer trial found that concurrent chemoradiation (CCRT) with fluorouracil (5-FU) plus mitomycin had a significant impact on disease-free survival (DFS) and overall survival (OS) compared with induction plus concurrent 5-FU plus cisplatin. The intent of the current analysis was to determine the impact of tumor node (TN) category of disease on survival (DFS and OS), colostomy failure (CF), and relapse (local-regional failure [LRF] and distant metastases [DM]) in this patient group. Methods and Materials: DFS and OS were estimated univariately by using the Kaplan-Meier method, and 6 TN categoriesmore » were compared by the log–rank test (T2N0, T3N0, T4N0, T2N1-3, T3N1-3, and T4N1-3). Time to relapse and colostomy were estimated by the cumulative incidence method, and TN categories were compared using Gray's test. Results: Of 682 patients, 620 were analyzable for outcomes by TN category. All endpoints showed statistically significant differences among the TN categories of disease (OS, P<.0001; DFS, P<.0001; LRF, P<.0001; DM, P=.0011; CF, P=.01). Patients with the poorest OS, DFS, and LRF outcomes were those with T3-4N-positive (+) disease. CF was lowest for T2N0 and T2N+ (11%, 11%, respectively) and worst for the T4N0, T3N+, and T4N+ categories (26%, 27%, 24%, respectively). Conclusions: TN category of disease has a statistically significant impact on OS, DFS, LRF, DM, and CF in patients treated with CCRT and provides excellent prognostic information for outcomes in patients with anal carcinoma. Significant challenges remain for patients with T4N0 and T3-4N+ categories of disease with regard to survival, relapse, and CF and lesser challenges for T2-3N0/T2N+ categories.« less

Human Papillomavirus and Overall Survival After Progression of Oropharyngeal Squamous Cell Carcinoma

PubMed Central

Fakhry, Carole; Zhang, Qiang; Nguyen-Tan, Phuc Felix; Rosenthal, David; El-Naggar, Adel; Garden, Adam S.; Soulieres, Denis; Trotti, Andy; Avizonis, Vilija; Ridge, John Andrew; Harris, Jonathan; Le, Quynh-Thu; Gillison, Maura

2014-01-01

Purpose Risk of cancer progression is reduced for patients with human papillomavirus (HPV) –positive oropharynx cancer (OPC) relative to HPV-negative OPC, but it is unknown whether risk of death after progression is similarly reduced. Patients and Methods Patients with stage III-IV OPC enrolled onto Radiation Therapy Oncology Group trials 0129 or RTOG 0522 who had known tumor p16 status plus local, regional, and/or distant progression after receiving platinum-based chemoradiotherapy were eligible for a retrospective analysis of the association between tumor p16 status and overall survival (OS) after disease progression. Rates were estimated by Kaplan-Meier method and compared by log-rank; hazard ratios (HRs) were estimated by Cox models. Tests and models were stratified by treatment protocol. Results A total of 181 patients with p16-positive (n = 105) or p16-negative (n = 76) OPC were included in the analysis. Patterns of failure and median time to progression (8.2 v 7.3 months; P = .67) were similar for patients with p16-positive and p16-negative tumors. After a median follow-up period of 4.0 years after disease progression, patients with p16-positive OPC had significantly improved survival rates compared with p16-negative patients (2-year OS, 54.6% v 27.6%; median, 2.6 v 0.8 years; P < .001). p16-positive tumor status (HR, 0.48; 95% CI, 0.31 to 0.74) and receipt of salvage surgery (HR, 0.48; 95% CI; 0.27 to 0.84) reduced risk of death after disease progression whereas distant versus locoregional progression (HR, 1.99; 95% CI, 1.28 to 3.09) increased risk, after adjustment for tumor stage and cigarette pack-years at enrollment. Conclusion Tumor HPV status is a strong and independent predictor of OS after disease progression and should be a stratification factor for clinical trials for patients with recurrent or metastatic OPC. PMID:24958820

Superficial ocular malignancies treated with strontium-90 brachytherapy: long term outcomes

PubMed Central

Gurram, Lavanya; Laskar, Sarbani Ghosh; Chaudhari, Suresh; Khanna, Nehal; Upreti, Rituraj

2015-01-01

Purpose The incidence of conjunctival malignancies is less than 1%. Though surgical excision remains the mainstay of treatment, the incidence of positive surgical margins and local recurrence rates are high, which is approximately up to 33% in negative margins and 56% in positive margins. Radiotherapy reduces the risk of recurrence in these cases. Brachytherapy using β emitters such as strontium-90 (90Sr) is an ideal treatment technique for these tumors with the advantage of treating only a few millimeters of tissue while sparing the underlying normal eye. We report the long term outcomes in the form of local control and late sequelae of patients with conjunctival malignancies treated with 90Sr applicator brachytherapy. Material and methods During 1999-2013, 13 patients with conjunctival tumors, treated using 90Sr brachytherapy were analyzed. Brachytherapy was either in a post-operative adjuvant or in a recurrent setting. Local control (LC), disease free survival (DFS), overall survival (OS), and late sequelae were evaluated. Results The median age at presentation was 47 years (range: 11-71 years). Thirteen patients with 15 tumors were treated. The commonest histology was squamous cell carcinoma. The median dose was 44 Gy over 11 fractions. The median follow up of all the patients was 51 months (range: 3-139 months). The median follow up of patients with carcinoma only was 64 months with a LC and DFS of 90.9% at 5 years. None of the patients developed ≥ grade II Radiation Therapy Oncology Group (RTOG) acute toxicities. One patient developed a focal scar and another developed corneal opacification at the limbus. Vision was not impaired in any of the patients. Conclusions Strontium-90 brachytherapy used in early invasive conjunctival malignancies as an adjunct to surgery in primary and recurrent settings, results in optimal disease control and ocular functional outcomes. PMID:26622243

SU-E-J-53: Dosimetric Evaluation at Volumetric Modulated Arc Therapy for Treatment of Prostate Cancer Using Single Or Double Arcs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Silva, D; Salmon, H; Pavan, G

2014-06-01

Purpose: Evaluate and compare retrospective prostate treatment plan using Volumetric Modulated Arc Therapy (RapidArc™ - Varian) technique with single or double arcs at COI Group. Methods: Ten patients with present prostate and seminal vesicle neoplasia were replanned as a target treatment volume and a prescribed dose of 78 Gy. A baseline planning, using single arc, was developed for each case reaching for the best result on PTV, in order to minimize the dose on organs at risk (OAR). Maintaining the same optimization objectives used on baseline plan, two copies for optimizing single and double arcs, have been developed. The plansmore » were performed with 10 MV photon beam energy on Eclipse software, version 11.0, making use of Trilogy linear accelerator with Millenium HD120 multileaf collimator. Comparisons on PTV have been performed, such as: maximum, minimum and mean dose, gradient dose, as well as the quantity of monitor units, treatment time and homogeneity and conformity index. OARs constrains dose have been evaluated, comparing both optimizations. Results: Regarding PTV coverage, the difference of the minimum, maximum and mean dose were 1.28%, 0.7% and 0.2% respectively higher for single arc. When analyzed the index of homogeneity found a difference of 0.99% higher when compared with double arcs. However homogeneity index was 0.97% lower on average by using single arc. The doses on the OARs, in both cases, were in compliance to the recommended limits RTOG 0415. With the use of single arc, the quantity of monitor units was 10,1% lower, as well as the Beam-On time, 41,78%, when comparing double arcs, respectively. Conclusion: Concerning the optimization of patients with present prostate and seminal vesicle neoplasia, the use of single arc reaches similar objectives, when compared to double arcs, in order to decrease the treatment time and the quantity of monitor units.« less

A semi-automated tool for treatment plan-quality evaluation and clinical trial quality assurance

NASA Astrophysics Data System (ADS)

Wang, Jiazhou; Chen, Wenzhou; Studenski, Matthew; Cui, Yunfeng; Lee, Andrew J.; Xiao, Ying

2013-07-01

The goal of this work is to develop a plan-quality evaluation program for clinical routine and multi-institutional clinical trials so that the overall evaluation efficiency is improved. In multi-institutional clinical trials evaluating the plan quality is a time-consuming and labor-intensive process. In this note, we present a semi-automated plan-quality evaluation program which combines MIMVista, Java/MATLAB, and extensible markup language (XML). More specifically, MIMVista is used for data visualization; Java and its powerful function library are implemented for calculating dosimetry parameters; and to improve the clarity of the index definitions, XML is applied. The accuracy and the efficiency of the program were evaluated by comparing the results of the program with the manually recorded results in two RTOG trials. A slight difference of about 0.2% in volume or 0.6 Gy in dose between the semi-automated program and manual recording was observed. According to the criteria of indices, there are minimal differences between the two methods. The evaluation time is reduced from 10-20 min to 2 min by applying the semi-automated plan-quality evaluation program.

SU-F-T-538: CyberKnife with MLC for Treatment of Large Volume Tumors: A Feasibility Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bichay, T; Mayville, A

2016-06-15

Purpose: CyberKnife is a well-documented modality for SRS and SBRT treatments. Typical tumors are small and 1–5 fractions are usually used. We determined the feasibility of using CyberKnife, with an InCise multileaf collimator option, for larger tumors undergoing standard dose and fractionation. The intent was to understand the limitation of using this modality for other external beam radiation treatments. Methods: Five tumors from different anatomical sites with volumes from 127.8 cc to 1,320.5 cc were contoured and planned on a Multiplan V5.1 workstation. The target average diameter ranged from 7 cm to 13 cm. The dose fractionation was 1.8–2.0 Gy/fractionmore » and 25–45 fractions for total doses of 45–81 Gy. The sites planned were: pancreas, head and neck, prostate, anal, and esophagus. The plans were optimized to meet conventional dose constraints based on various RTOG protocols for conventional fractionation. Results: The Multiplan treatment planning system successfully generated clinically acceptable plans for all sites studied. The resulting dose distributions achieved reasonable target coverage, all greater than 95%, and satisfactory normal tissue sparing. Treatment times ranged from 9 minutes to 38 minutes, the longest being a head and neck plan with dual targets receiving different doses and with multiple adjacent critical structures. Conclusion: CyberKnife, with the InCise multileaf collimation option, can achieve acceptable dose distributions in large volume tumors treated with conventional dose and fractionation. Although treatment times are greater than conventional accelerator time; target coverage and dose to critical structures can be kept within a clinically acceptable range. While time limitations exist, when necessary CyberKnife can provide an alternative to traditional treatment modalities for large volume tumors.« less

A feasibility study of [sup 252]Cf neutron brachytherapy, cisplatin + 5-FU chemo-adjuvant and accelerated hyperfractionated radiotherapy for advanced cervical cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murayama, Y.; Wierzbicki, J.; Bowen, M.G.

The purpose was to evaluate the feasibility and toxicity of [sup 252]Cf neutron brachytherapy combined with hyperaccelerated chemoradiotherapy for Stage III and IV cervical cancers. Eleven patients with advanced Stage IIIB-IVA cervical cancers were treated with [sup 252]Cf neutron brachytherapy in an up-front schedule followed by cisplatin (CDDP; 50 mg/m[sup 2]) chemotherapy and hyperfractionated accelerated (1.2 Gy bid) radiotherapy given concurrently with intravenous infusion of 5-Fluorouracil (5-FU) (1000 mg/m[sup 2]/day [times] 4 days) in weeks 1 and 4 with conventional radiation (weeks 2, 3, 5, and 6). Total dose at a paracervical point A isodose surface was 80-85 Gy-eq bymore » external and intracavitary therapy and 60 Gy at the pelvic sidewalls. Patients tolerated the protocol well. There was 91% compliance with the chemotherapy and full compliance with the [sup 252]Cf brachytherapy and the external beam radiotherapy. There were no problems with acute chemo or radiation toxicity. One patient developed a rectovaginal fistula (Grade 3-4 RTOG criteria) but no other patients developed significant late cystitis, proctitis or enteritis. There was complete response (CR) observed in all cases. With mean follow-up to 26 months, local control has been achieved with 90% actuarial 3-year survival with no evidence of disease (NED). [sup 252]Cf neutrons can be combined with cisplatin and 5-FU infusion chemotherapy plus hyperaccelerated chemoradiotherapy without unusual side effects or toxicity and with a high local response and tumor control rate. Further study of [sup 252]Cf neutron-chemoradiotherapy for advanced and bulky cervical cancer are indicated. The authors found chemotherapy was more effective with the improved local tumor control. 18 refs., 2 tabs.« less

Phase II Results of RTOG 0537: A Phase II/III Study Comparing Acupuncture-like Transcutaneous Electrical Nerve Stimulation Versus Pilocarpine in Treating Early Radiation-Induced Xerostomia

PubMed Central

Wong, Raimond K. W.; James, Jennifer L.; Sagar, Stephen; Wyatt, Gwen; Nguyen-Tân, Phuc Felix; Singh, Anurag K.; Lukaszczyk, Barbara; Cardinale, Francis; Yeh, Alexander M.; Berk, Lawrence

2011-01-01

Purpose This phase II component of a multi-institutional phase II/III randomized trial assessed the feasibility and preliminary efficacy of acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) in reducing radiation-induced xerostomia. Methods Head and neck cancer patients who were 3–24 months from completing radiotherapy ± chemotherapy (RT±C) and experiencing xerostomia symptoms with basal whole saliva production ≥0.1 ml/min and without recurrence were eligible. Patients received twice weekly ALTENS sessions (24 over 12 weeks) using a Codetron™ unit. The primary objective assessed the feasibility of ALTENS treatment. A patient was considered compliant if 19/24 ALTENS were delivered, with a targeted 85% compliance rate. Secondary objectives measured treatment-related toxicities and ALTENS effect on overall radiation-induced xerostomia burden using the University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS). Results Of 48 accrued patients, 47 were evaluable. Median age was 60 years; 84% were male, 70% completed RT±C for > 12 months and 21% had received prior pilocarpine. All ALTENS sessions were completed in 34 patients, but 9 and 1 completed 20–23 and 19 sessions respectively, representing a 94% total compliance rate. 6-month XeQOLS scores were available for 35 patients; 30 (86%) achieved a positive treatment response with a mean reduction of 35.9% (SD 36.1). Five patients developed grade 1–2 gastrointestinal toxicity and one had grade 1 pain event. Conclusions ALTENS treatment for radiation-induced xerostomia can be uniformly delivered in a cooperative multicenter setting and has possible beneficial treatment response. Given these results, the phase III component of this study was initiated. PMID:22252927

Pancreatic cancer planning: Complex conformal vs modulated therapies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chapman, Katherine L.; Witek, Matthew E.; Chen, Hongyu

To compare the roles of intensity-modulated radiation therapy (IMRT) and volumetric- modulated arc therapy (VMAT) therapy as compared to simple and complex 3-dimensional chemoradiotherpy (3DCRT) planning for resectable and borderline resectable pancreatic cancer. In all, 12 patients who received postoperative radiotherapy (8) or neoadjuvant concurrent chemoradiotherapy (4) were evaluated retrospectively. Radiotherapy planning was performed for 4 treatment techniques: simple 4-field box, complex 5-field 3DCRT, 5 to 6-field IMRT, and single-arc VMAT. All volumes were approved by a single observer in accordance with Radiation Therapy Oncology Group (RTOG) Pancreas Contouring Atlas. Plans included tumor/tumor bed and regional lymph nodes to 45more » Gy; with tumor/tumor bed boosted to 50.4 Gy, at least 95% of planning target volume (PTV) received the prescription dose. Dose-volume histograms (DVH) for multiple end points, treatment planning, and delivery time were assessed. Complex 3DCRT, IMRT, and VMAT plans significantly (p < 0.05) decreased mean kidney dose, mean liver dose, liver (V{sub 30}, V{sub 35}), stomach (D{sub 10}%), stomach (V{sub 45}), mean right kidney dose, and right kidney (V{sub 15}) as compared with the simple 4-field plans that are most commonly reported in the literature. IMRT plans resulted in decreased mean liver dose, liver (V{sub 35}), and left kidney (V{sub 15}, V{sub 18}, V{sub 20}). VMAT plans decreased small bowel (D{sub 10}%, D{sub 15}%), small bowel (V{sub 35}, V{sub 45}), stomach (D{sub 10}%, D{sub 15}%), stomach (V{sub 35}, V{sub 45}), mean liver dose, liver (V{sub 35}), left kidney (V{sub 15}, V{sub 18}, V{sub 20}), and right kidney (V{sub 18}, V{sub 20}). VMAT plans significantly decreased small bowel (D{sub 10}%, D{sub 15}%), left kidney (V{sub 20}), and stomach (V{sub 45}) as compared with IMRT plans. Treatment planning and delivery times were most efficient for simple 4-field box and VMAT. Excluding patient setup and imaging, average treatment delivery was within 10 minutes for simple and complex 3DCRT, IMRT, and VMAT treatments. This article shows significant improvements in 3D plan performance with complex planning over the more frequently compared 3- or 4-field simple 3D planning techniques. VMAT plans continue to demonstrate potential for the most organ sparing. However, further studies are required to identify if dosimetric benefits associated with inverse optimized planning can be translated into clinical benefits and if these treatment techniques are value-added therapies for this group of patients with cancer.« less

Radiobiological Impact of Reduced Margins and Treatment Technique for Prostate Cancer in Terms of Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jensen, Ingelise, E-mail: inje@rn.d; Carl, Jesper; Lund, Bente

2011-07-01

Dose escalation in prostate radiotherapy is limited by normal tissue toxicities. The aim of this study was to assess the impact of margin size on tumor control and side effects for intensity-modulated radiation therapy (IMRT) and 3D conformal radiotherapy (3DCRT) treatment plans with increased dose. Eighteen patients with localized prostate cancer were enrolled. 3DCRT and IMRT plans were compared for a variety of margin sizes. A marker detectable on daily portal images was presupposed for narrow margins. Prescribed dose was 82 Gy within 41 fractions to the prostate clinical target volume (CTV). Tumor control probability (TCP) calculations based on themore » Poisson model including the linear quadratic approach were performed. Normal tissue complication probability (NTCP) was calculated for bladder, rectum and femoral heads according to the Lyman-Kutcher-Burman method. All plan types presented essentially identical TCP values and very low NTCP for bladder and femoral heads. Mean doses for these critical structures reached a minimum for IMRT with reduced margins. Two endpoints for rectal complications were analyzed. A marked decrease in NTCP for IMRT plans with narrow margins was seen for mild RTOG grade 2/3 as well as for proctitis/necrosis/stenosis/fistula, for which NTCP <7% was obtained. For equivalent TCP values, sparing of normal tissue was demonstrated with the narrow margin approach. The effect was more pronounced for IMRT than 3DCRT, with respect to NTCP for mild, as well as severe, rectal complications.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lawton, Colleen A.F., E-mail: clawton@mcw.edu; Lin, Xiaolei; Hanks, Gerald E.

Purpose: Trial RTOG 9202 was a phase 3 randomized trial designed to determine the optimal duration of androgen deprivation therapy (ADT) when combined with definitive radiation therapy (RT) in the treatment of locally advanced nonmetastatic adenocarcinoma of the prostate. Long-term follow-up results of this study now available are relevant to the management of this disease. Methods and Materials: Men (N=1554) with adenocarcinoma of the prostate (cT2c-T4, N0-Nx) with a prostate-specific antigen (PSA) <150 ng/mL and no evidence of distant metastasis were randomized (June 1992 to April 1995) to short-term ADT (STAD: 4 months of flutamide 250 mg 3 times per day and goserelinmore » 3.6 mg per month) and definitive RT versus long-term ADT (LTAD: STAD with definitive RT plus an additional 24 months of monthly goserelin). Results: Among 1520 protocol-eligible and evaluable patients, the median follow-up time for this analysis was 19.6 years. In analysis adjusted for prognostic covariates, LTAD improved disease-free survival (29% relative reduction in failure rate, P<.0001), local progression (46% relative reduction, P=.02), distant metastases (36% relative reduction, P<.0001), disease-specific survival (30% relative reduction, P=.003), and overall survival (12% relative reduction, P=.03). Other-cause mortality (non–prostate cancer) did not differ (5% relative reduction, P=.48). Conclusions: LTAD and RT is superior to STAD and RT for the treatment of locally advanced nonmetastatic adenocarcinoma of the prostate and should be considered the standard of care.« less

Self‐expanding stent effects on radiation dosimetry in esophageal cancer

PubMed Central

Francis, Samual R.; Wang, Brian; Williams, Greg V.; Cox, Kristen; Adler, Douglas G.; Shrieve, Dennis C.; Salter, Bill J.

2013-01-01

It is the purpose of this study to evaluate how self‐expanding stents (SESs) affect esophageal cancer radiation planning target volumes (PTVs) and dose delivered to surrounding organs at risk (OARs). Ten patients were evaluated, for whom a SES was placed before radiation. A computed tomography (CT) scan obtained before stent placement was fused to the post‐stent CT simulation scan. Three methods were used to represent pre‐stent PTVs: 1) image fusion (IF), 2) volume approximation (VA), and 3) diameter approximation (DA). PTVs and OARs were contoured per RTOG 1010 protocol using Eclipse Treatment Planning software. Post‐stent dosimetry for each patient was compared to approximated pre‐stent dosimetry. For each of the three pre‐stent approximations (IF, VA, and DA), the mean lung and liver doses and the estimated percentages of lung volumes receiving 5 Gy, 10 Gy, 20 Gy, and 30 Gy, and heart volumes receiving 40 Gy were significantly lower (p‐values <0.02) than those estimated in the post‐stent treatment plans. The lung V5, lung V10, and heart V40 constraints were achieved more often using our pre‐stent approximations. Esophageal SES placement increases the dose delivered to the lungs, heart, and liver. This may have clinical importance, especially when the dose‐volume constraints are near the recommended thresholds, as was the case for lung V5, lung V10, and heart V40. While stents have established benefits for treating patients with significant dysphagia, physicians considering stent placement and radiation therapy must realize the effects stents can have on the dosimetry. PACS number: 87.55.dk PMID:23835387

Self-expanding stent effects on radiation dosimetry in esophageal cancer.

PubMed

Francis, Samual R; Anker, Christopher J; Wang, Brian; Williams, Greg V; Cox, Kristen; Adler, Douglas G; Shrieve, Dennis C; Salter, Bill J

2013-07-08

It is the purpose of this study to evaluate how self-expanding stents (SESs) affect esophageal cancer radiation planning target volumes (PTVs) and dose delivered to surrounding organs at risk (OARs). Ten patients were evaluated, for whom a SES was placed before radiation. A computed tomography (CT) scan obtained before stent placement was fused to the post-stent CT simulation scan. Three methods were used to represent pre-stent PTVs: 1) image fusion (IF), 2) volume approximation (VA), and 3) diameter approximation (DA). PTVs and OARs were contoured per RTOG 1010 protocol using Eclipse Treatment Planning software. Post-stent dosimetry for each patient was compared to approximated pre-stent dosimetry. For each of the three pre-stent approximations (IF, VA, and DA), the mean lung and liver doses and the estimated percentages of lung volumes receiving 5 Gy, 10 Gy, 20 Gy, and 30 Gy, and heart volumes receiving 40 Gy were significantly lower (p-values < 0.02) than those estimated in the post-stent treatment plans. The lung V5, lung V10, and heart V40 constraints were achieved more often using our pre-stent approximations. Esophageal SES placement increases the dose delivered to the lungs, heart, and liver. This may have clinical importance, especially when the dose-volume constraints are near the recommended thresholds, as was the case for lung V5, lung V10, and heart V40. While stents have established benefits for treating patients with significant dysphagia, physicians considering stent placement and radiation therapy must realize the effects stents can have on the dosimetry.

Randomized, Double-Blinded, Placebo-Controlled Crossover Trial of Treating Erectile Dysfunction with Sildenafil After Radiotherapy and Short-Term Androgen Deprivation Therapy: Results of RTOG 0215

PubMed Central

Bruner, Deborah Watkins; James, Jennifer L.; Bryan, Charlene J.; Pisansky, Thomas M.; Rotman, Marvin; Corbett, Thomas; Speight, Joycelyn; Byhardt, Roger; Sandler, Howard; Bentzen, Søren; Kachnic, Lisa; Berk, Lawrence

2013-01-01

Introduction Erectile dysfunction (ED) may be the most commonly observed adverse event (AE) associated with the combination of radiation therapy (RT) and androgen deprivation therapy (ADT). A significant number of men are trying phosphodiesterase type 5 inhibitors (PDE5s) such as sildenafil to treat ED, yet sildenafil studies to date shed little light on the response to ED after ADT. Aim The purpose of this trial was to evaluate sildenafil in the treatment of ED in prostate cancer patients previously treated with external beam RT and neoadjuvant and concurrent ADT. Methods In this randomized, double-blinded crossover trial, eligible patients received RT/ADT for intermediate risk prostate cancer and currently had ED as defined by the International Index of Erectile Function (IIEF). Patients were randomized to 12 weeks of sildenafil or placebo followed by 1 week of no treatment then 12 weeks of the alternative. Treatment differences were evaluated using a marginal model for binary crossover data. Main Outcome Measures The primary end point was improved erectile function, as measured by the IIEF. Results The study accrued 115 patients and 61 (55%) completed all three IIEF assessments. Sildenafil effect was significant (P = 0.009) with a difference in probabilities of erectile response of 0.17 (95% confidence interval: 0.06, 0.29), and 0.21 (0.06, 0.38) for patients receiving ≤120 days of ADT. However, as few as 21% of patients had a treatment-specific response, only improving during sildenafil but not during the placebo phase. Conclusions This is the first controlled trial to suggest a positive sildenafil response for ED treatment in patients previously treated with RT/ADT, however, only a minority of patients responded to treatment. ADT duration may be associated with response and requires further study. The overall low response rate suggests the need for study of additional or preventative strategies for ED after RT/ADT for prostate cancer. PMID:21235716

Phase II Trial of Combined High-Dose-Rate Brachytherapy and External Beam Radiotherapy for Adenocarcinoma of the Prostate: Preliminary Results of RTOG 0321

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsu, I-Chow, E-mail: ihsu@radonc.ucsf.ed; Bae, Kyounghwa; Shinohara, Katsuto

2010-11-01

Purpose: To estimate the rate of late Grade 3 or greater genitourinary (GU) and gastrointestinal (GI) adverse events (AEs) after treatment with external beam radiotherapy and prostate high-dose-rate (HDR) brachytherapy. Methods and Materials: Each participating institution submitted computed tomography-based HDR brachytherapy dosimetry data electronically for credentialing and for each study patient. Patients with locally confined Stage T1c-T3b prostate cancer were eligible for the present study. All patients were treated with 45 Gy in 25 fractions using external beam radiotherapy and one HDR implant delivering 19 Gy in two fractions. All AEs were graded according to the Common Terminology Criteria formore » Adverse Events, version 3.0. Late GU/GI AEs were defined as those occurring >9 months from the start of the protocol treatment, in patients with {>=}18 months of potential follow-up. Results: A total of 129 patients from 14 institutions were enrolled in the present study. Of the 129 patients, 125 were eligible, and AE data were available for 112 patients at analysis. The pretreatment characteristics of the patients were as follows: Stage T1c-T2c, 91%; Stage T3a-T3b, 9%; prostate-specific antigen level {<=}10 ng/mL, 70%; prostate-specific antigen level >10 but {<=}20 ng/mL, 30%; and Gleason score 2-6, 10%; Gleason score 7, 72%; and Gleason score 8-10, 18%. At a median follow-up of 29.6 months, three acute and four late Grade 3 GU/GI AEs were reported. The estimated rate of late Grade 3-5 GU and GI AEs at 18 months was 2.56%. Conclusion: This is the first prospective, multi-institutional trial of computed tomography-based HDR brachytherapy and external beam radiotherapy. The technique and doses used in the present study resulted in acceptable levels of AEs.« less

Emerging biomarkers in anaplastic oligodendroglioma: implications for clinical investigation and patient management.

PubMed

Sahebjam, Solmaz; McNamara, Mairéad G; Mason, Warren P

2013-07-01

Oligodendrogliomas are heterogeneous tumors with a variable response to treatment. This clinical variability underlines the urgent need for markers that can reliably aid diagnosis and guide clinical decision-making. Long-term follow-up data from the EORTC 26951 and RTOG 9402 clinical trials in newly diagnosed anaplastic oligodendroglioma have established chromosome 1p19q codeletion as a predictive marker of response to procarbazine, lomustine and vincristine chemotherapy in anaplastic oligodendrogliomas. In addition, MGMT promoter hypermethylation has been strongly associated with glioma CpG island hypermethylation phenotype (G-CIMP+) status, this has been suggested as an epiphenomenon of genome-wide methylation, conferring a more favorable prognosis. Molecular profiling of these tumors has identified several other markers with potential clinical significance: mutations of IDH, CIC, FUBP1 and CDKN2A require further validation before they can be implemented as clinical decision-making tools. Additionally, recent data on the clinical significance of intrinsic glioma subtyping appears promising. Indeed, existing evidence suggests that comprehensive analyses such as intrinsic glioma subtyping or G-CIMP status are superior to single molecular markers. Clearly, with evolving treatment strategies and in the era of individualized therapy, broader omics-based molecular evaluations are required to improve outcome prediction and to identify patients who will benefit from specific treatment strategies.

SU-G-BRA-15: Dosimetric Evaluation of Dynamic Tumor Tracking Radiation Therapy Using Digital Phantom: A Study On Margin and Desired Accuracy of Tracking

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uchida, T; Osanai, M; Homma, N

2016-06-15

Purpose: Dynamic tumor tracking radiation therapy can potentially reduce internal margin without prolongation of irradiation time. However, dynamic tumor tracking technique requires an extra margin (tracking margin, TM) for the uncertainty of tumor localization, prediction, and beam repositioning. The purpose of this study was to evaluate a dosimetric impact caused by TM. Methods: We used 4D XCAT to create 9 digital phantom datasets of different tumor size and motion range: tumor diameter TD=(1, 3, 5) cm and motion range MR=(1, 2, 3) cm. For each dataset, respiratory gating (30%–70% phase) and tumor tracking treatment plans were created using 8-field 3D-CRTmore » by 4D dose calculation implemented in RayStation. The dose constraint was based on RTOG0618. For the tracking plan, TMs of (0, 2.5, 5) mm were considered by surrounding a normal setup margin: SM=5 mm. We calculated V20 of normal lung to evaluate the dosimetric impact for each case, and estimated an equivalent TM that affects the same impact on V20 obtained by the gated plan. Results: The equivalent TMs for (TD=1 cm, MR=2 cm), (TD=1 cm, MR=3 cm), (TD=5 cm, MR=2 cm), and (TD=5 cm, MR=3 cm) were estimated as 1.47 mm, 3.95 mm, 1.04 mm, and 2.13 mm, respectively. The larger the tumor size, the equivalent TM became smaller. On the other hand, the larger the motion range, the equivalent TM was found to be increased. Conclusion: Our results showed the equivalent TM changes depending on tumor size and motion range. The tracking plan with TM less than the equivalent TM achieves a dosimetric impact better than the gated plan in less treatment time. This study was partially supported by JSPS Kakenhi and Varian Medical Systems.« less

Sci-Fri PM: Radiation Therapy, Planning, Imaging, and Special Techniques - 02: Feasibility of using multileaf collimation for stereotactic radiosurgery of arteriovenous malformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Young; Ruschin, Mark

SRS using linac and cones offers steep dose fall-off but a tradeoff exists between conformality and treatment time, which depends on the number of isocentres. Purpose of this study is to quantify planning metrics between cones- and MLC-based SRS for arteriovenous malformation(AVM). Seven AVM cases treated with cones were re-planned with MLC on Pinnacle treatment planning system. Planning target volume(PTV) was created with 1mm uniform margin to the AVM to account for MLC positional variation. Clinically-planned prescription dose(15–25Gy) was used. Four plans were generated per case:non-coplanar VMAT(ncV), single-arc VMAT(saV), non-coplanar IMRT(ncI), non-coplanar conformal(ncC). Plans were compared for conformity(CI), heterogeneity(HI) andmore » gradient(GI) indices and brain doses. Estimated treatment times and monitor units(MU) were compared. Cone-based plans required 2–6 isocentres. Though CI-RTOG was similar for plans(median=0.98), CI-Paddick was most favourable for ncV(median=0.86) and worst for cones(0.54). HI for MLC plans(median=1.19–1.27) were lower than cone-based plans(1.43). GI was similar for all plans. For 2/7 ncC had brainstem maximum dose>16.7Gy and therefore were clinically unacceptable. Brain V12Gy,V10Gy,V2Gy were lowest in the cones plan. ncV brain V12Gy,V10Gy,V2Gy were lowest of all MLC-based plans studied. Treatment MUs were similar for MLC-based plans and up to 70% lower than clinically delivered plans. ncV showed best conformality in this study. Of the MLC-based plans, ncV also showed lowest normal tissue dose with reasonable treatment time.« less

Acute toxicity and its dosimetric correlates for high-risk prostate cancer treated with moderately hypofractionated radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arunsingh, Moses; Mallick, Indranil, E-mail: imallick@gmail.com; Prasath, Sriram

Aims: To report the acute toxicity and the dosimetric correlates after moderately hypofractionated radiotherapy for localized prostate cancer. Methods: A total of 101 patients with localized prostate cancer were treated with image-guided intensity-modulated radiation therapy. Patients were treated to 65 Gy/25 Fr/5 weeks (n = 18), or 60 Gy/20 Fr/4 weeks (n = 83). Most (82.2%) had high-risk or pelvic node-positive disease. Acute toxicity was assessed using Radiation Therapy Oncology Group (RTOG) acute morbidity scoring criteria. Dose thresholds for acute rectal and bladder toxicity were identified. Results: The incidence of acute grade 2 GI toxicity was 20.8%, and grade 2more » genitourinary (GU) toxicity was 6.9%. No Grade 3 to 4 toxicity occurred. Small bowel toxicity was uncommon (Gr 2 = 4%). The 2 Gy equivalent doses (EQD2) to the rectum and bladder (α/β = 3) calculated showed that the absolute doses were more consistent predictors of acute toxicities than the relative volumes. Those with grade 2 or more GI symptoms had significantly higher V{sub EQD2-60} {sub Gy} (13.2 vs 9.9 cc, p = 0.007) and V{sub EQD2-50} {sub Gy} (20.6 vs 15.4 cc, p = 0.005). Those with grade 2 or more GU symptoms had significantly higher V{sub EQD2-70} {sub Gy} (30.4 vs 18.4 cc, p = 0.001) and V{sub EQD2-65} {sub Gy} (44.0 vs 28.8 cc, p = 0.001). The optimal cutoff value for predicting grade 2 acute proctitis, for V{sub EQD2-60} {sub Gy} was 9.7 cc and for V{sub EQD2-50} {sub Gy} was 15.9 cc. For grade 2 GU symptoms, the threshold values were 23.6 cc for V{sub EQD2-70} {sub Gy} and 38.1 cc for V{sub EQD2-65} {sub Gy}. Conclusions: Hypofractionated radiotherapy for prostate cancer is well tolerated and associated with manageable acute side effects. The absolute dose-volume parameters of rectum and bladder predict for acute toxicities.« less

The Effect of Dose-Volume Parameters and Interfraction Interval on Cosmetic Outcome and Toxicity After 3-Dimensional Conformal Accelerated Partial Breast Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leonard, Kara Lynne, E-mail: karalynne.kerr@gmail.com; Hepel, Jaroslaw T.; Department of Radiation Oncology, Rhode Island Hospital, Warren Alpert School of Medicine of Brown University, Providence, Rhode Island

2013-03-01

Purpose: To evaluate dose-volume parameters and the interfraction interval (IFI) as they relate to cosmetic outcome and normal tissue effects of 3-dimensional conformal radiation therapy (3D-CRT) for accelerated partial breast irradiation (APBI). Methods and Materials: Eighty patients were treated by the use of 3D-CRT to deliver APBI at our institutions from 2003-2010 in strict accordance with the specified dose-volume constraints outlined in the National Surgical Adjuvant Breast and Bowel Project B39/Radiation Therapy Oncology Group 0413 (NSABP-B39/RTOG 0413) protocol. The prescribed dose was 38.5 Gy in 10 fractions delivered twice daily. Patients underwent follow-up with assessment for recurrence, late toxicity, andmore » overall cosmetic outcome. Tests for association between toxicity endpoints and dosimetric parameters were performed with the chi-square test. Univariate logistic regression was used to evaluate the association of interfraction interval (IFI) with these outcomes. Results: At a median follow-up time of 32 months, grade 2-4 and grade 3-4 subcutaneous fibrosis occurred in 31% and 7.5% of patients, respectively. Subcutaneous fibrosis improved in 5 patients (6%) with extended follow-up. Fat necrosis developed in 11% of women, and cosmetic outcome was fair/poor in 19%. The relative volume of breast tissue receiving 5%, 20%, 50%, 80%, and 100% (V5-V100) of the prescribed dose was associated with risk of subcutaneous fibrosis, and the volume receiving 50%, 80%, and 100% (V50-V100) was associated with fair/poor cosmesis. The mean IFI was 6.9 hours, and the minimum IFI was 6.2 hours. The mean and minimum IFI values were not significantly associated with late toxicity. Conclusions: The incidence of moderate to severe late toxicity, particularly subcutaneous fibrosis and fat necrosis and resulting fair/poor cosmesis, remains high with continued follow-up. These toxicity endpoints are associated with several dose-volume parameters. Minimum and mean IFI values were not associated with late toxicity.« less

Long-Term Results of Radiation Therapy Oncology Group 9903: A Randomized Phase 3 Trial to Assess the Effect of Erythropoietin on Local-Regional Control in Anemic Patients Treated With Radiation Therapy for Squamous Cell Carcinoma of the Head and Neck

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shenouda, George, E-mail: George.shenouda@muhc.mcgill.ca; Zhang, Qiang; Ang, K. Kian

2015-04-01

Purpose: This paper reports long-term results of RTOG 9903, to determine whether the addition of erythropoietin (EPO) would improve the outcomes of radiation therapy (RT) in mildly to moderately anemic patients with head and neck squamous cell carcinoma (HNSCCa). Methods and Materials: The trial included HNSCCa patients treated with definitive RT. Patients with stage III or IV disease received concomitant chemoradiation therapy or accelerated fractionation. Pretreatment hemoglobin levels were required to be between 9.0 and 13.5 g/dL (12.5 g/dL for females). EPO, 40,000 U, was administered weekly starting 7 to 10 days before RT was initiated in the RT + EPO arm. Results: A total ofmore » 141 of 148 enrolled patients were evaluable. The baseline median hemoglobin level was 12.1 g/dL. In the RT + EPO arm, the mean hemoglobin level at 4 weeks increased by 1.66 g/dL, whereas it decreased by 0.24 g/dL in the RT arm. With a median follow-up of 7.95 years (range: 1.66-10.08 years) for surviving patients and 3.33 years for all patients (range: 0.03-10.08 years), the 5-year estimate of local-regional failure was 46.2% versus 39.4% (P=.42), local-regional progression-free survival was 31.5% versus 37.6% (P=.20), and overall survival was 36.9% versus 38.2% (P=.54) for the RT + EPO and RT arms, respectively. Late toxicity was not different between the 2 arms. Conclusions: This long-term analysis confirmed that despite the ability of EPO to raise hemoglobin levels in anemic patients with HNSCCa, it did not improve outcomes when added to RT. The possibility of a detrimental effect of EPO could not be ruled out.« less

SU-E-T-593: Outcomes and Toxicities From a Clinical Trial of APBI Using MERT+IMRT with the Same XMLC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jimenez-Ortega, E.; Ureba, A.; Barbeiro, A.R.

2015-06-15

Purpose: We present the results from a clinical trial of accelerated partial breast irradiation (APBI), using mixed modulated photon and electron beams (MERT+IMRT) with the same photon multileaf collimator (xMLC). Methods: Seven patients were enrolled in the first year of the APBI clinical trial. Patients were selected following the conditions included in the NSABP B-39/RTOG 0413 protocol. The targets and clinically relevant normal structures were contoured on the CT images following this protocol for APBI-EBRT. All treatments were delivered using combined modulated electron and photon beams by means of the same xMLC installed in a SIEMENS Primus linac, with amore » reduced SSD equal to 60 cm for electron beams. The plans were performed with a treatment planning system based on full Monte Carlo simulations, called CARMEN, developed by our group. Simultaneously, an alternative IMRT plan was calculated with the commercial TPS PINNACLE v8.0m (Philips), and both plans were compared. An ad-hoc breast phantom with semi-spherical geometry called NAOMI was designed for a specific QA protocol. Patients received a total dose of 38.5 Gy, delivered in 10 fractions over 5 consecutive days, with a twice-a-day hypofractionated schema.Follow-up visits during 2.5 years on average were repeated at 1 month post-treatment, every 3 months for the first year, and every 6 months for the second year. Toxicity was scored according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 3.0). Results: This APBI technique achieved high loco-regional control rates and showed low acute toxicity (grade 1 of CTCAE) and no toxicities from first month onwards. Photographic assessment of cosmesis showed skin excellent results. Conclusion: The clinical results achieved with MERT+IMRT by using the same xMLC are comparable or even better than those obtained with other APBI techniques, thanks to a software solution without any additional equipment or specific device.« less

Randomized Phase III Trial of Concurrent Accelerated Radiation Plus Cisplatin With or Without Cetuximab for Stage III to IV Head and Neck Carcinoma: RTOG 0522

PubMed Central

Ang, K. Kian; Zhang, Qiang; Rosenthal, David I.; Nguyen-Tan, Phuc Felix; Sherman, Eric J.; Weber, Randal S.; Galvin, James M.; Bonner, James A.; Harris, Jonathan; El-Naggar, Adel K.; Gillison, Maura L.; Jordan, Richard C.; Konski, Andre A.; Thorstad, Wade L.; Trotti, Andy; Beitler, Jonathan J.; Garden, Adam S.; Spanos, William J.; Yom, Sue S.; Axelrod, Rita S.

2014-01-01

Purpose Combining cisplatin or cetuximab with radiation improves overall survival (OS) of patients with stage III or IV head and neck carcinoma (HNC). Cetuximab plus platinum regimens also increase OS in metastatic HNC. The Radiation Therapy Oncology Group launched a phase III trial to test the hypothesis that adding cetuximab to the radiation-cisplatin platform improves progression-free survival (PFS). Patients and Methods Eligible patients with stage III or IV HNC were randomly assigned to receive radiation and cisplatin without (arm A) or with (arm B) cetuximab. Acute and late reactions were scored using Common Terminology Criteria for Adverse Events (version 3). Outcomes were correlated with patient and tumor features and markers. Results Of 891 analyzed patients, 630 were alive at analysis (median follow-up, 3.8 years). Cetuximab plus cisplatin-radiation, versus cisplatin-radiation alone, resulted in more frequent interruptions in radiation therapy (26.9% v 15.1%, respectively); similar cisplatin delivery (mean, 185.7 mg/m2 v 191.1 mg/m2, respectively); and more grade 3 to 4 radiation mucositis (43.2% v 33.3%, respectively), rash, fatigue, anorexia, and hypokalemia, but not more late toxicity. No differences were found between arms A and B in 30-day mortality (1.8% v 2.0%, respectively; P = .81), 3-year PFS (61.2% v 58.9%, respectively; P = .76), 3-year OS (72.9% v 75.8%, respectively; P = .32), locoregional failure (19.9% v 25.9%, respectively; P = .97), or distant metastasis (13.0% v 9.7%, respectively; P = .08). Patients with p16-positive oropharyngeal carcinoma (OPC), compared with patients with p16-negative OPC, had better 3-year probability of PFS (72.8% v 49.2%, respectively; P < .001) and OS (85.6% v 60.1%, respectively; P < .001), but tumor epidermal growth factor receptor (EGFR) expression did not distinguish outcome. Conclusion Adding cetuximab to radiation-cisplatin did not improve outcome and hence should not be prescribed routinely. PFS and OS were higher in patients with p16-positive OPC, but outcomes did not differ by EGFR expression. PMID:25154822

Variation in the Gross Tumor Volume and Clinical Target Volume for Preoperative Radiotherapy of Primary Large High-Grade Soft Tissue Sarcoma of the Extremity Among RTOG Sarcoma Radiation Oncologists

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Dian, E-mail: dwang@mcw.edu; Bosch, Walter; Kirsch, David G.

