A higher incidence rate of acute coronary syndrome following radiation therapy in patients with breast cancer and a history of coronary artery diseases.

PubMed

Lee, Yen-Chien; Chuang, Jen-Pin; Hsieh, Pi-Ching; Chiou, Meng-Jiun; Li, Chung-Yi

2015-07-01

This study aims to investigate whether patients with breast cancer and a history of cardiovascular diseases (CADs) are at an increased incidence of acute coronary syndrome (ACS) after receiving radiation therapy (RT). In Taiwan, 5828 patients who had a history of CAD were newly diagnosed of breast cancer and received mastectomy between 1999 and 2009. Among these patients, 1851 also received RT. The study cohort was prospectively followed to the end of 2010 for estimating the incidence of ACS in association with exposure to RT. A Cox proportional hazard model that was adjusted for covariates was used to estimate the hazard ratio (HR) of ACS. Over the study period, the incident rates of ACS for RT and control patients were estimated at 1.51 and 1.77 per 100 person-years, respectively. Covariate-adjusted regression analysis indicated that the hazard of ACS significantly increased in RT patients at an adjusted HR of 1.48 [95% confidence interval (CI) 1.18-1.87]. Both hypertension and diabetes significantly increased the hazard of ACS in this patient cohort, with adjusted HRs of 3.31 (95% CI 1.94-5.66) and 1.50 (95% CI 1.19-1.89), respectively. This 12-year follow-up study suggested excess of ACS events in association with RT exposure in patients with breast cancer who had a higher cardiovascular risk. In consideration of the benefit associated with RT, intensive cardiac care should be given to patients with breast cancer and high cardiovascular risk.

Randomized Phase III Noninferiority Study Comparing Two Radiotherapy Fractionation Schedules in Patients With Low-Risk Prostate Cancer

PubMed Central

Dignam, James J.; Amin, Mahul B.; Bruner, Deborah W.; Low, Daniel; Swanson, Gregory P.; Shah, Amit B.; D’Souza, David P.; Michalski, Jeff M.; Dayes, Ian S.; Seaward, Samantha A.; Hall, William A.; Nguyen, Paul L.; Pisansky, Thomas M.; Faria, Sergio L.; Chen, Yuhchyau; Koontz, Bridget F.; Paulus, Rebecca; Sandler, Howard M.

2016-01-01

Purpose Conventional radiotherapy (C-RT) treatment schedules for patients with prostate cancer typically require 40 to 45 treatments that take place from > 8 to 9 weeks. Preclinical and clinical research suggest that hypofractionation—fewer treatments but at a higher dose per treatment—may produce similar outcomes. This trial was designed to assess whether the efficacy of a hypofractionated radiotherapy (H-RT) treatment schedule is no worse than a C-RT schedule in men with low-risk prostate cancer. Patients and Methods A total of 1,115 men with low-risk prostate cancer were randomly assigned 1:1 to C-RT (73.8 Gy in 41 fractions over 8.2 weeks) or to H-RT (70 Gy in 28 fractions over 5.6 weeks). This trial was designed to establish (with 90% power and an α of .05) that treatment with H-RT results in 5-year disease-free survival (DFS) that is not worse than C-RT by more than 7.65% (H-RT/C-RT hazard ratio [HR] < 1.52). Results A total of 1,092 men were protocol eligible and had follow-up information; 542 patients were assigned to C-RT and 550 to H-RT. Median follow-up was 5.8 years. Baseline characteristics were not different according to treatment assignment. The estimated 5-year DFS was 85.3% (95% CI, 81.9 to 88.1) in the C-RT arm and 86.3% (95% CI, 83.1 to 89.0) in the H-RT arm. The DFS HR was 0.85 (95% CI, 0.64 to 1.14), and the predefined noninferiority criterion that required that DFS outcomes be consistent with HR < 1.52 was met (P < .001). Late grade 2 and 3 GI and genitourinary adverse events were increased (HR, 1.31 to 1.59) in patients who were treated with H-RT. Conclusion In men with low-risk prostate cancer, the efficacy of 70 Gy in 28 fractions over 5.6 weeks is not inferior to 73.8 Gy in 41 fractions over 8.2 weeks, although an increase in late GI/genitourinary adverse events was observed in patients treated with H-RT. PMID:27044935

Randomized Phase III Noninferiority Study Comparing Two Radiotherapy Fractionation Schedules in Patients With Low-Risk Prostate Cancer.

PubMed

Lee, W Robert; Dignam, James J; Amin, Mahul B; Bruner, Deborah W; Low, Daniel; Swanson, Gregory P; Shah, Amit B; D'Souza, David P; Michalski, Jeff M; Dayes, Ian S; Seaward, Samantha A; Hall, William A; Nguyen, Paul L; Pisansky, Thomas M; Faria, Sergio L; Chen, Yuhchyau; Koontz, Bridget F; Paulus, Rebecca; Sandler, Howard M

2016-07-10

Conventional radiotherapy (C-RT) treatment schedules for patients with prostate cancer typically require 40 to 45 treatments that take place from > 8 to 9 weeks. Preclinical and clinical research suggest that hypofractionation-fewer treatments but at a higher dose per treatment-may produce similar outcomes. This trial was designed to assess whether the efficacy of a hypofractionated radiotherapy (H-RT) treatment schedule is no worse than a C-RT schedule in men with low-risk prostate cancer. A total of 1,115 men with low-risk prostate cancer were randomly assigned 1:1 to C-RT (73.8 Gy in 41 fractions over 8.2 weeks) or to H-RT (70 Gy in 28 fractions over 5.6 weeks). This trial was designed to establish (with 90% power and an α of .05) that treatment with H-RT results in 5-year disease-free survival (DFS) that is not worse than C-RT by more than 7.65% (H-RT/C-RT hazard ratio [HR] < 1.52). A total of 1,092 men were protocol eligible and had follow-up information; 542 patients were assigned to C-RT and 550 to H-RT. Median follow-up was 5.8 years. Baseline characteristics were not different according to treatment assignment. The estimated 5-year DFS was 85.3% (95% CI, 81.9 to 88.1) in the C-RT arm and 86.3% (95% CI, 83.1 to 89.0) in the H-RT arm. The DFS HR was 0.85 (95% CI, 0.64 to 1.14), and the predefined noninferiority criterion that required that DFS outcomes be consistent with HR < 1.52 was met (P < .001). Late grade 2 and 3 GI and genitourinary adverse events were increased (HR, 1.31 to 1.59) in patients who were treated with H-RT. In men with low-risk prostate cancer, the efficacy of 70 Gy in 28 fractions over 5.6 weeks is not inferior to 73.8 Gy in 41 fractions over 8.2 weeks, although an increase in late GI/genitourinary adverse events was observed in patients treated with H-RT. © 2016 by American Society of Clinical Oncology.

Role of clinical and laboratory parameters for treatment choice in patients with inherited FVII deficiency undergoing surgical procedures: evidence from the STER registry.

PubMed

Di Minno, Matteo N D; Napolitano, Mariasanta; Dolce, Alberto; Mariani, Guglielmo

2018-02-01

Perioperative bleeding is a major concern in patients with factor VII (FVII) deficiency. Evaluating data of 95 FVII-deficient patients undergoing 110 surgical procedures (61 major, 49 minor), we assessed the impact of type of surgery, bleeding phenotype and FVII coagulant activity (FVII:C) levels on perioperative replacement therapy (RT). Compared to those with higher FVII:C levels, patients with <3% FVII:C received a higher number of RT doses (8 vs. 2, P = 0·003) for a longer RT duration (3 days vs. 1 day, P = 0·001), with no difference in RT dose. Similarly, patients with a history of major bleeds received a higher number of RT doses (8·5 vs. 2-3, P = 0·013) for a longer RT duration (2 days vs. 1 day, P = 0·005) as compared to those with a history of minor bleeds or to asymptomatic patients. No difference in RT was found among major and minor surgical procedures. Overall, multivariate analysis showed that history of major bleeding was the only independent predictor of number of RT doses (β = 0·352, P = 0·001) and RT duration (β = 0·405, P = 0·018). Overall, a ≈20 μg/kg perioperative RT was efficacious in 95·5% of cases. The infusion should be repeated ≈8 times in high-risk subsets (i.e. patients with a history of major bleeding). © 2017 John Wiley & Sons Ltd.

Propensity-Weighted Comparison of Long-Term Risk of Urinary Adverse Events in Elderly Women Treated For Cervical Cancer

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

Elliott, Sean P., E-mail: selliott@umn.edu; Fan, Yunhua; Jarosek, Stephanie

Purpose: Cervical cancer treatment is associated with a risk of urinary adverse events (UAEs) such as ureteral stricture and vesicovaginal fistula. We sought to measure the long-term UAE risk after surgery and radiation therapy (RT), with confounding controlled through propensity-weighted models. Methods and Materials: From the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we identified women ≥66 years old with nonmetastatic cervical cancer treated with simple surgery (SS), radical hysterectomy (RH), external beam RT plus brachytherapy (EBRT+BT), or RT+surgery. We matched them to noncancer controls 1:3. Differences in demographic and cancer characteristics were balanced by propensity weighting. Grade 3 tomore » 4 UAEs were identified by diagnosis codes plus treatment codes. Cumulative incidence was measured using Kaplan-Meier methods. The hazard associated with different cancer treatments was compared using Cox models. Results: UAEs occurred in 272 of 1808 cases (17%) and 222 of 5424 (4%) controls; most (62%) were ureteral strictures. The raw cumulative incidence of UAEs was highest in advanced cancers. UAEs occurred in 31% of patients after EBRT+BT, 25% of patients after RT+surgery, and 15% of patients after RH; however, after propensity weighting, the incidence was similar. In adjusted Cox models (reference = controls), the UAE risk was highest after RT+surgery (hazard ratio [HR], 5.07; 95% confidence interval [CI], 2.32-11.07), followed by EBRT+BT (HR, 3.33; 95% CI, 1.45-7.65), RH (HR, 3.65; 95% CI, 1.41-9.46) and SS (HR, 0.99; 95% CI, 0.32-3.01). The higher risk after RT+surgery versus EBRT+BT was statistically significant, whereas, EBRT+BT and RH were not significantly different from each other. Conclusions: UAEs are common after cervical cancer treatment, particularly in patients with advanced cancers. UAEs are more common after RT, but these women tend to have the advanced cancers. After propensity weighting, the risk after RT was similar to that after surgery.« less

The Impact of Body Mass Index on Heterotopic Ossification

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

Mourad, Waleed Fouad, E-mail: Waleed246@gmail.com; Department of Radiation Oncology, Beth Israel Medical Center, New York, NY; Department of Radiation Oncology, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY

2012-04-01

Purpose: To analyze the impact of different body mass index (BMI) as a surrogate marker for heterotopic ossification (HO) in patients who underwent surgical repair (SR) for displaced acetabular fractures (DAF) followed by radiation therapy (RT). Methods and Materials: This is a single-institution retrospective study of 395 patients. All patients underwent SR for DAF followed by RT {+-} indomethacin. All patients received postoperative RT, 7 Gy, within 72 h. The patients were separated into four groups based on their BMI: <18.5, 18.5-24.9, 25-29.9, and >30. The end point of this study was to evaluate the efficacy of RT {+-} indomethacinmore » in preventing HO in patients with different BMI. Results: Analysis of BMI showed an increasing incidence of HO with increasing BMI: <18.5, (0%) 0/6 patients; 18.5-24.9 (6%), 6 of 105 patients developed HO; 25-29.9 (19%), 22 of 117; >30 (31%), 51 of 167. Chi-square and multivariate logistic regression analysis showed that the correlation between odds of HO and BMI is significant, p < 0.0001. As the BMI increased, the risk of HO and Brooker Classes 3, 4 HO increased. The risk of developing HO is 1.0 Multiplication-Sign (10%) more likely among those with higher BMI compared with those with lower BMI. For a one-unit increase in BMI the log odds of HO increases by 1.0, 95% CI (1.06-1.14). Chi-square test shows no significant difference among all other factors and HO (e.g., indomethacin, race, gender). Conclusions: Despite similar surgical treatment and prophylactic measures (RT {+-} indomethacin), the risk of HO appears to significantly increase in patients with higher BMI after DAF. Higher single-fraction doses or multiple fractions and/or combination therapy with nonsteroidal inflammatory drugs may be of greater benefit to these patients.« less

On the importance of accounting for competing risks in pediatric cancer trials designed to delay or avoid radiotherapy: I. Basic concepts and first analyses.

PubMed

Tai, Bee-Choo; Grundy, Richard G; Machin, David

2010-04-01

In trials designed to delay or avoid irradiation among children with malignant brain tumor, although irradiation after disease progression is an important event, patients who have disease progression may decline radiotherapy (RT), or those without disease progression may opt for elective RT. To accurately describe the cumulative need for RT in such instances, it is crucial to account for these distinct events and to evaluate how each contributes to the delay or advancement of irradiation via a competing risks analysis. We describe the summary of competing events in such trials using competing risks methods based on cumulative incidence functions and Gray's test. The results obtained are contrasted with standard survival methods based on Kaplan-Meier curves, cause-specific hazard functions and log-rank test. The Kaplan-Meier method overestimates all event-specific rates. The cause-specific hazard analysis showed reduction in hazards for all events (A: RT after progression; B: no RT after progression; C: elective RT) among children with ependymoma. For event A, a higher cumulative incidence was reported for ependymoma. Although Gray's test failed to detect any difference (p = 0.331) between histologic subtypes, the log-rank test suggested marginal evidence (p = 0.057). Similarly, for event C, the log-rank test found stronger evidence of reduction in hazard among those with ependymoma (p = 0.005) as compared with Gray's test (p = 0.086). To evaluate treatment differences, failing to account for competing risks using appropriate methodology may lead to incorrect interpretations.

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

Castle, Katherine O., E-mail: kocastle@mdanderson.org; Hoffman, Karen E.; Levy, Lawrence B.

Purpose: The benefit of adding androgen deprivation therapy (ADT) to dose-escalated radiation therapy (RT) for men with intermediate-risk prostate cancer is unclear; therefore, we assessed the impact of adding ADT to dose-escalated RT on freedom from failure (FFF). Methods: Three groups of men treated with intensity modulated RT or 3-dimensional conformal RT (75.6-78 Gy) from 1993-2008 for prostate cancer were categorized as (1) 326 intermediate-risk patients treated with RT alone, (2) 218 intermediate-risk patients treated with RT and ≤6 months of ADT, and (3) 274 low-risk patients treated with definitive RT. Median follow-up was 58 months. Recursive partitioning analysis basedmore » on FFF using Gleason score (GS), T stage, and pretreatment PSA concentration was applied to the intermediate-risk patients treated with RT alone. The Kaplan-Meier method was used to estimate 5-year FFF. Results: Based on recursive partitioning analysis, intermediate-risk patients treated with RT alone were divided into 3 prognostic groups: (1) 188 favorable patients: GS 6, ≤T2b or GS 3+4, ≤T1c; (2) 71 marginal patients: GS 3+4, T2a-b; and (3) 68 unfavorable patients: GS 4+3 or T2c disease. Hazard ratios (HR) for recurrence in each group were 1.0, 2.1, and 4.6, respectively. When intermediate-risk patients treated with RT alone were compared to intermediate-risk patients treated with RT and ADT, the greatest benefit from ADT was seen for the unfavorable intermediate-risk patients (FFF, 74% vs 94%, respectively; P=.005). Favorable intermediate-risk patients had no significant benefit from the addition of ADT to RT (FFF, 94% vs 95%, respectively; P=.85), and FFF for favorable intermediate-risk patients treated with RT alone approached that of low-risk patients treated with RT alone (98%). Conclusions: Patients with favorable intermediate-risk prostate cancer did not benefit from the addition of ADT to dose-escalated RT, and their FFF was nearly as good as patients with low-risk disease. In patients with GS 4+3 or T2c disease, the addition of ADT to dose-escalated RT did improve FFF.« less

Survival Outcomes of Whole-Pelvic Versus Prostate-Only Radiation Therapy for High-Risk Prostate Cancer Patients With Use of the National Cancer Data Base

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

Amini, Arya; Jones, Bernard L.; Yeh, Norman

Purpose/Objectives: The addition of whole pelvic (WP) compared with prostate-only (PO) radiation therapy (RT) for clinically node-negative prostate cancer remains controversial. The purpose of our study was to evaluate the survival benefit of adding WPRT versus PO-RT for high-risk, node-negative prostate cancer, using the National Cancer Data Base (NCDB). Methods and Materials: Patients with high-risk prostate cancer treated from 2004 to 2006, with available data for RT volume, coded as prostate and pelvis (WPRT) or prostate alone (PO-RT) were included. Multivariate analysis (MVA) and propensity-score matched analysis (PSM) were performed. Recursive partitioning analysis (RPA) based on overall survival (OS) usingmore » Gleason score (GS), T stage, and pretreatment prostate-specific antigen (PSA) was also conducted. Results: A total of 14,817 patients were included: 7606 (51.3%) received WPRT, and 7211 (48.7%) received PO-RT. The median follow-up time was 81 months (range, 2-122 months). Under MVA, the addition of WPRT for high-risk patients had no OS benefit compared with PO-RT (HR 1.05; P=.100). On subset analysis, patients receiving dose-escalated RT also did not benefit from WPRT (HR 1.01; P=.908). PSM confirmed no survival benefit with the addition of WPRT for high-risk patients (HR 1.05; P=.141). In addition, RPA was unable to demonstrate a survival benefit of WPRT for any subset. Other prognostic factors for inferior OS under MVA included older age (HR 1.25; P<.001), increasing comorbidity scores (HR 1.46; P<.001), higher T stage (HR 1.17; P<.001), PSA (HR 1.81; P<.001), and GS (HR 1.29; P<.001), and decreasing median county household income (HR 1.15; P=.011). Factors improving OS included the addition of androgen deprivation therapy (HR 0.92; P=.033), combination external beam RT plus brachytherapy boost (HR 0.71; P<.001), and treatment at an academic/research institution (HR 0.84; P=.002). Conclusion: In the largest reported analysis of WPRT for patients with high-risk prostate cancer treated in the dose-escalated era, the addition of WPRT demonstrated no survival advantage compared with PO-RT.« less

Factors Predictive of Receiving Adjuvant Radiotherapy in High-Intermediate-Risk Stage I Endometrial Cancer.

PubMed

McGunigal, Mary; Pollock, Ariel; Doucette, John T; Liu, Jerry; Chadha, Manjeet; Kalir, Tamara; Gupta, Vishal

2018-06-01

Randomized trials have shown a local control benefit with adjuvant radiotherapy (RT) in high-intermediate-risk endometrial cancer patients, although not all such patients receive RT. We reviewed the National Cancer Data Base to investigate which patient/tumor-related factors are associated with delivery of adjuvant RT. The National Cancer Data Base was queried for patients diagnosed with International Federation of Gynecology and Obstetrics 2009 stage I endometrioid adenocarcinoma from 1998 to 2012 who underwent surgery +/- adjuvant RT. Exclusion criteria were unknown stage/grade, nonsurgical primary therapy, less than 30 days' follow-up, RT of more than 6 months after surgery, or palliative treatment. High-intermediate risk was defined based on Post Operative Radiation Therapy in Endometrial Carcinoma 2 criteria: older than 60 years with stage IA grade 3 or stage IB grade 1-2. Seventeen thousand five hundred twenty-four met inclusion criteria, and the 13,651 patients with complete data were subjected to a multiple logistic regression analysis; 7814 (57.2%) received surgery alone, and 5837 (42.8%) received surgery + RT. Receipt of adjuvant RT was more likely among black women and women with higher income, Northeastern residence, diagnosis after 2010, greater than 50% myometrial invasion, and receipt of adjuvant chemotherapy (P < 0.05). Patients older than 80 years or those undergoing lymph node dissection were less likely to receive adjuvant RT (P < 0.05). Of those treated with RT, 44.0% received external beam therapy, 54.8% received vaginal cuff brachytherapy, and 0.6% received both. Among irradiated women, patients older than 80 years and those with Northeastern residence, treatment at academic facilities, diagnosis after 2004, and lymph node dissection were more likely to undergo brachytherapy over external beam radiation therapy (P < 0.05). Overall use of adjuvant RT was 28.8% between 1998 and 2004, 42.0% between 2005 and 2010, and 43.4% between 2011 and 2012; the difference between 1998-2004 and 2005-2010 was not statistically significant. Fewer than half of patients with high-intermediate-risk endometrial cancer by Post Operative Radiation Therapy in Endometrial Carcinoma 2 criteria received adjuvant RT despite evidence demonstrating improved local control. Both patient- and tumor-related factors are associated with delivery of adjuvant RT and the modality selected.

Effects of Neck Radiation Therapy on Extra-Cranial Carotid Arteries Atherosclerosis Disease Prevalence: Systematic Review and a Meta-Analysis

PubMed Central

Bashar, Khalid; Healy, Donagh; Clarke-Moloney, Mary; Burke, Paul; Kavanagh, Eamon; Walsh, Stewart-Redmond

2014-01-01

Introduction Radiation arteritis following neck irradiation as a treatment for head and neck malignancy has been well documented. The long-term sequelae of radiation exposure of the carotid arteries may take years to manifest clinically, and extra-cranial carotid artery (ECCA) stenosis is a well-recognised vascular complication. These carotid lesions should not be regarded as benign and should be treated in the same manner as standard carotid stenosis. Previous studies have noted increased cerebrovascular events such as stroke in this cohort of patients because of high-grade symptomatic carotid stenosis resulting in emboli. Aim To evaluate the effect of radiation therapy on ECCA atherosclerosis progression. Methods Online search for case-control studies and randomised clinical trials that reported on stenosis in extra-cranial carotid arteries in patients with neck malignancies who received radiation therapy (RT) comparing them to patients with neck malignancies who did not receive RT. Results Eight studies were included in the final analysis with total of 1070 patients – 596 received RT compared to 474 in the control group. There was statistically significant difference in overall stenosis rate (Pooled risk ratio  =  4.38 [2.98, 6.45], P  =  0.00001) and severe stenosis (Pooled risk ratio  =  7.51 [2.78, 20.32], P <0.0001), both being higher in the RT group. Pooled analysis of the five studies that reported on mild stenosis also showed significant difference (Pooled risk ratio  =  2.74 [1.75, 4.30], 95% CI, P  =  0.0001). Conclusion The incidence of severe ECCA stenosis is higher among patients who received RT for neck malignancies. Those patients should be closely monitored and screening programs should be considered in all patients who receive neck RT. PMID:25329500

Outcome According to Elective Pelvic Radiation Therapy in Patients With High-Risk Localized Prostate Cancer: A Secondary Analysis of the GETUG 12 Phase 3 Randomized Trial.

PubMed

Blanchard, Pierre; Faivre, Laura; Lesaunier, François; Salem, Naji; Mesgouez-Nebout, Nathalie; Deniau-Alexandre, Elisabeth; Rolland, Frédéric; Ferrero, Jean-Marc; Houédé, Nadine; Mourey, Loïc; Théodore, Christine; Krakowski, Ivan; Berdah, Jean-François; Baciuchka, Marjorie; Laguerre, Brigitte; Davin, Jean-Louis; Habibian, Muriel; Culine, Stéphane; Laplanche, Agnès; Fizazi, Karim

2016-01-01

The role of pelvic elective nodal irradiation (ENI) in the management of prostate cancer is controversial. This study analyzed the role of pelvic radiation therapy (RT) on the outcome in high-risk localized prostate cancer patients included in the Groupe d'Etude des Tumeurs Uro-Genitales (GETUG) 12 trial. Patients with a nonpretreated high-risk localized prostate cancer and a staging lymphadenectomy were randomly assigned to receive either goserelin every 3 months for 3 years and 4 cycles of docetaxel plus estramustine or goserelin alone. Local therapy was administered 3 months after the start of systemic treatment. Performance of pelvic ENI was left to the treating physician. Only patients treated with primary RT were included in this analysis. The primary endpoint was biochemical progression-free survival (bPFS). A total of 413 patients treated from 2002 to 2006 were included, of whom 358 were treated using primary RT. A total of 208 patients received pelvic RT and 150 prostate-only RT. Prostate-specific antigen (PSA) concentration, Gleason score, or T stage did not differ according to performance of pelvic RT; pN+ patients more frequently received pelvic RT than pN0 patients (P<.0001). Median follow-up was 8.8 years. In multivariate analysis, bPFS was negatively impacted by pN stage (hazard ratio [HR]: 2.52 [95% confidence interval [CI]: 1.78-3.54], P<.0001), Gleason score 8 or higher (HR: 1.41 [95% CI: 1.03-1.93], P=.033) and PSA higher than 20 ng/mL (HR: 1.41 [95% CI: 1.02-1.96], P=.038), and positively impacted by the use of chemotherapy (HR: 0.66 [95% CI: 0.48-0.9], P=.009). There was no association between bPFS and use of pelvic ENI in multivariate analysis (HR: 1.10 [95% CI: 0.78-1.55], P=.60), even when analysis was restricted to pN0 patients (HR: 0.88 [95% CI: 0.59-1.31], P=.53). Pelvic ENI was not associated with increased acute or late patient reported toxicity. This unplanned analysis of a randomized trial failed to demonstrate a benefit of pelvic ENI on bPFS in high-risk localized prostate cancer patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Prostate cancer-specific mortality after radical prostatectomy or external beam radiation therapy in men with 1 or more high-risk factors.

PubMed

D'Amico, Anthony V; Chen, Ming-Hui; Catalona, William J; Sun, Leon; Roehl, Kimberly A; Moul, Judd W

2007-07-01

Estimates of prostate cancer-specific mortality (PCSM) were determined after radical prostatectomy (RP) or radiation therapy (RT) in men with >or=1 high-risk factors. The study cohort comprised 948 men who underwent RP (N = 660) or RT (N = 288) for localized prostate cancer between 1988 and 2004 and had at least 1 of the following high-risk factors: a prostate-specific antigen (PSA) velocity >2 ng/mL/year during the year before diagnosis, a biopsy Gleason score of >or=7, a PSA level of >or=10 ng/mL, or clinical category T2b or high disease. Grays regression was used to evaluate whether the number and type of high-risk factors were associated with time to PCSM. Multiple determinants of high risk were found to be significantly associated with a shorter time to PCSM after RP (P < .001) or RT (P 2 ng/mL/year was associated with an increased risk of PCSM after RP (hazards ratio [HR] of 7.3; 95% confidence interval [95% CI], 1.0-59 [P = .05]) or RT (HR of 12.1; 95% CI, 1.4-105 [P = .02]) when compared with men with any other single high-risk factor. Men with a PSA velocity >2 ng/mL/year had a significantly higher risk of PCSM compared with men who had any other single high-risk factor. These men should be considered for randomized trials evaluating the impact on PCSM from adding systemic agents to standards of care for men with high-risk PC. Copyright (c) 2007 American Cancer Society.

Clinical Outcomes Among Children With Standard-Risk Medulloblastoma Treated With Proton and Photon Radiation Therapy: A Comparison of Disease Control and Overall Survival

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

Eaton, Bree R.; Esiashvili, Natia; Kim, Sungjin

Purpose: The purpose of this study was to compare long-term disease control and overall survival between children treated with proton and photon radiation therapy (RT) for standard-risk medulloblastoma. Methods and Materials: This multi-institution cohort study includes 88 children treated with chemotherapy and proton (n=45) or photon (n=43) RT between 2000 and 2009. Overall survival (OS), recurrence-free survival (RFS), and patterns of failure were compared between the 2 cohorts. Results: Median (range) age was 6 years old at diagnosis (3-21 years) for proton patients versus 8 years (3-19 years) for photon patients (P=.011). Cohorts were similar with respect to sex, histology, extent of surgical resection,more » craniospinal irradiation (CSI) RT dose, total RT dose, whether the RT boost was delivered to the posterior fossa (PF) or tumor bed (TB), time from surgery to RT start, or total duration of RT. RT consisted of a median (range) CSI dose of 23.4 Gy (18-27 Gy) and a boost of 30.6 Gy (27-37.8 Gy). Median follow-up time is 6.2 years (95% confidence interval [CI]: 5.1-6.6 years) for proton patients versus 7.0 years (95% CI: 5.8-8.9 years) for photon patients. There was no significant difference in RFS or OS between patients treated with proton versus photon RT; 6-year RFS was 78.8% versus 76.5% (P=.948) and 6-year OS was 82.0% versus 87.6%, respectively (P=.285). On multivariate analysis, there was a trend for longer RFS with females (P=.058) and higher CSI dose (P=.096) and for longer OS with females (P=.093). Patterns of failure were similar between the 2 cohorts (P=.908). Conclusions: Disease control with proton and photon radiation therapy appears equivalent for standard risk medulloblastoma.« less

Management of patients with cardiac implantable electronic devices (CIED) undergoing radiotherapy: A consensus document from Associazione Italiana Aritmologia e Cardiostimolazione (AIAC), Associazione Italiana Radioterapia Oncologica (AIRO), Associazione Italiana Fisica Medica (AIFM).

PubMed

Zecchin, Massimo; Severgnini, Mara; Fiorentino, Alba; Malavasi, Vincenzo Livio; Menegotti, Loris; Alongi, Filippo; Catanzariti, Domenico; Jereczek-Fossa, Barbara Alicja; Stasi, Michele; Russi, Elvio; Boriani, Giuseppe

2018-03-15

The management of patients with a cardiac implanted electronic device (CIED) receiving radiotherapy (RT) is challenging and requires a structured multidisciplinary approach. A consensus document is presented as a result of a multidisciplinary working group involving cardiac electrophysiologists, radiation oncologists and physicists in order to stratify the risk of patients with CIED requiring RT and approaching RT sessions appropriately. When high radiation doses and beam energy higher than 6MV are used, CIED malfunctions can occur during treatment. In our document, we reviewed the different types of RT and CIED behavior in the presence of ionizing radiations and electromagnetic interferences, from the cardiologist's, radiation oncologist's and medical physicist's point of view. We also reviewed in vitro and in vivo literature data and other national published guidelines on this issue so far. On the basis of literature data and consensus of experts, a detailed approach based on risk stratification and appropriate management of RT patients with CIEDs is suggested, with important implications for clinical practice. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Long-term Impact of Adjuvant Versus Early Salvage Radiation Therapy in pT3N0 Prostate Cancer Patients Treated with Radical Prostatectomy: Results from a Multi-institutional Series.

PubMed

Fossati, Nicola; Karnes, R Jeffrey; Boorjian, Stephen A; Moschini, Marco; Morlacco, Alessandro; Bossi, Alberto; Seisen, Thomas; Cozzarini, Cesare; Fiorino, Claudio; Noris Chiorda, Barbara; Gandaglia, Giorgio; Dell'Oglio, Paolo; Joniau, Steven; Tosco, Lorenzo; Shariat, Shahrokh; Goldner, Gregor; Hinkelbein, Wolfgang; Bartkowiak, Detlef; Haustermans, Karin; Tombal, Bertrand; Montorsi, Francesco; Van Poppel, Hein; Wiegel, Thomas; Briganti, Alberto

2017-06-01

Three prospective randomised trials reported discordant findings regarding the impact of adjuvant radiation therapy (aRT) versus observation for metastasis-free survival (MFS) and overall survival (OS) among patients with pT3N0 prostate cancer treated with radical prostatectomy (RP). None of these trials systematically included patients who underwent early salvage radiation therapy (esRT). To test the hypothesis that aRT was associated with better cancer control and survival compared with observation followed by esRT. Using a multi-institutional cohort from seven tertiary referral centres, we retrospectively identified 510 pT3pN0 patients with undetectable prostate-specific antigen (PSA) after RP between 1996 and 2009. Patients were stratified into two groups: aRT (group 1) versus observation followed by esRT in case of PSA relapse (group 2). Specifically, esRT was administered at a PSA level ≤0.5ng/ml. We compared aRT versus observation followed by esRT. The evaluated outcomes were MFS and OS. Multivariable Cox regression analyses tested the association between groups (aRT vs observation followed by esRT) and oncologic outcomes. Covariates consisted of pathologic stage (pT3a vs pT3b or higher), pathologic Gleason score (≤6, 7, or ≥8), surgical margin status (negative vs positive), and year of surgery. An interaction with groups and baseline patient risk was tested for the hypothesis that the impact of aRT versus observation followed by esRT was different by pathologic characteristics. The nonparametric curve fitting method was used to explore graphically the relationship between MFS and OS at 8 yr and baseline patient risk (derived from the multivariable analysis). Overall, 243 patients (48%) underwent aRT, and 267 (52%) underwent initial observation. Within the latter group, 141 patients experienced PSA relapse and received esRT. Median follow-up after RP was 94 mo (interquartile range [IQR]: 53-126) and 92 mo (IQR: 70-136), respectively (p=0.2). MFS (92% vs 91%; p=0.9) and OS (89% vs 92%; p=0.9) at 8 yr after surgery were not significantly different between the two groups. These results were confirmed in multivariable analysis, in which observation followed by esRT was not associated with a significantly higher risk of distant metastasis (hazard ratio [HR]: 1.35; p=0.4) and overall mortality (HR: 1.39; p=0.4) compared with aRT. Using the nonparametric curve fitting method, a comparable proportion of MFS and OS at 8 yr among groups was observed regardless of pathologic cancer features (p=0.9 and p=0.7, respectively). Limitations consisted of the retrospective nature of the study and the relatively small size of the patient population. At long-term follow-up, no significant differences between aRT and esRT were observed for MFS and OS. Our study, although based on retrospective data, suggests that esRT does not compromise cancer control and potentially reduces overtreatment associated with aRT. At long-term follow-up, no significant differences in terms of distant metastasis and mortality were observed between immediate postoperative adjuvant radiation therapy (aRT) and initial observation followed by early salvage radiation therapy (esRT) in case of prostate-specific antigen relapse. Our study suggests that esRT does not compromise cancer control and potentially reduces overtreatment associated with aRT. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Regional Radiation Therapy Impacts Outcome for Node-Positive Cutaneous Melanoma.

PubMed

Strom, Tobin; Torres-Roca, Javier F; Parekh, Akash; Naghavi, Arash O; Caudell, Jimmy J; Oliver, Daniel E; Messina, Jane L; Khushalani, Nikhil I; Zager, Jonathan S; Sarnaik, Amod; Mulé, James J; Trotti, Andy M; Eschrich, Steven A; Sondak, Vernon K; Harrison, Louis B

2017-04-01

Background: Regional radiation therapy (RT) has been shown to reduce the risk of regional recurrence with node-positive cutaneous melanoma. However, risk factors for regional recurrence, especially in the era of sentinel lymph node biopsy (SLNB), are less clear. Our goals were to identify risk factors associated with regional recurrence and to determine whether a radiosensitivity index (RSI) gene expression signature (GES) could identify patients who experience a survival benefit with regional RT. Methods: A single-institution, Institutional Review Board-approved study was performed including 410 patients treated with either SLNB with or without completion lymph node dissection (LND; n=270) or therapeutic LND (n=91). Postoperative regional RT was delivered to the involved nodal basin in 83 cases (20.2%), to a median dose of 54 Gy (range, 30-60 Gy) in 27 fractions (range, 5-30). Primary outcomes were regional control and overall survival by RSI GES status. Results: Median follow-up was 69 months (range, 13-180). Postoperative regional RT was associated with a reduced risk of regional recurrence among all patients on univariate (5-year estimate: 95.0% vs 83.3%; P =.036) and multivariate analysis (hazard ratio[HR], 0.15; 95% CI, 0.05-0.43; P <.001). Among higher-risk subgroups, regional RT was associated with a lower risk of regional recurrence among patients with clinically detected lymph nodes (n=175; 5-year regional control: 94.1% vs 69.5%; P =.003) and extracapsular extension (ECE) present (n=138; 5-year regional control: 96.7% vs 62.2%; P <.001). Among a subset of radiated patients with gene expression data available, a low RSI GES (radiosensitive) tumor status was associated with improved survival compared with a high RSI GES (5-year: 75% vs 0%; HR, 10.68; 95% CI, 1.24-92.14). Conclusions: Regional RT was associated with a reduced risk of regional recurrence among patients with ECE and clinically detected nodal disease. Gene expression data show promise for better predicting radiocurable patients in the future. In the era of increasingly effective systemic therapies, the value of improved regional control potentially takes on greater significance. Copyright © 2017 by the National Comprehensive Cancer Network.

Effect of local therapy on locoregional recurrence in postmenopausal women with breast cancer in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial.

PubMed

van Hezewijk, Marjan; Bastiaannet, Esther; Putter, Hein; Scholten, Astrid N; Liefers, Gerrit-Jan; Rea, Daniel; Hasenburg, Annette; Paridaens, Robert; Hozumi, Yasuo; Markopoulos, Christos; Seynaeve, Caroline; Jones, Stephen E; Marijnen, Corrie A M; van de Velde, Cornelis J H

2013-08-01

The TEAM trial investigated the efficacy and safety of adjuvant endocrine therapy consisting of either exemestane or the sequence of tamoxifen followed by exemestane in postmenopausal hormone-sensitive breast cancer. The present analyses explored the association between locoregional therapy and recurrence (LRR) in this population. Between 2001 and 2006, 9779 patients were randomized. Local treatment was breast conserving surgery plus radiotherapy (BCS+RT), mastectomy without radiotherapy (MST-only), or mastectomy plus radiotherapy (MST+RT). Patients with unknown data on surgery, radiotherapy, tumor or nodal stage (n=199), and patients treated by lumpectomy without radiotherapy (n=349) were excluded. After a median follow-up of 5.2 years, 270 LRRs occurred (2.9%) among 9231 patients. The 5-years actuarial incidence of LRR was 4.2% (95% CI 3.3-4.9%) for MST-only, 3.4% (95% CI 2.4-4.2%) for MST+RT and 1.9% (95% CI 1.5-2.3%) for BCS+RT. After adjustment for prognostic factors, the hazard ratio (HR, reference BCS+RT) for LRR remained significantly higher for MST-only (HR 1.53; 95% CI 1.10-2.11), not for MST+RT (HR 0.78; 95% CI 0.50-1.22). This explorative analysis showed a higher LRR risk after MST-only than after BCS+RT, even after adjustment for prognostic factors. As this effect was not seen for MST+RT versus BCS+RT, it might be explained by the beneficial effects of radiation treatment. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Co-infection of two beta-herpesviruses (CMV and HHV-7) as an increased risk factor for 'CMV disease' in patients undergoing renal transplantation.

PubMed

Chapenko, S; Folkmane, I; Tomsone, V; Amerika, D; Rozentals, R; Murovska, M

2000-10-01

The ubiquity of human cytomegalovirus (CMV) and human herpesvirus-7 (HHV-7), as well as activation of these viruses during immunosuppression, allows the suggestion that both viruses could participate in the development of 'CMV disease' in patients after renal transplantation (RT). The aim of our research was to study the prevalence of latent CMV and HHV-7 infections in patients before RT, to determine interaction between these viruses in dual infection and possible association of their reactivation with the progression of 'CMV disease' after RT. Peripheral blood samples were collected from 49 patients before and up to 10-12 wk after RT. The methods used for diagnostics of viral infections were: serology, nested polymerase chain reaction (nPCR) analysis of peripheral blood leukocytes (PBL) and plasma, and virus isolation in cell cultures (morphological changes, nPCR analysis of cellular and cell-free samples, indirect immunofluorescence analysis). Before RT, CMV and HHV-7 DNAs were detected in PBL but not in the plasma samples, which indicates the presence of latent viral infection in patients. Latent dual (CMV + HHV-7) infection was prevalent (51.0%) in 49 patients, while CMV and HHV-7 infections alone were detected in 26.5 and 12.2% of patients, respectively. Risk of viral disease after RT, for recipients with latent dual infection before RT, was 12- and 2.2-fold higher in comparison with CMV and HHV-7 infections alone, respectively. Frequency of dual infection in 18 recipients with 'viral syndrome' or 'CMV disease' after RT was reliably higher (13/18, 81.3%) than CMV (1/18, 6.2%) (p < 0.025) and HHV-7 (2/18, 12.5%) (p < 0.025) infections alone. HHV-7 reactivation preceded CMV reactivation in 77.0% of the cases of dual infection in the recipients with viral disease and reactivation of both viruses preceded the development of viral disease. Severe 'CMV disease' developed in 2 out of 2 recipients with CMV primary infection and 'viral syndrome' in 1 recipient with CMV reinfection. The reactivation of CMV was detected in all recipients prior to onset of the disease. Correlation was shown between reactivation of latent HHV-7 infection and development of febrile syndrome in 2 out of 2 recipients with HHV-7 infection alone. Taking into account that dual infection is an increased risk factor for 'viral syndrome' and 'CMV disease' development, screening diagnostic should include testing for both viral infections in transplant donors as well as in recipients before and after RT.

Characteristics and Impact Factors of Renal Threshold for Glucose Excretion in Patients with Type 2 Diabetes Mellitus.

PubMed

Yue, Xiao Dan; Wang, Jing Yu; Zhang, Xin Rong; Yang, Ju Hong; Shan, Chun Yan; Zheng, Miao Yan; Ren, Hui Zhu; Zhang, Yi; Yang, Shao Hua; Guo, Zhen Hong; Chang, Bai; Chang, Bao Cheng

2017-04-01

Sodium glucose co-transporter 2 (SGLT-2) inhibitors are newly developed but promising medicine for type 2 diabetes. However, patients with a different renal threshold for glucose excretion (RT(G)) may have a different reaction to this medicine. Therefore, the objective of this study was to investigate the characteristics of RT(G) and its impact factors in patients with type 2 diabetes mellitus (T2DM). The clinical and laboratory data of 36 healthy individuals and 168 in-hospital patients with T2DM were collected and analyzed, RT(G) was calculated using blood glucose (BG) measured by dynamic BG monitoring, urinary glucose excretion (UGE) and estimated glomerular filtration rate (eGFR). The characteristics of RT(G) were investigated. The risk factors for high RT(G) were analyzed using non-conditional logistic regression analysis. Our results found that RT(G) of the T2DM group was higher than that of the healthy individuals (P < 0.05); and 22.22% from the healthy individuals group but 58.33% from the T2DM group had high RT(G). Age, duration of diabetes, body mass index (BMI), and homeostasis model assessment insulin resistance index (HOMA-IR) were independently associated with high RT(G) (P < 0.05). Further stratified analysis revealed that RT(G) in T2DM patients increased with age, duration of diabetes, and BMI. In conclusion, RT(G) is increased in patients with T2DM, especially in those with longer diabetic duration, higher BMI, and those who are older. Therefore, these patients may be more sensitive to SGLT-2 inhibitors. © 2017 The Korean Academy of Medical Sciences.

Outcome According to Elective Pelvic Radiation Therapy in Patients With High-Risk Localized Prostate Cancer: A Secondary Analysis of the GETUG 12 Phase 3 Randomized Trial

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

Blanchard, Pierre, E-mail: pierre.blanchard@gustaveroussy.fr; University of Paris-Sud, Cancer Campus, Villejuif; Faivre, Laura

Purpose: The role of pelvic elective nodal irradiation (ENI) in the management of prostate cancer is controversial. This study analyzed the role of pelvic radiation therapy (RT) on the outcome in high-risk localized prostate cancer patients included in the Groupe d'Etude des Tumeurs Uro-Genitales (GETUG) 12 trial. Methods and Materials: Patients with a nonpretreated high-risk localized prostate cancer and a staging lymphadenectomy were randomly assigned to receive either goserelin every 3 months for 3 years and 4 cycles of docetaxel plus estramustine or goserelin alone. Local therapy was administered 3 months after the start of systemic treatment. Performance of pelvic ENI was leftmore » to the treating physician. Only patients treated with primary RT were included in this analysis. The primary endpoint was biochemical progression-free survival (bPFS). Results: A total of 413 patients treated from 2002 to 2006 were included, of whom 358 were treated using primary RT. A total of 208 patients received pelvic RT and 150 prostate-only RT. Prostate-specific antigen (PSA) concentration, Gleason score, or T stage did not differ according to performance of pelvic RT; pN+ patients more frequently received pelvic RT than pN0 patients (P<.0001). Median follow-up was 8.8 years. In multivariate analysis, bPFS was negatively impacted by pN stage (hazard ratio [HR]: 2.52 [95% confidence interval [CI]: 1.78-3.54], P<.0001), Gleason score 8 or higher (HR: 1.41 [95% CI: 1.03-1.93], P=.033) and PSA higher than 20 ng/mL (HR: 1.41 [95% CI: 1.02-1.96], P=.038), and positively impacted by the use of chemotherapy (HR: 0.66 [95% CI: 0.48-0.9], P=.009). There was no association between bPFS and use of pelvic ENI in multivariate analysis (HR: 1.10 [95% CI: 0.78-1.55], P=.60), even when analysis was restricted to pN0 patients (HR: 0.88 [95% CI: 0.59-1.31], P=.53). Pelvic ENI was not associated with increased acute or late patient reported toxicity. Conclusions: This unplanned analysis of a randomized trial failed to demonstrate a benefit of pelvic ENI on bPFS in high-risk localized prostate cancer patients.« less

Human Papillomavirus Status and the Risk of Cerebrovascular Events Following Radiation Therapy for Head and Neck Cancer.