Purpose: To evaluate variability in the definition of preoperative radiotherapy gross tumor volume (GTV) and clinical target volume (CTV) delineated by sarcoma radiation oncologists. Methods and Materials: Extremity sarcoma planning CT images along with the corresponding diagnostic MRI from two patients were distributed to 10 Radiation Therapy Oncology Group sarcoma radiation oncologists with instructions to define GTV and CTV using standardized guidelines. The CT data with contours were then returned for central analysis. Contours representing statistically corrected 95% (V95) and 100% (V100) agreement were computed for each structure. Results: For the GTV, the minimum, maximum, mean (SD) volumes (mL) weremore » 674, 798, 752 {+-} 35 for the lower extremity case and 383, 543, 447 {+-} 46 for the upper extremity case. The volume (cc) of the union, V95 and V100 were 882, 761, and 752 for the lower, and 587, 461, and 455 for the upper extremity, respectively. The overall GTV agreement was judged to be almost perfect in both lower and upper extremity cases (kappa = 0.9 [p < 0.0001] and kappa = 0.86 [p < 0.0001]). For the CTV, the minimum, maximum, mean (SD) volumes (mL) were 1145, 1911, 1605 {+-} 211 for the lower extremity case and 637, 1246, 1006 {+-} 180 for the upper extremity case. The volume (cc) of the union, V95, and V100 were 2094, 1609, and 1593 for the lower, and 1533, 1020, and 965 for the upper extremity cases, respectively. The overall CTV agreement was judged to be almost perfect in the lower extremity case (kappa = 0.85 [p < 0.0001]) but only substantial in the upper extremity case (kappa = 0.77 [p < 0.0001]). Conclusions: Almost perfect agreement existed in the GTV of these two representative cases. Tshere was no significant disagreement in the CTV of the lower extremity, but variation in the CTV of upper extremity was seen, perhaps related to the positional differences between the planning CT and the diagnostic MRI.« less

Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522.

PubMed

Ang, K Kian; Zhang, Qiang; Rosenthal, David I; Nguyen-Tan, Phuc Felix; Sherman, Eric J; Weber, Randal S; Galvin, James M; Bonner, James A; Harris, Jonathan; El-Naggar, Adel K; Gillison, Maura L; Jordan, Richard C; Konski, Andre A; Thorstad, Wade L; Trotti, Andy; Beitler, Jonathan J; Garden, Adam S; Spanos, William J; Yom, Sue S; Axelrod, Rita S

2014-09-20

Combining cisplatin or cetuximab with radiation improves overall survival (OS) of patients with stage III or IV head and neck carcinoma (HNC). Cetuximab plus platinum regimens also increase OS in metastatic HNC. The Radiation Therapy Oncology Group launched a phase III trial to test the hypothesis that adding cetuximab to the radiation-cisplatin platform improves progression-free survival (PFS). Eligible patients with stage III or IV HNC were randomly assigned to receive radiation and cisplatin without (arm A) or with (arm B) cetuximab. Acute and late reactions were scored using Common Terminology Criteria for Adverse Events (version 3). Outcomes were correlated with patient and tumor features and markers. Of 891 analyzed patients, 630 were alive at analysis (median follow-up, 3.8 years). Cetuximab plus cisplatin-radiation, versus cisplatin-radiation alone, resulted in more frequent interruptions in radiation therapy (26.9% v. 15.1%, respectively); similar cisplatin delivery (mean, 185.7 mg/m2 v. 191.1 mg/m2, respectively); and more grade 3 to 4 radiation mucositis (43.2% v. 33.3%, respectively), rash, fatigue, anorexia, and hypokalemia, but not more late toxicity. No differences were found between arms A and B in 30-day mortality (1.8% v. 2.0%, respectively; P = .81), 3-year PFS (61.2% v. 58.9%, respectively; P = .76), 3-year OS (72.9% v. 75.8%, respectively; P = .32), locoregional failure (19.9% v. 25.9%, respectively; P = .97), or distant metastasis (13.0% v. 9.7%, respectively; P = .08). Patients with p16-positive oropharyngeal carcinoma (OPC), compared with patients with p16-negative OPC, had better 3-year probability of PFS (72.8% v. 49.2%, respectively; P < .001) and OS (85.6% v. 60.1%, respectively; P < .001), but tumor epidermal growth factor receptor (EGFR) expression did not distinguish outcome. Adding cetuximab to radiation-cisplatin did not improve outcome and hence should not be prescribed routinely. PFS and OS were higher in patients with p16-positive OPC, but outcomes did not differ by EGFR expression.

Radiobiological impact of reduced margins and treatment technique for prostate cancer in terms of tumor control probability (TCP) and normal tissue complication probability (NTCP).

PubMed

Jensen, Ingelise; Carl, Jesper; Lund, Bente; Larsen, Erik H; Nielsen, Jane

2011-01-01

Dose escalation in prostate radiotherapy is limited by normal tissue toxicities. The aim of this study was to assess the impact of margin size on tumor control and side effects for intensity-modulated radiation therapy (IMRT) and 3D conformal radiotherapy (3DCRT) treatment plans with increased dose. Eighteen patients with localized prostate cancer were enrolled. 3DCRT and IMRT plans were compared for a variety of margin sizes. A marker detectable on daily portal images was presupposed for narrow margins. Prescribed dose was 82 Gy within 41 fractions to the prostate clinical target volume (CTV). Tumor control probability (TCP) calculations based on the Poisson model including the linear quadratic approach were performed. Normal tissue complication probability (NTCP) was calculated for bladder, rectum and femoral heads according to the Lyman-Kutcher-Burman method. All plan types presented essentially identical TCP values and very low NTCP for bladder and femoral heads. Mean doses for these critical structures reached a minimum for IMRT with reduced margins. Two endpoints for rectal complications were analyzed. A marked decrease in NTCP for IMRT plans with narrow margins was seen for mild RTOG grade 2/3 as well as for proctitis/necrosis/stenosis/fistula, for which NTCP <7% was obtained. For equivalent TCP values, sparing of normal tissue was demonstrated with the narrow margin approach. The effect was more pronounced for IMRT than 3DCRT, with respect to NTCP for mild, as well as severe, rectal complications. Copyright © 2011 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Feasibility and radiation induced toxicity regarding the first application of transperineal implementation of biocompatible balloon for high dose radiotherapy in patients with prostate carcinoma

PubMed Central

2013-01-01

Objective To evaluate the feasibility of the transperineal implementation of biocompatible balloon (Prospace) and the acute toxicity of high dose 3DCRT in patients with localized low risk prostate cancer. Materials and methods Between December 2011 and April 2012, fifteen patients were treated with external 3DCRT consisted of 76–78 Gy in 38–39 daily fractions (2.0 Gy/ fraction). Before 3DCRT, we placed the Prospace though the perineum by a minimally invasive procedure in the intermediate space between the rectum and the prostate. The primary study endpoint was the evaluation of acute toxicity according to the EORTC/RTOG radiation toxicity scale. Erectile function was evaluated with the IIEF-5 questionnaire. Rectosigmoidoscopy was performed at baseline, at the end of 3DCRT and 3 months thereafter in order to assess also the rectal toxicity according to Subjective-RectoSigmoid (S-RS) scale. The evaluation of pain related to Prospace implementation was done with the visual analogue score (VAS). Results The acute toxicities were as follows: grade I GI toxicity in two patients and for GU toxicity, three patients with grade I of nocturia, four patients with grade I of frequency, two patients with grade I and two patients with grade II of dysouria. The mean score of rectal toxicity according to S-RS score was 1.8(±0.6). The mean VAS score related to Prospace was 1.4(±0.5). Erectile function was unchanged. The Prospace device was found stable in sequential CTs during irradiation. Conclusions The implementation of PROSPACE was feasible, while the acute radiation toxicity was low and comparable with IMRT techniques. PMID:23566526

Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial

PubMed Central

Brown, Paul D.; Pugh, Stephanie; Laack, Nadia N.; Wefel, Jeffrey S.; Khuntia, Deepak; Meyers, Christina; Choucair, Ali; Fox, Sherry; Suh, John H.; Roberge, David; Kavadi, Vivek; Bentzen, Soren M.; Mehta, Minesh P.; Watkins-Bruner, Deborah

2013-01-01

Background To determine the protective effects of memantine on cognitive function in patients receiving whole-brain radiotherapy (WBRT). Methods Adult patients with brain metastases received WBRT and were randomized to receive placebo or memantine (20 mg/d), within 3 days of initiating radiotherapy for 24 weeks. Serial standardized tests of cognitive function were performed. Results Of 554 patients who were accrued, 508 were eligible. Grade 3 or 4 toxicities and study compliance were similar in the 2 arms. There was less decline in delayed recall in the memantine arm at 24 weeks (P = .059), but the difference was not statistically significant, possibly because there were only 149 analyzable patients at 24 weeks, resulting in only 35% statistical power. The memantine arm had significantly longer time to cognitive decline (hazard ratio 0.78, 95% confidence interval 0.62–0.99, P = .01); the probability of cognitive function failure at 24 weeks was 53.8% in the memantine arm and 64.9% in the placebo arm. Superior results were seen in the memantine arm for executive function at 8 (P = .008) and 16 weeks (P = .0041) and for processing speed (P = .0137) and delayed recognition (P = .0149) at 24 weeks. Conclusions Memantine was well tolerated and had a toxicity profile very similar to placebo. Although there was less decline in the primary endpoint of delayed recall at 24 weeks, this lacked statistical significance possibly due to significant patient loss. Overall, patients treated with memantine had better cognitive function over time; specifically, memantine delayed time to cognitive decline and reduced the rate of decline in memory, executive function, and processing speed in patients receiving WBRT. RTOG 0614, ClinicalTrials.gov number CT00566852. PMID:23956241

Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial.

PubMed

Brown, Paul D; Pugh, Stephanie; Laack, Nadia N; Wefel, Jeffrey S; Khuntia, Deepak; Meyers, Christina; Choucair, Ali; Fox, Sherry; Suh, John H; Roberge, David; Kavadi, Vivek; Bentzen, Soren M; Mehta, Minesh P; Watkins-Bruner, Deborah

2013-10-01

To determine the protective effects of memantine on cognitive function in patients receiving whole-brain radiotherapy (WBRT). Adult patients with brain metastases received WBRT and were randomized to receive placebo or memantine (20 mg/d), within 3 days of initiating radiotherapy for 24 weeks. Serial standardized tests of cognitive function were performed. Of 554 patients who were accrued, 508 were eligible. Grade 3 or 4 toxicities and study compliance were similar in the 2 arms. There was less decline in delayed recall in the memantine arm at 24 weeks (P = .059), but the difference was not statistically significant, possibly because there were only 149 analyzable patients at 24 weeks, resulting in only 35% statistical power. The memantine arm had significantly longer time to cognitive decline (hazard ratio 0.78, 95% confidence interval 0.62-0.99, P = .01); the probability of cognitive function failure at 24 weeks was 53.8% in the memantine arm and 64.9% in the placebo arm. Superior results were seen in the memantine arm for executive function at 8 (P = .008) and 16 weeks (P = .0041) and for processing speed (P = .0137) and delayed recognition (P = .0149) at 24 weeks. Memantine was well tolerated and had a toxicity profile very similar to placebo. Although there was less decline in the primary endpoint of delayed recall at 24 weeks, this lacked statistical significance possibly due to significant patient loss. Overall, patients treated with memantine had better cognitive function over time; specifically, memantine delayed time to cognitive decline and reduced the rate of decline in memory, executive function, and processing speed in patients receiving WBRT. RTOG 0614, ClinicalTrials.gov number CT00566852.

Analysis of peripheral doses for base of tongue treatment by linear accelerator and helical TomoTherapy IMRT

PubMed Central

Lamba, Michael A. S.; Elson, Howard R.

2010-01-01

The purpose of this study was to compare the peripheral doses to various organs from a typical head and neck intensity‐modulated radiation therapy (IMRT) treatment delivered by linear accelerator (linac) and helical TomoTherapy. Multiple human CT data sets were used to segment critical structures and organs at risk, fused and adjusted to an anthropomorphic phantom. Eighteen contours were designated for thermoluminescent dosimeter (TLD) placement. Following the RTOG IMRT Protocol 0522, treatment of the primary tumor and involved nodes (PTV70) and subclinical disease sites (PTV56) was planned utilizing IMRT to 70 Gy and 56 Gy. Clinically acceptable treatment plans were produced for linac and TomoTherapy treatments. TLDs were placed and each treatment plan was delivered to the anthropomorphic phantom four times. Within 2.5 cm (one helical TomoTherapy field width) superior and inferior to the field edges, normal tissue doses were on average 45% lower using linear accelerator. Beyond 2.5 cm, the helical TomoTherapy normal tissue dose was an average of 52% lower. The majority of points proved to be statistically different using the Student's t‐test with p<0.05. Using one method of calculation, probability of a secondary malignancy was 5.88% for the linear accelerator and 4.08% for helical TomoTherapy. Helical TomoTherapy delivers more dose than a linac immediately above and below the treatment field, contributing to the higher peripheral doses adjacent to the field. At distances beyond one field width (where leakage is dominant), helical TomoTherapy doses are lower than linear accelerator doses. PACS number: 87.50.cm Dosimetry/exposure assessment

A preliminary study of in-house Monte Carlo simulations: an integrated Monte Carlo verification system.

PubMed

Mukumoto, Nobutaka; Tsujii, Katsutomo; Saito, Susumu; Yasunaga, Masayoshi; Takegawa, Hideki; Yamamoto, Tokihiro; Numasaki, Hodaka; Teshima, Teruki

2009-10-01

To develop an infrastructure for the integrated Monte Carlo verification system (MCVS) to verify the accuracy of conventional dose calculations, which often fail to accurately predict dose distributions, mainly due to inhomogeneities in the patient's anatomy, for example, in lung and bone. The MCVS consists of the graphical user interface (GUI) based on a computational environment for radiotherapy research (CERR) with MATLAB language. The MCVS GUI acts as an interface between the MCVS and a commercial treatment planning system to import the treatment plan, create MC input files, and analyze MC output dose files. The MCVS consists of the EGSnrc MC codes, which include EGSnrc/BEAMnrc to simulate the treatment head and EGSnrc/DOSXYZnrc to calculate the dose distributions in the patient/phantom. In order to improve computation time without approximations, an in-house cluster system was constructed. The phase-space data of a 6-MV photon beam from a Varian Clinac unit was developed and used to establish several benchmarks under homogeneous conditions. The MC results agreed with the ionization chamber measurements to within 1%. The MCVS GUI could import and display the radiotherapy treatment plan created by the MC method and various treatment planning systems, such as RTOG and DICOM-RT formats. Dose distributions could be analyzed by using dose profiles and dose volume histograms and compared on the same platform. With the cluster system, calculation time was improved in line with the increase in the number of central processing units (CPUs) at a computation efficiency of more than 98%. Development of the MCVS was successful for performing MC simulations and analyzing dose distributions.

Model-based approach for quantitative estimates of skin, heart, and lung toxicity risk for left-side photon and proton irradiation after breast-conserving surgery.

PubMed

Tommasino, Francesco; Durante, Marco; D'Avino, Vittoria; Liuzzi, Raffaele; Conson, Manuel; Farace, Paolo; Palma, Giuseppe; Schwarz, Marco; Cella, Laura; Pacelli, Roberto

2017-05-01

Proton beam therapy represents a promising modality for left-side breast cancer (BC) treatment, but concerns have been raised about skin toxicity and poor cosmesis. The aim of this study is to apply skin normal tissue complication probability (NTCP) model for intensity modulated proton therapy (IMPT) optimization in left-side BC. Ten left-side BC patients undergoing photon irradiation after breast-conserving surgery were randomly selected from our clinical database. Intensity modulated photon (IMRT) and IMPT plans were calculated with iso-tumor-coverage criteria and according to RTOG 1005 guidelines. Proton plans were computed with and without skin optimization. Published NTCP models were employed to estimate the risk of different toxicity endpoints for skin, lung, heart and its substructures. Acute skin NTCP evaluation suggests a lower toxicity level with IMPT compared to IMRT when the skin is included in proton optimization strategy (0.1% versus 1.7%, p < 0.001). Dosimetric results show that, with the same level of tumor coverage, IMPT attains significant heart and lung dose sparing compared with IMRT. By NTCP model-based analysis, an overall reduction in the cardiopulmonary toxicity risk prediction can be observed for all IMPT compared to IMRT plans: the relative risk reduction from protons varies between 0.1 and 0.7 depending on the considered toxicity endpoint. Our analysis suggests that IMPT might be safely applied without increasing the risk of severe acute radiation induced skin toxicity. The quantitative risk estimates also support the potential clinical benefits of IMPT for left-side BC irradiation due to lower risk of cardiac and pulmonary morbidity. The applied approach might be relevant on the long term for the setup of cost-effectiveness evaluation strategies based on NTCP predictions.

A National-Level Validation of the New American Joint Committee on Cancer 8th Edition Subclassification of Stage IIA and B Anal Squamous Cell Cancer.

PubMed

Goffredo, Paolo; Garancini, Mattia; Robinson, Timothy J; Frakes, Jessica; Hoshi, Hisakazu; Hassan, Imran

2018-06-01

The 8th edition of the American Joint Committee on Cancer (AJCC) updated the staging system of anal squamous cell cancer (ASCC) by subdividing stage II into A (T2N0M0) and B (T3N0M0) based on a secondary analysis of the RTOG 98-11 trial. We aimed to validate this new subclassification utilizing two nationally representative databases. The National Cancer Database (NCDB) [2004-2014] and the Surveillance, Epidemiology, and End Results (SEER) database [1988-2013] were queried to identify patients with stage II ASCC. A total of 6651 and 2579 stage IIA (2-5 cm) and 1777 and 641 stage IIB (> 5 cm) patients were identified in the NCDB and SEER databases, respectively. Compared with stage IIB patients, stage IIA patients within the NCDB were more often females with fewer comorbidities. No significant differences were observed between age, race, receipt of chemotherapy and radiation, and mean radiation dose. Demographic, clinical, and pathologic characteristics were comparable between patients in both datasets. The 5-year OS was 72% and 69% for stage IIA versus 57% and 50% for stage IIB in the NCDB and SEER databases, respectively (p < 0.001). After adjustment for available demographic and clinical confounders, stage IIB was significantly associated with worse survival in both cohorts (hazard ratio 1.58 and 2.01, both p < 0.001). This study validates the new AJCC subclassification of stage II anal cancer into A and B based on size (2-5 cm vs. > 5 cm) in the general ASCC population. AJCC stage IIB patients represent a higher risk category that should be targeted with more aggressive/novel therapies.

Whole-brain Irradiation Field Design: A Comparison of Parotid Dose.

PubMed

Wu, Cheng-Chia; Wuu, Yen-Ruh; Jani, Ashish; Saraf, Anurag; Tai, Cheng-Hung; Lapa, Matthew E; Andrew, Jacquelyn I S; Tiwari, Akhil; Saadatmand, Heva J; Isaacson, Steven R; Cheng, Simon K; Wang, Tony J C

2017-01-01

Whole-brain radiation therapy (WBRT) plays an important role in patients with diffusely metastatic intracranial disease. Whether the extent of the radiation field design to C1 or C2 affects parotid dose and risk for developing xerostomia is unknown. The goal of this study is to examine the parotid dose based off of the inferior extent of WBRT field to either C1 or C2. Patients treated with WBRT with either 30 Gy or 37.5 Gy from 2011 to 2014 at a single institution were examined. Parotid dose constraints were compared with Radiation Therapy Oncology Group (RTOG) 0615 nasopharyngeal carcinoma for a 33-fraction treatment: mean <26 Gy, volume constraint at 20 Gy (V20) < 20 cc, and dose at 50% of the parotid volume (D50) < 30 Gy. Biologically effective dose (BED) conversions with an α/β of 3 for normal parotid were performed to compare with 10-fraction and 15-fraction treatments of WBRT. The constraints are as follows: mean < BED 32.83 Gy, V15.76 (for 10-fraction WBRT) or V17.35 (for 15-fraction WBRT) < 20 cc, and D50 < BED 39.09 Gy. Nineteen patients treated to C1 and 26 patients treated to C2 were analyzed. Comparing WBRT to C1 with WBRT to C2, the mean left, right, and both parotids' doses were lower when treated to C1. Converting mean dose to BED 3 , the parotid doses were lower than BED 3 constraint of 32.83 Gy: left (30.12 Gy), right (30.69 Gy), and both parotids (30.32 Gy). V20 to combined parotids was lower in patients treated to C1. When accounting for fractionation of WBRT received, the mean corrected V20 volume was less than 20 cc when treating to C1. D50 for C1 was lower than C2 for the left parotid, right parotid, and both parotids. BED 3 conversion for the mean D50 of the left, right, and both parotids was less than 39.09 Gy. In conclusion, WBRT to C1 limits parotid dose, and parotid dose constraints are achievable compared with inferior border at C2. A possible mean parotid dose constraint with BED 3 should be less than 32.83 Gy. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Whole-brain Irradiation Field Design: A Comparison of Parotid Dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Cheng-Chia; Wuu, Yen-Ruh; Jani, Ashish

Whole-brain radiation therapy (WBRT) plays an important role in patients with diffusely metastatic intracranial disease. Whether the extent of the radiation field design to C1 or C2 affects parotid dose and risk for developing xerostomia is unknown. The goal of this study is to examine the parotid dose based off of the inferior extent of WBRT field to either C1 or C2. Patients treated with WBRT with either 30 Gy or 37.5 Gy from 2011 to 2014 at a single institution were examined. Parotid dose constraints were compared with Radiation Therapy Oncology Group (RTOG) 0615 nasopharyngeal carcinoma for a 33-fraction treatment: meanmore » <26 Gy, volume constraint at 20 Gy (V20) < 20 cc, and dose at 50% of the parotid volume (D50) < 30 Gy. Biologically effective dose (BED) conversions with an α/β of 3 for normal parotid were performed to compare with 10-fraction and 15-fraction treatments of WBRT. The constraints are as follows: mean < BED 32.83 Gy, V15.76 (for 10-fraction WBRT) or V17.35 (for 15-fraction WBRT) < 20 cc, and D50 < BED 39.09 Gy. Nineteen patients treated to C1 and 26 patients treated to C2 were analyzed. Comparing WBRT to C1 with WBRT to C2, the mean left, right, and both parotids' doses were lower when treated to C1. Converting mean dose to BED{sub 3}, the parotid doses were lower than BED{sub 3} constraint of 32.83 Gy: left (30.12 Gy), right (30.69 Gy), and both parotids (30.32 Gy). V20 to combined parotids was lower in patients treated to C1. When accounting for fractionation of WBRT received, the mean corrected V20 volume was less than 20 cc when treating to C1. D50 for C1 was lower than C2 for the left parotid, right parotid, and both parotids. BED{sub 3} conversion for the mean D50 of the left, right, and both parotids was less than 39.09 Gy. In conclusion, WBRT to C1 limits parotid dose, and parotid dose constraints are achievable compared with inferior border at C2. A possible mean parotid dose constraint with BED{sub 3} should be less than 32.83 Gy.« less

Dose impact in radiographic lung injury following lung SBRT: Statistical analysis and geometric interpretation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Victoria; Kishan, Amar U.; Cao, Minsong

2014-03-15

Purpose: To demonstrate a new method of evaluating dose response of treatment-induced lung radiographic injury post-SBRT (stereotactic body radiotherapy) treatment and the discovery of bimodal dose behavior within clinically identified injury volumes. Methods: Follow-up CT scans at 3, 6, and 12 months were acquired from 24 patients treated with SBRT for stage-1 primary lung cancers or oligometastic lesions. Injury regions in these scans were propagated to the planning CT coordinates by performing deformable registration of the follow-ups to the planning CTs. A bimodal behavior was repeatedly observed from the probability distribution for dose values within the deformed injury regions. Basedmore » on a mixture-Gaussian assumption, an Expectation-Maximization (EM) algorithm was used to obtain characteristic parameters for such distribution. Geometric analysis was performed to interpret such parameters and infer the critical dose level that is potentially inductive of post-SBRT lung injury. Results: The Gaussian mixture obtained from the EM algorithm closely approximates the empirical dose histogram within the injury volume with good consistency. The average Kullback-Leibler divergence values between the empirical differential dose volume histogram and the EM-obtained Gaussian mixture distribution were calculated to be 0.069, 0.063, and 0.092 for the 3, 6, and 12 month follow-up groups, respectively. The lower Gaussian component was located at approximately 70% prescription dose (35 Gy) for all three follow-up time points. The higher Gaussian component, contributed by the dose received by planning target volume, was located at around 107% of the prescription dose. Geometrical analysis suggests the mean of the lower Gaussian component, located at 35 Gy, as a possible indicator for a critical dose that induces lung injury after SBRT. Conclusions: An innovative and improved method for analyzing the correspondence between lung radiographic injury and SBRT treatment dose has been demonstrated. Bimodal behavior was observed in the dose distribution of lung injury after SBRT. Novel statistical and geometrical analysis has shown that the systematically quantified low-dose peak at approximately 35 Gy, or 70% prescription dose, is a good indication of a critical dose for injury. The determined critical dose of 35 Gy resembles the critical dose volume limit of 30 Gy for ipsilateral bronchus in RTOG 0618 and results from previous studies. The authors seek to further extend this improved analysis method to a larger cohort to better understand the interpatient variation in radiographic lung injury dose response post-SBRT.« less

Hypofractionated Proton Boost Combined with External Beam Radiotherapy for Treatment of Localized Prostate Cancer

PubMed Central

Johansson, Silvia; Åström, Lennart; Sandin, Fredrik; Isacsson, Ulf; Montelius, Anders; Turesson, Ingela

2012-01-01

Proton boost of 20 Gy in daily 5 Gy fractions followed by external beam radiotherapy (EBRT) of 50 Gy in daily 2 Gy fractions were given to 278 patients with prostate cancer with T1b to T4N0M0 disease. Fifty-three percent of the patients received neoadjuvant androgen deprivation therapy (N-ADT). The medium followup was 57 months. The 5-year PSA progression-free survival was 100%, 95%, and 74% for low-, intermediate-, and high-risk patients, respectively. The toxicity evaluation was supported by a patient-reported questionnaire before every consultant visit. Cumulative probability and actuarial prevalence of genitourinary (GU) and gastrointestinal (GI) toxicities are presented according to the RTOG classification. N-ADT did not influence curability. Mild pretreatment GU-symptoms were found to be a strong predictive factor for GU-toxicity attributable to treatment. The actuarial prevalence declined over 3 to 5 years for both GU and GI toxicities, indicating slow resolution of epithelial damage to the genitourinary and gastrointestinal tract. Bladder toxicities rather than gastrointestinal toxicities seem to be dose limiting. More than 5-year followup is necessary to reveal any sign of true progressive late side effects of the given treatment. Hypofractionated proton-boost combined with EBRT is associated with excellent curability of localized PC and acceptable frequencies of treatment toxicity. PMID:22848840

MO-FG-BRA-04: A Novel Time Weighted Density Correction for Stereotactic Lung Radiotherapy: A Phantom Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mohatt, D; Malhotra, H

Purpose: Conventional treatment plans for lung radiotherapy are created using either the free breathing (FB) scheme which represents the tumor at an arbitrary breathing phase of the patient’s respiratory cycle, or the average computed tomography (ACT) intensity projection over 10-binned phases. Neither method is entirely accurate because of the absence of time dependence of tumor movement. In the present “Hybrid” method, the HU of tumor in 3D space is determined by relative weighting of the HU of the tumor and lung in proportion to the time they spend at that location during the entire breathing cycle. Methods: A Quasar respiratorymore » motion phantom was employed to simulate lung tumor movement. Utilizing 4DCT image scans, volumetric modulated arc therapy (VMAT) plans were generated for three treatment planning scenarios which included conventional FB and ACT schemes, along with a third alternative Hybrid approach. Our internal target volume (ITV) hybrid structure was created using Boolean operation in Eclipse (ver. 11) treatment planning system, where independent sub-regions created by the gross tumor volume (GTV) overlap from the 10 motion phases were each assigned a time weighted CT value. The dose-volume-histograms (DVH) for each scheme were compared and analyzed. Results: Using our hybrid technique, we have demonstrated a reduction of 1.9% – 3.4% in total monitor units with respect to conventional treatment planning strategies, along with a 6 fold improvement in high dose spillage over the FB plan. The higher density ACT and Hybrid schemes also produced a slight enhancement in target conformity and reduction in low dose spillage. Conclusion: All treatment plans created in this study exceeded RTOG protocol criteria. Our results determine the free breathing approach yields an inaccurate account of the target treatment density. A significant decrease in unnecessary lung irradiation can be achieved by implementing Hybrid HU method with ACT method second best.« less

SU-G-BRC-14: Multi-Lesion, Multi-Rx, Brain Radiosurgery with Novel Single Isocenter Technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Honig, N; Alani, S; Schlocker, A

Purpose: There is a strong trend to treat multiple brain metastases with radiosurgery rather than whole brain irradiation. This feasibility study investigates a novel planning technique for radio-surgical treatment of multiple brain lesions with differing dose prescriptions, a single isocenter, and dynamic conformal arcs. The novel technique will be compared to the well-established single-isocenter volumetric modulated arc therapy (VMAT) technique commonly used for treating brain lesions. Methods: Six patients with metastatic brain lesions were selected for a prospective treatment planning study to evaluate Interdigitating MLC Dynamic Conformal Arc (IMDCA) technique. Arcs were planned for simultaneous irradiation to maximize beam deliverymore » efficiency. To accommodate varying PTV dose prescriptions, selected arcs were re-irradiated in reverse. Beam weights were adjusted until all prescription constraints were met. The number of lesions ranged between 2 to 4 (mode = 3). For comparison, SRS VMAT plans were generated utilizing an established single-isocenter, 3 arc planning template. All plans were compared by means of Paddick conformity index (PCI), RTOG Conformity Index (RCI), gradient index (GI), and the normal brain volume receiving 10% (V10) of the highest prescription dose. The monitor units and delivery time were tabulated for each plan. Results: IMDCA achieved conformal plans (PCI = 0.72±0.03, RCI = 1.33±0.03) with steep dose fall-off (GI = 3.79±0.03) on average for all of the plans evaluated. The VMAT plans had slightly better conformity (PCI = 0.85 ± 0.03, RCI = 1.13 ± 0.03) than IMDCA, but overall worse GI (4.29 ± 0.06). IMDCA plans had lower V10% values, required 50% fewer MUs, and had 34% shorter beam delivery time on average compared to VMAT plans. Conclusion: IMDCA plans with varying dose prescriptions for multiple lesions, had comparable dosimetric coverage as VMAT plans, but were obtained with significantly lower integral dose, fewer monitor units, and quicker delivery time.« less

NOTE: MMCTP: a radiotherapy research environment for Monte Carlo and patient-specific treatment planning

NASA Astrophysics Data System (ADS)

Alexander, A.; DeBlois, F.; Stroian, G.; Al-Yahya, K.; Heath, E.; Seuntjens, J.

2007-07-01

Radiotherapy research lacks a flexible computational research environment for Monte Carlo (MC) and patient-specific treatment planning. The purpose of this study was to develop a flexible software package on low-cost hardware with the aim of integrating new patient-specific treatment planning with MC dose calculations suitable for large-scale prospective and retrospective treatment planning studies. We designed the software package 'McGill Monte Carlo treatment planning' (MMCTP) for the research development of MC and patient-specific treatment planning. The MMCTP design consists of a graphical user interface (GUI), which runs on a simple workstation connected through standard secure-shell protocol to a cluster for lengthy MC calculations. Treatment planning information (e.g., images, structures, beam geometry properties and dose distributions) is converted into a convenient MMCTP local file storage format designated, the McGill RT format. MMCTP features include (a) DICOM_RT, RTOG and CADPlan CART format imports; (b) 2D and 3D visualization views for images, structure contours, and dose distributions; (c) contouring tools; (d) DVH analysis, and dose matrix comparison tools; (e) external beam editing; (f) MC transport calculation from beam source to patient geometry for photon and electron beams. The MC input files, which are prepared from the beam geometry properties and patient information (e.g., images and structure contours), are uploaded and run on a cluster using shell commands controlled from the MMCTP GUI. The visualization, dose matrix operation and DVH tools offer extensive options for plan analysis and comparison between MC plans and plans imported from commercial treatment planning systems. The MMCTP GUI provides a flexible research platform for the development of patient-specific MC treatment planning for photon and electron external beam radiation therapy. The impact of this tool lies in the fact that it allows for systematic, platform-independent, large-scale MC treatment planning for different treatment sites. Patient recalculations were performed to validate the software and ensure proper functionality.

Defining the role of tyrosine kinase inhibitors in early stage non-small cell lung cancer.

PubMed

Lampaki, Sofia; Lazaridis, George; Zarogoulidis, Konstantinos; Kioumis, Ioannis; Papaiwannou, Antonis; Tsirgogianni, Katerina; Karavergou, Anastasia; Tsiouda, Theodora; Karavasilis, Vasilis; Yarmus, Lonny; Darwiche, Kaid; Freitag, Lutz; Sakkas, Antonios; Kantzeli, Angeliki; Baka, Sofia; Hohenforst-Schmidt, Wolfgang; Zarogoulidis, Paul

2015-01-01

Historical, the non-small cell lung cancer (NSCLC) was as a united disease entity and the chemotherapy to the metastatic cancer had limited results. Recent studies for the metastatic non-small cell lung cancer led to the ascertainment that the NSCLC does not constitute exclusively a disease entity, but different neoplasms guided from different molecular paths, different biological behavior and at extension requires different confrontation. Thus the new direction for the therapeutic approach of NSCLC is henceforth the most individualized approach based on the activated molecular paths of tumor. Distinct subtypes of NSCLC are driven by a specific genetic alteration, like EGFR, ALK, ROS1 or BRAF mutations, and these genetic alterations are sensitized to the inhibition of specific oncogenic pathways. The benefit from the use of tyrosine kinase inhibitors in patients with EGFR mutations it was confirmed by six randomized studies of phase III that investigated the role of gefitinib, erlotinib and afatinib. In these studies the response rates vary in the impressive percentages from 55% to 86% and were connected with a remarkable median progression free survival of approximately 8 to 13 months, and with better quality of life compared to that of chemotherapy. In early stages NSCLC is needed the individualization of systemic treatment in order to reduce toxicity that is observed in the classic chemotherapy and to impact outcome. The role of EGFR TKI's has been evaluated in the adjuvant chemotherapy in early stage resected NSCLC. The data from these studies suggest that adjuvant TKI therapy might not increase the overall survival, but delay the recurrences. Prospective trials restricted to EGFR or ALK driven NSCLC subsets potentially offering the opportunity for a definitive answer in early disease adjuvant setting (ALCHEMIST) or as induction treatment before stage III chemo-radiotherapy (RTOG 1210/Alliance 31101), are ongoing. Ongoing prospective trials may offer the opportunity for a definitive answer of the role of tyrosine kinase inhibitors in induction treatment before chemo-radiotherapy or in early disease adjuvant therapy.

WE-AB-202-01: Evaluating the Toxicity Reduction with CT-Ventilation Functional Avoidance Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vinogradskiy, Y; Miyasaka, Y; Kadoya, N

Purpose: CT-ventilation is an exciting new imaging modality that uses 4DCTs to calculate lung ventilation. Studies have proposed to use 4DCT-ventilation imaging for functional avoidance radiotherapy which implies designing treatment plans to spare functional portions of the lung. Although retrospective studies have been performed to evaluate the dosimetric gains to functional lung; no work has been done to translate the dosimetric gains to an improvement in pulmonary toxicity. The purpose of our work was to evaluate the potential reduction in toxicity for 4DCT-ventilation based functional avoidance. Methods: 70 lung cancer patients with 4DCT imaging were used for the study. CT-ventilationmore » maps were calculated using the patient’s 4DCT, deformable image registrations, and a density-change-based algorithm. Radiation pneumonitis was graded using imaging and clinical information. Log-likelihood methods were used to fit a normal-tissue-complication-probability (NTCP) model predicting grade 2+ radiation pneumonitis as a function of doses (mean and V20) to functional lung (>15% ventilation). For 20 patients a functional plan was generated that reduced dose to functional lung while meeting RTOG 0617-based constraints. The NTCP model was applied to the functional plan to determine the reduction in toxicity with functional planning Results: The mean dose to functional lung was 16.8 and 17.7 Gy with the functional and clinical plans respectively. The corresponding grade 2+ pneumonitis probability was 26.9% with the clinically-used plan and 24.6% with the functional plan (8.5% reduction). The V20-based grade 2+ pneumonitis probability was 23.7% with the clinically-used plan and reduced to 19.6% with the functional plan (20.9% reduction). Conclusion: Our results revealed a reduction of 9–20% in complication probability with functional planning. To our knowledge this is the first study to apply complication probability to convert dosimetric results to toxicity improvement. The results presented in the current work provide seminal data for prospective clinical trials in functional avoidance. YV discloses funding from State of Colorado. TY discloses National Lung Cancer Partnership; Young Investigator Research grant.« less

SU-E-J-206: Adaptive Radiotherapy for Gynecological Malignancies with MRIGuided Cobolt-60 Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lamb, J; Kamrava, M; Agazaryan, N

Purpose: Even in the IMRT era, bowel toxicity and bone marrow irradiation remain concerns with pelvic irradiation. We examine the potential gain from an adaptive radiotherapy workflow for post-operative gynecological patients treated to pelvic targets including lymph nodes using MRI-guided Co-60 radiation therapy. Methods: An adaptive workflow was developed with the intent of minimizing time overhead of adaptive planning. A pilot study was performed using retrospectively analyzed images from one patient’s treatment. The patient’s treated plan was created using conventional PTV margins. Adaptive treatment was simulated on the patient’s first three fractions. The daily PTV was created by removing non-targetmore » tissue, including bone, muscle and bowel, from the initial PTV based on the daily MRI. The number of beams, beam angles, and optimization parameters were kept constant, and the plan was re-optimized. Normal tissue contours were not adjusted for the re-optimization, but were adjusted for evaluation of plan quality. Plan quality was evaluated based on PTV coverage and normal tissue DVH points per treatment protocol. Bowel was contoured as the entire bowel bag per protocol at our institution. Pelvic bone marrow was contoured per RTOG protocol 1203. Results: For the clinically treated plan, the volume of bowel receiving 45 Gy was 380 cc, 53% of the rectum received 30 Gy, 35% of the bladder received 45 Gy, and 28% of the pelvic bone marrow received 40 Gy. For the adaptive plans, the volume of bowel receiving 45 Gy was 175–201 cc, 55–62% of the rectum received 30 Gy, 21– 27% of the bladder received 45 Gy, and 13–17% of the pelvic bone marrow received 40 Gy. Conclusion: Adaptive planning led to a large reduction of bowel and bone marrow dose in this pilot study. Further study of on-line adaptive techniques for the radiotherapy of pelvic lymph nodes is warranted. Dr. Low is a member of the scientific advisory board of ViewRay, Inc.« less

Phase III randomized study of radiation and temozolomide versus radiation and nitrosourea therapy for anaplastic astrocytoma: results of NRG Oncology RTOG 9813.

PubMed

Chang, Susan; Zhang, Peixin; Cairncross, J Gregory; Gilbert, Mark R; Bahary, Jean-Paul; Dolinskas, Carol A; Chakravarti, Arnab; Aldape, Kenneth D; Bell, Erica H; Schiff, David; Jaeckle, Kurt; Brown, Paul D; Barger, Geoffrey R; Werner-Wasik, Maria; Shih, Helen; Brachman, David; Penas-Prado, Marta; Robins, H Ian; Belanger, Karl; Schultz, Christopher; Hunter, Grant; Mehta, Minesh

2017-02-01

The primary objective of this study was to compare the overall survival (OS) of patients with anaplastic astrocytoma (AA) treated with radiotherapy (RT) and either temozolomide (TMZ) or a nitrosourea (NU). Secondary endpoints were time to tumor progression (TTP), toxicity, and the effect of IDH1 mutation status on clinical outcome. Eligible patients with centrally reviewed, histologically confirmed, newly diagnosed AA were randomized to receive either RT+TMZ (n = 97) or RT+NU (n = 99). The study closed early because the target accrual rate was not met. Median follow-up time for patients still alive was 10.1 years (1.9-12.6 y); 66% of the patients died. Median survival time was 3.9 years in the RT/TMZ arm (95% CI, 3.0-7.0) and 3.8 years in the RT/NU arm (95% CI, 2.2-7.0), corresponding to a hazard ratio (HR) of 0.94 (P = .36; 95% CI, 0.67-1.32). The differences in progression-free survival (PFS) and TTP between the 2 arms were not statistically significant. Patients in the RT+NU arm experienced more grade ≥3 toxicity (75.8% vs 47.9%, P < .001), mainly related to myelosuppression. Of the 196 patients, 111 were tested for IDH1-R132H status (60 RT+TMZ and 51 RT+NU). Fifty-four patients were IDH negative and 49 were IDH positive with a better OS in IDH-positive patients (median survival time 7.9 vs 2.8 y; P = .004, HR = 0.50; 95% CI, 0.31-0.81). RT+TMZ did not appear to significantly improve OS or TTP for AA compared with RT+ NU. RT+TMZ was better tolerated. IDH1-R132H mutation was associated with longer survival. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

SU-F-T-585: A Novel Phantom for Dosimetric Validation of SBRT for Spinal Lesions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Papanikolaou, KN; Ha, C; Kirby, N

2016-06-15

Purpose: SBRT is proving to be a very efficacious treatment modality for an increasing number of indications, including spine lesions. We have developed a novel phantom to serve as an end-to-end QA tool for either patient specific QA or commissioning QA of SBRT for spine lesions. Methods: In this feasibility study, we have selected a patient with a single metastatic lesion in the L5 vertebral body. The patient’s CT simulation scan was used to develop a VMAT treatment plan delivering 18Gy to at least 90% of the target volume, following the guidelines of RTOG 0631. The treatment plan was developedmore » with the Pinnacle planning system using the adaptive convolution superposition calculation mode. The approved plan was re-calculated using the Monaco planning system. We performed a pseudo-in-vivo study whereby we manufactured two copies of a phantom to the exact shape and anatomy of the patient. The phantom was made from the CT images of the patient using a 3D printer with sub-millimeter accuracy. One phantom was filled with a gel dosimeter and the other was made with two ion chamber inserts to allow us to obtain point dose measurements in the target’s center and the spinal cord. Results: The prescribed dose of 18Gy was planned for the target while keeping the maximum spinal cord dose to less than 14Gy in 0.03cc of the cord. The VMAT plan was delivered to both the gel dosimeter filed phantom and the phantom with the ion chambers. The 3D gel dosimetry revealed a very good agreement between the monte carlo and measured point and volumetric dose. Conclusion: A patient like phantom was developed and validated for use as an end-to-end tool of dose verification for SBRT of spine lesions. We found that gel dosimetry is ideally suited to assess positional and dosimetric accuracy in 3D. RTsafe provided the phantoms and the gel dosimeter used for this study.« less

Total skin electron irradiation for mycosis fungoides: relationship between acute toxicities and measured dose at different anatomic sites.

PubMed

Desai, K R; Pezner, R D; Lipsett, J A; Vora, N L; Luk, K H; Wong, J Y; Chan, S L; Findley, D O; Hill, L R; Marin, L A

1988-09-01

From June 1978 to June 1986, 50 patients with primary and recurrent mycosis fungoides were treated with total skin electron irradiation (TSEI), using the Stanford technique, to a total dose of 3600 cGy. TSEI was used alone, or in combination with low dose total body photon irradiation, or MOPP. Thermoluminescent dosimeter (TLD) measurements of the prescribed skin dose were obtained on twenty patients. The dorsum of the foot was 24% higher. The axillae, the bottom, and the arch of the foot were significantly underdosed. Frequencies of acute toxicities noted at 2000 cGy were: Skin, Grade I-II (RTOG) 80%. Partial epilation: scalp, 100%; eyebrows and at eyelashes, 20%. Nail dystrophy, 48%. Edema: hands and feet, 44%. Bullae: dorsum of feet, 8%; hands, 4%; and 3600 cGy: Skin, grade III 22%. Total epilation: scalp, 66%; eyebrows and eyelashes, 56%. Nail loss, 38%. Edema: hands and feet, 76%. Bullae: dorsum of feet, 34%; hands, 12%. Conjunctivitis, 4%. Large bullae, were more significant on the dorsum of the feet. Severe moist desquamation occurred in eight patients who had ulcerated lesions on initial presentation. Three patients were hospitalized due to ulceration and skin infection. All patients completed treatment after a short to moderate break. No patient developed skin necrosis, or corneal ulceration. No correlation exists between dose level, degree and onset of toxicity with previous chemotherapy or TBI. We conclude that the overall toxicity of TSEI is well tolerated.

Late Side Effects After Image Guided Intensity Modulated Radiation Therapy Compared to 3D-Conformal Radiation Therapy for Prostate Cancer: Results From 2 Prospective Cohorts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wortel, Ruud C.; Incrocci, Luca; Pos, Floris J.

Purpose: Technical developments in the field of external beam radiation therapy (RT) enabled the clinical introduction of image guided intensity modulated radiation therapy (IG-IMRT), which improved target conformity and allowed reduction of safety margins. Whether this had an impact on late toxicity levels compared to previously applied three-dimensional conformal radiation therapy (3D-CRT) is currently unknown. We analyzed late side effects after treatment with IG-IMRT or 3D-CRT, evaluating 2 prospective cohorts of men treated for localized prostate cancer to investigate the hypothesized reductions in toxicity. Methods and Materials: Patients treated with 3D-CRT (n=189) or IG-IMRT (n=242) to 78 Gy in 39 fractionsmore » were recruited from 2 Dutch randomized trials with identical toxicity scoring protocols. Late toxicity (>90 days after treatment) was derived from self-assessment questionnaires and case report forms, according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG-EORTC) scoring criteria. Grade ≥2 endpoints included gastrointestinal (GI) rectal bleeding, increased stool frequency, discomfort, rectal incontinence, proctitis, and genitourinary (GU) obstruction, increased urinary frequency, nocturia, urinary incontinence, and dysuria. The Cox proportional hazards regression model was used to compare grade ≥2 toxicities between both techniques, adjusting for other modifying factors. Results: The 5-year cumulative incidence of grade ≥2 GI toxicity was 24.9% for IG-IMRT and 37.6% following 3D-CRT (adjusted hazard ratio [HR]: 0.59, P=.005), with significant reductions in proctitis (HR: 0.37, P=.047) and increased stool frequency (HR: 0.23, P<.001). GU grade ≥2 toxicity levels at 5 years were comparable with 46.2% and 36.4% following IG-IMRT and 3D-CRT, respectively (adjusted HR: 1.19, P=.33). Other strong predictors (P<.01) of grade ≥2 late toxicity were baseline complaints, acute toxicity, and age. Conclusions: Treatment with IG-IMRT reduced the risk of late grade ≥2 complications, whereas GU toxicities remained comparable. This clinically relevant observation demonstrates that IMRT and image-guidance should therefore be the preferred treatment option, provided that margin reduction is implemented with caution.« less

Esophageal Dose Tolerance to Hypofractionated Stereotactic Body Radiation Therapy: Risk Factors for Late Toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stephans, Kevin L., E-mail: stephak@ccf.org; Djemil, Toufik; Diaconu, Claudiu

2014-09-01

Purpose: To identify factors associated with grade ≥3 treatment related late esophageal toxicity after lung or liver stereotactic body radiation therapy (SBRT). Methods and Materials: This was a retrospective review of 52 patients with a planning target volume within 2 cm of the esophagus from a prospective registry of 607 lung and liver SBRT patients treated between 2005 and 2011. Patients were treated using a risk-adapted dose regimen to a median dose of 50 Gy in 5 fractions (range, 37.5-60 Gy in 3-10 fractions). Normal structures were contoured using Radiation Therapy Oncology Group (RTOG) defined criteria. Results: The median esophageal point dose andmore » 1-cc dose were 32.3 Gy (range, 8.9-55.4 Gy) and 24.0 Gy (range, 7.8-50.9 Gy), respectively. Two patients had an esophageal fistula at a median of 8.4 months after SBRT, with maximum esophageal point doses of 51.5 and 52 Gy, and 1-cc doses of 48.1 and 50 Gy, respectively. These point and 1-cc doses were exceeded by 9 and 2 patients, respectively, without a fistula. The risk of a fistula for point doses exceeding 40, 45, and 50 Gy was 9.5% (n=2/21), 10.5% (n=2/19), and 12.5% (n=2/16), respectively. The risk of fistula for 1-cc doses exceeding 40, 45, and 50 Gy was 25% (n=2/9), 50% (n=2/4), and 50% (n=2/4), respectively. Eighteen patients received systemic therapy after SBRT (11 systemic chemotherapy, and 6 biologic agents, and 1 both). Both patients with fistulas had received adjuvant anti-angiogenic (vascular endothelial growth factor) agents within 2 months of completing SBRT. No patient had a fistula in the absence of adjuvant VEGF-modulating agents. Conclusions: Esophageal fistula is a rare complication of SBRT. In this series, fistula was seen with esophageal point doses exceeding 51 Gy and 1-cc doses greater than 48 Gy. Notably, however, fistula was seen only in those patients who also received adjuvant VEGF-modulating agents after SBRT. The potential interaction of dose and adjuvant therapy should be considered when delivering SBRT near the esophagus.« less

Esophageal dose tolerance to hypofractionated stereotactic body radiation therapy: risk factors for late toxicity.

PubMed

Stephans, Kevin L; Djemil, Toufik; Diaconu, Claudiu; Reddy, Chandana A; Xia, Ping; Woody, Neil M; Greskovich, John; Makkar, Vinit; Videtic, Gregory M M

2014-09-01

To identify factors associated with grade ≥3 treatment related late esophageal toxicity after lung or liver stereotactic body radiation therapy (SBRT). This was a retrospective review of 52 patients with a planning target volume within 2 cm of the esophagus from a prospective registry of 607 lung and liver SBRT patients treated between 2005 and 2011. Patients were treated using a risk-adapted dose regimen to a median dose of 50 Gy in 5 fractions (range, 37.5-60 Gy in 3-10 fractions). Normal structures were contoured using Radiation Therapy Oncology Group (RTOG) defined criteria. The median esophageal point dose and 1-cc dose were 32.3 Gy (range, 8.9-55.4 Gy) and 24.0 Gy (range, 7.8-50.9 Gy), respectively. Two patients had an esophageal fistula at a median of 8.4 months after SBRT, with maximum esophageal point doses of 51.5 and 52 Gy, and 1-cc doses of 48.1 and 50 Gy, respectively. These point and 1-cc doses were exceeded by 9 and 2 patients, respectively, without a fistula. The risk of a fistula for point doses exceeding 40, 45, and 50 Gy was 9.5% (n=2/21), 10.5% (n=2/19), and 12.5% (n=2/16), respectively. The risk of fistula for 1-cc doses exceeding 40, 45, and 50 Gy was 25% (n=2/9), 50% (n=2/4), and 50% (n=2/4), respectively. Eighteen patients received systemic therapy after SBRT (11 systemic chemotherapy, and 6 biologic agents, and 1 both). Both patients with fistulas had received adjuvant anti-angiogenic (vascular endothelial growth factor) agents within 2 months of completing SBRT. No patient had a fistula in the absence of adjuvant VEGF-modulating agents. Esophageal fistula is a rare complication of SBRT. In this series, fistula was seen with esophageal point doses exceeding 51 Gy and 1-cc doses greater than 48 Gy. Notably, however, fistula was seen only in those patients who also received adjuvant VEGF-modulating agents after SBRT. The potential interaction of dose and adjuvant therapy should be considered when delivering SBRT near the esophagus. Copyright © 2014 Elsevier Inc. All rights reserved.

SU-E-T-410: Evaluation of Treatment Modalities for Stereotactic Lung Radiation Therapy: A Phantom Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mohatt, D; Malhotra, H

Purpose: To evaluate and verify the accuracy of alternative treatment modalities for stereotactic lung therapy with end-to-end testing. We compared three dimensional conformal therapy (3DCRT), dynamic conformal arc therapy (DCAT), intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) treatment using 6 MV, 6 MV flattening filter free (FFF) and 10 MV FFF photons. Methods: A QUASAR respiratory motion phantom was utilized with custom ion chamber and gafchromatic EBT2 film inserts. The phantom contained a low density lung medium with a cylindrical polystyrene tumor (35 cc). Pseudo representative structures for various organs at risk (OAR) were created. Allmore » treatment plans were created using Eclipse ver. 11 using the same image and structure sets, and delivered via Varian TrueBeam STx linear accelerator equipped with high definition MLC. Evaluation of plan quality followed ROTG 0813 criterion for conformity index (CI100%), high dose spillage, D2cm, and R50%. Results: All treatment plans met the OAR dose constraints per protocol and could be delivered without any beam hold offs or other interlocks and hence were deemed clinically safe. For equivalent beam energies, target conformity was improved for all modalities when switching to FFF mode. Treatment efficiency increased for VMAT FFF by a factor of 3–4 over IMRT, and up to factor of 7 when compared to 3DCRT. Pass rates were > 97% for all treatment using gamma criteria of 3%, 3mm. Absolute dose at iso-center was verified with ion chamber, and found to be within 2% of the treatment planning system. Conclusion: The higher dose rate associated with FFF not only reduces delivery times, but in most cases enhances plan quality. The one modality with succeeding best results for all RTOG criterions was VMAT 6 MV FFF. This end-to-end testing provides necessary confidence in the entire dose delivery chain for lung SBRT patients.« less

A Randomized Phase 2 Trial of Prophylactic Manuka Honey for the Reduction of Chemoradiation Therapy–Induced Esophagitis During the Treatment of Lung Cancer: Results of NRG Oncology RTOG 1012

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fogh, Shannon E., E-mail: Shannon.Fogh@ucsf.edu; Deshmukh, Snehal; Berk, Lawrence B.

Purpose: Randomized trials have shown that honey is effective for the prevention of radiation-induced mucositis in head and neck cancer patients. Because there is no efficacious preventative for radiation esophagitis in lung cancer patients, this trial compared liquid honey, honey lozenges, and standard supportive care for radiation esophagitis. Methods: The patients were stratified by percentage of esophagus receiving specific radiation dose (V60 Gy esophagus <30% or ≥30%) and were then randomized between supportive care, 10 mL of liquid manuka honey 4 times a day, and 2 lozenges (10 mL of dehydrated manuka honey) 4 times a day during concurrent chemotherapy and radiation therapy.more » The primary endpoint was patient-reported pain on swallowing, with the use of an 11-point (0-10) scale at 4 weeks (Numerical Rating Pain Scale, NRPS). The study was designed to detect a 15% relative reduction of change in NRPS score. The secondary endpoints were trend of pain over time, opioid use, clinically graded and patient-reported adverse events, weight loss, dysphagia, nutritional status, and quality of life. Results: 53 patients were randomized to supportive care, 54 were randomized to liquid honey, and 56 were randomized to lozenge honey. There was no significant difference in the primary endpoint of change in the NRPS at 4 weeks between arms. There were no differences in any of the secondary endpoints except for opioid use at 4 weeks during treatment between the supportive care and liquid honey arms, which was found to be significant (P=.03), with more patients on the supportive care arm taking opioids. Conclusion: Honey as prescribed within this protocol was not superior to best supportive care in preventing radiation esophagitis. Further testing of other types of honey and research into the mechanisms of action are needed.« less

SU-F-J-132: Evaluation of CTV-To-PTV Expansion for Whole Breast Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burgdorf, B; Freedman, G; Teo, B

2016-06-15

Purpose: The current standard CTV-to-PTV expansion for whole breast radiotherapy (WBRT) is 7mm, as recommended by RTOG-1005.This expansion is derived from the uncertainty due to patient positioning (±5mm) and respiratory motion (±5mm). We evaluated the expansion needed for respiratory motion uncertainty using 4DCT. After determining the appropriate expansion margins, RT plans were generated to evaluate the reduction in heart and lung dose. Methods: 4DCT images were acquired during treatment simulation and retrospectively analyzed for 34 WBRT patients. Breast CTVs were contoured on the maximum inhale and exhale phase. Breast CTV displacement was measured in the L-R, A-P, and SUP-INF directionsmore » using rigid registration between phase images. Averaging over the 34 patients, we determined the margin due to respiratory motion. Plans were generated for 10 left-sided cases comparing the new expansion with the 7mm PTV expansion. Results: The results for respiratory motion uncertainty are shown in Table 1. Drawing on previous work by White et al at Princess Margaret Hospital (1) (see supporting document for reference) which studied the uncertainty due to patient positioning, we concluded that, in total, a 5mm expansion was sufficient. The results for our suggested PTV margin are shown in Table 2, combining the patient positioning results from White et al with our respiratory motion results. The planning results demonstrating the heart and lung dose differences in the 5mm CTV-to-PTV expanded plan compared to the 7mm plan are shown in Table 3. Conclusion: Our work evaluating the expansion needed for respiratory motion along with previous work evaluating the expansion needed for setup uncertainty shows that a CTV-to-PTV expansion of 5mm is acceptable and conservative. By reducing the PTV expansion, significant dose reduction to the heart and lung are achievable.« less

SU-E-J-129: Atlas Development for Cardiac Automatic Contouring Using Multi-Atlas Segmentation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, R; Yang, J; Pan, T

Purpose: To develop a set of atlases for automatic contouring of cardiac structures to determine heart radiation dose and the associated toxicity. Methods: Six thoracic cancer patients with both contrast and non-contrast CT images were acquired for this study. Eight radiation oncologists manually and independently delineated cardiac contours on the non-contrast CT by referring to the fused contrast CT and following the RTOG 1106 atlas contouring guideline. Fifteen regions of interest (ROIs) were delineated, including heart, four chambers, four coronary arteries, pulmonary artery and vein, inferior and superior vena cava, and ascending and descending aorta. Individual expert contours were fusedmore » using the simultaneous truth and performance level estimation (STAPLE) algorithm for each ROI and each patient. The fused contours became atlases for an in-house multi-atlas segmentation. Using leave-one-out test, we generated auto-segmented contours for each ROI and each patient. The auto-segmented contours were compared with the fused contours using the Dice similarity coefficient (DSC) and the mean surface distance (MSD). Results: Inter-observer variability was not obvious for heart, chambers, and aorta but was large for other structures that were not clearly distinguishable on CT image. The average DSC between individual expert contours and the fused contours were less than 50% for coronary arteries and pulmonary vein, and the average MSD were greater than 4.0 mm. The largest MSD of expert contours deviating from the fused contours was 2.5 cm. The mean DSC and MSD of auto-segmented contours were within one standard deviation of expert contouring variability except the right coronary artery. The coronary arteries, vena cava, and pulmonary vein had DSC<70% and MSD>3.0 mm. Conclusion: A set of cardiac atlases was created for cardiac automatic contouring, the accuracy of which was comparable to the variability in expert contouring. However, substantial modification may need for auto-segmented contours of indistinguishable small structures.« less

Dosimetric analysis of the alopecia preventing effect of hippocampus sparing whole brain radiation therapy.

PubMed

Mahadevan, Anand; Sampson, Carrie; LaRosa, Salvatore; Floyd, Scott R; Wong, Eric T; Uhlmann, Erik J; Sengupta, Soma; Kasper, Ekkehard M

2015-11-26

Whole brain radiation therapy (WBRT) is widely used for the treatment of brain metastases. Cognitive decline and alopecia are recognized adverse effects of WBRT. Recently hippocampus sparing whole brain radiation therapy (HS-WBRT) has been shown to reduce the incidence of memory loss. In this study, we found that multi-field intensity modulated radiation therapy (IMRT), with strict constraints to the brain parenchyma and to the hippocampus, reduces follicular scalp dose and prevents alopecia. Suitable patients befitting the inclusion criteria of the RTOG 0933 trial received Hippocampus sparing whole brain radiation. On follow up, they were noticed to have full scalp hair preservation. 5 mm thickness of follicle bearing scalp in the radiation field was outlined in the planning CT scans. Conventional opposed lateral WBRT radiation fields were applied to these patient-specific image sets and planned with the same nominal dose of 30 Gy in 10 fractions. The mean and maximum dose to follicle bearing skin and Dose Volume Histogram (DVH) data were analyzed for conventional and HS-WBRT. Paired t-test was used to compare the means. All six patients had fully preserved scalp hair and remained clinically cognitively intact 1-3 months after HS-WBRT. Compared to conventional WBRT, in addition to the intended sparing of the Hippocampus, HS-WBRT delivered significantly lower mean dose (22.42 cGy vs. 16.33 cGy, p < 0.0001), V24 (9 cc vs. 44 cc, p < 0.0000) and V30 (9 cc vs. 0.096 cc, p = 0.0106) to follicle hair bearing scalp and prevented alopecia. There were no recurrences in the Hippocampus area. HS-WBRT, with an 11-field set up as described, while attempting to conserve hippocampus radiation and maintain radiation dose to brain inadvertently spares follicle-bearing scalp and prevents alopecia.

A unique hypofractionated radiotherapy schedule with 51.3 Gy in 18 fractions three times per week for early breast cancer: outcomes including local control, acute and late skin toxicity.

PubMed

Vassilis, Kouloulias; Ioannis, Gogalis; Anna, Zygogianni; Christina, Armpilia; Christos, Antypas; John, Kokakis; Porfyrios, Koromperlis; Vassiliki, Gennimata; John, Kouvaris

2017-03-01

Evaluation of local control and acute and late toxicity regarding a hypofractionated RT schedule for breast cancer patients. Between October 2007 and October 2009, 80 women with early breast cancer were treated by 42.75 Gy in 15 fractions over 5 weeks. This treatment involved three fractions per week (Monday-Wednesday-Friday). All patients received an additional boost dose to the tumor bed of 8.55 Gy in 3 fractions using 6 MV photons. The primary endpoint included any local recurrence in the treated breast. Secondary endpoint included acute and late radiation skin toxicity. The median follow-up time was 63 months (range 60-72). Radiation toxicity was graded according the RTOG/EORTC criteria. Neither local nor distant recurrence was noted in any patient during this 3-year follow-up. Grade 0, 1, 2 acute skin toxicity was observed in 56/80 (70.0 %), in 19/80 (23.8 %) and in 5/80 (6.3 %), respectively. Three months post-RT, toxicity grades 0, 1, 2 skin toxicity were 64/80 (80 %), 14/80 (17.5 %) and 2/80 (2.5 %), respectively. Late toxicity as grade 0, 1 was observed in 72/80 (90.0 %) and in 8/80 (10.0 %), respectively, 6 months post-RT, whereas after 1 year they were 78/80 (97.5 %) and 2/80 (2.5 %), respectively. Preliminary results regarding skin reactions, cosmetic appearance and local control are consistent with published data that support the use of shorter fractionation schedules in early breast cancer patients after breast conservative surgery. Longer follow-up and a randomized prospective study stand in need for the extraction of safe conclusions.

Direct plan comparison of RapidArc and CyberKnife for spine stereotactic body radiation therapy

NASA Astrophysics Data System (ADS)

Choi, Young Eun; Kwak, Jungwon; Song, Si Yeol; Choi, Eun Kyung; Ahn, Seung Do; Cho, Byungchul

2015-07-01

We compared the treatment planning performance of RapidArc (RA) vs. CyberKnife (CK) for spinal stereotactic body radiation therapy (SBRT). Ten patients with spinal lesions who had been treated with CK were re-planned with RA, which consisted of two complete arcs. Computed tomography (CT) and volumetric dose data of CK, generated using the Multiplan (Accuray) treatment planning system (TPS) and the Ray-trace algorithm, were imported to Varian Eclipse TPS in Dicom format, and the data were compared with the RA plan by using an analytical anisotropic algorithm (AAA) dose calculation. The optimized dose priorities for both the CK and the RA plans were similar for all patients. The highest priority was to provide enough dose coverage to the planned target volume (PTV) while limiting the maximum dose to the spinal cord. Plan quality was evaluated with respect to PTV coverage, conformity index (CI), high-dose spillage, intermediate-dose spillage (R50% and D2cm), and maximum dose to the spinal cord, which are criteria recommended by the RTOG 0631 spine and 0915 lung SBRT protocols. The mean CI' SD values of the PTV were 1.11' 0.03 and 1.17' 0.10 for RA and CK ( p = 0.02), respectively. On average, the maximum dose delivered to the spinal cord in CK plans was approximately 11.6% higher than that in RA plans, and this difference was statistically significant ( p < 0.001). High-dose spillages were 0.86% and 2.26% for RA and CK ( p = 0.203), respectively. Intermediate-dose spillage characterized by D2cm was lower for RA than for CK; however, R50% was not statistically different. Even though both systems can create highly conformal volumetric dose distributions, the current study shows that RA demonstrates lower high- and intermediate-dose spillages than CK. Therefore, RA plans for spinal SBRT may be superior to CK plans.

A Randomized Phase II Trial of Prophylactic Manuka Honey for the Reduction of Chemoradiation Therapy Induced Esophagitis During the Treatment of Lung Cancer: Results of NRG Oncology RTOG 1012

PubMed Central

Fogh, Shannon; Deshmukh, Snehal; Berk, Lawrence B.; Dueck, Amylou C.; Roof, Kevin; Yacoub, Sherif; Gergel, Thomas; Stephans, Kevin; Rimner, Andreas; DeNittis, Albert; Pablo, John; Rineer, Justin; Williams, Terence M.; Bruner, Deborah

2017-01-01

Purpose Randomized trials have shown that honey is effective for prevention of radiation-induced mucositis in head and neck cancer patients. Because there is no efficacious preventative for radiation esophagitis in lung cancer patients, this trial compared liquid honey, honey lozenges, and standard supportive care for radiation esophagitis. Methods Patients were stratified by percentage of esophagus receiving specific radiation dose (V60Gy esophagus < or ≥ 30%), then randomized between supportive care, 10 ml of liquid Manuka honey four times a day or 2 lozenges (10 ml of dehydrated Manuka honey) four times a day during concurrent chemotherapy and radiotherapy. The primary endpoint was patient-reported pain on swallowing utilizing an eleven point (0–10) scale at 4 weeks (Numerical Rating Pain Scale, NRPS). The study was designed to detect 15% relative reduction of change in NRPS score. Secondary endpoints were trend of pain over time, opioid use, clinically-graded and patient-reported adverse events, weight loss, dysphagia, nutritional status and quality of life. Results 53 patients were randomized to supportive care, 54 randomized to liquid honey and 56 to lozenge honey. There was no significant difference in the primary endpoint of change in the NRPS at 4 weeks between arms. There were no differences in any of the secondary endpoints except for opioid use at 4 weeks during treatment between the supportive care and liquid honey arms which was found to be significant (p=0.03) with more patients on the supportive care arm taking opioids. Conclusion Honey as prescribed within this protocol was not superior to best supportive care in preventing radiation esophagitis. Further testing of other types of honey and research into the mechanisms of action are needed. PMID:28244415

A Randomized Phase 2 Trial of Prophylactic Manuka Honey for the Reduction of Chemoradiation Therapy-Induced Esophagitis During the Treatment of Lung Cancer: Results of NRG Oncology RTOG 1012.

PubMed

Fogh, Shannon E; Deshmukh, Snehal; Berk, Lawrence B; Dueck, Amylou C; Roof, Kevin; Yacoub, Sherif; Gergel, Thomas; Stephans, Kevin; Rimner, Andreas; DeNittis, Albert; Pablo, John; Rineer, Justin; Williams, Terence M; Bruner, Deborah

2017-03-15

Randomized trials have shown that honey is effective for the prevention of radiation-induced mucositis in head and neck cancer patients. Because there is no efficacious preventative for radiation esophagitis in lung cancer patients, this trial compared liquid honey, honey lozenges, and standard supportive care for radiation esophagitis. The patients were stratified by percentage of esophagus receiving specific radiation dose (V60 Gy esophagus <30% or ≥30%) and were then randomized between supportive care, 10 mL of liquid manuka honey 4 times a day, and 2 lozenges (10 mL of dehydrated manuka honey) 4 times a day during concurrent chemotherapy and radiation therapy. The primary endpoint was patient-reported pain on swallowing, with the use of an 11-point (0-10) scale at 4 weeks (Numerical Rating Pain Scale, NRPS). The study was designed to detect a 15% relative reduction of change in NRPS score. The secondary endpoints were trend of pain over time, opioid use, clinically graded and patient-reported adverse events, weight loss, dysphagia, nutritional status, and quality of life. 53 patients were randomized to supportive care, 54 were randomized to liquid honey, and 56 were randomized to lozenge honey. There was no significant difference in the primary endpoint of change in the NRPS at 4 weeks between arms. There were no differences in any of the secondary endpoints except for opioid use at 4 weeks during treatment between the supportive care and liquid honey arms, which was found to be significant (P=.03), with more patients on the supportive care arm taking opioids. Honey as prescribed within this protocol was not superior to best supportive care in preventing radiation esophagitis. Further testing of other types of honey and research into the mechanisms of action are needed. Copyright © 2016. Published by Elsevier Inc.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Su, M; Sura, S

Purpose: To evaluate dosimetric impact of two axillary nodes (AX) boost techniques: (1) posterior-oblique optimized field boost (POB), (2) traditional posterior-anterior boost (PAB) with field optimization (O-PAB), for a postmastectomy breast patient with positive axillary lymph nodes. Methods: Five patients, 3 left and 2 right chest walls, were included in this study. All patients were simulated in 5mm CT slice thickness. Supraclavicular (SC) and level I/II/III AX were contoured based on the RTOG atlas guideline. Five treatment plans, (1) tangential chest wall, (2) oblique SC including AX, (3) PAB, O-PAB and POB, were created for each patient. Three plan sumsmore » (PS) were generated by sum one of (3) plan with plan (1) and (2). The field optimization was done through PS dose distribution, which included a field adjustment, a fractional dose, a calculation location and a gantry angle selection for POB. A dosimetric impact was evaluated by comparing a SC and AX coverage, a PS maximum dose, an irradiated area percentage volume received dose over 105% prescription dose (V105), an ipsi-laterial mean lung dose (MLD), an ipsi-laterial mean humeral head dose (MHHD), a mean heart dose (MHD) (for left case only) and their DVH amount these three technique. Results: O-PAB, POB and PAB dosimetric results showed that there was no significant different on SC and AX coverage (p>0.43) and MHD (p>0.16). The benefit of sparing lung irradiation from PAB to O-PAB to POB was significant (p<0.004). PAB showed a highest PS maximum dose (p<0.005), V105 (p<0.023) and MLD (compared with OPAB, p=0.055). MHHD showed very sensitive to the patient arm positioning and anatomy. O-PAB convinced a lower MHHD than PAB (p=0.03). Conclusion: 3D CT contouring plays main role in accuracy radiotherapy. Dosimetric advantage of POB and O-PAB was observed for a better normal tissue irradiation sparing.« less

TU-F-CAMPUS-J-01: Inference of Prostate PTV Margins in VMAT Delivery From Intra-Fraction Prostate Motion During SBRT Delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thind, K; Wong, R; Gerdes, C

2015-06-15

Purpose: To retrospectively quantify the intra-fraction prostate motion during stereotactic body radiation therapy (SBRT) treatment using CyberKnife’s target tracking system, which may provide insight into expansion margins from GTV to PTV used in gantry-based treatments. CyberKnife is equipped with an active tracking system (InTempo) that tracks the four fiducials placed in the prostate gland. The system acquires intra-fraction orthogonal kV images at 45° and 315° in a sequential fashion. Methods: A total of 38 patients treated with SBRT using CyberKnife between 2011 and 2013 were studied. Dose-regime was 36.25 Gy in 5 fractions (7.25 Gy/fraction, twice per week) as permore » RTOG 0938 guidelines. The CyberKnife image tracking logs for all SBRT treatments using InTempo were examined. A total of 13663 images were examined for the superior/inferior (SI), anterior/posterior (AP) and left/right (LR) translation as well as roll, pitch and yaw rotations for the target position relative to the last known model position. Results: The mean ± 2 SD of intra-fraction motion was contained within 3 mm for SI and LR and 4.5 mm for AP directions at 5 minutes into the treatment delivery. It was contained within 4 mm for SI and LR and 5 mm for AP at 10 minutes. At 15 minutes into delivery, all translations were contained within 5 mm. The mean ± 2 SD of prostate roll, pitch and yaw increased with time but were contained within 5 degree at 5, 10 and 15 minutes into treatment. Additionally, target translations and rotations were within ± 1 mm and ± 1 degree for 90% and 78% of the time. Conclusion: The organ motion component of PTV margin for 10 minute VMAT delivery is contained within 4 mm in SI and LR direction and within 5 mm in the AP direction.« less

SU-F-T-418: Evaluation of Organs at Risk (OAR) Sparing in Left Breast Irradiation Techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saini, A; Hwang, C; Das, I

Purpose: To compare dose to organs at risk (OAR) for left sided breast radiation therapy with comparable planning target volume (PTV) coverage in three techniques; free breathing in supine position (FB), deep inspirational breath hold in supine (DIBH) and free breathing in prone position (PP). Methods: Ten left sided breast cancer patients suitable for this study underwent a CT scan in three techniques e.g. supine, FB and DIBH and prone position (PP). One radiation oncologist contoured the PTV and OAR (cardiac components) based on RTOG guidelines. Treatment plans were optimized using field-in-field technique with AAA algorithm. Each plan was optimizedmore » to provide identical coverage to PTV such that a reasonable comparison in OAR dosimetry can be evaluated. The prescribed dose to PTV were 42.56 Gy; 2.66 Gy in 16 fractions. Results: Average lung dose parameters; Dmean, V10, V20 and V30 were 0.5 Gy, 0.6%, 0.2%, and 0.1% respectively in PP which is significantly lower than FB (5.9 Gy, 14.2%, 10.7 %, and 8.4%) and DIBH (5.8 Gy, 14.3%, 10.2%, 7.8%). Similarly average heart Dmean, V2.5, V5, V10, and V20 were much lower in PP (1.2Gy, 9.1%, 2.1%, 0.8%, and 0.4%), and in DIBH (1.2 Gy, 10.6%, 1.7%, 0.5%, and 0.1%) compared to FB (2.6 Gy, 21%, 7.2%, 4.4% and 3.3%) respectively. Similar findings were also noted in the heart component left anterior descending artery (LAD) and Left ventricle (LV) which are correlated to radiation related toxicity. Conclusion: Based on the calculated dose, FB technique provides highest heart and lung dose. Prone has lowest lung dose, and DIBH has lowest LAD dose. It is found that PP is always superior for heart, LV, LAD and lung as compared to FB. This conclusion is in contrast to some published study concluding that prone position has no benefit for heart sparing.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lafata, K; Ren, L; Wu, Q

Purpose: To develop a data-mining methodology based on quantum clustering and machine learning to predict expected dosimetric endpoints for lung SBRT applications based on patient-specific anatomic features. Methods: Ninety-three patients who received lung SBRT at our clinic from 2011–2013 were retrospectively identified. Planning information was acquired for each patient, from which various features were extracted using in-house semi-automatic software. Anatomic features included tumor-to-OAR distances, tumor location, total-lung-volume, GTV and ITV. Dosimetric endpoints were adopted from RTOG-0195 recommendations, and consisted of various OAR-specific partial-volume doses and maximum point-doses. First, PCA analysis and unsupervised quantum-clustering was used to explore the feature-space tomore » identify potentially strong classifiers. Secondly, a multi-class logistic regression algorithm was developed and trained to predict dose-volume endpoints based on patient-specific anatomic features. Classes were defined by discretizing the dose-volume data, and the feature-space was zero-mean normalized. Fitting parameters were determined by minimizing a regularized cost function, and optimization was performed via gradient descent. As a pilot study, the model was tested on two esophageal dosimetric planning endpoints (maximum point-dose, dose-to-5cc), and its generalizability was evaluated with leave-one-out cross-validation. Results: Quantum-Clustering demonstrated a strong separation of feature-space at 15Gy across the first-and-second Principle Components of the data when the dosimetric endpoints were retrospectively identified. Maximum point dose prediction to the esophagus demonstrated a cross-validation accuracy of 87%, and the maximum dose to 5cc demonstrated a respective value of 79%. The largest optimized weighting factor was placed on GTV-to-esophagus distance (a factor of 10 greater than the second largest weighting factor), indicating an intuitively strong correlation between this feature and both endpoints. Conclusion: This pilot study shows that it is feasible to predict dose-volume endpoints based on patient-specific anatomic features. The developed methodology can potentially help to identify patients at risk for higher OAR doses, thus improving the efficiency of treatment planning. R01-184173.« less

SU-F-J-123: CT-Based Determination of DIBH Variability and Its Dosimetric Impact On Post-Mastectomy Plus Regional Nodal Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malin, M; Kang, H; Tatebe, K

Purpose: Breast cancer radiotherapy delivered using voluntary deep inspiration breath-hold (DIBH) requires reproducible breath holds, particularly when matching supraclavicular fields to tangential fields. We studied the impact of variation in DIBHs on CTV and OAR dose metrics by comparing the dose distribution computed on two DIBH CT scans taken at the time of simulation. Methods: Ten patients receiving 50Gy in 25 fractions to the left chestwall and regional lymph nodes were studied. Two simulation CT scans were taken during separate DIBHs along with a free-breathing (FB) scan. The treatment was planned using one DIBH CT. The dose was recomputed onmore » the other two scans using adaptive planning (Pinnacle 9.10) in which the scans are registered using a cross-correlation algorithm. The chestwall, lymph nodes and OARs were contoured on the scans following the RTOG consensus guidelines. The overall translational and rotational variation between the DIBH scans was used to estimate positional variation between breath-holds. Dose metrics between plans were compared using paired t-tests (p < 0.05) and means and standard deviations were reported. Results: The registration parameters were sub-millimeter and sub-degree. Although DIBH significantly reduced mean heart dose by 2.4Gy compared to FB (p < 0.01), no significant changes in dose were observed for targets or OARs between the two DIBH scans. Nodal coverage as assessed by V90% was 90%±8% and 89%±8% for supraclavicular and 99%±2% and 97%±22% for IM nodes. Though a significant decrease (10.5%±12.4%) in lung volume in the second DIBH CT was observed, the lung V20Gy was unchanged (14±2% and 14±3%) between the two DIBH scans. Conclusion: While the lung volume often varied between DIBHs, the CTV and OAR dose metrics were largely unchanged. This indicates that manual DIBH has the potential to provide consistent dose delivery to the chestwall and regional nodes targets when using matched fields.« less

SU-F-T-254: Dose Volume Histogram (DVH) Analysis of Breath Hold Vs Free Breathing Techniques for Esophageal Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Badkul, R; Doke, K; Pokhrel, D

Purpose: Lung and heart doses and associated toxicity are of concern in radiotherapy for esophageal cancer. This study evaluates the dosimetry of deep-inspiration-breath-hold (DIBH) technique as compared to freebreathing( FB) using 3D-conformal treatment(3D-CRT) of esophageal cancer. Methods: Eight patients were planned with FB and DIBH CT scans. DIBH scans were acquired using Varian RPM system. FB and DIBH CTs were contoured per RTOG-1010 to create the planning target volume(PTV) as well as organs at risk volumes(OAR). Two sets of gross target volumes(GTV) with 5cm length were contoured for each patient: proximal at the level of the carina and distal atmore » the level of gastroesophageal junction and were enlarged with appropriate margin to generate Clinical Target Volume and PTV. 3D-CRT plans were created on Eclipse planning system for 45Gy to cover 95% of PTV in 25 fractions for both proximal and distal tumors on FB and DIBH scans. For distal tumors celiac nodes were covered electively. DVH parameters for lung and heart OARs were generated and analyzed. Results: All DIBH DVH parameters were normalized to FB plan values. Average of heart-mean and heart-V40 was 0.70 and 0.66 for proximal lesions. For distal lesions ratios were 1.21 and 2.22 respectively. For DIBH total lung volume increased by 2.43 times versus FB scan. Average of lung-mean, V30, V20, V10, V5 are 0.82, 0.92, 0.76, 0.77 and 0.79 for proximal lesions and 1.17,0.66,0.87,0.93 and 1.03 for distal lesions. Heart doses were lower for breath-hold proximal lesions but higher for distal lesions as compared to free-breathing plans. Lung doses were lower for both proximal and distal breath-hold lesions except mean lung dose and V5 for distal lesions. Conclusion: This study showed improvement of OAR doses for esophageal lesions at mid-thoracic level utilizing DIBH vs FB technique but did not show consistent OAR sparing with DIBH for distal lesions.« less

Revised Modelling of the Addition of Synchronous Chemotherapy to Radiotherapy in Squamous Cell Carcinoma of the Head and Neck-A Low α/β?

PubMed

Best, James; Fong, Charles; Benghiat, Helen; Mehanna, Hisham; Glaholm, John; Hartley, Andrew

2018-06-13

Background: The effect of synchronous chemotherapy in squamous cell carcinoma of the head and neck (SCCHN) has been modelled as additional Biologically Effective Dose (BED) or as a prolonged tumour cell turnover time during accelerated repopulation. Such models may not accurately predict the local control seen when hypofractionated accelerated radiotherapy is used with synchronous chemotherapy. Methods: For the purposes of this study three isoeffect relationships were assumed: Firstly, from the RTOG 0129 trial, synchronous cisplatin chemotherapy with 70 Gy in 35 fractions over 46 days results in equivalent local control to synchronous cisplatin chemotherapy with 36 Gy in 18# followed by 36 Gy in 24# (2# per day) over a total of 39 days. Secondly, in line with primary local control outcomes from the PET-Neck study, synchronous cisplatin chemotherapy with 70 Gy in 35# over 46 days results in equivalent local control to synchronous cisplatin chemotherapy delivered with 65 Gy in 30# over 39 days. Thirdly, from meta-analysis data, 70 Gy in 35# over 46 days with synchronous cisplatin results in equivalent local control to 84 Gy in 70# over 46 days delivered without synchronous chemotherapy. Using the linear quadratic equation the above isoeffect relationships were expressed algebraically to determine values of α , α/β , and k for SCCHN when treated with synchronous cisplatin using standard parameters for the radiotherapy alone schedule ( α = 0.3 Gy −1 , α/β = 10 Gy, and k = 0.42 Gy 10 day −1 ). Results: The values derived for α/β , α and k were 2 Gy, 0.20 and 0.21 Gy −1 , and 0.65 and 0.71 Gy₂day −1 . Conclusions: Within the limitations of the assumptions made, this model suggests that accelerated repopulation may remain a significant factor when synchronous chemotherapy is delivered with radiotherapy in SCCHN. The finding of a low α/β for SCCHN treated with cisplatin suggests a greater tumour susceptibility to increasing dose per fraction and underlines the importance of the completion of randomized trials examining the role of hypofractionated acceleration in SCCHN.

Confirmation of skin doses resulting from bolus effect of intervening alpha-cradle and carbon fiber couch in radiotherapy.

PubMed

Chan, Maria F; Chiu-Tsao, Sou-Tung; Li, Jingdong; Schupak, Karen; Parhar, Preeti; Burman, Chandra

2012-12-01

In this study, we verified the treatment planning calculations of skin doses with the incorporation of the bolus effect due to the intervening alpha-cradle (AC) and carbon fiber couch (CFC) using radiochromic EBT2 films. A polystyrene phantom (25 × 25 × 15 cm(3)) with six EBT2 films separated by polystyrene slabs, at depths of 0, 0.1, 0.2, 0.5, 1, 1.4 cm, was positioned above an AC, which was ~1 cm thick. The phantom and AC assembly were CT scanned and the CT-images were transferred to the treatment planning system (TPS) for calculations in three scenarios: (A) ignoring AC and CFC, (B) accounting for AC only, (C) accounting for both AC and CFC. A single posterior 10 × 10 cm(2) field, a pair of posterior-oblique 10 × 10 cm(2) fields, and a posterior IMRT field (6 MV photons from a Varian Trilogy linac) were planned. For each radiation field configuration, the same MU were used in all three scenarios in the TPS. Each plan for scenario C was delivered to expose a stack of EBT2 films in the phantom through AC and CFC. In addition, in vivo EBT2 film measurement on a lung cancer patient immobilized with AC undergoing IMRT was also included in this study. Point doses and planar distributions generated from the TPS for the three scenarios were compared with the data from the EBT2 film measurements. For all the field arrangements, the EBT2 film data including the in vivo measurement agreed with the doses calculated for scenario (C), within the uncertainty of the EBT2 measurements (~4%). For the single posterior field (a pair of posterior-oblique fields), the TPS generated doses were lower than the EBT2 doses by 34%, 33%, 31%, 13% (34%, 31%, 31%, 11%) for scenario A and by 27%, 25%, 22%, 8% (25%, 21%, 21%, 6%) for scenario B at the depths of 0, 0.1, 0.2, 0.5 cm, respectively. For the IMRT field, the 2D dose distributions at each depth calculated in scenario C agree with those measured data. When comparing the central axis doses for the IMRT field, we found the TPS generated doses for scenario A (B) were lower than the EBT2 data by 35%, 34%, 31%, 16% (29%, 26%, 23%, 10%) at the depths of 0, 0.1, 0.2, 0.5 cm, respectively. There were no significant differences for the depths of 1.0 and 1.4 cm for all the radiation fields studied. TPS calculation of doses in the skin layers accounting for AC and CFC was verified by EBT2 film data. Ignoring the presence of AC and/or CFC in TPS calculation would significantly underestimate the doses in the skin layers. For the clinicians, as more hypofractionated regimens and stereotactic regimens are being used, this information will be useful to avoid potential serious skin toxicities, and also assist in clinical decisions and report these doses accurately to relevant clinical trials/cooperative groups, such as RTOG.

Treatment planning and 3D dose verification of whole brain radiation therapy with hippocampal avoidance in rats

NASA Astrophysics Data System (ADS)

Yoon, S. W.; Miles, D.; Cramer, C.; Reinsvold, M.; Kirsch, D.; Oldham, M.