PubMed

Addison, Daniel; Seidelmann, Sara B; Janjua, Sumbal A; Emami, Hamed; Staziaki, Pedro V; Hallett, Travis R; Szilveszter, Bálint; Lu, Michael T; Cambria, Richard P; Hoffmann, Udo; Chan, Annie W; Wirth, Lori J; Neilan, Tomas G

2017-08-30

Radiation therapy (RT) is a standard treatment for head and neck cancer; however, it is associated with inflammation, accelerated atherosclerosis, and cerebrovascular events (CVEs; stroke or transient ischemic attack). Human papillomavirus (HPV) is found in nearly half of head and neck cancers and is associated with inflammation and atherosclerosis. Whether HPV confers an increased risk of CVEs after RT is unknown. Using an institutional database, we identified all consecutive patients treated with RT from 2002 to 2012 for head and neck cancer who were tested for HPV. The outcome of interest was the composite of ischemic stroke and transient ischemic attack, and the association between HPV and CVEs was assessed using Cox proportional hazard models, competing risk analysis, and inverse probability weighting. Overall, 326 participants who underwent RT for head and neck cancer were tested for HPV (age 59±12 years, 75% were male, 9% had diabetes mellitus, 45% had hypertension, and 61% were smokers), of which 191 (59%) were tumor HPV positive. Traditional risk factors for CVEs were similar between HPV-positive and -negative patients. Over a median follow-up of 3.4 years, there were 18 ischemic strokes and 5 transient ischemic attacks (event rate of 1.8% per year). The annual event rate was higher in the HPV-positive patients compared with the HPV-negative patients (2.6% versus 0.9%, P =0.002). In a multivariable model, HPV-positive status was associated with a >4 times increased risk of CVEs (hazard ratio: 4.4; 95% confidence interval, 1.5-13.2; P =0.008). In this study, HPV-positive status is associated with an increased risk of stroke or transient ischemic attack following RT for head and neck cancer. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Women with Low-Risk DCIS Eligible for the LORIS Trial After Complete Surgical Excision: How Low Is Their Risk After Standard Therapy?

PubMed

Pilewskie, Melissa; Olcese, Cristina; Patil, Sujata; Van Zee, Kimberly J

2016-12-01

Identifying DCIS patients at low risk for disease progression could obviate need for standard therapy. The LORIS (surgery versus active monitoring for low-risk DCIS) trial is studying the safety of monitoring low-risk DCIS, although ipsilateral breast tumor recurrence (IBTR) rates in patients meeting enrollment criteria after complete surgical excision are unknown. Women with pure DCIS treated with breast-conserving surgery (BCS) with/without radiation therapy (RT) from 1/1996-1/2011 were included from a prospectively maintained database. IBTR rates were compared between those who did and did not meet LORIS eligibility criteria (age ≥ 46 years, screen-detected calcifications, nipple discharge absence, minimal family history, non-high-grade DCIS) after complete surgical excision. A total of 2394 women were identified; 401 met LORIS criteria. Median follow-up was 5.9 years; 431 had ≥10 years follow-up. LORIS cohort median age was 61 years (range 46-86 years); 207 (52 %) underwent RT, 79 (20 %) received endocrine therapy. Of 401 patients, 24 experienced an IBTR. Overall 10-year IBTR rates were 10.3 % (LORIS) versus 15.4 % (non-LORIS) (p = 0.08); without RT, 12.1 versus 21.4 %, respectively (p = 0.06). The 10-year invasive-IBTR rates for women meeting LORIS criteria were: 5.3 % BCS overall, 6.0 % without RT. Women meeting LORIS criteria (after complete surgical excision) are at somewhat lower risk for IBTR. Among such women undergoing excision without RT, the 10-year invasive-IBTR rate was 6 %. Given that approximately 20 % of women with core biopsy-proven non-high-grade DCIS have invasive cancer at excision, women managed without excision would be expected to incur higher invasive cancer rates. Additional criteria are needed to identify women not requiring intervention for DCIS.

Aspirin resistance as cardiovascular risk after kidney transplantation

NASA Astrophysics Data System (ADS)

Sandor, Barbara; Varga, Adam; Rabai, Miklos; Toth, Andras; Papp, Judit; Toth, Kalman; Szakaly, Peter

2014-05-01

International surveys have shown that the leading cause of death after kidney transplantation has cardiovascular origin with a prevalence of 35-40%. As a preventive strategy these patients receive aspirin (ASA) therapy, even though their rate of aspirin resistance is still unknown. In our study, platelet aggregation measurements were performed between 2009 and 2012 investigating the laboratory effect of low-dose aspirin (100 mg) treatment using a CARAT TX4 optical aggregometer. ASA therapy was considered clinically effective in case of low ( i.e., below 40%) epinephrine-induced (10 μM) platelet aggregation index. Rate of aspirin resistance, morbidity and mortality data of kidney transplanted patients (n = 255, mean age: 49 ± 12 years) were compared to a patient population with cardio- and cerebrovascular diseases (n = 346, mean age: 52.6 ± 11 years). Rate of aspirin resistance was significantly higher in the renal transplantation group (RT) compared to the positive control group (PC) (35.9% vs. 25.6%, p < 0.002). Morbidity analysis demonstrated significantly higher incidence of myocardial infarction, hypertension and diabetes mellitus in the RT group (p < 0.05). The subgroup analysis revealed significantly higher incidence of infarction and stroke in the ASA resistant RT group compared to the RT patients without ASA resistance (p < 0.05). Furthermore, the incidence of myocardial infarction and hypertension was significantly higher in the non-resistant RT group than in the group of PC patients without ASA resistance (p < 0.05). These results may suggest that the elevated rate of aspirin resistance contributes to the high cardiovascular mortality after kidney transplantation.

Sequencing of Local Therapy Affects the Pattern of Treatment Failure and Survival in Children With Atypical Teratoid Rhabdoid Tumors of the Central Nervous System

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

Pai Panandiker, Atmaram S., E-mail: atmaram.pai-panandiker@stjude.org; Merchant, Thomas E.; Beltran, Chris

Purpose: To assess the pattern of treatment failure associated with current therapeutic paradigms for childhood atypical teratoid rhabdoid tumors (AT/RT). Methods and Materials: Pediatric patients with AT/RT of the central nervous system treated at our institution between 1987 and 2007 were retrospectively evaluated. Overall survival (OS), progression-free survival, and cumulative incidence of local failure were correlated with age, sex, tumor location, extent of disease, and extent of surgical resection. Radiotherapy (RT) sequencing, chemotherapy, dose, timing, and volume administered after resection were also evaluated. Results: Thirty-one patients at a median age of 2.3 years at diagnosis (range, 0.45-16.87 years) were enrolledmore » into protocols that included risk- and age-stratified RT. Craniospinal irradiation with focal tumor bed boost (median dose, 54 Gy) was administered to 18 patients. Gross total resection was achieved in 16. Ten patients presented with metastases at diagnosis. RT was delayed more than 3 months in 20 patients and between 1 and 3 months in 4; 7 patients received immediate postoperative irradiation preceding high-dose alkylator-based chemotherapy. At a median follow-up of 48 months, the cumulative incidence of local treatment failure was 37.5% {+-} 9%; progression-free survival was 33.2% {+-} 10%; and OS was 53.5% {+-} 10%. Children receiving delayed RT ({>=}1 month postoperatively) were more likely to experience local failure (hazard ratio [HR] 1.23, p = 0.007); the development of distant metastases before RT increased the risk of progression (HR 3.49, p = 0.006); and any evidence of disease progressionbefore RT decreased OS (HR 20.78, p = 0.004). Disease progression occurred in 52% (11/21) of children with initially localized tumors who underwent gross total resection, and the progression rate increased proportionally with increasing delay from surgery to RT. Conclusions: Delayed RT is associated with a higher rate of local and metastatic disease progression in children with AT/RT. Current treatment regimens for pediatric patients with AT/RT are distinctly age stratified; novel protocols investigating RT volumes and sequencing are needed.« less

The impact of patient compliance with adjuvant radiotherapy: a comprehensive cohort study

PubMed Central

Badakhshi, Harun; Gruen, Arne; Sehouli, Jalid; Budach, Volker; Boehmer, Dirk

2013-01-01

Postoperative radiotherapy (RT) is the standard of care for early stage breast cancer. It reduces the risk for local recurrence and prolongs survival. We assessed whether, the omission of RT because of patient's preference may influence the prognosis and, thus, the quality of cancer care. Detailed information from a prospectively collected database of a breast cancer center was analyzed. Multiple regression analysis and univariate and multivariate analysis for risk factors for recurrence were performed. The entire cohort of primary breast cancer patients in a given time period was analyzed. Data from 1903 patients undergoing treatment at breast cancer center between 2003 and 2008 were used. All patient underwent breast conserving surgery and RT was performed for all patients of the cohort. Local tumor control and disease-free survival were calculated. After a median follow-up of 2.18 years (maximum 6.39 years), 5.5% of patients did not follow guideline-based recommendations for RT. There was a significant correlation between noncompliance and patient's age, adjuvant hormonal therapy (97.0%), and adjuvant chemotherapy (96.8%). Seventy local recurrences occurred that corresponds to a local recurrence rate of 3.9%. The difference in regard to local recurrence-free 5-year survival between the compliant patients and the noncompliant patients is absolute 17.9 (93.3% and 75.4%). Noncompliant patients had suffered a 5.02-fold increased risk of local recurrence than compliant patients. The omission of RT after breast-conserving surgery results in a higher local failure rate and significantly worsens clinical outcome. Age may play an important role because of the comorbidities of aged patients or the assumed low RT tolerance in this group. On a clinical level, this data suggests that improvement is needed to correct this situation, and the question remains as to how best to improve RT compliance. PMID:24403236

The impact of patient compliance with adjuvant radiotherapy: a comprehensive cohort study.

PubMed

Badakhshi, Harun; Gruen, Arne; Sehouli, Jalid; Budach, Volker; Boehmer, Dirk

2013-10-01

Postoperative radiotherapy (RT) is the standard of care for early stage breast cancer. It reduces the risk for local recurrence and prolongs survival. We assessed whether, the omission of RT because of patient's preference may influence the prognosis and, thus, the quality of cancer care. Detailed information from a prospectively collected database of a breast cancer center was analyzed. Multiple regression analysis and univariate and multivariate analysis for risk factors for recurrence were performed. The entire cohort of primary breast cancer patients in a given time period was analyzed. Data from 1903 patients undergoing treatment at breast cancer center between 2003 and 2008 were used. All patient underwent breast conserving surgery and RT was performed for all patients of the cohort. Local tumor control and disease-free survival were calculated. After a median follow-up of 2.18 years (maximum 6.39 years), 5.5% of patients did not follow guideline-based recommendations for RT. There was a significant correlation between noncompliance and patient's age, adjuvant hormonal therapy (97.0%), and adjuvant chemotherapy (96.8%). Seventy local recurrences occurred that corresponds to a local recurrence rate of 3.9%. The difference in regard to local recurrence-free 5-year survival between the compliant patients and the noncompliant patients is absolute 17.9 (93.3% and 75.4%). Noncompliant patients had suffered a 5.02-fold increased risk of local recurrence than compliant patients. The omission of RT after breast-conserving surgery results in a higher local failure rate and significantly worsens clinical outcome. Age may play an important role because of the comorbidities of aged patients or the assumed low RT tolerance in this group. On a clinical level, this data suggests that improvement is needed to correct this situation, and the question remains as to how best to improve RT compliance. © 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Identifying prognostic intratumor heterogeneity using pre- and post-radiotherapy 18F-FDG PET images for pancreatic cancer patients.

PubMed

Yue, Yong; Osipov, Arsen; Fraass, Benedick; Sandler, Howard; Zhang, Xiao; Nissen, Nicholas; Hendifar, Andrew; Tuli, Richard

2017-02-01

To stratify risks of pancreatic adenocarcinoma (PA) patients using pre- and post-radiotherapy (RT) PET/CT images, and to assess the prognostic value of texture variations in predicting therapy response of patients. Twenty-six PA patients treated with RT from 2011-2013 with pre- and post-treatment 18F-FDG-PET/CT scans were identified. Tumor locoregional texture was calculated using 3D kernel-based approach, and texture variations were identified by fitting discrepancies of texture maps of pre- and post-treatment images. A total of 48 texture and clinical variables were identified and evaluated for association with overall survival (OS). The prognostic heterogeneity features were selected using lasso/elastic net regression, and further were evaluated by multivariate Cox analysis. Median age was 69 y (range, 46-86 y). The texture map and temporal variations between pre- and post-treatment were well characterized by histograms and statistical fitting. The lasso analysis identified seven predictors (age, node stage, post-RT SUVmax, variations of homogeneity, variance, sum mean, and cluster tendency). The multivariate Cox analysis identified five significant variables: age, node stage, variations of homogeneity, variance, and cluster tendency (with P=0.020, 0.040, 0.065, 0.078, and 0.081, respectively). The patients were stratified into two groups based on the risk score of multivariate analysis with log-rank P=0.001: a low risk group (n=11) with a longer mean OS (29.3 months) and higher texture variation (>30%), and a high risk group (n=15) with a shorter mean OS (17.7 months) and lower texture variation (<15%). Locoregional metabolic texture response provides a feasible approach for evaluating and predicting clinical outcomes following treatment of PA with RT. The proposed method can be used to stratify patient risk and help select appropriate treatment strategies for individual patients toward implementing response-driven adaptive RT.

Risk of myeloid neoplasms after radiotherapy among older women with localized breast cancer: A population-based study

PubMed Central

Long, Jessica B.; Wang, Rong; Hu, Xin; Yu, James B.; Huntington, Scott F.; Abel, Gregory A.; Mougalian, Sarah S.; Podoltsev, Nikolai A.; Gore, Steven D.; Gross, Cary P.; Ma, Xiaomei; Davidoff, Amy J.

2017-01-01

Background There are inconsistent and limited data regarding the risk of myeloid neoplasms (MN) among breast cancer survivors who received radiotherapy (RT) in the absence of chemotherapy. Concern about subsequent MN might influence the decision to use adjuvant RT for women with localized disease. As patients with therapy-related MN have generally poor outcomes, the presumption of subsequent MN being therapy-related could affect treatment recommendations. Methods We used the Surveillance, Epidemiology, and End Results (SEER)–Medicare linked database to study older women with in-situ or stage 1–3 breast cancer diagnosed 2001–2009 who received surgery. Chemotherapy and RT were ascertained using Medicare claims, and new MN diagnoses were captured using both SEER registry and Medicare claims. We excluded women who received chemotherapy for initial treatment, and censored at receipt of subsequent chemotherapy. Competing-risk survival analysis was used to assess the association between RT and risk of subsequent MN adjusting for relevant characteristics. Results Median follow-up for 60,426 eligible patients was 68 months (interquartile range, 46 to 92 months), with 47.6% receiving RT. In total, 316 patients (0.52%) were diagnosed with MN; the cumulative incidence per 10,000 person-years was 10.6 vs 9.0 among RT-treated vs non-RT-treated women, respectively (p = .004); the increased risk of subsequent MN persisted in the adjusted analysis (hazard ratio = 1.36, 95% confidence interval: 1.03–1.80). The results were consistent in multiple sensitivity analyses. Conclusions Our data suggest that RT is associated with a significant risk of subsequent MN among older breast cancer survivors, though the absolute risk increase is very small. These findings suggest the benefits of RT outweigh the risks of development of subsequent MN. PMID:28902882

Impact of conventional fractionated RT to pelvic lymph nodes and dose-escalated hypofractionated RT to prostate gland using IMRT treatment delivery in high-risk prostate cancer

NASA Astrophysics Data System (ADS)

Pervez, Nadeem

Prostate cancer is the most common cancer among Canadian men. The standard treatment in high-risk category is radical radiation, with androgen suppression treatment (AST). Significant disease progression is reported despite this approach. Radiation dose escalation has been shown to improve disease-free survival; however, it results in higher toxicities. Hypofractionated radiation schedules (larger dose each fraction in shorter overall treatment time) are expected to deliver higher biological doses. A hypofractionated scheme was used in this study to escalate radiation doses with AST. Treatment was well tolerated acutely. Early results of self-administered quality of life reported by patients shows a decrease in QOL which is comparable to other treatment schedules. Significant positional variation of the prostate was observed during treatment. Therefore, we suggest daily target verification to avoid a target miss. Initial late effects are reasonable and early treatment outcomes are promising. Longer follow-up is required for full outcomes assessments.

Equipoise among recanalization strategies.

PubMed

Tomsick, T A; Khatri, P; Jovin, T; Demaerschalk, B; Malisch, T; Demchuk, A; Hill, M D; Jauch, E; Spilker, J; Broderick, J P

2010-03-30

Modern acute ischemic stroke therapy is based on the premise that recanalization and subsequent reperfusion are essential for the preservation of brain tissue and favorable clinical outcomes. We outline key issues that we think underlie equipoise regarding the comparative clinical efficacy of IV recombinant tissue-type plasminogen activator (rt-PA) and intra-arterial (IA) reperfusion therapies for acute ischemic stroke. On the one hand, IV rt-PA therapy has the benefit of speed with presumed lower rates of recanalization of large artery occlusions as compared to IA methods. More recent reports of major arterial occlusions treated with IV rt-PA, as measured by transcranial Doppler and magnetic resonance angiography, demonstrate higher rates of recanalization. Conversely, IA therapies report higher recanalization rates, but are hampered by procedural delays and risks, even failing to be applied at all in occasional patients where time to reperfusion remains a critical factor. Higher rates of recanalization in IA trials using clot-removal devices have not translated into improved patient functional outcome as compared to trials of IV therapy. Combined IV-IA therapy promises to offer advantages of both, but perhaps only when applied in the timeliest of fashions, compared to IV therapy alone. Where equipoise exists, randomizing subjects to either IV rt-PA therapy or IV therapy followed by IA intervention, while incorporating new interventions into the study design, is a rational and appropriate research approach.

Short-term effects of sports taping on navicular height, navicular drop and peak plantar pressure in healthy elite athletes: A within-subject comparison.

PubMed

Kim, Taegyu; Park, Jong-Chul

2017-11-01

Medial tibial stress syndrome (MTSS) is one of the most common exercise-induced leg pain. The navicular drop (ND) was identified as a risk factor for MTSS. This study aimed to evaluate the short-term effects of sports taping applied to the supporting lower leg during sitting, standing, walking, and jogging to restrict the ND in healthy elite athletes.Twenty-four healthy elite athletes without a history of exercise-induced pain or injuries in the lower limbs participated in this study (median age: 21.00 years; 1st--3rd quartiles; 19.25-22.00). The 4 taping conditions were used: rigid taping (RT), kinesiology taping (KT), placebo taping (PT), and non-taping (NT). The order of taping techniques was randomly assigned. Normalized navicular height (NH), ND, and normalized ND evaluated using 3-dimensional motion analysis, and normalized peak plantar pressure (PP) were compared in 4 taping conditions during sitting, standing, walking, and jogging.During sitting, the normalized NH of RT is higher than that of NT, KT, and PT (χ = 17.30, P = .001), while during jogging, the normalized NH of RT is higher than that of NT and PT (χ = 10.55, P = .014). The normalized peak PP of NT is higher than that of PT (χ = 8.871, P = .031) in the lateral midfoot region.This study showed the RT technique maintained NH during sitting and jogging, and the RT technique could be an effective preventive and treatment strategy for MTSS.

Cerebral Microbleeds are an Independent Predictor of Hemorrhagic Transformation Following Intravenous Alteplase Administration in Acute Ischemic Stroke.

PubMed

Nagaraja, Nandakumar; Tasneem, Nudrat; Shaban, Amir; Dandapat, Sudeepta; Ahmed, Uzair; Policeni, Bruno; Olalde, Heena; Shim, Hyungsub; Samaniego, Edgar A; Pieper, Connie; Ortega-Gutierrez, Santiago; Leira, Enrique C; Adams, Harold P

2018-05-01

Intravenous alteplase (rt-PA) increases the risk of hemorrhagic transformation of acute ischemic stroke. The objective of our study was to evaluate clinical, laboratory, and imaging predictors on forecasting the risk of hemorrhagic transformation following treatment with rt-PA. We also evaluated the factors associated with cerebral microbleeds that increase the risk of hemorrhagic transformation. Consecutive patients with acute ischemic stroke admitted between January 1, 2009 and December 31, 2013 were included in the study if they received IV rt-PA, had magnetic resonance imaging (MRI) of the brain on admission, and computed tomography or MRI of the brain at 24 (18-36) hours later to evaluate for the presence of hemorrhagic transformation. The clinical data, lipid levels, platelet count, MRI, and computed tomography images were retrospectively reviewed. The study included 366 patients, with mean age 67 ± 15 years; 46% were women and 88% were white. The median National Institutes of Health Stroke Scale (NIHSS) score was 6 (interquartile range 3-15). Hemorrhagic transformation was observed in 87 (23.8%) patients and cerebral microbleeds were noted in 95 (25.9%). Patients with hemorrhagic transformation tended to be older, nonwhite, have atrial fibrillation, higher baseline NIHSS score, lower cholesterol and triglyceride levels, and cerebral microbleeds and nonlacunar infarcts. Patients with cerebral microbleeds were more likely to be older, have hypertension, hyperlipidemia, previous history of stroke, and prior use of antithrombotics. On multivariate analysis race, NIHSS score, nonlacunar infarct, and presence of cerebral microbleeds were independently associated with hemorrhagic transformation following treatment with rt-PA. Presence of cerebral microbleeds is an independent predictor of hemorrhagic transformation of acute ischemic stroke following treatment with rt-PA. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Co-morbid conditions in use of recombinant tissue plasminogen activator (rt-PA) for the treatment of acute ischaemic stroke.

PubMed

Nathaniel, Thomas I; Cochran, Thomas; Chaves, Jose; Fulmer, Eric; Sosa, Crystal; Yi, Sara; Fredwall, Megan; Sternberg, Shannon; Blackhurst, Dawn; Nelson, Alfred; Leacock, Rodney

2016-01-01

The objective of this study was to characterize the comorbidities in a population of patients with an acute ischaemic stroke, comparing patients that received recombinant tissue plasminogen activator (rt-PA) to those that did not receive rt-PA. In a retrospective sample of 663 patients admitted for acute ischaemic stroke, this study analysed the effects of co-morbid conditions in the use of rt-PA. It determined non-cerebrovascular risk factors (comorbidities) that differentiate patients who received rt-PA from those who did not receive rt-PA. Patients with a history of carotid stenosis, CHF and previous strokes are significantly (p < 0.05) associated with high risk of not receiving rt-PA. A significant number of patients with a history of hypertension and smoking received rt-PA (p < 0.05). The findings indicate that certain risk factors including carotid stenosis, CHF and previous stroke history impact the treatment of patients with acute ischaemic stroke, specifically the decision to administer rt-PA. Treatment with rt-PA is dependent on stroke severity and onset to treatment time, but the findings suggest that rt-PA use may also depend on patient comorbidities.

Cost-Effectiveness Analysis of Preoperative Versus Postoperative Radiation Therapy in Extremity Soft Tissue Sarcoma

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

Qu, Xuanlu M.; Louie, Alexander V.; Ashman, Jonathan

Purpose: Surgery combined with radiation therapy (RT) is the cornerstone of multidisciplinary management of extremity soft tissue sarcoma (STS). Although RT can be given in either the preoperative or the postoperative setting with similar local recurrence and survival outcomes, the side effect profiles, costs, and long-term functional outcomes are different. The aim of this study was to use decision analysis to determine optimal sequencing of RT with surgery in patients with extremity STS. Methods and Materials: A cost-effectiveness analysis was conducted using a state transition Markov model, with quality-adjusted life years (QALYs) as the primary outcome. A time horizon ofmore » 5 years, a cycle length of 3 months, and a willingness-to-pay threshold of $50,000/QALY was used. One-way deterministic sensitivity analyses were performed to determine the thresholds at which each strategy would be preferred. The robustness of the model was assessed by probabilistic sensitivity analysis. Results: Preoperative RT is a more cost-effective strategy ($26,633/3.00 QALYs) than postoperative RT ($28,028/2.86 QALYs) in our base case scenario. Preoperative RT is the superior strategy with either 3-dimensional conformal RT or intensity-modulated RT. One-way sensitivity analyses identified the relative risk of chronic adverse events as having the greatest influence on the preferred timing of RT. The likelihood of preoperative RT being the preferred strategy was 82% on probabilistic sensitivity analysis. Conclusions: Preoperative RT is more cost effective than postoperative RT in the management of resectable extremity STS, primarily because of the higher incidence of chronic adverse events with RT in the postoperative setting.« less

A Pragmatic Evaluation of the National Cancer Institute Physician Data Query (PDQ)®-Based Brief Counseling on Cancer-Related Fatigue among Patients Undergoing Radiation Therapy

PubMed Central

Bauml, Joshua; Xie, Sharon X; Penn, Courtney; Desai, Krupali; Dong, Kimberly W; Bruner, Deborah Watkins; Vapiwala, Neha; Mao, Jun James

2018-01-01

Purpose Cancer-Related Fatigue (CRF) negatively affects quality of life among cancer patients. This study seeks to evaluate the outcome and patient receptiveness of a brief counseling program based on National Cancer Institute (NCI) PDQ® information to manage CRF when integrated into Radiation Therapy (RT). Methods We conducted a prospective cohort study among patients undergoing non-palliative RT. Patients with stage I–III tumors and with Karnofsky score 60 or better were given a ten-minute behavioral counseling session during the first two weeks of RT. The Brief Fatigue Inventory (BFI) was administered at baseline/end of RT. Results Of 93 patients enrolled, 89% found the counseling useful and practical. By the end of RT, 59% reported increased exercise, 41.6% sought nutrition counseling, 72.7% prioritized daily activities, 74.4% took daytime naps, and 70.5% talked with other cancer patients. Regarding counseling, patients who had received chemotherapy prior to RT had no change in fatigue (−0.2), those who received RT alone had mild increase in fatigue (0.7, p=0.02), and those who received concurrent chemotherapy experienced a substantial increase in fatigue (3.0 to 5.2, p=0.05). Higher baseline fatigue and receipt of chemotherapy were predictive of worsened fatigue in a multivariate model (both p<0.01). Conclusion Our data suggests that brief behavioral counseling based on NCI guidelines is well accepted by patients showing an uptake in many activities to cope with CRF. Those who receive concurrent chemotherapy and with higher baseline fatigue are at risk for worsening fatigue despite of guideline-based therapy. PMID:29479490

Robotic versus Open Thyroidectomy for Differentiated Thyroid Cancer: An Evidence-Based Review.

PubMed

Liu, Shirley Yuk Wah; Ng, Enders Kwok Wai

2016-01-01

While open thyroidectomy (OT) is advocated as the gold standard treatment for differentiated thyroid cancer, the contemporary use of robotic thyroidectomy (RT) is often controversial. Although RT combines the unique benefits of the surgical robot and remote access thyroidectomy, its applicability on cancer patients is challenged by the questionable oncological benefits and safety. This review aims to analyze the current literature evidence in comparing RT to OT on thyroid cancers for their perioperative and oncological outcomes. To date, no randomized controlled trial is available in comparing RT to OT. All published studies are nonrandomized or retrospective comparisons. Current data suggests that RT compares less favorably than OT for longer operative time, higher cost, and possibly inferior oncological control with lower number of central lymph nodes retrieved. In terms of morbidity, quality of life outcomes, and short-term recurrence rates, RT and OT are comparable. While conventional OT continues to be appropriate for most thyroid cancers, RT should better be continued by expert surgeons on selected patients who have low-risk thyroid cancers and have high expectations on cosmetic outcomes. Future research should embark on prospective randomized studies for unbiased comparisons. Long-term follow-up studies are also needed to evaluate outcomes on recurrence and survival.

Seroepidemiology and molecular characterization of hepatitis E virus infection in swine and occupationally exposed workers in Punjab, India.

PubMed

Bansal, M; Kaur, S; Deka, D; Singh, R; Gill, J P S

2017-12-01

Hepatitis E virus (HEV) has two discrete epidemiological patterns: waterborne epidemics in developing countries only, caused by HEV genotype I, and sporadic zoonotic outbreaks in developing and developed countries caused by genotypes III and IV. This study was designed to investigate seroprevalence, molecular detection and the characterization of HEV by nested RT-PCR in swine as well as the occupational risk to exposed human population in Punjab state of north-western India. The occupational risk-exposed group comprised of swine farmers (organized - mixed feed feeders and unorganized - swill feeders), slaughterhouse workers, sewage workers and veterinary internes. During the study period, blood and faecal samples were collected from 320 swine and 360 humans with both high and low occupational exposure risks. The overall seroprevalence of swine HEV was 65.00%, with a significantly higher seropositivity in growing pigs (2-8 months of age). The prevalence of HEV RNA in swine faecal samples by nRT-PCR was 8.75% with a significantly higher detection in swill-fed pigs. With humans in the high occupational exposure risk population, significantly higher anti-HEV IgG seropositivity was observed (60.48%) as compared to control population (10.71%). Strong evidence of association between human anti-HEV IgG seropositivity and certain occupational exposure risk groups was observed (p < 0.05). This indicates that unorganized swine farmers, slaughterhouse workers and sewage workers have higher odds of HEV infection in this study region. Percentage of nucleotide similarity between swine and human HEV isolates was less than that found in countries with zoonotic HEV outbreaks. Molecular characterization revealed the circulation of G IV and G I genotypes among swine and human population in Punjab state, respectively. © 2017 Blackwell Verlag GmbH.

Three-month posttreatment prostate-specific antigen level as a biomarker of treatment response in patients with intermediate-risk or high-risk prostate cancer treated with androgen deprivation therapy and radiotherapy.

PubMed

Bryant, Alex K; D'Amico, Anthony V; Nguyen, Paul L; Einck, John P; Kane, Christopher J; McKay, Rana R; Simpson, Daniel R; Mundt, Arno J; Murphy, James D; Rose, Brent S

2018-05-04

Prostate-specific antigen (PSA) measurement after definitive radiotherapy (RT) and androgen deprivation therapy for localized prostate cancer has been proposed as an early prognostic biomarker. In the current study, the authors investigated the association between 3-month post-RT PSA level and biochemical progression-free survival (bPFS), prostate cancer-specific survival (PCSS), and overall survival (OS). A total of 5783 patients with intermediate-risk or high-risk localized prostate cancer who were diagnosed between 2000 and 2015 and treated with RT and androgen deprivation therapy were identified from Veterans Affairs data. Patients were divided into groups based on 3-month post-RT PSA values: <0.10 ng/mL, 0.10 to 0.49 ng/mL, and ≥0.50 ng/mL. The effect of the 3-month PSA group on bPFS, PCSS, and OS was evaluated in multivariable Cox models adjusting for potential confounders. There were 2651 patients with intermediate-risk and 3132 with high-risk disease; approximately 11% had a 3-month PSA level of ≥0.50 ng/mL. A higher 3-month PSA level was found to be strongly associated with each outcome; compared with patients in the group with a 3-month PSA value <0.10 ng/mL, the authors noted greater hazards for the patients with a 3-month PSA value ≥0.50 ng/mL (hazard ratio for bPFS: 5.23; PCSS: 3.97; and OS: 1.50 [P<.001 for all]) and the patients with a 3-month PSA value of 0.10 to 0.49 ng/mL (hazard ratio for bPFS: 2.41 [P<.001]; PCSS: 2.29 [P<.001]; and OS: 1.21 [P = .003]). When analyzed separately, the 3-month PSA level was found to be predictive of OS in the high-risk group (P<.001) but not the intermediate-risk group (P = .21). The 3-month post-RT PSA level appears to be a strong prognostic biomarker for bPFS, PCSS, and OS in patients with intermediate-risk and high-risk prostate cancer, particularly those with high-risk disease. The 3-month PSA measurement may augment clinical decision making and holds promise as a potential surrogate endpoint in clinical trials. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

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

Son, Christina H.; Law, Ethel; Oh, Jung Hun

Purpose: Although vaginal stenosis (VS) is a recognized toxicity in women who receive pelvic radiation therapy (RT), the relationship between RT dose and the volume and extent of toxicity has not been analyzed. We modeled this relationship to identify predictors of VS. Methods and Materials: We evaluated 54 women, aged 29 to 78 years, who underwent pelvic RT for rectal or anal cancer during 2008 to 2011 and were enrolled in a prospective study evaluating vaginal dilator use. Maximum dilator size was measured before RT (baseline) and 1 month and 12 months after RT. Dilator use was initiated at 1 month. The difference (D)more » in dilator size before and after RT was recorded. Those with D ≤−1 were classified as having VS (n=35); those with D ≥0 were classified as having no VS (n=19 at 1 month). Dose-volume parameters were extracted, and the generalized equivalent uniform dose (gEUD) was used to build a predictive model. Results: The mean vaginal doses were 50.0 Gy and 36.8 Gy for anal and rectal cancer patients, respectively. One month after RT, a gEUD model using a wide range of a values suggests that sparing of vaginal volume to a low dose may be important. When gEUD (a = −1) was <35 Gy and the mean vaginal dose was <43 Gy, severe VS was reduced (P=.02). A 1-year analysis suggests increasingly negative D values with increasing mean dose. However, patients with compliance <40% were more likely to have toxicity. Conclusions: Vaginal stenosis is influenced by multiple RT dose-volume characteristics. Mean dose and gEUD constraints together may reduce the risk of severe VS. Patients receiving higher mean vaginal doses should have greater compliance with dilator therapy to minimize risk of toxicity. Further validation with independent datasets is needed.« less

Robot-assisted laparoscopic prostatectomy is not associated with early postoperative radiation therapy.

PubMed

Chino, Junzo; Schroeck, Florian R; Sun, Leon; Lee, W Robert; Albala, David M; Moul, Judd W; Koontz, Bridget F

2009-11-01

To compare open radical prostatectomy (RP) and robot-assisted laparoscopic prostatectomy (RALP), and to determine whether RALP is associated with a higher risk of features that determine recommendations for postoperative radiation therapy (RT). Patients undergoing RP from 2003 to 2007 were stratified into two groups: open RP and RALP. Preoperative (PSA level, T stage and Gleason score), pathological factors (T stage, Gleason score, extracapsular extension [ECE] and the status of surgical margins and seminal vesicle invasion [SVI]) and early treatment with RT or referral for RT within 6 months were compared between the groups. Multivariate analysis was used to control for selection bias in the RALP group. In all, 904 patients were identified; 368 underwent RALP and 536 underwent open RP (retropubic or perineal). Patients undergoing open RP had a higher pathological stage with ECE present in 24.8% vs 19.3% in RALP (P = 0.05) and SVI in 10.3% vs 3.8% (P < 0.001). In the RALP vs open RP group, there were positive surgical margins in 31.5% vs 31.9% (P = 0.9) and there were postoperative PSA levels of (3) 0.2 ng/mL in 5.7% vs 6.3% (P = 0.7), respectively. On multivariate analysis to control for selection bias, RALP was not associated with indication for RT (odds ratio (OR) 1.10, P = 0.55), or referral for RT (OR 1.04, P = 0.86). RALP was not associated with an increase in either indication or referral for early postoperative RT.

Effect of micro mist sauna bathing on thermoregulatory and circulatory functions and thermal sensation in humans

NASA Astrophysics Data System (ADS)

Iwase, Satoshi; Kawahara, Yuko; Nishimura, Naoki; Sugenoya, Junichi

2016-05-01

To examine the effects of micro mist sauna bathing, produced by water crushing method, we exposed ten male subjects to five cases of micro mist sauna, namely (1) room temperature (RT) 38 °C with 100 % (actually 91 %) relative humidity (RH), (2) RT 41.5 °C with 80 % (actually 81 %) RH, (3) RT 41.5 °C with 100 % (actually 96 %) RH, (4) RT 45.0 °C with 64 % (actually 61 %) RH, and (5) RT 45.0 °C with 100 % (actually 86 %) RH, and measured tympanic temperature, mean skin temperature, heart rate (HR), and cheek moisture content, as well as ratings of thermal and sweating sensation tympanic temperatures at RT 45 °C were significantly higher at 86 % RH than those at 61 % RH; however, those at RT 45 °C with 61 % RH were higher than those with 86 % RH during recovery. There were no significant differences at RT 41.5 °C between with 81 % RH and with 96 % RH. Mean skin temperature was the highest at RT 45 °C 86 % RH case, followed by at RT 41.5 °C 96 % RH, RT 45 °C 61 % RH, RT 41.5 °C 81 % RH, and finally at RT 38 °C 91 % RH. HR change showed the same order as for mean skin temperature. A significant difference in cheek moisture content was observed between RT 41.5 °C with 81 % RH and RT 45 °C with 86 % RH 10 min after the micro mist bathing. There were no significant differences between ratings of thermal sensation at RT 41.5 °C with 81 % RH and at RT 45 °C with 61 % RH and RT 45 °C with 61 % RH and RT 45 °C with 86 % RH. Between RT 45 °C with 86 % RH and RT 41.5 °C with 81 % RH, there was a tendency for interaction (0.05 < p < 0.1). Other cases showed significant higher ratings of thermal sensation at higher room temperature or higher relative humidity. The ratings of sweating sensation 10 min after the mist sauna bathing were significantly higher at higher RT and RH except between RT 41.5 °C 96 % RH and RT 45 °C 86 % RH which exhibited no significant difference. We concluded that the micro mist sauna produced by water crushing method induced more moderate and effective thermal effect during micro mist sauna bathing than the conventional mist sauna bathing. In addition, micro mist sauna is as effective for heating the human subjects as bathtub bathing as well as more moderate thermal and sweating sensations.

Prostate Cancer Radiation Therapy and Risk of Thromboembolic Events

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

Bosco, Cecilia, E-mail: Cecilia.t.bosco@kcl.ac.uk; Garmo, Hans; Regional Cancer Centre, Uppsala, Akademiska Sjukhuset, Uppsala

Purpose: To investigate the risk of thromboembolic disease (TED) after radiation therapy (RT) with curative intent for prostate cancer (PCa). Patients and Methods: We identified all men who received RT as curative treatment (n=9410) and grouped according to external beam RT (EBRT) or brachytherapy (BT). By comparing with an age- and county-matched comparison cohort of PCa-free men (n=46,826), we investigated risk of TED after RT using Cox proportional hazard regression models. The model was adjusted for tumor characteristics, demographics, comorbidities, PCa treatments, and known risk factors of TED, such as recent surgery and disease progression. Results: Between 2006 and 2013, 6232more » men with PCa received EBRT, and 3178 underwent BT. A statistically significant association was found between EBRT and BT and risk of pulmonary embolism in the crude analysis. However, upon adjusting for known TED risk factors these associations disappeared. No significant associations were found between BT or EBRT and deep venous thrombosis. Conclusion: Curative RT for prostate cancer using contemporary methodologies was not associated with an increased risk of TED.« less

Factors associated with cardiovascular target organ damage in children after renal transplantation.

PubMed

Borchert-Mörlins, Bianca; Thurn, Daniela; Schmidt, Bernhard M W; Büscher, Anja K; Oh, Jun; Kier, Tanja; Bauer, Elena; Baig, Sabrina; Kanzelmeyer, Nele; Kemper, Markus J; Büscher, Rainer; Melk, Anette

2017-11-01

Cardiovascular disease is the second-most common cause of death in pediatric renal transplant recipients. The aim of this study was to evaluate subclinical cardiovascular target organ damage defined as the presence of arterio- and atherosclerotic lesions and cardiac remodeling and to analyze contributing risk factors in a large cohort of children after renal transplantation (RT). A total of 109 children aged 13.1 ± 3.3 years who had undergone RT at one of three German transplant centers were enrolled in this study. Patients had been transplanted a mean of 5.5 (±4.0) years prior to being enrolled in the study. Anthropometric data, laboratory values and office- and 24-h ambulatory blood pressure monitoring (ABPM) were evaluated. Cardiovascular target organ damage was determined through non-invasive measurements of aortic pulse wave velocity (PWV), carotid intima-media thickness (IMT) and left ventricular mass (LVM). Elevated PWV or IMT values were detected in 22 and 58% of patients, respectively. Left ventricular hypertrophy was found in as many as 43% of patients. The prevalence of uncontrolled or untreated hypertension was 41%, of which 16% of cases were only detected by ABPM measurements. In the multivariable analysis, higher diastolic blood pressure, everolimus intake and lower estimated glomerular filtration rate were independently associated with high PWV. Higher systolic blood pressure and body mass index were associated with elevated LVM. Our results showed an alarming burden of cardiovascular subclinical organ damage in children after RT. Hypertension, obesity, immunosuppressive regimen and renal function emerged as independent risk factors of organ damage. Whereas the latter is not modifiable, the results of our study strongly indicate that the management of children after RT should focus on the control of blood pressure and weight.

A prognostic role for Nm23-H1 in laryngeal carcinoma treated with postoperative radiotherapy: an introductory investigation.

PubMed

Lionello, Marco; Blandamura, Stella; Agostini, Marco; Staffieri, Claudia; Lovato, Andrea; Tealdo, Giulia; Favaretto, Niccolò; Giacomelli, Luciano; Loreggian, Lucio; Staffieri, Alberto; Marioni, Gino

2013-01-01

Postoperative RT is generally recommended for laryngeal carcinomas (LSCCs) at high risk of recurrence after surgery. There are currently no clinicopathological parameters available to predict response to such adjuvant RT in LSCC, and only a few potentially predictive biomarkers have been investigated. Nm23-H1 protein is reportedly related to the tumor cells' metastatic potential, and low Nm23-H1 expression levels in human carcinomas often correlate with a poor prognosis. The novel aim of the present preliminary study was to investigate the prognostic value of Nm23-H1 expression and subcellular localization in a series of patients given postoperative RT for LSCC. A retrospective clinicopathological investigation was conducted at an academic tertiary referral center of 28 consecutive patients given postoperative RT for LSCC. Image analysis of immunohistochemical reactions was performed to measure Nm23-H1 total and nuclear expression levels. Disease-free survival (DFS) was significantly shorter among LSCC patients with total Nm23-H1 levels <50.0 % (p = 0.03); the mean total Nm23-H1 expression was lower in patients with recurrent disease than in patients without it (statistical trend, p = 0.07). The disease recurrence rate was significantly higher (p = 0.021) and the DFS shorter (statistical trend, p = 0.052) among LSCC patients with nuclear Nm23-H1 levels <5.0 %. The locoregional recurrence-risk ratio in LSCC patients with nuclear Nm23-H1 levels <5.0 % was 9.16. Nm23-H1 warrants further investigation of its potential role as a predictive biomarker with a view to providing tailored treatments after surgery, such as combinations of chemotherapy and RT instead of RT alone, in patients whose LSCCs have low or no Nm23-H1 expression.

Thyroid hormone concentrations, disease, physical function, and mortality in elderly men.

PubMed

van den Beld, Annewieke W; Visser, Theo J; Feelders, Richard A; Grobbee, Diederick E; Lamberts, Steven W J

2005-12-01

Physiological changes in thyroid hormone concentrations might be related to changes in the overall physical function in the elderly. We determined to what extent thyroid hormone concentrations are related to physical function and mortality in elderly men. A longitudinal population study (the Zoetermeer study) was conducted. Mortality was registered in the subsequent 4 yr. Four hundred three independently and ambulatory living men (aged 73-94 yr) participated. The study examined the association between serum thyroid hormones and parameters of physical function as well as the association with mortality. TSH, free T4 (FT4) total T4, T3, rT3, and T4-binding globulin were measured. Physical function was estimated by the number of problems in activities of daily living, a measure of physical performance score (PPS), leg extensor strength and grip strength, bone density, and body composition. Serum rT3 increased significantly with age and the presence of disease. Sixty-three men met the biochemical criteria for the low T3 syndrome (decreased serum T3 and increased serum rT3). This was associated with a lower PPS, independent of disease. Furthermore, higher serum FT4 (within the normal range of healthy adults) and rT3 (above the normal range of healthy adults) were related with a lower grip strength and PPS, independent of age and disease. Isolated low T3 was associated with a better PPS and a higher lean body mass. Low FT4 was related to a decreased risk of 4-yr mortality. In a population of independently living elderly men, higher FT4 and rT3 concentrations are associated with a lower physical function. High serum rT3 may result from a decreased peripheral metabolism of thyroid hormones due to the aging process itself and/or disease and may reflect a catabolic state. Low serum FT4 is associated with a better 4-yr survival; this may reflect an adaptive mechanism to prevent excessive catabolism.

Patient views and correlates of radiotherapy omission in a population-based sample of older women with favorable-prognosis breast cancer.