2017-05-01

Despite increasing use of stereotactic radiosurgery, whole brain radiotherapy (WBRT) continues to have a therapeutic role in a selected subset of patients. Selectively avoiding the hippocampus during such treatment (HA-WBRT) emerged as a strategy to reduce the cognitive morbidity associated with WBRT and gave rise to a recently published the phase II trial (RTOG 0933) and now multiple ongoing clinical trials. While conceptually hippocampal avoidance is supported by pre-clinical evidence showing that the hippocampus plays a vital role in memory, there is minimal pre-clinic data showing that selectively avoiding the hippocampus will reduce radiation-induced cognitive decline. Largely the lack of pre-clinical evidence can be attributed to the technical hurdles associated with delivering precise conformal treatment the rat brain. In this work we develop a novel conformal HA-WBRT technique for Wistar rats, utilizing a 225kVp micro-irradiator with precise 3D-printed radiation blocks designed to spare hippocampus while delivering whole brain dose. The technique was verified on rodent-morphic Presage® 3D dosimeters created from micro-CT scans of Wistar rats with Duke Large Field-of-View Optical Scanner (DLOS) at 1mm isotropic voxel resolution. A 4-field box with parallel opposed AP-PA and two lateral opposed fields was explored with conformal hippocampal sparing aided by 3D-printed radiation blocks. The measured DVH aligned reasonably well with that calculated from SmART Plan Monte Carlo simulations with simulated blocks for 4-field HA-WBRT with both demonstrating hippocampal sparing of 20% volume receiving less than 30% the prescription dose.

Potential impact of 68Ga-PSMA-11 PET/CT on prostate cancer definitive radiation therapy planning.

PubMed

Calais, Jérémie; Kishan, Amar U; Cao, Minsong; Fendler, Wolfgang P; Eiber, Matthias; Herrmann, Ken; Ceci, Francesco; Reiter, Robert E; Rettig, Matthew B; Hegde, John V; Shaverdian, Narek; King, Christopher R; Steinberg, Michael L; Czernin, Johannes; Nickols, Nicholas G

2018-04-13

Background: Standard-of-care imaging for initial staging of prostate cancer (PCa) underestimates disease burden. Prostate specific membrane antigen (PSMA) positron emission tomography/ computed tomography (PET/CT) detects PCa metastasis with superior accuracy with potential impact definitive radiation therapy (RT) planning for non-metastatic PCa. Objectives: i) To determine how often definitive PCa RT planning based on standard target volumes cover 68 Ga-PSMA-11 PET/CT defined disease, and ii) To assess the potential impact of 68 Ga-PSMA-11 PET/CT on definitive PCa RT planning. Patients and Methods: This is a post-hoc analysis of an intention to treat population of 73 patients with localized PCa without prior local therapy who underwent 68 Ga-PSMA PET/CT for initial staging as part of an Investigational New Drug trial. 11/73 were intermediate-risk (15%), 33/73 were high-risk (45%), 22/73 were very high risk (30%), and 7/73 were N1 (9.5%). Clinical target volumes (CTVs) that included the prostate, seminal vesicles, and pelvic lymph nodes (LNs) using Radiation Therapy Oncology Group (RTOG) consensus guidelines were contoured on the CT portion of the PET/CT by a radiation oncologist blinded to the PET findings. 68 Ga-PSMA-11 PET/CT images were analyzed by a nuclear medicine physician. PSMA-positive lesions not covered by planning volumes based on the CTVs were considered to have a major potential impact on treatment planning. Results: All patients had PSMA-positive primary prostate lesion(s). 25/73 (34%) and 7/73 (9.5%) had PSMA-positive pelvic nodal and distant metastases, respectively. The sites of nodal metastases in decreasing order of frequency were external iliac (20.5%), common iliac (13.5%), internal iliac (12.5%) obturator (12.5%), perirectal (4%), abdominal (4%), upper-diaphragm (4%), and presacral (1.5%). The median size of the nodal lesions was 6 mm (range 4-24 mm). RT planning based on the CTVs covered 69/73 (94.5%) of primary disease and 20/25 (80%) of pelvic nodal disease, on a per-patient analysis. Conclusion: 68 Ga-PSMA-11 PET/CT had a major impact on intended definitive PCa RT planning in 12/73 of patients (16.5%) when RT fields covered the prostate, seminal vesicles and the pelvic LNs, and in 25/66 of patients (37%) when RT fields covered only the prostate and seminal vesicles (without pelvic LNs). Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

SU-E-T-573: Normal Tissue Dose Effect of Prescription Isodose Level Selection in Lung Stereotactic Body Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Q; Lei, Y; Zheng, D

Purpose: To evaluate dose fall-off in normal tissue for lung stereotactic body radiation therapy (SBRT) cases planned with different prescription isodose levels (IDLs), by calculating the dose dropping speed (DDS) in normal tissue on plans computed with both Pencil Beam (PB) and Monte-Carlo (MC) algorithms. Methods: The DDS was calculated on 32 plans for 8 lung SBRT patients. For each patient, 4 dynamic conformal arc plans were individually optimized for prescription isodose levels (IDL) ranging from 60% to 90% of the maximum dose with 10% increments to conformally cover the PTV. Eighty non-overlapping rind structures each of 1mm thickness weremore » created layer by layer from each PTV surface. The average dose in each rind was calculated and fitted with a double exponential function (DEF) of the distance from the PTV surface, which models the steep- and moderate-slope portions of the average dose curve in normal tissue. The parameter characterizing the steep portion of the average dose curve in the DEF quantifies the DDS in the immediate normal tissue receiving high dose. Provided that the prescription dose covers the whole PTV, a greater DDS indicates better normal tissue sparing. The DDS were compared among plans with different prescription IDLs, for plans computed with both PB and MC algorithms. Results: For all patients, the DDS was found to be the lowest for 90% prescription IDL and reached a highest plateau region for 60% or 70% prescription. The trend was the same for both PB and MC plans. Conclusion: Among the range of prescription IDLs accepted by lung SBRT RTOG protocols, prescriptions to 60% and 70% IDLs were found to provide best normal tissue sparing.« less

External Beam Accelerated Partial Breast Irradiation Yields Favorable Outcomes in Patients with Prior Breast Augmentation

PubMed Central

Lei, Rachel Y.; Leonard, Charles E.; Howell, Kathryn T.; Henkenberns, Phyllis L.; Johnson, Timothy K.; Hobart, Tracy L.; Kercher, Jane M.; Widner, Jodi L.; Kaske, Terese; Barke, Lora D.; Carter, Dennis L.

2014-01-01

Purpose: To report outcomes in breast cancer patients with prior breast augmentation treated with external beam accelerated partial breast irradiation (EB-APBI) utilizing intensity-modulated radiotherapy or 3-dimensional conformal radiotherapy, both with IGRT. Materials and Methods: Sixteen stage 0/1 breast cancer patients with previous elective bilateral augmentation were treated post-lumpectomy on institutional EB-APBI trials (01185132 and 01185145 on clinicaltrials.gov). Patients received 38.5 Gy in 10 fractions over five consecutive days. Breast/chest wall pain and cosmesis were rated by patient; cosmesis was additionally evaluated by physician per RTOG criteria. Results: The median follow-up from accelerated partial breast irradiation (APBI) completion was 23.9 months (range, 1.2–58.6). Little to no change in cosmesis or pain from baseline was reported. Cosmetic outcomes at last follow-up were judged by patients as excellent/good in 81.2% (13/16), and by physicians as excellent/good in 93.8% (15/16). Ten patients (62.5%) reported no breast/chest wall pain, five (31.2%) reported mild pain, and one (6.2%) reported moderate pain. All patients remain disease free at last follow-up. The median ipsilateral breast, planning target volume (PTV), and implant volumes were 614, 57, and 333 cm3. The median ratios of PTV/ipsilateral breast volume (implant excluded) and PTV/total volume (implant included) were 9 and 6%. Conclusion: These 16 breast cancer cases with prior bilateral augmentation treated with EB-APBI demonstrate favorable clinical outcomes. Further exploration of EB-APBI as a treatment option for this patient population is warranted. PMID:24995159

Limiting the risk of cardiac toxicity with esophageal-sparing intensity modulated radiotherapy for locally advanced lung cancers.

PubMed

Woodford, Katrina; Panettieri, Vanessa; Ruben, Jeremy D; Senthi, Sashendra

2016-05-01

Intensity modulated radiotherapy (IMRT) is routinely utilized in the treatment of locally advanced non-small cell lung cancer (NSCLC). RTOG 0617 found that overall survival was impacted by increased low (5 Gy) and intermediate (30 Gy) cardiac doses. We evaluated the impact of esophageal-sparing IMRT on cardiac doses with and without the heart considered in the planning process and predicted toxicity compared to 3D-conventional radiotherapy (3DCRT). Ten consecutive patients with N2 Stage III NSCLC treated to 60 Gy in 30 fractions, between February 2012 and September 2014, were evaluated. For each patient, 3DCRT and esophageal-sparing IMRT plans were generated. IMRT plans were then created with and without the heart considered in the optimization process. To compare plans, the dose delivered to 95% and 99% of the target (D95% and D99%), and doses to the esophagus, lung and heart were compared by determining the volume receiving X dose (VXGy) and the normal tissue complication probability (NTCP) calculated. IMRT reduced maximum esophagus dose to below 60 Gy in all patients and produced significant reductions to V50Gy, V40Gy and esophageal NTCP. The cost of this reduction was a non-statistically, non-clinically significant increase in low dose (5 Gy) lung exposure that did not worsen lung NTCP. IMRT plans produced significant cardiac sparing, with the amount of improvement correlating to the amount of heart overlapping with the target. When included in plan optimization, for selected patients further sparing of the heart and improvement in heart NTCP was possible. Esophageal-sparing IMRT can significantly spare the heart even if it is not considered in the optimization process. Further sparing can be achieved if plan optimization constrains low and intermediate heart doses, without compromising lung doses.

Neoadjuvant Interdigitated Chemoradiotherapy Using Mesna, Doxorubicin, and Ifosfamide for Large, High-grade, Soft Tissue Sarcomas of the Extremity: Improved Efficacy and Reduced Toxicity.

PubMed

Chowdhary, Mudit; Sen, Neilayan; Jeans, Elizabeth B; Miller, Luke; Batus, Marta; Gitelis, Steven; Wang, Dian; Abrams, Ross A

2018-05-18

Patients with large, high-grade extremity soft tissue sarcoma (STS) are at high risk for both local and distant recurrence. RTOG 95-14, using a regimen of neoadjuvant interdigitated chemoradiotherapy with mesna, doxorubicin, ifosfamide, and dacarbazine followed by surgery and 3 cycles of adjuvant mesna, doxorubicin, ifosfamide, and dacarbazine, demonstrated high rates of disease control at the cost of significant toxicity (83% grade 4, 5% grade 5). As such, this regimen has not been widely adopted. Herein, we report our institutional outcomes utilizing a modified interdigitated chemoradiotherapy regimen, without dacarbazine, and current radiotherapy planning and delivery techniques for high-risk STS. Adults with large (≥5 cm; median, 12.9 cm), grade 3 extremity STS who were prospectively treated as part of our institutional standard of care from 2008 to 2016 are included. Neoadjuvant chemoradiotherapy consisted of 3 cycles of mesna, doxorubicin, and ifosfamide (MAI) and 44 Gy (22 Gy in 11 fractions between cycles of MAI) after which patients underwent surgical resection and received 3 additional cycles of MAI. Twenty-six patients received the MAI treatment protocol. At a median follow-up of 47.3 months, 23 (88.5%) patients are still alive. Three year locoregional recurrence-free survival, disease-free survival, and overall survival are 95.0%, 64.0%, and 95.0%, respectively. There have been no therapy-related deaths or secondary malignancies. The nonhematologic grade 4 toxicity rate was 7.7%. Neoadjuvant interdigitated MAI radiotherapy followed by resection and 3 cycles of adjuvant MAI has resulted in acceptable and manageable toxicity and highly favorable survival in patients at greatest risk for treatment failure.

A Prostate Fossa Contouring Instructional Module: Implementation and Evaluation.

PubMed

Gunther, Jillian R; Liauw, Stanley L; Choi, Seungtaek; Mohamed, Abdallah S R; Thaker, Nikhil G; Fuller, Clifton D; Stepaniak, Christopher J; Das, Prajnan; Golden, Daniel W

2016-07-01

Radiation oncology trainees frequently learn to contour through clinical experience and lectures. A hands-on contouring module was developed to teach delineation of the postoperative prostate clinical target volume (CTV) and improve contouring accuracy. Medical students independently contoured a prostate fossa CTV before and after receiving educational materials and live instruction detailing the RTOG approach to contouring this CTV. Metrics for volume overlap and surface distance (Dice similarity coefficient, Hausdorff distance (HD), and mean distance) determined discordance between student and consensus contours. An evaluation assessed perception of session efficacy (1 = "not at all" to 5 = "extremely"; reported as median[interquartile range]). Non-parametric statistical tests were used. Twenty-four students at two institutions completed the module, and 21 completed the evaluation (88% response). The content was rated as "quite" important (4[3.5-5]). The module improved comfort contouring a prostate fossa (pre 1[1-2] vs. post 4[3-4], p<.01), ability to find references (pre 2[1-3] vs. post 4[3.5-4], p<0.01), knowledge of CT prostate/pelvis anatomy (pre 2[1.5-3] vs. post 3[3-4], p<.01), and ability to use contouring software tools (pre 2[2-3.5] vs. post 3[3-4], p=.01). After intervention, mean DSC increased (0.29 to 0.68, p<0.01) and HD and mean distance both decreased, respectively (42.8 to 30.0, p<.01; 11.5 to 1.9, p<.01). A hands-on module to teach CTV delineation to medical students was developed and implemented. Student and expert contours exhibited near "excellent agreement" (as defined in the literature) after intervention. Additional modules to teach target delineation to all educational levels can be developed using this model. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Image-Guided Intensity-Modulated Radiotherapy for Pancreatic Carcinoma

PubMed Central

Fuss, Martin; Wong, Adrian; Fuller, Clifton D.; Salter, Bill J.; Fuss, Cristina; Thomas, Charles R.

2007-01-01

Purpose To present the techniques and preliminary outcomes of ultrasound-based image-guided intensity-modulated radiotherapy (IG-IMRT) for pancreatic cancer. Materials and Methods Retrospective analysis of 41 patients treated between November 2000 and March 2005 with IG-IMRT to mean total doses of 55 Gy (range, 45–64 Gy). We analyzed the clinical feasibility of IG-IMRT, dosimetric parameters, and outcomes, including acute gastrointestinal toxicity (RTOG grading). Survival was assessed for adenocarcinoma (n = 35) and other histologies. Results Mean daily image-guidance corrective shifts were 4.8 ± 4.3 mm, 7.5 ± 7.2 mm, and 4.6 ± 5.9 mm along the x-, y-, and z-axes, respectively (mean 3D correction vector, 11.7 ± 8.4 mm). Acute upper gastrointestinal toxicity was grade 0–1 in 22 patients (53.7%), grade 2 in 16 patients (39%), and grade 3 in 3 patients (7.3%). Lower gastrointestinal toxicity was grade 0–1 in 32 patients (78%), grade 2 in 7 patients (17.1%), and grade 4 in 2 patients (4.9%). Treatment was stopped early in 4 patients following administration of 30 to 54 Gy. Median survival for adenocarcinoma histology was 10.3 months (18.6 months in patients alive at analysis; n = 8) with actuarial 1- and 2-year survivals of 38% and 25%, respectively. Conclusion Daily image-guidance during delivery of IMRT for pancreatic carcinoma is clinically feasible. The data presented support the conclusion that safety margin reduction and moderate dose escalation afforded by implementation of these new radiotherapy technologies yields preliminary outcomes at least comparable with published survival data. PMID:19262697

Treatment Planning and Delivery of Whole Brain Irradiation with Hippocampal Avoidance in Rats.

PubMed

Cramer, C K; Yoon, S W; Reinsvold, M; Joo, K M; Norris, H; Hood, R C; Adamson, J D; Klein, R C; Kirsch, D G; Oldham, M

2015-01-01

Despite the clinical benefit of whole brain radiotherapy (WBRT), patients and physicians are concerned by the long-term impact on cognitive functioning. Many studies investigating the molecular and cellular impact of WBRT have used rodent models. However, there has not been a rodent protocol comparable to the recently reported Radiation Therapy Oncology Group (RTOG) protocol for WBRT with hippocampal avoidance (HA) which is intended to spare cognitive function. The aim of this study was to develop a hippocampal-sparing WBRT protocol in Wistar rats. The technical and clinical challenges encountered in hippocampal sparing during rat WBRT are substantial. Three key challenges were identified: hippocampal localization, treatment planning, and treatment localization. Hippocampal localization was achieved with sophisticated imaging techniques requiring deformable registration of a rat MRI atlas with a high resolution MRI followed by fusion via rigid registration to a CBCT. Treatment planning employed a Monte Carlo dose calculation in SmART-Plan and creation of 0.5 cm thick lead blocks custom-shaped to match DRR projections. Treatment localization necessitated the on-board image-guidance capability of the XRAD C225Cx micro-CT/micro-irradiator (Precision X-Ray). Treatment was accomplished with opposed lateral fields with 225 KVp X-rays at a current of 13 mA filtered through 0.3 mm of copper using a 40x40 mm square collimator and the lead blocks. A single fraction of 4 Gy was delivered (2 Gy per lateral field) with a 41 second beam on time per field at a dose rate of 304.5 cGy/min. Dosimetric verification of hippocampal sparing was performed using radiochromic film. In vivo verification of HA was performed after delivery of a single 4 Gy fraction either with or without HA using γ-H2Ax staining of tissue sections from the brain to quantify the amount of DNA damage in rats treated with HA, WBRT, or sham-irradiated (negative controls). The mean dose delivered to radiochromic film beneath the hippocampal block was 0.52 Gy compared to 3.93 Gy without the block, indicating an 87% reduction in the dose delivered to the hippocampus. This difference was consistent with doses predicted by Monte Carlo dose calculation. The Dose Volume Histogram (DVH) generated via Monte Carlo simulation showed an underdose of the target volume (brain minus hippocampus) with 50% of the target volume receiving 100% of the prescription isodose as a result of the lateral blocking techniques sparing some midline thalamic and subcortical tissue. Staining of brain sections with anti-phospho-Histone H2A.X (reflecting double-strand DNA breaks) demonstrated that this treatment protocol limited radiation dose to the hippocampus in vivo. The mean signal intensity from γ-H2Ax staining in the cortex was not significantly different from the signal intensity in the cortex of rats treated with WBRT (5.40 v. 5.75, P = 0.32). In contrast, the signal intensity in the hippocampus of rats treated with HA was significantly lower than rats treated with WBRT (4.55 v. 6.93, P = 0.012). Despite the challenges of planning conformal treatments for small volumes in rodents, our dosimetric and in vivo data show that WBRT with HA is feasible in rats. This study provides a useful platform for further application and refinement of the technique.

Proton therapy may allow for comprehensive elective nodal coverage for patients receiving neoadjuvant radiotherapy for localized pancreatic head cancers.

PubMed

Lee, Richard Y; Nichols, Romaine C; Huh, Soon N; Ho, Meng W; Li, Zuofeng; Zaiden, Robert; Awad, Ziad T; Ahmed, Bestoun; Hoppe, Bradfors S

2013-12-01

Neoadjuvant radiotherapy has the potential to improve local disease control for patients with localized pancreatic cancers. Concern about an increased risk of surgical complications due to small bowel and gastric exposure, however, has limited enthusiasm for this approach. Dosimetric studies have demonstrated the potential for proton therapy to reduce intestinal exposure compared with X-ray-based therapy. We sought to determine if neoadjuvant proton therapy allowed for field expansions to cover high-risk nodal stations in addition to the primary tumor. Twelve consecutive patients with nonmetastatic cancers of the pancreatic head underwent proton-based planning for neoadjuvant radiotherapy. Gross tumor volume was contoured using diagnostic computed tomography (CT) scans with oral and intravenous contrast. Four-dimensional planning scans were utilized to define an internal clinical target volume (ICTV). Five-mm planning target volume (PTV) expansions on the ICTV were generated to establish an initial PTV (PTV1). A second PTV was created using the initial PTV but was expanded to include the high-risk nodal targets as defined by the RTOG contouring atlas (PTV2). Optimized proton plans were generated for both PTVs for each patient. All PTVs received a dose of 50.4 cobalt gray equivalent (CGE). Normal-tissue exposures to the small bowel space, stomach, right kidney, left kidney and liver were recorded. Point spinal cord dose was limited to 45 CGE. Median PTV1 volume was 308.75 cm(3) (range, 133.33-495.61 cm(3)). Median PTV2 volume was 541.75 cm(3) (range, 399.44-691.14 cm(3)). In spite of the substantial enlargement of the PTV when high-risk lymph nodes were included in the treatment volume, normal-tissue exposures (stomach, bowel space, liver, and kidneys) were only minimally increased relative to the exposures seen when only the gross tumor target was treated. Proton therapy appears to allow for field expansions to cover high-risk lymph nodes without significantly increasing critical normal-tissue exposure in the neoadjuvant setting.

SU-F-T-387: A Novel Optimization Technique for Field in Field (FIF) Chestwall Radiation Therapy Using a Single Plan to Improve Delivery Safety and Treatment Planning Efficiency

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tabibian, A; Kim, A; Rose, J

Purpose: A novel optimization technique was developed for field-in-field (FIF) chestwall radiotherapy using bolus every other day. The dosimetry was compared to currently used optimization. Methods: The prior five patients treated at our clinic to the chestwall and supraclavicular nodes with a mono-isocentric four-field arrangement were selected for this study. The prescription was 5040 cGy in 28 fractions, 5 mm bolus every other day on the tangent fields, 6 and/or 10 MV x-rays, and multileaf collimation.Novelly, tangents FIF segments were forward planned optimized based on the composite bolus and non-bolus dose distribution simultaneously. The prescription was spilt into 14 fractionsmore » for both bolus and non-bolus tangents. The same segments and monitor units were used for the bolus and non-bolus treatment. The plan was optimized until the desired coverage was achieved, minimized 105% hotspots, and a maximum dose of less than 108%. Each tangential field had less than 5 segments.Comparison plans were generated using FIF optimization with the same dosimetric goals, but using only the non-bolus calculation for FIF optimization. The non-bolus fields were then copied and bolus was applied. The same segments and monitor units were used for the bolus and non-bolus segments. Results: The prescription coverage of the chestwall, as defined by RTOG guidelines, was on average 51.8% for the plans that optimized bolus and non-bolus treatments simultaneous (SB) and 43.8% for the plans optimized to the non-bolus treatments (NB). Chestwall coverage of 90% prescription averaged to 80.4% for SB and 79.6% for NB plans. The volume receiving 105% of the prescription was 1.9% for SB and 0.8% for NB plans on average. Conclusion: Simultaneously optimizing for bolus and non-bolus treatments noticeably improves prescription coverage of the chestwall while maintaining similar hotspots and 90% prescription coverage in comparison to optimizing only to non-bolus treatments.« less

Randomized Trial of Hyperfractionation Versus Conventional Fractionation in T2 Squamous Cell Carcinoma of the Vocal Cord (RTOG 9512)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trotti, Andy, E-mail: andy.trotti@moffitt.org; Zhang, Qiang; Bentzen, Søren M.

2014-08-01

Purpose: To compare hyperfractionation versus standard fractionation for T2N0 vocal cord carcinoma in a randomized controlled trial. Methods and Materials: Patients with T2 vocal cord cancer were stratified by substage (T2a vs T2b) and randomly assigned to receive either hyperfractionation (HFX) to 79.2 Gy in 66 fractions of 1.2 Gy given twice a day, or standard fractionation (SFX) to 70 Gy in 35 fractions given once a day. The trial was designed to detect a 55% reduction in the local failure hazard rate with 80% statistical power. Results: Between April 1996 and July 2003, a total of 250 patients were enrolled. Of 239more » patients analyzable for outcomes, 94% were male, 83% had a Karnofsky performance status of 90-100, and 62% had T2a tumor. Median follow-up for all surviving patients was 7.9 years (range, 0.6-13.1 years). The 5-year local control (LC) rate was 8 points higher but not statistically significant (P=.14 for HFX [78%] vs SFX [70%]), corresponding to a 30% hazard rate reduction. The 5-year disease-free survival (DFS) was 49% versus 40% (P=.13) and overall survival (OS) was 72% versus 63% (P=.29). HFX was associated with higher rates of acute skin, mucosal, and laryngeal toxicity. Grade 3-4 late effects were similar with a 5-year cumulative incidence of 8.5% (3.4%-13.6%) after SFX and 8.5% (3.4%-13.5%) after HFX. Conclusions: The 5-year local control was modestly higher with HFX compared to SFX for T2 glottic carcinoma, but the difference was not statistically significant. These results are consistent with prior studies of hyperfractionation showing a benefit in local control. Substaging by T2a versus T2b carries prognostic value for DFS and OS. For cost and convenience reasons other altered fractionation schedules have been adopted in routine practice.« less

SU-F-T-600: Influence of Acuros XB and AAA Dose Calculation Algorithms On Plan Quality Metrics and Normal Lung Doses in Lung SBRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yaparpalvi, R; Mynampati, D; Kuo, H

Purpose: To study the influence of superposition-beam model (AAA) and determinant-photon transport-solver (Acuros XB) dose calculation algorithms on the treatment plan quality metrics and on normal lung dose in Lung SBRT. Methods: Treatment plans of 10 Lung SBRT patients were randomly selected. Patients were prescribed to a total dose of 50-54Gy in 3–5 fractions (10?5 or 18?3). Doses were optimized accomplished with 6-MV using 2-arcs (VMAT). Doses were calculated using AAA algorithm with heterogeneity correction. For each plan, plan quality metrics in the categories- coverage, homogeneity, conformity and gradient were quantified. Repeat dosimetry for these AAA treatment plans was performedmore » using AXB algorithm with heterogeneity correction for same beam and MU parameters. Plan quality metrics were again evaluated and compared with AAA plan metrics. For normal lung dose, V{sub 20} and V{sub 5} to (Total lung- GTV) were evaluated. Results: The results are summarized in Supplemental Table 1. PTV volume was mean 11.4 (±3.3) cm{sup 3}. Comparing RTOG 0813 protocol criteria for conformality, AXB plans yielded on average, similar PITV ratio (individual PITV ratio differences varied from −9 to +15%), reduced target coverage (−1.6%) and increased R50% (+2.6%). Comparing normal lung doses, the lung V{sub 20} (+3.1%) and V{sub 5} (+1.5%) were slightly higher for AXB plans compared to AAA plans. High-dose spillage ((V105%PD - PTV)/ PTV) was slightly lower for AXB plans but the % low dose spillage (D2cm) was similar between the two calculation algorithms. Conclusion: AAA algorithm overestimates lung target dose. Routinely adapting to AXB for dose calculations in Lung SBRT planning may improve dose calculation accuracy, as AXB based calculations have been shown to be closer to Monte Carlo based dose predictions in accuracy and with relatively faster computational time. For clinical practice, revisiting dose-fractionation in Lung SBRT to correct for dose overestimates attributable to algorithm may very well be warranted.« less

Accelerated partial breast irradiation using robotic radiotherapy: a dosimetric comparison with tomotherapy and three-dimensional conformal radiotherapy.

PubMed

Rault, Erwann; Lacornerie, Thomas; Dang, Hong-Phuong; Crop, Frederik; Lartigau, Eric; Reynaert, Nick; Pasquier, David

2016-02-27

Accelerated partial breast irradiation (APBI) is a new breast treatment modality aiming to reduce treatment time using hypo fractionation. Compared to conventional whole breast irradiation that takes 5 to 6 weeks, APBI is reported to induce worse cosmetic outcomes both when using three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT). These late normal tissue effects may be attributed to the dose volume effect because a large portion of the non-target breast tissue volume (NTBTV) receives a high dose. In the context of APBI, non-coplanar beams could spare the NTBTV more efficiently. This study evaluates the dosimetric benefit of using the Cyberknife (CK) for APBI in comparison to IMRT (Tomotherapy) and three dimensional conformal radiotherapy (3D-CRT). The possibility of using surgical clips, implanted during surgery, to track target movements is investigated first. A phantom of a female thorax was designed in-house using the measurements of 20 patients. Surgical clips of different sizes were inserted inside the breast. A treatment plan was delivered to the mobile and immobile phantom. The motion compensation accuracy was evaluated using three radiochromic films inserted inside the breast. Three dimensional conformal radiotherapy (3D-CRT), Tomotherapy (TOMO) and CK treatment plans were calculated for 10 consecutive patients who received APBI in Lille. To ensure a fair comparison of the three techniques, margins applied to the CTV were set to 10 mm. However, a second CK plan was prepared using 3 mm margins to evaluate the benefits of motion compensation. Only the larger clips (VITALITEC Medium-Large) could be tracked inside the larger breast (all gamma indices below 1 for 1 % of the maximum dose and 1 mm). All techniques meet the guidelines defined in the NSABP/RTOG and SHARE protocols. As the applied dose volume constraints are very strong, insignificant dosimetric differences exist between techniques regarding the PTV coverage and the sparing of the lung and heart. However, the CK may be used to reduce high doses received by the NTBTV more efficiently. Robotic stereotactic radiotherapy may be used for APBI to more efficiently spare the NTBTV and improve cosmetic results of APBI.

A Randomized Phase 2 Study Comparing 2 Stereotactic Body Radiation Therapy Schedules for Medically Inoperable Patients With Stage I Peripheral Non-Small Cell Lung Cancer: NRG Oncology RTOG 0915 (NCCTG N0927)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Videtic, Gregory M.M., E-mail: videtig@ccf.org; Hu, Chen; Johns Hopkins University School of Medicine, Baltimore, Maryland

Purpose: To compare 2 stereotactic body radiation therapy (SBRT) schedules for medically inoperable early-stage lung cancer to determine which produces the lowest rate of grade ≥3 protocol-specified adverse events (psAEs) at 1 year. Methods and Materials: Patients with biopsy-proven peripheral (≥2 cm from the central bronchial tree) T1 or T2, N0 (clinically node negative by positron emission tomography), M0 tumors were eligible. Patients were randomized to receive either 34 Gy in 1 fraction (arm 1) or 48 Gy in 4 consecutive daily fractions (arm 2). Rigorous central accreditation and quality assurance confirmed treatment per protocol guidelines. This study was designed to detect a psAEsmore » rate >17% at a 10% significance level (1-sided) and 90% power. Secondary endpoints included rates of primary tumor control (PC), overall survival (OS), and disease-free survival (DFS) at 1 year. Designating the better of the 2 regimens was based on prespecified rules of psAEs and PC for each arm. Results: Ninety-four patients were accrued between September 2009 and March 2011. The median follow-up time was 30.2 months. Of 84 analyzable patients, 39 were in arm 1 and 45 in arm 2. Patient and tumor characteristics were balanced between arms. Four (10.3%) patients on arm 1 (95% confidence interval [CI] 2.9%-24.2%) and 6 (13.3%) patients on arm 2 (95% CI 5.1%-26.8%) experienced psAEs. The 2-year OS rate was 61.3% (95% CI 44.2%-74.6%) for arm 1 patients and 77.7% (95% CI 62.5%-87.3%) for arm 2. The 2-year DFS was 56.4% (95% CI 39.6%-70.2%) for arm 1 and 71.1% (95% CI 55.5%-82.1%) for arm 2. The 1-year PC rate was 97.0% (95% CI 84.2%-99.9%) for arm 1 and 92.7% (95% CI 80.1%-98.5%) for arm 2. Conclusions: 34 Gy in 1 fraction met the prespecified criteria and, of the 2 schedules, warrants further clinical research.« less

Patient reported outcomes in NRG Oncology RTOG 0938, evaluating two ultrahypofractionated regimens for prostate cancer.

PubMed

Lukka, Himanshu R; Pugh, Stephanie L; Bruner, Deborah W; Bahary, Jean-Paul; Lawton, Colleen A F; Efstathiou, Jason A; Kudchadker, Rajat J; Ponsky, Lee E; Seaward, Samantha A; Dayes, Ian S; Gopaul, Darindra D; Michalski, Jeff M; Delouya, Guila; Kaplan, Irving D; Horwitz, Eric M; Roach, Mack; Pinover, Wayne H; Beyer, David C; Amanie, John O; Sandler, Howard M; Kachnic, Lisa A

2018-06-15

There is considerable interest in very short (ultrahypofractionated) radiotherapy regimens to treat prostate cancer based on potential radiobiological advantages, patient convenience and resource allocation benefits. To demonstrate that detectable changes in health related quality of life measured by the bowel and urinary domains of the Expanded Prostate Cancer Index Composite (EPIC-50) were not substantially worse than baseline. XXXX is a non-blinded randomized phase II study of NCCN low risk prostate cancer where each arm is compared to a historical control. Patients were randomized to five fractions (7.25Gy in two weeks), or twelve fractions (4.3Gy in 2.5 weeks). The co-primary endpoints were the proportion of patients with a change in EPIC bowel score at one year (baseline to one-year) >five points and in EPIC urinary score >two points tested with a one-sample binomial test. and Limitations: 127 patients were enrolled to five fractions (121 analyzed) and 128 to twelve fractions (125 analyzed). Median follow-up for all patients at the time of analysis was 3.8 years. The one year frequency for >five point change in bowel score for five and twelve fractions were 29.8%(p<0.001) and 28.4%(p<0.001) respectively. The one year frequency for >two point change in urinary score for five and twelve fractions were 45.7%(p<0.001) and 42.2%(p<0.001) respectively. For five and twelve fractions 32.9% of patients had a drop in 1 year EPIC sexual score ≥ 11 points (p=0.34) while 30.9% of patients had a drop in 1 year EPIC sexual score ≥11 points (p=0.20) in the twelve fraction arm respectively. DFS at two years is 93.3% (95% CI: 88.8, 97.8) and 88.3% (95% CI: 82.5, 94.0) in the five and twelve fraction arms, respectively. There was no late grade 4 or 5 treatment-related urinary or bowel toxicity. This study confirms that based on changes in bowel and urinary domains and toxicity (acute and late) the five and twelve fractions regimens are well tolerated. These ultrahypofractionated approaches need to be compared to current standard radiotherapy regimens. Copyright © 2018. Published by Elsevier Inc.

Is the Deep Inspiration Breath-Hold Technique Superior to the Free Breathing Technique in Cardiac and Lung Sparing while Treating both Left-Sided Post-Mastectomy Chest Wall and Supraclavicular Regions?

PubMed

Darapu, Anupama; Balakrishnan, Rajesh; Sebastian, Patricia; Hussain, Mohamathu Rafic Kather; Ravindran, Paul; John, Subhashini

2017-01-01

To evaluate the efficacy of the deep inspirational breath-hold (DIBH) technique and its dosimetric advantages over the free breathing (FB) technique in cardiac (heart and left anterior descending artery [LAD]) and ipsilateral lung sparing in left-sided post-mastectomy field-in-field conformal radiotherapy. DIBH is highly reproducible, and this study aims to find out its dosimetric benefits over FB. Nineteen left-sided mastectomy patients were immobilized using breast boards with both arms positioned above the head. All patients had 2 sets of planning CT images (one in FB and another in DIBH) with a Biograph TruePoint HD CT scanner in the same setup. DIBH was performed by tracking the respiratory cycles using a Varian Real-Time Position Management system. The target (chest wall and supraclavicular region), organs at risk (OARs; ipsilateral lung, contralateral lung, heart, LAD, and contralateral breast), and other organs of interests were delineated as per the RTOG (Radiation Therapy Oncology Group) contouring guidelines. The single-isocenter conformal fields in the field treatment plans were generated with the Eclipse Treatment Planning System (Varian Medical Systems) for both FB and DIBH images, and the doses to the target and OARs were compared. The standard fractionation regimen of 50 Gy in 25 fractions over a period of 5 weeks was used for all patients in this study. The target coverage parameters (V95, V105, V107, and D_mean) were found to be 97.8 ± 0.9, 6.1 ± 3.4, 0.2 ± 0.3, and 101.9 ± 0.5% in the FB plans and 98.1 ± 0.8, 6.1 ± 3.2, 0.2 ± 0.3, and 101.9 ± 0.4% in the DIBH plans, respectively. The plan quality indices (conformity index and homogeneity index) also showed 1.3 ± 0.2 and 0.1 for the FB plans and 1.2 ± 0.3 and 0.1 for the DIBH plans, respectively. There was a significant reduction in dose to the heart in the DIBH plans compared to the FB plans, with p values of nearly 0 for the V5, V10, V25, V30, and D_mean dosimetric parameters. The difference in ipsilateral lung doses between FB and DIBH showed statistically significant p values, and the differences in mean doses were found to be 7, 15.7, 11.8, and 10.7% for V5, V20, V30, and D_mean, respectively. There was a significant reduction in dose to the LAD in the DIBH compared to the FB plans. DIBH resulted in significant reductions in doses to the heart, LAD, and lungs, since with this technique there was an increase in the distance between the target and the OARs. With appropriate patient selection and adequate training, the DIBH technique is acceptable and achievable for radiotherapy to the chest, and therefore should be considered for all suitable patients, as this could result in fewer radiotherapy-related complications. However, this technique is time-consuming, since the setup is complex, results in an increased time for treatment delivery, and needs patient cooperation and technical expertise.

(11)C-Choline PET/CT as a guide to radiation treatment planning of lymph-node relapses in prostate cancer patients.

PubMed

Picchio, M; Berardi, G; Fodor, A; Busnardo, E; Crivellaro, C; Giovacchini, G; Fiorino, C; Kirienko, M; Incerti, E; Messa, C; Gianolli, L; Di Muzio, N

2014-07-01

To evaluate, in prostate cancer (PCa) patients the potential of (11)C-choline PET/CT as a guide to helical tomotherapy (HTT) of lymph-node (LN) relapses with simultaneous integrated boost (SIB). The efficacy and feasibility of HTT in terms of acute toxicity were assessed. We enrolled 83 PCa patients (mean age 68 years, range 51 - 82 years) with biochemical recurrence after radical primary treatment (mean serum PSA 7.61 ng/ml, range 0.37 - 187.00 ng/ml; PSA0) who showed pathological findings on (11)C-choline PET/CT only at the LN site. (11)C-Choline PET/CT was performed for restaging and then for radiation treatment planning (PET/CT0). Of the 83 patients, 8 experienced further LN relapse, of whom 5 were retreated once and 3 were retreated twice (total 94 radiotherapy treatments). All pelvic and/or abdominal LNs positive on PET/CT0 were treated with high doses using SIB. Doses were in the range 36 - 74 Gy administered in 28 fractions. After the end of HTT (mean 83 days, range 16 - 365 days), serum PSA was measured in all patients (PSA1) and compared with PSA0 to evaluate early biochemical response. In 47 patients PET/CT was repeated (PET/CT1) to assess metabolic responses at the treated areas. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) were used to assess acute toxicity. PET/CT0 revealed pathological LNs in the pelvis in 49 patients, pathological LNs in the abdomen in 15 patients pathological LNs in both the pelvis and abdomen in 18 patients, and pathological LNs in the pelvis or abdomen and other sites in 12 patients. All these sites were treated with HTT. With respect to PSA0, PSA1 (mean 6.28 ng/ml, range 0.00 - 220.46 ng/ml) showed a complete biochemical response after 66 of the 94 HTT treatments, a partial response after 12 treatments, stable disease after 1 treatment and progression of disease after 15 treatments. Of the 47 patients receiving PET/CT1, 20 showed a complete metabolic response at the treated area, 22 a partial metabolic response, 3 progression of disease and 2 stable disease. HTT with SIB was well tolerated in all patients. Grade 3 acute toxicity in the genitourinary tract was observed in two patients. (11)C-Choline PET/CT is a valuable tool for planning and monitoring HTT in LN relapse after primary treatment. High-dose hypofractionated (11)C-choline PET/CT-guided HTT with SIB is well tolerated and is associated with a high early biochemical response rate.

Implementation of three dimensional conformal radiation therapy: prospects, opportunities, and challenges.

PubMed

Vijayakumar, S; Chen, G T

1995-12-01

To briefly review scientific rationale of 3D conformal radiation therapy (3DCRT) and discuss the prospects, opportunities, and challenges in the implementation of 3DCRT. Some of these ideas were discussed during a workshop on "Implementation of Three-Dimensional Conformal Radiation Therapy" in April 1994 at Bethesda, MD, and others have been discussed elsewhere in the literature. Local-regional control of cancer is an important component in the overall treatment strategy in any patient with cancer. It has been shown that failure to achieve local-regional control can lead to (a) an increase in chances of distant metastases, and (b) a decrease in the survival. In many disease sites, the doses delivered currently are inadequate to achieve satisfactory local tumor control rates; this is because in many sites, only limited doses of radiotherapy can be delivered due to the proximity of cancer to radiosensitive normal tissues. By conforming the radiotherapy beams to the tumor, doses to the tumors can be enhanced and doses to the normal tissues can be reduced. With the advances in 3DCRT, such conformation is possible now and is the rationale for using 3DCRT. However, a number of questions do remain that are not limited to the following: (a) What are the implications in terms of target volume definitions when implementing 3DCRT? (b) Are there some sites where research efforts can be focused to document the efficacy and cost effectiveness of 3DCRT? (c) How do we implement day-to-day 3DCRT treatment efficiently? (d) How do we transfer the technology from the university centers to the community without compromising quality? (e) What are all the quality assurance/quality improvement questions that need to be addressed and how do we ascertain quality assurance of 3DCRT? (f) Have we looked at cost-benefit ratios and quality of life (QOL) issues closely? There is a need for defining multiple target volumes: gross tumor volume, clinical target volume(s), and planning target volume(s). Such definitions should make implementation of 3DCRT more complex, yet will make high-dose delivery a possibility. There are many sites in which single and multiinstitutional studies are ongoing that include prostate, lung, head and neck, and brain. In other areas, cooperative group trials are required because of the inability of single institutions to accrue enough patients to answer clinically relevant questions with statistical validity. Although implementation of 3DCRT will require multiple steps, these multiple steps can be brought into clinical practice gradually and one does not have to wait until all steps required for implementation of 3DCRT are available. In this respect, "3DCRT" should be used in a very broad sense, from beam's eye view blocking, use of multibeam dose distribution, use of dose-volume histograms in choosing alternative plans, noncoplanar beam arrangements, intensity modulation, inverse planning, to totally automated implementation of 3DCRT. To transfer the 3DCRT capabilities to the community from the University Centers, there is a necessity to develop quality assurance programs. RTOG and the Three-Dimensional Oncology Group are spearheading these efforts. Three-dimensional conformal radiation therapy has potential not only to improve local control and decrease toxicity, but also to improve the cost benefit ratio in the use of radiotherapy as well as in improving quality of life in patients with cancer. Achieving many potential benefits of 3DCRT (improvement in local control, decreasing toxicity, organs-function preservation, improvement in cost effectiveness) will require further physics-related and clinical research in carefully conceived and successfully completed future clinical trials.

Phase III Trial of Chemoradiotherapy for Anaplastic Oligodendroglioma: Long-Term Results of RTOG 9402

PubMed Central

Cairncross, Gregory; Wang, Meihua; Shaw, Edward; Jenkins, Robert; Brachman, David; Buckner, Jan; Fink, Karen; Souhami, Luis; Laperriere, Normand; Curran, Walter; Mehta, Minesh

2013-01-01

Purpose Anaplastic oligodendrogliomas, pure (AO) and mixed (anaplastic oligoastrocytoma [AOA]), are chemosensitive, especially if codeleted for 1p/19q, but whether patients live longer after chemoradiotherapy is unknown. Patients and Methods Eligible patients with AO/AOA were randomly assigned to procarbazine, lomustine, and vincristine (PCV) plus radiotherapy (RT) versus RT alone. The primary end point was overall survival (OS). Results Two hundred ninety-one eligible patients were randomly assigned: 148 to PCV plus RT and 143 to RT. For the entire cohort, there was no difference in median survival by treatment (4.6 years for PCV plus RT v 4.7 years for RT; hazard ratio [HR] = 0.79; 95% CI, 0.60 to 1.04; P = .1). Patients with codeleted tumors lived longer than those with noncodeleted tumors (PCV plus RT: 14.7 v 2.6 years, HR = 0.36, 95% CI, 0.23 to 0.57, P < .001; RT: 7.3 v 2.7 years, HR = 0.40, 95% CI, 0.27 to 0.60, P < .001), and the median survival of those with codeleted tumors treated with PCV plus RT was twice that of patients receiving RT (14.7 v 7.3 years; HR = 0.59; 95% CI, 0.37 to 0.95; P = .03). For those with noncodeleted tumors, there was no difference in median survival by treatment arm (2.6 v 2.7 years; HR = 0.85; 95% CI, 0.58 to 1.23; P = .39). In Cox models that included codeletion status, the adjusted OS for all patients was prolonged by PCV plus RT (HR = 0.67; 95% CI, 0.50 to 0.91; P = .01). Conclusion For the subset of patients with 1p/19q codeleted AO/AOA, PCV plus RT may be an especially effective treatment, although this observation was derived from an unplanned analysis. PMID:23071247

SU-F-T-231: Improving the Efficiency of a Radiotherapy Peer-Review System for Quality Assurance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsu, S; Basavatia, A; Garg, M

Purpose: To improve the efficiency of a radiotherapy peer-review system using a commercially available software application for plan quality evaluation and documentation. Methods: A commercial application, FullAccess (Radialogica LLC, Version 1.4.4), was implemented in a Citrix platform for peer-review process and patient documentation. This application can display images, isodose lines, and dose-volume histograms and create plan reports for peer-review process. Dose metrics in the report can also be benchmarked for plan quality evaluation. Site-specific templates were generated based on departmental treatment planning policies and procedures for each disease site, which generally follow RTOG protocols as well as published prospective clinicalmore » trial data, including both conventional fractionation and hypo-fractionation schema. Once a plan is ready for review, the planner exports the plan to FullAccess, applies the site-specific template, and presents the report for plan review. The plan is still reviewed in the treatment planning system, as that is the legal record. Upon physician’s approval of a plan, the plan is packaged for peer review with the plan report and dose metrics are saved to the database. Results: The reports show dose metrics of PTVs and critical organs for the plans and also indicate whether or not the metrics are within tolerance. Graphical results with green, yellow, and red lights are displayed of whether planning objectives have been met. In addition, benchmarking statistics are collected to see where the current plan falls compared to all historical plans on each metric. All physicians in peer review can easily verify constraints by these reports. Conclusion: We have demonstrated the improvement in a radiotherapy peer-review system, which allows physicians to easily verify planning constraints for different disease sites and fractionation schema, allows for standardization in the clinic to ensure that departmental policies are maintained, and builds a comprehensive database for potential clinical outcome evaluation.« less

Real-time inverse planning for Gamma Knife radiosurgery.

PubMed

Wu, Q Jackie; Chankong, Vira; Jitprapaikulsarn, Suradet; Wessels, Barry W; Einstein, Douglas B; Mathayomchan, Boonyanit; Kinsella, Timothy J

2003-11-01

The challenges of real-time Gamma Knife inverse planning are the large number of variables involved and the unknown search space a priori. With limited collimator sizes, shots have to be heavily overlapped to form a smooth prescription isodose line that conforms to the irregular target shape. Such overlaps greatly influence the total number of shots per plan, making pre-determination of the total number of shots impractical. However, this total number of shots usually defines the search space, a pre-requisite for most of the optimization methods. Since each shot only covers part of the target, a collection of shots in different locations and various collimator sizes selected makes up the global dose distribution that conforms to the target. Hence, planning or placing these shots is a combinatorial optimization process that is computationally expensive by nature. We have previously developed a theory of shot placement and optimization based on skeletonization. The real-time inverse planning process, reported in this paper, is an expansion and the clinical implementation of this theory. The complete planning process consists of two steps. The first step is to determine an optimal number of shots including locations and sizes and to assign initial collimator size to each of the shots. The second step is to fine-tune the weights using a linear-programming technique. The objective function is to minimize the total dose to the target boundary (i.e., maximize the dose conformity). Results of an ellipsoid test target and ten clinical cases are presented. The clinical cases are also compared with physician's manual plans. The target coverage is more than 99% for manual plans and 97% for all the inverse plans. The RTOG PITV conformity indices for the manual plans are between 1.16 and 3.46, compared to 1.36 to 2.4 for the inverse plans. All the inverse plans are generated in less than 2 min, making real-time inverse planning a reality.

Improving IMRT delivery efficiency using intensity limits during inverse planning.

PubMed

Coselmon, Martha M; Moran, Jean M; Radawski, Jeffrey D; Fraass, Benedick A

2005-05-01

Inverse planned intensity modulated radiotherapy (IMRT) fields can be highly modulated due to the large number of degrees of freedom involved in the inverse planning process. Additional modulation typically results in a more optimal plan, although the clinical rewards may be small or offset by additional delivery complexity and/or increased dose from transmission and leakage. Increasing modulation decreases delivery efficiency, and may lead to plans that are more sensitive to geometrical uncertainties. The purpose of this work is to assess the use of maximum intensity limits in inverse IMRT planning as a simple way to increase delivery efficiency without significantly affecting plan quality. Nine clinical cases (three each for brain, prostate, and head/neck) were used to evaluate advantages and disadvantages of limiting maximum intensity to increase delivery efficiency. IMRT plans were generated using in-house protocol-based constraints and objectives for the brain and head/neck, and RTOG 9406 dose volume objectives in the prostate. Each case was optimized at a series of maximum intensity ratios (the product of the maximum intensity and the number of beams divided by the prescribed dose to the target volume), and evaluated in terms of clinical metrics, dose-volume histograms, monitor units (MU) required per fraction (SMLC and DMLC delivery), and intensity map variation (a measure of the beam modulation). In each site tested, it was possible to reduce total monitor units by constraining the maximum allowed intensity without compromising the clinical acceptability of the plan. Monitor unit reductions up to 38% were observed for SMLC delivery, while reductions up to 29% were achieved for DMLC delivery. In general, complicated geometries saw a smaller reduction in monitor units for both delivery types, although DMLC delivery required significantly more monitor units in all cases. Constraining the maximum intensity in an inverse IMRT plan is a simple way to improve delivery efficiency without compromising plan objectives.

MO-F-CAMPUS-T-05: Correct Or Not to Correct for Rotational Patient Set-Up Errors in Stereotactic Radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Briscoe, M; Ploquin, N; Voroney, JP

2015-06-15

Purpose: To quantify the effect of patient rotation in stereotactic radiation therapy and establish a threshold where rotational patient set-up errors have a significant impact on target coverage. Methods: To simulate rotational patient set-up errors, a Matlab code was created to rotate the patient dose distribution around the treatment isocentre, located centrally in the lesion, while keeping the structure contours in the original locations on the CT and MRI. Rotations of 1°, 3°, and 5° for each of the pitch, roll, and yaw, as well as simultaneous rotations of 1°, 3°, and 5° around all three axes were applied tomore » two types of brain lesions: brain metastasis and acoustic neuroma. In order to analyze multiple tumour shapes, these plans included small spherical (metastasis), elliptical (acoustic neuroma), and large irregular (metastasis) tumour structures. Dose-volume histograms and planning target volumes were compared between the planned patient positions and those with simulated rotational set-up errors. The RTOG conformity index for patient rotation was also investigated. Results: Examining the tumour volumes that received 80% of the prescription dose in the planned and rotated patient positions showed decreases in prescription dose coverage of up to 2.3%. Conformity indices for treatments with simulated rotational errors showed decreases of up to 3% compared to the original plan. For irregular lesions, degradation of 1% of the target coverage can be seen for rotations as low as 3°. Conclusions: This data shows that for elliptical or spherical targets, rotational patient set-up errors less than 3° around any or all axes do not have a significant impact on the dose delivered to the target volume or the conformity index of the plan. However the same rotational errors would have an impact on plans for irregular tumours.« less

SU-F-T-618: Evaluation of a Mono-Isocentric Treatment Planning Software for Stereotactic Radiosurgery of Multiple Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sham, E; Sattarivand, M; Mulroy, L

Purpose: To evaluate planning performance of an automated treatment planning software (BrainLAB; Elements) for stereotactic radiosurgery (SRS) of multiple brain metastases. Methods: Brainlab’s Multiple Metastases Elements (MME) uses single isocentric technique to treat up to 10 cranial planning target volumes (PTVs). The planning algorithm of the MME accounts for multiple PTVs overlapping with one another on the beam eyes view (BEV) and automatically selects a subset of all overlapping PTVs on each arc for sparing normal tissues in the brain. The algorithm also optimizes collimator angles, margins between multi-leaf collimators (MLCs) and PTVs, as well as monitor units (MUs) usingmore » minimization of conformity index (CI) for all targets. Planning performance was evaluated by comparing the MME-calculated treatment plan parameters with the same parameters calculated with the Volumetric Modulated Arc Therapy (VMAT) optimization on Varian’s Eclipse platform. Results: Figures 1 to 3 compare several treatment plan outcomes calculated between the MME and VMAT for 5 clinical multi-targets SRS patient plans. Prescribed target dose was volume-dependent and defined based on the RTOG recommendation. For a total number of 18 PTV’s, mean values for the CI, PITV, and GI were comparable between the MME and VMAT within one standard deviation (σ). However, MME-calculated MDPD was larger than the same VMAT-calculated parameter. While both techniques delivered similar maximum point doses to the critical cranial structures and total MU’s for the 5 patient plans, the MME required less treatment planning time by an order of magnitude compared to VMAT. Conclusion: The MME and VMAT produce similar plan qualities in terms of MUs, target dose conformation, and OAR dose sparing. While the selective use of PTVs for arc-optimization with the MME reduces significantly the total planning time in comparison to VMAT, the target dose homogeneity was also compromised due to its simplified inverse planning algorithm used.« less

Early-stage Node-negative (T1-T2N0) Anal Cancer Treated with Simultaneous Integrated Boost Radiotherapy and Concurrent Chemotherapy.

PubMed

Franco, Pierfrancesco; Arcadipane, Francesca; Ragona, Riccardo; Mistrangelo, Massimiliano; Cassoni, Paola; Rondi, Nadia; Morino, Mario; Racca, Patrizia; Ricardi, Umberto

2016-04-01

To report clinical outcomes of a consecutive series of patients with early-stage (T1-T1N0) anal cancer treated with intensity-modulated radiotherapy (IMRT) and a simultaneous integrated boost (SIB) approach similarly to the RTOG 05-29 trial. A cohort of 43 patients underwent SIB-IMRT employing a schedule consisting of 50.4 Gy/28 fractions to the gross tumor volume and 42 Gy/28 fractions to the elective nodal volumes for cT1N0 cases, and 54 Gy/30 fractions and 45 Gy/30 fractions to the same volumes for cT2N0 cases. Chemotherapy was administered concurrently following Nigro's regimen. The primary endpoint was colostomy-free survival (CFS). Secondary endpoints were locoregional control (LRC), disease-free (DFS), cancer-specific (CSS) and overall (OS) survival. Median follow-up was 39.7 months. The actuarial 3-year CFS was 79.4% [95% confidence interval (CI)=61.4-89.7%]. Actuarial 3-year OS and CSS were 90.8% (95% CI=74.1-96.9%) and 93.8% (95% CI=77.3-98.4%), while DFS was 75.5% (95% CI=56.4-87.1%). Actuarial 3-year LRC was 86.1% (95% CI=69.6-94%). On multivariate analysis, tumor size >3 cm showed a trend towards significance in predicting CFS [hazard ratio (HR)=8.6, 95% CI=84.7-88.1%; p=0.069]. Maximum detected adverse events included: skin (G3): 18%; gastrointestinal tract (G2): 67%; genitourinary tract (G3): 3%; genitalia (G2): 30%; anemia (G2): 7%; leukopenia (G3): 26%, leukopenia (G4):7%; neutropenia (G3): 15%; neutropenia (G4): 12%; thrombocytopenia (G3): 9%. Our clinical results support the use of SIB-IMRT in the combined modality treatment of patients with anal cancer. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

SU-F-T-201: Acceleration of Dose Optimization Process Using Dual-Loop Optimization Technique for Spot Scanning Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hirayama, S; Fujimoto, R

Purpose: The purpose was to demonstrate a developed acceleration technique of dose optimization and to investigate its applicability to the optimization process in a treatment planning system (TPS) for proton therapy. Methods: In the developed technique, the dose matrix is divided into two parts, main and halo, based on beam sizes. The boundary of the two parts is varied depending on the beam energy and water equivalent depth by utilizing the beam size as a singular threshold parameter. The optimization is executed with two levels of iterations. In the inner loop, doses from the main part are updated, whereas dosesmore » from the halo part remain constant. In the outer loop, the doses from the halo part are recalculated. We implemented this technique to the optimization process in the TPS and investigated the dependence on the target volume of the speedup effect and applicability to the worst-case optimization (WCO) in benchmarks. Results: We created irradiation plans for various cubic targets and measured the optimization time varying the target volume. The speedup effect was improved as the target volume increased, and the calculation speed increased by a factor of six for a 1000 cm3 target. An IMPT plan for the RTOG benchmark phantom was created in consideration of ±3.5% range uncertainties using the WCO. Beams were irradiated at 0, 45, and 315 degrees. The target’s prescribed dose and OAR’s Dmax were set to 3 Gy and 1.5 Gy, respectively. Using the developed technique, the calculation speed increased by a factor of 1.5. Meanwhile, no significant difference in the calculated DVHs was found before and after incorporating the technique into the WCO. Conclusion: The developed technique could be adapted to the TPS’s optimization. The technique was effective particularly for large target cases.« less

Linear accelerator-based stereotactic radiosurgery for brainstem metastases: the Dana-Farber/Brigham and Women's Cancer Center experience.

PubMed

Kelly, Paul J; Lin, Yijie Brittany; Yu, Alvin Y C; Ropper, Alexander E; Nguyen, Paul L; Marcus, Karen J; Hacker, Fred L; Weiss, Stephanie E

2011-09-01

To review the safety and efficacy of linear accelerator-based stereotactic radiosurgery (SRS) for brainstem metastases. We reviewed all patients with brain metastases treated with SRS at DF/BWCC from 2001 to 2009 to identify patients who had SRS to a single brainstem metastasis. Overall survival and freedom-from-local failure rates were calculated from the date of SRS using the Kaplan-Meier method. Prognostic factors were evaluated using the log-rank test and Cox proportional hazards model. A total of 24 consecutive patients with brainstem metastases had SRS. At the time of SRS, 21/24 had metastatic lesions elsewhere within the brain. 23/24 had undergone prior WBRT. Primary diagnoses included eight NSCLC, eight breast cancer, three melanoma, three renal cell carcinoma and two others. Median dose was 13 Gy (range, 8-16). One patient had fractionated SRS 5 Gy ×5. Median target volume was 0.2 cc (range, 0.02-2.39). The median age was 57 years (range, 42-92). Follow-up information was available in 22/24 cases. At the time of analysis, 18/22 patients (82%) had died. The median overall survival time was 5.3 months (range, 0.8-21.1 months). The only prognostic factor that trended toward statistical significance for overall survival was the absence of synchronous brain metastasis at the time of SRS; 1-year overall survival was 31% with versus 67% without synchronous brain metastasis (log rank P = 0.11). Non-significant factors included primary tumor histology and status of extracranial disease (progressing vs. stable/absent). Local failure occurred in 4/22 cases (18%). Actuarial freedom from local failure for all cases was 78.6% at 1 year. RTOG grade 3 toxicities were recorded in two patients (ataxia, confusion). Linac-based SRS for small volume brainstem metastases using a median dose of 13 Gy is associated with acceptable local control and low morbidity.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guy, C; Weiss, E; Jan, N

Purpose: Large geometric changes which occur during thoracic radiotherapy alter normal anatomy and target position and may induce clinically important dose changes. This study investigates variation of organ-at-risk (OAR) dose caused by atelectasis resolution during radiotherapy. Methods: 3D IMRT treatment plans were obtained for 14 non-small-cell lung cancer patients. Dose of the clinical plan was recalculated on a baseline scan in which lung was collapsed and on a midtreatment scan in which lung re-aeration had occurred. The changes in OAR doses were compared between the two time points. RTOG-0617 and inhouse dose-volume constraints were chosen for investigation and included spinalmore » cord, esophagus, heart, and healthy lung. Results: 17 dose metrics were evaluated. The mean (SD) of change in mean lung dose, from baseline to mid-treatment (average taken across all patients), was 0.2 Gy (2.2 Gy) and ranged from −3.2 Gy to 6.0 Gy. 50% of patients experienced relative changes in mean lung dose of greater than 5% of baseline value. The mean (SD) of changes in heart V{sub 40}, V{sub 45}, and V{sup 60} were 3.2% (3.4%), 3.0% (2.9%), and 1.4% (2.1%), respectively, and were significant for the study cohort (Wilcoxon signed-rank test, p=0.0107 for V{sub 40}, p=0.0052 for V{sub 45}, and p= 0.0353 for V{sub 60}. Ranges in changes of Heart V{sub 40}, V{sub 45}, and V{sub 60} were −1.9% to 8.6%, −1.7% to 7.5%, and −2.1% to 4.5%, respectively. The mean (SD) of changes in Esophagus PRV Dmean and V{sub 60} were 0.3 Gy (3.3 Gy) and 0.8% (7.7%), respectively, and ranged from −4.8 Gy to 6.8 Gy for Dmean and −15.2% to 14.6% for V{sub 60}. Conclusion: Patients with atelectasis present at the start of radiotherapy experience significant increases in heart dose. Substantial increases in mean lung dose also occur in a subset of patients. This work supported by the National Cancer Institute of National Institutes of Health under Award Number R01CA166119. Disclosures: Phillips Medical systems (Hugo, Weiss), National Institutes of Health (Hugo, Weiss, Christensen), and Roger Koch (Christensen) support, UpToDate (Weiss) royalties, and Varian Medical Systems (Hugo, Weiss) license. No potential conflicts of interest.« less

TH-AB-202-03: A Novel Tool for Computing Deliverable Doses in Dynamic MLC Tracking Treatments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fast, M; Kamerling, C; Menten, M

2016-06-15

Purpose: In tracked dynamic multi-leaf collimator (MLC) treatments, segments are continuously adapted to the target centroid motion in beams-eye-view. On-the-fly segment adaptation, however, potentially induces dosimetric errors due to the finite MLC leaf width and non-rigid target motion. In this study, we outline a novel tool for computing the 4d dose of lung SBRT plans delivered with MLC tracking. Methods: The following automated workflow was developed: A) centroid tracking, where the initial segments are morphed to each 4dCT phase based on the beams-eye-view GTV shift (followed by a dose calculation on each phase); B) re-optimized tracking, in which all morphedmore » initial plans from (A) are further optimised (“warm-started”) in each 4dCT phase using the initial optimisation parameters but phase-specific volume definitions. Finally, both dose sets are accumulated to the reference phase using deformable image registration. Initial plans were generated according to the RTOG-1021 guideline (54Gy, 3-Fx, equidistant 9-beam IMRT) on the peak-exhale (reference) phase of a phase-binned 4dCT. Treatment planning and delivery simulations were performed in RayStation (research v4.6) using our in-house segment-morphing algorithm, which directly links to RayStation through a native C++ interface. Results: Computing the tracking plans and 4d dose distributions via the in-house interface takes 5 and 8 minutes respectively for centroid and re-optimized tracking. For a sample lung SBRT patient with 14mm peak-to-peak motion in sup-inf direction, mainly perpendicular leaf motion (0-collimator) resulted in small dose changes for PTV-D95 (−13cGy) and GTV-D98 (+18cGy) for the centroid tracking case compared to the initial plan. Modest reductions of OAR doses (e.g. spinal cord D2: −11cGy) were achieved in the idealized tracking case. Conclusion: This study presents an automated “1-click” workflow for computing deliverable MLC tracking doses in RayStation. Adding a non-deliverable re-optimized tracking scenario is expected to help quantify plan robustness for more challenging patients with anatomy deformations. We acknowledge support of the MLC tracking research from Elekta AB. MFF is supported by Cancer Research UK under Programme C33589/A19908. Research at ICR is also supported by Cancer Research UK under Programme C33589/A19727 and NHS funding to the NIHR Biomedical Research Centre at RMH and ICR.« less

Dosimetric comparison of 3D conformal, IMRT, and V-MAT techniques for accelerated partial-breast irradiation (APBI)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiu, Jian-Jian; Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai

2014-07-01

The purpose is to dosimetrically compare the following 3 delivery techniques: 3-dimensional conformal radiation therapy (3D-CRT), intensity-modulated arc therapy (IMRT), and volumetric-modulated arc therapy (V-MAT) in the treatment of accelerated partial-breast irradiation (APBI). Overall, 16 patients with T1/2N0 breast cancer were treated with 3D-CRT (multiple, noncoplanar photon fields) on the RTOG 0413 partial-breast trial. These cases were subsequently replanned using static gantry IMRT and V-MAT technology to understand dosimetric differences among these 3 techniques. Several dosimetric parameters were used in plan quality evaluation, including dose conformity index (CI) and dose-volume histogram analysis of normal tissue coverage. Quality assurance studies includingmore » gamma analysis were performed to compare the measured and calculated dose distributions. The IMRT and V-MAT plans gave more conformal target dose distributions than the 3D-CRT plans (p < 0.05 in CI). The volume of ipsilateral breast receiving 5 and 10 Gy was significantly less using the V-MAT technique than with either 3D-CRT or IMRT (p < 0.05). The maximum lung dose and the ipsilateral lung volume receiving 10 (V{sub 10}) or 20 Gy (V{sub 20}) were significantly less with both V-MAT and IMRT (p < 0.05). The IMRT technique was superior to 3D-CRT and V-MAT of low dose distributions in ipsilateral lung (p < 0.05 in V{sub 5} and D{sub 5}). The total mean monitor units (MUs) for V-MAT (621.0 ± 111.9) were 12.2% less than those for 3D-CRT (707.3 ± 130.9) and 46.5% less than those for IMRT (1161.4 ± 315.6) (p < 0.05). The average machine delivery time was 1.5 ± 0.2 minutes for the V-MAT plans, 7.0 ± 1.6 minutes for the 3D-CRT plans, and 11.5 ± 1.9 minutes for the IMRT plans, demonstrating much less delivery time for V-MAT. Based on this preliminary study, V-MAT and IMRT techniques offer improved dose conformity as compared with 3D-CRT techniques without increasing dose to the ipsilateral lung. In terms of MU and delivery time, V-MAT is significantly more efficient for APBI than for conventional 3D-CRT and static-beam IMRT.« less

SU-E-T-548: How To Decrease Spine Dose In Patients Who Underwent Sterotactic Spine Radiosurgery?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Acar, H; Altinok, A; Kucukmorkoc, E

2014-06-01

Purpose: Stereotactic radiosurgery for spine metastases involves irradiation using a single high dose fraction. The purpose of this study was to dosimetrically compare stereotactic spine radiosurgery(SRS) plans using a recently new volumetric modulated arc therapy(VMAT) technique against fix-field intensity-modulated radiotherapy(IMRT). Plans were evaluated for target conformity and spinal cord sparing. Methods: Fifteen previously treated patients were replanned using the Eclipse 10.1 TPS AAA calculation algorithm. IMRT plans with 7 fields were generated. The arc plans used 2 full arc configurations. Arc and IMRT plans were normalized and prescribed to deliver 16.0 Gy in a single fraction to 90% of themore » planning target volume(PTV). PTVs consisted of the vertebral body expanded by 3mm, excluding the PRV-cord, where the cord was expanded by 2mm.RTOG 0631 recommendations were applied for treatment planning. Partial spinal cord volume was defined as 5mm above and below the radiosurgery target volume. Plans were compared for conformity and gradient index as well as spinal cord sparing. Results: The conformity index values of fifteen patients for two different treatment planning techniques were shown in table 1. Conformity index values for 2 full arc planning (average CI=0.84) were higher than that of IMRT planning (average CI=0.79). The gradient index values of fifteen patients for two different treatment planning techniques were shown in table 2. Gradient index values for 2 full arc planning (average GI=3.58) were higher than that of IMRT planning (average GI=2.82).The spinal cord doses of fifteen patients for two different treatment planning techniques were shown in table 3. D0.35cc, D0.03cc and partial spinal cord D10% values in 2 full arc plannings (average D0.35cc=819.3cGy, D0.03cc=965.4cGy, 10%partial spinal=718.1cGy) were lower than IMRT plannings (average D0.35cc=877.4cGy, D0.03c=1071.4cGy, 10%partial spinal=805.1cGy). Conclusions: The two arc VMAT technique is superior to 7 field IMRT technique in terms of both spinal cord sparing and better conformity and gradient indexes.« less

TU-AB-202-07: A Novel Method for Registration of Mid-Treatment PET/CT Images Under Conditions of Tumor Regression for Patients with Locally Advanced Lung Cancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sharifi, Hoda; Department of Physics, Oakland University, Rochester, MI; Zhang, Hong

Purpose: In PET-guided adaptive radiotherapy (RT), changes in the metabolic activity at individual voxels cannot be derived until the duringtreatment CT images are appropriately registered to pre-treatment CT images. However, deformable image registration (DIR) usually does not preserve tumor volume. This may induce errors when comparing to the target. The aim of this study was to develop a DIR-integrated mechanical modeling technique to track radiation-induced metabolic changes on PET images. Methods: Three patients with non-small cell lung cancer (NSCLC) were treated with adaptive radiotherapy under RTOG 1106. Two PET/CT image sets were acquired 2 weeks before RT and 18 fractionsmore » after the start of treatment. DIR was performed to register the during-RT CT to the pre-RT CT using a B-spline algorithm and the resultant displacements in the region of tumor were remodeled using a hybrid finite element method (FEM). Gross tumor volume (GTV) was delineated on the during-RT PET/CT image sets and deformed using the 3D deformation vector fields generated by the CT-based registrations. Metabolic tumor volume (MTV) was calculated using the pre- and during–RT image set. The quality of the PET mapping was evaluated based on the constancy of the mapped MTV and landmark comparison. Results: The B-spline-based registrations changed MTVs by 7.3%, 4.6% and −5.9% for the 3 patients and the correspondent changes for the hybrid FEM method −2.9%, 1% and 6.3%, respectively. Landmark comparisons were used to evaluate the Rigid, B-Spline, and hybrid FEM registrations with the mean errors of 10.1 ± 1.6 mm, 4.4 ± 0.4 mm, and 3.6 ± 0.4 mm for three patients. The hybrid FEM method outperforms the B-Spline-only registration for patients with tumor regression Conclusion: The hybrid FEM modeling technique improves the B-Spline registrations in tumor regions. This technique may help compare metabolic activities between two PET/CT images with regressing tumors. The author gratefully acknowledges the financial support from the National Institutes of Health Grant.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pokhrel, D; Sood, S; Badkul, R

Purpose: To evaluate the dosimetric performance of X-ray Voxel Monte Carlo(XVMC) algorithm in effort to clinically validate Monte Carlo-approach in heterogeneous liver phantom and liver SBRT plans. Methods: An anthropomorphic RPC liver phantom incorporating a liver structure with two cylindrical targets and organs-at-risk (OARs) was used in phantom validation. Subsequently, five patients with metastatic liver cancer were treated using heterogeneity-corrected pencil-beam(PB-hete)algorithm were analyzed following RTOG-1112 criteria .ITV was delineated on MinIP and OARs were contoured on MeanIP images of 4D-CT. PTV was generated from ITV with 5-10mm uniform margin. Mean PTV was 81.3±46.4cc. Prescription was 30–45Gy in 5 fractions, withmore » at least PTV(D95%)=100%. Hybrid SBRT plans were generated with noncoplanar/3D-conformal arcs plus static-beams at Novalis-TX consisting of HD-MLC and 6MV-SRS. SBRT plans were re-computed using XVMC algorithm utilizing identical beam-geometry, MLC-positions, and monitor units and subsequently compared to clinical PB-hete plans. Results: Our results using RPC liver motion phantom validation were all compliance with MD Anderson standards. However, compared to PB-hete, average target volume encompassed by the prescribed percent isodose (Vp) was 9.1% and 8.5% less for PTV1 and PTV2 with XVMC. For the clinical liver SBRT plans, PB-hete systematically overestimated PTV dose (D95, Dmean and D10) within ±2.0% (p<0.05) compared to XVMC. Mean value of Vp was about 3.8% less with XVMC compared to PB-hete (ranged 2.9–5.7% (p<0.003)). However, mean liver dose (MLD) was 3.2% higher (p<0.003), on average, with XVMC compared to clinical PB-hete (ranged −1.0to−3.9%). OARs doses were statistically insignificant. Conclusion: Results from our XVMC dose calculations and validation study for liver SBRT indicate small-to-moderate under-dosing of the tumor volume when compared to PB-hete. Results were consistent with phantom validation and patients plans. However, Vp was less by up to 5.7% for some liver SBRT patients with XVMC–suggesting under-dosing of the target volume and overdosing of MLD by up to 3.9% occurred with PB-hete plan. These differences between PB-hete and XVMC dose calculations may be of clinical interest.« less

Monte Carlo evaluation of RapidArc™ oropharynx treatment planning strategies for sparing of midline structures

NASA Astrophysics Data System (ADS)

Bush, K.; Zavgorodni, S.; Gagne, I.; Townson, R.; Ansbacher, W.; Beckham, W.

2010-08-01

The aim of the study was to perform the Monte Carlo (MC) evaluation of RapidArc™ (Varian Medical Systems, Palo Alto, CA) dose calculations for four oropharynx midline sparing planning strategies. Six patients with squamous cell cancer of the oropharynx were each planned with four RapidArc head and neck treatment strategies consisting of single and double photon arcs. In each case, RTOG0522 protocol objectives were used during planning optimization. Dose calculations performed with the analytical anisotropic algorithm (AAA) are compared against BEAMnrc/DOSXYZnrc dose calculations for the 24-plan dataset. Mean dose and dose-to-98%-of-structure-volume (D98%) were used as metrics in the evaluation of dose to planning target volumes (PTVs). Mean dose and dose-to-2%-of-structure-volume (D2%) were used to evaluate dose differences within organs at risk (OAR). Differences in the conformity index (CI) and the homogeneity index (HI) as well as 3D dose distributions were also observed. AAA calculated PTV mean dose, D98%, and HIs showed very good agreement with MC dose calculations within the 0.8% MC (statistical) calculation uncertainty. Regional node volume (PTV-80%) mean dose and D98% were found to be overestimated (1.3%, σ = 0.8% and 2.3%, σ = 0.8%, respectively) by the AAA with respect to MC calculations. Mean dose and D2% to OAR were also observed to be consistently overestimated by the AAA. Increasing dose calculation differences were found in planning strategies exhibiting a higher overall fluence modulation. From the plan dataset, the largest local dose differences were observed in heavily shielded regions and within the esophageal and sinus cavities. AAA dose calculations as implemented in RapidArc™ demonstrate excellent agreement with MC calculations in unshielded regions containing moderate inhomogeneities. Acceptable agreement is achieved in regions of increased MLC shielding. Differences in dose are attributed to inaccuracies in the AAA-modulated fluence modeling, modeling of material inhomogeneities and dose deposition within low-density materials. The use of MC dose calculations leads to the same general conclusion as using AAA that a two arc delivery with limited collimator opening can provide the greatest amount of midline sparing compared to the other techniques investigated.

Addition of docetaxel or bisphosphonates to standard of care in men with localised or metastatic, hormone-sensitive prostate cancer: a systematic review and meta-analyses of aggregate data

PubMed Central

Vale, Claire L; Burdett, Sarah; Rydzewska, Larysa H M; Albiges, Laurence; Clarke, Noel W; Fisher, David; Fizazi, Karim; Gravis, Gwenaelle; James, Nicholas D; Mason, Malcolm D; Parmar, Mahesh K B; Sweeney, Christopher J; Sydes, Matthew R; Tombal, Bertrand; Tierney, Jayne F

2016-01-01

Summary Background Results from large randomised controlled trials combining docetaxel or bisphosphonates with standard of care in hormone-sensitive prostate cancer have emerged. In order to investigate the effects of these therapies and to respond to emerging evidence, we aimed to systematically review all relevant trials using a framework for adaptive meta-analysis. Methods For this systematic review and meta-analysis, we searched MEDLINE, Embase, LILACS, and the Cochrane Central Register of Controlled Trials, trial registers, conference proceedings, review articles, and reference lists of trial publications for all relevant randomised controlled trials (published, unpublished, and ongoing) comparing either standard of care with or without docetaxel or standard of care with or without bisphosphonates for men with high-risk localised or metastatic hormone-sensitive prostate cancer. For each trial, we extracted hazard ratios (HRs) of the effects of docetaxel or bisphosphonates on survival (time from randomisation until death from any cause) and failure-free survival (time from randomisation to biochemical or clinical failure or death from any cause) from published trial reports or presentations or obtained them directly from trial investigators. HRs were combined using the fixed-effect model (Mantel-Haenzsel). Findings We identified five eligible randomised controlled trials of docetaxel in men with metastatic (M1) disease. Results from three (CHAARTED, GETUG-15, STAMPEDE) of these trials (2992 [93%] of 3206 men randomised) showed that the addition of docetaxel to standard of care improved survival. The HR of 0·77 (95% CI 0·68–0·87; p<0·0001) translates to an absolute improvement in 4-year survival of 9% (95% CI 5–14). Docetaxel in addition to standard of care also improved failure-free survival, with the HR of 0·64 (0·58–0·70; p<0·0001) translating into a reduction in absolute 4-year failure rates of 16% (95% CI 12–19). We identified 11 trials of docetaxel for men with locally advanced disease (M0). Survival results from three (GETUG-12, RTOG 0521, STAMPEDE) of these trials (2121 [53%] of 3978 men) showed no evidence of a benefit from the addition of docetaxel (HR 0·87 [95% CI 0·69–1·09]; p=0·218), whereas failure-free survival data from four (GETUG-12, RTOG 0521, STAMPEDE, TAX 3501) of these trials (2348 [59%] of 3978 men) showed that docetaxel improved failure-free survival (0·70 [0·61–0·81]; p<0·0001), which translates into a reduced absolute 4-year failure rate of 8% (5–10). We identified seven eligible randomised controlled trials of bisphosphonates for men with M1 disease. Survival results from three of these trials (2740 [88%] of 3109 men) showed that addition of bisphosphonates improved survival (0·88 [0·79–0·98]; p=0·025), which translates to 5% (1–8) absolute improvement, but this result was influenced by the positive result of one trial of sodium clodronate, and we found no evidence of a benefit from the addition of zoledronic acid (0·94 [0·83–1·07]; p=0·323), which translates to an absolute improvement in survival of 2% (−3 to 7). Of 17 trials of bisphosphonates for men with M0 disease, survival results from four trials (4079 [66%] of 6220 men) showed no evidence of benefit from the addition of bisphosphonates (1·03 [0·89–1·18]; p=0·724) or zoledronic acid (0·98 [0·82–1·16]; p=0·782). Failure-free survival definitions were too inconsistent for formal meta-analyses for the bisphosphonate trials. Interpretation The addition of docetaxel to standard of care should be considered standard care for men with M1 hormone-sensitive prostate cancer who are starting treatment for the first time. More evidence on the effects of docetaxel on survival is needed in the M0 disease setting. No evidence exists to suggest that zoledronic acid improves survival in men with M1 or M0 disease, and any potential benefit is probably small. Funding Medical Research Council UK. PMID:26718929

The use of spatial dose gradients and probability density function to evaluate the effect of internal organ motion for prostate IMRT treatment planning

NASA Astrophysics Data System (ADS)

Jiang, Runqing; Barnett, Rob B.; Chow, James C. L.; Chen, Jeff Z. Y.

2007-03-01

The aim of this study is to investigate the effects of internal organ motion on IMRT treatment planning of prostate patients using a spatial dose gradient and probability density function. Spatial dose distributions were generated from a Pinnacle3 planning system using a co-planar, five-field intensity modulated radiation therapy (IMRT) technique. Five plans were created for each patient using equally spaced beams but shifting the angular displacement of the beam by 15° increments. Dose profiles taken through the isocentre in anterior-posterior (A-P), right-left (R-L) and superior-inferior (S-I) directions for IMRT plans were analysed by exporting RTOG file data from Pinnacle. The convolution of the 'static' dose distribution D0(x, y, z) and probability density function (PDF), denoted as P(x, y, z), was used to analyse the combined effect of repositioning error and internal organ motion. Organ motion leads to an enlarged beam penumbra. The amount of percentage mean dose deviation (PMDD) depends on the dose gradient and organ motion probability density function. Organ motion dose sensitivity was defined by the rate of change in PMDD with standard deviation of motion PDF and was found to increase with the maximum dose gradient in anterior, posterior, left and right directions. Due to common inferior and superior field borders of the field segments, the sharpest dose gradient will occur in the inferior or both superior and inferior penumbrae. Thus, prostate motion in the S-I direction produces the highest dose difference. The PMDD is within 2.5% when standard deviation is less than 5 mm, but the PMDD is over 2.5% in the inferior direction when standard deviation is higher than 5 mm in the inferior direction. Verification of prostate organ motion in the inferior directions is essential. The margin of the planning target volume (PTV) significantly impacts on the confidence of tumour control probability (TCP) and level of normal tissue complication probability (NTCP). Smaller margins help to reduce the dose to normal tissues, but may compromise the dose coverage of the PTV. Lower rectal NTCP can be achieved by either a smaller margin or a steeper dose gradient between PTV and rectum. With the same DVH control points, the rectum has lower complication in the seven-beam technique used in this study because of the steeper dose gradient between the target volume and rectum. The relationship between dose gradient and rectal complication can be used to evaluate IMRT treatment planning. The dose gradient analysis is a powerful tool to improve IMRT treatment plans and can be used for QA checking of treatment plans for prostate patients.

The use of spatial dose gradients and probability density function to evaluate the effect of internal organ motion for prostate IMRT treatment planning.

PubMed

Jiang, Runqing; Barnett, Rob B; Chow, James C L; Chen, Jeff Z Y

2007-03-07

The aim of this study is to investigate the effects of internal organ motion on IMRT treatment planning of prostate patients using a spatial dose gradient and probability density function. Spatial dose distributions were generated from a Pinnacle3 planning system using a co-planar, five-field intensity modulated radiation therapy (IMRT) technique. Five plans were created for each patient using equally spaced beams but shifting the angular displacement of the beam by 15 degree increments. Dose profiles taken through the isocentre in anterior-posterior (A-P), right-left (R-L) and superior-inferior (S-I) directions for IMRT plans were analysed by exporting RTOG file data from Pinnacle. The convolution of the 'static' dose distribution D0(x, y, z) and probability density function (PDF), denoted as P(x, y, z), was used to analyse the combined effect of repositioning error and internal organ motion. Organ motion leads to an enlarged beam penumbra. The amount of percentage mean dose deviation (PMDD) depends on the dose gradient and organ motion probability density function. Organ motion dose sensitivity was defined by the rate of change in PMDD with standard deviation of motion PDF and was found to increase with the maximum dose gradient in anterior, posterior, left and right directions. Due to common inferior and superior field borders of the field segments, the sharpest dose gradient will occur in the inferior or both superior and inferior penumbrae. Thus, prostate motion in the S-I direction produces the highest dose difference. The PMDD is within 2.5% when standard deviation is less than 5 mm, but the PMDD is over 2.5% in the inferior direction when standard deviation is higher than 5 mm in the inferior direction. Verification of prostate organ motion in the inferior directions is essential. The margin of the planning target volume (PTV) significantly impacts on the confidence of tumour control probability (TCP) and level of normal tissue complication probability (NTCP). Smaller margins help to reduce the dose to normal tissues, but may compromise the dose coverage of the PTV. Lower rectal NTCP can be achieved by either a smaller margin or a steeper dose gradient between PTV and rectum. With the same DVH control points, the rectum has lower complication in the seven-beam technique used in this study because of the steeper dose gradient between the target volume and rectum. The relationship between dose gradient and rectal complication can be used to evaluate IMRT treatment planning. The dose gradient analysis is a powerful tool to improve IMRT treatment plans and can be used for QA checking of treatment plans for prostate patients.