PubMed

Shumway, Dean A; Griffith, Kent A; Hawley, Sarah T; Wallner, Lauren P; Ward, Kevin C; Hamilton, Ann S; Morrow, Monica; Katz, Steven J; Jagsi, Reshma

2018-04-18

The omission of radiotherapy (RT) after lumpectomy is a reasonable option for many older women with favorable-prognosis breast cancer. In the current study, we sought to evaluate patient perspectives regarding decision making about RT. Women aged 65 to 79 years with AJCC 7th edition stage I and II breast cancer who were reported to the Georgia and Los Angeles County Surveillance, Epidemiology, and End Results registries were surveyed (response rate, 70%) regarding RT decisions, the rationale for omitting RT, decision-making values, and understanding of disease recurrence risk. We also surveyed their corresponding surgeons (response rate, 77%). Patient characteristics associated with the omission of RT were evaluated using multilevel, multivariable logistic regression, accounting for patient clustering within surgeons. Of 999 patients, 135 omitted RT (14%). Older age, lower tumor grade, and having estrogen receptor-positive disease each were found to be strongly associated with omission of RT in multivariable analyses, whereas the number of comorbidities was not. Non-English speakers were more likely to omit RT (adjusted odds ratio, 5.9; 95% confidence interval, 1.4-24.5). The most commonly reported reasons for RT omission were that a physician advised the patient that it was not needed (54% of patients who omitted RT) and patient choice (41%). Risk of local disease recurrence was overestimated by all patients: by approximately 2-fold among those who omitted RT and by approximately 8-fold among those who received RT. The risk of distant disease recurrence was overestimated by approximately 3-fold on average. To some extent, decisions regarding RT omission are appropriately influenced by patient age, tumor grade, and estrogen receptor status, but do not appear to be optimally tailored according to competing comorbidities. Many women who are candidates for RT omission overestimate their risk of disease recurrence. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Criteria for and Appropriateness of Renal Transplantation in Elderly Patients With End-Stage Renal Disease: A Literature Review and Position Statement on Behalf of the European Renal Association-European Dialysis and Transplant Association Descartes Working Group and European Renal Best Practice.

PubMed

Segall, Liviu; Nistor, Ionuţ; Pascual, Julio; Mucsi, Istvan; Guirado, Lluis; Higgins, Robert; Van Laecke, Steven; Oberbauer, Rainer; Van Biesen, Wim; Abramowicz, Daniel; Gavrilovici, Cristina; Farrington, Ken; Covic, Adrian

2016-10-01

During the last 20 years, waiting lists for renal transplantation (RT) have grown significantly older. However, elderly patients (ie ≥65 years of age) are still more rarely referred or accepted to waiting lists and, if enlisted, have less chances of actually receiving a kidney allograft, than younger counterparts. In this review, we looked at evidence for the benefits and risks of RT in the elderly trying to answer the following questions: Should RT be advocated for elderly patients? What should be the criteria to accept elderly patients on the waiting list for RT? What strategies might be used to increase the rate of RT in waitlisted elderly candidates? For selected elderly patients, RT was shown to be superior to dialysis in terms of patient survival. Virtually all guidelines recommend that patients should not be deemed ineligible for RT based on age alone, although a short life expectancy generally might preclude RT. Concerning the assessment of comorbidities in the elderly, special attention should be paid to cardiac evaluation and screening for malignancy. Comorbidity scores and frailty assessment scales might help the decision making on eligibility. Psychosocial issues should also be evaluated. To overcome the scarcity of organ donors, elderly RT candidates should be encouraged to consider expanded criteria donors and living donors, as alternatives to deceased standard criteria donors. It has been demonstrated that expanded criteria donor RT in patients 60 years or older is associated with higher survival rates than remaining on dialysis, whereas living donor RT is superior to all other options.

Dose-response relationship of robot-assisted stroke motor rehabilitation: the impact of initial motor status.

PubMed

Hsieh, Yu-wei; Wu, Ching-yi; Lin, Keh-chung; Yao, Grace; Wu, Kuen-yuh; Chang, Ya-ju

2012-10-01

The increasing availability of robot-assisted therapy (RT), which provides quantifiable, reproducible, interactive, and intensive practice, holds promise for stroke rehabilitation, but data on its dose-response relation are scanty. This study used 2 different intensities of RT to examine the treatment effects of RT and the effect on outcomes of the severity of initial motor deficits. Fifty-four patients with stroke were randomized to a 4-week intervention of higher-intensity RT, lower-intensity RT, or control treatment. The primary outcome, the Fugl-Meyer Assessment, was administered at baseline, midterm, and posttreatment. Secondary outcomes included the Medical Research Council scale, the Motor Activity Log, and the physical domains of the Stroke Impact Scale. The higher-intensity RT group showed significantly greater improvements on the Fugl-Meyer Assessment than the lower-intensity RT and control treatment groups at midterm (P=0.003 and P=0.02) and at posttreatment (P=0.04 and P=0.02). Within-group gains on the secondary outcomes were significant, but the differences among the 3 groups did not reach significance. Recovery rates of the higher-intensity RT group were higher than those of the lower-intensity RT group, particularly on the Fugl-Meyer Assessment. Scatterplots with curve fitting showed that patients with moderate motor deficits gained more improvements than those with severe or mild deficits after the higher-intensity RT. This study demonstrated the higher treatment intensity provided by RT was associated with better motor outcome for patients with stroke, which may shape further stroke rehabilitation. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique identifier: NCT00917605.

Use of External Beam Radiotherapy Is Associated With Reduced Incidence of Second Primary Head and Neck Cancer: A SEER Database Analysis

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

Rusthoven, Kyle; Chen Changhu; Raben, David

2008-05-01

Purpose: Patients with head and neck cancer have a significant risk of developing a second primary cancer of the head and neck. We hypothesized that treatment with external beam radiotherapy (RT) might reduce this risk, because RT can eradicate occult foci of second head and neck cancer (HNCA). Methods and Materials: The data of patients with Surveillance, Epidemiology, and End Results Historic Stage A localized squamous cell carcinoma of the oral cavity, larynx, and pharynx were queried using the Surveillance, Epidemiology, and End Results database. For patients treated with or without RT, the incidence of second HNCA was determined andmore » compared using the log-rank method. Cox proportional hazards analysis was performed for each site, evaluating the influence of covariates on the risk of second HNCA. Results: Between 1973 and 1997, 27,985 patients were entered with localized HNCA. Of these patients, 44% had received RT and 56% had not. The 15-year incidence of second HNCA was 7.7% with RT vs. 10.5% without RT (hazard ratio 0.71, p <0.0001). The effect of RT was more profound in patients diagnosed between 1988 and 1997 (hazard ratio 0.53, p <0.0001) and those with pharynx primaries (hazard ratio 0.47, p <0.0001). On multivariate analysis, RT was associated with a reduced risk of second HNCA for pharynx (p <0.0001) and larynx (p = 0.04) tumors. For oral cavity primaries, RT was associated with an increased risk of second HNCA in patients treated before 1988 (p <0.001), but had no influence on patients treated between 1988 and 1997 (p = 0.91). Conclusion: For localized HNCA, RT is associated with a reduced incidence of second HNCA. These observations are consistent with the eradication of microscopic foci of second HNCA with external beam RT.« less

Associations between waist circumference, metabolic risk and executive function in adolescents: A cross-sectional mediation analysis.

PubMed

Bugge, Anna; Möller, Sören; Westfall, Daniel R; Tarp, Jakob; Gejl, Anne K; Wedderkopp, Niels; Hillman, Charles H

2018-01-01

The main objective of this study was to investigate the associations between waist circumference, metabolic risk factors, and executive function in adolescents. The study was cross-sectional and included 558 adolescents (mean age 14.2 years). Anthropometrics and systolic blood pressure (sysBP) were measured and fasting blood samples were analyzed for metabolic risk factors. A metabolic risk factor cluster score (MetS-cluster score) was computed from the sum of standardized sysBP, triglycerides (TG), inverse high-density lipid cholesterol (HDLc) and insulin resistance (homeostasis model assessment). Cognitive control was measured with a modified flanker task. Regression analyses indicated that after controlling for demographic variables, HDLc exhibited a negative and TG a positive association with flanker reaction time (RT). Waist circumference did not demonstrate a statistically significant total association with the cognitive outcomes. In structural equation modeling, waist circumference displayed an indirect positive association with incongruent RT through a higher MetS-cluster score and through lower HDLc. The only statistically significant direct association between waist circumference and the cognitive outcomes was for incongruent RT in the model including HDLc as mediator. These findings are consonant with the previous literature reporting an adverse association between certain metabolic risk factors and cognitive control. Accordingly, these results suggest specificity between metabolic risk factors and cognitive control outcomes. Further, results of the present study, although cross-sectional, provide new evidence that specific metabolic risk factors may mediate an indirect association between adiposity and cognitive control in adolescents, even though a direct association between these variables was not observed. However, taking the cross-sectional study design into consideration, these results should be interpreted with caution and future longitudinal or experimental studies should verify the findings of this study.

Development and validation of a gene profile predicting benefit of postmastectomy radiotherapy in patients with high-risk breast cancer: a study of gene expression in the DBCG82bc cohort.

PubMed

Tramm, Trine; Mohammed, Hayat; Myhre, Simen; Kyndi, Marianne; Alsner, Jan; Børresen-Dale, Anne-Lise; Sørlie, Therese; Frigessi, Arnoldo; Overgaard, Jens

2014-10-15

To identify genes predicting benefit of radiotherapy in patients with high-risk breast cancer treated with systemic therapy and randomized to receive or not receive postmastectomy radiotherapy (PMRT). The study was based on the Danish Breast Cancer Cooperative Group (DBCG82bc) cohort. Gene-expression analysis was performed in a training set of frozen tumor tissue from 191 patients. Genes were identified through the Lasso method with the endpoint being locoregional recurrence (LRR). A weighted gene-expression index (DBCG-RT profile) was calculated and transferred to quantitative real-time PCR (qRT-PCR) in corresponding formalin-fixed, paraffin-embedded (FFPE) samples, before validation in FFPE from 112 additional patients. Seven genes were identified, and the derived DBCG-RT profile divided the 191 patients into "high LRR risk" and "low LRR risk" groups. PMRT significantly reduced risk of LRR in "high LRR risk" patients, whereas "low LRR risk" patients showed no additional reduction in LRR rate. Technical transfer of the DBCG-RT profile to FFPE/qRT-PCR was successful, and the predictive impact was successfully validated in another 112 patients. A DBCG-RT gene profile was identified and validated, identifying patients with very low risk of LRR and no benefit from PMRT. The profile may provide a method to individualize treatment with PMRT. ©2014 American Association for Cancer Research.

Long-Term Outcomes Among Adult Survivors of Childhood Central Nervous System Malignancies in the Childhood Cancer Survivor Study

PubMed Central

Liu, Qi; Yasui, Yutaka; Huang, Sujuan; Ness, Kirsten K.; Leisenring, Wendy; Hudson, Melissa M.; Donaldson, Sarah S.; King, Allison A.; Stovall, Marilyn; Krull, Kevin R.; Robison, Leslie L.; Packer, Roger J.

2009-01-01

Background Adult survivors of childhood central nervous system (CNS) malignancies are at high risk for long-term morbidity and late mortality. However, patterns of late mortality, the long-term risks of subsequent neoplasms and debilitating medical conditions, and sociodemographic outcomes have not been comprehensively characterized for individual diagnostic and treatment groups. Methods We collected information on treatment, mortality, chronic medical conditions, and neurocognitive functioning of adult 5-year survivors of CNS malignancies diagnosed between 1970 and 1986 within the Childhood Cancer Survivor Study. Using competing risk framework, we calculated cumulative mortality according to cause of death and cumulative incidence of subsequent neoplasms according to exposure and dose of cranial radiation therapy (RT). Neurocognitive impairment and socioeconomic outcomes were assessed with respect to dose of CNS radiotherapy to specific brain regions. Cumulative incidence of chronic medical conditions was compared between survivors and siblings using Cox regression models. All tests of statistical significance were two-sided. Results Among all eligible 5-year survivors (n = 2821), cumulative late mortality at 30 years was 25.8% (95% confidence interval [CI] = 23.4% to 28.3%), due primarily to recurrence and/or progression of primary disease. Patients who received cranial RT of 50 Gy or more (n = 813) had a cumulative incidence of a subsequent neoplasm within the CNS of 7.1% (95% CI = 4.5% to 9.6%) at 25 years from diagnosis compared with 1.0% (95% CI = 0% to 2.3%) for patients who had no RT. Survivors had higher risk than siblings of developing new endocrine, neurological, or sensory complications 5 or more years after diagnosis. Neurocognitive impairment was high and proportional to radiation dose for specific tumor types. There was a dose-dependent association between RT to the frontal and/or temporal lobes and lower rates of employment, and marriage. Conclusions Survivors of childhood CNS malignancies are at high risk for late mortality and for developing subsequent neoplasms and chronic medical conditions. Care providers should be informed of these risks so they can provide risk-directed care and develop screening guidelines. PMID:19535780

Radiotherapy before and after radical prostatectomy for high-risk and locally advanced prostate cancer.

PubMed

Perez, Bradford A; Koontz, Bridget F

2015-05-01

Men with localized high-risk prostate cancer carry significant risk of prostate cancer-specific mortality. The best treatment approach to minimize this risk is unclear. In this review, we evaluate the role of radiation before and after radical prostatectomy. A critical review of the literature was performed regarding the application of external radiation therapy (RT) in combination with prostatectomy for high-risk localized prostate cancer. Up to 70% of men with high-risk localized disease may require adjuvant therapy because of adverse pathologic features or biochemical recurrence in the absence of systemic disease. The utility of adjuvant RT among men with adverse pathologic features are well established at least regarding minimizing biochemical recurrence risk. The optimal timing of salvage radiation is the subject of ongoing studies. Neoadjuvant RT requires further study but is a potentially attractive method because of decreased radiation field sizes and potential radiobiologic benefits of delivering RT before surgery. Salvage prostatectomy is effective at treating local recurrence after radiation but is associated with significant surgical morbidity. Combining local therapies including radical prostatectomy and RT can be a reasonable approach. Care should be taken at the initial presentation of high-risk localized prostate cancer to consider and plan for the likelihood of multimodality care. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical impact of IMPORT HIGH trial (CRUK/06/003) on breast radiotherapy practices in the United Kingdom

PubMed Central

Ciurlionis, Laura; Kirby, Anna M; Locke, Imogen; Venables, Karen; Yarnold, John R; Titley, Jenny; Bliss, Judith; Coles, Charlotte E

2015-01-01

Objective: IMPORT HIGH is a multicentre randomized UK trial testing dose-escalated intensity-modulated radiotherapy (IMRT) after tumour excision in females with early breast cancer and higher than average local recurrence risk. A survey was carried out to investigate the impact of this trial on the adoption of advanced breast radiotherapy (RT) techniques in the UK. Methods: A questionnaire was sent to all 26 IMPORT HIGH recruiting RT centres to determine whether the trial has influenced non-trial breast RT techniques in terms of volume delineation, dosimetry, treatment delivery and verification. In order to compare the clinical practice of breast RT between IMPORT HIGH and non–IMPORT HIGH centres, parts of the Royal College of Radiologists (RCR) breast RT audit result were used in this study. Results: 26/26 participating centres completed the questionnaire. After joining the trial, the number of centres routinely using tumour bed clips to guide whole-breast RT rose from 5 (19%) to 21 (81%). 20/26 (77%) centres now contour target volumes and organs at risk (OARs) in some or all patients compared with 14 (54%) before the trial. 14/26 (54%) centres offer inverse-planned IMRT for selected non-trial patients with breast cancer, and 10/14 (71%) have adopted the IMPORT HIGH trial protocol for target volume and OARs dose constraints. Only 2/26 (8%) centres used clip information routinely for breast treatment verification prior to IMPORT HIGH, a minority that has since risen to 7/26 (27%). Data on 1386 patients was included from the RCR audit. This suggested that more cases from IMPORT HIGH centres had surgical clips implanted (83 vs 67%), were treated using CT guided planning with full three-dimensional dose compensation (100 vs 75%), and were treated with photon boost RT (30 vs 8%). Conclusion: The study suggests that participation in the IMPORT HIGH trial has played an important part in providing the guidance and support networks needed for the safe integration of advanced RT techniques, where appropriate, as a standard of care for breast cancer patients treated at participating cancer centres. Advances in knowledge: We investigated the impact of the IMPORT HIGH trial on the adoption of advanced breast RT techniques in the UK and the trial has influenced non-trial breast RT techniques in terms of volume delineation, dosimetry, treatment delivery and verification. PMID:26492402

Clinical impact of IMPORT HIGH trial (CRUK/06/003) on breast radiotherapy practices in the United Kingdom.

PubMed

Tsang, Yat; Ciurlionis, Laura; Kirby, Anna M; Locke, Imogen; Venables, Karen; Yarnold, John R; Titley, Jenny; Bliss, Judith; Coles, Charlotte E

2015-01-01

IMPORT HIGH is a multicentre randomized UK trial testing dose-escalated intensity-modulated radiotherapy (IMRT) after tumour excision in females with early breast cancer and higher than average local recurrence risk. A survey was carried out to investigate the impact of this trial on the adoption of advanced breast radiotherapy (RT) techniques in the UK. A questionnaire was sent to all 26 IMPORT HIGH recruiting RT centres to determine whether the trial has influenced non-trial breast RT techniques in terms of volume delineation, dosimetry, treatment delivery and verification. In order to compare the clinical practice of breast RT between IMPORT HIGH and non-IMPORT HIGH centres, parts of the Royal College of Radiologists (RCR) breast RT audit result were used in this study. 26/26 participating centres completed the questionnaire. After joining the trial, the number of centres routinely using tumour bed clips to guide whole-breast RT rose from 5 (19%) to 21 (81%). 20/26 (77%) centres now contour target volumes and organs at risk (OARs) in some or all patients compared with 14 (54%) before the trial. 14/26 (54%) centres offer inverse-planned IMRT for selected non-trial patients with breast cancer, and 10/14 (71%) have adopted the IMPORT HIGH trial protocol for target volume and OARs dose constraints. Only 2/26 (8%) centres used clip information routinely for breast treatment verification prior to IMPORT HIGH, a minority that has since risen to 7/26 (27%). Data on 1386 patients was included from the RCR audit. This suggested that more cases from IMPORT HIGH centres had surgical clips implanted (83 vs 67%), were treated using CT guided planning with full three-dimensional dose compensation (100 vs 75%), and were treated with photon boost RT (30 vs 8%). The study suggests that participation in the IMPORT HIGH trial has played an important part in providing the guidance and support networks needed for the safe integration of advanced RT techniques, where appropriate, as a standard of care for breast cancer patients treated at participating cancer centres. We investigated the impact of the IMPORT HIGH trial on the adoption of advanced breast RT techniques in the UK and the trial has influenced non-trial breast RT techniques in terms of volume delineation, dosimetry, treatment delivery and verification.

Patterns and Predictors of Early Biochemical Recurrence After Radical Prostatectomy and Adjuvant Radiation Therapy in Men With pT{sub 3}N{sub 0} Prostate Cancer: Implications for Multimodal Therapies

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

Briganti, Alberto, E-mail: briganti.alberto@hsr.it; Joniau, Steven; Gandaglia, Giorgio

Purpose: The aim of our study was to evaluate patterns and predictors of early biochemical recurrence (eBCR) after radical prostatectomy (RP) and adjuvant radiation therapy (aRT) in order to identify which individuals might benefit from additional treatments. Methods and Materials: We evaluated 390 patients with pT{sub 3}N{sub 0} prostate cancer (PCa) receiving RP and aRT at 6 European centers between 1993 and 2006. Patients who were free from BCR at <2 years' follow-up were excluded. This resulted in 374 assessable patients. Early BCR was defined as 2 consecutive prostate-specific antigen (PSA) test values >0.2 ng/mL within 2 or 3 yearsmore » after aRT. Uni- and multivariable Cox regression analyses predicting overall and eBCR after aRT were fitted. Covariates consisted of preoperative PSA results, surgical margins, pathological stage, Gleason score, and aRT dose. Results: Overall, 5- and 8-year BCR-free survival rates were 77.1% and 70.8%, respectively. At a median follow-up of 86 months after aRT, 33 (8.8%) and 55 (14.6%) men experienced BCR within 2 or 3 years after aRT, respectively. In multivariable analyses, Gleason scores of 8 to 10 represented the only independent predictor of eBCR after aRT (all, P≤.01). The risk of BCR was significantly higher in patients with a Gleason score of 8 to 10 disease than in those with Gleason 2 to 6 within 24 months after treatment, after adjusting for all covariates (all, P≤.04). However, given a 24-month BCR free period, the risk of subsequent BCR for men with poorly differentiated disease was equal to that of men with less aggressive disease (all, P≥.3). Conclusions: High Gleason score represents the only predictor of eBCR after RP and aRT in patients affected by pT{sub 3}N{sub 0} PCa. Given the association between early PSA recurrence, clinical progression, and mortality, these patients might be considered candidates for adjuvant medical therapy and/or prophylactic whole-pelvis radiation therapy in addition to aRT, delivered to the prostatic bed.« less

Risk Factors for Tremor in a Population of Patients with Severe Mental Illness: An 18-year Prospective Study in a Geographically Representative Sample (The Curacao Extrapyramidal Syndromes Study XI)

PubMed Central

Mentzel, Charlotte L.; Bakker, P. Roberto; van Os, Jim; Drukker, Marjan; van den Oever, Michiel R. H.; Matroos, Glenn E.; Hoek, Hans W.; Tijssen, Marina AJ; van Harten, Peter N.

2017-01-01

Background The aim was to assess incidence, prevalence and risk factors of medication-induced tremor in African-Caribbean patients with severe mental illness (SMI). Method A prospective study of SMI patients receiving care from the only mental health service of the previous Dutch Antilles. Eight clinical assessments, over 18 years, focused on movement disorders, medication use, and resting tremor (RT) and (postural) action tremor (AT). Risk factors were modeled with logistic regression for both current (having) tremor and for tremor at the next time point (developing). The latter used a time-lagged design to assess medication changes prior to a change in tremor state. Results Yearly tremor incidence rate was 2.9% and mean tremor point prevalence was 18.4%. Over a third of patients displayed tremor during the study. Of the patients, 5.2% had AT with 25% of cases persisting to the next time point, while 17.1% of patients had RT of which 65.3% persisted. When tremor data were examined in individual patients, they often had periods of tremor interspersed with periods of no tremor. Having RT was associated with age (OR=1.07 per year; 95% confidence interval 1.03–1.11), sex (OR=0.17 for males; 0.05–0.78), cocaine use (OR=10.53; 2.22–49.94), dyskinesia (OR=0.90; 0.83–0.97), and bradykinesia (OR=1.16; 1.09–1.22). Developing RT was strongly associated with previous measurement RT (OR=9.86; 3.80–25.63), with previous RT severity (OR=1.22; 1.05–1.41), and higher anticholinergic load (OR= 1.24; 1.08–1.43). Having AT was associated with tremor-inducing medication (OR= 4.54; 1.90–10.86), cocaine use (OR=14.04; 2.38–82.96), and bradykinesia (OR=1.07; 1.01–1.15). Developing AT was associated with, previous AT severity (OR=2.62 per unit; 1.64–4.18) and tremor reducing medication (OR=0.08; 0.01–0.55). Conclusions Long-stay SMI patients are prone to developing tremors, which show a relapsing–remitting course. Differentiation between RT and AT is important as risk factors differ and they require different prevention and treatment strategies. PMID:28690921

Delivery and Evaluation of Synchronous Online Reading Tutoring to Students At-Risk of Reading Failure

ERIC Educational Resources Information Center

Vasquez, Eleazar, III; Forbush, David E.; Mason, Lee L.; Lockwood, April R.; Gleed, Linsey

2011-01-01

In a technological society, demands for higher literacy are ever increasing, creating grievous consequences for those who fail to meet these demands (National Research Council, 1998). Both legislative mandates, such as NCLB, and developments in the provision of reading instruction, such as RtI, have increased the demand for high quality tutoring…

Genomic Prostate Cancer Classifier Predicts Biochemical Failure and Metastases in Patients After Postoperative Radiation Therapy

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

Den, Robert B., E-mail: Robert.Den@jeffersonhospital.org; Feng, Felix Y.; Showalter, Timothy N.

2014-08-01

Purpose: To test the hypothesis that a genomic classifier (GC) would predict biochemical failure (BF) and distant metastasis (DM) in men receiving radiation therapy (RT) after radical prostatectomy (RP). Methods and Materials: Among patients who underwent post-RP RT, 139 were identified for pT3 or positive margin, who did not receive neoadjuvant hormones and had paraffin-embedded specimens. Ribonucleic acid was extracted from the highest Gleason grade focus and applied to a high-density-oligonucleotide microarray. Receiver operating characteristic, calibration, cumulative incidence, and Cox regression analyses were performed to assess GC performance for predicting BF and DM after post-RP RT in comparison with clinical nomograms.more » Results: The area under the receiver operating characteristic curve of the Stephenson model was 0.70 for both BF and DM, with addition of GC significantly improving area under the receiver operating characteristic curve to 0.78 and 0.80, respectively. Stratified by GC risk groups, 8-year cumulative incidence was 21%, 48%, and 81% for BF (P<.0001) and for DM was 0, 12%, and 17% (P=.032) for low, intermediate, and high GC, respectively. In multivariable analysis, patients with high GC had a hazard ratio of 8.1 and 14.3 for BF and DM. In patients with intermediate or high GC, those irradiated with undetectable prostate-specific antigen (PSA ≤0.2 ng/mL) had median BF survival of >8 years, compared with <4 years for patients with detectable PSA (>0.2 ng/mL) before initiation of RT. At 8 years, the DM cumulative incidence for patients with high GC and RT with undetectable PSA was 3%, compared with 23% with detectable PSA (P=.03). No outcome differences were observed for low GC between the treatment groups. Conclusion: The GC predicted BF and metastasis after post-RP irradiation. Patients with lower GC risk may benefit from delayed RT, as opposed to those with higher GC; however, this needs prospective validation. Genomic-based models may be useful for improved decision-making for treatment of high-risk prostate cancer.« less

Obesity and Risk of Biochemical Failure for Patients Receiving Salvage Radiotherapy After Prostatectomy

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

King, Christopher R.; Spiotto, Michael T.; Kapp, Daniel S.

Purpose: Obesity has been proposed as an independent risk factor for patients undergoing surgery or radiotherapy (RT) for prostate cancer. Using body mass index (BMI) as a measure of obesity, we tested its role as a risk factor for patients receiving salvage RT after prostatectomy. Methods and Materials: Rates of subsequent biochemical relapse were examined in 90 patients who underwent salvage RT between 1984 and 2004 for biochemical failure after radical prostatectomy. Median follow-up was 3.7 years. The BMI was tested as a continuous and categorical variable (stratified as <25, 25-<30, and {>=}30 kg/m{sup 2}). Univariate and multivariate proportional hazardsmore » regression analyses were performed for clinical, pathologic, and treatment factors associated with time to relapse after salvage RT. Results: There were 40 biochemical failures after salvage RT with a median time to failure of 1.2 years. The BMI was not associated with adverse clinical, pathologic, or treatment factors. On multivariate analysis, obesity was independently significant (hazard ratio [HR], 1.2; p = 0.01), along with RT dose (HR, 0.7; p = 0.003) and pre-RT prostate-specific antigen level (HR, 1.2; p = 0.0003). Conclusions: This study is weakly suggestive that obesity may be a risk factor for salvage RT patients. Whether this results from greater biologic aggressiveness or technical inadequacies cannot be answered by this study. Given the very high failure rate observed for severely obese patients, we propose that technical difficulties with RT are at play. This hypothesis is supported by the RT literature and could be prospectively investigated. Techniques that optimize targeting, especially in obese patients, perhaps seem warranted at this time.« less

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

Weiss, Christian; Roemer, Felix von; Capalbo, Gianni

Purpose: The objectives of this study were to investigate the expression of survivin in tumor samples from patients with high-risk T1 bladder cancer and to correlate its expression with clinicopathologic features as well as clinical outcomes after initial transurethral resection (TURBT) followed by radiotherapy (RT) or radiochemotherapy (RCT). Methods and Materials: Survivin protein expression was evaluated by immunohistochemistry on tumor specimen (n = 48) from the initial TURBT, and was correlated with clinical and histopathologic characteristics as well as with 5-year rates of local failure, tumor progression, and death from urothelial cancer after primary bladder sparring treatment with RT/RCT. Results:more » Survivin was not expressed in normal bladder urothelium but was overexpressed in 67% of T1 tumors. No association between survivin expression and clinicopathologic factors (age, gender, grading, multifocality, associated carcinoma in situ) could be shown. With a median follow-up of 27 months (range, 3-140 months), elevated survivin expression was significantly associated with an increased probability of local failure after TURBT and RCT/RT (p = 0.003). There was also a clear trend toward a higher risk of tumor progression (p = 0.07) and lower disease-specific survival (p = 0.10). Conclusions: High survivin expression is a marker of tumor aggressiveness and may help to identify a subgroup of patients with T1 bladder cancer at a high risk for recurrence when treated with primary organ-sparing approaches such as TURBT and RCT.« less

The effect of recombinant tissue plasminogen activator on MMP-2 and MMP-9 activities in vitro.

PubMed

Golab, Piotr; Kielbus, Michal; Bielewicz, Joanna; Kurzepa, Jacek

2015-01-01

One of the most significant side effects during recombinant tissue plasminogen activator (rtPA) for acute stroke treatment is intracranial bleeding. Gelatinases [matrix metalloproteinase (MMP)-2 and MMP-9] are one of the agents involved in the blood-brain barrier destruction resulting in secondary bleeding into the ischemic area during stroke. Previous papers revealed that patients with high baseline MMP-9 serum level have higher risk of intracranial bleeding after thrombolytic therapy. Our objective was to evaluate rtPA influence on serum MMP-2 and MMP-9 activities in vitro. Nine sera obtained from healthy donors were applied for experiment. The commercially available rtPA (Actylise) were diluted with included solvent and additionally with phosphate-buffered saline (PBS) to get concentrations: 2, 4, 8, and 16 μg/ml. Next, 100 μl of serum was mixed with equal proportion with different concentrations of rtPA to obtain final rtPA concentrations: 1, 2, 4, and 8 μg/ml. The sera together with rtPA were incubated for 1 or 2 hours at 37 °C. The activity of gelatinases was estimated with zymography. The activities of MMP-9 (92 kDa) and MMP-2 (72 kDa) were increased by incubation with rtPA in a dose-dependent manner. Simultaneously, the activity of band at 200 kDa (MMP-9/MMP-9 homodimer) was decreased. The activity of gelatinases incubated for 2 hours was elevated in comparison with 1-hour incubation; however, the increase was observed even for sample without rtPA. In conclusion, this study showed that rtPA can increase the biological activity of MMP-2 and MMP-9 on posttranslational level.

Validating a Local Failure Risk Stratification for Use in Prospective Studies of Adjuvant Radiation Therapy for Bladder Cancer

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

Baumann, Brian C.; He, Jiwei; Hwang, Wei-Ting

Purpose: To inform prospective trials of adjuvant radiation therapy (adj-RT) for bladder cancer after radical cystectomy, a locoregional failure (LF) risk stratification was proposed. This stratification was developed and validated using surgical databases that may not reflect the outcomes expected in prospective trials. Our purpose was to assess sources of bias that may affect the stratification model's validity or alter the LF risk estimates for each subgroup: time bias due to evolving surgical techniques; trial accrual bias due to inclusion of patients who would be ineligible for adj-RT trials because of early disease progression, death, or loss to follow-up shortlymore » after cystectomy; bias due to different statistical methods to estimate LF; and subgrouping bias due to different definitions of the LF subgroups. Methods and Materials: The LF risk stratification was developed using a single-institution cohort (n=442, 1990-2008) and the multi-institutional SWOG 8710 cohort (n=264, 1987-1998) treated with radical cystectomy with or without chemotherapy. We evaluated the sensitivity of the stratification to sources of bias using Fine-Gray regression and Kaplan-Meier analyses. Results: Year of radical cystectomy was not associated with LF risk on univariate or multivariate analysis after controlling for risk group. By use of more stringent inclusion criteria, 26 SWOG patients (10%) and 60 patients from the single-institution cohort (14%) were excluded. Analysis of the remaining patients confirmed 3 subgroups with significantly different LF risks with 3-year rates of 7%, 17%, and 36%, respectively (P<.01), nearly identical to the rates without correcting for trial accrual bias. Kaplan-Meier techniques estimated higher subgroup LF rates than competing risk analysis. The subgroup definitions used in the NRG-GU001 adj-RT trial were validated. Conclusions: These sources of bias did not invalidate the LF risk stratification or substantially change the model's LF estimates.« less

Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix.

PubMed

Peters, W A; Liu, P Y; Barrett, R J; Stock, R J; Monk, B J; Berek, J S; Souhami, L; Grigsby, P; Gordon, W; Alberts, D S

2000-04-01

To determine whether the addition of cisplatin-based chemotherapy (CT) to pelvic radiation therapy (RT) will improve the survival of early-stage, high-risk patients with cervical carcinoma. Patients with clinical stage IA(2), IB, and IIA carcinoma of the cervix, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes and/or positive margins and/or microscopic involvement of the parametrium were eligible for this study. Patients were randomized to receive RT or RT + CT. Patients in each group received 49.3 GY RT in 29 fractions to a standard pelvic field. Chemotherapy consisted of bolus cisplatin 70 mg/m(2) and a 96-hour infusion of fluorouracil 1,000 mg/m(2)/d every 3 weeks for four cycles, with the first and second cycles given concurrent to RT. Between 1991 and 1996, 268 patients were entered onto the study. Two hundred forty-three patients were assessable (127 RT + CT patients and 116 RT patients). Progression-free and overall survival are significantly improved in the patients receiving CT. The hazard ratios for progression-free survival and overall survival in the RT only arm versus the RT + CT arm are 2.01 (P =.003) and 1.96 (P =. 007), respectively. The projected progression-free survivals at 4 years is 63% with RT and 80% with RT + CT. The projected overall survival rate at 4 years is 71% with RT and 81% with RT + CT. Grades 3 and 4 hematologic and gastrointestinal toxicity were more frequent in the RT + CT group. The addition of concurrent cisplatin-based CT to RT significantly improves progression-free and overall survival for high-risk, early-stage patients who undergo radical hysterectomy and pelvic lymphadenectomy for carcinoma of the cervix.

Lack of Benefit for the Addition of Androgen Deprivation Therapy to Dose-Escalated Radiotherapy in the Treatment of Intermediate- and High-Risk Prostate Cancer

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

Krauss, Daniel, E-mail: dkrauss@beaumont.edu; Kestin, Larry; Ye, Hong

2011-07-15

Purpose: Assessment of androgen deprivation therapy (ADT) benefits for prostate cancer treated with dose-escalated radiotherapy (RT). Methods and Materials: From 1991 to 2004, 1,044 patients with intermediate- (n = 782) or high-risk (n = 262) prostate cancer were treated with dose-escalated RT at William Beaumont Hospital. Patients received external-beam RT (EBRT) alone, brachytherapy (high or low dose rate), or high dose rate brachytherapy plus pelvic EBRT. Intermediate-risk patients had Gleason score 7, prostate-specific antigen (PSA) 10.0-19.9 ng/mL, or Stage T2b-T2c. High-risk patients had Gleason score 8-10, PSA {>=}20, or Stage T3. Patients were additionally divided specifically by Gleason score, presencemore » of palpable disease, and PSA level to further define subgroups benefitting from ADT. Results: Median follow-up was 5 years; 420 patients received ADT + dose-escalated RT, and 624 received dose-escalated RT alone. For all patients, no advantages in any clinical endpoints at 8 years were associated with ADT administration. No differences in any endpoints were associated with ADT administration based on intermediate- vs. high-risk group or RT modality when analyzed separately. Patients with palpable disease plus Gleason {>=}8 demonstrated improved clinical failure rates and a trend toward improved survival with ADT. Intermediate-risk patients treated with brachytherapy alone had improved biochemical control when ADT was given. Conclusion: Benefits of ADT in the setting of dose-escalated RT remain poorly defined. This question must continue to be addressed in prospective study.« less

Effects of resistance training on the inflammatory response

PubMed Central

Calle, Mariana C

2010-01-01

Resistance training (RT) is associated with reduced risk of low grade inflammation related diseases, such as cardiovascular disease and type 2 diabetes. The majority of the data studying cytokines and exercise comes from endurance exercise. In contrast, evidence establishing a relationship between RT and inflammation is more limited. This review focuses on the cytokine responses both following an acute bout, and after chronic RT. In addition, the effect of RT on low grade systemic inflammation such as individuals at risk for type 2 diabetes is reviewed. Cytokines are secreted proteins that influence the survival, proliferation, and differentiation of immune cells and other organ systems. Cytokines function as intracellular signals and almost all cells in the body either secrete them or have cytokine receptors. Thus, understanding cytokine role in a specific physiological situation such as a bout of RT can be exceedingly complex. The overall effect of long term RT appears to ameliorate inflammation, but the specific effects on the inflammatory cytokine, tumor necrosis factor alpha are not clear, requiring further research. Furthermore, it is critical to differentiate between chronically and acute Interleukin-6 levels and its sources. The intensity of the RT and the characteristics of the training protocol may exert singular cytokine responses and as a result different adaptations to exercise. More research is needed in the area of RT in healthy populations, specifically sorting out gender and age RT acute responses. More importantly, studies are needed in obese individuals who are at high risk of developing low grade systemic inflammatory related diseases. Assuring adherence to the RT program is essential to get the benefits after overcoming the first acute RT responses. Hence RT could be an effective way to prevent, and delay low grade systemic inflammatory related diseases. PMID:20827340

Association between access to accelerated partial breast irradiation and use of adjuvant radiotherapy.

PubMed

Wang, Elyn H; Park, Henry S; Rutter, Charles E; Gross, Cary P; Soulos, Pamela R; Yu, James B; Evans, Suzanne B

2017-02-01

The current study was performed to determine whether access to facilities performing accelerated partial breast irradiation (APBI) is associated with differences in the use of adjuvant radiotherapy (RT). Using the National Cancer Data Base, the authors performed a retrospective study of women aged ≥50 years who were diagnosed with early-stage breast cancer between 2004 and 2013 and treated with breast-conserving surgery (BCS). Facilities performing APBI in ≥10% of their eligible patients within a given year were defined as APBI facilities whereas those not performing APBI were defined as non-APBI facilities. All other facilities were excluded. The authors identified independent factors associated with RT use using multivariable logistic regression with clustering in the overall sample as well as in subsets of patients with standard-risk invasive cancer, low-risk invasive cancer, and ductal carcinoma in situ. Among 222,544 patients, 76.6% underwent BCS plus RT and 23.4% underwent BCS alone. The likelihood of RT receipt in the overall sample did not appear to differ significantly between APBI and non-APBI facilities (adjusted odds ratio [AOR], 1.02; P = .61). Subgroup multivariable analysis demonstrated that among patients with standard-risk invasive cancer, there was no association between evaluation at an APBI facility and receipt of RT (AOR, 0.98; P = .69). However, patients with low-risk invasive cancer were found to be significantly more likely to receive RT (54.4% vs 59.5%; AOR, 1.22 [P<.001]), whereas patients with ductal carcinoma in situ were less likely to receive RT (56.9% vs 55.3%; AOR, 0.89 [P = .04]) at APBI facilities. Patients who were eligible for observation were more likely to receive RT in APBI facilities but no difference was observed among patients with standard-risk invasive cancer who would most benefit from RT. Cancer 2017;123:502-511. © 2016 American Cancer Society. © 2016 American Cancer Society.

Associations between adjuvant radiotherapy and different causes of death in a German breast cancer cohort.

PubMed

Obi, Nadia; Eulenburg, Christine; Seibold, Petra; Eilber, Ursula; Thöne, Kathrin; Behrens, Sabine; Chang-Claude, Jenny; Flesch-Janys, Dieter

2018-04-01

Studies of cohorts of breast cancer (BC) patients diagnosed before 1990 showed radiotherapy (RT) to be associated with increased cardiovascular (CVD) and lung cancer mortality many years after diagnosis. In the late 1990s, improvements in RT planning techniques reduced radiation doses to normal tissues. Recent studies did not consistently report higher RT-related mortality for CVD and second cancers. Aim of the study was to analyze specific causes of death after 3D-conformal RT in a recent BC cohort. Stage I-III BC patients diagnosed 2001-2005 and enrolled in the population based MARIEplus study were followed-up for 11.9 years (median). Associations between adjuvant RT and cause-specific mortality were analyzed by using competing risks models, yielding subdistribution hazard ratios (SHR) for RT directly related to cumulative incidences. Models were adjusted for differences in baseline characteristics applying inverse-probability-of-treatment-weighting (IPTW). Of the 2951 patients, 2439 (83.0%) received RT. No significant association of RT with lung cancer mortality (SHR IPTW 0.88, 0.35-2.12), other cancer mortality (SHR IPTW 1.04, 95% CI 0.62-1.73) or cardiac mortality was observed (SHR IPTW 1.57, 0.75-3.29). Mortality from lung and other diseases were significantly lower in irradiated women (SHR IPTW 0.39, 95% CI 0.17-0.90 and SHR IPTW 0.58, 95% CI 0.34-0.97, respectively). In line with recent studies, 3D-conformal RT did not significantly increase mortality from non-BC causes in the German MARIEplus cohort. Since long-term data are still sparse and event rates low in BC-cohorts, who received modern RT, investigation of possible late RT effects on mortality beyond 14 years of follow-up is warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

Treatment Guidelines for Preoperative Radiation Therapy for Retroperitoneal Sarcoma: Preliminary Consensus of an International Expert Panel

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

Baldini, Elizabeth H., E-mail: ebaldini@partners.org; Wang, Dian; Haas, Rick L.M.

Purpose: Evidence for external beam radiation therapy (RT) as part of treatment for retroperitoneal sarcoma (RPS) is limited. Preoperative RT is the subject of a current randomized trial, but the results will not be available for many years. In the meantime, many practitioners use preoperative RT for RPS, and although this approach is used in practice, there are no radiation treatment guidelines. An international expert panel was convened to develop consensus treatment guidelines for preoperative RT for RPS. Methods and Materials: An expert panel of 15 academic radiation oncologists who specialize in the treatment of sarcoma was assembled. A systematicmore » review of reports related to RT for RPS, RT for extremity sarcoma, and RT-related toxicities for organs at risk was performed. Due to the paucity of high-quality published data on the subject of RT for RPS, consensus recommendations were based largely on expert opinion derived from clinical experience and extrapolation of relevant published reports. It is intended that these clinical practice guidelines be updated as pertinent data become available. Results: Treatment guidelines for preoperative RT for RPS are presented. Conclusions: An international panel of radiation oncologists who specialize in sarcoma reached consensus guidelines for preoperative RT for RPS. Many of the recommendations are based on expert opinion because of the absence of higher level evidence and, thus, are best regarded as preliminary. We emphasize that the role of preoperative RT for RPS has not been proven, and we await data from the European Organization for Research and Treatment of Cancer (EORTC) study of preoperative radiotherapy plus surgery versus surgery alone for patients with RPS. Further data are also anticipated pertaining to normal tissue dose constraints, particularly for bowel tolerance. Nonetheless, as we await these data, the guidelines herein can be used to establish treatment uniformity to aid future assessments of efficacy and toxicity.« less

"Mind the gap"--the impact of variations in the duration of the treatment gap and overall treatment time in the first UK Anal Cancer Trial (ACT I).

PubMed

Glynne-Jones, Rob; Sebag-Montefiore, David; Adams, Richard; McDonald, Alec; Gollins, Simon; James, Roger; Northover, John M A; Meadows, Helen M; Jitlal, Mark

2011-12-01

The United Kingdom Coordinating Committee on Cancer Research anal cancer trial demonstrated the benefit of combined modality treatment (CMT) using radiotherapy (RT), infusional 5-fluorouracil, and mitomycin C over RT alone. The present study retrospectively examines the impact of the recommended 6-week treatment gap and local RT boost on long-term outcome. A total of 577 patients were randomly assigned RT alone or CMT. After a 6-week gap responders received a boost using either additional external beam radiotherapy (EBRT) (15 Gy) or iridium-192 implant (25 Gy). The effect of boost, the gap between initial treatment (RT alone or CMT) and boost (Tgap), and overall treatment time (OTT) were examined for their impact on outcome. Among the 490 good responders, 436 (89%) patients received a boost after initial treatment. For boosted patients, the risk of anal cancer death decreased by 38% (hazard ratio [HR]: 0.62, 99% CI 0.35-1.12; p=0.04), but there was no evidence this was mediated via a reduction in locoregional failure (LRF) (HR: 0.90, 99% CI 0.48-1.68; p=0.66). The difference in Tgap was only 1.4 days longer for EBRT boost, compared with implant (p=0.51). OTT was longer by 6.1 days for EBRT (p=0.006). Tgap and OTT were not associated with LRF. Radionecrosis was reported in 8% of boosted, compared with 0% in unboosted patients (p=0.03). These results question the benefit of a radiotherapy boost after a 6-week gap. The higher doses of a boost may contribute more to an increased risk of late morbidity, rather than local control. Copyright © 2011 Elsevier Inc. All rights reserved.