SU-E-T-309: Dosimetric Comparison of Simultaneous Integrated Boost Treatment Plan Between Intensity Modulated Radiotherapies (IMRTs), Dual Arc Volumetric Modulated Arc Therapy (DA-VMAT) and Single Arc Volumetric Modulated Arc Therapy (SA-VMAT) for Nasopharyngeal Carcinoma (NPC)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sivakumar, R; Janardhan, N; Bhavani, P

Purpose: To compare the plan quality and performance of Simultaneous Integrated Boost (SIB) Treatment plan between Seven field (7F) and Nine field(9F) Intensity Modulated Radiotherapies and Single Arc (SA) and Dual Arc (DA) Volumetric Modulated Arc Therapy( VMAT). Methods: Retrospective planning study of 16 patients treated in Elekta Synergy Platform (mlci2) by 9F-IMRT were replanned with 7F-IMRT, Single Arc VMAT and Dual Arc VMAT using CMS, Monaco Treatment Planning System (TPS) with Monte Carlo simulation. Target delineation done as per Radiation Therapy Oncology Protocols (RTOG 0225&0615). Dose Prescribed as 70Gy to Planning Target Volumes (PTV70) and 61Gy to PTV61 inmore » 33 fraction as a SIB technique. Conformity Index(CI), Homogeneity Index(HI) were used as analysis parameter for Target Volumes as well as Mean dose and Max dose for Organ at Risk(OAR,s).Treatment Delivery Time(min), Monitor unit per fraction (MU/fraction), Patient specific quality assurance were also analysed. Results: A Poor dose coverage and Conformity index (CI) was observed in PTV70 by 7F-IMRT among other techniques. SA-VMAT achieved poor dose coverage in PTV61. No statistical significance difference observed in OAR,s except Spinal cord (P= 0.03) and Right optic nerve (P=0.03). DA-VMAT achieved superior target coverage, higher CI (P =0.02) and Better HI (P=0.03) for PTV70 other techniques (7F-IMRT/9F-IMRT/SA-VMAT). A better dose spare for Parotid glands and spinal cord were seen in DA-VMAT. The average treatment delivery time were 5.82mins, 6.72mins, 3.24mins, 4.3mins for 7F-IMRT, 9F-IMRT, SA-VMAT and DA-VMAT respectively. Significance difference Observed in MU/fr (P <0.001) and Patient quality assurance pass rate were >95% (Gamma analysis (Γ3mm, 3%). Conclusion: DA-VAMT showed better target dose coverage and achieved better or equal performance in sparing OARs among other techniques. SA-VMAT offered least Treatment Time than other techniques but achieved poor target coverage. DA-VMAT offered shorter delivery time than 7F-IMRT and 9F-IMRT without compromising the plan quality.« less

SU-E-T-417: The Impact of Normal Tissue Constraints On PTV Dose Homogeneity for Intensity Modulated Radiotherapy (IMRT), Volume Modulated Arc Therapy (VMAT) and Tomotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peng, J; McDonald, D; Ashenafi, M

2014-06-01

Purpose: Complex intensity modulated arc therapy tends to spread low dose to normal tissue(NT)regions to obtain improved target conformity and homogeneity and OAR sparing.This work evaluates the trade-offs between PTV homogeneity and reduction of the maximum dose(Dmax)spread to NT while planning of IMRT,VMAT and Tomotherapy. Methods: Ten prostate patients,previously planned with step-and-shoot IMRT,were selected.To fairly evaluate how PTV homogeneity was affected by NT Dmax constraints,original IMRT DVH objectives for PTV and OARs(femoral heads,and rectal and bladder wall)applied to 2 VMAT plans in Pinnacle(V9.0), and Tomotherapy(V4.2).The only constraint difference was the NT which was defined as body contours excluding targets,OARs andmore » dose rings.NT Dmax constraint for 1st VMAT was set to the prescription dose(Dp).For 2nd VMAT(VMAT-NT)and Tomotherapy,it was set to the Dmax achieved in IMRT(~70-80% of Dp).All NT constraints were set to the lowest priority.Three common homogeneity indices(HI),RTOG-HI=Dmax/Dp,moderated-HI=D95%/D5% and complex-HI=(D2%-D98%)/Dp*100 were calculated. Results: All modalities with similar dosimetric endpoints for PTV and OARs.The complex-HI shows the most variability of indices,with average values of 5.9,4.9,9.3 and 6.1 for IMRT,VMAT,VMAT-NT and Tomotherapy,respectively.VMAT provided the best PTV homogeneity without compromising any OAR/NT sparing.Both VMAT-NT and Tomotherapy,planned with more restrictive NT constraints,showed reduced homogeneity,with VMAT-NT showing the worst homogeneity(P<0.0001)for all HI.Tomotherapy gave the lowest NT Dmax,with slightly decreased homogeneity compared to VMAT. Finally, there was no significant difference in NT Dmax or Dmean between VMAT and VMAT-NT. Conclusion: PTV HI is highly dependent on permitted NT constraints. Results demonstrated that VMAT-NT with more restrictive NT constraints does not reduce Dmax NT,but significantly receives higher Dmax and worse target homogeneity.Therefore, it is critical that planners do not use too restrictive NT constraints during VMAT optimization.Tomotherapy plan was not as sensitive to NT constraints,however,care shall be taken to ensure NT is not pushed too hard.These results are relevant for clinical practice.The biological effect of higher Dmax and increased target heterogeneity needs further study.« less

SU-E-T-43: A Methodology for Quality Control of IMPT Treatment Plan Based On VMAT Plan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, S; Tianjin Medical University Cancer Institute and Hospital; Yang, Y

Purpose: IMPT plan design is highly dependent on planner’s experiences. VMAT plan design is relatively mature and can even be automated. The quality of IMPT plan designed by in-experienced planner could be inferior to that of VMAT plan designed by experienced planner or automatic planning software. Here we introduce a method for designing IMPT plan based on VMAT plan to ensure the IMPT plan be superior to IMRT/VMAT plan for majority clinical scenario. Methods: To design a new IMPT plan, a VMAT plan is first generated either by experienced planner or by in-house developed automatic planning system. An in-house developedmore » tool is used to generate the dose volume constrains for the IMPT plan as plan template to Eclipse TPS. The beam angles for IMPT plan are selected based on the preferred angles in the VMAT plan. IMPT plan is designed by importing the plan objectives generated from VMAT plan. Majority thoracic IMPT plans are designed using this plan approach in our center. In this work, a thoracic IMPT plan under RTOG 1308 protocol is selected to demonstrate the effectiveness and efficiency of this approach. The dosimetric indices of IMPT are compared with VMAT plan. Results: The PTV D95, lung V20, MLD, mean heart dose, esophagus D1, cord D1 are 70Gy, 31%, 17.8Gy, 25.5Gy, 73Gy, 45Gy for IMPT plan and 65.3Gy, 34%, 21.6Gy, 35Gy, 74Gy, 48Gy for VMAT plan. For majority cases, the high dose region of the normal tissue which is in proximity of PTV is comparable between IMPT and VMAT plan. The low dose region of the IMPT plan is significantly better than VMAT plan. Conclusion: Using the knowledge gained in VMAT plan design can help efficiently and effectively design high quality IMPT plan. The quality of IMPT plan can be controlled to ensure the superiority of IMPT plan compared to VMAT/IMRT plan.« less

Analysis of Local Control in Patients Receiving IMRT for Resected Pancreatic Cancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yovino, Susannah; Maidment, Bert W.; Herman, Joseph M.

2012-07-01

Purpose: Intensity-modulated radiotherapy (IMRT) is increasingly incorporated into therapy for pancreatic cancer. A concern regarding this technique is the potential for geographic miss and decreased local control. We analyzed patterns of first failure among patients treated with IMRT for resected pancreatic cancer. Methods and Materials: Seventy-one patients who underwent resection and adjuvant chemoradiation for pancreas cancer are included in this report. IMRT was used for all to a median dose of 50.4 Gy. Concurrent chemotherapy was 5-FU-based in 72% of patients and gemcitabine-based in 28%. Results: At median follow-up of 24 months, 49/71 patients (69%) had failed. The predominant failuremore » pattern was distant metastases in 35/71 patients (49%). The most common site of metastases was the liver. Fourteen patients (19%) developed locoregional failure in the tumor bed alone in 5 patients, regional nodes in 4 patients, and concurrently with metastases in 5 patients. Median overall survival (OS) was 25 months. On univariate analysis, nodal status, margin status, postoperative CA 19-9 level, and weight loss during treatment were predictive for OS. On multivariate analysis, higher postoperative CA19-9 levels predicted for worse OS on a continuous basis (p < 0.01). A trend to worse OS was seen among patients with more weight loss during therapy (p = 0.06). Patients with positive nodes and positive margins also had significantly worse OS (HR for death 2.8, 95% CI 1.1-7.5; HR for death 2.6, 95% CI 1.1-6.2, respectively). Grade 3-4 nausea and vomiting was seen in 8% of patients. Late complication of small bowel obstruction occurred in 4 (6%) patients. Conclusions: This is the first comprehensive report of patterns of failure among patients treated with adjuvant IMRT for pancreas cancer. IMRT was not associated with an increase in local recurrences in our cohort. These data support the use of IMRT in the recently activated EORTC/US Intergroup/RTOG 0848 adjuvant pancreas trial.« less

The prognostic role of hemoglobin levels in patients undergoing concurrent chemo-radiation for anal cancer.

PubMed

Franco, Pierfrancesco; Montagnani, Francesco; Arcadipane, Francesca; Casadei, Chiara; Andrikou, Kalliopi; Martini, Stefania; Iorio, Giuseppe Carlo; Scartozzi, Mario; Mistrangelo, Massimiliano; Fornaro, Lorenzo; Cassoni, Paola; Cascinu, Stefano; Ricardi, Umberto; Casadei Gardini, Andrea

2018-05-02

Concurrent chemo-radiation (CT-RT) is a standard therapy for squamous cell carcinoma of anal canal. Different clinical and biological factors may potentially affect outcome. We investigated the prognostic role of baseline hemoglobin (Hb) in a cohort of anal cancer patients submitted to CT-RT with 5-fluorouracil and mitomycin C. Up to 161 patients with clinical stage T1-T4/N0-N3/M0 were treated. Response was assessed at 6 weeks and thereafter at 3, 6 and 12 months. Two different approaches were used:a)simultaneous integrated boost following RTOG 05-29 indications;b)first sequence of 45Gy/25 fractions to the pelvis followed by 9-14.4 Gy/5-8 fractions to the macroscopic disease. Primary endpoints were progression-free survival (PFS) and overall survival (OS). On multivariate analysis, pre-treatment Hb level had a significant correlation to OS (HR:0.53;95% CI:0.33-0.87; p = 0.001), but not to PFS (HR:0.78;95% CI:0.53-1.15; p = 0.12) Patients with pre-treatment Hb ≥ 12 g/dl had 5-year PFS and OS of 82.2%, compared to 29.3% and 32.8% for those below the threshold. The likelihood to achieve a complete remission increased by 5.6% for every single-unit (g/dl) increase in baseline Hb level over 11 g/dl. On multivariate analysis, response to treatment had a significant correlation to PFS (incomplete vs complete response - HR:5.43;95% CI:2.75-10.7; p < 0.0001) and OS (HR: 6.96;95% CI:2.96-16.5; p < 0.0001). We showed that baseline Hb level is a strong indicator for poor response to RT-CT in anal cancer patients. A close clinical monitoring for incomplete response to treatment should be advised in patients with low pre-treatment Hb. The hypothesis that the preservation of adequate Hb level during treatment may lead to a better outcome needs prospective evaluation.

Phase 1/2 Trials of Temozolomide, Motexafin Gadolinium, and 60-Gy Fractionated Radiation for Newly Diagnosed Supratentorial Glioblastoma Multiforme: Final Results of RTOG 0513

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brachman, David G., E-mail: david.brachman@dignityhealth.org; Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; Pugh, Stephanie L.

Purpose: The purpose of phase 1 was to determine the maximum tolerated dose (MTD) of motexafin gadolinium (MGd) given concurrently with temozolomide (TMZ) and radiation therapy (RT) in patients with newly diagnosed supratentorial glioblastoma multiforme (GBM). Phase 2 determined whether this combination improved overall survival (OS) and progression-free survival (PFS) in GBM recursive partitioning analysis class III to V patients compared to therapies for recently published historical controls. Methods and Materials: Dose escalation in phase 1 progressed through 3 cohorts until 2 of 6 patients experienced dose-limiting toxicity or a dose of 5 mg/kg was reached. Once MTD was established, amore » 1-sided 1-sample log-rank test at significance level of .1 had 85% power to detect a median survival difference (13.69 vs 18.48 months) with 60 deaths over a 12-month accrual period and an additional 18 months of follow-up. OS and PFS were estimated using the Kaplan-Meier method. Results: In phase 1, 24 patients were enrolled. The MTD established was 5 mg/kg, given intravenously 5 days a week for the first 10 RT fractions, then 3 times a week for the duration of RT. The 7 patients enrolled in the third dose level and the 94 enrolled in phase 2 received this dose. Of these 101 patients, 87 were eligible and evaluable. Median survival time was 15.6 months (95% confidence interval [CI]: 12.9-17.6 months), not significantly different from that of the historical control (P=.36). Median PFS was 7.6 months (95% CI: 5.7-9.6 months). One patient (1%) experienced a grade 5 adverse event possibly related to therapy during the concurrent phase, and none experience toxicity during adjuvant TMZ therapy. Conclusions: Treatment was well tolerated, but median OS did not reach improvement specified by protocol compared to historical control, indicating that the combination of standard RT with TMZ and MGd did not achieve a significant survival advantage.« less

SU-E-T-320: Dosimetric Evaluation of Intracranial Stereotactic Radiotherapy Plans Using Jaws-Only Collimation On a LINAC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mistry, N; Kim, A; Schaum, J

2015-06-15

Purpose: To evaluate the dosimetry of cranial stereotactic radiotherapy (SRT) plans using jaws-only collimation on linac that meets appropriate TG-142 tolerances. Methods: Seventeen spherical targets were generated in the center of a head phantom with diameters ranging from 8 mm to 40 mm. Plans balanced treatment time with dose gradient and conformity using 13 static fields and 3 couch angles: 9 non-opposed and coplanar fields and 4 non-coplanar fields. The symmetrical jaws field size was target diameter plus 2 mm. The prescription (Rx) was 7 Gy per fraction to the 80% isodose line. Two plans were created for each target:more » one kept the collimator at 0° (C0), one adjusted the collimator angle 40° for each field to create a 360° sweep over the 9 coplanar fields (CR).Conformity of the Rx to the target was evaluated using a ratio of Rx to target volume (PITV). Heterogeneity was determined using a ratio of maximum dose to Rx dose. Falloff was scored using CGIg: the difference of effective radii of spheres equal to half and full Rx volumes. Results: All plans met RTOG SRS criteria for conformity and heterogeneity. The use of collimator rotation improved conformity by 3.2% on average, the mean PITV was 1.7±0.1 for C0 plans and 1.6±0.1 for CR. Mean heterogeneity was 1.25±0.0 for both C0 and CR. The mean CGIg was 75.9±16.4 for C0 plans and 74.4±17.0 for CR; with a mean dose falloff degradation of 2.5% by CR. Conclusion: Clinically acceptable SRT plans for spherical targets were created using jaws-only collimation with static fields. The addition of sweeping collimator rotation improves conformity at the expense of gradient. This technique can expand the availability of SRT to patients especially to those who cannot travel to a facility with a dedicated stereotactic radiosurgery machine.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Badkul, R; Nicolai, W; Pokhrel, D

Purpose: To compare the impact of Pencil Beam(PB) and Anisotropic Analytic Algorithm(AAA) dose calculation algorithms on OARs and planning target volume (PTV) in thoracic spine stereotactic body radiation therapy (SBRT). Methods: Ten Spine SBRT patients were planned on Brainlab iPlan system using hybrid plan consisting of 1–2 non-coplanar conformal-dynamic arcs and few IMRT beams treated on NovalisTx with 6MV photon. Dose prescription varied from 20Gy to 30Gy in 5 fractions depending on the situation of the patient. PB plans were retrospectively recalculated using the Varian Eclipse with AAA algorithm using same MUs, MLC pattern and grid size(3mm).Differences in dose volumemore » parameters for PTV, spinal cord, lung, and esophagus were analyzed and compared for PB and AAA algorithms. OAR constrains were followed per RTOG-0631. Results: Since patients were treated using PB calculation, we compared all the AAA DVH values with respect to PB plan values as standard, although AAA predicts the dose more accurately than PB. PTV(min), PTV(Max), PTV(mean), PTV(D99%), PTV(D90%) were overestimated with AAA calculation on average by 3.5%, 1.84%, 0.95%, 3.98% and 1.55% respectively as compared to PB. All lung DVH parameters were underestimated with AAA algorithm mean deviation of lung V20, V10, V5, and 1000cc were 42.81%,19.83%, 18.79%, and 18.35% respectively. AAA overestimated Cord(0.35cc) by mean of 17.3%; cord (0.03cc) by 12.19% and cord(max) by 10.5% as compared to PB. Esophagus max dose were overestimated by 4.4% and 5cc by 3.26% for AAA algorithm as compared to PB. Conclusion: AAA overestimated the PTV dose values by up to 4%.The lung DVH had the greatest underestimation of dose by AAA versus PB. Spinal cord dose was overestimated by AAA versus PB. Given the critical importance of accuracy of OAR and PTV dose calculation for SBRT spine, more accurate algorithms and validation of calculated doses in phantom models are indicated.« less

SU-E-T-06: 4D Particle Swarm Optimization to Enable Lung SBRT in Patients with Central And/or Large Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Modiri, A; Gu, X; Hagan, A

2015-06-15

Purpose: Patients presenting with large and/or centrally-located lung tumors are currently considered ineligible for highly potent regimens such as SBRT due to concerns of toxicity to normal tissues and organs-at-risk (OARs). We present a particle swarm optimization (PSO)-based 4D planning technique, designed for MLC tracking delivery, that exploits the temporal dimension as an additional degree of freedom to significantly improve OAR-sparing and reduce toxicity to levels clinically considered as acceptable for SBRT administration. Methods: Two early-stage SBRT-ineligible NSCLC patients were considered, presenting with tumors of maximum dimensions of 7.4cm (central-right lobe; 1.5cm motion) and 11.9cm (upper-right lobe; 1cm motion). Inmore » each case, the target and normal structures were manually contoured on each of the ten 4DCT phases. Corresponding ten initial 3D-conformal plans (Pt#1: 7-beams; Pt#2: 9-beams) were generated using the Eclipse planning system. Using 4D-PSO, fluence weights were optimized over all beams and all phases (70 and 90 apertures for Pt1&2, respectively). Doses to normal tissues and OARs were compared with clinicallyestablished lung SBRT guidelines based on RTOG-0236. Results: The PSO-based 4D SBRT plan yielded tumor coverage and dose—sparing for parallel and serial OARs within the SBRT guidelines for both patients. The dose-sparing compared to the clinically-delivered conventionallyfractionated plan for Patient 1 (Patient 2) was: heart Dmean = 11% (33%); lung V20 = 16% (21%); lung Dmean = 7% (20%); spinal cord Dmax = 5% (16%); spinal cord Dmean = 7% (33%); esophagus Dmax = 0% (18%). Conclusion: Truly 4D planning can significantly reduce dose to normal tissues and OARs. Such sparing opens up the possibility of using highly potent and effective regimens such as lung SBRT for patients who were conventionally considered SBRT non-eligible. Given the large, non-convex solution space, PSO represents an attractive, parallelizable tool to successfully achieve a globally optimal solution for this problem. This work was supported through funding from the National Institutes of Health and Varian Medical Systems.« less

FIVE-YEAR RESULTS OF ADJUVANT RADIOTHER

PubMed Central

Osa, Etin-Osa O.; DeWyngaert, Keith; Roses, Daniel; Speyer, James; Guth, Amber; Axelrod, Deborah; Kerimian, Maria Fenton; Goldberg, Judith D.; Formenti, Silvia C.

2015-01-01

Purpose/Objective A technique of prone breast radiotherapy delivered by a regimen of accelerated intensity modulated radiation therapy (IMRT) with a concurrent boost to the tumor bed, was developed at our institution. We report the five year results of this approach. Methods and Materials Between 2003–2006, 404 patients with Stage I–II breast cancer were prospectively enrolled into two consecutive protocols, institutional trials 03–30 and 05–181, that used the same regimen of 40.5Gy/15 fractions delivered to the index breast over 3 weeks, with a concomitant daily boost to the tumor bed of 0.5Gy (total dose=48Gy). All patients were treated after segmental mastectomy, had negative margins, and nodal assessment. Patients were set up prone: only if lung or heart volumes were in the field was a supine set-up attempted, and chosen if found to better spare these organs. Results 92% of patients were treated prone, 8% supine. 72% had stage I, 28% stage II invasive breast cancer. In-field lung volume ranged from 0 –228.27cc, mean: 19.65cc. In-field heart volume for left breast cancer patients ranged from 0–21.24cc, mean: 1.59cc. There was no heart in the field for right breast cancer patients. At a median follow-up of five years, the five-year cumulative incidence of isolated ipsilateral breast tumor recurrence was 0.82% (95% CI: 0.65–1.04). The five-year cumulative incidence of regional recurrence was 0.53% (95% CI:0.41–0.69) and the five-year overall cumulative death rate was 1.28% (95% CI: 0.48–3.38). 82% (95% CI: 77–85) of patients judged their final cosmetic result as excellent/good. Conclusions Prone accelerated IMRT with a concomitant boost results in excellent local control, optimal sparing of heart and lung, with good cosmesis. RTOG 10–05, a phase III, multi-institutional, randomized trial is ongoing and is evaluating the equivalence of a similar dose and fractionation approach to standard six weeks radiotherapy with a sequential boost. PMID:24867535

SU-F-BRA-14: Optimization of Dosimetric Guidelines for Accelerated Partial Breast Irradiation (APBI) Using the Strut-Adjusted Volume Implant (SAVI)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mooney, K; Altman, M; Garcia-Ramirez, J

Purpose: Treatment planning guidelines for accelerated partial breast irradiation (ABPI) using the strut-adjusted volume implant (SAVI) are inconsistent between the manufacturer and NSABP B-39/RTOG 0413 protocol. Furthermore neither set of guidelines accounts for different applicator sizes. The purpose of this work is to establish guidelines specific to the SAVI that are based on clinically achievable dose distributions. Methods: Sixty-two consecutive patients were implanted with a SAVI and prescribed to receive 34 Gy in 10 fractions twice daily using high dose-rate (HDR) Ir-192 brachytherapy. The target (PTV-EVAL) was defined per NSABP. The treatments were planned and evaluated using a combination ofmore » dosimetric planning goals provided by the NSABP, the manufacturer, and our prior clinical experience. Parameters evaluated included maximum doses to skin and ribs, and volumes of PTV-EVAL receiving 90%, 95%, 100%, 150%, and 200% of the prescription (V90, etc). All target parameters were evaluated for correlation with device size using the Pearson correlation coefficient. Revised dosimetric guidelines for target coverage and heterogeneity were determined from this population. Results: Revised guidelines for minimum target coverage (ideal in parentheses): V90≥95%(97%), V95≥90%(95%), V100≥88%(91%). The only dosimetric parameters that were significantly correlated (p<0.05) with device size were V150 and V200. Heterogeneity criteria were revised for the 6–1 Mini/6-1 applicators to V150≤30cc and V200≤15cc, and unchanged for the other sizes. Re-evaluation of patient plans showed 90% (56/62) met the revised minimum guidelines and 76% (47/62) met the ideal guidelines. All and 56/62 patients met our institutional guidelines for maximum skin and rib dose, respectively. Conclusions: We have optimized dosimetric guidelines for the SAVI applicators, and found that implementation of these revised guidelines for SAVI treatment planning yielded target coverage exceeding that required by existing guidelines while preserving heterogeneity constraints and minimizing dose to organs at risk.« less

Final Results of Local-Regional Control and Late Toxicity of RTOG 9003: A Randomized Trial of Altered Fractionation Radiation for Locally Advanced Head and Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beitler, Jonathan J., E-mail: jjbeitl@emory.edu; Zhang, Qiang; Fu, Karen K.

Purpose: To test whether altered radiation fractionation schemes (hyperfractionation [HFX], accelerated fractionation, continuous [AFX-C], and accelerated fractionation with split [AFX-S]) improved local-regional control (LRC) rates for patients with squamous cell cancers (SCC) of the head and neck when compared with standard fractionation (SFX) of 70 Gy. Methods and Materials: Patients with stage III or IV (or stage II base of tongue) SCC (n=1076) were randomized to 4 treatment arms: (1) SFX, 70 Gy/35 daily fractions/7 weeks; (2) HFX, 81.6 Gy/68 twice-daily fractions/7 weeks; (3) AFX-S, 67.2 Gy/42 fractions/6 weeks with a 2-week rest after 38.4 Gy; and (4) AFX-C, 72 Gy/42 fractions/6 weeks. The 3 experimental arms were to bemore » compared with SFX. Results: With patients censored for LRC at 5 years, only the comparison of HFX with SFX was significantly different: HFX, hazard ratio (HR) 0.79 (95% confidence interval 0.62-1.00), P=.05; AFX-C, 0.82 (95% confidence interval 0.65-1.05), P=.11. With patients censored at 5 years, HFX improved overall survival (HR 0.81, P=.05). Prevalence of any grade 3, 4, or 5 toxicity at 5 years; any feeding tube use after 180 days; or feeding tube use at 1 year did not differ significantly when the experimental arms were compared with SFX. When 7-week treatments were compared with 6-week treatments, accelerated fractionation appeared to increase grade 3, 4 or 5 toxicity at 5 years (P=.06). When the worst toxicity per patient was considered by treatment only, the AFX-C arm seemed to trend worse than the SFX arm when grade 0-2 was compared with grade 3-5 toxicity (P=.09). Conclusions: At 5 years, only HFX improved LRC and overall survival for patients with locally advanced SCC without increasing late toxicity.« less

Screening for depression in cancer patients receiving radiotherapy: Feasibility and identification of effective tools in the NRG Oncology RTOG 0841 trial.

PubMed

Wagner, Lynne I; Pugh, Stephanie L; Small, William; Kirshner, Jeffrey; Sidhu, Kulbir; Bury, Martin J; DeNittis, Albert S; Alpert, Tracy E; Tran, Binh; Bloom, Beatrice F; Mai, Julie; Yeh, Alexander; Sarma, Kalika; Becker, Mark; James, Jennifer; Bruner, Deborah Watkins

2017-02-01

Brief tools are needed to screen oncology outpatients for depressive symptoms. Patients starting radiotherapy for the first diagnosis of any tumor completed distress screening tools, including the 9-item Patient Health Questionnaire (PHQ-9), the 2-item Patient Health Questionnaire (PHQ-2), the National Comprehensive Cancer Network Distress Thermometer (NCCN-DT), and the Hopkins Symptom Checklist (HSCL) (25-item version). Patients exceeding validated cutoff scores and a systematic sample of patients whose screening was negative completed the Structured Clinical Interview for DSM-IV (SCID) mood disorder modules via telephone. Four hundred sixty-three patients from 35 community-based radiation oncology sites and 2 academic radiation oncology sites were recruited. Sixty-six percent of the 455 eligible patients (n = 299) were women, and the eligible patients had breast (45%), gastrointestinal (11%), lung (10%), gynecologic (6%), or other cancers (27%). Seventy-five (16.5%) exceeded screening cutoffs for depressive symptoms. Forty-two of these patients completed the SCID. Another 37 patients whose screening was negative completed the SCID. Among the 79 patients completing the SCID, 8 (10.1%) met the criteria for major depression, 2 (2.5%) met the criteria for dysthymia, and 6 (7.6%) met the criteria for an adjustment disorder. The PHQ-2 demonstrated good psychometric properties for screening for mood disorders with a cutoff score of ≥3 (receiver operating characteristic area under the curve [AUC], 0.83) and was comparable to the PHQ-9 ( > 9; AUC = 0.85). The NCCN-DT did not detect depression (AUC = 0.59). The PHQ-2 demonstrated good psychometric properties for screening for mood disorders, which were equivalent to the PHQ-9 and superior to the NCCN-DT. These findings support using the PHQ-2 to identify patients in need of further assessment for depression, which has a low prevalence but is a clinically significant comorbidity. These findings could inform the implementation of distress screening accreditation standards. Cancer 2017;123:485-493. © 2016 American Cancer Society. © 2016 American Cancer Society.

Effect of Midtreatment PET/CT-Adapted Radiation Therapy With Concurrent Chemotherapy in Patients With Locally Advanced Non–Small-Cell Lung Cancer

PubMed Central

Kong, Feng-Ming; Ten Haken, Randall K.; Schipper, Matthew; Frey, Kirk A.; Hayman, James; Gross, Milton; Ramnath, Nithya; Hassan, Khaled A.; Matuszak, Martha; Ritter, Timothy; Bi, Nan; Wang, Weili; Orringer, Mark; Cease, Kemp B.; Lawrence, Theodore S.; Kalemkerian, Gregory P.

2017-01-01

IMPORTANCE Our previous studies demonstrated that tumors significantly decrease in size and metabolic activity after delivery of 45 Gy of fractionated radiatiotherapy (RT), and that metabolic shrinkage is greater than anatomic shrinkage. This study aimed to determine whether 18F-fludeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) acquired during the course of treatment provides an opportunity to deliver higher-dose radiation to the more aggressive areas of the tumor to improve local tumor control without increasing RT-induced lung toxicity (RILT), and possibly improve survival. OBJECTIVE To determine whether adaptive RT can target high-dose radiation to the FDG-avid tumor on midtreatment FDG-PET to improve local tumor control of locally advanced non–small-cell lung cancer (NSCLC). DESIGN, SETTING, AND PARTICIPANTS A phase 2 clinical trial conducted at 2 academic medical centers with 42 patients who had inoperable or unresectable stage II to stage III NSCLC enrolled from November 2008, to May 2012. Patients with poor performance, more than 10% weight loss, poor lung function, and/or oxygen dependence were included, providing that the patients could tolerate the procedures of PET scanning and RT. INTERVENTION Conformal RT was individualized to a fixed risk of RILT (grade >2) and adaptively escalated to the residual tumor defined on midtreatment FDG-PET up to a total dose of 86 Gy in 30 daily fractions. Medically fit patients received concurrent weekly carboplatin plus paclitaxel followed by 3 cycles of consolidation. MAIN OUTCOMES AND MEASURES The primary end point was local tumor control. The trial was designed to achieve a 20% improvement in 2-year control from 34% of our prior clinical trial experience with 63 to 69 Gy in a similar patient population. RESULTS The trial reached its accrual goal of 42 patients: median age, 63 years (range, 45–83 years); male, 28 (67%); smoker or former smoker, 39 (93%); stage III, 38 (90%). Median tumor dose delivered was 83 Gy (range, 63–86 Gy) in 30 daily fractions. Median follow-up for surviving patients was 47 months. The 2-year rates of infield and overall local regional tumor controls (ie, including isolated nodal failure) were 82% (95% CI, 62%–92%) and 62% (95% CI, 43%–77%), respectively. Median overall survival was 25 months (95% CI, 12–32 months). The 2-year and 5-year overall survival rates were 52% (95% CI, 36%–66%) and 30% (95% CI, 16%–45%), respectively. CONCLUSIONS AND RELEVANCE Adapting RT-escalated radiation dose to the FDG-avid tumor detected by midtreatment PET provided a favorable local-regional tumor control. The RTOG 1106 trial is an ongoing clinical trial to validate this finding in a randomized fashion. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01190527 PMID:28570742

Effect of the Addition of Cetuximab to Paclitaxel, Cisplatin, and Radiation Therapy for Patients With Esophageal Cancer: The NRG Oncology RTOG 0436 Phase 3 Randomized Clinical Trial.

PubMed

Suntharalingam, Mohan; Winter, Kathryn; Ilson, David; Dicker, Adam P; Kachnic, Lisa; Konski, André; Chakravarthy, A Bapsi; Anker, Christopher J; Thakrar, Harish; Horiba, Naomi; Dubey, Ajay; Greenberger, Joel S; Raben, Adam; Giguere, Jeffrey; Roof, Kevin; Videtic, Gregory; Pollock, Jondavid; Safran, Howard; Crane, Christopher H

2017-11-01

The role of epidermal growth factor receptor (EGFR) inhibition in chemoradiation strategies in the nonoperative treatment of patients with esophageal cancer remains uncertain. To evaluate the benefit of cetuximab added to concurrent chemoradiation therapy for patients undergoing nonoperative treatment of esophageal carcinoma. A National Cancer Institute (NCI) sponsored, multicenter, phase 3, randomized clinical trial open to patients with biopsy-proven carcinoma of the esophagus. The study accrued 344 patients from 2008 to 2013. Patients were randomized to weekly concurrent cisplatin (50 mg/m2), paclitaxel (25 mg/m2), and daily radiation of 50.4 Gy/1.8 Gy fractions with or without weekly cetuximab (400 mg/m2 on day 1 then 250 mg/m2 weekly). Overall survival (OS) was the primary endpoint, with a study designed to detect an increase in 2-year OS from 41% to 53%; 80% power and 1-sided α = .025. Between June 30, 2008, and February 8, 2013, 344 patients were enrolled. This analysis used all data received at NRG Oncology through April 12, 2015. Sixteen patients were ineligible, resulting in 328 evaluable patients, 159 in the experimental arm and 169 in the control arm. Patients were well matched between the treatment arms for patient and tumor characteristics: 263 (80%) with T3 or T4 disease, 215 (66%) N1, and 62 (19%) with celiac nodal involvement. Incidence of grade 3, 4, or 5 treatment-related adverse events at any time was 71 (46%), 35 (23%), or 6 (4%) in the experimental arm and 83 (50%), 28 (17%), or 2 (1%) in the control arm, respectively. A clinical complete response (cCR) rate of 81 (56%) was observed in the experimental arm vs 92 (58%) in the control arm (Fisher exact test, P = .66). No differences were seen in cCR between treatment arms for either histology (adenocarcinoma or squamous cell). Median follow-up for all patients was 18.6 months. The 24- and 36-month local failure for the experimental arm was 47% (95% CI, 38%-57%) and 49% (95% CI, 40%-59%) vs 49% (95% CI, 41%-58%) and 49% (95% CI, 41%-58%) for the control arm (HR, 0.92; 95% CI, 0.66-1.28; P = .65). The 24- and 36-month OS rates for the experimental arm were 45% (95% CI, 37%-53%) and 34% (95% CI, 26%-41%) vs 44% (95% CI, 36%-51%) and 28% (95% CI, 21%-35%) for the control arm (HR, 0.90; 95% CI, 0.70-1.16; P = .47). The addition of cetuximab to concurrent chemoradiation did not improve OS. These phase 3 trial results point to little benefit to current EGFR-targeted agents in an unselected patient population, and highlight the need for predictive biomarkers in the treatment of esophageal cancer. clinicaltrials.gov Identifier: NCT00655876.

SU-C-BRE-02: BED Vs. Local Control: Radiobiological Effect of Tumor Volume in Monte Carlo (MC) Lung SBRT Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pokhrel, D; Badkul, R; Jiang, H

2014-06-15

Purpose: SBRT with hypofractionated dose schemata has emerged a compelling treatment modality for medically inoperable early stage lung cancer patients. It requires more accurate dose calculation and treatment delivery technique. This report presents the relationship between tumor control probability(TCP) and size-adjusted biological effective dose(sBED) of tumor volume for MC lung SBRT patients. Methods: Fifteen patients who were treated with MC-based lung SBRT to 50Gy in 5 fractions to PTVV100%=95% were studied. ITVs were delineated on MIP images of 4DCT-scans. PTVs diameter(ITV+5mm margins) ranged from 2.7–4.9cm (mean 3.7cm). Plans were generated using non-coplanar conformal arcs/beams using iPlan XVMC algorithm (BrainLABiPlan ver.4.1.2)more » for Novalis-TX with HD-MLCs and 6MVSRS(1000MU/min) mode, following RTOG-0813 dosimetric guidelines. To understand the known uncertainties of conventional heterogeneities-corrected/uncorrected pencil beam (PBhete/ PB-homo) algorithms, dose distributions were re-calculated with PBhete/ PB-homo using same beam configurations, MLCs and monitor units. Biologically effective dose(BED10) was computed using LQ-model with α/β=10Gy for meanPTV and meanITV. BED10-c*L, gave size-adjusted BED(sBED), where c=10Gy/cm and L=PTV diameter in centimeter. The TCP model was adopted from Ohri et al.(IJROBP, 2012): TCP = exp[sBEDTCD50]/ k /(1.0 + exp[sBED-TCD50]/k), where k=31Gy corresponding to TCD50=0Gy; and more realistic MC-based TCP was computed for PTV(V99%). Results: Mean PTV PB-hete TCP value was 6% higher, but, mean PTV PB-homo TCP value was 4% lower compared to mean PTV MC TCP. Mean ITV PB-hete/PB-homo TCP values were comparable (within ±3.0%) to mean ITV MC TCP. The mean PTV(V99%)had BED10=90.9±3.7%(median=92.2%),sBED=54.1±8.2%(median=53.5%) corresponding to mean MC TCP value of 84.8±3.3%(median=84.9%) at 2- year local control. Conclusion: The TCP model which incorporates BED10 and tumor diameter indicates that radiobiological effect of target volume and dose calculation algorithm significantly affects TCP for lung SBRT patients. Dose calculation using MC-based algorithm is more realistic with tissue heterogeneities and is routinely performed in our clinic. Patients will be followed up to determine whether TCP prediction correlate clinical outcomes.« less

SU-F-T-604: Dosimetric Evaluation of Intracranial Stereotactic Radiotherapy Plans On a LINAC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheth, N; Tabibian, A; Rose, J

2016-06-15

Purpose: To evaluate the dosimetry of cranial stereotactic radiotherapy (SRT) plans of varying techniques on linac that meets appropriate TG-142 tolerances using 1 cm leaf width multileaf collimator (MLC). Methods: Seventeen spherical targets were generated in the center of a head phantom with diameters ranging 8 mm to 40 mm. SRT plans used 100° non-coplanar arcs and 5 couch angles with 35° spacing. The field size was target plus 1 mm margin. Four plans were created for each target: symmetrical jaws blocking for 5 arcs with 0° collimator (J1C), symmetrical jaws blocking with 5 clockwise arcs with 0° collimator andmore » 5 counter-clockwise arcs with 45° collimator (J2C), MLC blocking for 5 dynamic conformal arcs with 0° collimator (M1C), and MLC blocking for 5 clockwise dynamic conformal arcs with 0° collimators and 5 counter-clockwise dynamic conformal arcs with 45° collimator (M2C).Conformity was evaluated using a ratio of Rx to target volume (PITV). Heterogeneity was determined using a ratio of maximum dose to Rx dose. Falloff was scored using CGIg: difference of effective radii of spheres equal to half and full Rx volumes. Results: All plans met RTOG SRS criteria for conformity and heterogeneity. The mean PITV was 1.52±0.07, 1.49±0.08, 1.39±0.05, and 1.37±0.04 for J1C, J2C, M1C, and M2C plans respectively. The mean CGIg was 75.35±15.79, 74.19±16.66, 77.14±15.12, and 76.28±15.78 for J1C, J2C, M1C, and M2C plans respectively. The mean MDPD was 1.25±0.00 for all techniques. Conclusion: Clinically acceptable SRT plans for spherical targets were created on a linac with 1 cm MLC. Adding two collimator angles and MLC to arcs each improved conformity. The MLC improved the dose falloff while two collimator angles degraded it. This technique can expand the availability of SRT to patients especially to those who cannot travel to a facility with a dedicated stereotactic radiosurgery machine.« less

Agreement Among RTOG Sarcoma Radiation Oncologists in Contouring Suspicious Peritumoral Edema for Preoperative Radiation Therapy of Soft Tissue Sarcoma of the Extremity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bahig, Houda; Roberge, David, E-mail: david.roberge.chum@ssss.gouv.qc.ca; Bosch, Walter

Purpose: Peritumoral edema may harbor sarcoma cells. The extent of suspicious edema (SE) included in the treatment volume is subject to clinical judgment, balancing the risk of missing tumor cells with excess toxicity. Our goal was to determine variability in SE delineation by sarcoma radiation oncologists (RO). Methods and Materials: Twelve expert ROs were provided with T1 gadolinium and T2-weighted MR images of 10 patients with high-grade extremity soft-tissue sarcoma. Gross tumor volume, clinical target volume (CTV)3cm (3 cm longitudinal and 1.5 cm radial margin), and CTV2cm (2 cm longitudinal and 1 cm radial margin) were contoured by a singlemore » observer. Suspicious peritumoral edema, defined as abnormal signal on T2 images, was independently delineated by all 12 ROs. Contouring agreement was analyzed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. Results: The mean volumes of GTV, CTV2cm, and CTV3cm were, respectively, 130 cm{sup 3} (7-413 cm{sup 3}), 280 cm{sup 3} and 360 cm{sup 3}. The mean consensus volume computed using the STAPLE algorithm at 95% confidence interval was 188 cm{sup 3} (24-565 cm{sup 3}) with a substantial overall agreement corrected for chance (mean kappa = 0.71; range: 0.32-0.87). The minimum, maximum, and mean volume of SE (excluding the GTV) were 4, 182, and 58 cm{sup 3} (representing a median of 29% of the GTV volume). The median volume of SE not included in the CTV2cm and in the CTV3cm was 5 and 0.3 cm{sup 3}, respectively. There were 3 large tumors with >30 cm{sup 3} of SE not included in the CTV3cm volume. Conclusion: Despite the fact that SE would empirically seem to be a more subjective volume, a substantial or near-perfect interobserver agreement was observed in SE delineation in most cases with high-grade soft-tissue sarcomas of the extremity. A median of 97% of the consensus SE is within the CTV2cm (99.8% within the CTV3cm). In a minority of cases, however, significant expansion of the CTVs is required to cover SE.« less

Agreement among RTOG sarcoma radiation oncologists in contouring suspicious peritumoral edema for preoperative radiation therapy of soft tissue sarcoma of the extremity.

PubMed

Bahig, Houda; Roberge, David; Bosch, Walter; Levin, William; Petersen, Ivy; Haddock, Michael; Freeman, Carolyn; Delaney, Thomas F; Abrams, Ross A; Indelicato, Danny J; Baldini, Elizabeth H; Hitchcock, Ying; Kirsch, David G; Kozak, Kevin R; Wolfson, Aaron; Wang, Dian

2013-06-01

Peritumoral edema may harbor sarcoma cells. The extent of suspicious edema (SE) included in the treatment volume is subject to clinical judgment, balancing the risk of missing tumor cells with excess toxicity. Our goal was to determine variability in SE delineation by sarcoma radiation oncologists (RO). Twelve expert ROs were provided with T1 gadolinium and T2-weighted MR images of 10 patients with high-grade extremity soft-tissue sarcoma. Gross tumor volume, clinical target volume (CTV)3cm (3 cm longitudinal and 1.5 cm radial margin), and CTV2cm (2 cm longitudinal and 1 cm radial margin) were contoured by a single observer. Suspicious peritumoral edema, defined as abnormal signal on T2 images, was independently delineated by all 12 ROs. Contouring agreement was analyzed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. The mean volumes of GTV, CTV2cm, and CTV3cm were, respectively, 130 cm(3) (7-413 cm(3)), 280 cm(3) and 360 cm(3). The mean consensus volume computed using the STAPLE algorithm at 95% confidence interval was 188 cm(3) (24-565 cm(3)) with a substantial overall agreement corrected for chance (mean kappa = 0.71; range: 0.32-0.87). The minimum, maximum, and mean volume of SE (excluding the GTV) were 4, 182, and 58 cm(3) (representing a median of 29% of the GTV volume). The median volume of SE not included in the CTV2cm and in the CTV3cm was 5 and 0.3 cm(3), respectively. There were 3 large tumors with >30 cm(3) of SE not included in the CTV3cm volume. Despite the fact that SE would empirically seem to be a more subjective volume, a substantial or near-perfect interobserver agreement was observed in SE delineation in most cases with high-grade soft-tissue sarcomas of the extremity. A median of 97% of the consensus SE is within the CTV2cm (99.8% within the CTV3cm). In a minority of cases, however, significant expansion of the CTVs is required to cover SE. Copyright © 2013 Elsevier Inc. All rights reserved.

Correlation Between the Severity of Cetuximab-Induced Skin Rash and Clinical Outcome for Head and Neck Cancer Patients: The RTOG Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bar-Ad, Voichita, E-mail: voichita.bar-ad@jefferson.edu; Zhang, Qiang; Harari, Paul M.

Purpose: To evaluate the severity of cetuximab-induced skin rash and its correlation with clinical outcome and late skin toxicity in patients with head and neck squamous cell carcinoma treated with chemoradiation therapy and cetuximab. Methods and Materials: Analysis included patients who received loading dose and ≥1 cetuximab dose concurrent with definitive chemoradiation therapy (70 Gy + cisplatin) or postoperative chemoradiation therapy (60-66 Gy + docetaxel or cisplatin). Results: Six hundred two patients were analyzed; 383 (63.6%) developed grade 2 to 4 cetuximab rash. Patients manifesting grade 2 to 4 rash had younger age (P<.001), fewer pack-years smoking history (P<.001), were more likely to be males (P=.04), and hadmore » p16-negative (P=.04) oropharyngeal tumors (P=.003). In univariate analysis, grade 2 to 4 rash was associated with better overall survival (hazard ratio [HR] 0.58, P<.001) and progression-free survival (HR 0.75, P=.02), and reduced distant metastasis rate (HR 0.61, P=.03), but not local-regional failure (HR 0.79, P=.16) relative to grade 0 to 1 rash. In multivariable analysis, HRs for overall survival, progression-free survival, distant metastasis, and local-regional failure were, respectively, 0.68 (P=.008), 0.85 (P=.21), 0.64 (P=.06), and 0.89 (P=.48). Grade ≥2 rash was associated with improved survival in p16-negative patients (HR 0.28 [95% confidence interval 0.11-0.74]) but not in p16-positive patients (HR 1.10 [0.42-2.89]) (P=.05 for interaction). Twenty-five percent of patients with grade 2 to 4 acute in-field radiation dermatitis experienced grade 2 to 4 late skin fibrosis, versus 14% of patients with grade 0 to 1 acute in-field radiation dermatitis (P=.002). Conclusion: Grade 2 to 4 cetuximab rash was associated with better survival, possibly due to reduction of distant metastasis. This observation was noted mainly in p16-negative patients. Grade 2 to 4 acute in-field radiation dermatitis was associated with higher rate of late grade 2 to 4 skin fibrosis.« less

Heart dose exposure as prognostic marker after radiotherapy for resectable stage IIIA/B non-small-cell lung cancer: secondary analysis of a randomized trial.