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

Glynne-Jones, Rob, E-mail: rob.glynnejones@nhs.net; Sebag-Montefiore, David; Adams, Richard

Purpose: The United Kingdom Coordinating Committee on Cancer Research anal cancer trial demonstrated the benefit of combined modality treatment (CMT) using radiotherapy (RT), infusional 5-fluorouracil, and mitomycin C over RT alone. The present study retrospectively examines the impact of the recommended 6-week treatment gap and local RT boost on long-term outcome. Methods and Materials: A total of 577 patients were randomly assigned RT alone or CMT. After a 6-week gap responders received a boost using either additional external beam radiotherapy (EBRT) (15 Gy) or iridium-192 implant (25 Gy). The effect of boost, the gap between initial treatment (RT alone ormore » CMT) and boost (Tgap), and overall treatment time (OTT) were examined for their impact on outcome. Results: Among the 490 good responders, 436 (89%) patients received a boost after initial treatment. For boosted patients, the risk of anal cancer death decreased by 38% (hazard ratio [HR]: 0.62, 99% CI 0.35-1.12; p = 0.04), but there was no evidence this was mediated via a reduction in locoregional failure (LRF) (HR: 0.90, 99% CI 0.48-1.68; p = 0.66). The difference in Tgap was only 1.4 days longer for EBRT boost, compared with implant (p = 0.51). OTT was longer by 6.1 days for EBRT (p = 0.006). Tgap and OTT were not associated with LRF. Radionecrosis was reported in 8% of boosted, compared with 0% in unboosted patients (p = 0.03). Conclusions: These results question the benefit of a radiotherapy boost after a 6-week gap. The higher doses of a boost may contribute more to an increased risk of late morbidity, rather than local control.« less

Assessment of radiation-induced secondary cancer risk in the Brazilian population from left-sided breast-3D-CRT using MCNPX.

PubMed

Mendes, Bruno Melo; Trindade, Bruno Machado; Fonseca, Telma Cristina Ferreira; de Campos, Tarcisio Passos Ribeiro

2017-12-01

The aim of this work was to simulate a 6MV conventional breast 3D conformational radiation therapy (3D-CRT) with physical wedges (50 Gy/25#) in the left breast, calculate the mean absorbed dose in the body organs using robust models and computational tools and estimate the secondary cancer-incidence risk to the Brazilian population. The VW female phantom was used in the simulations. Planning target volume (PTV) was defined in the left breast. The 6MV parallel-opposed fields breast-radiotherapy (RT) protocol was simulated with MCNPx code. The absorbed doses were evaluated in all the organs. The secondary cancer-incidence risk induced by radiotherapy was calculated for different age groups according to the BEIR VII methodology. RT quality indexes indicated that the protocol was properly simulated. Significant absorbed dose values in red bone marrow, RBM (0.8 Gy) and stomach (0.6 Gy) were observed. The contralateral breast presented the highest risk of incidence of a secondary cancer followed by leukaemia, lung and stomach. The risk of a secondary cancer-incidence by breast-RT, for the Brazilian population, ranged between 2.2-1.7% and 0.6-0.4%. RBM and stomach, usually not considered as OAR, presented high second cancer incidence risks of 0.5-0.3% and 0.4-0.1%, respectively. This study may be helpful for breast-RT risk/benefit assessment. Advances in knowledge: MCNPX-dosimetry was able to provide the scatter radiation and dose for all body organs in conventional breast-RT. It was found a relevant risk up to 2.2% of induced-cancer from breast-RT, considering the whole thorax organs and Brazilian cancer-incidence.

Colorectal cancer: intrinsic characteristics modulate cancer energy expenditure and the risk of cachexia.

PubMed

Ravasco, Paula; Monteiro-Grillo, Isabel; Camilo, Maria

2007-08-01

To conduct a prospective longitudinal study in colorectal cancer (CRC) patients: 1) to evaluate resting energy expenditure (REE), weight/dietary intake changes, and response to treatment, taking into consideration cancer stage and histology; 2) to determine their potential interrelations; and 3) to quantify the relative contributions to REE of cancer/nutrition/treatment. 101 CRC patients proposed for neoadjuvant radiotherapy (RT) were evaluated before and after RT: REE (indirect calorimetry measurements), percentage of weight loss, usual diet (diet history), current diet (24 hour recall), and treatment response. REE was higher in Stages III/IV versus I/II, at the RT onset (p < 0.002) and end (p = 0.02), and in moderately/poorly/undifferentiated cancers vs well differentiated (onset, p < 0.001) and (RT end, p = 0.01); weight/intake reductions were also greater in Stages III/IV versus I/II (p < 0.01) and in moderately/poorly/undifferentiated cancers versus well differentiated (p < 0.02). According to patients' response to treatment, REE was increased in Stage III/IV (p < 0.005) and Grade 2/3 histology (p < 0.003). In nonresponders, REE increased 7.2 +/- 1.3 kcal/kg/day and decreased 2.8 +/- 0.4 kcal/kg/day in responders. REE changes were not-significantly influenced by weight/intake. Relative contributions to baseline REE were determined in 25 percent by stage, in 25 percent by histology, in 3 percent by intake and in 4 percent by weight loss. At the end of RT, higher REE was attributed in 26 percent to stage, in 27 percent to histology, in 30 percent to nontreatment response, in 9 percent to intake, and in 8 percent to weight loss. In this CRC patient population, higher metabolic rates were mainly determined by the tumor burden and aggressiveness in association with response to treatment clearly disclaiming the effect of weight loss and/or dietary intake reductions.

Gender specific effect of psychological stress and cortisol reactivity on adolescent risk taking.

PubMed

Daughters, Stacey B; Gorka, Stephanie M; Matusiewicz, Alexis; Anderson, Katelyn

2013-07-01

The purpose of this study was to evaluate how psychological stress, gender and cortisol response to stress relate to risk behavior among 132 14-18 year old adolescents. Participants completed a laboratory based risk task prior to and immediately after a computerized psychological stress task, and salivary cortisol was collected from pre-stress to 60 min following initial stress exposure. Results indicate that adolescent boys (n = 59) and girls (n = 73) demonstrate different patterns of risk taking (RT) in response to stress, such that boys evidenced an increase in RT following stress exposure, whereas girls evidenced a decrease in RT. In addition, a gender by cortisol interaction demonstrated that for boys, both a smaller total cortisol output (AUCg) and peak cortisol response to stress (PC) was associated with greater stress-induced RT. Both cortisol measures were unrelated to stress-induced RT among girls. Taken together, data suggest that among boys, a blunted cortisol response to stress underlies an increase in risk taking in the context of psychological stress. Further research with an additional behavioral stress task is needed prior to drawing conclusions regarding the relation between female gender, cortisol response to stress, and risk taking in the context of psychological stress.

Storytelling for promoting colorectal cancer screening among underserved Latina women: a randomized pilot study.

PubMed

Larkey, Linda K; Lopez, Ana Maria; Minnal, Archana; Gonzalez, Julie

2009-01-01

In a low socioeconomic-status population of Latina women, we evaluated the potential of storytelling (ST) as a culturally aligned narrative method to promote colorectal cancer (CRC) prevention and screening, compared to a risk tool (RT)-based intervention. Seventy-eight women were randomized in this pilot study to one of two brief interventions to communicate CRC risk reduction options: ST or an RT. Measures of behavioral intentions relative to CRC prevention and screening were obtained following the intervention. Mean scores for intent to obtain and recommend endoscopy to others were significantly better for participants receiving ST than RT (P = .038 and P = .011, respectively). All participants expressed intent to increase fruit and vegetable consumption and physical activity in response to interventions. Post-intervention perceptions of cancer risk and fear of CRC were not significantly different for participants receiving ST compared with RT. Pre- to post-intervention perceptions of risk increased in ST and decreased in RT, while decreases in fear were similar across both intervention groups. Storytelling may be an effective approach for changing CRC risk-related behavioral intentions among Latinas. Mediating factors (such as perceived risk or fear) often used to predict behavior change may not adequately explain the potential persuasive mechanisms of storytelling.

SU-F-J-174: A Series of Computational Human Phantoms in DICOM-RT Format for Normal Tissue Dose Reconstruction in Epidemiological Studies

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

Pyakuryal, A; Moroz, B; Lee, C

2016-06-15

Purpose: Epidemiological studies of second cancer risk in radiotherapy patients often require individualized dose estimates of normal tissues. Prior to 3D conformal radiation therapy planning, patient anatomy information was mostly limited to 2D radiological images or not even available. Generic patient CT images are often used in commercial radiotherapy treatment planning system (TPS) to reconstruct normal tissue doses. The objective of the current work was to develop a series of reference size computational human phantoms in DICOM-RT format for direct use in dose reconstruction in TPS. Methods: Contours of 93 organs and tissues were extracted from a series of pediatricmore » and adult hybrid computational human phantoms (newborn, 1-, 5-, 10-, 15-year-old, and adult males and females) using Rhinoceros software. A MATLAB script was created to convert the contours into the DICOM-RT structure format. The simulated CT images with the resolution of 1×1×3 mm3 were also generated from the binary phantom format and coupled with the DICOM-structure files. Accurate volumes of the organs were drawn in the format using precise delineation of the contours in converted format. Due to complex geometry of organs, higher resolution (1×1×1 mm3) was found to be more efficient in the conversion of newborn and 1-year-old phantoms. Results: Contour sets were efficiently converted into DICOM-RT structures in relatively short time (about 30 minutes for each phantom). A good agreement was observed in the volumes between the original phantoms and the converted contours for large organs (NRMSD<1.0%) and small organs (NRMSD<7.7%). Conclusion: A comprehensive series of computational human phantoms in DICOM-RT format was created to support epidemiological studies of second cancer risks in radiotherapy patients. We confirmed the DICOM-RT phantoms were successfully imported into the TPS programs of major vendors.« less

Second cancers in patients with Chronic Lymphocytic Leukemia who received frontline FCR therapy – Distribution and clinical outcomes

PubMed Central

Benjamini, Ohad; Jain, Preetesh; Trinh, Long; Qiao, Wei; Strom, Sara S.; Lerner, Susan; Wang, Xuemei; Burger, Jan; Ferrajoli, Alessandra; Kantarjian, Hagop; O’Brien, Susan; Wierda, William; Estrov, Zeev; Keating, Michael

2015-01-01

Patients with Chronic Lymphocytic Leukemia (CLL) are known to have an increased incidence of second cancers, but the contribution of commonly used frontline therapies to the incidence of second cancers is unclear. We report on the characteristics, incidence, outcomes and factors associated with second cancers in 234 patients receiving Fludarabine, Cyclophosphamide, and Rituximab (FCR) based regimens in the frontline setting. The risk of second cancers was 2.38 times higher than the expected risk in the general population. Ninety three patients (40%) had other cancers before and 66 patients (28%) after FCR. The rates of t-AML/MDS (5.1%) and Richter’s transformation (RT) (9%) were high while solid tumors were not increased. Overall survival of patients with second cancers after frontline FCR was shorter (median of 4.5 years) compared to patients with and without prior cancers. Second cancer risk after frontline FCR is mainly due to high rates of t-AML/MDS and RT and as speculated the survival of affected patients is shorter. PMID:25308294

HIV risk perception and testing behaviours among men having sex with men (MSM) reporting potential transmission risks in the previous 12 months from a large online sample of MSM living in Germany.

PubMed

Marcus, Ulrich; Gassowski, Martyna; Drewes, Jochen

2016-10-22

HIV testing and serostatus awareness are essential to implement biomedical strategies (treatment as prevention; oral chemoprophylaxis), and for effective serostatus-based behaviours (HIV serosorting; strategic positioning). The analysis focuses on the associations between reported sexual risks, the perceived risk for HIV infection, and HIV testing behaviour in order to identify the most relevant barriers for HIV test uptake among MSM living in Germany. MSM were recruited to a nationwide anonymous online-survey in 2013 on MSM social networking/dating sites. Questions covered testing behaviours, reasons for testing decisions, and HIV risk perception (5-point scale). Additional questions addressed arguments in favour of home/ home collection testing (HT). Using descriptive statistics and logistic regression we compared men reporting recent HIV testing (RT; previous 12 month) with men never tested (NT) in a subsample not previously diagnosed with HIV and reporting ≥2 episodes of condomless anal intercourse (CLAI) with a non-steady partner of unknown HIV serostatus in the previous 12 months. The subsample consisted of 775 RT (13 % of RT) and 396 NT (7 % of NT). The number of CLAI episodes in the last 12 months with non-steady partners of unknown HIV status did not differ significantly between the groups, but RT reported significantly higher numbers of partners (>5 AI partners: 65 vs. 44 %). While perceived risks regarding last AI were comparable between the groups, 49vs. 30 % NT were <30 years, lived more often in towns/villages <100,000 residents (60 vs. 39 %), were less out-particularly towards care providers-about being attracted to men (aOR 10.1; 6.9-14.8), more often identified as bisexual (aOR 3.5; 2.5-4.8), and reported lower testing intentions (aOR 0.08; 0.06-0.11). Perceived risks (67 %) and routine testing (49 %) were the most common testing reasons for RT, while the strong belief not to be infected (59 %) and various worries (41 %) and fears of testing positive (35 %) were predominant reasons of NT. Greater anonymity (aOR 3.2; 2.4-4.4), less embarrassment, (aOR 2.8; 1.9-4.1), and avoiding discussions on sexual behaviour (aOR 1.6; 1.1-2.2) were emphasized in favour of HT by NT. Perceived partner knowledge and reasons reflecting perceived gay- and HIV-related stigma predicted testing decisions rather than risk perception. Access barriers for testing should be further lowered, e.g. by making affordable HT available, addressing structural barriers (stigma), and emphasizing beneficial aspects of serostatus awareness.

Impact of patient-specific factors, irradiated left ventricular volume, and treatment set-up errors on the development of myocardial perfusion defects after radiation therapy for left-sided breast cancer

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

Evans, Elizabeth S.; Prosnitz, Robert G.; Yu Xiaoli

2006-11-15

Purpose: The aim of this study was to assess the impact of patient-specific factors, left ventricle (LV) volume, and treatment set-up errors on the rate of perfusion defects 6 to 60 months post-radiation therapy (RT) in patients receiving tangential RT for left-sided breast cancer. Methods and Materials: Between 1998 and 2005, a total of 153 patients were enrolled onto an institutional review board-approved prospective study and had pre- and serial post-RT (6-60 months) cardiac perfusion scans to assess for perfusion defects. Of the patients, 108 had normal pre-RT perfusion scans and available follow-up data. The impact of patient-specific factors onmore » the rate of perfusion defects was assessed at various time points using univariate and multivariate analysis. The impact of set-up errors on the rate of perfusion defects was also analyzed using a one-tailed Fisher's Exact test. Results: Consistent with our prior results, the volume of LV in the RT field was the most significant predictor of perfusion defects on both univariate (p = 0.0005 to 0.0058) and multivariate analysis (p = 0.0026 to 0.0029). Body mass index (BMI) was the only significant patient-specific factor on both univariate (p = 0.0005 to 0.022) and multivariate analysis (p = 0.0091 to 0.05). In patients with very small volumes of LV in the planned RT fields, the rate of perfusion defects was significantly higher when the fields set-up 'too deep' (83% vs. 30%, p = 0.059). The frequency of deep set-up errors was significantly higher among patients with BMI {>=}25 kg/m{sup 2} compared with patients of normal weight (47% vs. 28%, p = 0.068). Conclusions: BMI {>=}25 kg/m{sup 2} may be a significant risk factor for cardiac toxicity after RT for left-sided breast cancer, possibly because of more frequent deep set-up errors resulting in the inclusion of additional heart in the RT fields. Further study is necessary to better understand the impact of patient-specific factors and set-up errors on the development of RT-induced perfusion defects.« less

The use of refused tea as litter material for broiler chickens.

PubMed

Atapattu, N S B M; Wickramasinghe, K P

2007-05-01

A completely randomized design experiment was conducted to determine the suitability of refused tea (RT) as a litter material for broiler chickens. Physiochemical properties of RT were compared with paddy husk (PH). Subsequently, broilers were raised on RT- or PH-based litter to compare the performances and litter qualities. Twenty-day-old broiler chicks (n = 150) were randomly allocated into 6 deep litter pens so that each treatment had 3 replicates. Chicks received 0.8 ft(2) of floor spacing until d 28 and 1.3 ft(2) thereafter. Each cage had a feeder and a drinker. Litter materials and litter samples taken on 28, 35, and 39 d were analyzed for bulk density, moisture, ash, and N. Chick mortality was low (1.3%) and similar on 2 types of litters. Live weights on d 28, 35, 39, and weight gains, feed intakes, dressing percentages, and feed conversion ratios were not affected by the type of litter material. The bulk density, moisture level, and pH of the RT were comparable with PH. Even though the water-holding capacity of PH (213%) was significantly higher (P < 0.01) than RT (70%), the latter material had significantly higher (P < 0.01) water-releasing capacity compared with the former (17.9 vs. 13.6%). Throughout the experiment the RT litter had around 10% units higher moisture level than PH litter. By d 39, the moisture content of the RT litter was (48%) significantly higher (P = 0.05) than PH litter (37%). The N contents of RT litter were higher (P < 0.05) than those of PH on d 28, 35, and 39, being 8.1, 7.8, and 7% and 3.4, 3.6, and 3%, respectively. It was concluded that RT could be successfully used as an alternative litter material for broilers. A higher N content in RT-based spent broiler litter would make it be a better organic fertilizer and ruminant feed compared with PH-based litter.

Utility of the General Ability Index (GAI) and Cognitive Proficiency Index (CPI) with Survivors of Pediatric Brain Tumors: Comparison to Full Scale IQ and Premorbid IQ Estimates

PubMed Central

Kahalley, Lisa S.; Winter-Greenberg, Amanda; Stancel, Heather; Ris, M. Douglas; Gragert, Marsha

2016-01-01

Introduction Pediatric brain tumor survivors are at risk for working memory and processing speed impairment. The General Ability Index (GAI) provides an estimate of intellectual functioning that is less influenced by working memory and processing speed than a Full Scale IQ (FSIQ). The Cognitive Proficiency Index (CPI) provides a measure of efficient information processing derived from working memory and processing speed tasks. We examined the utility of the GAI and CPI to quantify neurocognitive outcomes in a sample of pediatric brain tumor survivors. Methods GAI, CPI, and FSIQ scores from the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) were examined for 57 pediatric brain tumor survivors (ages 6–16) treated with cranial radiation therapy (RT). Results GAI scores were higher than FSIQ and CPI scores, both p < .001. Lower CPI scores were associated with history of craniospinal irradiation and time since RT. Lower FSIQ and GAI scores were associated with higher RT dose and time since RT. The rate of clinically significant GAI-FSIQ discrepancies in our sample was greater than observed in the WISC-IV standardization sample, p < .001. Estimated premorbid IQ scores were higher than GAI, p < .01, and FSIQ scores, p < .001. Conclusions Pediatric brain tumor survivors exhibit weaker cognitive proficiency than expected for age, while general reasoning ability remains relatively spared. The GAI may be useful to quantify the intellectual potential of a survivor when appropriate accommodations are in place for relative cognitive proficiency weaknesses. The CPI may be a particularly sensitive outcome measure of treatment-related cognitive change in this population. PMID:27295192

Racial and ethnic disparities in the use of intravenous recombinant tissue plasminogen activator and outcomes for acute ischemic stroke.

PubMed

Nasr, Deena M; Brinjikji, Waleed; Cloft, Harry J; Rabinstein, Alejandro A

2013-02-01

Racial and ethnic disparities in acute stroke care in the United States have been previously reported. This study investigated possible racial and ethnic disparities in the administration and outcome of recombinant tissue plasminogen activator (rtPA) therapy for acute ischemic stroke in whites, blacks, Hispanics, and Asian/Pacific Islanders. Using the National Inpatient Sample for 2001-2008, we selected patients with a primary diagnosis of acute ischemic stroke who received treatment with rtPA. Patient data were stratified by race (white, black, Hispanic, and Asian/Pacific Islander). We analyzed the association of patient race on rtPA utilization rate, in-hospital morbidity (ie, discharge to long-term facility), intracranial hemorrhage (ICH) rate, and in-hospital mortality. We performed a multivariate logistic regression analysis to determine independent predictors of poor outcomes. White patients had a higher rate of tPA utilization than black and Hispanic patients (2.3% vs 1.8% and 2.0%, respectively; P < .0001 for both groups). There was no difference in the rate of tPA utilization between whites and Asian/Pacific Islanders (2.3% vs 2.2% P = .07). Multivariate analysis of morbidity, mortality, and ICH rates found that Asian/Pacific Islanders had significantly higher rates of mortality (odds ratio, 1.22, 95% confidence interval, 1.03-1.44; P = .02) and ICH (odds ratio, 2.01; 95% confidence interval, 1.91-2.11; P < .0001) compared with whites. rtPA utilization was greater in white and Asian/Pacific Islander patients than in black and Hispanic patients. Asian/Pacific Islander race was associated with increased risk of ICH and mortality after rtPA administration. Copyright © 2013. Published by Elsevier Inc.

Integrative approach to diagnosis of genital human papillomaviruses (HPV) infection of female.

PubMed

Dunjic, Momir; Stanisic, Slavisa; Krstic, Dejan; Stanisic, Miodrag; Ignjatic, Z Jovanovic; Dunjic, Marija

2014-01-01

Human papillomavirus (HPV) is a virus from the papillomavirus family that is capable of infecting humans. Some types of HPVs cause warts, while others can lead to cancers of the cervix, vulva, vagina, penis, oropharynx and anus. High-risk human papillomavirus (hr HPV) has been detected in almost all cervical squamous cell carcinomas and adenocarcinomas. All patients examined by colposcopy. Cervical swab is routinely done and patients are screened with both HPV DNA by Real Time Polimerase Chain Reaction (RT PCR) testing and Pap testing. Pictures obtained by colposcopy were examined by indirect Bi-Digital O-Ring Test (BDORT) by using reference control substance (RCS): HPV 16, HPV 18, and Integrin α5 β1. BDORT was developed by Prof. Omura Y. of New York and received U.S. patent in 1993. For detection of HPV DNA we used RT PCR and standard Qiagen method which detect 18 types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 6, 11, 42, 43, 44) of HPV from smear. From 63 patients where is BDORT indicated presence of HPV, in 49 patients (77.8%) RT PCR confirmed presence of HPV. From 63 patients in 54 patients (85.7%), we detected, by colposcopic exam, some kind of lesions associated with HPV infection. Results obtained by RT PCR: one type (1/18) of DNA HPV in 25 patients (51.02%), 2 types (2/18) in 15 patients (30.61%) and 3 types (3/18) in 9 patients (18.37%). Although BDORT results usually have higher sensitivity and detection rate is much higher, it can be used together with RT PCR in detection of HPV and cervical lesions associated with HPV infection.

Image-guided intensity-modulated radiotherapy for prostate cancer: Dose constraints for the anterior rectal wall to minimize rectal toxicity

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

Peterson, Jennifer L., E-mail: peterson.jennifer2@mayo.edu; Buskirk, Steven J.; Heckman, Michael G.

2014-04-01

Rectal adverse events (AEs) are a major concern with definitive radiotherapy (RT) treatment for prostate cancer. The anterior rectal wall is at the greatest risk of injury as it lies closest to the target volume and receives the highest dose of RT. This study evaluated the absolute volume of anterior rectal wall receiving a high dose to identify potential ideal dose constraints that can minimize rectal AEs. A total of 111 consecutive patients with Stage T1c to T3a N0 M0 prostate cancer who underwent image-guided intensity-modulated RT at our institution were included. AEs were graded according to the Common Terminologymore » Criteria for Adverse Events, version 4.0. The volume of anterior rectal wall receiving 5 to 80 Gy in 2.5-Gy increments was determined. Multivariable Cox regression models were used to identify cut points in these volumes that led to an increased risk of early and late rectal AEs. Early AEs occurred in most patients (88%); however, relatively few of them (13%) were grade ≥2. At 5 years, the cumulative incidence of late rectal AEs was 37%, with only 5% being grade ≥2. For almost all RT doses, we identified a threshold of irradiated absolute volume of anterior rectal wall above which there was at least a trend toward a significantly higher rate of AEs. Most strikingly, patients with more than 1.29, 0.73, or 0.45 cm{sup 3} of anterior rectal wall exposed to radiation doses of 67.5, 70, or 72.5 Gy, respectively, had a significantly increased risk of late AEs (relative risks [RR]: 2.18 to 2.72; p ≤ 0.041) and of grade ≥ 2 early AEs (RR: 6.36 to 6.48; p = 0.004). Our study provides evidence that definitive image-guided intensity-modulated radiotherapy (IG-IMRT) for prostate cancer is well tolerated and also identifies dose thresholds for the absolute volume of anterior rectal wall above which patients are at greater risk of early and late complications.« less

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

Beta-carotene Antioxidant Use During Radiation Therapy and Prostate Cancer Outcome in the Physicians' Health Study

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

Margalit, Danielle N., E-mail: dmargalit@lroc.harvard.edu; Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts

2012-05-01

Purpose: The safety of antioxidant supplementation during radiation therapy (RT) for cancer is controversial. Antioxidants could potentially counteract the pro-oxidant effects of RT and compromise therapeutic efficacy. We performed a prospective study nested within the Physicians' Health Study (PHS) randomized trial to determine if supplemental antioxidant use during RT for prostate cancer is associated with an increased risk of prostate cancer death or metastases. Methods and Materials: PHS participants (383) received RT for prostate cancer while randomized to receive beta-carotene (50 mg on alternate days) or placebo. The primary endpoint was time from RT to lethal prostate cancer, defined asmore » prostate cancer death or bone metastases. The Kaplan-Meier method was used to estimate survival probabilities and the log-rank test to compare groups. Cox proportional hazards regression was used to estimate the effect of beta-carotene compared with that of placebo during RT. Results: With a median follow-up of 10.5 years, there was no significant difference between risk of lethal prostate cancer with the use of beta-carotene during RT compared with that of placebo (hazard ratio = 0.72; 95% confidence interval [CI], 0.42-1.24; p = 0.24). After we adjusted for age at RT, prostate-specific antigen serum level, Gleason score, and clinical stage, the difference remained nonsignificant. The 10-year freedom from lethal prostate cancer was 92% (95% CI, 87-95%) in the beta-carotene group and 89% (95% CI, 84-93%) in the placebo group. Conclusion: The use of supplemental antioxidant beta-carotene during RT was not associated with an increased risk of prostate cancer death or metastases. This study suggests a lack of harm from supplemental beta-carotene during RT for prostate cancer.« less

Adjuvant Treatment after Surgery in Stage IIIA Endometrial Adenocarcinoma

PubMed Central

Yoon, Mee Sun; Huh, Seung Jae; Kim, Hak Jae; Kim, Young Seok; Kim, Yong Bae; Kim, Joo-Young; Lee, Jong-Hoon; Kim, Hun Jung; Cha, Jihye; Kim, Jin Hee; Kim, Juree; Yoon, Won Sup; Choi, Jin Hwa; Chun, Mison; Choi, Youngmin; Lee, Kang Kyoo; Kim, Myungsoo; Jeong, Jae-Uk; Chang, Sei Kyung; Park, Won

2016-01-01

Purpose We evaluated the role of adjuvant therapy in stage IIIA endometrioid adenocarcinoma patients who underwent surgery followed by radiotherapy (RT) alone or chemoradiotherapy (CTRT) according to risk group. Materials and Methods A multicenter retrospective study was conducted including patients with surgical stage IIIA endometrial cancertreated by radical surgery and adjuvant RT or CTRT. Disease-free survival (DFS) and overall survival (OS) were analyzed. Results Ninety-three patients with stage IIIA disease were identified. Nineteen patients (20.4%) experienced recurrence, mostly distant metastasis (17.2%). Combined CTRT did not affect DFS (74.1% vs. 82.4%, p=0.130) or OS (96.3% vs. 91.9%, p=0.262) in stage IIIA disease compared with RT alone. Patients with age ≥ 60 years, grade G2/3, and lymphovascular space involvement had a significantly worse DFS and those variables were defined as risk factors. The high-risk group showed a significant reduction in 5-year DFS (≥ 2 risk factors) (49.0% vs. 88.0%, p < 0.001) compared with the low-risk group (< 2). Multivariate analysis confirmed that more than one risk factor was the only predictor of worse DFS (hazard ratio, 5.45; 95% confidence interval, 2.12 to 13.98; p < 0.001). Of patients with no risk factors, a subset treated with RT alone showed an excellent 5-year DFS and OS (93.8% and 100%, respectively). Conclusion We identified a low-risk subset of stage IIIA endometrioid adenocarcinoma patients who might be reasonable candidates for adjuvant RT alone. Further randomized studies are needed to determine which subset might benefit from combined CTRT. PMID:26511800

Risk Factors and Characteristics of Low Pathogenic Avian Influenza Virus Isolated from Commercial Poultry in Tunisia

PubMed Central

Tombari, Wafa; Paul, Mathilde; Bettaieb, Jihene; Larbi, Imen; Nsiri, Jihene; Elbehi, Imen; Gribaa, Latifa; Ghram, Abdeljelil

2013-01-01

Objective Estimate the seroprevalence of influenza A virus in various commercial poultry farms and evaluate specific risk factors as well as analyze their genetic nature using molecular assays. Materials and Methods This report summarizes the findings of a national survey realized from October 2010 to May 2011 on 800 flocks in 20 governorates. Serum samples were screened for the presence of specific influenza virus antibodies using cELISA test. Additionally, swab samples were tested by real time and conventional RT-PCR and compared with results obtained by others assays. Phylogenetic and genetic analyses of the glycoproteins were established for some strains. Results Out of the 800 chicken and turkey flocks tested by cELISA, 223 showed positive anti-NP antibodies (28.7%, 95% CI: 25.6–32.1). Significantly higher seroprevalence was found among the coastal areas compared to inland and during the autumn and winter. Broiler flocks showed significantly lower seroprevalence than layers and broiler breeders. The influenza virus infection prevalence increased after the laying phase among layer flocks. In addition, AIV seropositivity was significantly associated with low biosecurity measures. The Ag EIA and rRT-PCR tests revealed significantly higher numbers of AI positive samples as compared to cell cultures or egg inoculation. All new strains were subtyped as H9N2 by real time and conventional RT-PCR. Drift mutations, addition or deletion of glycosylation sites were likely to have occurred in the HA and NA glycoproteins of Tunisian strains resulting in multiple new amino acid substitutions. This fact may reflect different evolutionary pressures affecting these glycoproteins. The role of these newly detected substitutions should be tested. Conclusion Our findings highlight the potential risk of AIV to avian health. Strict enforcement of biosecurity measures and possible vaccination of all poultry flocks with continuous monitoring of poultry stations may ensure reduction of AIV prevalence and avoid emergence of more pathogenic strains. PMID:23326449

Evaluation of the utilization of external radiotherapy in the treatment of localized prostate cancer in Andalusia, Spain.

PubMed

Expósito, José; Linares, Isabel; Castillo, Isabel; Martínez, Miguel; Vargas, Pilar; Herruzo, Ismael; Medina, José Antonio; Palacios, Amalia; Bayo, Eloísa; Peracaula, Francisco; Jaén, Javier; Sánchez, José Antonio; Ortiz, María José

2015-12-30

Around 27,000 new cases of prostate cancer are diagnosed every year in Spain and 5400 die from this disease. Radiotherapy (RT), alone or combined, has proven to be effective as initial treatment in patients with localized disease. Our objective was to evaluate the use of external beam RT (EBRT) in our region, comparing the indication rate and irradiation rate and examining variability in its application among hospitals. We conducted a review of RT guidelines and indication studies for prostate cancer (% expected irradiation). Data were gathered from all twelve public healthcare centers in Andalusia (Spain) on RT-treated prostate cancer patients during 2013 (% actual irradiation) and from nine of the centers on RT discharge reports. Information was classified according to type of hospital, tumor risk category and RT treatment (technique, dosage, volume, toxicity). The estimated RT rate was 67 % (1289/1917), 43 % were aged > 70 years, 44.7 % had ECOG performance status of 0); 44.7 % had high-risk tumors; 57 % underwent RT associated with hormone therapy; 70 % of patients receiving RT were treated with 3D planning (30 % IGRT); and doses were 70-76 Gy in 70 % of cases and >76 Gy in 10.7 %. Acute gastrointestinal and genitourinary toxicities were < grade 2 in 79 and 89 % of patients, respectively. An irradiation rate significantly below the mean for the study was found in four provinces. There was a significant difference among provinces in the distribution of risk groups. Underutilization of EBRT was estimated to be around 30 % in prostate cancer patients, with an elevated variability in irradiation rates among hospitals related to differences in available technology and in the distribution of patients with different risk levels. These data should be a matter of concern to regional health managers, given the negative and measurable impact on the survival of patients.

Effects of adjuvant radiotherapy on borderline and malignant phyllodes tumors: A systematic review and meta-analysis

PubMed Central

ZENG, SHIYAN; ZHANG, XINDAN; YANG, DEJUAN; WANG, XIAOYI; REN, GUOSHENG

2015-01-01

The standard treatment for borderline and malignant phyllodes tumors is wide local excision (margins ≥1 cm), in the context of either breast-conserving surgery (BCS) or total mastectomy (TM). Due to the high risk of local recurrence (LR) following surgical intervention alone, the addition of adjuvant radiotherapy (RT) has been previously investigated; however, the conclusions have been inconsistent. This systematic review and meta-analysis was designed to assess the efficacy of adjuvant RT for borderline and malignant phyllodes tumors. Pubmed and Web of Science were systematically searched to identify relevant studies assessing the effect of adjuvant RT on borderline and malignant phyllodes tumors from the inception of this technique through May, 2014. A total of 8 studies were identified among 332 citations. In this meta-analysis, patients who received adjuvant RT had a lower relative risk of LR [hazard ratio (HR) = 0.43, 95% confidence interval (CI): 0.23–0.64]. The absolute risk difference was 10.1% (95% CI: 4.9–17.6), corresponding to a number needed to treat of 10. Our pooled meta-analysis clearly demonstrated a decreased risk of LR in patients with borderline and malignant phyllodes tumors who received RT following BCS (HR=0.31, 95% CI: −0.10–0.72). However, the combined HR for LR in the TM group did not demonstrate that adjuvant RT was superior to no RT (HR=0.68, 95% CI: −0.28–1.64). No significant differences were observed in overall survival (OS) or disease-free survival (DFS) between the two groups. Our analysis suggested that adjuvant RT for borderline and malignant phyllodes tumors decreased the LR rate in patients undergoing BCS. However, adjuvant RT was not found to exert an effect on OS or DFS. PMID:26137284

How the risky features of previous selection affect subsequent decision-making: evidence from behavioral and fMRI measures.

PubMed

Dong, Guangheng; Zhang, Yifen; Xu, Jiaojing; Lin, Xiao; Du, Xiaoxia

2015-01-01

Human decision making is rarely conducted in temporal isolation. It is often biased and affected by environmental variables, particularly prior selections. In this study, we used a task that simulates a real gambling process to explore the effect of the risky features of a previous selection on subsequent decision making. Compared with decision making after an advantageous risk-taking situation (Risk_Adv), that after a disadvantageous risk-taking situation (Risk_Disadv) is associated with a longer response time (RT, the time spent in making decisions) and higher brain activations in the caudate and the dorsolateral prefrontal cortex (DLPFC). Compared with decisions after Risk_Adv, those after Risk_Disadv in loss trials are associated with higher brain activations in the left superior temporal gyrus (STG) and the precuneus. Brain activity and relevant RTs significantly correlated. Overall, people who experience disadvantageous risk-taking selections tend to focus on current decision making and engage cognitive endeavors in value evaluation and in the regulation of their risk-taking behaviors during decision making.

Local Control With 21-Gy Radiation Therapy for High-Risk Neuroblastoma

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

Casey, Dana L.; Kushner, Brian H.; Cheung, Nai-Kong V.

2016-10-01

Purpose: To evaluate local control after 21-Gy radiation therapy (RT) to the primary site in patients with high-risk neuroblastoma. Methods and Materials: After receiving dose-intensive chemotherapy and gross total resection (GTR), 246 patients (aged 1.2-17.9 years, median 4.0 years) with high-risk neuroblastoma underwent RT to the primary site at Memorial Sloan Kettering from 2000 to 2014. Radiation therapy consisted of 21 Gy in twice-daily fractions of 1.5 Gy each. Local failure (LF) was correlated with biologic prognostic factors and clinical findings at the time of diagnosis and start of RT. Results: Median follow-up of surviving patients was 6.4 years. Cumulative incidence of LF was 7.1%more » at 2 years after RT and 9.8% at 5 years after RT. The isolated LF rate was 3.0%. Eighty-six percent of all local failures were within the RT field. Local control was worse in patients who required more than 1 surgical resection to achieve GTR (22.4% vs 8.3%, P=.01). There was also a trend toward inferior local control with MYCN-amplified tumors or serum lactate dehydrogenase ≥1500 U/L (P=.09 and P=.06, respectively). Conclusion: After intensive chemotherapy and maximal surgical debulking, hyperfractionated RT with 21 Gy in high-risk neuroblastoma results in excellent local control. Given the young patient age, concern for late effects, and local control >90%, dose reduction may be appropriate for patients without MYCN amplification who achieve GTR.« less

Shielding of the Hip Prosthesis During Radiation Therapy for Heterotopic Ossification is Associated with Increased Failure of Prophylaxis

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

Balboni, Tracy A.; Gaccione, Peter; Gobezie, Reuben

2007-04-01

Purpose: Radiation therapy (RT) is frequently administered to prevent heterotopic ossification (HO) after total hip arthroplasty (THA). The purpose of this study was to determine if there is an increased risk of HO after RT prophylaxis with shielding of the THA components. Methods and Materials: This is a retrospective analysis of THA patients undergoing RT prophylaxis of HO at Brigham and Women's Hospital between June 1994 and February 2004. Univariate and multivariate logistic regressions were used to assess the relationships of all variables to failure of RT prophylaxis. Results: A total of 137 patients were identified and 84 were eligiblemore » for analysis (61%). The median RT dose was 750 cGy in one fraction, and the median follow-up was 24 months. Eight of 40 unshielded patients (20%) developed any progression of HO compared with 21 of 44 shielded patients (48%) (p = 0.009). Brooker Grade III-IV HO developed in 5% of unshielded and 18% of shielded patients (p 0.08). Multivariate analysis revealed shielding (p = 0.02) and THA for prosthesis infection (p = 0.03) to be significant predictors of RT failure, with a trend toward an increasing risk of HO progression with age (p = 0.07). There was no significant difference in the prosthesis failure rates between shielded and unshielded patients. Conclusions: A significantly increased risk of failure of RT prophylaxis for HO was noted in those receiving shielding of the hip prosthesis. Shielding did not appear to reduce the risk of prosthesis failure.« less

Testicular cancer: A narrative review of the role of socioeconomic position from risk to survivorship

PubMed Central

Richardson, Lisa C.; Neri, Antonio J.; Tai, Eric; Glenn, Jeffrey D.

2015-01-01

Background Testicular cancer (TC) is one of the most curable cancers. Given survival rates of close to 100% with appropriate therapy, ensuring proper treatment is essential. We reviewed and summarized the literature on the association of socioeconomic position (SEP) along the cancer control spectrum from risk factors to survivorship. Methods We searched PubMed from 1966 to 2011 using the following terms: testicular cancer, testicular neoplasm, poverty, and socioeconomic factors, retrieving 119 papers. After excluding papers for the non-English (10) language and non-relevance (46), we reviewed 63 papers. We abstracted information on socioeconomic position (SEP), including occupation, education, income, and combinations of the 3. Five areas were examined: risk factors, diagnosis, treatment, survival, and survivorship. Results Most studies examined area-based measures, not individual measures of SEP. The majority of studies found an increased risk of developing TC with high SEP though recent papers have indicated increased risk in low-income populations. Regarding diagnosis, recent papers have indicated that lower levels of education and SEP are risk factors for later-stage TC diagnosis and hence higher TC mortality. For treatment, 1 study that examined the use of radiation therapy (RT) in stage I seminoma reported that living in a county with lower educational attainment led to lower use of RT. For survival (mortality), several studies found that men living in lower SEP geographic areas experience lower survival and higher mortality. Conclusion The strongest evidence for SEP impact on testicular germ cell tumor (TGCT) was found for the risk of developing cancer as well as survival. The association of SEP with TGCT risk appears to have changed over the last decade. Given the highly curable nature of TGCT, more research is needed to understand how SEP impacts diagnosis and treatment for TGCT and to design interventions to address disparities in TGCT outcomes and SEP. Published by Elsevier Inc. PMID:22127018

Sphincter-sparing local excision and hypofractionated radiation therapy for anorectal melanoma: a 20-year experience.

PubMed

Kelly, Patrick; Zagars, Gunar K; Cormier, Jancie N; Ross, Merrick I; Guadagnolo, B Ashleigh

2011-10-15

Anorectal melanoma is a rare disease with a poor prognosis. Because survival is determined by distant failure, many centers have adopted sphincter-sparing excision for primary tumor control. However, this approach is associated with high rates of local failure (∼50%). In this study, the authors report their 20-year experience with sphincter-sparing excision combined with radiation therapy (RT) for the treatment of localized anorectal melanoma. The authors reviewed the records of 54 patients with localized anorectal melanoma who were treated at the University of Texas MD Anderson Cancer Center from 1989 to 2008. All patients underwent definitive local excision with or without sentinel lymph node biopsy or lymph node dissection. RT (25-36 grays in 5-6 fractions) was delivered to extended fields that targeted the primary site and draining pelvic/inguinal lymphatics in 39 patients and to limited fields that targeted only the primary site in 15 patients. The 5-year rates of local control (LC), lymph node control (NC), and sphincter preservation were 82%, 88%, and 96%, respectively. However, because of the high rate of distant metastasis, the overall survival (OS) rate at 5 years was only 30%. Although there were no significant differences in LC, NC, or OS based on RT field extent, patients who received extended-field RT had higher rates of lymphedema than patients who received limited-field RT. The current results indicated that combined sphincter-sparing local excision and RT is a well tolerated approach that provides effective LC for patients with anorectal melanoma. Inclusion of the inguinal lymph node basins in the RT fields did not improve outcomes and was associated with an increased risk of lymphedema. Copyright © 2011 American Cancer Society.

Simulating the Effect of Spectroscopic MRI as a Metric for Radiation Therapy Planning in Patients with Glioblastoma

PubMed Central

Cordova, J. Scott; Kandula, Shravan; Gurbani, Saumya; Zhong, Jim; Tejani, Mital; Kayode, Oluwatosin; Patel, Kirtesh; Prabhu, Roshan; Schreibmann, Eduard; Crocker, Ian; Holder, Chad A.; Shim, Hyunsuk; Shu, Hui-Kuo

2017-01-01

Due to glioblastoma’s infiltrative nature, an optimal radiation therapy (RT) plan requires targeting infiltration not identified by anatomical magnetic resonance imaging (MRI). Here, high-resolution, whole-brain spectroscopic MRI (sMRI) is used to describe tumor infiltration alongside anatomical MRI and simulate the degree to which it modifies RT target planning. In 11 patients with glioblastoma, data from preRT sMRI scans were processed to give high-resolution, whole-brain metabolite maps normalized by contralateral white matter. Maps depicting choline to N-Acetylaspartate (Cho/NAA) ratios were registered to contrast-enhanced T1-weighted RT planning MRI for each patient. Volumes depicting metabolic abnormalities (1.5−, 1.75−, and 2.0-fold increases in Cho/NAA ratios) were compared with conventional target volumes and contrast-enhancing tumor at recurrence. sMRI-modified RT plans were generated to evaluate target volume coverage and organ-at-risk dose constraints. Conventional clinical target volumes and Cho/NAA abnormalities identified significantly different regions of microscopic infiltration with substantial Cho/NAA abnormalities falling outside of the conventional 60 Gy isodose line (41.1, 22.2, and 12.7 cm3, respectively). Clinical target volumes using Cho/NAA thresholds exhibited significantly higher coverage of contrast enhancement at recurrence on average (92.4%, 90.5%, and 88.6%, respectively) than conventional plans (82.5%). sMRI-based plans targeting tumor infiltration met planning objectives in all cases with no significant change in target coverage. In 2 cases, the sMRI-modified plan exhibited better coverage of contrast-enhancing tumor at recurrence than the original plan. Integration of the high-resolution, whole-brain sMRI into RT planning is feasible, resulting in RT target volumes that can effectively target tumor infiltration while adhering to conventional constraints. PMID:28105468

Primary treatments for clinically localised prostate cancer: a comprehensive lifetime cost-utility analysis.

PubMed

Cooperberg, Matthew R; Ramakrishna, Naren R; Duff, Steven B; Hughes, Kathleen E; Sadownik, Sara; Smith, Joseph A; Tewari, Ashutosh K

2013-03-01

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Multiple treatment alternatives exist for localised prostate cancer, with few high-quality studies directly comparing their comparative effectiveness and costs. The present study is the most comprehensive cost-effectiveness analysis to date for localised prostate cancer, conducted with a lifetime horizon and accounting for survival, health-related quality-of-life, and cost impact of secondary treatments and other downstream events, as well as primary treatment choices. The analysis found minor differences, generally slightly favouring surgical methods, in quality-adjusted life years across treatment options. However, radiation therapy (RT) was consistently more expensive than surgery, and some alternatives, e.g. intensity-modulated RT for low-risk disease, were dominated - that is, both more expensive and less effective than competing alternatives. To characterise the costs and outcomes associated with radical prostatectomy (open, laparoscopic, or robot-assisted) and radiation therapy (RT: dose-escalated three-dimensional conformal RT, intensity-modulated RT, brachytherapy, or combination), using a comprehensive, lifetime decision analytical model. A Markov model was constructed to follow hypothetical men with low-, intermediate-, and high-risk prostate cancer over their lifetimes after primary treatment; probabilities of outcomes were based on an exhaustive literature search yielding 232 unique publications. In each Markov cycle, patients could have remission, recurrence, salvage treatment, metastasis, death from prostate cancer, and death from other causes. Utilities for each health state were determined, and disutilities were applied for complications and toxicities of treatment. Costs were determined from the USA payer perspective, with incorporation of patient costs in a sensitivity analysis. Differences across treatments in quality-adjusted life years across methods were modest, ranging from 10.3 to 11.3 for low-risk patients, 9.6-10.5 for intermediate-risk patients and 7.8-9.3 for high-risk patients. There were no statistically significant differences among surgical methods, which tended to be more effective than RT methods, with the exception of combined external beam + brachytherapy for high-risk disease. RT methods were consistently more expensive than surgical methods; costs ranged from $19 901 (robot-assisted prostatectomy for low-risk disease) to $50 276 (combined RT for high-risk disease). These findings were robust to an extensive set of sensitivity analyses. Our analysis found small differences in outcomes and substantial differences in payer and patient costs across treatment alternatives. These findings may inform future policy discussions about strategies to improve efficiency of treatment selection for localised prostate cancer. © 2012 BJU International.

Interval to Testosterone Recovery After Hormonal Therapy for Prostate Cancer and Risk of Death

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

D'Amico, Anthony V.; Chen, M.-H.; Renshaw, Andrew A.

Purpose: To assess whether the risk of death is associated with the time to testosterone recovery (TTR) after radiotherapy (RT) and hormonal therapy (HT) for prostate cancer (PCa). Patients and Methods: Between 1995 and 2001, 206 men with localized, unfavorable-risk PCa were randomized to receive RT or RT plus 6 months of HT. A multivariate postrandomization Cox regression analysis was used to assess whether the TTR in years was associated with the risk of death after adjusting for the known prognostic factors, age, Adult Comorbidity Evaluation-27 score, and the use of HT for recurrence. Results: Of the 102 men randomizedmore » to receive RT and HT, 57 (56%) had a TTR of >2 years, and none of these men had died of PCa after a median follow-up of 7.6 years. As the TTR increased, the risk of death decreased significantly (adjusted hazard ratio, 0.60; 95% confidence interval, 0.43-0.84; p = .003). A significant interaction was noted between the TTR and the comorbidity score (p = .002). The survival estimates were similar (p = 0.17) across the TTR values in men with moderate to severe comorbidity; however, these estimates increased significantly (p < .001) with decreasing PCa-specific mortality (p = .006) as the TTR increased in men with no or minimal comorbidity. Conclusion: The results of our study have shown that a longer TTR after RT plus 6 months of HT for unfavorable-risk PCa is associated with a lower risk of death in men with no or minimal comorbidity.« less

Dose constraints in the rectum and bladder following carbon-ion radiotherapy for uterus carcinoma: a retrospective pooled analysis.

PubMed

Okonogi, Noriyuki; Fukahori, Mai; Wakatsuki, Masaru; Ohkubo, Yu; Kato, Shingo; Miyasaka, Yuhei; Tsuji, Hiroshi; Nakano, Takashi; Kamada, Tadashi

2018-06-25

Carbon-ion radiotherapy (C-ion RT) provides better dose distribution in cancer treatment compared to photons. Additionally, carbon-ion beams provide a higher biological effectiveness, and thus a higher tumor control probability. However, information regarding the dose constraints for organs at risk in C-ion RT is limited. This study aimed to determine the predictive factors for late morbidities in the rectum and bladder after carbon-ion C-ion RT for uterus carcinomas. Between June 1995 and January 2010, 134 patients with uterus carcinomas were treated with C-ion RT with curative intent; prescription doses of 52.8-74.4 Gy (relative biological effectiveness) were delivered in 20-24 fractions. Of these patients, 132 who were followed up for > 6 months were analyzed. We separated the data in two subgroups, a 24 fractions group and a 20 fractions group. Late morbidities, proctitis, and cystitis were assessed according to the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer criteria. The correlations of clinical and dosimetric parameters, V10-V60, D 5cc , D 2cc , and Dmax, with the incidence of ≥grade 1 morbidities were retrospectively analyzed. In the 24 fractions group, the 3-year actuarial occurrence rates of ≥grade 1 rectal and bladder morbidities were 64 and 9%, respectively. In addition, in the 20 fractions group, the 3-year actuarial occurrence rates of ≥grade 1 rectal and bladder morbidities were 32 and 19%, respectively. Regarding the dose-volume histogram data on the rectum, the D 5cc and D 2cc were significantly higher in patients with ≥grade 1 proctitis than in those without morbidity. In addition, the D 5cc for the bladder was significantly higher in patients with ≥grade 1 cystitis than in those without morbidity. Results of univariate analyses showed that D 2cc of the rectum was correlated with the development of ≥grade 1 late proctitis. Moreover, D 5cc of the bladder was correlated with the development of ≥grade 1 late cystitis. The present study identified the dose-volume relationships in C-ion RT regarding the occurrence of late morbidities in the rectum and bladder. Assessment of the factors discussed herein would be beneficial in preventing late morbidities after C-ion RT for pelvic malignancies. Retrospectively registered ( NIRS: 16-040 ).

Mandibular osteoradionecrosis in squamous cell carcinoma of the oral cavity and oropharynx: incidence and risk factors.

PubMed

Monnier, Yan; Broome, Martin; Betz, Michael; Bouferrache, Kahina; Ozsahin, Mahmut; Jaques, Bertrand

2011-05-01

Mandibular osteoradionecrosis (ORN) is a serious complication of radiotherapy (RT) in head and neck cancer patients. The aim of this study was to analyze the incidence of and risk factors for mandibular ORN in squamous cell carcinoma (SCC) of the oral cavity and oropharynx. Case series with chart review. University tertiary care center for head and neck oncology. Seventy-three patients treated for stage I to IV SCC of the oral cavity and oropharynx between 2000 and 2007, with a minimum follow-up of 2 years, were included in the study. Treatment modalities included both RT with curative intent and adjuvant RT following tumor surgery. The log-rank test and Cox model were used for univariate and multivariate analyses. The incidence of mandibular ORN was 40% at 5 years. Using univariate analysis, the following risk factors were identified: oral cavity tumors (P < .01), bone invasion (P < .02), any surgery prior to RT (P < .04), and bone surgery (P < .0001). By multivariate analysis, mandibular surgery proved to be the most important risk factor and the only one reaching statistical significance (P < .0002). Mandibular ORN is a frequent long-term complication of RT for oral cavity and oropharynx cancers. Mandibular surgery before irradiation is the only independent risk factor. These aspects must be considered when planning treatment for these tumors.

Influence of Comorbidity on the Risk of Mortality in Men With Unfavorable-Risk Prostate Cancer Undergoing High-Dose Radiation Therapy Alone

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

Huynh, Mai Anh, E-mail: mahuynh@lroc.harvard.edu; Chen, Ming-Hui; Wu, Jing

Purpose: To explore whether a subgroup of men with unfavorable-risk prostate cancer (PC) exists in whom high-dose radiation therapy (RT) alone is sufficient to avoid excess PC death due to competing risk from cardiometabolic comorbidity. Methods and Materials: This was a cohort study of 7399 men in whom comorbidity (including congestive heart failure, diabetes mellitus, or myocardial infarction) was assessed and recorded with T1-3NxM0 PC treated with brachytherapy with or without neoadjuvant RT, October 1997 to May 2013 at a single providing institution. Cox and competing risks regression analyses were used to assess whether men with unfavorable–intermediate/high-risk versus favorable–intermediate/low-risk PC weremore » at increased risk of PC-specific, all-cause, or other-cause mortality (PCSM, ACM, OCM), adjusting for number of comorbidities, age at and year of brachytherapy, RT use, and an RT treatment propensity score. Results: After a median follow-up of 7.7 years, 935 men died: 80 of PC and 855 of other causes. Among men with no comorbidity, PCSM risk (adjusted hazard ratio [AHR] 2.74 [95% confidence interval (CI) 1.49-5.06], P=.001) and ACM risk (AHR 1.30 [95% CI 1.07-1.58], P=.007) were significantly increased in men with unfavorable–intermediate/high-risk PC versus favorable–intermediate/low-risk PC, with no difference in OCM (P=.07). Although PCSM risk was increased in men with 1 comorbidity (AHR 2.87 [95% CI 1.11-7.40], P=.029), ACM risk was not (AHR 1.03 [95% CI 0.78-1.36], P=.84). Neither PCSM risk (AHR 4.39 [95% CI 0.37-51.98], P=.24) or ACM risk (AHR 1.43 [95% CI 0.83-2.45], P=.20) was increased in men with 2 comorbidities. Conclusions: To minimize death from PC, high-dose RT alone may be sufficient treatment in men with 2 or more cardiometabolic comorbidities and unfavorable–intermediate- and high-risk PC.« less

Effect of resistance training and hypocaloric diets with different protein content on body composition and lipid profile in hypercholesterolemic obese women.

PubMed

García-Unciti, M; Martinez, J A; Izquierdo, M; Gorostiaga, E M; Grijalba, A; Ibañez, J

2012-01-01

Lifestyle changes such as following a hypocaloric diet and regular physical exercise are recognized as effective non-pharmacological interventions to reduce body fat mass and prevent cardiovascular disease risk factors. To evaluate the interactions of a higher protein (HP) vs. a lower protein (LP) diet with or without a concomitant progressive resistance training program (RT) on body composition and lipoprotein profile in hypercholesterolemic obese women. Retrospective study derived from a 16-week randomized controlled-intervention clinical trial. Twenty five sedentary, obese (BMI: 30-40 kg/m²) women, aged 40-60 with hypercholesterolemia were assigned to a 4-arm trial using a 2 x 2 factorial design (Diet x Exercise). Prescribed diets had the same calorie restriction (-500 kcal/day), and were categorized according to protein content as: lower protein (< 22% daily energy intake, LP) vs. higher protein (> 22% daily energy intake, HP). Exercise comparisons involved habitual activity (control) vs. a 16-week supervised whole-body resistance training program (RT), two sessions/wk. A significant decrease in weight and waist circumference was observed in all groups. A significant decrease in LDL-C and Total-Cholesterol levels was observed only when a LP diet was combined with a RT program, the RT being the most determining factor. Interestingly, an interaction between diet and exercise was found concerning LDL-C values. In this study, resistance training plays a key role in improving LDL-C and Total-Cholesterol; however, a lower protein intake (< 22% of daily energy intake as proteins) was found to achieve a significantly greater reduction in LDL-C.

Predictors of Local Recurrence After Rituximab-Based Chemotherapy Alone in Stage III and IV Diffuse Large B-Cell Lymphoma: Guiding Decisions for Consolidative Radiation

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

Jegadeesh, Naresh; Rajpara, Raj; Esiashvili, Natia

Purpose: The role of consolidative radiation therapy (RT) for stage III and IV diffuse large B-cell lymphoma (DLBCL) in the era of rituximab is not well defined. There is evidence that some patients with bulky disease may benefit, but patient selection criteria are not well established. We sought to identify a subset of patients who experienced a high local failure rate after receiving rituximab-based chemotherapy alone and hence may benefit from the addition of consolidative RT. Methods and Materials: Two hundred eleven patients with stage III and IV DLBCL treated between August 1999 and January 2012 were reviewed. Of these,more » 89 had a complete response to systemic therapy including rituximab and received no initial RT. Kaplan-Meier analysis and Cox proportional hazards regression were performed, with local recurrence (LR) as the primary outcome. Results: The median follow-up time was 43.9 months. Fifty percent of patients experienced LR at 5 years. In multivariate analysis, tumor ≥5 cm and stage III disease were associated with increased risk of LR. The 5-year LR-free survival was 47.4% for patients with ≥5-cm lesions versus 74.7% for patients with <5-cm lesions (P=.01). In patients with <5-cm tumors, the maximum standardized uptake value (SUVmax) was ≥15 in all patients with LR. The 5-year LR-free survival was 100% in SUV<15 versus 68.8% in SUV≥15 (P=.10). Conclusions: Advanced-stage DLBCL patients with stage III disease or with disease ≥5 cm appear to be at an increased risk for LR. Patients with <5-cm disease and SUVmax ≥15 may be at higher risk for LR. These patients may benefit from consolidative RT after chemoimmunotherapy.« less

Measuring Burden of Unhealthy Behaviours Using a Multivariable Predictive Approach: Life Expectancy Lost in Canada Attributable to Smoking, Alcohol, Physical Inactivity, and Diet.

PubMed

Manuel, Douglas G; Perez, Richard; Sanmartin, Claudia; Taljaard, Monica; Hennessy, Deirdre; Wilson, Kumanan; Tanuseputro, Peter; Manson, Heather; Bennett, Carol; Tuna, Meltem; Fisher, Stacey; Rosella, Laura C

2016-08-01

Behaviours such as smoking, poor diet, physical inactivity, and unhealthy alcohol consumption are leading risk factors for death. We assessed the Canadian burden attributable to these behaviours by developing, validating, and applying a multivariable predictive model for risk of all-cause death. A predictive algorithm for 5 y risk of death-the Mortality Population Risk Tool (MPoRT)-was developed and validated using the 2001 to 2008 Canadian Community Health Surveys. There were approximately 1 million person-years of follow-up and 9,900 deaths in the development and validation datasets. After validation, MPoRT was used to predict future mortality and estimate the burden of smoking, alcohol, physical inactivity, and poor diet in the presence of sociodemographic and other risk factors using the 2010 national survey (approximately 90,000 respondents). Canadian period life tables were generated using predicted risk of death from MPoRT. The burden of behavioural risk factors attributable to life expectancy was estimated using hazard ratios from the MPoRT risk model. The MPoRT 5 y mortality risk algorithms were discriminating (C-statistic: males 0.874 [95% CI: 0.867-0.881]; females 0.875 [0.868-0.882]) and well calibrated in all 58 predefined subgroups. Discrimination was maintained or improved in the validation cohorts. For the 2010 Canadian population, unhealthy behaviour attributable life expectancy lost was 6.0 years for both men and women (for men 95% CI: 5.8 to 6.3 for women 5.8 to 6.2). The Canadian life expectancy associated with health behaviour recommendations was 17.9 years (95% CI: 17.7 to 18.1) greater for people with the most favourable risk profile compared to those with the least favourable risk profile (88.2 years versus 70.3 years). Smoking, by itself, was associated with 32% to 39% of the difference in life expectancy across social groups (by education achieved or neighbourhood deprivation). Multivariable predictive algorithms such as MPoRT can be used to assess health burdens for sociodemographic groups or for small changes in population exposure to risks, thereby addressing some limitations of more commonly used measurement approaches. Unhealthy behaviours have a substantial collective burden on the life expectancy of the Canadian population.

Measuring Burden of Unhealthy Behaviours Using a Multivariable Predictive Approach: Life Expectancy Lost in Canada Attributable to Smoking, Alcohol, Physical Inactivity, and Diet

PubMed Central

Perez, Richard; Taljaard, Monica; Hennessy, Deirdre; Wilson, Kumanan; Tanuseputro, Peter; Bennett, Carol; Tuna, Meltem; Fisher, Stacey; Rosella, Laura C.

2016-01-01

Background Behaviours such as smoking, poor diet, physical inactivity, and unhealthy alcohol consumption are leading risk factors for death. We assessed the Canadian burden attributable to these behaviours by developing, validating, and applying a multivariable predictive model for risk of all-cause death. Methods A predictive algorithm for 5 y risk of death—the Mortality Population Risk Tool (MPoRT)—was developed and validated using the 2001 to 2008 Canadian Community Health Surveys. There were approximately 1 million person-years of follow-up and 9,900 deaths in the development and validation datasets. After validation, MPoRT was used to predict future mortality and estimate the burden of smoking, alcohol, physical inactivity, and poor diet in the presence of sociodemographic and other risk factors using the 2010 national survey (approximately 90,000 respondents). Canadian period life tables were generated using predicted risk of death from MPoRT. The burden of behavioural risk factors attributable to life expectancy was estimated using hazard ratios from the MPoRT risk model. Findings The MPoRT 5 y mortality risk algorithms were discriminating (C-statistic: males 0.874 [95% CI: 0.867–0.881]; females 0.875 [0.868–0.882]) and well calibrated in all 58 predefined subgroups. Discrimination was maintained or improved in the validation cohorts. For the 2010 Canadian population, unhealthy behaviour attributable life expectancy lost was 6.0 years for both men and women (for men 95% CI: 5.8 to 6.3 for women 5.8 to 6.2). The Canadian life expectancy associated with health behaviour recommendations was 17.9 years (95% CI: 17.7 to 18.1) greater for people with the most favourable risk profile compared to those with the least favourable risk profile (88.2 years versus 70.3 years). Smoking, by itself, was associated with 32% to 39% of the difference in life expectancy across social groups (by education achieved or neighbourhood deprivation). Conclusions Multivariable predictive algorithms such as MPoRT can be used to assess health burdens for sociodemographic groups or for small changes in population exposure to risks, thereby addressing some limitations of more commonly used measurement approaches. Unhealthy behaviours have a substantial collective burden on the life expectancy of the Canadian population. PMID:27529741

Incidental Statin Use and the Risk of Stroke or Transient Ischemic Attack after Radiotherapy for Head and Neck Cancer

PubMed Central

Addison, Daniel; Lawler, Patrick R.; Emami, Hamed; Janjua, Sumbal A.; Staziaki, Pedro V.; Hallett, Travis R.; Hennessy, Orla; Lee, Hang; Szilveszter, Bálint; Lu, Michael; Mousavi, Negar; Nayor, Matthew G.; Delling, Francesca N.; Romero, Javier M.; Wirth, Lori J.; Chan, Annie W.; Hoffmann, Udo; Neilan, Tomas G.

2018-01-01

Background and Purpose Interventions to reduce the risk for cerebrovascular events (CVE; stroke and transient ischemic attack [TIA]) after radiotherapy (RT) for head and neck cancer (HNCA) are needed. Among broad populations, statins reduce CVEs; however, whether statins reduce CVEs after RT for HNCA is unclear. Therefore, we aimed to test whether incidental statin use at the time of RT is associated with a lower rate of CVEs after RT for HNCA. Methods From an institutional database we identified all consecutive subjects treated with neck RT from 2002 to 2012 for HNCA. Data collection and event adjudication was performed by blinded teams. The primary outcome was a composite of ischemic stroke and TIA. The secondary outcome was ischemic stroke. The association between statin use and events was determined using Cox proportional hazard models after adjustment for traditional and RT-specific risk factors. Results The final cohort consisted of 1,011 patients (59±13 years, 30% female, 44% hypertension) with 288 (28%) on statins. Over a median follow-up of 3.4 years (interquartile range, 0.1 to 14) there were 102 CVEs (89 ischemic strokes and 13 TIAs) with 17 in statin users versus 85 in nonstatins users. In a multivariable model containing known predictors of CVE, statins were associated with a reduction in the combination of stroke and TIA (hazard ratio [HR], 0.4; 95% confidence interval [CI], 0.2 to 0.8; P=0.01) and ischemic stroke alone (HR, 0.4; 95% CI, 0.2 to 0.8; P=0.01). Conclusions Incidental statin use at the time of RT for HNCA is associated with a lower risk of stroke or TIA. PMID:29402065

Phase II multi-institutional clinical trial on a new mixed beam RT scheme of IMRT on pelvis combined with a carbon ion boost for high-risk prostate cancer patients.

PubMed

Marvaso, Giulia; Jereczek-Fossa, Barbara A; Vischioni, Barbara; Ciardo, Delia; Giandini, Tommaso; Hasegawa, Azusa; Cattani, Federica; Carrara, Mauro; Ciocca, Mario; Bedini, Nice; Villa, Sergio; Morlino, Sara; Russo, Stefania; Zerini, Dario; Colangione, Sarah Pia; Panaino, Costanza Maria Vittoria; Fodor, Cristiana; Santoro, Luigi; Pignoli, Emanuele; Valvo, Francesca; Valdagni, Riccardo; De Cobelli, Ottavio; Orecchia, Roberto

2017-05-12

Definition of the optimal treatment schedule for high-risk prostate cancer is under debate. A combination of photon intensity modulated radiotherapy (IMRT) on pelvis with a carbon ion boost might be the optimal treatment scheme to escalate the dose on prostate and deliver curative dose with respect to normal tissue and quality of dose distributions. In fact, carbon ion beams offer the advantage to deliver hypofractionated radiotherapy (RT) using a significantly smaller number of fractions compared to conventional RT without increasing risks of late effects. This study is a prospective phase II clinical trial exploring safety and feasibility of a mixed beam scheme of carbon ion prostate boost followed by photon IMRT on pelvis. The study is designed to enroll 65 patients with localized high-risk prostate cancer at 3 different oncologic hospitals: Istituto Europeo di Oncologia, Fondazione IRCCS Istituto Nazionale dei Tumori, and Centro Nazionale di Adroterapia Oncologica. The primary endpoint is the evaluation of safety and feasibility with acute toxicity scored up to 1 month after the end of RT. Secondary endpoints are treatment early (3 months after the end of RT) and long-term tolerability, quality of life, and efficacy. The study is not yet recruiting; in silico studies are ongoing and we expect to start recruitment by 2017. The present clinical trial aims at improving the current treatment for high-risk prostate cancer, evaluating safety and feasibility of a new RT mixed-beam scheme including photons and carbon ions. Encouraging results are coming from carbon ion facilities worldwide on the treatment of different tumors including prostate cancers. Carbon ions combine physical properties allowing for high dose conformity and advantageous radiobiological characteristics. The proposed mixed beam treatment has the advantage to combine a photon high conformity standard of care IMRT phase with a hypofractionated carbon ion RT boost delivered in a short overall treatment time.

PSA Response to Neoadjuvant Androgen Deprivation Therapy Is a Strong Independent Predictor of Survival in High-Risk Prostate Cancer in the Dose-Escalated Radiation Therapy Era

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

McGuire, Sean E., E-mail: semcguir@mdanderson.org; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas; Lee, Andrew K.

2013-01-01

Purpose: The aim of the study was to evaluate the prognostic value of prostate-specific antigen (PSA) response to neoadjuvant androgen deprivation therapy (ADT) prior to dose-escalated radiation therapy (RT) and long-term ADT in high-risk prostate cancer. Methods and Materials: We reviewed the charts of all patients diagnosed with high-risk prostate cancer and treated with a combination of long-term ADT (median, 24 months) and dose-escalated (median, 75.6 Gy) RT between 1990 and 2007. The associations among patient, tumor, and treatment characteristics with biochemical response to neoadjuvant ADT and their effects on failure-free survival (FFS), time to distant metastasis (TDM), prostate cancer-specificmore » mortality (PCSM) and overall survival (OS) were examined. Results: A total of 196 patients met criteria for inclusion. Median follow-up time for patients alive at last contact was 7.0 years (range, 0.5-18.1 years). Multivariate analysis identified the pre-RT PSA concentration (<0.5 vs {>=}0.5 ng/mL) as a significant independent predictor of FFS (P=.021), TDM (P=.009), PCSM (P=.039), and OS (P=.037). On multivariate analysis, pretreatment PSA (iPSA) and African-American race were significantly associated with failure to achieve a pre-RT PSA of <0.5 ng/mL. Conclusions: For high-risk prostate cancer patients treated with long-term ADT and dose-escalated RT, a pre-RT PSA level {>=}0.5 ng/mL after neoadjuvant ADT predicts for worse survival measures. Both elevated iPSA and African-American race are associated with increased risk of having a pre-RT PSA level {>=}0.5 ng/mL. These patients should be considered for clinical trials that test newer, more potent androgen-depleting therapies such as abiraterone and MDV3100 in combination with radiation.« less

Androgen deprivation with or without radiation therapy for clinically node-positive prostate cancer. Lin CC, Gray PJ, Jemal A, Efstathiou JA, Surveillance and Health Services Research Program, Intramural Research, American Cancer Society, Atlanta, GA (CCL, AJ); Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (PJG, JAE); e-mail: jefstathiou@partners.org. J Natl Cancer Inst. 2015 May 9;107(7). pii: djv119. [Print 2015 Jul]. doi: 10.1093/jnci/djv119.

PubMed

Scott, Eggener

2017-03-01

Clinically lymph node-positive (cN+) prostate cancer (PCa) is an often-fatal disease. Its optimal management remains largely undefined given a lack of prospective, randomized data to inform practice. We sought to describe modern practice patterns in the management of cN+PCa and assess the effect of adding radiation therapy (RT) to androgen deprivation therapy (ADT) on survival using the National Cancer Data Base. Patients with cN+PCa and without distant metastases diagnosed between 2004 and 2011 were included. Five-year overall survival for patients diagnosed between 2004 and 2006 and treated with ADT alone or ADT+RT were compared. Propensity score (PS) matching was used to balance baseline characteristics, and Cox multivariate regression analysis was used to estimate hazard ratios (HRs) for all-cause mortality. Of 3,540 total patients, 32.2% were treated with ADT alone and 51.4% received ADT+RT. Compared with ADT alone, patients treated with ADT+RT were younger and more likely to have private insurance, lower comorbidity scores, higher Gleason scores, and lower PSA values. After PS matching, 318 patients remained in each group. Compared with ADT alone, ADT+RT was associated with a 50% decreased risk of five-year all-cause mortality (HR = 0.50, 95% CI: 0.37-0.67, two-sided P<0.001; crude OS rate: 71.5% vs. 53.2%). Using a large national database, we have identified a statistically significant survival benefit for patients with cN+PCa treated with ADT+RT. These data, if appropriately validated by randomized trials, suggest that a substantial proportion of such patients at high risk for prostate cancer death may be undertreated, warranting a reevaluation of current practice guidelines. Copyright © 2017. Published by Elsevier Inc.

Congenital cytomegalovirus, parvovirus and enterovirus infection in Mozambican newborns at birth: A cross-sectional survey.

PubMed

Madrid, Lola; Varo, Rosauro; Maculuve, Sonia; Nhampossa, Tacilta; Muñoz-Almagro, Carmen; Calderón, Enrique J; Esteva, Cristina; Carrilho, Carla; Ismail, Mamudo; Vieites, Begoña; Friaza, Vicente; Lozano-Dominguez, María Del Carmen; Menéndez, Clara; Bassat, Quique

2018-01-01

Congenital cytomegalovirus (cCMV) infection is the most prevalent congenital infection acquired worldwide, with higher incidence in developing countries and among HIV-exposed children. Less is known regarding vertical transmission of parvovirus B19 (B19V) and enterovirus (EV). We aimed to assess the prevalence of CMV, B19V and EV vertical transmission and compare results of screening of congenital CMV obtained from two different specimens in a semirural Mozambican maternity. A cross sectional study was conducted among pregnant mothers attending Manhiça District Hospital upon delivery. Information on maternal risk factors was ascertained. Dried umbilical cord (DUC) samples were collected in filter paper for CMV, B19V and EV detection by real-time polymerase chain reaction (RT-PCR), and nasopharyngeal aspirates (NPA) to test for CMV by RT-PCR. Maternal blood samples and placental biopsy samples were also obtained to investigate CMV maternal serology, HIV status and immunopathology. From September 2014 to January 2015, 118 mothers/newborn pairs were recruited. Prevalence of maternal HIV infection was 31.4% (37/118). CMV RT-PCR was positive in 3/115 (2.6%) of DUC samples and in 3/96 (6.3%) of NPA samples obtained from neonates. The concordance of the RT-PCR assay through DUC with their correspondent NPA sample was moderate (Kappa = 0.42 and p<0.001. No differences on cCMV prevalence were found among HIV-exposed and unexposed. All (100%) mothers were seropositive for CMV IgG. RT-PCR of EV and B19V in DUC were both negative in all screened cases. No histological specific findings were found in placental tissues. No risk factors associated to vertical transmission of these viral infections were found. This study indicates the significant occurrence of vertical transmission of CMV in southern Mozambique. Larger studies are needed to evaluate the true burden, clinical relevance and consequences of congenital infections with such pathogens in resource-constrained settings.

Congenital cytomegalovirus, parvovirus and enterovirus infection in Mozambican newborns at birth: A cross-sectional survey

PubMed Central

Varo, Rosauro; Maculuve, Sonia; Nhampossa, Tacilta; Muñoz-Almagro, Carmen; Calderón, Enrique J.; Esteva, Cristina; Carrilho, Carla; Ismail, Mamudo; Vieites, Begoña; Friaza, Vicente; Lozano-Dominguez, María del Carmen; Menéndez, Clara; Bassat, Quique

2018-01-01

Background Congenital cytomegalovirus (cCMV) infection is the most prevalent congenital infection acquired worldwide, with higher incidence in developing countries and among HIV-exposed children. Less is known regarding vertical transmission of parvovirus B19 (B19V) and enterovirus (EV). We aimed to assess the prevalence of CMV, B19V and EV vertical transmission and compare results of screening of congenital CMV obtained from two different specimens in a semirural Mozambican maternity. Methods A cross sectional study was conducted among pregnant mothers attending Manhiça District Hospital upon delivery. Information on maternal risk factors was ascertained. Dried umbilical cord (DUC) samples were collected in filter paper for CMV, B19V and EV detection by real-time polymerase chain reaction (RT-PCR), and nasopharyngeal aspirates (NPA) to test for CMV by RT-PCR. Maternal blood samples and placental biopsy samples were also obtained to investigate CMV maternal serology, HIV status and immunopathology. Results From September 2014 to January 2015, 118 mothers/newborn pairs were recruited. Prevalence of maternal HIV infection was 31.4% (37/118). CMV RT-PCR was positive in 3/115 (2.6%) of DUC samples and in 3/96 (6.3%) of NPA samples obtained from neonates. The concordance of the RT-PCR assay through DUC with their correspondent NPA sample was moderate (Kappa = 0.42 and p<0.001. No differences on cCMV prevalence were found among HIV-exposed and unexposed. All (100%) mothers were seropositive for CMV IgG. RT-PCR of EV and B19V in DUC were both negative in all screened cases. No histological specific findings were found in placental tissues. No risk factors associated to vertical transmission of these viral infections were found. Conclusions This study indicates the significant occurrence of vertical transmission of CMV in southern Mozambique. Larger studies are needed to evaluate the true burden, clinical relevance and consequences of congenital infections with such pathogens in resource-constrained settings. PMID:29538464

Incidence of second tumors after treatment with or without radiation for rectal cancer.

PubMed

Rombouts, A J M; Hugen, N; Elferink, M A G; Feuth, T; Poortmans, P M P; Nagtegaal, I D; de Wilt, J H W

2017-03-01

The aim of this study was to analyze the association between radiation therapy (RT) for rectal cancer and the development of second tumors. Data on all surgically treated non-metastatic primary rectal cancer patients diagnosed between 1989 and 2007 were retrieved from the Netherlands population-based cancer registry. Fine and Gray's competing risk model was used for estimation of the cumulative incidence of second tumors. Multivariable analysis was conducted using Cox regression. The cohort consisted of 29 027 patients of which 15 467 patients had undergone RT. Median follow-up was 7.7 years (range 0-27). Among all 4398 patients who were diagnosed with a second primary tumor, 1030 had one or more pelvic tumors. The standardized incidence risk for any second tumor was 1.16 (95% confidence interval [CI] 1.12-1.19), resulting in 27.7/10 000 excess cancer cases per year in patients treated for rectal cancer compared with the general population. RT reduced the cumulative incidence of second pelvic tumors compared with patients who did not receive RT (subhazard ratio [SHR] 0.77, CI 0.68-0.88). Second prostate tumors were less common in patients who received RT (SHR 0.54, CI 0.46-0.64), gynecological tumors were more frequently observed in patients who received RT (SHR 1.49, CI 1.11-2.00). Patients with previous rectal cancer had a marginally increased risk of a second tumor compared with the general population. Gynecological tumors occurred more often in females who received RT, but this did not result in an overall increased risk for a second cancer. RT even seemed to have a protective effect on the development of other second pelvic tumors, pre-dominantly for prostate cancer. These findings are highly important and can contribute to improved patient counseling. © The Author 2016. 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.

Multi-Institution Prospective Trial of Reduced-Dose Craniospinal Irradiation (23.4 Gy) Followed by Conformal Posterior Fossa (36 Gy) and Primary Site Irradiation (55.8 Gy) and Dose-Intensive Chemotherapy for Average-Risk Medulloblastoma

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

Merchant, Thomas E.; Kun, Larry E.; Krasin, Matthew J.

2008-03-01

Purpose: Limiting the neurocognitive sequelae of radiotherapy (RT) has been an objective in the treatment of medulloblastoma. Conformal RT to less than the entire posterior fossa (PF) after craniospinal irradiation might reduce neurocognitive sequelae and requires evaluation. Methods and Materials: Between October 1996 and August 2003, 86 patients, 3-21 years of age, with newly diagnosed, average-risk medulloblastoma were treated in a prospective, institutional review board-approved, multi-institution trial of risk-adapted RT and dose-intensive chemotherapy. RT began within 28 days of definitive surgery and consisted of craniospinal irradiation (23.4 Gy), conformal PF RT (36.0 Gy), and primary site RT (55.8 Gy). Themore » planning target volume for the primary site included the postoperative tumor bed surrounded by an anatomically confined margin of 2 cm that was then expanded with a geometric margin of 0.3-0.5 cm. Chemotherapy was initiated 6 weeks after RT and included four cycles of high-dose cyclophosphamide, cisplatin, and vincristine. Results: At a median follow-up of 61.2 months (range, 5.2-115.0 months), the estimated 5-year event-free survival and cumulative incidence of PF failure rate was 83.0% {+-} 5.3% and 4.9% {+-} 2.4% ({+-} standard error), respectively. The targeting guidelines used in this study resulted in a mean reduction of 13% in the volume of the PF receiving doses >55 Gy compared with conventionally planned RT. The reductions in the dose to the temporal lobes, cochleae, and hypothalamus were statistically significant. Conclusion: This prospective trial has demonstrated that irradiation of less than the entire PF after 23.4 Gy craniospinal irradiation for average-risk medulloblastoma results in disease control comparable to that after treatment of the entire PF.« less

Improved Biochemical Outcomes With Statin Use in Patients With High-Risk Localized Prostate Cancer Treated With Radiotherapy

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

Kollmeier, Marisa A.; Katz, Matthew S.; Mak, Kimberley

Purpose: To investigate the association between 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and biochemical and survival outcomes after high-dose radiotherapy (RT) for prostate cancer. Methods and Materials: A total of 1711 men with clinical stage T1-T3 prostate cancer were treated with conformal RT to a median dose of 81 Gy during 1995-2007. Preradiotherapy medication data were available for 1681 patients. Three hundred eighty-two patients (23%) were taking a statin medication at diagnosis and throughout RT. Nine hundred forty-seven patients received a short-course of neoadjuvant and concurrent androgen-deprivation therapy (ADT) with RT. The median follow-up was 5.9 years. Results: The 5-more » and 8-year PSA relapse-free survival (PRFS) rates for statin patients were 89% and 80%, compared with 83% and 74% for those not taking statins (p = 0.002). In a multivariate analysis, statin use (hazard ratio [HR]0.69, p = 0.03), National Comprehensive Cancer Network (NCCN) low-risk group, and ADT use were associated with improved PRFS. Only high-risk patients in the statin group demonstrated improvement in PRFS (HR 0.52, p = 0.02). Across all groups, statin use was not associated with improved distant metastasis-free survival (DMFS) (p = 0.51). On multivariate analysis, lower NCCN risk group (p = 0.01) and ADT use (p = 0.005) predicted improved DMFS. Conclusions: Statin use during high-dose RT for clinically localized prostate cancer was associated with a significant improvement in PRFS in high-risk patients. These data suggest that statins have anticancer activity and possibly provide radiosensitization when used in conjunction with RT in the treatment of prostate cancer.« less

Feasibility of radiotherapy after high-dose dense chemotherapy with epirubicin, preceded by dexrazoxane, and paclitaxel for patients with high-risk Stage II-III breast cancer

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

De Giorgi, Ugo; Giannini, Massimo; Department of Radiotherapy, Pierantoni Hospital, Forli

Purpose: To verify the feasibility of, and quantify the risk of, pneumonitis from locoregional radiotherapy (RT) after high-dose dense chemotherapy with epirubicin and paclitaxel with peripheral blood progenitor cell support in patients with high-risk Stage II-III breast cancer. Methods and Materials: Treatment consisted of a mobilizing course of epirubicin 150 mg/m{sup 2}, preceded by dexrazoxane (Day 1), paclitaxel 175 mg/m{sup 2} (Day 2), and filgrastim; followed by three courses of epirubicin 150 mg/m{sup 2}, preceded by dexrazoxane (Day 1), paclitaxel 400 mg/m{sup 2} (Day 2), and peripheral blood progenitor cell support and filgrastim, every 16-19 days. After chemotherapy, patients weremore » treated with locoregional RT, which included the whole breast or the chest wall, axilla, and supraclavicular area. Results: Overall, 64 of 69 patients were evaluable. The interval between the end of chemotherapy and the initiation of RT was at least 1.5-2 months (mean 2). No treatment-related death was reported. After a median follow-up of 27 months from RT (range 5-77 months), neither clinically relevant radiation pneumonitis nor congestive heart failure had been reported. Minor and transitory lung and cardiac toxicities were observed. Conclusion: Sequential high doses of epirubicin, preceded by dexrazoxane, and paclitaxel did not adversely affect the tolerability of locoregional RT in breast cancer patients. The risk of pneumonitis was not affected by the use of sequential paclitaxel with an interval of at least 1.5-2 months between the end of chemotherapy and the initiation of RT. Long-term follow-up is needed to define the risk of cardiotoxicity in these patients.« less

Assessment of the Rate of Adherence to International Guidelines for Androgen Deprivation Therapy with External-beam Radiation Therapy: A Population-based Study.

PubMed

Dell'Oglio, Paolo; Abou-Haidar, Hiba; Leyh-Bannurah, Sami-Ramzi; Tian, Zhe; Larcher, Alessandro; Gandaglia, Giorgio; Fossati, Nicola; Shariat, Shahrokh F; Capitanio, Umberto; Briganti, Alberto; Montorsi, Francesco; Graefen, Markus; Saad, Fred; Karakiewicz, Pierre I

2016-09-01

The National Comprehensive Cancer Network and the European Association of Urology guidelines recommend using radiation therapy (RT) with androgen deprivation therapy (ADT) to treat high-risk and locally advanced prostate cancer patients. To evaluate the degree of adherence to these guidelines. Between 2003 and 2009, in the Surveillance Epidemiology and End Results (SEER)-Medicare database, 14 180 patients were diagnosed with high-risk (T1-T2 with World Health Organization histologic grade 3) or locally advanced (T3-T4 with any histologic grade) prostatic adenocarcinoma. Administration of RT-ADT versus RT alone. We assessed the rate of adherence to guidelines with respect to use of RT-ADT in the overall population and after stratification according to stage-grade groupings (T1-T2 G3 vs T3-T4 any grade), age (66-69, 70-74, 75-79, ≥80 yr), Charlson Comorbidity Index (CCI) (0, 1, ≥2), and preexisting baseline cardiovascular (CV) disease. We depicted the rate of RT-ADT administration graphically over the study period. Multivariable logistic regression analyses were performed to assess the predictors of RT-ADT use. RT-ADT rates and guideline adherence were 58-75%, with the highest rate (75%) in 2003 and the lowest (58%) in 2009. When stratified according to stage-grade groupings, age, CCI, and preexisting baseline CV disease, similar results were obtained. In multivariable analyses, year of diagnosis (p<0.001), patient age (p<0.001), stage-grade groupings (p<0.001), CCI (p=0.036), race (p<0.001), marital status (p<0.001), population density (p<0.001), and US regions (p<0.001) were independent predictors of RT-ADT use. The limitations of our study include age >65 yr and exclusive Medicare coverage. The rate of guideline adherence regarding the use of RT-ADT is suboptimal and decreases with time instead of increasing. This population-based study provides evidence of low adherence to international urologic guidelines regarding the combination of radiation therapy (RT) with androgen deprivation therapy (ADT) for high-risk and locally advanced prostate cancer (PCa) patients. Despite the increasing number of randomized controlled trials over time that showed a survival benefit for patients with high-risk and locally advanced PCa treated with RT-ADT compared with RT alone, the rate of adherence to guidelines decreased with time. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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

Application of Reverse Transcriptase -PCR (RT-PCR) for rapid detection of viable Escherichia coli in drinking water samples.

PubMed

Molaee, Neda; Abtahi, Hamid; Ghannadzadeh, Mohammad Javad; Karimi, Masoude; Ghaznavi-Rad, Ehsanollah

2015-01-01

Polymerase chain reaction (PCR) is preferred to other methods for detecting Escherichia coli (E. coli) in water in terms of speed, accuracy and efficiency. False positive result is considered as the major disadvantages of PCR. For this reason, reverse transcriptase-polymerase chain reaction (RT-PCR) can be used to solve this problem. The aim of present study was to determine the efficiency of RT-PCR for rapid detection of viable Escherichia coli in drinking water samples and enhance its sensitivity through application of different filter membranes. Specific primers were designed for 16S rRNA and elongation Factor II genes. Different concentrations of bacteria were passed through FHLP and HAWP filters. Then, RT-PCR was performed using 16srRNA and EF -Tu primers. Contamination of 10 wells was determined by RT-PCR in Arak city. To evaluate RT-PCR efficiency, the results were compared with most probable number (MPN) method. RT-PCR is able to detect bacteria in different concentrations. Application of EF II primers reduced false positive results compared to 16S rRNA primers. The FHLP hydrophobic filters have higher ability to absorb bacteria compared with HAWB hydrophilic filters. So the use of hydrophobic filters will increase the sensitivity of RT-PCR. RT-PCR shows a higher sensitivity compared to conventional water contamination detection method. Unlike PCR, RT-PCR does not lead to false positive results. The use of EF-Tu primers can reduce the incidence of false positive results. Furthermore, hydrophobic filters have a higher ability to absorb bacteria compared to hydrophilic filters.

Cerebrovascular Diseases in Childhood Cancer Survivors: Role of the Radiation Dose to Willis Circle Arteries

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

El-Fayech, Chiraz; Haddy, Nadia; Allodji, Rodrigue Sètchéou

Background and Purpose: The aim of this study was to investigate the role of radiation dose received to the circle of Willis (WC) during radiation therapy (RT) and of potential dose-response modifiers on the risk of stroke after treatment of childhood cancer. Methods: We evaluated the risk factors for stroke in a cohort of 3172 5-year survivors of childhood cancer who were followed up for a median time of 26 years. Radiation doses to the WC and brain structures were estimated for each of the 2202 children who received RT. Results: Fifty-four patients experienced a confirmed stroke; 39 were ischemic. Patientsmore » not receiving RT had a stroke risk similar to that of the general population, whereas those who received RT had an 8.5-fold increased risk (95% confidence interval [CI]: 6.3-11.0). The excess of incidence of stroke increased yearly. The dose of radiation to the WC, rather than to other brain structures, was found to be the best predictor of stroke. The relative risk was 15.7 (95% CI: 4.9-50.2) for doses of 40 Gy or more. At 45 years of age, the cumulative stroke incidence was 11.3% (95% CI: 7.1%-17.7%) in patients who received 10 Gy or more to the WC, compared with 1% expected from general population data. Radiation doses received to the heart and neck also increased the risk. Surgery for childhood brain cancer was linked to hemorrhagic strokes in these patients. Conclusion: The WC should be considered as a major organ at risk during RT for childhood brain cancers. The incidence of radiation-induced ischemic stroke strongly increases with long-term follow-up.« less

Creating Meaning from Collaboration to Implement RtI for At-Risk Students

ERIC Educational Resources Information Center

Diakakis, Julia Ann

2014-01-01

The purpose of this qualitative exploratory case study based on Danielson's (2002) assertion that when teachers learn, student achievement improves was to examine how teachers created a collaborative learning experience through Professional Learning Community (PLC) concepts to implement Response to Intervention (RtI) with at-risk students. The…

Disease Severity and Exercise Testing Reduce Subcutaneous Implantable Cardioverter-Defibrillator Left Sternal ECG Screening Success in Hypertrophic Cardiomyopathy.