PubMed

Guberina, M; Eberhardt, W; Stuschke, M; Gauler, T; Heinzelmann, F; Cheufou, D; Kimmich, M; Friedel, G; Schmidberger, H; Darwiche, K; Jendrossek, V; Schuler, M; Stamatis, G; Pöttgen, C

2017-05-01

Heart exposure to ionizing irradiation can cause ischaemic heart disease. The partial heart volume receiving ≥5 Gy (heartV5) was supposed to be an independent prognostic factor for survival after radiochemotherapy for locally advanced non-small-cell lung cancer (NSCLC). But validation of the latter hypothesis is needed under the concurrent risks of lung cancer patients. The ESPATUE phase III trial recruited patients with potentially operable IIIA(N2)/selected IIIB NSCLC between 01/2004 and 01/2013. Cisplatin/paclitaxel induction chemotherapy was given followed by neoadjuvant radiochemotherapy (RT/CT) to 45 Gy (1.5 Gy bid/concurrent cisplatin/vinorelbine). Operable patients were randomized to definitive RT/CT(arm A) or surgery (arm B) and therefore were treated at two different total dose levels of radiotherapy. HeartV5 and mean heart dose (MHD) were obtained from the 3D radiotherapy plans, the prognostic value was analysed using multivariable proportional hazard analysis. A total of 161 patients were randomized in ESPATUE, heartV5 and MHD were obtained from the 3D radiotherapy plans for 155 of these [male/female:105/50, median age 58 (33-74) years, stage IIIA/IIIB: 54/101]. Power analysis revealed a power of 80% of this dataset to detect a prognostic value of heartV5 of the size found in RTOG 0617. Multivariable analysis did not identify heartV5 as an independent prognostic factor for survival adjusting for tumour and clinical characteristics with [hazard ratio 1.005 (0.995-1.015), P = 0.30] or without lower lobe tumour location [hazard ratio 0.999 (0.986-1.012), P = 0.83]. There was no influence of heartV5 on death without tumour progression. Tumour progression, and pneumonia were the leading causes of death representing 65% and 14% of the observed deaths. HeartV5 could not be validated as an independent prognostic factor for survival after neoadjuvant or definitive conformal radiochemotherapy. Tumour progression was the predominant cause of death. Z5 - 22461/2 - 2002-017 (German Federal Office for Radiation Protection). © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Patterns of practice of regional nodal irradiation in breast cancer: results of the European Organization for Research and Treatment of Cancer (EORTC) NOdal Radiotherapy (NORA) survey.

PubMed

Belkacemi, Y; Kaidar-Person, O; Poortmans, P; Ozsahin, M; Valli, M-C; Russell, N; Kunkler, I; Hermans, J; Kuten, A; van Tienhoven, G; Westenberg, H

2015-03-01

Predicting outcome of breast cancer (BC) patients based on sentinel lymph node (SLN) status without axillary lymph node dissection (ALND) is an area of uncertainty. It influences the decision-making for regional nodal irradiation (RNI). The aim of the NORA (NOdal RAdiotherapy) survey was to examine the patterns of RNI. A web-questionnaire, including several clinical scenarios, was distributed to 88 EORTC-affiliated centers. Responses were received between July 2013 and January 2014. A total of 84 responses were analyzed. While three-dimensional (3D) radiotherapy (RT) planning is carried out in 81 (96%) centers, nodal areas are delineated in only 51 (61%) centers. Only 14 (17%) centers routinely link internal mammary chain (IMC) and supraclavicular node (SCN) RT indications. In patients undergoing total mastectomy (TM) with ALND, SCN-RT is recommend by 5 (6%), 53 (63%) and 51 (61%) centers for patients with pN0(i+), pN(mi) and pN1, respectively. Extra-capsular extension (ECE) is the main factor influencing decision-making RNI after breast conserving surgery (BCS) and TM. After primary systemic therapy (PST), 49 (58%) centers take into account nodal fibrotic changes in ypN0 patients for RNI indications. In ypN0 patients with inner/central tumors, 23 (27%) centers indicate SCN-RT and IMC-RT. In ypN1 patients, SCN-RT is delivered by less than half of the centers in patients with ypN(i+) and ypN(mi). Twenty-one (25%) of the centers recommend ALN-RT in patients with ypN(mi) or 1-2N+ after ALND. Seventy-five (90%) centers state that age is not considered a limiting factor for RNI. The NORA survey is unique in evaluating the impact of SLNB/ALND status on adjuvant RNI decision-making and volumes after BCS/TM with or without PST. ALN-RT is often indicated in pN1 patients, particularly in the case of ECE. Besides the ongoing NSABP-B51/RTOG and ALLIANCE trials, NORA could help to design future specific RNI trials in the SLNB era without ALND in patients receiving or not PST. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Student Use of Out-of-Class Study Groups in an Introductory Undergraduate Biology Course

PubMed Central

Rybczynski, Stephen M.; Schussler, Elisabeth E.

2011-01-01

Self-formed out-of-class study groups may benefit student learning; however, few researchers have quantified the relationship between study group use and achievement or described changes in study group usage patterns over a semester. We related study group use to performance on content exams, explored patterns of study group use, and qualitatively described student perceptions of study groups. A pre- and posttest were used to measure student content knowledge. Internet-based surveys were used to collect quantitative data on exam performance and qualitative data on study group usage trends and student perceptions of study groups. No relationship was found between gains in content knowledge and study group use. Students who participated in study groups did, however, believe they were beneficial. Four patterns of study group use were identified: students either always (14%) or never (55%) used study groups, tried but quit using them (22%), or utilized study groups only late in the semester (9%). Thematic analysis revealed preconceptions and in-class experiences influence student decisions to utilize study groups. We conclude that students require guidance in the successful use of study groups. Instructors can help students maximize study group success by making students aware of potential group composition problems, helping students choose group members who are compatible, and providing students materials on which to focus their study efforts. PMID:21364102

Me against we: in-group transgression, collective shame, and in-group-directed hostility.

PubMed

Piff, Paul K; Martinez, Andres G; Keltner, Dacher

2012-01-01

People can experience great distress when a group to which they belong (in-group) is perceived to have committed an immoral act. We hypothesised that people would direct hostility toward a transgressing in-group whose actions threaten their self-image and evoke collective shame. Consistent with this theorising, three studies found that reminders of in-group transgression provoked several expressions of in-group-directed hostility, including in-group-directed hostile emotion (Studies 1 and 2), in-group-directed derogation (Study 2), and in-group-directed punishment (Study 3). Across studies, collective shame-but not the related group-based emotion collective guilt-mediated the relationship between in-group transgression and in-group-directed hostility. Implications for group-based emotion, social identity, and group behaviour are discussed.

Study Groups: Conduit for Reform.

ERIC Educational Resources Information Center

Makibbin, Shirley S.; Sprague, Marsha M.

This conference presentation describes study groups as a mechanism for changing teacher behavior. The history of study groups is discussed, beginning with the first American study groups organized by Benjamin Franklin; the Chautauqua Literary and Scientific Circle; the waning of study groups in the early 20th century as college enrollment…

Study groups: are they effective in preparing students for NCLEX-RN?

PubMed

Ashley, J; O'Neil, J

1994-10-01

The effectiveness of faculty-directed study groups as an intervention to prepare nurse candidates for NCLEX-RN was evaluated. The NCLEX-RN performance of a baccalaureate class who had participated in study groups was compared to the performance of a prior class who had not participated in study groups. Academic subgroups within the classes were compared to determine if study groups were equally effective across levels of academic achievement. The possible reasons for the significant difference in the NCLEX-RN passing rate between "at-risk" students who participated in study groups and at-risk students who did not participate in study groups are discussed. Discussion also considers possible factors influencing the generally better performance of study group participants at all academic levels. Suggestions for future intervention research direct attention to time intensity of interventions and research control through random assignments to treatment groups.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pokhrel, D; Badkul, R; Jiang, H

Purpose: To compare dose distributions calculated using the iPlan XVMC algorithm and heterogeneities corrected/uncorrected Pencil Beam (PB-hete/PB-homo) algorithms for SBRT treatments of lung tumors. Methods: Ten patients with centrally located solitary lung tumors were treated using MC-based SBRT to 60Gy in 5 fractions for PTVV100%=95%. ITV was delineated on MIP-images based on 4D-CT scans. PTVs(ITV+5mm margins) ranged from 10.1–106.5cc(mean=48.6cc). MC-SBRT plans were generated with a combination of non-coplanar conformal arcs/beams using iPlan-XVMC-algorithm (BrainLABiPlan ver.4.1.2) for Novalis-TX consisting of HD-MLCs and 6MV-SRS(1000MU/min) mode, following RTOG 0813 dosimetric criteria. For comparison, PB-hete/PB-homo algorithms were used to re-calculate dose distributions using same beammore » configurations, MLCs/monitor units. Plans were evaluated with isocenter/maximal/mean doses to PTV. Normal lung doses were evaluated with V5/V10/V20 and mean-lung-dose(MLD), excluding PTV. Other OAR doses such as maximal spinal cord/2cc-esophagus/max bronchial tree (BT/maximal heart doses were tabulated. Results: Maximal/mean/isocenter doses to PTV calculated by PB-hete were uniformly larger than MC plans by a factors of 1.09/1.13/1.07, on average, whereas they were consistently lower by PB-homo by a factors of 0.9/0.84/0.9, respectively. The volume covered by 5Gy/10Gy/20Gy isodose-lines of the lung were comparable (average within±3%) when calculated by PB-hete compared to XVMC, but, consistently lower by PB-homo by a factors of 0.90/0.88/0.85, respectively. MLD was higher with PB-hete by 1.05, but, lower by PB-homo by 0.9, on average, compared to XVMC. XVMC max-cord/max-BT/max-heart and 2cc of esophagus doses were comparable to PB-hete; however, PB-homo underestimates by a factors of 0.82/0.89/0.88/0.86, on average, respectively. Conclusion: PB-hete significantly overestimates dose to PTV relative to XVMC -hence underdosing the target. MC is more complex and accurate with tissue-heterogeneities.The magnitude of variation significantly varies with ‘small-island-tumor’ surrounded by low-density lung tissues -PB algorithms lacks later electron scattering. Dose calculation with XVMC for lung SBRT is routinely performed in our clinic, its performance for head'neck/sinus cases will also be investigated.« less

Clinical observation of 73 nasopharyngeal carcinoma patients treated by helical tomotherapy: the China experience.

PubMed

Ren, G; Du, L; Ma, L; Feng, L-C; Zhou, G-X; Qu, B-L; Xu, S-P; Xie, C-B; Ou, G-M; Li, F; Zhang, X-X; Yang, J

2011-06-01

The preliminary short-term clinical outcome of 73 nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy at our cancer institute has been evaluated. Between September 2007 and September 2009, 73 newly diagnosed NPC patients were treated with helical tomotherapy. The distributions of clinical stages according to the UICC 2002 Staging System were: 6, 27, 24, and 16 for Stage I, IIa-b, III, and IVa-b, respectively. The prescription dose was 70-74 Gy/33F to planning gross tumor volume containing the primary tumor and positive lymph nodes, with 60-62.7 Gy/33F to high risk planning target volume, while delivering 52-56 Gy/33F to low risk planning target volume. Twenty-four patients were treated with radiation therapy as single modality, 25 with concurrent cisplatin-based chemotherapy with or without anti-EGFR monoclonal antibody therapy, and 24 with concurrent anti-EGFR monoclonal antibody therapy. Setup errors were analyzed. Side-effects were evaluated with the established RTOG/EORTC criteria. Average beam-on-time was 468.8 sec/F (396.7-696.1 sec). The setup errors in the lateral, longitudinal and vertical directions were 0.00 ± 1.79 mm, -0.55± 2.17 mm and 0.38 ± 1.43 mm, corresponding to 3.80 mm, 4.20 mm, and 2.46 mm as the CTV-PTV margin in these directions. The grade 0, 1, 2 and 3 acute skin toxicity was 2.7%, 76.7%, 13.8% and 6.8%; the grade 0, 1, 2 and 3 acute mucositis was 1.4%, 32.9%, 60.2% and 5.5%; and the grade 0, 1, 2 and 3 acute xerostomia was 4.0%, 45.3%, 50.7% and 0, respectively. Only 5 patients suffered from grade 3 or 4 leucopenia. Xerostomia resolved with passing of time and no grade 2 or more xerostomia was noted one year after radiation therapy. Concurrent chemotherapy significantly increased incidence of severe acute toxicities. One month after radiation therapy the remission rates of primary tumor and positive lymph nodes were 91.8% and 98.1%, respectively. The median follow-up was 14.8 months. The one-year relapse-free survival, distant metastasis-free survival and overall survival was 95.6%, 97.2% and 94.8%, respectively. In conclusion, the incidence of severe acute toxicities and late xerostomia was relatively infrequent for NPC patients treated with helical tomotherapy. The long-term clinical outcome for these patients is under investigation.

Dosimetric Comparison between Single and Dual Arc-Volumetric Modulated Arc Radiotherapy and Intensity Modulated Radiotherapy for Nasopharyngeal Carcinoma Using a Simultaneous Integrated Boost Technique

PubMed Central

Radhakrishnan, Sivakumar; Chandrasekaran, Anuradha; Sarma, Yugandhar; Balakrishnan, Saranganathan; Nandigam, Janardhan

2017-01-01

Backround: Plan quality and performance of dual arc (DA) volumetric modulated arc therapy (VMAT), single arc (SA) VMAT and nine field (9F) intensity modulated radiotherapy were compared using a simultaneous integrated boost (SIB) technique. Methods: Twelve patients treated in Elekta Synergy Platform (mlci2) by 9F-IMRT were replanned with SA/DA-VMAT using a CMS Monaco Treatment Planning System (TPS) with Monte Carlo simulation. Target delineation was conducted as per Radiation Therapy Oncology Protocols (RTOG0225 and 0615). A 70Gy dose prescribed to PTV70 and 61Gy to PTV61 in 33 fractions was applied for the SIB technique. The conformity index (CI) and homogeneity index (HI) for targets and the mean dose and maximum dose for OAR’s, treatment delivery time (min), monitor units (MUs) per fraction, normal tissue integral dose and patient specific quality assurance were analysed. Results: Acceptable target coverage was achieved for PTV70 and PTV61 with all the planning techniques. No significant differences were observed except for D98 (PTV61), CI(PTV70) and HI(PTV61). Maximum dose (Dmax) to the spinal cord was lower in DA-VMAT than 9F-IMRT (p=0.002) and SA-VMAT (p=0.001). D50 (%) of parotid glands was better controlled by 9F-IMRT (p=0.001) and DA-VMAT (p=0.001) than SA-VMAT. A lower mean dose to the larynx was achieved with 9F-IMRT (P=0.001) and DA-VMAT (p=0.001) than with SA-VMAT. DA-VMAT achieved higher CI of PTV70 (P= 0.005) than SA-VMAT. For PTV61, DA-VMAT (P=0.001) and 9F-IMRT (P=0.001) achieved better HI than SA-VMAT. The average treatment delivery times were 7.67mins, 3.35 mins, 4.65 mins for 9F-IMRT, SA-VMAT and DA-VMAT, respectively. No significant difference were observed in MU/fr (p=0.9) and NTID (P=0.90) and the patient quality assurance pass rates were >95% (gamma analysis I3mm, 3%). Conclusion: DA-VMAT showed better conformity over target dose and spared the OARs better or equal to IMRT. SA-VMAT could not spare the OARs well. DA-VMAT offered shorter delivery time than IMRT without compromising the plan quality. PMID:28612593

Dosimetric Comparison between Single and Dual Arc-Volumetric Modulated Arc Radiotherapy and Intensity Modulated Radiotherapy for Nasopharyngeal Carcinoma Using a Simultaneous Integrated Boost Technique

PubMed

Radhakrishnan, Sivakumar; Chandrasekaran, Anuradha; Sarma, Yugandhar; Balakrishnan, Saranganathan; Nandigam, Janardhan

2017-05-01

Backround: Plan quality and performance of dual arc (DA) volumetric modulated arc therapy (VMAT) , single arc (SA) VMAT and nine field (9F) intensity modulated radiotherapy were compared using a simultaneous integrated boost (SIB) technique. Methods: Twelve patients treated in Elekta Synergy Platform (mlci2) by 9F-IMRT were replanned with SA/DA-VMAT using a CMS Monaco Treatment Planning System (TPS) with Monte Carlo simulation. Target delineation was conducted as per Radiation Therapy Oncology Protocols (RTOG0225 and 0615). A 70Gy dose prescribed to PTV70 and 61Gy to PTV61 in 33 fractions was applied for the SIB technique. The conformity index (CI) and homogeneity index (HI) for targets and the mean dose and maximum dose for OAR’s, treatment delivery time (min), monitor units (MUs) per fraction, normal tissue integral dose and patient specific quality assurance were analysed. Results: Acceptable target coverage was achieved for PTV70 and PTV61 with all the planning techniques. No significant differences were observed except for D98 (PTV61), CI(PTV70) and HI(PTV61). Maximum dose (Dmax) to the spinal cord was lower in DA-VMAT than 9F-IMRT (p=0.002) and SA-VMAT (p=0.001). D50 (%) of parotid glands was better controlled by 9F-IMRT (p=0.001) and DA-VMAT (p=0.001) than SA-VMAT. A lower mean dose to the larynx was achieved with 9F-IMRT (P=0.001) and DA-VMAT (p=0.001) than with SA-VMAT. DA-VMAT achieved higher CI of PTV70 (P= 0.005) than SA-VMAT. For PTV61, DA-VMAT (P=0.001) and 9F-IMRT (P=0.001) achieved better HI than SA-VMAT. The average treatment delivery times were 7.67mins, 3.35 mins, 4.65 mins for 9F- IMRT, SA-VMAT and DA-VMAT, respectively. No significant difference were observed in MU/fr (p=0.9) and NTID (P=0.90) and the patient quality assurance pass rates were >95% (gamma analysis Ґ3mm, 3%). Conclusion: DA-VMAT showed better conformity over target dose and spared the OARs better or equal to IMRT. SA-VMAT could not spare the OARs well. DA-VMAT offered shorter delivery time than IMRT without compromising the plan quality. Creative Commons Attribution License

Watching MOOCs Together: Investigating Co-Located MOOC Study Groups

ERIC Educational Resources Information Center

Li, Nan; Verma, Himanshu; Skevi, Afroditi; Zufferey, Guillaume; Blom, Jan; Dillenbourg, Pierre

2014-01-01

Research suggests that massive open online course (MOOC) students prefer to study in groups, and that social facilitation within the study groups may render the learning of difficult concepts a pleasing experience. We report on a longitudinal study that investigates how co-located study groups watch and study MOOC videos together. The study was…

The effect of deep shoulder infections on patient outcomes after arthroscopic rotator cuff repair: a retrospective comparative study.

PubMed

Atesok, Kivanc; MacDonald, Peter; Leiter, Jeff; McRae, Sheila; Singh, Mandip; Stranges, Greg; Old, Jason

2017-01-01

The purpose of this study was to evaluate the effects of deep shoulder infections after RCR on patient outcomes. A retrospective chart review was conducted involving all patients with deep shoulder infections after arthroscopic RCR (study group). Another group of patients who were matched with the study group by age, gender and rotator cuff tear size, and did not develop deep shoulder infections after arthroscopic RCR were randomly identified (control group). The two groups were compared in terms of time to start physiotherapy, shoulder function, and delay in return to work. There were 10 patients in each group. The mean time to start physiotherapy after surgery was 145.3 (SD=158.8) days for the study group and 40.0 (SD=13.7) days for the control group (p=.051). The average forward elevation of the operated shoulder was 133 (SD=33.4) degrees for the study group, and 172 (SD=12.0) degrees for the control group (p=0.003). The average time to return to work at preoperative level was 5.6 months for the study group and 3 months for the control group. Deep shoulder infections after RCR significantly impedes time to start physiotherapy, shoulder function, and patients' ability to return to work. III b [retrospective comparative (case-control) study].

Auditory evoked potentials: predicting speech therapy outcomes in children with phonological disorders.

PubMed

Leite, Renata Aparecida; Wertzner, Haydée Fiszbein; Gonçalves, Isabela Crivellaro; Magliaro, Fernanda Cristina Leite; Matas, Carla Gentile

2014-03-01

This study investigated whether neurophysiologic responses (auditory evoked potentials) differ between typically developed children and children with phonological disorders and whether these responses are modified in children with phonological disorders after speech therapy. The participants included 24 typically developing children (Control Group, mean age: eight years and ten months) and 23 children clinically diagnosed with phonological disorders (Study Group, mean age: eight years and eleven months). Additionally, 12 study group children were enrolled in speech therapy (Study Group 1), and 11 were not enrolled in speech therapy (Study Group 2). The subjects were submitted to the following procedures: conventional audiological, auditory brainstem response, auditory middle-latency response, and P300 assessments. All participants presented with normal hearing thresholds. The study group 1 subjects were reassessed after 12 speech therapy sessions, and the study group 2 subjects were reassessed 3 months after the initial assessment. Electrophysiological results were compared between the groups. Latency differences were observed between the groups (the control and study groups) regarding the auditory brainstem response and the P300 tests. Additionally, the P300 responses improved in the study group 1 children after speech therapy. The findings suggest that children with phonological disorders have impaired auditory brainstem and cortical region pathways that may benefit from speech therapy.

Outcomes of Group Care for Youth: A Review of Comparative Studies

ERIC Educational Resources Information Center

Lee, Bethany R.; Bright, Charlotte L.; Svoboda, Deborah V.; Fakunmoju, Sunday; Barth, Richard P.

2011-01-01

Objective: The purpose of this study was to review empirical evidence of the effects of placement in group care compared to other interventions. Method: Two-group empirical studies were identified and effect sizes for all reported outcomes were calculated. Results: Nineteen two-group studies were found that compared group care with family foster…

The Role of Perceived In-group Moral Superiority in Reparative Intentions and Approach Motivation.

PubMed

Szabó, Zsolt P; Mészáros, Noémi Z; Csertő, István

2017-01-01

Three studies examined how members of a national group react to in-group wrongdoings. We expected that perceived in-group moral superiority would lead to unwillingness to repair the aggression. We also expected that internal-focused emotions such as group-based guilt and group-based shame would predict specific, misdeed-related reparative intentions but not general approach motivation toward the victim groups. In Study 1, facing the in-group's recent aggression, participants who believed that the Hungarians have been more moral throughout their history than members of other nations, used more exonerating cognitions, experienced less in-group critical emotions and showed less willingness to provide reparations for the members of the victim group. Study 2 and Study 3 confirmed most findings of Study 1. Perceived in-group moral superiority directly or indirectly reduced willingness to provide either general or specific reparations, while internally focused in-group critical emotions predicted specific misdeed-related reparative intentions but not general approach motivation. The role of emotional attachment to the in-group is considered.

[Efficacy and safety of Xiaoaiping combined with chemotherapy in the treatment of advanced esophageal cancer].

PubMed

Wang, F; Fan, Q X; Wang, H H; Han, D M; Song, N S; Lu, H

2017-06-23

Objective: To evaluate the efficacy and safety of Xiaoaiping combined with chemotherapy in the treatment of advanced esophageal cancer. Methods: This is a multi-center, randomized, open label and parallel controlled study. A total of 124 advanced esophageal cancer patients with Karnofsky Performance Status (KPS) score ≥60 and expected survival time≥3 months were enrolled. We adopted design and divided the patients into study and control group. The patients in study group received Xiaoaiping combined with S-1 and cisplatin. The control group received S-1 and cisplatin. Each group included 62 patients and 21 days as a treatment cycle. The efficacy and adverse events in patients of the two groups were observed and compared. Results: 57 patients in the study group and 55 in the control group were included in efficacy assessment. The response rate was 54.4% and 34.5% in the study group and control group, respectively( P <0.05). Disease control rates were 86.0% and 69.1%, respectively( P <0.05). The median progression-free survival (PFS) was 7.97 in the study group and 6.43 months in the control group( P <0.05). The median overall survival(OS) was 12.93 in the study group and 10.93 months in the control group( P <0.05). The most common adverse events in the two groups were nausea and vomiting, thrombocytopenia, anemia, neutropenia, liver damage, pigmentation, oral mucositis, renal impairment and diarrhea. The incidences of nausea, vomiting, thrombocytopenia, leukopenia, neutropenia and diarrhea in the study group were significantly higher than those in the control group( P <0.05). Conclusion: Xiaoaiping combined with S-1 and cisplatin significantly increased response rate, and prolongedpatients' survival in patients with advanced esophageal cancer.

Comparison of epidemiology and outcomes of arthroscopic rotator cuff repair for anterosuperior and posterosuperior rotator cuff tears.

PubMed

Teratani, Takeshi

2017-12-01

The purpose of this study was to investigate the prevalence, epidemiology, and outcomes of anterosuperior (A group) rotator cuff tears (RCTs) and posterosuperior (P group) RCTs treated by arthroscopic rotator cuff repair (ARCR). A total of 67 A group patients and 14 P group patients were included in the study. The prevalence of the A group (82.3%) was significantly higher than that of the P group (17.7%). The outcomes in both groups were good, even though the A group had a higher rate of injury to the LHB than the P group. Level III, case-control Study, treatment study.

[A Critical Condition of Clinical Studies in Japan -- A Battle of Clinical Study Groups].

PubMed

Furukawa, Hiroshi

2016-04-01

The post-marketing clinical study groups have been losing their activity due to stop of financial support. As the result, clinical study groups cannot achieve any EBM for treatment guidelines. Financial supports should be restarted immediately not to extinguish the post-marketing clinical studies and study groups.

Feel like you belong: on the bidirectional link between emotional fit and group identification in task groups

PubMed Central

Delvaux, Ellen; Meeussen, Loes; Mesquita, Batja

2015-01-01

Three studies investigated the association between members’ group identification and the emotional fit with their group. In the first study, a cross-sectional study in a large organization, we replicated earlier research by showing that group identification and emotional fit are positively associated, using a broader range of emotions and using profile correlations to measure group members’ emotional fit. In addition, in two longitudinal studies, where groups of students were followed at several time points during their collaboration on a project, we tested the directionality of the relationship between group identification and emotional fit. The results showed a bidirectional, positive link between group identification and emotional fit, such that group identification and emotional fit either mutually reinforce or mutually dampen each other over time. We discuss how these findings increase insights in group functioning and how they may be used to change group processes for better or worse. PMID:26300806

[Teaching of clinical reasoning to medical students using prototypical clinical cases].

PubMed

Montaldo L, Gustavo; Herskovic L, Pedro

2013-07-01

Clinical reasoning is the most important competente in the training process of a physician. To develop a method for teaching clinical reasoning based on prototypes of clinical cases. The study was conducted on sixty-four third year medical students. The study and control groups attended lectures and tutorial sessions with patients. The study group attended additionally discussion seminars of prototypical clinical cases. A clinical reasoning test was applied at the start and end of the learning period to both groups. At the end of the study, the opinions of students of the study group were collected in a focus group. After the learning period, both groups significantly increased their clinical reasoning skills. However, the improvement in the study group was more than double than that of the control group. The absolute improvement in the study group was 30.9%. Students interviewed in the focus group were unanimous in expressing their satisfaction in each and every aspect discussed. The teaching of clinical reasoning to third year medical students by means of pattern recognition in seminars with clinical cases improved significantly their skills.

Group virtue: the importance of morality (vs. competence and sociability) in the positive evaluation of in-groups.

PubMed

Leach, Colin Wayne; Ellemers, Naomi; Barreto, Manuela

2007-08-01

Although previous research has focused on competence and sociability as the characteristics most important to positive group evaluation, the authors suggest that morality is more important. Studies with preexisting and experimentally created in-groups showed that a set of positive traits constituted distinct factors of morality, competence, and sociability. When asked directly, Study 1 participants reported that their in-group's morality was more important than its competence or sociability. An unobtrusive factor analytic method also showed morality to be a more important explanation of positive in-group evaluation than competence or sociability. Experimental manipulations of morality and competence (Study 4) and morality and sociability (Study 5) showed that only in-group morality affected aspects of the group-level self-concept related to positive evaluation (i.e., pride in, or distancing from, the in-group). Consistent with this finding, identification with experimentally created (Study 2b) and preexisting (Studies 4 and 5) in-groups predicted the ascription of morality, but not competence or sociability, to the in-group.

[A strategic family medicine model for controlling borderline and mild arterial hypertension].

PubMed

Uzcátegui Contreras, D; Granadillo Vera, D; Salinas, P J; Alvarez, N

1999-10-31

To research on the relationship of the patient and his/her family as a non-pharmacological factor for blood hypertension. To determine whether a hyposodic, hypocaloric, hypofat, and hypocholesterolemic diet decreases the blood tension. To determine whether physical exercises in the patient and his/her family help to reduce the hypertension. To observe whether the psychological therapy of muscles relaxation helps to reduce the hypertension. To evaluate in the sample of families, the experience of each member, as well as their suggestions and complaints about the programme. To design the strategic model to control the blood tension by ambulatory means. Controlled intervention study, descriptive, non-randomized, prospective. PLACEMENT: Primary care. Study group of 10 patients, 10 wives, and 12 children, and control group of 10 patients excluding family members. With both groups (study and control) there were meetings every 15 days for 6 months according to an established schedule. In the meetings there were given talks, pamphlets, physical exercises, muscles relaxation therapy, all about blood hypertension. There were questionnaires before and after each activity. MEASURING AND MAIN RESULTS: In both groups (study and control) there was a statistically significant (t < 0.01) reduction in the weight. The blood systolic tension decreased in both positions, seated and standing, in the study group (difference statistically significant) but not so in the control group, although there was a non-significant difference (decrease of 1.5 mmHg) in the seated position. The diastolic tension decreased significantly in the study group both in seated and standing positions, not so in the control group. The study sample showed that systolic tension seated and standing had a statistically significant reduction in the study group but not so in the control group. The weight had statistically significant reduction in both study and control groups. Total cholesterol had statistically significant decrease in the study group but not in the control group. HDL-C had statistically significant reduction in the study group; in the control group there was a decrease but not statistically significant. The triglycerides did not decrease statistically significant in any of the groups (study and control).

[An efficacy and safety study of bifidobacterium tetragenous viable bacteria tablets in the treatment of constipation in patients with type 2 diabetes mellitus].

PubMed

Yuan, T; Zhao, W G; Cao, Y; Li, Q; Yao, M X; Hao, X X; Yu, H; Jiang, C E; Wang, H F; Wang, S P; Wei, X B; Qiu, W

2018-04-01

Objective: The incidence of gastrointestinal symptoms in diabetes is higher than that of non-diabetes. Thus, the aim of the present study was to observe the efficacy and safety of bifidobacterium tetragenous viable bacteria tablets in the treatment of constipation in patients with type 2 diabetes mellitus. Methods: This is a multicenter, randomized, double-blind, placebo-controlled, parallel group-comparison clinical research. The subjects were randomly divided into study group and control group according to 1∶1 ratio by computer generated random number method. The subjects were either treated with bifidobacterium tetragenous viable bacteria tablets (study group) or placebo (control group) for eight weeks, and they were followed up for four weeks without changing foundation therapy for diabetes. The primary outcome was the change of complete spontaneous bowel movements (CSBMs). Results: A total of 234 subjects (the study group:116 cases; the control group: 118 cases) from 7 centers were included in the present study. The baseline characteristics were comparable between the two groups. In the study group, the CSBMs at 0, 2, 4, 8 and 12 weeks were 0.0 (0.0, 1.0) , 1.0 (0.5, 2.0) , 2.0 (1.0, 3.0) , 3.0 (2.0, 3.5) , 2.0 (1.0, 3.0) times per week, respectively, while the CSBMs of the control group at each corresponding weeks were 0.0 (0.0, 1.0) , 1.0 (0.0, 1.5) , 1.0 (0.0, 1.5) , 1.0 (0.0, 2.0) , 1.0 (0.0, 1.5) times per week, respectively. There is significant difference in CSBMs between the two groups ( P< 0.05). Moreover, after 12 weeks treatment, the CSBMs over spontaneous bowel movements (SBMs) ratio in the study group was higher than that in the control group [0.53 (0.40, 0.67) vs 0.33 (0.00,0.50), P= 0.048], indicating a more complete evacuation sensation in the study group. More subjects in the study group (66.38%) reached Bristol stool classification of normal criteria than those in the control group (48.31%, P= 0.005). There were significantly improvement of bowel function index in the study group [study group 42.7 (33.3, 56.7), control group 60.6 (51.7, 75.7), P< 0.000 1]. Furthermore, the symptoms of constipation was improved, and the satisfaction for the treatment was high in the study group. There were no significant differences of the safety indicators between the two groups. Conclusions: Bifidobacterium tetragenous viable bacteria tablets can be used in patients with type 2 diabetes mellitus and constipation. Compared with placebo, it improves constipation and has no obvious adverse effects.

Recruitment Modeling: An Analysis and an Application to the Study of Male-Female Differences in Intelligence

ERIC Educational Resources Information Center

Hunt, Earl; Madhyastha, Tara

2008-01-01

Studies of group differences in intelligence often invite conclusions about groups in general from studies of group differences in selected populations. The same design is used in the study of group differences in other traits as well. Investigators observe samples from two groups (e.g. men and women) in some accessible population, but seek to…

Endotoxemia and mortality prediction in ICU and other settings: underlying risk and co-detection of gram negative bacteremia are confounders

PubMed Central

2012-01-01

Introduction The interdependence between endotoxemia, gram negative (GN) bacteremia and mortality has been extensively studied. Underlying patient risk and GN bacteremia types are possible confounders of the relationship. Methods Published studies with ≥10 patients in either ICU or non-ICU settings, endotoxemia detection by limulus assay, reporting mortality proportions and ≥1 GN bacteremia were included. Summary odds ratios (OR) for mortality were derived across all studies by meta-analysis for the following contrasts: sub-groups with either endotoxemia (group three), GN bacteremia (group two) or both (group one) each versus the group with neither detected (group four; reference group). The mortality proportion for group four is the proxy measure of study level risk within L'Abbé plots. Results Thirty-five studies were found. Among nine studies in an ICU setting, the OR for mortality was borderline (OR <2) or non-significantly increased for groups two (GN bacteremia alone) and three (endotoxemia alone) and patient group one (GN bacteremia and endotoxemia co-detected) each versus patient group four (neither endotoxemia nor GN bacteremia detected). The ORs were markedly higher for group one versus group four (OR 6.9; 95% confidence interval (CI), 4.4 -to 11.0 when derived from non-ICU studies. The distributions of Pseudomonas aeruginosa and Escherichia coli bacteremias among groups one versus two are significantly unequal. Conclusions The co-detection of GN bacteremia and endotoxemia is predictive of increased mortality risk versus the detection of neither but only in studies undertaken in a non-ICU setting. Variation in GN bacteremia species types and underlying risk are likely unrecognized confounders in the individual studies. PMID:22871090

Visual indices of motor vehicle drivers in relation to road safety in Nigeria.

PubMed

Emerole, C G; Nneli, R O

2013-06-30

This study assessed the visual profile of motor vehicle drivers in Owerri, Nigeria and to analyse the relationship between the various aspects of visual function in relation to road safety. A cross-sectional descriptive study of 150 commercial vehicles drivers and 130 private vehicles drivers was conducted between November 2005 and February 2006. Data were obtained using structured interviewer administered questionnaires and clinical examination was done. Standards procedures were used to determine visual indices. Data from the better eye (eye with a better visual acuity according to international and national standards) were reported, except in the analysis of near vision of the respondents. Twenty percent of the study group had normal visual acuity of ≥6/6 compared with 46.2% in the control group. The tonometric value in 88.0% and 93.1% of study and control groups respectively was less than 24mmHg. Both groups (96.8%) had normal confrontation visual field while 95.3% of study group and 97.7% of control group had normal colour vision. The most prevailing eye conditions that may reduce visual acuity were pterygium (51.3% in study group and 13.8% in the control group), retinopathy (16.7% of study group and 6.2% of control group) and glaucoma (12.0% and 6.9% of study and control groups respectively). Nineteen percent of the study group had regular eye examination compared with 38.5% in the control group. Alcohol consumption was 64.7% in the study group and 32.3% in the control group. Most of the commercial motor drivers in Owerri, Nigeria did not meet the Federal Road Safety Commission visual acuity standard for commercial motor drivers. Visual impairments and poor visibility are strongly associated with RTA among Nigerian motor vehicle drivers. Visual acuity and visual health care were poor among commercial motor drivers. There is need for renewed efforts to enforce a compulsory periodic visual examination for drivers, and to ensure that visual requirements for driving are met.

The cross-category effect: mere social categorization is sufficient to elicit an own-group bias in face recognition.

PubMed

Bernstein, Michael J; Young, Steven G; Hugenberg, Kurt

2007-08-01

Although the cross-race effect (CRE) is a well-established phenomenon, both perceptual-expertise and social-categorization models have been proposed to explain the effect. The two studies reported here investigated the extent to which categorizing other people as in-group versus out-group members is sufficient to elicit a pattern of face recognition analogous to that of the CRE, even when perceptual expertise with the stimuli is held constant. In Study 1, targets were categorized as members of real-life in-groups and out-groups (based on university affiliation), whereas in Study 2, targets were categorized into experimentally created minimal groups. In both studies, recognition performance was better for targets categorized as in-group members, despite the fact that perceptual expertise was equivalent for in-group and out-group faces. These results suggest that social-cognitive mechanisms of in-group and out-group categorization are sufficient to elicit performance differences for in-group and out-group face recognition.

Role of intrapartum transcervical amnioinfusion in patients with meconium-stained amniotic fluid.

PubMed

Bhatia, Pushpa; Reena, Kumari; Nangia, Sangita

2013-03-01

The study was undertaken to evaluate maternal, perinatal outcomes following transcervical intrapartum amnioinfusion in women with meconium-stained amniotic fluid. A prospective comparative study was conducted on 100 women with meconium-stained amniotic fluid in labor. Group A: study group (50 cases) received amnioinfusion. Group B: control group (50 cases) did not receive amnioinfusion. FHR monitoring was done using cardiotocography. Significant relief from variable decelerations was seen in 68.18 % cases in the amnioinfusion group as compared to 7.1 % cases in the control group. 78 % cases who were given amnioinfusion had vaginal delivery as compared to 18 % cases in the control group. Fourteen percent cases in the study group had cesarean delivery as compared to 68 % cases in the control group. Meconium aspiration syndrome was seen in six percent neonates in the study group as compared to 20 % in the control group. Two neonates died in the control group due to meconium aspiration syndrome. There was no maternal mortality or major maternal complication. Intrapartum transcervical amnioinfusion is valuable in patients with meconium-stained amniotic fluid.

The Role of Perceived In-group Moral Superiority in Reparative Intentions and Approach Motivation

PubMed Central

Szabó, Zsolt P.; Mészáros, Noémi Z.; Csertő, István

2017-01-01

Three studies examined how members of a national group react to in-group wrongdoings. We expected that perceived in-group moral superiority would lead to unwillingness to repair the aggression. We also expected that internal-focused emotions such as group-based guilt and group-based shame would predict specific, misdeed-related reparative intentions but not general approach motivation toward the victim groups. In Study 1, facing the in-group’s recent aggression, participants who believed that the Hungarians have been more moral throughout their history than members of other nations, used more exonerating cognitions, experienced less in-group critical emotions and showed less willingness to provide reparations for the members of the victim group. Study 2 and Study 3 confirmed most findings of Study 1. Perceived in-group moral superiority directly or indirectly reduced willingness to provide either general or specific reparations, while internally focused in-group critical emotions predicted specific misdeed-related reparative intentions but not general approach motivation. The role of emotional attachment to the in-group is considered. PMID:28620333

Clinical applications of advanced rotational radiation therapy

NASA Astrophysics Data System (ADS)

Nalichowski, Adrian

Purpose: With a fast adoption of emerging technologies, it is critical to fully test and understand its limits and capabilities. In this work we investigate new graphic processing unit (GPU) based treatment planning algorithm and its applications in helical tomotherapy dose delivery. We explore the limits of the system by applying it to challenging clinical cases of total marrow irradiation (TMI) and stereotactic radiosurgery (SRS). We also analyze the feasibility of alternative fractionation schemes for total body irradiation (TBI) and TMI based on reported historical data on lung dose and interstitial pneumonitis (IP) incidence rates. Methods and Materials: An anthropomorphic phantom was used to create TMI plans using the new GPU based treatment planning system and the existing CPU cluster based system. Optimization parameters were selected based on clinically used values for field width, modulation factor and pitch. Treatment plans were also created on Eclipse treatment planning system (Varian Medical Systems Inc, Palo Alto, CA) using volumetric modulated arc therapy (VMAT) for dose delivery on IX treatment unit. A retrospective review was performed of 42 publications that reported IP rates along with lung dose, fractionation regimen, dose rate and chemotherapy. The analysis consisted of nearly thirty two hundred patients and 34 unique radiation regimens. Multivariate logistic regression was performed to determine parameters associated with IP and establish does response function. Results: The results showed very good dosimetric agreement between the GPU and CPU calculated plans. The results from SBRT study show that GPU planning system can maintain 90% target coverage while meeting all the constraints of RTOG 0631 protocol. Beam on time for Tomotherapy and flattening filter free RapidArc was much faster than for Vero or Cyberknife. Retrospective data analysis showed that lung dose and Cyclophosphomide (Cy) are both predictors of IP in TBI/TMI treatments. The dose rate was not found to be an independent risk factor for IP. The model failed to establish accurate dose response function, but the discrete data indicated a radiation dose threshold of 7.6Gy (EQD2_repair) and 120 mg/kg of Cy below which no IP cases were reported. Conclusion: The TomoTherapy GPU based dose engine is capable of calculating TMI treatment plans with plan quality nearly identical to plans calculated using the traditional CPU/cluster based system, while significantly reducing the time required for optimization and dose calculation. The new system was able to achieve more uniform dose distribution throughout the target volume and steeper dose fall off, resulting in superior OAR sparing when compared to Eclipse treatment planning system for VMAT delivery. The machine optimization parameters tested for TMI cases provide a comprehensive overview of the capabilities of the treatment planning station and associated helical delivery system. The new system also proved to be dosimetrically compatible with other leading modalities for treatments of small and complicated target volumes and was even superior when treatment delivery times were compared. These finding demonstrate that the advanced treatment planning and delivery system from TomoTherapy is well suitable for treatments of complicated cases such as TMI and SRS and it's often dosimetrically and/or logistically superior to other modalities. The new planning system can easily meet the constraint of threshold lung dose established in this study. The results presented here on the capabilities of Tomotherapy and on the identified lung dose threshold provide an opportunity to explore alternative fractionation schemes without sacrificing target coverage or lung toxicity. (Abstract shortened by ProQuest.).

Having a Lot of a Good Thing: Multiple Important Group Memberships as a Source of Self-Esteem

PubMed Central

Jetten, Jolanda; Branscombe, Nyla R.; Haslam, S. Alexander; Haslam, Catherine; Cruwys, Tegan; Jones, Janelle M.; Cui, Lijuan; Dingle, Genevieve; Liu, James; Murphy, Sean; Thai, Anh; Walter, Zoe; Zhang, Airong

2015-01-01

Membership in important social groups can promote a positive identity. We propose and test an identity resource model in which personal self-esteem is boosted by membership in additional important social groups. Belonging to multiple important group memberships predicts personal self-esteem in children (Study 1a), older adults (Study 1b), and former residents of a homeless shelter (Study 1c). Study 2 shows that the effects of multiple important group memberships on personal self-esteem are not reducible to number of interpersonal ties. Studies 3a and 3b provide longitudinal evidence that multiple important group memberships predict personal self-esteem over time. Studies 4 and 5 show that collective self-esteem mediates this effect, suggesting that membership in multiple important groups boosts personal self-esteem because people take pride in, and derive meaning from, important group memberships. Discussion focuses on when and why important group memberships act as a social resource that fuels personal self-esteem. PMID:26017554

ABO blood groups, Rhesus factor, and anaphylactic reactions due to Hymenoptera stings.