PubMed

Srinivasan, Neil T; Patel, Kiran H; Qamar, Kashif; Taylor, Amy; Bacà, Marco; Providência, Rui; Tome-Esteban, Maria; Elliott, Perry M; Lambiase, Pier D

2017-04-01

The features of the hypertrophic cardiomyopathy (HCM) ECG make it a challenge for subcutaneous implantable cardioverter-defibrillator (S-ICD) screening. We aimed to investigate the causes of screening failure at rest and on exercise to inform optimal S-ICD ECG vector development. One hundred and thirty-one HCM patients (age, 50±16 years; 92 males and 39 females) with ≥1 HCM risk factor for sudden death underwent S-ICD ECG screening at rest and on exercise. Fifty patients (38%) were ineligible for S-ICD because of screening failure in every lead vector: 33 (66%) failed in the supine position, 12 (24%) failed in the standing position, and 5 (10%) failed on exercise. In patients who could exercise and passed screening at rest, 31 (44%) had 1 vector safety, 16 (23%) had 2 vector safety, and 24 (33%) had 3 vector safety. Increased R:T wave ratio in the S-ICD screening ECG (odds ratio, 4.0; confidence interval, 3.0-5.3; P <0.001) was associated with screening failure, while R/T ratio <3 in aVF (odds ratio, 0.3; confidence interval, 0.12-0.69; P =0.006) and increasing age (odds ratio, 0.97; confidence interval, 0.95-0.99; P =0.03) was associated with reduced screening failure. European Society of Cardiology risk score was higher in those failing screening (risk score 5.5% [interquartile range, 3.2-8.7] in failed versus 4.5% [interquartile range, 2.9-7.4] in passed; P =0.04). HCM patients have a significant incidence of screening failure, which is determined primarily by the increased R:T ratio on the screening ECG and lead aVF. High-risk patients have an increased screening failure rate. Optimization of sensing algorithms is required to ensure that the highest risk HCM patients can benefit from S-ICD implantation. © 2017 American Heart Association, Inc.

Chemotherapy Toxicity Risk Score for Treatment Decisions in Older Adults with Advanced Solid Tumors.

PubMed

Nishijima, Tomohiro F; Deal, Allison M; Williams, Grant R; Sanoff, Hanna K; Nyrop, Kirsten A; Muss, Hyman B

2018-05-01

The decision whether to treat older adults with advanced cancer with standard therapy (ST) or reduced therapy (RT) is complicated by heterogeneity in aging. We assessed the potential utility of the chemotherapy toxicity risk score (CTRS) [J Clin Oncol 2011;29:3457-3465] for treatment decisions in older adults. This was a prospective observational study of patients aged ≥65 years receiving first-line chemotherapy for advanced cancer for which combination chemotherapy is the standard of care. Patients were categorized as high risk (CTRS ≥10), for whom RT (dose-reduced combination or single-agent chemotherapy) is deemed appropriate, or nonhigh risk (CTRS <10), for whom ST is deemed appropriate for toxicity. The primary objective was to estimate the agreement in chemotherapy choice (ST vs. RT) between the treating physician and the CTRS using a κ statistic. Fifty-eight patients (median age, 71 years) were enrolled. Thirty-eight patients received ST (21 had CTRS <10, and 17 had CTRS ≥10), and 20 patients received RT (12 had CTRS ≥10, and 8 had CTRS <10), with minimal agreement in chemotherapy choice (κ = 0.14; 95% CI, -0.10 to 0.38). Grade 3-4 toxicity and hospitalization occurred in 60% and 27% of 55 patients with follow-up data, respectively. Among patients receiving ST, patients with CTRS ≥10 had a higher incidence of toxicity (88% vs. 40%, p  = .006) and hospitalization (50% vs. 15%, p  = .03) than those with CTRS <10. Older patients with cancer with a high CTRS who receive combination chemotherapy have an exceedingly high rate of severe toxicity and hospitalization. The potential utility of the chemotherapy toxicity risk score (CTRS) in old adults with advanced solid tumors receiving first-line chemotherapy was assessed. Little agreement was found between chemotherapy treatment decisions based on the clinical impression versus what was recommended based on the CTRS. Among patients treated with standard-dose combination chemotherapy, patients with CTRS ≥10 had a very high incidence of grade 3-4 toxicities and hospitalization, which was significantly greater than that of patients with a low CTRS (<10). These findings suggest that the addition of CTRS to the clinical impression has a potential to improve treatment decisions. © AlphaMed Press 2018.

Does Bleomycin Lung Toxicity Increase the Risk of Radiation Pneumonitis in Hodgkin Lymphoma?

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

Abou Yehia, Zeinab; Mikhaeel, George N.; Smith, Grace

Purpose: Bleomycin pulmonary toxicity (BPT) is a well-known complication of treatment in patients with Hodgkin lymphoma (HL). We undertook the present study to investigate the risk of radiation pneumonitis (RP) in the setting of BPT and to determine the need for delay or omission of radiation therapy (RT) in these patients. Methods and Materials: We identified 123 HL patients treated with ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) followed by RT to the chest from January 2009 to December 2014. The medical records were reviewed for clinical, pathologic, and treatment information and toxicities. Our primary outcome was RP of any grade. Univariatemore » and multivariate analyses were used to assess the association of BPT, baseline patient characteristics, and treatment variables with the incidence of RP. Results: A total of 123 patients were included, of whom 99 (80%) received consolidation intensity modulated RT after ABVD treatment. We identified 31 patients (25.2%) with BPT after frontline ABVD. Seventeen patients (13.8%) developed RP a median of 8 weeks (range 1-39) after RT completion. BPT did not correlate with the risk of developing RP (P=.36). We evaluated the RP outcomes with respect to the bleomycin to RT interval (≤6 weeks vs >6 weeks), and we found that this interval did not predict for RP risk (P=.60). Dosimetric parameters such as the volume covered by 5 Gy and the mean lung dose were analyzed. A volume covered by 5 Gy of >55% and mean lung dose >13.5 Gy increased the risk of RP by 1.14-fold (P=.002) and 4.24-fold (P=.007), respectively. Conclusions: The results of our study suggest that BPT does not increase the risk of developing RP. Furthermore, RT initiation does not need to be delayed after chemotherapy, except to allow for the completion of steroid therapy or clinical recovery from BPT.« less

Evaluating the Impacts of NASA/SPoRT Daily Greenness Vegetation Fraction on Land Surface Model and Numerical Weather Forecasts

NASA Technical Reports Server (NTRS)

Bell, Jordan R.; Case, Jonathan L.; LaFontaine, Frank J.; Kumar, Sujay V.

2012-01-01

The NASA Short-term Prediction Research and Transition (SPoRT) Center has developed a Greenness Vegetation Fraction (GVF) dataset, which is updated daily using swaths of Normalized Difference Vegetation Index data from the Moderate Resolution Imaging Spectroradiometer (MODIS) data aboard the NASA EOS Aqua and Terra satellites. NASA SPoRT began generating daily real-time GVF composites at 1-km resolution over the Continental United States (CONUS) on 1 June 2010. The purpose of this study is to compare the National Centers for Environmental Prediction (NCEP) climatology GVF product (currently used in operational weather models) to the SPoRT-MODIS GVF during June to October 2010. The NASA Land Information System (LIS) was employed to study the impacts of the SPoRT-MODIS GVF dataset on a land surface model (LSM) apart from a full numerical weather prediction (NWP) model. For the 2010 warm season, the SPoRT GVF in the western portion of the CONUS was generally higher than the NCEP climatology. The eastern CONUS GVF had variations both above and below the climatology during the period of study. These variations in GVF led to direct impacts on the rates of heating and evaporation from the land surface. In the West, higher latent heat fluxes prevailed, which enhanced the rates of evapotranspiration and soil moisture depletion in the LSM. By late Summer and Autumn, both the average sensible and latent heat fluxes increased in the West as a result of the more rapid soil drying and higher coverage of GVF. The impacts of the SPoRT GVF dataset on NWP was also examined for a single severe weather case study using the Weather Research and Forecasting (WRF) model. Two separate coupled LIS/WRF model simulations were made for the 17 July 2010 severe weather event in the Upper Midwest using the NCEP and SPoRT GVFs, with all other model parameters remaining the same. Based on the sensitivity results, regions with higher GVF in the SPoRT model runs had higher evapotranspiration and lower direct surface heating, which typically resulted in lower (higher) predicted 2-m temperatures (2-m dewpoint temperatures). Portions of the Northern Plains states experienced substantial increases in convective available potential energy as a result of the higher SPoRT/MODIS GVFs. These differences produced subtle yet quantifiable differences in the simulated convective precipitation systems for this event.

Tailoring the field and indication of adjuvant pelvic radiation for patients with FIGO stage Ib lymph nodes-negative cervical carcinoma following radical surgery based on the GOG score--a pilot study.

PubMed

Rushdan, M N; Tay, E H; Khoo-Tan, H S; Lee, K M; Low, J H; Ho, T H; Yam, K L

2004-07-01

The traditional indications for adjuvant pelvic radiotherapy (RT) for International Federation of Obstetrics and Gynecology (FIGO) stage Ib1 lymph nodes-negative cervix carcinoma following radical surgery based on histopathological factors, such as deep stromal invasion and lymphovascular space invasion (LVSI), were often inconsistently applied. The perceived risk of relapse was subjectively determined. This pilot study attempts to determine if the treatment outcome will be affected when the indication for RT is based on the Gynecologic Oncology Group (GOG) Risk Score (RS) and the field of adjuvant RT is tailored to the RS. From 1997 to 1999, 55 patients with FIGO stage Ib1 lymph nodes-negative cervical carcinoma limited to the cervix were prescribed RT following radical surgery, based on their RS, as follows: RS <40, RT is omitted; RS >40 to <120, modified (smaller) field RT; and RS >120, standard field pelvic RT. Their incidence and site of recurrence were compared with a similar cohort of 40 patients who were treated prior to 1997. Prior to 1997, of the 40 patients, 10 patients were given standard field RT. There were 2 (5%) recurrent diseases. The mean duration of follow-up was 61.6 months (range, 1 to 103 months). The RS of 23 of the 30 patients who were not given RT were available. The mean RS was 22 with 5 patients having a score of >40. From 1997 onwards, of the 55 patients, 28 (51%) did not require RT, 13 (23%) were treated with modified (smaller) field RT and 14 (26%) were given standard field RT. There were 2 (3.6%) cases of relapse. The mean duration of follow-up was 36.4 months (range, 5 to 60 months). All patients with a RS of <40 did not suffer any relapse. Their survival outcomes were better when compared to patients who did not have any RT in the GOG Study. The results of this study indicated that postoperative adjuvant RT given to patients with a high GOG RS of >120, significantly improved their 5-year recurrence rate and disease-free survival, as compared with the similar group of patients who were without adjuvant therapy in the GOG study. Patients with a GOG risk-score of <40 may be safely spared from adjuvant pelvic RT. The current treatment protocol did not compromise the outcome in patients, compared with the use of a less precise treatment protocol in the past.

Clinical and Dosimetric Predictors of Acute Severe Lymphopenia During Radiation Therapy and Concurrent Temozolomide for High-Grade Glioma

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

Huang, Jiayi, E-mail: jhuang@radonc.wustl.edu; DeWees, Todd A.; Badiyan, Shahed N.

Purpose: Acute severe lymphopenia (ASL) frequently develops during radiation therapy (RT) and concurrent temozolomide (TMZ) for high-grade glioma (HGG) and is associated with decreased survival. The current study was designed to identify potential predictors of ASL, with a focus on actionable RT-specific dosimetric parameters. Methods and Materials: From January 2007 to December 2012, 183 patients with HGG were treated with RT+TMZ and had available data including total lymphocyte count (TLC) and radiation dose-volume histogram parameters. ASL was defined as TLC of <500/μL within the first 3 months from the start of RT. Stepwise logistic regression analysis was used to determine themore » most important predictors of ASL. Results: Fifty-three patients (29%) developed ASL. Patients with ASL had significantly worse overall survival than those without (median: 12.5 vs 20.2 months, respectively, P<.001). Stepwise logistic regression analysis identified female sex (odds ratio [OR]: 5.30; 95% confidence interval [CI]: 2.46-11.41), older age (OR: 1.05; 95% CI: 1.02-1.09), lower baseline TLC (OR: 0.92; 95% CI: 0.87-0.98), and higher brain volume receiving 25 Gy (V{sub 25Gy}) (OR: 1.03; 95% CI: 1.003-1.05) as the most significant predictors for ASL. Brain V{sub 25Gy} <56% appeared to be the optimal threshold (OR: 2.36; 95% CI: 1.11-5.01), with an ASL rate of 38% versus 20% above and below this threshold, respectively (P=.006). Conclusions: Female sex, older age, lower baseline TLC, and higher brain V{sub 25Gy} are significant predictors of ASL during RT+TMZ therapy for HGG. Maintaining the V{sub 25Gy} of brain below 56% may reduce the risk of ASL.« less

Comparison of aerobic versus resistance exercise training effects on metabolic syndrome (from the Studies of a Targeted Risk Reduction Intervention Through Defined Exercise - STRRIDE-AT/RT).

PubMed

Bateman, Lori A; Slentz, Cris A; Willis, Leslie H; Shields, A Tamlyn; Piner, Lucy W; Bales, Connie W; Houmard, Joseph A; Kraus, William E

2011-09-15

Aerobic training (AT) improves the metabolic syndrome (MS) and its component risk factors; however, to our knowledge, no randomized clinical studies have addressed whether resistance training (RT) improves the MS when performed alone or combined with AT. Sedentary, overweight dyslipidemic men and women, aged 18 to 70 years completed a 4-month inactive run-in period and were randomized to 1 of 3 eight-month exercise programs (n = 196). The exercise programs were (1) RT (3 days/week, 3 sets/day of 8 to 12 repetitions of 8 different exercises targeting all major muscle groups); (2) AT (∼120 minutes/week at 75% of the maximum oxygen uptake), and (3) AT and RT combined (AT/RT) (exact combination of AT and RT). Of the 196 randomized patients, 144 completed 1 of the 3 exercise programs. The 86 participants with complete data for all 5 MS criteria were used in the present analysis, and a continuous MS z score was calculated. Eight months of RT did not change the MS score. AT improved the MS score (p <0.07) and showed a trend toward significance compared to RT (p <0.10). AT/RT significantly decreased the MS score and was significantly different from RT alone. In conclusion, RT was not effective at improving the MS score; however, AT was effective. Combined AT and RT was similarly effective but not different from AT alone. When weighing the time commitment versus health benefit, the data suggest that AT alone was the most efficient mode of exercise for improving cardiometabolic health. Published by Elsevier Inc.

Coproscopy and molecular screening for detection of intestinal protozoa.

PubMed

Abu-Madi, Marawan; Boughattas, Sonia; Behnke, Jerzy M; Sharma, Aarti; Ismail, Ahmed

2017-09-06

Intestinal parasitosis is one of several health concerns about immigrants who travel from endemic to non-endemic regions. Reliable rapid sensitive diagnostic tools, for use in non-endemic regions, are urgently required to enable frequent assessment of immigrant workers in jobs where risk of local transmission is a particular concern (e.g. food-handlers). We assessed the burden of intestinal protozoa in newly arrived immigrants and those applying for renewal of work permits in Qatar (n = 735), by both microscopic examination of stool samples and by Real Time PCR methodology. Prevalence was considerably higher using RT-PCR compared with coproscopy (Blastocystis hominis: 65.2 vs 7.6%; Giardia duodenalis: 14.3 vs 2.9%; Entamoeba histolytica: 1.6 vs 1.2%). Dientamoeba fragilis was sought only by RT-PCR (prevalence of 25.4%). Prevalence of G. duodenalis was significantly higher in male subjects, associated with blue collar workers and declined over time. Prevalence of B. hominis varied significantly with region of origin of subjects with highest values recorded among African immigrants. Prevalence of D. fragilis also varied with region of origin of subjects, and was lower in young female subjects and in renewal applicants compared with first-time applicants for work permits. We strongly recommend that, henceforth, intestinal protozoa should be screened by RT-PCR, with a particular focus on frequent assessment of immigrant food-handlers.

Effect of Neoadjuvant Radiation Dose on Surgical and Oncological Outcome in Locally Advanced Esophageal Cancer.

PubMed

Van Daele, E; Ceelen, W; Boterberg, T; Varinl, O; Van Nieuwenhove, Y; Putte, D Van de; Geboes, K; Pattyn, P

2015-01-01

Neoadjuvant chemoradiation (CRT) confers a survival benefit in locally advanced esophageal cancer. The optimal dose of radiotherapy remains undefined. From a prospective database, we identified patients who received CRT followed by Ivor Lewis esophagectomy. Surgical complications, pathological response, and oncological outcome were compared between patients who received a radiotherapy (RT) dose of 36 Gy (group1) versus a dose of > 40 Gy (group 1). 147 patients were evaluated: 109 received 36 Gy, while 38 received 41-50Gy. Mean age was 61 ± 9 years (84% male). Median hospital stay was 16 days. Anastomotic leakage occurred in 4.0%. Pulmonary complications occurred in 41.8%, neither being influenced by RT dose. Complete resection (R0) was achieved in 95% (group 1) and 100% (group 2), P = 0.3. Pathological complete response (pCR) was observed in 19% (group 1) and 37% (group 1), P = 0.04. Local recurrence developed in 9% in group 1, and 3% in group 2 (P = 0.3), but regional recurrence developed significantly higher in the low dose group (18% vs 3%, P < 0.001). Metastatic recurrence occurred in 48% in group 1 and 13% in group 1 (P < 0.001). In patients with locally advanced esophageal cancer a higher RT dose does not affect surgical outcome, enhances pCR rate, and reduces the locoregional and metastatic recurrence risk.

Analysis of in-field control and late toxicity for adults with early-stage Hodgkin's disease treated with chemotherapy followed by radiotherapy.

PubMed

Chronowski, Gregory M; Wilder, Richard B; Tucker, Susan L; Ha, Chul S; Younes, Anas; Fayad, Luis; Rodriguez, Maria A; Hagemeister, Fredrick B; Barista, Ibrahim; Cabanillas, Fernando; Cox, James D

2003-01-01

We analyzed in-field (IF) control in adults with early-stage Hodgkin's disease who received chemotherapy followed by radiotherapy (RT) in terms of the (1) chemotherapeutic regimen used and number of cycles delivered, (2) response to chemotherapy, and (3) initial tumor size. Cardiac toxicity and second malignancies, particularly the incidence of solid tumors in terms of the RT field size treated, were also examined. From 1980 to 1995, 286 patients ranging in age from 16 to 88 years (median: 28 years) with Ann Arbor clinical Stage I or II Hodgkin's disease underwent chemotherapy followed 3 to 4 weeks later by RT. There were 516 nodal sites measuring 0.5 to 19.0 cm at the start of chemotherapy, including 134 cases of bulky mediastinal disease. NOVP, MOPP, ABVD, CVPP/ABDIC, and other chemotherapeutic regimens were given to 161, 67, 19, 18, and 21 patients, respectively. Patients received 1-8 (median: 3) cycles of induction chemotherapy. All 533 gross nodal and extranodal sites of disease were included in the RT fields. The median prescribed RT dose for gross disease was 40.0 Gy given in 20 daily 2.0-Gy fractions. There was little variation in the RT dose. Eighty-five patients were treated with involved-field or regional RT (to one side of the diaphragm), and 201 patients were treated with extended-field RT (to both sides of the diaphragm), based on the protocol on which they were enrolled. Follow-up of surviving patients ranged from 1.3 to 19.9 years (median: 7.4 years). Based on a review of simulation films, there were 16 IF, 8 marginal, and 15 out-of-field recurrences. The chemotherapeutic regimen used and the number of cycles of chemotherapy delivered did not significantly affect IF control. IF control also did not significantly depend on the response to induction chemotherapy. In cases where there was a confirmed or unconfirmed complete response as opposed to a partial response or stable disease in response to induction chemotherapy for bulky nodal disease, the 5-year IF control rates were 99% and 92%, respectively (p = 0.0006). The 15-year actuarial risks of coronary artery disease requiring surgical intervention and of solid tumors were 4.1% and 16.8%, respectively. There was a trend toward a greater risk of solid tumors in patients who received extended-field RT rather than involved-field or regional RT (p = 0.08). In patients with nonbulky disease, induction chemotherapy followed by RT to a median dose of 40.0 Gy resulted in excellent IF control, regardless of the chemotherapeutic regimen used, the fact that only 1-2 cycles of chemotherapy were delivered, and the response to chemotherapy. There was a trend toward a higher incidence of solid tumors in patients who received consolidation RT to both sides rather than only one side of the diaphragm. Ongoing Phase III trials will help clarify whether lower RT doses and smaller RT fields after chemotherapy can maintain the IF control seen in our study, but with a lower incidence of late complications in patients with Stage I or II Hodgkin's disease.

Hypothyroidism as a Consequence of Intensity-Modulated Radiotherapy With Concurrent Taxane-Based Chemotherapy for Locally Advanced Head-and-Neck Cancer

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

Diaz, Roberto; Jaboin, Jerry J.; Morales-Paliza, Manuel

Purpose: To conduct a retrospective review of 168 consecutively treated locally advanced head-and-neck cancer (LAHNC) patients treated with intensity-modulated radiotherapy (IMRT)/chemotherapy, to determine the rate and risk factors for developing hypothyroidism. Methods and Materials: Intensity-modulated radiotherapy was delivered in 33 daily fractions to 69.3 Gy to gross disease and 56.1 Gy to clinically normal cervical nodes. Dose-volume histograms (DVHs) of IMRT plans were used to determine radiation dose to thyroid and were compared with DVHs using conventional three-dimensional radiotherapy (3D-RT) in 10 of these same patients randomly selected for replanning and with DVHs of 16 patients in whom the thyroidmore » was intentionally avoided during IMRT. Weekly paclitaxel (30 mg/m{sup 2}) and carboplatin area under the curve-1 were given concurrently with IMRT. Results: Sixty-one of 128 evaluable patients (47.7%) developed hypothyroidism after a median of 1.08 years after IMRT (range, 2.4 months to 3.9 years). Age and volume of irradiated thyroid were associated with hypothyroidism development after IMRT. Compared with 3D-RT, IMRT with no thyroid dose constraints resulted in significantly higher minimum, maximum, and median dose (p < 0.0001) and percentage thyroid volume receiving 10, 20, and 60 Gy (p < 0.05). Compared with 3D-RT, IMRT with thyroid dose constraints resulted in lower median dose and percentage thyroid volume receiving 30, 40, and 50 Gy (p < 0.005) but higher minimum and maximum dose (p < 0.005). Conclusions: If not protected, IMRT for LAHNC can result in higher radiation to the thyroid than with conventional 3D-RT. Techniques to reduce dose and volume of radiation to thyroid tissue with IMRT are achievable and recommended.« less

Human papillomavirus detection using the Abbott RealTime high-risk HPV tests compared with conventional nested PCR coupled to high-throughput sequencing of amplification products in cervical smear specimens from a Gabonese female population.

PubMed

Moussavou-Boundzanga, Pamela; Koumakpayi, Ismaël Hervé; Labouba, Ingrid; Leroy, Eric M; Belembaogo, Ernest; Berthet, Nicolas

2017-12-21

Cervical cancer is the fourth most common malignancy in women worldwide. However, screening with human papillomavirus (HPV) molecular tests holds promise for reducing cervical cancer incidence and mortality in low- and middle-income countries. The performance of the Abbott RealTime High-Risk HPV test (AbRT) was evaluated in 83 cervical smear specimens and compared with a conventional nested PCR coupled to high-throughput sequencing (HTS) to identify the amplicons. The AbRT assay detected at least one HPV genotype in 44.57% of women regardless of the grade of cervical abnormalities. Except for one case, good concordance was observed for the genotypes detected with the AbRT assay in the high-risk HPV category determined with HTS of the amplicon generated by conventional nested PCR. The AbRT test is an easy and reliable molecular tool and was as sensitive as conventional nested PCR in cervical smear specimens for detection HPVs associated with high-grade lesions. Moreover, sequencing amplicons using an HTS approach effectively identified the genotype of the hrHPV identified with the AbRT test.

Outcome of Radiation Monotherapy for High-risk Patients with Stage I Esophageal Cancer.

PubMed

Shirakawa, Yasuhiro; Noma, Kazuhiro; Maeda, Naoaki; Tanabe, Shunsuke; Kuroda, Shinji; Kagawa, Shunsuke; Katsui, Kuniaki; Katayama, Norihisa; Kanazawa, Susumu; Fujiwara, Toshiyoshi

2017-04-01

Currently, chemoradiation is the most widely used nonsurgical treatment for esophageal cancer. However, some patients, particularly the very elderly or those with severe vital organ dysfunction, face difficulty with the chemotherapy component. We therefore examined the outcome of radiation therapy (RT) alone for patients with esophageal cancer at our facility. Between January 2005 and December 2014, 84 patients underwent RT at our hospital, and 78 of these patients received concomitant chemotherapy. The remaining 6 patients underwent RT alone; these patients were considered to be high-risk and to have no lymph node metastasis (stage I). Five of them received irradiation up to a curative dose: 4 showed a complete response (CR) and 1 showed a partial response (PR). Of the patients exhibiting CR, 3 are currently living recurrence-free, whereas 1 patient underwent endoscopic submucosal dissection (ESD) as salvage therapy for local recurrence, with no subsequent recurrence. High-risk stage I esophageal cancer patients can be treated radically with RT alone under certain conditions. In the future, to broaden the indications for RT monotherapy to include some degree of advanced cancers, a novel concurrent therapy should be identified.

Factors associated with the rectal temperature of Holstein dairy cows during the first 10 days in milk.

PubMed

Wenz, J R; Moore, D A; Kasimanickam, R

2011-04-01

Daily evaluation of rectal temperature (RT) during the first 10 d in milk (DIM) is used to facilitate the early identification of postpartum complications, particularly metritis in dairy cows. The factors associated with RT of postpartum dairy cows have not been clearly established and the RT threshold used to define fever has been variable. The objectives were to identify factors associated with the RT of postpartum dairy cows and provide descriptive statistics of the RT during the first 10 DIM to clarify the normal range of RT for cows. Daily RT was evaluated from 1 to 10 DIM for all cows calving during 2 consecutive summers on a single 1,500-cow Holstein dairy. Cows were placed into metabolic/digestive (METB), infectious (INF), and no recorded disease (NONE) groups based on disease diagnoses during the first 10 DIM. Cows were grouped based on calving difficulty and parity. Multiple linear regression models with repeated measures were used to evaluate the factors associated with RT. Three hundred and ninety-two cows were evaluated, of which 45% were primiparous and 32% required assistance at calving. No difference was observed in calving assistance by parity. First disease diagnoses peaked in the INF and METB groups at 3 and 1 DIM, respectively. The RT of primiparous cows was 0.1 to 0.2°C higher than that of multiparous cows from 1 to 8 DIM, accounting for calving difficulty, twin births, month of calving, and disease group in the model. The INF group cows had a higher RT than did NONE group cows (38.9±0.04 to 39.2±0.73 vs. 38.7±0.03°C, respectively) on each of the first 10 DIM, which was approximately 0.6°C higher from 3 to 5 DIM. The RT of cows with metritis was at least 0.1°C higher (38.8±0.05°C) than that of NONE group cows beginning 4 d before diagnosis. The mean RT of primiparous, defined healthy (NONE group) cows was 38.8±0.02°C, with an upper normal limit (mean+2 SD) of 39.6°C. The mean RT of multiparous cows in the NONE group during the first 10 DIM was 38.7±0.01°C, with an upper normal limit of 39.5°C. The RT of dairy cattle during the first 10 DIM was associated with parity, month of calving, and an infectious disease diagnosis, particularly the diagnosis of metritis. The normal RT of dairy cattle in the immediate postpartum period, during the warm summer months, is potentially higher than that generally reported. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Use of tomotherapy in treatment of synchronous bilateral breast cancer: dosimetric comparison study

PubMed Central

Wadasadawala, T; Sarin, R; Upreti, R R; Paul, S; Phurailatpam, R

2015-01-01

Objective: Synchronous malignancy in both breasts is a rare incidence. The present study aims at dosimetric comparison of conventional bitangential radiotherapy (RT) technique with conventional [field-in-field (FIF)] and rotational [Helical TomoTherapy® and TomoDirect™ (TD); Accuray Inc., Sunnyvale, CA] intensity-modulated RT for patients with synchronous bilateral breast cancer (SBBC). Methods: CT data sets of 10 patients with SBBC were selected for the present study. RT was planned for all patients on both sides to whole breast and/or chest wall using the above-mentioned techniques. Six females with breast conservation on at least one side also had a composite plan along with tumour bed (TB) boost using sequential electrons for bitangential and FIF techniques or sequential helical tomotherapy (HT) boost (for TD) or simultaneous integrated boost (SIB) for HT. Results: All techniques produced acceptable target coverage. The hotspot was significantly lower with FIF technique and HT but higher with TD. For the organs at risk doses, HT resulted in significant reduction of the higher dose volumes. Similarly, TD resulted in significant reduction of the mean dose to the heart and total lung by reducing the lower dose volumes. All techniques of delivering boost to the TB were comparable in terms of target coverage. HT-SIB markedly reduced mean doses to the total lung and heart by specifically lowering the higher dose volumes. Conclusion: This study demonstrates the cardiac and pulmonary sparing ability of tomotherapy in the setting of SBBC. Advances in knowledge: This is the first study demonstrating feasibility of treatment of SBBC using tomotherapy. PMID:25605345

Shoulder injuries attributed to resistance training: a brief review.

PubMed

Kolber, Morey J; Beekhuizen, Kristina S; Cheng, Ming-Shun S; Hellman, Madeleine A

2010-06-01

The popularity of resistance training (RT) is evident by the more than 45 million Americans who engage in strength training regularly. Although the health and fitness benefits ascribed to RT are generally agreed upon, participation is not without risk. Acute and chronic injuries attributed to RT have been cited in the epidemiological literature among both competitive and recreational participants. The shoulder complex in particular has been alluded to as one of the most prevalent regions of injury. The purpose of this manuscript is to present an overview of documented shoulder injuries among the RT population and where possible discern mechanisms of injury and risk factors. A literature search was conducted in the PUBMED, CINAHL, SPORTDiscus, and OVID databases to identify relevant articles for inclusion using combinations of key words: resistance training, shoulder, bodybuilding, weightlifting, shoulder injury, and shoulder disorder. The results of the review indicated that up to 36% of documented RT-related injuries and disorders occur at the shoulder complex. Trends that increased the likelihood of injury were identified and inclusive of intrinsic risk factors such as joint and muscle imbalances and extrinsic risk factors, namely, that of improper attention to exercise technique. A majority of the available research was retrospective in nature, consisting of surveys and descriptive epidemiological reports. A paucity of research was available to identify predictive variables leading to injury, suggesting the need for future prospective-based investigations.

Perspectives on Culturally and Linguistically Responsive RtI Pedagogics through a Cultural and Linguistic Lens

ERIC Educational Resources Information Center

Montalvo, Ricardo; Combes, Bertina H.; Kea, Cathy D.

2014-01-01

Response to intervention (RtI) originates from national legislation and critical research of evidence-based practices for low performing students and students at-risk of failing or receiving special education services. RtI proactively facilitates culturally and linguistically responsive pedagogy for culturally and linguistically diverse (CLD)…

Need for Resourcefulness Training for Women Caregivers of Elders with Dementia.

PubMed

Zauszniewski, Jaclene A; Lekhak, Nirmala; Yolpant, Wichiya; Morris, Diana L

2015-01-01

Nearly ten million American women are caregivers of elders with dementia and may experience overwhelming stress that adversely affects their mental health. Interventions to teach them resourcefulness skills for managing stress can promote optimal mental health and facilitate continued caregiving. However, effectiveness of resourcefulness training (RT) cannot be examined until its need is established. This pilot trial with 138 women caregivers of someone with dementia examined the need for RT using subjective and objective data. Data were collected before and after RT. Data analysis focused on baseline resourcefulness scores (higher scores = lower need); scores in relation to attrition; correlations among resourcefulness, stress, and depressive symptoms; and post-RT evaluation of the need for RT. Baseline resourcefulness scores were normally distributed and showed that 74% of the caregivers had a moderate to high need for RT. Reasons for attrition were unrelated to the need for RT; however, caregivers who dropped out had resourcefulness scores that averaged two points higher than those who remained in the study. Lower resourcefulness was associated greater stress (r = -.37, p < .001) and depressive symptoms (r = -.52, p < .001). Of the 63 caregivers who received RT, 82% (n = 52) reported a felt need for RT and 94% (n = 59) believed that other caregivers need RT. The results suggest a substantial need for resourcefulness training in women dementia caregivers and support moving forward to test RT's effectiveness for reducing caregiver stress and depressive symptoms.

Morphology and Molecular Mechanisms of Hepatic Injury in Rats under Simulated Weightlessness and the Protective Effects of Resistance Training.

PubMed

Du, Fang; Ding, Ye; Zou, Jun; Li, Zhili; Tian, Jijing; She, Ruiping; Wang, Desheng; Wang, Huijuan; Lv, Dongqiang; Chang, Lingling

2015-01-01

This study investigated the effects of long-term simulated weightlessness on liver morphology, enzymes, glycogen, and apoptosis related proteins by using two-month rat-tail suspension model (TS), and liver injury improvement by rat-tail suspension with resistance training model (TS&RT). Microscopically the livers of TS rats showed massive granular degeneration, chronic inflammation, and portal fibrosis. Mitochondrial and endoplasmic reticulum swelling and loss of membrane integrity were observed by transmission electron microscopy (TEM). The similar, but milder, morphological changes were observed in the livers of TS&RT rats. Serum biochemistry analysis revealed that the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly higher (p<0.05) in TS rats than in controls. The levels of ALT and AST in TS&RT rats were slightly lower than in RT rats, but they were insignificantly higher than in controls. However, both TS and TS&RT rats had significantly lower levels (p<0.05) of serum glucose and hepatic glycogen than in controls. Immunohistochemistry demonstrated that the expressions of Bax, Bcl-2, and active caspase-3 were higher in TS rats than in TS&RT and control rats. Real-time polymerase chain reaction (real-time PCR) showed that TS rats had higher mRNA levels (P < 0.05) of glucose-regulated protein 78 (GRP78) and caspase-12 transcription than in control rats; whereas mRNA expressions of C/EBP homologous protein (CHOP) and c-Jun N-terminal kinase (JNK) were slightly higher in TS rats. TS&RT rats showed no significant differences of above 4 mRNAs compared with the control group. Our results demonstrated that long-term weightlessness caused hepatic injury, and may trigger hepatic apoptosis. Resistance training slightly improved hepatic damage.

Morphology and Molecular Mechanisms of Hepatic Injury in Rats under Simulated Weightlessness and the Protective Effects of Resistance Training

PubMed Central

Zou, Jun; Li, Zhili; Tian, Jijing; She, Ruiping; Wang, Desheng; Wang, Huijuan; Lv, Dongqiang; Chang, Lingling

2015-01-01

This study investigated the effects of long-term simulated weightlessness on liver morphology, enzymes, glycogen, and apoptosis related proteins by using two-month rat-tail suspension model (TS), and liver injury improvement by rat-tail suspension with resistance training model (TS&RT). Microscopically the livers of TS rats showed massive granular degeneration, chronic inflammation, and portal fibrosis. Mitochondrial and endoplasmic reticulum swelling and loss of membrane integrity were observed by transmission electron microscopy (TEM). The similar, but milder, morphological changes were observed in the livers of TS&RT rats. Serum biochemistry analysis revealed that the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly higher (p<0.05) in TS rats than in controls. The levels of ALT and AST in TS&RT rats were slightly lower than in RT rats, but they were insignificantly higher than in controls. However, both TS and TS&RT rats had significantly lower levels (p<0.05) of serum glucose and hepatic glycogen than in controls. Immunohistochemistry demonstrated that the expressions of Bax, Bcl-2, and active caspase-3 were higher in TS rats than in TS&RT and control rats. Real-time polymerase chain reaction (real-time PCR) showed that TS rats had higher mRNA levels (P < 0.05) of glucose-regulated protein 78 (GRP78) and caspase-12 transcription than in control rats; whereas mRNA expressions of C/EBP homologous protein (CHOP) and c-Jun N-terminal kinase (JNK) were slightly higher in TS rats. TS&RT rats showed no significant differences of above 4 mRNAs compared with the control group. Our results demonstrated that long-term weightlessness caused hepatic injury, and may trigger hepatic apoptosis. Resistance training slightly improved hepatic damage. PMID:26000905

Comparison of Detection Rate and Mutational Pattern of Drug-Resistant Mutations Between a Large Cohort of Genotype B and Genotype C Hepatitis B Virus-Infected Patients in North China.

PubMed

Li, Xiaodong; Liu, Yan; Xin, Shaojie; Ji, Dong; You, Shaoli; Hu, Jinhua; Zhao, Jun; Wu, Jingjing; Liao, Hao; Zhang, Xin-Xin; Xu, Dongping

2017-06-01

The study aimed to investigate the association of prevalent genotypes in China (HBV/C and HBV/B) with HBV drug-resistant mutations. A total of 13,847 nucleos(t)ide analogue (NA)-treated patients with chronic HBV infection from North China were enrolled. HBV genotypes and resistant mutations were determined by direct sequencing and confirmed by clonal sequencing if necessary. HBV/B, HBV/C, and HBV/D occupied 14.3%, 84.9%, and 0.8% across the study population, respectively. NA usage had no significant difference between HBV/B- and HBV/C-infected patients. Lamivudine-resistant mutations were more frequently detected in HBV/C-infected patients, compared with HBV/B-infected patients (31.67% vs. 25.26%, p < 0.01). Adefovir- and entecavir-resistant mutation detection rates were similar, but the mutational pattern was different between the two genotypes. For adefovir-resistant mutations, HBV/C-infected patients had a higher detection rate of rtA181 V (HBV/C 5.29% vs. HBV/B 1.36%, p < 0.01) and a lower detection rate of rtN236T (2.70% vs. 6.54%, p < 0.01). For entecavir-resistant mutations, HBV/C-infected patients had a higher detection rate of rtM204 V/I+T184 substitution or S202G/C (3.66% vs. 2.16%, p < 0.01) and a lower detection rate of rtM204 V/I+M250 V/I/L substitution (0.67% vs. 1.46%, p < 0.01). Multidrug-resistant mutations (defined as coexistence of mutation to nucleoside and nucleotide analogues) were detected in 104 patients. HBV/C-infected patients had a higher detection rate of multidrug-resistant mutation than HBV/B-infected patients (0.83% vs. 0.35%, p < 0.05). The study for the first time clarified that HBV/C-infected patients had a higher risk to develop multidrug-resistant mutations, compared with HBV/B-infected patients; and HBV/C- and HBV/B-infected patients had different inclinations in the ETV-resistant mutational pattern.

A regression tree for identifying combinations of fall risk factors associated to recurrent falling: a cross-sectional elderly population-based study.

PubMed

Kabeshova, A; Annweiler, C; Fantino, B; Philip, T; Gromov, V A; Launay, C P; Beauchet, O

2014-06-01

Regression tree (RT) analyses are particularly adapted to explore the risk of recurrent falling according to various combinations of fall risk factors compared to logistic regression models. The aims of this study were (1) to determine which combinations of fall risk factors were associated with the occurrence of recurrent falls in older community-dwellers, and (2) to compare the efficacy of RT and multiple logistic regression model for the identification of recurrent falls. A total of 1,760 community-dwelling volunteers (mean age ± standard deviation, 71.0 ± 5.1 years; 49.4 % female) were recruited prospectively in this cross-sectional study. Age, gender, polypharmacy, use of psychoactive drugs, fear of falling (FOF), cognitive disorders and sad mood were recorded. In addition, the history of falls within the past year was recorded using a standardized questionnaire. Among 1,760 participants, 19.7 % (n = 346) were recurrent fallers. The RT identified 14 nodes groups and 8 end nodes with FOF as the first major split. Among participants with FOF, those who had sad mood and polypharmacy formed the end node with the greatest OR for recurrent falls (OR = 6.06 with p < 0.001). Among participants without FOF, those who were male and not sad had the lowest OR for recurrent falls (OR = 0.25 with p < 0.001). The RT correctly classified 1,356 from 1,414 non-recurrent fallers (specificity = 95.6 %), and 65 from 346 recurrent fallers (sensitivity = 18.8 %). The overall classification accuracy was 81.0 %. The multiple logistic regression correctly classified 1,372 from 1,414 non-recurrent fallers (specificity = 97.0 %), and 61 from 346 recurrent fallers (sensitivity = 17.6 %). The overall classification accuracy was 81.4 %. Our results show that RT may identify specific combinations of risk factors for recurrent falls, the combination most associated with recurrent falls involving FOF, sad mood and polypharmacy. The FOF emerged as the risk factor strongly associated with recurrent falls. In addition, RT and multiple logistic regression were not sensitive enough to identify the majority of recurrent fallers but appeared efficient in detecting individuals not at risk of recurrent falls.

Combined Modality Management of Retroperitoneal Sarcomas: A Single-Institution Series of 121 Patients

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

Bishop, Andrew J.; Zagars, Gunar K.; Torres, Keila E.

2015-09-01

Purpose: The purpose of this study was to investigate local control, survival outcomes, and complication rates of patients treated with aggressive surgery and radiation therapy (RT) for retroperitoneal sarcomas (RPS). Methods and Materials: We reviewed the medical records of 121 consecutive patients treated for RPS with surgery and RT between 1965 and 2012. The most common histology was liposarcoma (n=42; 35%). The median follow-up was 100 months (range: 20-467 months). Eighty-six patients (71%) were treated for initial presentation of RPS, and 35 patients (29%) presented with and were treated for RPS recurrence. RT was preoperative in 88 patients (73%; median dose: 50.4 Gy)more » and postoperative in 33 patients (27%; median dose: 55 Gy). Results: Five-year local control and overall survival rates were 56% and 57%, respectively. Two factors were associated with higher risk of any intra-abdominal recurrence at 5 years: positive or uncertain margins (58% vs 30% for negative margins, P<.001; hazard ratio [HR]: 2.7; 95% confidence interval [CI]: 1.6-4.8) and disease recurrence after previous resection (76% vs 31% for de novo RPS, P<.001; HR: 4.4; 95% CI: 2.5-7.5). The 10-year complication rate was 5%, and RT-related complications were associated with postoperative RT (P<.001) and RT dose of ≥60 Gy (P<.001). Conclusions: Intra-abdominal RPS recurrence continues to be a significant challenge despite the use of aggressive surgery and radiation therapy. Given the complications associated with postoperative radiation therapy, we recommend that preoperative radiation therapy is the preferred strategy when combined modality therapy is recommended.« less

N08C9 (Alliance): A Phase 3 Randomized Study of Sulfasalazine Versus Placebo in the Prevention of Acute Diarrhea in Patients Receiving Pelvic Radiation Therapy

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

Miller, Robert C., E-mail: miller.robert@mayo.edu; Petereit, Daniel G.; Sloan, Jeff A.

Purpose: To provide confirmatory evidence on the use of sulfasalazine to reduce enteritis during pelvic radiation therapy (RT), following 2 prior single-institution trials suggestive that benefit existed. Methods and Materials: A multi-institution, randomized, double-blind, placebo-controlled phase 3 trial was designed to assess the efficacy of sulfasalazine versus placebo in the treatment of RT-related enteritis during RT including the posterior pelvis (45.0-53.5 Gy) and conducted through a multicenter national cooperative research alliance. Patients received 1000 mg of sulfasalazine or placebo orally twice daily during and for 4 weeks after RT. The primary endpoint was maximum severity of diarrhea (Common Terminology Criteria for Adverse Events versionmore » 4.0). Toxicity and bowel function were assessed by providers through a self-administered bowel function questionnaire taken weekly during RT and for 6 weeks afterward. Results: Eighty-seven patients were enrolled in the trial between April 29, 2011, and May 13, 2013, with evenly distributed baseline factors. At the time of a planned interim toxicity analysis, more patients with grade ≥3 diarrhea received sulfasalazine than received placebo (29% vs 11%, P=.04). A futility analysis showed that trial continuation would be unlikely to yield a positive result, and a research board recommended halting study treatment. Final analysis of the primary endpoint showed no significant difference in maximum diarrhea severity between the sulfasalazine and placebo arms (P=.41). Conclusions: Sulfasalazine does not reduce enteritis during pelvic RT and may be associated with a higher risk of adverse events than placebo. This trial illustrates the importance of confirmatory phase 3 trials in the evaluation of symptom-control agents.« less

Primary Surgery vs Radiotherapy for Early Stage Oral Cavity Cancer.

PubMed

Ellis, Mark A; Graboyes, Evan M; Wahlquist, Amy E; Neskey, David M; Kaczmar, John M; Schopper, Heather K; Sharma, Anand K; Morgan, Patrick F; Nguyen, Shaun A; Day, Terry A

2018-04-01

Objective The goal of this study is to determine the effect of primary surgery vs radiotherapy (RT) on overall survival (OS) in patients with early stage oral cavity squamous cell carcinoma (OCSCC). In addition, this study attempts to identify factors associated with receiving primary RT. Study Design Retrospective cohort study. Setting National Cancer Database (NCDB, 2004-2013). Subjects and Methods Reviewing the NCDB from 2004 to 2013, patients with early stage I to II OCSCC were identified. Kaplan-Meier estimates of survival, Cox regression analysis, and propensity score matching were used to examine differences in OS between primary surgery and primary RT. Multivariable logistic regression analysis was performed to identify factors associated with primary RT. Results Of the 20,779 patients included in the study, 95.4% (19,823 patients) underwent primary surgery and 4.6% (956 patients) underwent primary RT. After adjusting for covariates, primary RT was associated with an increased risk of mortality (adjusted hazard ratio [aHR], 1.97; 99% confidence interval [CI], 1.74-2.22). On multivariable analysis, factors associated with primary RT included age ≥70 years, black race, Medicaid or Medicare insurance, no insurance, oral cavity subsite other than tongue, clinical stage II disease, low-volume treatment facilities, and earlier treatment year. Conclusion Primary RT for early stage OCSCC is associated with increased mortality. Approximately 5% of patients receive primary RT; however, this percentage is decreasing. Patients at highest risk for receiving primary RT include those who are elderly, black, with public insurance, and treated at low-volume facilities.

Reference data on reaction time and aging using the Nintendo Wii Balance Board: A cross-sectional study of 354 subjects from 20 to 99 years of age.

PubMed

Blomkvist, Andreas W; Eika, Fredrik; Rahbek, Martin T; Eikhof, Karin D; Hansen, Mette D; Søndergaard, Malene; Ryg, Jesper; Andersen, Stig; Jørgensen, Martin G

2017-01-01

Falls among older adults is one of the major public health challenges facing the rapidly changing demography. The valid assessment of reaction time (RT) and other well-documented risk factors for falls are mainly restricted to specialized clinics due to the equipment needed. The Nintendo Wii Balance Board has the potential to be a multi-modal test and intervention instrument for these risk factors, however, reference data are lacking. To provide RT reference data and to characterize the age-related changes in RT measured by the Nintendo Wii Balance Board. Healthy participants were recruited at various locations and their RT in hands and feet were tested by six assessors using the Nintendo Wii Balance Board. Reference data were analysed and presented in age-groups, while the age-related change in RT was tested and characterized with linear regression models. 354 participants between 20 and 99 years of age were tested. For both hands and feet, mean RT and its variation increased with age. There was a statistically significant non-linear increase in RT with age. The averaged difference between male and female was significant, with males being faster than females for both hands and feet. The averaged difference between dominant and non-dominant side was non-significant. This study reported reference data with percentiles for a new promising method for reliably testing RT. The RT data were consistent with previously known effects of age and gender on RT.

Reference data on reaction time and aging using the Nintendo Wii Balance Board: A cross-sectional study of 354 subjects from 20 to 99 years of age

PubMed Central

Rahbek, Martin T.; Eikhof, Karin D.; Hansen, Mette D.; Søndergaard, Malene; Ryg, Jesper; Andersen, Stig; Jørgensen, Martin G.

2017-01-01

Background Falls among older adults is one of the major public health challenges facing the rapidly changing demography. The valid assessment of reaction time (RT) and other well-documented risk factors for falls are mainly restricted to specialized clinics due to the equipment needed. The Nintendo Wii Balance Board has the potential to be a multi-modal test and intervention instrument for these risk factors, however, reference data are lacking. Objective To provide RT reference data and to characterize the age-related changes in RT measured by the Nintendo Wii Balance Board. Method Healthy participants were recruited at various locations and their RT in hands and feet were tested by six assessors using the Nintendo Wii Balance Board. Reference data were analysed and presented in age-groups, while the age-related change in RT was tested and characterized with linear regression models. Results 354 participants between 20 and 99 years of age were tested. For both hands and feet, mean RT and its variation increased with age. There was a statistically significant non-linear increase in RT with age. The averaged difference between male and female was significant, with males being faster than females for both hands and feet. The averaged difference between dominant and non-dominant side was non-significant. Conclusion This study reported reference data with percentiles for a new promising method for reliably testing RT. The RT data were consistent with previously known effects of age and gender on RT. PMID:29287063

Androgen Deprivation Therapy Use in the Setting of High-dose Radiation Therapy and the Risk of Prostate Cancer–Specific Mortality Stratified by the Extent of Competing Mortality

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

Rose, Brent S., E-mail: brose44@gmail.com; Chen, Ming-Hui; Wu, Jing

Purpose: The addition of androgen deprivation therapy (ADT) to radiation therapy (RT) is the standard of care for men with intermediate- and high-risk prostate cancer (PC). However, whether competing mortality (CM) affects the ability of ADT to improve, survival remains unanswered. Methods and Materials: We calculated a CM risk score using a Fine-Gray semiparametric model that included age and cardiometabolic comorbidities from a cohort of 17,669 men treated with high-dose RT with or without supplemental ADT for nonmetastatic PC. Fine and Gray competing risk regression analysis was used to assess whether ADT reduced the risk of PC-specific mortality for menmore » with a low versus a high risk of CM among the 4550 patients within the intermediate- and high-risk cohort after adjustment for established PC prognostic factors, year of treatment, site, and ADT propensity score. Results: After a median follow-up of 8.4 years, 1065 men had died, 89 (8.36%) of PC. Among the men with a low CM score, ADT use was associated with a significant reduction in the risk of PC-specific mortality (adjusted hazard ratio 0.35, 95% confidence interval 0.14-0.87, P=.02) but was not for men with high CM (adjusted hazard ratio 1.33, 95% confidence interval 0.77-2.30, P=.30). Conclusions: Adding ADT to high-dose RT appears to be associated with decreased PC-specific mortality risk in men with a low but not a high CM score. These data should serve to heighten awareness about the importance of considering competing risks when determining whether to add ADT to RT for older men with intermediate- or high-risk PC.« less

The effect of adjuvant radiation on survival in early stage clear cell ovarian carcinoma.

PubMed

Hogen, Liat; Thomas, Gillian; Bernardini, Marcus; Bassiouny, Dina; Brar, Harinder; Gien, Lilian T; Rosen, Barry; Le, Lisa; Vicus, Danielle

2016-11-01

To assess the impact of adjuvant radiotherapy (RT) on survival in patients with stage I and II ovarian clear cell carcinoma (OCCC). Data collection and analysis of stage I and II OCCC patients treated at two tertiary centers in Toronto, between 1995 and 2014, was performed. Descriptive statistics and Kaplan-Meier survival probability estimates were completed. The log-rank test was used to compare survival curves. 163 patients were eligible. 44 (27%) patients were treated with adjuvant RT: 37 of them received adjuvant chemotherapy (CT), and 7 had RT only. In the no-RT group, there were 119 patients: 83 patients received adjuvant CT and 36 had no adjuvant treatment. The 10year progression free survival (PFS) was 65% for patients treated with RT, and 59% no-RT patients. There were a total of 41 (25%) recurrences in the cohort: 12 (27.2%) patients in RT group and 29 (24.3%) in the no-RT group. On multivariable analysis, adjuvant RT was not significantly associated with an increased PFS (0.85 (0.44-1.63) p=0.63) or overall survival (OS) (0.84 (0.39-1.82) p=0.66). In the subset of 59 patients defined as high-risk: stage IC with positive cytology and/or surface involvement and stage II: RT was not found to be associated with a better PFS (HR 1.18 (95% CI: 0.55-2.54) or O S(HR 1.04 (95% CI: 0.40-2.69)). Adjuvant RT was not found to be associated with a survival benefit in patients with stage I and II ovarian clear cell carcinoma or in a high risk subset of patients including stage IC cytology positive/surface involvement and stage II patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Long-term results of a phase 2 study of neoadjuvant chemotherapy and radiotherapy in the management of high-risk, high-grade, soft tissue sarcomas of the extremities and body wall: Radiation Therapy Oncology Group Trial 9514.

PubMed

Kraybill, William G; Harris, Jonathan; Spiro, Ira J; Ettinger, David S; DeLaney, Thomas F; Blum, Ronald H; Lucas, David R; Harmon, David C; Letson, G Douglas; Eisenberg, Burton

2010-10-01

The use of neoadjuvant and adjuvant chemotherapy in soft tissue sarcomas is controversial. This is a report of long-term (≥5 years) follow-up in patients with high-grade, high-risk soft tissue sarcomas treated with neoadjuvant chemotherapy, preoperative radiotherapy (RT), and adjuvant chemotherapy. Patients with high-grade soft tissue sarcoma≥8 cm in diameter of the extremities and body wall received 3 cycles of neoadjuvant chemotherapy (mesna, doxorubicin, ifosfamide, and dacarbazine) and preoperative RT (44 grays administered in split courses), and 3 cycles of postoperative chemotherapy (mesna, doxorubicin, ifosfamide, and dacarbazine). Sixty-four of 66 patients were analyzed. After chemotherapy and RT, 61 patients had surgery; 58 had R0 resections (5 amputations), and 3 had R1 resections. Ninety-seven percent experienced grade 3 or higher toxicity, including 3 deaths. These toxicities were short term. With a median follow-up of 7.7 years in surviving patients, the 5-year rates of locoregional failure (including amputation), and distant metastasis were 22.2% (95% confidence interval [CI], 11.8-32.6) and 28.1% (95% CI, 17.0-39.2). The most common site of metastasis was lung. Estimated 5-year rates of disease-free survival, distant disease-free survival, and overall survival were 56.1% (95% CI, 43.9-68.3), 64.1% (95% CI, 52.3-75.8), and 71.2% (95% CI, 60.0-82.5), respectively. Although the toxicity was significant, it was limited in its course and for the most part resolved by 1 year. The long-term outcome was better than might be expected in such high-risk tumors. Copyright © 2010 American Cancer Society.

Detection of interleukin 6 mRNA by RT-PCR in vaginal secretions: association with preterm delivery and neonatal infection in women with preterm labour and intact membranes.

PubMed

Goffinet, François; Kayem, Gilles; Maillard, Françoise; Trébéden, Hélène; Cabrol, Dominique; Weill, Bernard; Batteux, Frédéric

2005-12-01

To find a biological marker associated with preterm delivery or neonatal infection in pregnant women with preterm labour and intact membranes. Cervical secretions were collected from 286 women hospitalized for preterm labour with intact membranes at 24-34 weeks' gestation. The outcomes studied were delivery before 33 and 35 weeks' gestation, chorioamnionitis, and neonatal infection, and their association with the presence of IL-6 mRNA in cervical secretions as detected by RT-PCR. The other infectious markers tested were: bacterial vaginosis and fetal fibronectin in cervical secretions; serum CRP and white blood cell count. The vaginal secretions of 13 of 286 women (4.7%) contained IL-6 mRNA. The only other marker tested significantly associated with IL-6 mRNA+ was the presence of streptococcus in vaginal secretions (30.8% versus 9.4% in the IL-6+ and-groups, p = 0.03). Although the difference did not reach statistical significance (p<0.06 and 0.08, respectively), in women with IL-6 mRNA in cervical secretions we observed a tendency to give birth before 33 and 35 weeks more often than the population as a whole. This group was at higher risk of neonatal infection (38.5% versus 15.1%; p = 0.04). After adjustment for infectious risk factors, IL-6 remained significantly associated with neonatal infection (OR = 4.6, 95% CI [1.1-18.9]). The sensitivity of IL-6 mRNA for neonatal infection was 11.1%. The specificity was 96.7%. The detection of IL-6 mRNA by RT-PCR in vaginal secretions allows identification of a small group of women at high risk of neonatal infection, independently of other markers of infection.

Diagnosis and treatment for clinically localized prostate cancer. Adherence to the European Association of Urology clinical guidelines in a nationwide population-based study - GESCAP group.

PubMed

Gómez-Veiga, F; Rodríguez-Antolín, A; Miñana, B; Hernández, C; Suárez, J F; Fernández-Gómez, J M; Unda, M; Burgos, J; Alcaraz, A; Rodríguez, P; Medina, R; Castiñeiras, J; Moreno, C; Pedrosa, E; Cózar, J M

To assess the adherence to European Association of Urology (EAU) guidelines in the management of prostate cancer (PCa) in Spain. Epidemiological, population-based, study including a national representative sample of 3,918 incident patients with histopathological confirmation during 2010; 95% of the patient's sample was followed up for at least one year. Diagnosis along with treatment related variables (for localized PCa -low, intermediate, high and locally-advanced by D'Amico risk stratification) was recorded. Differences between groups were tested with Chi-squared and Kruskal-Wallis tests. Mean (SD) age of PCa patients was 68.48 (8.18). Regarding diagnostic by biopsy procedures, 64.56% of all patients had 8-12 cores in first biopsy and 46.5% of the patients over 75 years, with PSA<10ng/mL were biopsied. Staging by Computer Tomography (CT) or Bone Scan (BS) was used for determining tumor extension in 60.09% of high-risk cases and was applied differentially depending on patients' age; 3,293 (84.05%) patients received a treatment for localized PCa. Radical prostatectomy was done in 1,277 patients and 206 out of these patients also had a lymphadenectomy, being 4.64% low-risk, 22.81% intermediate-risk and 36.00% high-risk patients; 86.08% of 1,082 patients who had radiotherapy were treated with 3D or IMRT and 35.77% received a dose ≥75Gy; 419 patients were treated with brachytherapy (BT): 54.81% were low-risk patients, 22.84% intermediate-risk and 12.98% high-risk. Hormonotherapy (HT, n=521) was applied as single therapy in 9.46% of low-risk and 17.92% of intermediate-risk patients. Additionally, HT was combined with RT in 14.34% of lower-risk patients and 58.26% of high-risk patients, and 67.19% low-intermediate risk with RT and/or BT received neoadjuvant/concomitant/adjuvant HT. Finally, 83.75% of high-risk patients undergoing RT and/or BT also received HT. Although EAU guidelines for PCa management are easily available in Europe, the adherence to their recommendations is low, finding the highest discrepancies in the need for a prostate biopsy and the diagnostic methods. Improve information and educational programs could allow a higher adherence to the guidelines and reduce the variability in daily practice. (Controlled-trials.com: ISRCTN19893319). Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Sex-dependent effects of restraint on nociception and pituitary-adrenal hormones in the rat.

PubMed

Aloisi, A M; Steenbergen, H L; van de Poll, N E; Farabollini, F

1994-05-01

The sex-dependent effects of acute restraint (RT) on nociceptive and pituitary-adrenal responses were investigated in the rat. In a first experiment, the effect of 30 min RT on pain sensitivity was evaluated through repeated use of the tail withdrawal test during and after treatment. RT induced an increase in the nociceptive threshold, i.e., analgesia, in males and females, but the duration and time-course of this effect varied between sexes. The latencies returned to approximately control values in females in the second half of RT, but in males they remained higher for the whole period of RT and immediately afterwards. Twenty-four hours later, males displayed longer latencies than controls in response to simple reexposure to the environment. In a second experiment, ACTH and corticosterone plasma levels were measured immediately after 15 or 30 min of RT. ACTH and corticosterone were higher in restrained animals than in controls after both periods of treatment, and in both sexes; however, females showed higher basal and stress corticosterone levels than males. The role played by corticosteroids in the nociceptive responses of the two sexes is discussed.

Adjuvant and Salvage Radiotherapy After Prostatectomy for Prostate Cancer: A Literature Review

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

Pasquier, David; Ballereau, Charles

2008-11-15

Purpose: Given that postprostatectomy recurrence of prostate cancer occurs in 10-40% of patients, the best use of immediate postoperative radiotherapy (RT) in high-risk patients and salvage RT for biochemical recurrence remains a topic of debate. We assessed the levels of evidence (in terms of efficacy, prognostic factors, and toxicity) for the following treatment strategies: immediate postoperative RT alone, salvage RT alone, and the addition of androgen deprivation therapy to the two RT strategies. Methods and Materials: A systematic literature search for controlled randomized trials, noncontrolled trials, and retrospective studies between 1990 and 2008 was performed on PubMed, CancerLit, and MEDLINE.more » Only relevant articles that had appeared in peer-reviewed journals were selected. We report on the levels of evidence (according to the National Cancer Institute guidelines) supporting the various treatment strategies. Results: Immediate postoperative RT improves biochemical and clinical progression-free survival (Level of evidence, 1.ii) but has no significant effect on metastasis-free survival or overall survival. A pathologic review is of particular importance for correctly analyzing the treatment strategies. Low-grade morbidity has been significantly greater in the postoperative groups, but no severe toxicity has been observed. The influence of immediate postoperative RT on postprostatectomy continence appears to be slight; therefore, immediate postoperative RT should be considered in patients with major risk factors for local relapse (Level of evidence, 1.ii). On the basis of extensive retrospective data, salvage RT is effective in biochemical relapse after prostatectomy; some patients with few adverse prognostic factors might also benefit from salvage RT (Level of evidence, 3.ii). The addition of androgen deprivation therapy to immediate postoperative or salvage RT has only been supported by weak, retrospective data (Level of evidence, 3.ii). Conclusion: Prospective randomized trials are needed to compare immediate postoperative RT with salvage RT and to assess the value of androgen deprivation therapy in this setting.« less

The Effect of Radiation on Complication Rates and Patient Satisfaction in Breast Reconstruction using Temporary Tissue Expanders and Permanent Implants.

PubMed

Anker, Christopher J; Hymas, Richard V; Ahluwalia, Ravinder; Kokeny, Kristine E; Avizonis, Vilija; Boucher, Kenneth M; Neumayer, Leigh A; Agarwal, Jayant P

2015-01-01

The optimal method of reconstruction following mastectomy for breast cancer patients receiving radiation therapy (RT) is controversial. This study evaluated patient satisfaction and complication rates among patients who received implant-based breast reconstruction. The specific treatment algorithm analyzed included patients receiving mastectomy and immediate temporary tissue expander (TE), followed by placement of a permanent breast implant (PI). If indicated, RT was delivered to the fully expanded TE. Records of 218 consecutive patients with 222 invasive (85%) or in situ (15%) breast lesions from the Salt Lake City region treated between 1998 and 2009 were retrospectively reviewed, 28% of whom received RT. Median RT dose was 50.4 Gy, and 41% received a scar boost at a median dose of 10 Gy. Kaplan-Meier analyses were performed to evaluate the cumulative incidence of surgical complications, including permanent PI removal. Risk factors associated with surgical events were analyzed. To evaluate cosmetic results and patient satisfaction, an anonymous survey was administered. Mean follow-up was 44 months (range 6-144). Actuarial 5-year PI removal rates for non-RT and RT patients were 4% and 22%, respectively. On multivariate analysis (MVA), the only factor associated with PI removal was RT (p = 0.009). Surveys were returned describing the outcomes of 149 breasts. For the non-RT and RT groups, those who rated their breast appearance as good or better were 63% versus 62%, respectively. Under 1/3 of each group was dissatisfied with their reconstruction. RT did not significantly affect patient satisfaction scores, but on MVA RT was the only factor associated with increased PI removal. This reconstruction technique may be considered an acceptable option even if RT is needed, but the increased complication risk with RT must be recognized. © 2015 Wiley Periodicals, Inc.

Proton Radiotherapy for High-Risk Pediatric Neuroblastoma: Early Outcomes and Dose Comparison

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

Hattangadi, Jona A.; Rombi, Barbara; Provincial Agency for Proton Therapy, Trento

2012-07-01

Purpose: To report the early outcomes for children with high-risk neuroblastoma treated with proton radiotherapy (RT) and to compare the dose distributions for intensity-modulated photon RT (IMRT), three-dimensional conformal proton RT (3D-CPT), and intensity-modulated proton RT to the postoperative tumor bed. Methods and Materials: All patients with high-risk (International Neuroblastoma Staging System Stage III or IV) neuroblastoma treated between 2005 and 2010 at our institution were included. All patients received induction chemotherapy, surgical resection of residual disease, high-dose chemotherapy with stem cell rescue, and adjuvant 3D-CPT to the primary tumor sites. The patients were followed with clinical examinations, imaging, andmore » laboratory testing every 6 months to monitor disease control and side effects. IMRT, 3D-CPT, and intensity-modulated proton RT plans were generated and compared for a representative case of adjuvant RT to the primary tumor bed followed by a boost. Results: Nine patients were treated with 3D-CPT. The median age at diagnosis was 2 years (range 10 months to 4 years), and all patients had Stage IV disease. All patients had unfavorable histologic characteristics (poorly differentiated histologic features in 8, N-Myc amplification in 6, and 1p/11q chromosomal abnormalities in 4). The median tumor size at diagnosis was 11.4 cm (range 7-16) in maximal dimension. At a median follow-up of 38 months (range 11-70), there were no local failures. Four patients developed distant failure, and, of these, two died of disease. Acute side effects included Grade 1 skin erythema in 5 patients and Grade 2 anorexia in 2 patients. Although comparable target coverage was achieved with all three modalities, proton therapy achieved substantial normal tissue sparing compared with IMRT. Intensity-modulated proton RT allowed additional sparing of the kidneys, lungs, and heart. Conclusions: Preliminary outcomes reveal excellent local control with proton therapy for high-risk neuroblastoma, although distant failures continu to occur. Dosimetric comparisons demonstrate the advantage of proton RT compared with IMRT in this setting, allowing more conformal treatment and better normal tissue sparing.« less

Digestive and urologic hemorrhage after intravenous thrombolysis for acute ischemic stroke: Data from a Chinese stroke center.

PubMed

Chang, Hong; Wang, Xiaojuan; Yang, Xin; Song, Haiqing; Qiao, Yuchen; Liu, Jia

2017-02-01

Objective Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) is considered the most effective treatment method for AIS; however, it is associated with a risk of hemorrhage. We analyzed the risk factors for digestive and urologic hemorrhage during rt-PA therapy. Methods We retrospectively analyzed patients with AIS who underwent intravenous thrombolysis with rt-PA during a 5-year period in a Chinese stroke center. Data on the demographics, medical history, laboratory test results, and clinical outcomes were collected. Results 338 patients with AIS were eligible and included. Logistic regression multivariate analysis showed that gastric catheter was significantly correlated with digestive hemorrhage, while age and urinary catheter were significantly correlated with urologic hemorrhage. Most hemorrhagic events were associated with catheterization after 1 to 24 hours of rt-PA therapy. Conclusions In summary, gastric and urinary catheters were correlated with digestive and urologic hemorrhage in patients with AIS undergoing rt-PA therapy. Well-designed controlled studies with large samples are required to confirm our findings.

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

Comparison of the performance in detection of HPV infections between the high-risk HPV genotyping real time PCR and the PCR-reverse dot blot assays.

PubMed

Zhang, Lahong; Dai, Yibei; Chen, Jiahuan; Hong, Liquan; Liu, Yuhua; Ke, Qiang; Chen, Yiwen; Cai, Chengsong; Liu, Xia; Chen, Zhaojun

2018-01-01

A new multiplex real-time PCR assay, the high-risk HPV genotyping real time PCR assay (HR HPV RT-PCR), has been developed to detect 15 high-risk HPV types with respective viral loads. In this report, a total of 684 cervical specimens from women diagnosed with vaginitis were assessed by the HR HPV RT-PCR and the PCR reaction and reverse dot blot (PCR-RDB) assays, using a PCR-sequencing method as a reference standard. A total coincidence of 97.7% between the HR HPV RT PCR and the PCR-RDB assays was determined with a Kappa value of 0.953. The HR HPV RT PCR assay had sensitivity, specificity, and concordance rates (accuracy) of 99.7%, 99.7%, and 99.7%, respectively, as confirmed by PCR-sequencing, while the PCR-RDB assay had respective rates of 98.8%, 97.1%, and 98.0%. The overall rate of HPV infection, determined by PCR-sequencing, in women diagnosed with vaginitis was 49.85%, including 36.26% of single infection and 13.6% of multiple infections. The most common infections among the 15 high-risk HPV types in women diagnosed with vaginitis were HPV-52, HPV-16, and HPV-58, with a total detection rate of 10.23%, 7.75%, and 5.85%, respectively. We conclude that the HR HPV RT PCR assay exhibits better clinical performance than the PCR-RDB assay, and is an ideal alternative method for HPV genotyping. In addition, the HR HPV RT PCR assay provides HPV DNA viral loads, and could serve as a quantitative marker in the diagnosis and treatment of single and multiple HPV infections. © 2017 Wiley Periodicals, Inc.

Clinicopathological features and outcomes of progression of CLL on the BCL2 inhibitor venetoclax.

PubMed

Anderson, Mary Ann; Tam, Constantine; Lew, Thomas E; Juneja, Surender; Juneja, Manu; Westerman, David; Wall, Meaghan; Lade, Stephen; Gorelik, Alexandra; Huang, David C S; Seymour, John F; Roberts, Andrew W

2017-06-22

The BCL2 inhibitor venetoclax achieves responses in ∼79% of patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (RR-CLL/SLL), irrespective of risk factors associated with poor response to chemoimmunotherapy. A limitation of this targeted therapy is progressive disease (PD) in some patients. To define the risk factors for progression, the clinicopathological features of PD, and the outcomes for patients after venetoclax failure, we analyzed 67 heavily pretreated patients on 3 early phase clinical trials. Investigations at progression included positron emission tomography scan and biopsy. Twenty-five (37%) patients manifested PD on therapy: 17 with Richter transformation (RT) and 8 with progressive CLL/SLL. RT occurred significantly earlier (median 7.9 months) than progressive CLL (median 23.4 months) ( P = .003). Among patients who received the recommended phase 2 dose of venetoclax or higher (≥400 mg/d), fludarabine refractoriness and complex karyotype were associated with progression (hazard ratio 7.01 [95% confidence interval 1.7-28.5]; P = .002 and 6.6 [1.5-29.8]; P = .005, respectively), whereas del(17p) and/or TP53 mutation were not ( P = .75). Median postprogression survival was 13 (<1-49.9) months. Bruton tyrosine kinase inhibitors were active in progressive CLL, but outcomes were mixed. Patients with disease that is fludarabine refractory or who have complex cytogenetics should have occult RT excluded before initiating venetoclax therapy. © 2017 by The American Society of Hematology.

Superior sulcus non-small cell lung carcinoma: A comparison of IMRT and 3D-RT dosimetry.

PubMed

Truntzer, Pierre; Antoni, Delphine; Santelmo, Nicola; Schumacher, Catherine; Falcoz, Pierre-Emmanuel; Quoix, Elisabeth; Massard, Gilbert; Noël, Georges

2016-01-01

A dosimetric study comparing intensity modulated radiotherapy (IMRT) by TomoTherapy to conformational 3D radiotherapy (3D-RT) in patients with superior sulcus non-small cell lung cancer (NSCLC). IMRT became the main technique in modern radiotherapy. However it was not currently used for lung cancers. Because of the need to increase the dose to control lung cancers but because of the critical organs surrounding the tumors, the gains obtainable with IMRT is not still demonstrated. A dosimetric comparison of the planned target and organs at risk parameters between IMRT and 3D-RT in eight patients who received preoperative or curative intent irradiation. In the patients who received at least 66 Gy, the mean V95% was significantly better with IMRT than 3D-RT (p = 0.043). IMRT delivered a lower D2% compared to 3D-RT (p = 0.043). The IH was significantly better with IMRT (p = 0.043). The lung V 5 Gy and V 13 Gy were significantly higher in IMRT than 3D-RT (p = 0.043), while the maximal dose (D max) to the spinal cord was significantly lower in IMRT (p = 0.043). The brachial plexus D max was significantly lower in IMRT than 3D-RT (p = 0.048). For patients treated with 46 Gy, no significant differences were found. Our study showed that IMRT is relevant for SS-NSCLC. In patients treated with a curative dose, it led to a reduction of the exposure of critical organs, allowing a better dose distribution in the tumor. For the patients treated with a preoperative schedule, our results provide a basis for future controlled trials to improve the histological complete response by increasing the radiation dose.

Pathological Predictors for Site of Local Recurrence After Radiotherapy for Prostate Cancer

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

Chopra, Supriya; Princess Margaret Hospital, University Health Network, Toronto; Toi, Ants

2012-03-01

Purpose: Rational design of targeted radiotherapy (RT) in prostate cancer (Pca) hinges on a better understanding of spatial patterns of recurrence. We sought to identify pathological factors predictive for site of local recurrence (LR) after external beam RT. Methods and Materials: Prospective databases were reviewed to identify men with LR after RT from 1997 through 2009. Patients with biochemical failure and biopsy-confirmed Pca more than 2 years after RT were evaluated. Prediction for site of recurrence based on the following pretreatment factors was determined on independent and cluster-sextant basis: presence of malignancy, dominant vs. nondominant percentage core length (PCL) involvement,more » PCL {>=} or <40%, and Gleason score. Sites of dominant PCL were defined as sextants with peak PCL involvement minus 10%, and >5% for each patient. Results: Forty-one patients with low-intermediate risk Pca constituted the study cohort. Median time to biopsy after RT was 51 months (range, 24-145). Of 246 sextants, 74 were involved with tumor at baseline. When sextants are treated as independent observations the presence of malignancy (77% vs. 22%, p = 0.0001), dominant PCL (90% vs. 46%, p = 0.0001), and PCL {>=}40% (89% vs. 68 %, p = 0.04) were found to be significant predictors for LR, although PCL {>=}40% did not retain statistical significance if sextants were considered correlated. The vast majority of patients (95%) recurred at the original site of dominant PCL or PCL {>=}40%, and 44% also recurred in regions of nondominant PCL <40% (n = 8) and/or benign sampling (n = 14) at baseline. Conclusions: LR after RT predominantly occurs in regions bearing higher histological tumor burden but are not isolated to these sites. Our data highlights the value of spatially resolved baseline pathological sampling and may assist in the design of clinical trials tailoring RT dose prescriptions to subregions of the prostate gland.« less

Patterns of failure in patients with locally advanced head and neck cancer treated postoperatively with irradiation or concomitant irradiation with Mitomycin C and Bleomycin

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

Zakotnik, Branko; Budihna, Marjan; Smid, Lojze

2007-03-01

Purpose: The long term results and patterns of failure in patients with squamous cell head and neck carcinoma (SCHNC) treated in a prospective randomized trial in which concomitant postoperative radiochemotherapy with Mitomycin C and Bleomycin (CRT) was compared with radiotherapy only (RT), were analyzed. Patients and Methods: Between March 1997 and December 2001, 114 eligible patients with Stage III or IV SCHNC were randomized. Primary surgical treatment was performed with curative intent in all patients. Patients in both groups were postoperatively irradiated to the total dose of 56-70 Gy. Chemotherapy included Mitomycin C 15 mg/m{sup 2} after 10 Gy andmore » 5 mg of Bleomycin twice weekly during irradiation. Median follow-up was 76 months (48-103 months). Results: At 5 years in the RT and CRT arms, the locoregional control was 65% and 88% (p = 0.026), disease-free survival 33% and 53% (p = 0.035), and overall survival 37% and 55% (p = 0.091) respectively. Patients who benefited from chemotherapy were those with high-risk factors. The probability of distant metastases was 22% in RT and 20% in CRT arm (p = 0.913), of grade III or higher late toxicity 19% in RT and 26% in CRT arm (p = 0.52) and of thyroid dysfunction 36% in RT and 56% in CRT arm (p = 0.24). The probability to develop a second primary malignancy (SPM) was 34% in the RT and 8% in the CRT arm (p = 0.023). One third of deaths were due to infection, but there was no difference between the 2 groups. Conclusion: With concomitant radiochemotherapy, locoregional control and disease free survival were significantly improved. Second primary malignancies in the CRT arm compared to RT arm were significantly less frequent. The high probability of post treatment hypothyroidism in both arms warrants regular laboratory evaluation.« less

Development of an In-House Multiplex Nested RT-PCR Method for Detecting Acute HIV-1 Infection in High Risk Populations.

PubMed

Liu, Zhiying; Li, Wei; Xu, Meng; Sheng, Bo; Yang, Zixuan; Jiao, Yanmei; Zhang, Tong; Mou, Danlei; Chen, Dexi; Wu, Hao

2015-01-01

The detection of acute HIV infection (AHI) among high risk populations can help reduce secondary transmission of HIV. The nucleic acid testing (NAT) can shorten the test window period by up to 7-12 days. In this study, we describe an in-house NAT based on the multiplex nested RT-PCR method to detect the HIV RNA. We also evaluated it in a high risk cohort in Beijing. Four primer pairs were designed and evaluated for the detection of different HIV-1 subtypes in group M. Multiplex RT-PCR and nested PCR were performed. The sensitivity, specialty, primers compatibility among HIV subtypes were evaluated simultaneously. In an MSM cohort in Beijing during a 3-year period, a total of 11,808 blood samples that were negative by ELISA or indeterminate by Western blot were analyzed by this multiplex nested RT-PCR with pooling strategy. The multiplex nested RT-PCR was successfully applied for the detection of at least six HIV-1 subtypes. The sensitivity was 40 copies/ml and the specificity was 100%. A total of 29 people were tested HIV-1 positive with acute infection in a MSM cohort of Beijing during a 3 years period. This multiplex nested RT-PCR provides a useful tool for the rapid detection of acute HIV-1 infection. When used in combination with the 3(rd) generation ELISA, it can improve the detection rate of HIV infection, especially in the source limited regions.

Large institutional variations in use of androgen deprivation therapy with definitive radiotherapy in a population-based cohort of men with intermediate- and high-risk prostate cancer.

PubMed

Ong, Wee Loon; Foroudi, Farshad; Evans, Sue; Millar, Jeremy

2017-11-01

To evaluate the pattern of use of androgen deprivation therapy (ADT) with definitive radiotherapy (RT) in men with prostate cancer (PCa) in a population-based study in Australia. This is a prospective cohort of men with intermediate- and high-risk PCa, captured in the population-based Prostate Cancer Outcome Registry Victoria, who were treated with definitive prostate RT between January 2010 and December 2015. The primary outcome of interest was ADT utilization. Chi-squared test for trend was used to evaluate the temporal trend in the use of ADT over the study period. Multivariate logistic regressions were used to evaluate the effects of patient-, tumour- and treatment-related factors, and treatment institutions (public/ private and metropolitan/ regional) on the likelihood of ADT utilization. A total of 1806 men were included in the study, 199 of whom (11%) had favourable National Comprehensive Cancer Network (NCCN) intermediate-risk disease (i.e. only one intermediate-risk feature, primary Gleason grade 3, and <50% biopsy core involved), 687 (38%) had unfavourable NCCN intermediate-risk disease, and 920 (51%) had high-risk disease. Of the 1806 men, 1155 (64%) received ADT with RT. Men with NCCN high-risk PCa (84%) were more likely to have ADT than men with favourable NCCN intermediate-risk (32%) and unfavourable NCCN intermediate-risk (46%) PCa (P < 0.001). Men treated in public institutions (66%, vs 47% in private institutions; P < 0.001) and regional centres (78%, vs 59% in metropolitan institutions; P < 0.001) were more likely to receive ADT. There was a trend towards an increase in ADT utilization from 50% in 2010 to 64% in 2015 (P < 0.001). In multivariate analyses (adjusting for age, tumour-related factors, year of treatment and use of brachytherapy boost), treatment institution (public and regional) remained independently associated with increased likelihood of ADT utilization. Men with intermediate-risk PCa treated in regional and public institutions were 2.7 times (95% confidence interval [CI] 1.9-3.9; P < 0.001) and 2.8 times (95% CI 1.4-5.3; P = 0.002), more likely to receive ADT with RT, respectively, while men with high-risk PCa treated in regional and public institutions were 3.1 times (95% CI 1.7-5.7; P < 0.001) and 3.0 times (95% CI 1.7-5.4; P < 0.001), more likely to receive ADT with RT, respectively. This is the largest Australasian contemporary series reporting on the pattern of use of ADT with definitive prostate RT. While there was an increasing trend towards use of ADT over time, ADT still appeared to be underutilized in certain groups of patients who may benefit from ADT, with approximately one in five men with high-risk and one in two with unfavourable intermediate-risk PCa not receiving ADT with RT. There was notable variation in the use of ADT between public vs private and metropolitan vs regional institutions. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Cost-effectiveness assessment of lumpectomy cavity boost in elderly women with early stage estrogen receptor positive breast cancer receiving adjuvant radiotherapy.

PubMed

Lester-Coll, Nataniel H; Rutter, Charles E; Evans, Suzanne B

2016-04-01

Breast radiotherapy (RT) for elderly women with estrogen receptor positive early stage breast cancer (ER+ESBC) improves local recurrence (LR) rates without benefitting overall survival. Breast boost is a common practice, although the absolute benefit decreases with age. Consequently, an analysis of its cost-effectiveness in the elderly ESBC populations is warranted. A Markov model was used to compare cost-effectiveness of RT with or without a boost in elderly ER+ESBC patients. The ten-year probability of LR with boost was derived from the CALGB 9343 trial and adjusted by the hazard ratio for LR from boost radiotherapy trial data, yielding the LR rate without boost. Remaining parameters were estimated using published data. Boost RT was associated with an increase in mean cost ($7139 vs $6193) and effectiveness (5.66 vs 5.64 quality adjusted life years; QALYs) relative to no boost. The incremental cost-effectiveness ratio (ICER) for boost was $55,903 per QALY. On one-way sensitivity analysis, boost remained cost-effective if the hazard ratio of LR with boost was <0.67. Boost RT for ER+ESBC patients was cost-effective over a wide range of assumptions and inputs over commonly accepted willingness-to pay-thresholds, but particularly in women at higher risk for LR. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Integrated prostate cancer centers might cause an overutilization of radiotherapy for low-risk prostate cancer: A comparison of treatment trends in the United States and Germany from 2004 to 2011.

PubMed

Hager, Benjamin; Kraywinkel, Klaus; Keck, Bastian; Katalinic, Alexander; Meyer, Martin; Zeissig, Sylke Ruth; Stabenow, Roland; Froehner, Michael; Huber, Johannes

2015-04-01

Aim of the study was to analyze changes in primary treatment for low-risk prostate cancer across different healthcare systems. We compared "Surveillance Epidemiology and End Results" data (USA) with data from four German federal epidemiological cancer registries, both from 2004 to 2011. We excluded metastatic disease and patients aged ⩾80 years. Thereof, we identified 132,506 (USA) and 54,159 (Germany) patients with low-risk according to the 2014 EAU guidelines. We tested treatment trends for statistical significance with a linear regression model. Active treatment was radical prostatectomy (RP) in 36.1% vs. 66.2% and radiotherapy (RT) in 38.4% vs. 11.8%. No active treatment (NAT) was reported in 24.2% vs. 16.2% (p<0.001 each). Through the study period the use of RP decreased from 37.1% to 34.2% in the USA (p=0.04) and was constant at a mean of 66.2% in Germany (p=0.8). The use of RT in the USA decreased from 42.8% to 31.8% (p<0.001), while it was stable in Germany (p=0.09). The NAT group grew from 18.0% to 33.2% in the USA (p<0.001), while it was stable in Germany until 2009 (p=0.3). From 2009 to 2011 there also was an increase of the NAT group in Germany from 15.2% to 19.4% (p=0.001). In contrast to former evidence we found the relative use of RT for low-risk prostate cancer much higher in the USA compared to Germany. The implementation of integrated prostate cancer centers in the USA might explain this observation. Deferred and defensive treatment strategies showed a steady increase in the USA. This development seems delayed in Germany by several years. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A Phase I Trial of Samarium-153-Lexidronam Complex for Treatment of Clinically Nonmetastatic High-Risk Prostate Cancer: First Report of a Completed Study

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

Valicenti, Richard K., E-mail: richard.valicenti@ucdmc.ucdavis.ed; Trabulsi, Edouard; Intenzo, Charles

Purpose: We completed a Phase I trial to determine the maximum tolerated dose of samarium-153 EDTMP ({sup 153}Sm) with hormonal therapy (HT) and radiation therapy (RT) in high-risk clinically nonmetastatic prostate cancer. Methods and Materials: High-risk M0 prostate cancer patients (prostate-specific antigen >20 ng/mL, Gleason score >7, or >T3) were eligible for this prospective trial of dose-escalated radioactive {sup 153}Sm-EDTMP (.25-2.0 mCi/kg) as primary or postoperative therapy. After 1 month of HT, we administered {sup 153}Sm-EDTMP followed by 4 more months of HT, 46.8 Gy to the pelvic region and 23.4 Gy to the prostate target (TD = 70.2 Gy).more » The primary endpoint was Grade III toxicity or higher by the National Cancer Institute Common Toxicity Criteria. Results: Twenty-nine patients enrolled (median prostate-specific antigen = 8.2 ng/mL, 27/29 (93%) T stage {>=}T2b, 24/29 (83%) had Gleason >7) and received {sup 153}Sm-EDTMP (.25 mCi/kg, 4 patients; 0.5 mCi/kg, 4 patients; 0.75 mCi/kg, 6 patients; 1.0 mCi/kg, 6 patients; 1.5 mCi/kg, 5 patients; 2.0mCi/kg, 4 patients). Twenty-eight patients underwent all planned therapy without delays (1 patient required surgery before the start of RT). With a median follow-up time of 23 months, there were 2 patients (7 %) experiencing Grade III hematologic toxicity. There were no other Grade III or IV side effects. Conclusions: Our trial demonstrates that 2 mCi/kg {sup 153}Sm -EDTMP with HT and RT was safe and feasible in men with high-risk M0 prostate cancer. A Phase II study to test this treatment is currently underway by the Radiation Therapy Oncology Group.« less

Radiation-related heart disease after breast cancer radiation therapy in Korean women.

PubMed

Chang, Jee Suk; Ko, Byung Kyun; Bae, Jeoung Won; Yu, Jong-Han; Park, Min Ho; Jung, Yongsik; Jeon, Ye Won; Kim, Kyung Hwan; Shin, Jaeyong; Suh, Chang-Ok; Kim, Yong Bae

2017-11-01

To study the late cardiac toxicity of breast radiation therapy (RT) in Asian women. Female breast cancer patients in Korea who underwent breast conservation surgery followed by RT from 1990-2012 were identified from two large registries at institution and population levels. Cumulative incidences of acute coronary events (ACE) or cardiac mortality were estimated in relation to the laterality of breast cancer using a competing risks analysis. In an analysis of 2577 women from a single institution, 3.7% were obese (body mass index ≥30), and 3.4% were ever-smokers. Patients with a history of hypertension, diabetes, or coronary artery disease were 17.5, 5.7, and 2.8%, respectively. The mean heart doses were 6.2 and 1.5 Gy for left- and right-sided tumors, respectively. With a median follow-up of 7 (range 1-23) years, the overall and breast cancer-specific survivals at 10 years were 94.9 and 96.5%, respectively. The 10-year cumulative incidence of ACE was 2.96%. The mean time to ACE was 5.2 ± 3.9 years (range 1-17). There was no clinically relevant difference in rates of ACE between left-sided and right-sided patients, with an adjusted hazard ratio of 1.16 (CI 0.59-2.29). An analysis of 24,235 women in a nationwide registry validated these negative findings with respect to cardiac mortality, with an adjusted hazard ratio of 1.52 (CI 0.37-6.25). Increasing age, a higher body mass index, and a history of hypertension or ischemic heart disease were identified as risk factors. Our findings reassure that excess risk from breast RT may be small in healthy women, most of who not smoke, weigh less, and have fewer risk factors. A validation using a larger data set of National Health Insurance Corporation is ongoing.