PubMed

Pałgan, Krzysztof; Bartuzi, Zbigniew; Chrzaniecka, Elżbieta

2017-09-21

Numerous publications indicate that the prevalence of some infectious, neoplastic and immunological diseases are associated with ABO blood groups. The aim of this study was to verify whether ABO and Rh blood groups are associated with severe anaphylactic reactions after Hymenoptera stings. A study was undertaken of 71,441 Caucasian subjects living in the same geographic area. The study group included 353 patients with diagnosed systemic anaphylaxis to Hymenoptera venom. Control group included 71,088 healthy blood donors. Frequencies of ABO and Rhesus groups in the study and control groups were compared using univariate and multivariate analyses. No statistically significant interactions were observed between the ABO blood group and anaphylactic reactions to Hymenoptera.

Online support groups for women with breast cancer.

PubMed

McCaughan, Eilis; Parahoo, Kader; Hueter, Irene; Northouse, Laurel; Bradbury, Ian

2017-03-10

Survival rates for women with a diagnosis of breast cancer continue to improve. However, some women may experience physical, psychological and emotional effects post diagnosis, throughout treatment and beyond. Support groups can provide opportunities for people to share their experiences and learn from others. As the number of online support groups increases, more and more women with breast cancer will likely access them. To assess effects of online support groups on the emotional distress, uncertainty, anxiety, depression and quality of life (QoL) of women with breast cancer. We searched for trials in the Cochrane Breast Cancer Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 4), MEDLINE, Embase and PsycINFO on 2 May 2016, and we handsearched journals and reference lists. We also searched the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP) search portal and clinicaltrials.gov on 2 May 2016. We included randomised controlled trials (RCTs) assessing effects of online support groups on women with a diagnosis of breast cancer and women who have completed breast cancer treatment. We included studies comparing online support groups with a usual care group, and studies comparing two or more types of online support groups (without a usual care group). Two review authors independently extracted data and assessed risk of bias. We presented outcome data using mean differences (MDs) and standardised mean differences (SMDs) along with 95% confidence intervals (CIs), and we used the fixed-effect model when appropriate. We assessed the quality of the body of evidence using the GRADE approach. We included six studies (492 women) that assessed online support groups for women with breast cancer. Online support groups in these six trials lasted from six to 30 weeks. Women participated in these groups between 1.5 and 2.5 hours per week, and investigators conducted all studies in the USA. Participants were predominantly white and well educated and were moderate to high earners. Four studies compared an online support group versus a control group, and the other two compared a 'moderated' versus a 'peer-led' online support group, and a 'standard' versus an 'enhanced' online support group, respectively.None of the included studies measured 'emotional distress' or uncertainty. One study (78 women) for which data for analysis were missing reported no positive effects of online support on 'distress' and 'cancer-specific distress' versus support provided by a control group. Two studies measured anxiety: One study (72 women) found no difference in anxiety at the end of the intervention between the online support group and the control group (MD -0.40, 95% CI -6.42 to 5.62; low-quality evidence), and the second study (184 women) reported a reduction in anxiety levels at the end of the intervention when comparing the 'standard' support group (run by participants without prompting from health professionals) versus an 'enhanced' online support group (in which participants were specifically asked by the researcher to respond to one another's need for support).Five studies (414 women) measured depression. Three studies compared depression in the online support group with depression in the control group. Pooled data from two studies (120 women) showed a small to moderate reduction in depression in the online support group compared with control groups at the end of the intervention (SMD -0.37, 95% CI -0.75 to 0.00; very low-quality evidence). The third study, a pilot study (30 women), provided no data for analysis but reported no difference in depression between participants in support and control groups at the end of the intervention. Of the remaining two studies that measured depression, one study (60 women) provided no extractable data for comparison but reported no difference in depressive symptoms between a 'moderated' and a 'peer-led' support group; the other study (184 women) reported greater reduction in depression in the 'standard' support group than in the 'enhanced' online support group.Three studies measured quality of life. One pilot study (30 women) provided limited data for analysis but reported no change in quality of life at the end of the intervention. Only two studies (140 women) provided data for pooling and showed no positive effects on quality of life at four months post intervention compared with controls (SMD -0.11, 95% CI -0.47 to 0.24; very low-quality evidence). At 12 months post intervention, one study (78 women) reported that the intervention group did not attain better quality of life scores than the control group (MD -10.89, 95% CI -20.41 to -1.37; low-quality evidence).We found no data for subgroup analyses on stage of disease, treatment modality and types and doses of interventions. No studies measured adverse effects. This review did not find the evidence required to show whether participation in online support groups was beneficial for women with breast cancer, because identified trials were small and of low or very low quality. Large, rigorous trials with ethnically and economically diverse participants are needed to provide robust evidence regarding the psychosocial outcomes selected for this review.

Study guides: effective tools to improve self-directed learning skills of medical students.

PubMed

Khabaz Mafinejad, Mahboobeh; Aghili, Rokhsareh; Emami, Zahra; Malek, Mojtaba; Baradaran, Hamidreza; Taghavinia, Mansoureh; Khamseh, Mohammad E

2014-01-01

In medicine, there is a rapid development of a knowledge base. Medical professionals need to sustain and advance their competence to practice in response to these varieties. So, there is increased interest in self-directed learning methods. Study guides can make a major contribution to self-directed learning. This study was carried out to evaluate the effect of study guides on improving self-learning skills of medical students in the Iran University of Medical Sciences (IUMS). In this quasi-experimental study, 46 medical students were randomly assigned into two groups; the intervention group and the control group. Both groups participated in a diagnostic test at the beginning of the course (pre-test). The same test was taken at the end of the course (post-test). The intervention group was provided with study guides on thyroid disorders and diabetes. Meanwhile, they continued their routine clinical training. The control group was only involved in the conventional training program. Students in the intervention group were also asked to complete a designed questionnaire in regard to their attitude toward the study guides. At enrollment, there was no statistically significant difference between the two groups. The mean scores of the pre-test for the control group and the intervention group were 6.18 and 6.13 respectively (P=0.9). In the post-test, the mean score of the students in the intervention group was considerably higher: 9.25 vs. 12 (P=0.002). The students in the intervention group found the study guides useful. The study guides were potentially effective in motivating self-learning in this group of medical students and had a remarkable effect on their final score.

Canadian Mathematics Education Study Group = Groupe Canadien d'etude en didactique des mathematiques. Proceedings of the 1993 Annual Meeting (York, Ontario, Canada, May 28-June 1, 1993).

ERIC Educational Resources Information Center

Quigley, Martyn, Ed.

These proceedings contain papers presented at the 1993 annual meeting of the Canadian Mathematics Education Study Group. Papers are presented in four sections: (1) invited lectures; (2) working groups; (3) topic groups; and (4) ad hoc groups. Papers include: (1) "What is a Square Root? A Study of Geometrical Representation in Different…

Canadian Mathematics Education Study Group = Groupe Canadien d'etude en didactique des mathematiques. Proceedings of the 1994 Annual Meeting (Regina, Saskatchewan, Canada, June 3-7, 1994).

ERIC Educational Resources Information Center

Quigley, Martyn, Ed.

These proceedings contain papers from the 1994 annual meeting of the Canadian Mathematics Education Study Group. Papers are divided into the following sections: (1) invited lectures; (2) working groups; (3) topic groups; (4) ad hoc groups; and (5) reports on ICMI (International Committee on Mathematical Instruction) studies. Papers include: (1)…

What about N? A methodological study of sample-size reporting in focus group studies.

PubMed

Carlsen, Benedicte; Glenton, Claire

2011-03-11

Focus group studies are increasingly published in health related journals, but we know little about how researchers use this method, particularly how they determine the number of focus groups to conduct. The methodological literature commonly advises researchers to follow principles of data saturation, although practical advise on how to do this is lacking. Our objectives were firstly, to describe the current status of sample size in focus group studies reported in health journals. Secondly, to assess whether and how researchers explain the number of focus groups they carry out. We searched PubMed for studies that had used focus groups and that had been published in open access journals during 2008, and extracted data on the number of focus groups and on any explanation authors gave for this number. We also did a qualitative assessment of the papers with regard to how number of groups was explained and discussed. We identified 220 papers published in 117 journals. In these papers insufficient reporting of sample sizes was common. The number of focus groups conducted varied greatly (mean 8.4, median 5, range 1 to 96). Thirty seven (17%) studies attempted to explain the number of groups. Six studies referred to rules of thumb in the literature, three stated that they were unable to organize more groups for practical reasons, while 28 studies stated that they had reached a point of saturation. Among those stating that they had reached a point of saturation, several appeared not to have followed principles from grounded theory where data collection and analysis is an iterative process until saturation is reached. Studies with high numbers of focus groups did not offer explanations for number of groups. Too much data as a study weakness was not an issue discussed in any of the reviewed papers. Based on these findings we suggest that journals adopt more stringent requirements for focus group method reporting. The often poor and inconsistent reporting seen in these studies may also reflect the lack of clear, evidence-based guidance about deciding on sample size. More empirical research is needed to develop focus group methodology.

Treatment of hypermyoglobinemia after CRS + HIPEC for patients with peritoneal carcinomatosis: A retrospective comparative study.

PubMed

Liu, Gang; Ji, Zhong-He; Yu, Yang; Li, Xin-Bao; Zhang, Yan-Bin; Peng, Kai-Wen; Li, Yan

2017-11-01

This retrospective comparative study aims to explore the time courses of serum myoglobin (Mb) changes, and summarize our experience in treating patients with hypermyoglobinemia after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).This study covered 60 patients with peritoneal carcinomatosis treated with CRS + HIPEC as the study group, and another 25 cancer patients treated with conventional extensive surgery without HIPEC as the control group from February to October 2016. In the study group, patients with postoperative hypermyoglobinemia were on a comprehensive treatment regimen consisting intravenous injection of sodium bicarbonate solution according to the Mb level. In the control group, patients were recorded and treated with the same regimen except for special sodium bicarbonate solution. The preoperative and postoperative serum Mb, blood urine nitrogen (BUN), and creatinine (Cr) levels were evaluated.There were no significantly difference between the 2 groups in serum Mb, BUN, and Cr levels before surgery. Postoperative serum Mb levels were elevated in both groups and significantly higher on postoperative 0 to 2 days (P < .05) in the study group than the control group. The peak value of serum Mb levels (426.65 ± 108.386 μg/L) occurred on the surgery day. The serum Mb change rate was much bigger in the study group than the control group. Serum BUN levels in both groups revealed a slow increase during the early postoperative period and were significantly lower in the study group than the control group on days 1 and 2. The serum Cr levels were similar and stable between the 2 groups after surgery. The serum Cr change rates changed synchronously with same tendency in both groups, and on postoperative day 1 the increase rate was bigger in the control group than the study group.Hypermyoglobinemia is a common and prominent lab abnormality after CRS + HIPEC, and serum Mb levels could be an early and sensitive indicator for dramatic disturbances in the internal milieu after CRS + HIPEC. Adequate treatment with sodium bicarbonate could accelerate the reduction in serum Mb levels and reduce the risk for major organ damages.

Clinical success of implant-supported and tooth-implant-supported double crown-retained dentures.

PubMed

Bernhart, Gunda; Koob, Andreas; Schmitter, Marc; Gabbert, Olaf; Stober, Thomas; Rammelsberg, Peter

2012-08-01

The objective of this retrospective study was to compare biological and technical complications of implant-supported and tooth-implant-supported double crown-retained dentures (DCRDs) with those of tooth-supported DCRDs. Sixty-three DCRDs were monitored. One study group included 16 prostheses with a combination of implants and natural teeth as double crowns (ti group), whereas in the second study group, 19 dentures were retained exclusively on implants (ii group); a third study group with 28 exclusively tooth-supported dentures served as controls (tt group). Tooth loss, implant failure, and technical complications (loss of retention of primary crown, abutment screw loosening, loss of facing, fracture of resin denture teeth and fracture of saddle resin) were analysed. During the observation period of 24 months, no implants or teeth were lost in the ti group and three technical complications were recorded. In the ii group, two implants were lost, two cases of peri-implantitis occurred and four technical complications were observed. In the tt group, two cases of tooth loss and seven technical complications were observed. At the time of the last examination, all prostheses of the ti group and the ii group were functional. Patients of these two study groups reported high satisfaction with both function and aesthetics with no significant difference between the two groups. Treatment with DCRDs showed comparable results in the three study groups. The 2-year results indicate that double crowns can be recommended for implant and combined tooth-implant-retained dentures.

Testing Group Mean Differences of Latent Variables in Multilevel Data Using Multiple-Group Multilevel CFA and Multilevel MIMIC Modeling.

PubMed

Kim, Eun Sook; Cao, Chunhua

2015-01-01

Considering that group comparisons are common in social science, we examined two latent group mean testing methods when groups of interest were either at the between or within level of multilevel data: multiple-group multilevel confirmatory factor analysis (MG ML CFA) and multilevel multiple-indicators multiple-causes modeling (ML MIMIC). The performance of these methods were investigated through three Monte Carlo studies. In Studies 1 and 2, either factor variances or residual variances were manipulated to be heterogeneous between groups. In Study 3, which focused on within-level multiple-group analysis, six different model specifications were considered depending on how to model the intra-class group correlation (i.e., correlation between random effect factors for groups within cluster). The results of simulations generally supported the adequacy of MG ML CFA and ML MIMIC for multiple-group analysis with multilevel data. The two methods did not show any notable difference in the latent group mean testing across three studies. Finally, a demonstration with real data and guidelines in selecting an appropriate approach to multilevel multiple-group analysis are provided.

Building on what you know.

PubMed

Patry, Leslie Anne

2006-02-01

The author undertook a project to support nurses participating in study groups as part of their strategy to prepare for the Canadian Nurses Association certification exams. Feedback was obtained from CNA certified nurses, study group participants and facilitators and other key stakeholders to develop a study group resource manual. CNA certification is a voluntary national nursing specialty credential that offers Canadian nurses the opportunity to demonstrate their knowledge and skills by meeting eligibility criteria and successfully writing an examination. Initially, development of a study group manual was the principal aim of the project; however, nurses' insights into their study group experiences became the focal point. Nurses recognized that being part of a study group was an effective learning strategy and a valuable networking experience. The author highlights nurses' study group experiences, describes the use of a nursing leadership conceptual model to frame the project and discusses the concept of continuing competence.

Modeling and Simulation of Avionics Systems and Command, Control and Communications Systems

DTIC Science & Technology

1980-01-01

analytical and operational talent into a cohesive study group . This group becomes our critical mass for innovative analysis. For command and control problems...that focusing small integrated groups on specific aspects of a command and control problem sucoseds best. For example, Air Force Studies and Analyses...phase so called " study groups " should define "tactical requirement-papers", These study groups will be supported by operational analyses and by

Mentoring First Year Study Groups--Benefits from the Mentors' Perspective

ERIC Educational Resources Information Center

Dyrberg, Nadia Rahbek; Michelsen, Claus

2017-01-01

The "study group concept" at the University of Southern Denmark (SDU) was implemented to aid first year students' transitional challenges. A mentor (an older student) is affiliated each study group to facilitate productive group work, bring awareness to study habits, and share his/her own experiences with life as a student. The study…

The Next Linear Collider Program

Science.gov Websites

text only International Study Group (ISG) Meetings NLC Home Page NLC Technical SLAC Eleventh Linear Collider International Study Group at KEK, December 16 - 19, 2003 Tenth (X) Linear Collider International Study Group at SLAC, June, 2003 Nineth Linear Collider ,International Study Group at KEK, December 10-13

Stereotypes of Norwegian social groups

PubMed Central

Bye, Hege H; Herrebrøden, Henrik; Hjetland, Gunnhild J; Røyset, Guro Ø; Westby, Linda L

2014-01-01

We present a pilot study and two main studies that address the nature of stereotypes of social groups in Norway within the framework of the Stereotype Content Model (SCM). The first study focused on stereotypes of a wide range of groups across categories such as gender, age, religious conviction, socioeconomic and health status. The second study focused on stereotypes of immigrant groups. Participants (n = 244 and n = 63, respectively) rated the groups on perceived warmth, competence, status, and competition. Results from both studies support the applicability of the SCM in Norway and provides a unique insight into stereotypes of Norwegian social groups. PMID:24975918

Three-month treatment with triptorelin, letrozole and ulipristal acetate before hysteroscopic resection of uterine myomas: prospective comparative pilot study.

PubMed

Bizzarri, Nicolò; Ghirardi, Valentina; Remorgida, Valentino; Venturini, Pier Luigi; Ferrero, Simone

2015-09-01

To compare the usefulness of preoperative treatment with triptorelin, letrozole or ulipristal acetate or no treatment before hysteroscopic removal of uterine submucosal myomas. Single center prospective non-randomized comparative pilot study. The study included consecutive premenopausal patients undergoing hysteroscopic resection of myomas graded as type 0, type 1 or type 2 according to the FIGO classification with diameter between 20 and 35 mm. Exclusion criteria were: associated polyps, associated non-hysteroscopic surgical procedures, >2 myomas requiring hysteroscopic resection. This study enrolled patients who underwent either direct surgery (group S; n=23) or 3-month preoperative treatment with triptorelin (3.75 mg every 28 days; group T; n=20), letrozole (2.5 mg/day; group L; n=11) or ulipristal acetate (5 mg/day; group U; n=7). Patients underwent hysteroscopic resection of the myomas. All medical treatments caused a significant decrease in the volume of myomas (group T, p<.001; group L, p<.001; group U, p=.006); however, the percentage decrease in myoma volume was lower in group U than in group T (p=.001) and in group L (p=.010). The hysteroscopy time was higher in group S than in group T (p<.001) and in group L (p=.001); there was no significant difference in the hysteroscopy time between group S and group U (p=.206). Fluid absorption was lower in group T than in group S (p=.002) and in group L than in group S (p=.048); fluid absorption was similar in group S and group U (p=.110). Intra- and postoperative complications, postoperative pain, and patient satisfaction were similar in the four study groups. Surgeon's evaluation of operative difficulty was better in group T than in group S (p<.005). Preoperative treatment with triptorelin and letrozole decreases the hysteroscopy time and the volume of fluid absorbed during hysteroscopic resection of uterine submucosal myomas. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Unethical for the sake of the group: risk of social exclusion and pro-group unethical behavior.

PubMed

Thau, Stefan; Derfler-Rozin, Rellie; Pitesa, Marko; Mitchell, Marie S; Pillutla, Madan M

2015-01-01

This research tested the idea that the risk of exclusion from one's group motivates group members to engage in unethical behaviors that secure better outcomes for the group (pro-group unethical behaviors). We theorized that this effect occurs because those at risk of exclusion seek to improve their inclusionary status by engaging in unethical behaviors that benefit the group; we tested this assumption by examining how the effect of exclusion risk on pro-group unethical behavior varies as a function of group members' need for inclusion. A 2-wave field study conducted among a diverse sample of employees working in groups (Study 1) and a constructive replication using a laboratory experiment (Study 2) provided converging evidence for the theory. Study 1 found that perceived risk of exclusion from one's workgroup predicted employees' engagement in pro-group unethical behaviors, but only when employees have a high (not low) need for inclusion. In Study 2, compared to low risk of exclusion from a group, high risk of exclusion led to more pro-group (but not pro-self) unethical behaviors, but only for participants with a high (not low) need for inclusion. We discuss implications for theory and the management of unethical behaviors in organizations. (c) 2015 APA, all rights reserved.

Attachment theory and group processes: the association between attachment style and group-related representations, goals, memories, and functioning.

PubMed

Rom, Eldad; Mikulincer, Mario

2003-06-01

Four studies examined attachment-style differences in group-related cognitions and behaviors. In Studies 1-2, participants completed scales on group-related cognitions and emotions. In Studies 3-4, participants were divided into small groups, and their performance in group tasks as well as the cohesion of their group were assessed. Both attachment anxiety and avoidance in close relationships were associated with negative group-related cognitions and emotions. Anxiety was also related to the pursuit of closeness goals and impaired instrumental performance in group tasks. Avoidance was related to the pursuit of distance goals and deficits in socioemotional and instrumental performance. Group cohesion significantly moderated the effects of attachment anxiety. The discussion emphasizes the relevance of attachment theory within group contexts.

Safety of the use of group A plasma in trauma: the STAT study.

PubMed

Dunbar, Nancy M; Yazer, Mark H

2017-08-01

Use of universally ABO-compatible group AB plasma for trauma resuscitation can be challenging due to supply limitations. Many centers are now using group A plasma during the initial resuscitation of traumatically injured patients. This study was undertaken to evaluate the impact of this practice on mortality and hospital length of stay (LOS). Seventeen trauma centers using group A plasma in trauma patients of unknown ABO group participated in this study. Eligible patients were group A, B, and AB trauma patients who received at least 1 unit of group A plasma. Data collected included patient sex, age, mechanism of injury, Trauma Injury Severity Score (TRISS) probability of survival, and number of blood products transfused. The main outcome of this study was in-hospital mortality differences between group B and AB patients compared to group A patients. Data on early mortality (≤24 hr) and hospital LOS were also collected. There were 354 B and AB patients and 809 A patients. The two study groups were comparable in terms of age, sex, TRISS probability of survival, and total number of blood products transfused. The use of group A plasma during the initial resuscitation of traumatically injured patients of unknown ABO group was not associated with increased in-hospital mortality, early mortality, or hospital LOS for group B and AB patients compared to group A patients. These results support the practice of issuing thawed group A plasma for the initial resuscitation of trauma patients of unknown ABO group. © 2017 AABB.

Is pregnancy over 45 with very high parity related with adverse maternal and fetal outcomes?

PubMed

Kale, A; Kuyumcuoğlu, U; Güzel, A

2009-01-01

To examine whether very high parity and age over 45 years are related with adverse maternal and fetal outcomes. This study was carried out at the Department of Obstetrics and Gynecology from January 1, 2007 to December 31, 2007. Sixty-one pregnant women were enrolled in this prospective study. Mothers were classified in two groups: the study group (n = 23) included women with very high parity over 45 years of age (age > 45 and > or = 10 previous live births), and a control group (n = 38) included women with high parity between 40-45 years of age (between 40-45 years and 5-9 previous live births). Hypertensive disorders complicating pregnancy, preterm labor, breech presentation, cesarean section ratio, mean APGAR scores, birthweight, fetal sex, fetal macrosomia, and early neonatal death were compared within groups. Six (26%) patients in the study group and 12 (31.5%) patients in the control group had hypertensive disorders of pregnancies (p > 0.05). Twelve (52.1%) patients in the study group and 22 (57.8%) patients in the control group had preterm labor (p > 0.05). One (4%) patient in the study group and two (5.2%) patients in the control group had breech presentation during delivery (p > 00.5). Twelve (52.1%) patients in the study group and 21 (55.2%) patients in the control group had cesarean operations (p > 0.05). Mean APGAR scores (at 1 min and 5 min), mean birthweight, fetal sex ratio, fetal macrosomia ratio, and early neonatal death ratio due to prematurity were not statistically significant in the study group as compared with the control group. It is generally assumed that women with advanced age have an increased risk for complications during pregnancy. However, prospective population-based studies do not exist and available publications give conflicting views. Based on our results, we hypothesized that cases aged 45 or over with very high parity are not always related with adverse maternal and fetal outcomes.

A Systematic Review of Promising Strategies of Faith-Based Cancer Education and Lifestyle Interventions Among Racial/Ethnic Minority Groups.

PubMed

Hou, Su-I; Cao, Xian

2017-09-13

Church-based interventions have been used to reach racial/ethnic minorities. In order to develop effective programs, we conducted a comprehensive systematic review of faith-based cancer prevention studies (2005~2016) to examine characteristics and promising strategies. Combination terms "church or faith-based or religion," "intervention or program," and "cancer education or lifestyle" were used in searching the five major databases: CINAHL; ERIC; Health Technology Assessments; MEDLINE; and PsycInfo. A total of 20 studies met study criteria. CDC's Community Guide was used to analyze and review group interventions. Analyses were organized by two racial groups: African American (AA) and Latino/Hispanic American groups. Results showed most studies reviewed focused on breast cancer alone or in combination with other cancers. Studies of Latino/Hispanic groups targeted more on uninsured, Medicare, or Medicaid individuals, whereas AA studies generally did not include specific insurance criteria. The sample sizes of the AA studies were generally larger. The majority of these studies reviewed used pre-post, posttest only with control group, or quasi-experience designs. The Health Belief Model was the most commonly used theory in both groups. Community-based participatory research and empowerment/ecological frameworks were also used frequently in the Latino/Hispanic studies. Small media and group education were the top two most popular intervention strategies in both groups. Although one-on-one strategy was used in some Latino studies, neither group used reducing client out-of-pocket costs strategy. Client reminders could also be used more in both groups as well. Current review showed church-based cancer education programs were effective in changing knowledge, but not always screening utilization. Results show faith-based cancer educational interventions are promising. To maximize intervention impact, future studies might consider using stronger study designs, incorporating a variety of proven effective strategies, including those frequently used evidence-based strategies, as well as exploring promising strategies among specific target groups.

[Clinical evaluation of propess for induction of term pregnancy].

PubMed

Gai, Ming-ying; Zhang, Jian-ping; Li, Yang; Han, Hong-jing; Yang, Jian-qiu; Wang, Shan-mi; Su, Qi-feng; Wu, Lian-fang

2003-04-01

To explore the efficacy and safety of continuously released prostaglandin E(2) (PGE(2)) suppository-propess used for induction of term pregnancy. A multicenter, prospective, case control clinical study was carried out, propess was used in 100 cases as study group, the suppository without PGE(2) was used in 49 cases as control group. The cervical maturity (by Bishop scoring), the time to labor starting, membrane rupture and delivery, the application of oxytocin, ceserean section rate, fetal and neonatal condition were compared between 2 groups after inserting of the suppository. At the same time, side effects caused by propess were investigated. Bishop score was increased >or= 2 points in 93% cases, >or= 3 points in 87% cases in study group, whereas only 4% cases whose Bishop score increased >or= 2 points in control group. The time to labor starting, membrane rupture, and delivery was shortened obviously in study group than that in control group after inserting suppository. The application of oxytocin was much less in study group, cesarean section rate was reduced in study group (32% vs 61%). There was no significant difference between 2 groups in fetal and neonatal conditions. The overstimulation of uterine contraction and mild gastrointestinal tract reaction occurred in 3 cases and 2 cases respectively in study groups. Propess can be used for induction of term pregnancy effectively and safely.

Association between suicidal ideation and behavior, and depression, anxiety, and perceived social support in cancer patients.

PubMed

Balcı Şengül, Melike Ceyhan; Kaya, Vildan; Şen, Cenk Ahmet; Kaya, Kemal

2014-02-27

The aim of this study was to determine the relationship between suicidal behavior and associated factors such as depression, anxiety, and perceived social support level in cancer patients. The study group included 102 patients who were under treatment in the oncology department and the control group included 100 individuals with similar sociodemographic features. A sociodemographic information form, Beck depression inventory, Beck anxiety inventory, suicidal behavior inventory, suicidal ideation inventory, and multidimensional inventory of perceived social support were used. The mean Beck depression inventory and Beck anxiety inventory scores in the study group were significantly higher compared to the control group. Thirteen patients in the study group attempted suicide, whereas 3 individuals attempted suicide in the control group. Similarly, the mean suicide behavior and ideation scores in the study group were significantly higher compared to the control group. The mean total multidimensional inventories of perceived social support score, as well as the mean family and friend sub-inventory scores in the control group were significantly higher compared to the study group. This study revealed that depression and anxiety occur frequently in cancer patients. Suicide attempts and ideation are higher in cancer patients compared to the control group. Social support perceived from family and friends is lower in cancer patients. Suicide attempts are correlated with depression, anxiety, low level of perceived social support, and advanced disease stage.

Effects of kallidinogenase in patients undergoing vitrectomy for diabetic macular edema.

PubMed

Yoshizumi, Yuki; Ohara, Zaigen; Tabuchi, Hitoshi; Sumino, Hitomi; Maeda, Yukiko; Mochizuki, Hideki; Yamane, Ken; Kiuchi, Yoshiaki

2018-05-12

To evaluate the effectiveness of the combination of vitrectomy with kallidinogenase for diabetic macular edema (DME). This study was designed as a prospective, randomized, multicenter study comparing 19 eyes of 19 patients who received 150 units of kallidinogenase administered a day for 52 weeks from the day after vitrectomy (study group) with 20 eyes of 20 patients who received no kallidinogenase (control group). The main outcome measurements included logMAR visual acuity and central foveal thickness (CFT) before surgery and at 3, 6, 9, and 12 months after vitrectomy. During follow-up, 11 patients dropped out (six in the study group and five in the control group), leaving 28 eyes in 28 patients for analysis (13 in the study group and 15 in the control group). Visual acuity improved significantly at 12 months in both groups compared with before surgery. The degree of improvement did not differ significantly between the groups. At 12 months, the mean CFT decreased significantly in both groups, with no significant difference in the rate of change between the two groups. In the study group, the visual acuity and CFT significantly improved from 3 to 12 months and from 6 to 12 months, whereas these parameters did not continue to improve in the control group after 6 months (for visual acuity) or 3 months (for CFT). After vitrectomy for DME, visual acuity and CFT improved significantly in both groups, but only patients treated with kallidinogenase continued to have significant improvement throughout the study period.

Guided implant surgery with modification of the technique involving the raising of a semicircular miniflap: A preliminary study

PubMed Central

Viña, José; Maestre, Laura; Peñarrocha, David; Balaguer, José

2012-01-01

Objective: An evaluation is made of pain, swelling and peri-implant attached mucosal width after implant-based rehabilitation involving guided surgery and a modification of the technique with the raising of a semicircular miniflap, in single and partial replacements. Study design: A case-control study was carried out. The study group consisted of 12 patients with the placement of 19 implants using a guided surgery and miniflap technique. The control group consisted of 12 patients with the placement of 22 implants using the conventional technique. Each patient scored postoperative swelling and pain by means of a visual analog scale (VAS). Attached vestibular mucosa width was evaluated 12 weeks after implant placement. Results: Twelve operations were carried out in each group. Immediate aesthetics were established for all implants of the study group. One implant failed in each group. Maximum pain was recorded after 6 hours in both groups (mean VAS score 4 and 4.9 in the study and control group, respectively). Maximum swelling was recorded after 24 hours (mean VAS score 2.5) in the study group and on the second day (mean VAS score 3.4) in the control group. The mean attached vestibular mucosa width was 2.9 mm in the study group and 3.2 mm in the control group. Conclusion: In this preliminary study, guided implant surgery with a semicircular miniflap in single and partial replacements resulted in slightly less postoperative pain and swelling than with the conventional implant technique. The attached vestibular mucosa width was greater in the control group, though the differences were very small. Key words:Guided surgery, flapless surgery, miniflap, peri-implant mucosa. PMID:22549666

Effect of ezetimibe on the prevalence of cholelithiasis.

PubMed

Stein, Assaf; Hermoni, Doron; Elis, Avishay; Konikoff, Fred M

2012-10-28

To investigate the prevalence of cholelithiasis among patients treated with ezetimibe. A retrospective, case-control study based on computerized medical records from patients of the Clalit Health Services, Sharon-Shomron region, from 2000 to 2009. Patients 20-85 years of age, who had been treated with ezetimibe and statins or statins only for at least 6 mo, and who had an abdominal ultrasound were included in the study. Collected data included age, gender, ezetimibe treatment duration, presence of hypothyroidism or diabetes, and existence of cholelithiasis as determined by ultrasound. Excluded were subjects after gallbladder resection, with hemolysis, myeloproliferative or inflammatory bowel diseases, and those treated with ursodeoxycholic acid and fibrates. Patients treated with statins and ezetimibe (study group) were compared to patients treated with statins only (control group). The study group included 25 patients and the control group 168. All patients in the study were treated with statins. The study group included 13 males (52%) and 12 females (48%), the control group 76 males (45%) and 92 (55%) females (P = 0.544). The groups did not differ in age (mean age: 68 ± 8 years, range 53-85 years vs mean age: 71 ± 8 years, range 51-85 years; P = 0.153) or in the rate of diabetic and hypothyroid patients [11 (44%) vs 57 (33%), P = 0.347 in the study group and 5 (20%) vs 23 (14%), P = 0.449 in the control group, respectively]. Patients in the study group were treated with ezetimibe for an average of 798 ± 379 d. Cholelithiasis was found in 4 (16%) patients in the study group and in 33 (20%) patients in the control group (P = 0.666). Ezetimibe does not appear to influence the prevalence of gallstones.

Effects of Electronic Nicotine Delivery System on Larynx: Experimental Study.

PubMed

Salturk, Ziya; Çakır, Çağlar; Sünnetçi, Gürcan; Atar, Yavuz; Kumral, Tolgar Lütfi; Yıldırım, Güven; Berkiten, Güler; Uyar, Yavuz

2015-09-01

We aimed to assess the effects of electronic nicotine delivery system (ENDS) or also termed electronic cigarette vapor on the laryngeal mucosa of rats. Sixteen female Wistar albino rats were divided into two groups. The study group was exposed to ENDS vapor for 1 hour/day for 4 weeks. The control group was not subjected to any chemical or physical stimulus. The vocal folds of the study and control group rats were evaluated histopathologically by hematoxylin and eosin staining and immunohistochemically by Ki67 staining. Epithelial distribution, inflammation, hyperplasia, and metaplasia were evaluated. Epithelial distribution and inflammation did not differ between the two groups. Two cases of hyperplasia were detected in the study group but there was no hyperplasia in the control group. Four cases of metaplasia were detected in the study group and one case in the control group. Statistical analysis revealed no significant difference between the study and control groups (P = 0.131 and 0.106, respectively). Exposure to ENDS for 4 weeks caused hyperplasia and metaplasia of the laryngeal mucosa of rats but this was not significant statistically. These results implemented that further studies with larger cohort and longer duration are required to evaluate long-term effects. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Population genetic structure analysis and forensic evaluation of Xinjiang Uigur ethnic group on genomic deletion and insertion polymorphisms.

PubMed

Mei, Ting; Shen, Chun-Mei; Liu, Yao-Shun; Meng, Hao-Tian; Zhang, Yu-Dang; Guo, Yu-Xin; Dong, Qian; Wang, Xin-Xin; Yan, Jiang-Wei; Zhu, Bo-Feng; Zhang, Li-Ping

2016-01-01

The Uigur ethnic minority is the largest ethnic group in the Xinjiang Uygur Autonomous Region of China, and valuable resource for the study of ethnogeny. The objective of this study was to estimate the genetic diversities and forensic parameters of 30 insertion-deletion loci in Uigur ethnic group from Xinjiang Uigur Autonomous Region of China and to analyze the genetic relationships between Xinjiang Uigur group and other previously published groups based on population data of these loci. All the tested loci were conformed to Hardy-Weinberg equilibrium after Bonferroni correction. The observed and expected heterozygosity ranged from 0.3750 to 0.5515; and 0.4057 to 0.5037, respectively. The combined power of discrimination and probability of exclusion in the group were 0.99999999999940 and 0.9963, respectively. We analyzed the D A distance, interpopulation differentiations and population structure, conducted principal component analysis and neighbor-joining tree based on our studied group and 21 reference groups. The present results indicated that the studied Xinjiang Uigur group (represented our samples from the whole territory of Xinjiang Uigur Autonomous Region) had a close relationships with Urumchi Uigur (represented previously reported samples from Urumchi of Xinjiang) and Kazak groups. The present study may provide novel biological information for the study of population genetics, and can also increase our understanding of the genetic relationships between Xinjiang Uigur group and other groups.

Psychological collectivism: a measurement validation and linkage to group member performance.

PubMed

Jackson, Christine L; Colquitt, Jason A; Wesson, Michael J; Zapata-Phelan, Cindy P

2006-07-01

The 3 studies presented here introduce a new measure of the individual-difference form of collectivism. Psychological collectivism is conceptualized as a multidimensional construct with the following 5 facets: preference for in-groups, reliance on in-groups, concern for in-groups, acceptance of in-group norms, and prioritization of in-group goals. Study 1 developed and tested the new measure in a sample of consultants. Study 2 cross-validated the measure using an alumni sample of a Southeastern university, assessing its convergent validity with other collectivism measures. Study 3 linked scores on the measure to 4 dimensions of group member performance (task performance, citizenship behavior, counterproductive behavior, and withdrawal behavior) in a computer software firm and assessed discriminant validity using the Big Five. The results of the studies support the construct validity of the measure and illustrate the potential value of collectivism as a predictor of group member performance. ((c) 2006 APA, all rights reserved).

Effect of shoulder girdle strengthening on trunk alignment in patients with stroke.

PubMed

Awad, Amina; Shaker, Hussien; Shendy, Wael; Fahmy, Manal

2015-07-01

[Purpose] This study investigated the effect of shoulder girdle strengthening, particularly the scapular muscles, on poststroke trunk alignment. [Subjects and Methods] The study involved 30 patients with residual hemiparesis following cerebrovascular stroke. Patient assessment included measuring shoulder muscle peak torque, scapular muscles peak force, spinal lateral deviation angle, and motor functional performance. Patients were randomly allocated either to the control group or the study group and received an 18-session strengthening program including active resisted exercises for shoulder abductors and external rotators in addition to trunk control exercises. The study group received additional strengthening exercises for the scapular muscles. [Results] The two groups showed significant improvement in strength of all shoulder and scapular muscles, with higher improvement in the study group. Similarly, the lateral spinal deviation angles significantly improved in both groups, with significantly higher improvement in the study group. Transfer activity, sitting balance, upper limb functions, and hand movements significantly improved in the two groups, with higher improvement in the latter two functions in the study group. [Conclusion] Strengthening of shoulder girdle muscles, particularly scapular muscles, can significantly contribute to improving the postural alignment of the trunk in patients with poststroke hemiparesis.

Virtual study groups and online Observed Structured Clinical Examinations practices - enabling trainees to enable themselves.

PubMed

Davidson, Dennisa; Evans, Lois

2018-03-01

To explore online study groups as augmentation tools in preparing for the Royal Australian and New Zealand College of Psychiatrists Observed Structured Clinical Examinations (OSCE) for fellowship. An online survey of New Zealand trainees was carried out to assess exam preparedness and openness to virtual study groups and results analysed. Relevant material around virtual study groups for fellowship examinations was reviewed and used to inform a pilot virtual study group. Four New Zealand trainees took part in the pilot project, looking at using a virtual platform to augment OSCE preparation. Of the 50 respondents 36% felt adequately prepared for the OSCE. Sixty-four per cent were interested in using a virtual platform to augment their study. Virtual study groups were noted to be especially important for rural trainees, none of whom felt able to form study groups for themselves. The pilot virtual study group was trialled successfully. All four trainees reported the experience as subjectively beneficial to their examination preparation. Virtual platforms hold promise as an augmentation strategy for exam preparation, especially for rural trainees who are more geographically isolated and less likely to have peers preparing for the same examinations.

"The group facilitates everything": meanings patients with type 2 diabetes mellitus assigned to health education groups.

PubMed

de Melo, Lucas Pereira; de Campos, Edemilson Antunes

2014-01-01

to interpret the meanings patients with type 2 diabetes mellitus assign to health education groups. ethnographic study conducted with Hyperdia groups of a healthcare unit with 26 informants, with type 2 diabetes mellitus, and having participated in the groups for at least three years. Participant observation, social characterization, discussion groups and semi-structured interviews were used to collect data. Data were analyzed through the thematic coding technique. four thematic categories emerged: ease of access to the service and healthcare workers; guidance on diabetes; participation in groups and the experience of diabetes; and sharing knowledge and experiences. The most relevant aspect of this study is the social use the informants in relation to the Hyperdia groups under study. the studied groups are agents producing senses and meanings concerning the process of becoming ill and the means of social navigation within the official health system. We expect this study to contribute to the actions of healthcare workers coordinating these groups given the observation of the cultural universe of these individuals seeking professional care in the various public health care services.

Mathematics learning disability in girls with Turner syndrome or fragile X syndrome.

PubMed

Murphy, Melissa M; Mazzocco, Michèle M M; Gerner, Gwendolyn; Henry, Anne E

2006-07-01

Two studies were carried out to examine the persistence (Study 1) and characteristics (Study 2) of mathematics learning disability (MLD) in girls with Turner syndrome or fragile X during the primary school years (ages 5-9 years). In Study 1, the rate of MLD for each syndrome group exceeded the rate observed in a grade-matched comparison group, although the likelihood of MLD persisting through the primary school years was comparable for all three groups. In Study 2, formal and informal math skills were compared across the syndrome groups, a normative group, and children from the normative group who had MLD. Few differences were observed between the Turner syndrome and normative groups. Despite having rote counting and number representation skills comparable to those in the normative group, girls with fragile X had difficulty with counting rules (e.g., cardinality, number constancy). However, this difficulty did not distingush them from the MLD group. Overall, counting skills appear to distinguish the Turner syndrome and fragile X groups, suggesting that the specificity of math deficits emerges earlier for fragile X than Turner syndrome.

The Effect of Using Case Studies in Business Statistics

ERIC Educational Resources Information Center

Pariseau, Susan E.; Kezim, Boualem

2007-01-01

The authors evaluated the effect on learning of using case studies in business statistics courses. The authors divided students into 3 groups: a control group, a group that completed 1 case study, and a group that completed 3 case studies. Results evidenced that, on average, students whom the authors required to complete a case analysis received…

Adolescent peer group identification and characteristics: A review of the literature

PubMed Central

Sussman, Steve; Pokhrel, Pallav; Ashmore, Richard D.; Brown, B. Bradford

2011-01-01

This study provides an exhaustive review of 44 peer-reviewed quantitative or qualitative data-based peer-reviewed studies completed on adolescent peer group identification. Adolescent peer group identification is one’s self-perceived or other-perceived membership in discrete teenage peer groups. The studies reviewed suggest that adolescent peer groups consist of five general categories differentiable by lifestyle characteristics: Elites, Athletes, Academics, Deviants, and Others. We found that the Deviant adolescent group category reported relatively greater participation in drug use and other problem behaviors across studies, whereas Academics and Athletes exhibited the least participation in these problem behaviors. Additional research is needed in this arena to better understand the operation of adolescent group labels. PMID:17188815

Corporal artistic training influences attention: a pilot study.

PubMed

Ribeiro, Mônica Medeiros; Lima, Isabela; Malloy-Diniz, Leandro; Lage, Guilherme; Pimentel, Lucia Gouvêa; Teixeira, Antônio Lúcio

2014-06-01

This study assessed the effect of the Body Rhythmics (BRIM) on actors' attentional processes. BRIM is a combination of exercises using numbers and rules that enact musical parameters in the moving body through displacements. Male actors (N = 22) participated in the study: 7 in the BRIM (Study) group and 15 in the Control group (groups were equivalent on mean Raven's IQ). The Continuous Performance Test (CPT-II) was administered before and after an intensive period of BRIM training. There was no significant difference on the CPT-II before training. Group results for before vs after training showed a significant difference for reaction time for the Study group. There was also a trend to increased errors of commission in the Study group after BRIM training.