Retrospective Evaluation Reveals That Long-term Androgen Deprivation Therapy Improves Cause-Specific and Overall Survival in the Setting of Dose-Escalated Radiation for High-Risk Prostate Cancer

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

Feng, Felix Y., E-mail: ffeng@med.umich.edu; Department of Radiation Oncology, Veterans Affairs Medical Center, Ann Arbor, Michigan; Blas, Kevin

2013-05-01

Purpose: To evaluate the role of androgen deprivation therapy (ADT) and duration for high-risk prostate cancer patients treated with dose-escalated radiation therapy (RT). Methods and Materials: A retrospective analysis of high-risk prostate cancer patients treated with dose-escalated RT (minimum 75 Gy) with or without ADT was performed. The relationship between ADT use and duration with biochemical failure (BF), metastatic failure (MF), prostate cancer-specific mortality (PCSM), non-prostate cancer death (NPCD), and overall survival (OS) was assessed as a function of pretreatment characteristics, comorbid medical illness, and treatment using Fine and Gray's cumulative incidence methodology. Results: The median follow-up time was 64more » months. In men with National Comprehensive Cancer Network defined high-risk prostate cancer treated with dose-escalated RT, on univariate analysis, both metastasis (P<.0001; hazard ratio 0.34; 95% confidence interval 0.18-0.67; cumulative incidence at 60 months 13% vs 35%) and PCSM (P=.015; hazard ratio 0.41; 95% confidence interval 0.2-1.0; cumulative incidence at 60 months 6% vs 11%) were improved with the use of ADT. On multivariate analysis for all high-risk patients, Gleason score was the strongest negative prognostic factor, and long-term ADT (LTAD) improved MF (P=.002), PCSM (P=.034), and OS (P=.001). In men with prostate cancer and Gleason scores 8 to 10, on multivariate analysis after adjustment for other risk features, there was a duration-dependent improvement in BF, metastasis, PCSM, and OS, all favoring LTAD in comparison with STAD or RT alone. Conclusion: For men with high-risk prostate cancer treated with dose-escalated EBRT, this retrospective study suggests that the combination of LTAD and RT provided a significant improvement in clinical outcome, which was especially true for those with Gleason scores of 8 to 10.« less

Results of NCCTG N0275 (Alliance) - a phase II trial evaluating resection followed by adjuvant radiation therapy for patients with desmoplastic melanoma.

PubMed

Rule, William G; Allred, Jacob B; Pockaj, Barbara A; Markovic, Svetomir N; DiCaudo, David J; Erickson, Lori A; Deming, Richard L; Schild, Steven E

2016-08-01

To examine, in a prospective fashion, the utilization and efficacy of adjuvant radiation therapy (RT) in patients with resected desmoplastic melanoma (DM). Adult patients with resected, margin-negative, and nonmetastatic DM were eligible for this single-arm prospective phase II study. Patients were to receive postoperative RT, 30 Gy in five fractions, to the operative bed with 2- to 3-cm margins (depending on the tumor location). Nodal basin RT was not allowed. The primary study endpoint was the 2-year local recurrence rate (LRR). Secondary endpoints included the incidence of regional and distant metastatic disease, progression-free survival, overall survival (OS), and treatment-related toxicity. Twenty patients with a single de novo DM lesion meeting trial eligibility criteria were enrolled and treated. The 2-year LRR was 10%, with two patients demonstrating a LR within 2 years of completion of protocol therapy. No regional or distant failures occurred. OS at 2 and 5 years was 95 and 77%, respectively. There were no grade 3 or higher acute or late adverse events that were related to the protocol therapy. Adjuvant RT after wide local excision (WLE) for DM is efficacious and well tolerated. It should be considered for DM patients after margin-negative WLE. Additional study is needed to further refine low-risk patient populations that can potentially have adjuvant RT omitted as part of the treatment plan. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

A Cross-Sectional Cohort Study of Cerebrovascular Disease and Late Effects After Radiation Therapy for Craniopharyngioma.

PubMed

Lo, Andrea C; Howard, A Fuchsia; Nichol, Alan; Hasan, Haroon; Martin, Monty; Heran, Manraj; Goddard, Karen

2016-05-01

The study objective was to describe radiation-induced vascular abnormalities, stroke prevalence, and stroke risk factors in survivors of childhood craniopharyngioma. Twenty survivors of childhood craniopharyngioma who received radiotherapy (RT) were included in the study. A clinical history, quality of life assessment, cognitive functioning assessment, magnetic resonance angiogram or computed tomography angiogram, fasting lipid profile, and fasting glucose or hemoglobin A1c test were obtained. Median age at diagnosis was 10.3 years and median age at time of study was 29.0 years. Vascular abnormalities were detected in six (32%) of 19 patients' angiograms (vascular stenosis, decreased artery size, aneurysm, cavernoma, and small vessel disease). Five (25%) of 20 patients experienced a stroke after RT. Median time since RT was 27.8 versus 9.1 years in patients with versus without vascular abnormalities (P = 0.02). A low level of high-density lipoproteiin (HDL) was present in 100% (5/5) of patients who had a post-RT stroke as compared with 13% (2/15) of patients who did not have any post-RT stroke (P = 0.02). Previous stroke had occurred in 0% (0/5) of patients receiving growth hormone (GH) replacement at the time of study, compared to 40% (6/15) of patients who were not receiving GH replacement (P = 0.09). Patients with craniopharyngioma treated with RT have a high prevalence of stroke and vascular abnormalities, particularly those with low HDL and longer duration of time since RT. There is a trend to suggest that continual GH replacement may reduce the risk of stroke. These patients should undergo careful monitoring and aggressive modification of stroke risk factors. © 2016 Wiley Periodicals, Inc.

PET/CT-guided treatment planning for paediatric cancer patients: a simulation study of proton and conventional photon therapy

PubMed Central

Brodin, N P; Björk-Eriksson, T; Birk Christensen, C; Kiil-Berthelsen, A; Aznar, M C; Hollensen, C; Markova, E; Munck af Rosenschöld, P

2015-01-01

Objective: To investigate the impact of including fluorine-18 fludeoxyglucose (18F-FDG) positron emission tomography (PET) scanning in the planning of paediatric radiotherapy (RT). Methods: Target volumes were first delineated without and subsequently re-delineated with access to 18F-FDG PET scan information, on duplicate CT sets. RT plans were generated for three-dimensional conformal photon RT (3DCRT) and intensity-modulated proton therapy (IMPT). The results were evaluated by comparison of target volumes, target dose coverage parameters, normal tissue complication probability (NTCP) and estimated risk of secondary cancer (SC). Results: Considerable deviations between CT- and PET/CT-guided target volumes were seen in 3 out of the 11 patients studied. However, averaging over the whole cohort, CT or PET/CT guidance introduced no significant difference in the shape or size of the target volumes, target dose coverage, irradiated volumes, estimated NTCP or SC risk, neither for IMPT nor 3DCRT. Conclusion: Our results imply that the inclusion of PET/CT scans in the RT planning process could have considerable impact for individual patients. There were no general trends of increasing or decreasing irradiated volumes, suggesting that the long-term morbidity of RT in childhood would on average remain largely unaffected. Advances in knowledge: 18F-FDG PET-based RT planning does not systematically change NTCP or SC risk for paediatric cancer patients compared with CT only. 3 out of 11 patients had a distinct change of target volumes when PET-guided planning was introduced. Dice and mismatch metrics are not sufficient to assess the consequences of target volume differences in the context of RT. PMID:25494657

Enzymatic and viability RT-qPCR assays for evaluation of enterovirus, hepatitis A virus and norovirus inactivation: Implications for public health risk assessment.

PubMed

Monteiro, S; Santos, R

2018-04-01

To assess the potential of a viability dye and an enzymatic reverse transcription quantitative PCR (RT-qPCR) pretreatment to discriminate between infectious and noninfectious enteric viruses. Enterovirus (EntV), norovirus (NoV) GII.4 and hepatitis A virus (HAV) were inactivated at 95°C for 10 min, and four methods were used to compare the efficiency of inactivation: (i) cell culture plaque assay for HAV and EntV, (ii) RT-qPCR alone, (iii) RT-qPCR assay preceded by RNase treatment, and (iv) pretreatment with a viability dye (reagent D (RD)) followed by RT-qPCR. In addition, heat-inactivated NoV was treated with RD coupled with surfactants to increase the efficiency of the viability dye. No treatment was able to completely discriminate infectious from noninfectious viruses. RD-RT-qPCR reduced more efficiently the detection of noninfectious viruses with little to no removal observed with RNase. RD-RT-qPCR method was the closest to cell culture assay. The combination of surfactants and RD did not show relevant improvements on the removal of inactivated viruses signal compared with viability RT-qPCR, with the exception of Triton X-100. The use of surfactant/RD-RT-qPCR, although not being able to completely remove the signal from noninfectious viral particles, yielded a better estimation of viral infectivity. Surfactant/RD-RT-qPCR may be an advantageous tool for a better detection of infectious viruses with potential significant impact in the risk assessment of the presence of enteric viruses. © 2017 The Society for Applied Microbiology.

The Risk-Taking and Self-Harm Inventory for Adolescents: Development and Psychometric Evaluation

ERIC Educational Resources Information Center

Vrouva, Ioanna; Fonagy, Peter; Fearon, Pasco R. M.; Roussow, Trudie

2010-01-01

In this study, we report on the development and psychometric evaluation of the Risk-Taking (RT) and Self-Harm (SH) Inventory for Adolescents (RTSHIA), a self-report measure designed to assess adolescent RT and SH in community and clinical settings. 651 young people from secondary schools in England ranging in age from 11.6 years to 18.7 years and…

Effects of edaravone, the free radical scavenger, on outcomes in acute cerebral infarction patients treated with ultra-early thrombolysis of recombinant tissue plasminogen activator.

PubMed

Lee, Xian-Ru; Xiang, Gui-Ling

2018-04-01

Edaravone, a free radical scavenger, alleviates blood-brain barrier disruption in conjunction with suppression of the inflammatory reaction in acute cerebral infarction. Thrombolysis with recombinant tissue plasminogen activator (rtPA) is an established therapy for acute cerebral infarction patients. The purpose of this study was to assess the effects of edaravone on outcomes in acute cerebral infarction patients treated with ultra-early thrombolysis of iv-rt-PA. We conducted a retrospective cohort study using the database of Ningbo First Hospital. We identified patients who were admitted with a primary diagnosis of acute cerebral infarction and treated with intravenous rtPA(iv-rtPA) within 3 h of symptom onset from March 1st in 2014 to October 31st in 2016.Thenceforth,the patients were divided into 2 groups by treatment with(edaravone group) or without edaravone(non-edaravone group). Glasgow Coma Scale (GCS) scores and mRS score at admission were used. Clinical background, risk factors for acute cerebral infarction hemorrhagic transformation, 7-day mortality, recanalization rate, bleeding complications and blood rheology indexes were collected. We also collected the following factors: National Institutes of Health Stroke Scale scores, barthel index. 136 patients treated without edaravone during hospitalization were selected in non-edaravone group while edaravone group included 132 patients treated with edaravone during hospitalization. The patient baseline distributions were well balanced between non-edaravone group and edaravone group. The rate of hemorrhagic transformation in non-edaravone group was higher than that in edaravone group (P ＜ 0.05). The NIHSS scores 7 days and 14 days after symptom onset were higher in non-edaravone group than in edaravone group (both P ＜ 0.05). Edaravone group showed a higher recanalization rate and a lower bleeding complications rate at discharge than the non-edaravone group (both P ＜ 0.05). The differences of all the blood rheology indexes between the two groups were statistically significant (all P ＜ 0.05). Edaravone may improve outcomes of acute cerebral infarction patients treated with ultra-early thrombolysis of iv-rt-PA. Copyright © 2018 Elsevier B.V. All rights reserved.

Management of Adolescent Low-Risk Classical Hodgkin Lymphoma: Which Chemotherapy Backbone Gives the Best Chance of Omitting Radiotherapy Safely.

PubMed

Algiraigri, Ali H; Essa, Mohammed F

2016-03-01

Even though more than 90% of adolescents with low-risk classical Hodgkin lymphoma (LRcHL) will be cured with first-line therapy, many will suffer serious late toxic effects from radiotherapy (RT). The goals for care have shifted toward minimizing late toxic effects without compromising the outstanding cure rates by adapting a risk and response-based therapy. Recent published and ongoing randomized clinical trials, using functional imaging, may allow for better identification of those patients for whom RT may be safely omitted while maintaining excellent cure rates. To evaluate the best chemotherapy regimens with a reasonable toxicity profile and that are expected to have a high chance of omitting RT based on a response-directed therapy while maintaining high cure rates, a mini review was conducted of the recent clinical trials in pediatric and adult LRcHL. The UK RAPID trial chemotherapy backbone (3 × ABVD) followed by a response-based positron emission tomography scan offers up to a 75% chance of safely omitting RT without compromising the cure rate, which remained well above 90%.

Oral candidiasis in patients receiving radiation therapy for head and neck cancer.

PubMed

Deng, Zeyi; Kiyuna, Asanori; Hasegawa, Masahiro; Nakasone, Isamu; Hosokawa, Atsushi; Suzuki, Mikio

2010-08-01

To investigate oral candidiasis in patients with head and neck cancer before, during, and after radiation therapy, and to explore its association with clinical oropharyngeal symptoms. A cohort study. University hospital. Subjects who received radiation therapy (RT) for the treatment of head and neck cancer were divided into two groups: an oral cavity irradiated group (OIRR group, n = 29) and an oral cavity nonirradiated group (ONIRR group, n = 17). A control group consisted of 18 healthy subjects. Patients were examined for signs of oral candidiasis before, during, immediately after, and one month after RT. Mouth and throat soreness (MTS), dysphagia, and xerostomia were evaluated by self-reported questionnaires, and associations between oral candidiasis and these symptoms were analyzed. The incidence of oral candidiasis during RT was significantly higher in the OIRR group (55.2%) than in the ONIRR group (11.8%). Similarly, the occurrence of xerostomia during RT was significantly higher in the OIRR group (86.2%) than in the ONIRR group (52.9%). In the OIRR group, the mean MTS score at the 20th fraction of RT was significantly higher in patients with candidiasis (mean +/- SD, 5.8 +/- 2.1) than in those with RT-induced mucositis without candidiasis (3.7 +/- 2.0). In the OIRR group, 65.2 percent of patients who experienced dysphagia developed oral candidiasis, compared with only 10 percent in the ONIRR group. Oral candidiasis concurrent with oral mucositis due to RT may increase oropharyngeal discomfort during RT. Copyright (c) 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.

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

Wei Xiong; Liu, H. Helen; Tucker, Susan L.

Purpose: To identify clinical and dosimetric factors influencing the risk of pericardial effusion (PCE) in patients with inoperable esophageal cancer treated with definitive concurrent chemotherapy and radiation therapy (RT). Methods and Materials: Data for 101 patients with inoperable esophageal cancer treated with concurrent chemotherapy and RT from 2000 to 2003 at our institution were analyzed. The PCE was confirmed from follow-up chest computed tomography scans and radiologic reports, with freedom from PCE computed from the end of RT. Log-rank tests were used to identify clinical and dosimetric factors influencing freedom from PCE. Dosimetric factors were calculated from the dose-volume histogrammore » for the whole heart and pericardium. Results: The crude rate of PCE was 27.7% (28 of 101). Median time to onset of PCE was 5.3 months (range, 1.0-16.7 months) after RT. None of the clinical factors investigated was found to significantly influence the risk of PCE. In univariate analysis, a wide range of dose-volume histogram parameters of the pericardium and heart were associated with risk of PCE, including mean dose to the pericardium, volume of pericardium receiving a dose greater than 3 Gy (V3) to greater than 50 Gy (V50), and heart volume treated to greater than 32-38 Gy. Multivariate analysis selected V30 as the only parameter significantly associated with risk of PCE. Conclusions: High-dose radiation to the pericardium may strongly increase the risk of PCE. Such a risk may be reduced by minimizing the dose-volume of the irradiated pericardium and heart.« less

Concurrent Androgen Deprivation Therapy During Salvage Prostate Radiotherapy Improves Treatment Outcomes in High-Risk Patients

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

Soto, Daniel E., E-mail: dsoto2@partners.org; Passarelli, Michael N.; Daignault, Stephanie

2012-03-01

Purpose: To determine whether concurrent androgen deprivation therapy (ADT) during salvage radiotherapy (RT) improves prostate cancer treatment outcomes. Methods and Materials: A total of 630 postprostatectomy patients were retrospectively identified who were treated with three-dimensional conformal RT. Of these, 441 were found to be treated for salvage indications. Biochemical failure was defined as prostate-specific antigen (PSA) of 0.2 ng/mL or greater above nadir with another PSA increase or the initiation of salvage ADT. Progression-free survival (PFS) was defined as the absence of biochemical failure, continued PSA rise despite salvage therapy, initiation of systemic therapy, clinical progression, or distant failure. Multivariate-adjustedmore » Cox proportional hazards modeling was performed to determine which factors predict PFS. Results: Low-, intermediate-, and high-risk patients made up 10%, 24%, and 66% of patients, respectively. The mean RT dose was 68 Gy. Twenty-four percent of patients received concurrent ADT (cADT). Regional pelvic nodes were treated in 16% of patients. With a median follow-up of 3 years, the 3-year PFS was 4.0 years for cADT vs. 3.4 years for cADT patients (p = 0.22). Multivariate analysis showed that concurrent ADT (p = 0.05), Gleason score (p < 0.001), and pre-RT PSA (p = 0.03) were independent predictors of PFS. When patients were stratified by risk group, the benefits of cADT (hazard ratio, 0.65; p = 0.046) were significant only for high-risk patients. Conclusions: This retrospective study showed a PFS benefit of concurrent ADT during salvage prostate RT. This benefit was observed only in high-risk patients.« less

Reward-Based Learning as a Function of Severity of Substance Abuse Risk in Drug-Naïve Youth with ADHD.

PubMed

Parvaz, Muhammad A; Kim, Kristen; Froudist-Walsh, Sean; Newcorn, Jeffrey H; Ivanov, Iliyan

2018-06-20

Attention-deficit/hyperactivity disorder (ADHD) is associated with elevated risk for later development of substance use disorders (SUD), specifically because youth with ADHD, similar to individuals with SUD, exhibit deficits in learning abilities and reward processing. Another known risk factor for SUD is familial history of substance dependence. Youth with familial SUD history show reward processing deficits, higher prevalence of externalizing disorders, and higher impulsivity scores. Thus, the main objective of this proof-of-concept study is to investigate whether risk loading (ADHD and parental substance use) for developing SUD in drug-naïve youth impacts reward-related learning. Forty-one drug-naïve youth, stratified into three groups: Healthy Controls (HC, n = 13; neither ADHD nor parental SUD), Low Risk (LR, n = 13; ADHD only), and High Risk (HR, n = 15; ADHD and parental SUD), performed a novel Anticipation, Conflict, and Reward (ACR) task. In addition to conventional reaction time (RT) and accuracy analyses, we analyzed computational variables including learning rates and assessed the influence of learned predictions of reward probability and stimulus congruency on RT. The multivariate ANOVA on learning rate, congruence, and prediction revealed a significant main Group effect across these variables [F(3, 37) = 3.79, p = 0.018]. There were significant linear effects for learning rate (Contrast Estimate = 0.181, p = 0.038) and the influence of stimulus congruency on RTs (Contrast Estimate = 1.16, p = 0.017). Post hoc comparisons revealed that HR youth showed the most significant deficits in accuracy and learning rates, while stimulus congruency had a lower impact on RTs in this group. LR youth showed scores between those of the HC and HR youth. These preliminary results suggest that deficits in learning and in adjusting to task difficulty are a function of increasing risk loading for SUD in drug-naïve youth. These results also highlight the importance of developing and applying computational models to study intricate details in behavior that typical analytic methodology may not be sensitive to.

Dose-Volume Analysis of Predictors for Gastrointestinal Toxicity After Concurrent Full-Dose Gemcitabine and Radiotherapy for Locally Advanced Pancreatic Adenocarcinoma

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

Huang Jiayi; Robertson, John M., E-mail: jrobertson@beaumont.edu; Ye Hong

2012-07-15

Purpose: To identify dosimetric predictors for the development of gastrointestinal (GI) toxicity in patients with locally advanced pancreatic adenocarcinoma (LAPC) treated with concurrent full-dose gemcitabine and radiotherapy (GemRT). Methods and Materials: From June 2002 to June 2009, 46 LAPC patients treated with definitive GemRT were retrospectively analyzed. The stomach and duodenum were retrospectively contoured separately to determine their dose-volume histogram (DVH) parameters. GI toxicity was defined as Grade 3 or higher GI toxicity. The follow-up time was calculated from the start of RT to the date of death or last contact. Univariate analysis (UVA) and multivariate analysis (MVA) using Kaplan-Meiermore » and Cox regression models were performed to identify risk factors associated with GI toxicity. The receiver operating characteristic curve and the area under the receiver operating characteristic curve (AUC) were used to determine the best DVH parameter to predict for GI toxicity. Results: Of the patients, 28 (61%) received concurrent gemcitabine alone, and 18 (39%) had concurrent gemcitabine with daily erlotinib. On UVA, only the V{sub 20Gy} to V{sub 35Gy} of duodenum were significantly associated with GI toxicity (all p {<=} 0.05). On MVA, the V{sub 25Gy} of duodenum and the use of erlotinib were independent risk factors for GI toxicity (p = 0.006 and 0.02, respectively). For the entire cohort, the V{sub 25Gy} of duodenum is the best predictor for GI toxicity (AUC = 0.717), and the 12-month GI toxicity rate was 8% vs. 48% for V{sub 25Gy} {<=} 45% and V{sub 25Gy} > 45%, respectively (p = 0.03). However, excluding the erlotinib group, the V{sub 35Gy} is the best predictor (AUC = 0.725), and the 12-month GI toxicity rate was 0% vs. 41% for V{sub 35Gy} {<=} 20% and V{sub 35Gy} > 20%, respectively (p = 0.04). Conclusions: DVH parameters of duodenum may predict Grade 3 GI toxicity after GemRT for LAPC. Concurrent use of erlotinib during GemRT may increase GI toxicity.« less

Cardiac Mortality in Patients With Stage I and II Diffuse Large B-Cell Lymphoma Treated With and Without Radiation: A Surveillance, Epidemiology, and End-Results Analysis

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

Pugh, Thomas J., E-mail: thomas.pugh@ucdenver.ed; Ballonoff, Ari; Rusthoven, Kyle E.

2010-03-01

Purpose: Standard therapy for stage I and II diffuse large B-cell lymphoma consists of combined modality therapy with anthracycline-based chemotherapy, anti-CD20 antibody, and radiation therapy (RT). Curative approaches without RT typically utilize more intensive and/or protracted chemotherapy schedules. Anthracycline-based chemotherapy regimens are associated with a dose-dependent risk of left ventricular systolic dysfunction. We hypothesize that patients treated without RT, i.e., those who are treated with greater total chemotherapy cycles and hence cumulative anthracycline exposure, are at increased risk of cardiac mortality. Methods and Materials: The rate of cardiac-specific mortality (CSM) was analyzed in patients with stage I and II diffusemore » large B-cell lymphoma diagnosed between 1988 and 2004 by querying the National Cancer Institute Surveillance, Epidemiology, and End-Results database. Analyzable data included gender, age, race, stage, presence of extranodal disease, and RT administration. Results: A total of 15,454 patients met selection criteria; 6,021 (39%) patients received RT. The median follow-up was 36 months (range, 6-180 months). The median age was 64 years. The actuarial incidence rates of CSM at 5, 10, and 15 years were 4.3%, 9.0%, and 13.8%, respectively, in patients treated with RT vs. 5.9%, 10.8% and 16.1%, respectively, in patients treated without RT (p < 0.0001; hazard ratio, 1.35; 95% confidence interval [CI]: 1.16-1.56). The increase in cardiac deaths for patients treated without RT persisted throughout the follow-up period. On multivariate analysis, treatment without RT remained independently associated with an increased risk of CSM (Cox hazard ratio, 1.32; 95% CI: 1.13-1.54; p = 0.0005). Conclusions: Increased anthracycline exposure in patients treated only with chemotherapy regimens may result in an increase in cardiac deaths, detectable only through analysis of large sample sizes. Confirmatory evaluation through meta-analysis of randomized data and design of large prospective trials is warranted.« less

Is thyroid gland an organ at risk in breast cancer patients treated with locoregional radiotherapy? Results of a pilot study.

PubMed

Tunio, Mutahir Ali; Al Asiri, Mushabbab; Bayoumi, Yasser; Stanciu, Laura G; Al Johani, Naji; Al Saeed, Eyad Fawzi

2015-01-01

Aim was to evaluate the dose distribution within the thyroid gland its association with hypothyroidism in breast cancer (BC) patients receiving supraclavicular (SC) radiation therapy (RT). Consecutive 40 BC patients with baseline normal thyroid function tests (TFTs), were randomized into two groups: (a) Adjuvant chest wall/breast with SC-RT (20 patients) and (b) control group (adjuvant chest wall/breast RT only); 20 patients. The thyroid gland was contoured for each patient. Each patient's dose volume histogram (DVH), mean thyroid volume, the volume percentages of the thyroid absorbing respectively 5, 10, 20, 30, 40, and 50 Gy (V5, V10, V20, V30, V40, and V50), and Dmean (average dose in whole volume of thyroid) were then estimated. TFTs were performed at the time of the last follow-up and compared. Mean thyroid volume of cohort was 19.6 cm(3) (4.02-93.52) and Dmean of thyroid gland in SC-RT and control group was 25.8 Gy (16.4-52.2) and 5.6 Gy (0.7-12.8), respectively. Median values of V5, V10, V20, V30, V40, and V50 were 54%, 51%, 42.8%, 30.8%, 27.8%, and 7.64%, respectively, in SC-RT as compared to control group (V5;4.9%, V10;2.4%, V20;1.75%, V301%, V40;0%, and V50;0%, respectively) with P < 0.0001. At 52 months, a majority of patients (90%) had a normal thyroid function whereas four patients (10%) had hypothyroidism; 3/20 (15%) patients in SC-RT and 1/20 (5%) in control group with P < 0.001. Significant prognostic factors were; SC-RT (P = 0.001), V30 above 50% (P = 0.001), and smaller thyroid volume (P = 0.03). The risk of hypothyroidism in BC patients after SC-RT depends on the thyroid gland volume and V30 >50% and the risk can be minimized by thyroid gland shielding during RT.

Improving Outcomes for Esophageal Cancer using Proton Beam Therapy

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

Chuong, Michael D.; Hallemeier, Christopher L.; Jabbour, Salma K.

Radiation therapy (RT) plays an essential role in the management of esophageal cancer. Because the esophagus is a centrally located thoracic structure there is a need to balance the delivery of appropriately high dose to the target while minimizing dose to nearby critical structures. Radiation dose received by these critical structures, especially the heart and lungs, may lead to clinically significant toxicities, including pneumonitis, pericarditis, and myocardial infarction. Although technological advancements in photon RT delivery like intensity modulated RT have decreased the risk of such toxicities, a growing body of evidence indicates that further risk reductions are achieved with protonmore » beam therapy (PBT). Herein we review the published dosimetric and clinical PBT literature for esophageal cancer, including motion management considerations, the potential for reirradiation, radiation dose escalation, and ongoing esophageal PBT clinical trials. We also consider the potential cost-effectiveness of PBT relative to photon RT.« less

Improving Outcomes for Esophageal Cancer using Proton Beam Therapy.

PubMed

Chuong, Michael D; Hallemeier, Christopher L; Jabbour, Salma K; Yu, Jen; Badiyan, Shahed; Merrell, Kenneth W; Mishra, Mark V; Li, Heng; Verma, Vivek; Lin, Steven H

2016-05-01

Radiation therapy (RT) plays an essential role in the management of esophageal cancer. Because the esophagus is a centrally located thoracic structure there is a need to balance the delivery of appropriately high dose to the target while minimizing dose to nearby critical structures. Radiation dose received by these critical structures, especially the heart and lungs, may lead to clinically significant toxicities, including pneumonitis, pericarditis, and myocardial infarction. Although technological advancements in photon RT delivery like intensity modulated RT have decreased the risk of such toxicities, a growing body of evidence indicates that further risk reductions are achieved with proton beam therapy (PBT). Herein we review the published dosimetric and clinical PBT literature for esophageal cancer, including motion management considerations, the potential for reirradiation, radiation dose escalation, and ongoing esophageal PBT clinical trials. We also consider the potential cost-effectiveness of PBT relative to photon RT. Copyright © 2016 Elsevier Inc. All rights reserved.

Second harmonic generation for collagen I characterization in rectal cancer patients with and without preoperative radiotherapy

NASA Astrophysics Data System (ADS)

Blockhuys, Stéphanie; Agarwal, Nisha Rani; Hildesjö, Camilla; Jarlsfelt, Ingvar; Wittung-Stafshede, Pernilla; Sun, Xiao-Feng

2017-10-01

Rectal cancer is treated with preoperative radiotherapy (RT) to downstage the tumor, reduce local recurrence, and improve patient survival. Still, the treatment outcome varies significantly and new biomarkers are desired. Collagen I (Col-I) is a potential biomarker, which can be visualized label-free by second harmonic generation (SHG). Here, we used SHG to identify Col-I changes induced by RT in surgical tissue, with the aim to evaluate the clinical significance of RT-induced Col-I changes. First, we established a procedure for quantitative evaluation of Col-I by SHG in CDX2-stained tissue sections. Next, we evaluated Col-I properties in material from 31 non-RT and 29 RT rectal cancer patients. We discovered that the Col-I intensity and anisotropy were higher in the tumor invasive margin than in the inner tumor and normal mucosa, and RT increased and decreased the intensity in inner tumor and normal mucosa, respectively. Furthermore, higher Col-I intensity in the inner tumor was related to increased distant recurrence in the non-RT group but to longer survival in the RT group. In conclusion, we present a new application of SHG for quantitative analysis of Col-I in surgical material, and the first data suggest Col-I intensity as a putative prognostic biomarker in rectal cancer.

Genetic and Epigenetic Biomarkers for Recurrent Prostate Cancer After Radiotherapy

DTIC Science & Technology

2013-05-01

prostatectomy are urinary incontinence , erectile dysfunction, and typical post-operative complications. Radiation therapy (RT) shows several distinct...includes a low risk of urinary incontinence . Major disadvantage of external beam RT include a treatment course of 8-9 weeks. -50% of patients have some...this treatment include the risk of acute urinary retention. Currently, the level of PSA, clinical stage and the Gleason score are used to

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

Brooks, Jennifer D., E-mail: brooksj@mskcc.org; Boice, John D.; Stovall, Marilyn

Purpose: Our study examined whether reproductive and hormonal factors before, at the time of, or after radiation treatment for a first primary breast cancer modify the risk of radiation-induced second primary breast cancer. Methods and Materials: The Women's Environmental, Cancer and Radiation Epidemiology (WECARE) Study is a multicenter, population-based study of 708 women (cases) with asynchronous contralateral breast cancer (CBC) and 1399 women (controls) with unilateral breast cancer. Radiotherapy (RT) records, coupled with anthropomorphic phantom simulations, were used to estimate quadrant-specific radiation dose to the contralateral breast for each patient. Rate ratios (RR) and 95% confidence intervals (CI) were computedmore » to assess the relationship between reproductive factors and risk of CBC. Results: Women who were nulliparous at diagnosis and exposed to {>=}1 Gy to the contralateral breast had a greater risk for CBC than did matched unexposed nulliparous women (RR = 2.2; 95% CI, 1.2-4.0). No increased risk was seen in RT-exposed parous women (RR = 1.1; 95% CI, 0.8-1.4). Women treated with RT who later became pregnant (8 cases and 9 controls) had a greater risk for CBC (RR = 6.0; 95% CI, 1.3-28.4) than unexposed women (4 cases and 7 controls) who also became pregnant. The association of radiation with risk of CBC did not vary by number of pregnancies, history of breastfeeding, or menopausal status at the time of first breast cancer diagnosis. Conclusion: Nulliparous women treated with RT were at an increased risk for CBC. Although based on small numbers, women who become pregnant after first diagnosis also seem to be at an increased risk for radiation-induced CBC.« less

Dopamine Gene Profiling to Predict Impulse Control and Effects of Dopamine Agonist Ropinirole.

PubMed

MacDonald, Hayley J; Stinear, Cathy M; Ren, April; Coxon, James P; Kao, Justin; Macdonald, Lorraine; Snow, Barry; Cramer, Steven C; Byblow, Winston D

2016-07-01

Dopamine agonists can impair inhibitory control and cause impulse control disorders for those with Parkinson disease (PD), although mechanistically this is not well understood. In this study, we hypothesized that the extent of such drug effects on impulse control is related to specific dopamine gene polymorphisms. This double-blind, placebo-controlled study aimed to examine the effect of single doses of 0.5 and 1.0 mg of the dopamine agonist ropinirole on impulse control in healthy adults of typical age for PD onset. Impulse control was measured by stop signal RT on a response inhibition task and by an index of impulsive decision-making on the Balloon Analogue Risk Task. A dopamine genetic risk score quantified basal dopamine neurotransmission from the influence of five genes: catechol-O-methyltransferase, dopamine transporter, and those encoding receptors D1, D2, and D3. With placebo, impulse control was better for the high versus low genetic risk score groups. Ropinirole modulated impulse control in a manner dependent on genetic risk score. For the lower score group, both doses improved response inhibition (decreased stop signal RT) whereas the lower dose reduced impulsiveness in decision-making. Conversely, the higher score group showed a trend for worsened response inhibition on the lower dose whereas both doses increased impulsiveness in decision-making. The implications of the present findings are that genotyping can be used to predict impulse control and whether it will improve or worsen with the administration of dopamine agonists.

Effects of endurance, circuit, and relaxing training on cardiovascular risk factors in hypertensive elderly patients.

PubMed

Venturelli, Massimo; Cè, Emiliano; Limonta, Eloisa; Schena, Federico; Caimi, Barbara; Carugo, Stefano; Veicsteinas, Arsenio; Esposito, Fabio

2015-10-01

Recommendations for prevention of cardiovascular diseases (CVDs) risk factors among older adults highlighted the importance of exercise-based interventions, including endurance training (ET). However, the evidence of efficacy of other interventions based on short-bouts of exercise (circuit training, CT), and the practice of breath-control and meditation (relaxing training, RT) is growing. The aim of this study was to elucidate if CT or RT are equally effective in CVD risk factors reduction compared to ET. To this purpose, in 40 elderly participants, with clinically diagnosed grade 1 hypertension, resting blood pressure, blood glucose, and cholesterol levels, peak oxygen uptake ([Formula: see text]), mechanical efficiency and quality of life were evaluated before and after 12 weeks of ET, CT, and RT treatments. Resting blood pressure reduced significantly in all groups by ∼11 %. In ET, blood cholesterol levels (-18 %), [Formula: see text] (+8 %), mechanical efficiency (+9 %), and quality of life scores (+36 %) ameliorated. In CT blood glucose levels (-11 %), [Formula: see text] (+7 %) and quality of life scores (+35 %) were bettered. Conversely, in RT, the lower blood pressure went along only with an improvement in the mental component of quality of life (+42 %). ET and CT were both appropriate interventions to reduce CVDs risk factors, because blood pressure reduction was accompanied by decreases in blood glucose and cholesterol levels, increases in [Formula: see text], mechanical efficiency, and quality of life. Although RT influenced only blood pressure and quality of life, this approach would be an attractive alternative for old individuals unable or reluctant to carry out ET or CT.

Radiotherapy for benign disease; assessing the risk of radiation-induced cancer following exposure to intermediate dose radiation

PubMed Central

Hatfield, Paul; Prestwich, Robin JD; Shaffer, Richard E; Taylor, Roger E

2015-01-01

Most radiotherapy (RT) involves the use of high doses (>50 Gy) to treat malignant disease. However, low to intermediate doses (approximately 3–50 Gy) can provide effective control of a number of benign conditions, ranging from inflammatory/proliferative disorders (e.g. Dupuytren's disease, heterotopic ossification, keloid scarring, pigmented villonodular synovitis) to benign tumours (e.g. glomus tumours or juvenile nasopharyngeal angiofibromas). Current use in UK RT departments is very variable. This review identifies those benign diseases for which RT provides good control of symptoms with, for the most part, minimal side effects. However, exposure to radiation has the potential to cause a radiation-induced cancer (RIC) many years after treatment. The evidence for the magnitude of this risk comes from many disparate sources and is constrained by the small number of long-term studies in relevant clinical cohorts. This review considers the types of evidence available, i.e. theoretical models, phantom studies, epidemiological studies, long-term follow-up of cancer patients and those treated for benign disease, although many of the latter data pertain to treatments that are no longer used. Informative studies are summarized and considered in relation to the potential for development of a RIC in a range of key tissues (skin, brain etc.). Overall, the evidence suggests that the risks of cancer following RT for benign disease for currently advised protocols are small, especially in older patients. However, the balance of risk vs benefit needs to be considered in younger adults and especially if RT is being considered in adolescents or children. PMID:26462717

A high-protein diet with resistance exercise training improves weight loss and body composition in overweight and obese patients with type 2 diabetes.

PubMed

Wycherley, Thomas P; Noakes, Manny; Clifton, Peter M; Cleanthous, Xenia; Keogh, Jennifer B; Brinkworth, Grant D

2010-05-01

OBJECTIVE To evaluate the effects of two low-fat hypocaloric diets differing in the carbohydrate-to-protein ratio, with and without resistance exercise training (RT), on weight loss, body composition, and cardiovascular disease (CVD) risk outcomes in overweight/obese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A total of 83 men and women with type 2 diabetes (aged 56.1 +/- 7.5 years, BMI 35.4 +/- 4.6 kg/m(2)) were randomly assigned to an isocaloric, energy-restricted diet (female subjects 6 MJ/day, male subjects 7 MJ/day) of either standard carbohydrate (CON; carbohydrate:protein:fat 53:19:26) or high protein (HP; 43:33:22), with or without supervised RT (3 days/week) for 16 weeks. Body weight and composition, waist circumference (WC), and cardiometabolic risk markers were assessed. RESULTS Fifty-nine participants completed the study. There was a significant group effect (P or= 0.17). CONCLUSIONS An energy-restricted HP diet combined with RT achieved greater weight loss and more favorable changes in body composition. All treatments had similar improvements in glycemic control and CVD risk markers.

Long-Term Course of Patients With Stage IA Nodular Lymphocyte-Predominant Hodgkin Lymphoma: A Report From the German Hodgkin Study Group.

PubMed

Eichenauer, Dennis A; Plütschow, Annette; Fuchs, Michael; von Tresckow, Bastian; Böll, Boris; Behringer, Karolin; Diehl, Volker; Eich, Hans Theodor; Borchmann, Peter; Engert, Andreas

2015-09-10

The optimal treatment of stage IA nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is not well defined. Thus, we performed an analysis using the database of the German Hodgkin Study Group. The long-term outcome of 256 patients with stage IA NLPHL was evaluated. Patients had received combined-modality treatment (CMT; n = 72), extended-field radiotherapy (EF-RT; n = 49), involved-field radiotherapy (IF-RT; n = 108), or four weekly standard doses of rituximab (n = 27) within German Hodgkin Study Group clinical trial protocols between 1988 and 2009. The median age at NLPHL diagnosis was 39 years (range, 16 to 75 years). Most patients were male (76%). The whole patient group had a median follow-up of 91 months (CMT: 95 months; EF-RT: 110 months; IF-RT: 87 months; rituximab: 49 months). At 8 years, progression-free survival and overall survival rates were 88.5% and 98.6% for CMT, 84.3% and 95.7% for EF-RT, and 91.9% and 99.0% for IF-RT, respectively. Patients treated with rituximab had 4-year progression-free and overall survival rates of 81.0% and 100%, respectively. A second malignancy during the course of follow-up was diagnosed in 17 (6.6%) of 256 patients. A total of 12 deaths occurred. However, only one patient died from NLPHL. Tumor control in this analysis was equivalent with CMT, EF-RT, and IF-RT. Therefore, IF-RT, which is associated with the lowest risk for the development of toxic effects, should be considered as standard of care for patients with stage IA NLPHL. Rituximab alone is associated with an increased risk of relapse in this patient population. © 2015 by American Society of Clinical Oncology.

Radiation Therapy Noncompliance and Clinical Outcomes in an Urban Academic Cancer Center

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

Ohri, Nitin; Rapkin, Bruce D.; Guha, Chandan

Purpose: To examine associations between radiation therapy (RT) noncompliance and clinical outcomes. Methods and Materials: We reviewed all patients who completed courses of external beam RT with curative intent in our department from the years 2007 to 2012 for cancers of the head and neck, breast, lung, cervix, uterus, or rectum. Patients who missed 2 or more scheduled RT appointments (excluding planned treatment breaks) were deemed noncompliant. Univariate, multivariable, and propensity-matched analyses were performed to examine associations between RT noncompliance and clinical outcomes. Results: Of 1227 patients, 266 (21.7%) were noncompliant. With median follow-up of 50.9 months, 108 recurrences (8.8%) and 228more » deaths (18.6%) occurred. In univariate analyses, RT noncompliance was associated with increased recurrence risk (5-year cumulative incidence 16% vs 7%, P<.001), inferior recurrence-free survival (5-year actuarial rate 63% vs 79%, P<.001), and inferior overall survival (5-year actuarial rate 72% vs 83%, P<.001). In multivariable analyses that were adjusted for disease site and stage, comorbidity score, gender, ethnicity, race, and socioeconomic status (SES), RT noncompliance was associated with inferior recurrence, recurrence-free survival, and overall survival rates. Propensity score–matched models yielded results nearly identical to those seen in univariate analyses. Low SES was associated with RT noncompliance and was associated with inferior clinical outcomes in univariate analyses, but SES was not associated with inferior outcomes in multivariable models. Conclusion: For cancer patients being treated with curative intent, RT noncompliance is associated with inferior clinical outcomes. The magnitudes of these effects demonstrate that RT noncompliance can serve as a behavioral biomarker to identify high-risk patients who require additional interventions. Treatment compliance may mediate the associations that have been observed linking SES and clinical outcomes.« less

Evaluating the Impacts of NASA/SPoRT Daily Greenness Vegetation Fraction on Land Surface Model and Numerical Weather Forecasts

NASA Technical Reports Server (NTRS)

Bell, Jordan R.; Case, Jonathan L.; Molthan, Andrew L.

2011-01-01

The NASA Short-term Prediction Research and Transition (SPoRT) Center develops new products and techniques that can be used in operational meteorology. The majority of these products are derived from NASA polar-orbiting satellite imagery from the Earth Observing System (EOS) platforms. One such product is a Greenness Vegetation Fraction (GVF) dataset, which is produced from Moderate Resolution Imaging Spectroradiometer (MODIS) data aboard the NASA EOS Aqua and Terra satellites. NASA SPoRT began generating daily real-time GVF composites at 1-km resolution over the Continental United States (CONUS) on 1 June 2010. The purpose of this study is to compare the National Centers for Environmental Prediction (NCEP) climatology GVF product (currently used in operational weather models) to the SPoRT-MODIS GVF during June to October 2010. The NASA Land Information System (LIS) was employed to study the impacts of the new SPoRT-MODIS GVF dataset on land surface models apart from a full numerical weather prediction (NWP) model. For the 2010 warm season, the SPoRT GVF in the western portion of the CONUS was generally higher than the NCEP climatology. The eastern CONUS GVF had variations both above and below the climatology during the period of study. These variations in GVF led to direct impacts on the rates of heating and evaporation from the land surface. The second phase of the project is to examine the impacts of the SPoRT GVF dataset on NWP using the Weather Research and Forecasting (WRF) model. Two separate WRF model simulations were made for individual severe weather case days using the NCEP GVF (control) and SPoRT GVF (experimental), with all other model parameters remaining the same. Based on the sensitivity results in these case studies, regions with higher GVF in the SPoRT model runs had higher evapotranspiration and lower direct surface heating, which typically resulted in lower (higher) predicted 2-m temperatures (2-m dewpoint temperatures). The opposite was true for areas with lower GVF in the SPoRT model runs. These differences in the heating and evaporation rates produced subtle yet quantifiable differences in the simulated convective precipitation systems for the selected severe weather case examined.

PREDICTORS OF BIOCHEMICAL REMISSION AND RECURRENCE AFTER SURGICAL AND RADIATION TREATMENTS OF CUSHING DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS.

PubMed

Abu Dabrh, Abd Moain Abu; Singh Ospina, Naykky M; Al Nofal, Alaa; Farah, Wigdan H; Barrionuevo, Patricia; Sarigianni, Maria; Mohabbat, Arya B; Benkhadra, Khalid; Carranza Leon, Barbara G; Gionfriddo, Michael R; Wang, Zhen; Mohammed, Khaled; Ahmed, Ahmed T; Elraiyah, Tarig A; Haydour, Qusay; Alahdab, Fares; Prokop, Larry J; Murad, Mohammad Hassan

2016-04-01

We conducted a systematic review and meta-analysis to synthesize the evidence about predictors that may affect biochemical remission and recurrence after transsphenoidal surgery (TSS), radiosurgery (RS), and radiotherapy (RT) in Cushing disease. We searched multiple databases through December 2014 including original controlled and uncontrolled studies that enrolled patients with Cushing disease who received TSS (first-line), RS, or RT. We extracted data independently, in duplicates. Outcomes of interest were biochemical remission and recurrence. A meta-analysis was conducted using the random-effects model to estimate event rates with 95% confidence intervals (CIs). First-line TSS was associated with high remission (76% [95% CI, 72 to 79%]) and low recurrence rates (10% [95% CI, 6 to 16%]). Remission after TSS was higher in patients with microadenomas or positive-adrenocorticotropic hormone tumor histology. RT was associated with a high remission rate (RS, 68% [95% CI, 61 to 77%]; RT, 66% [95% CI, 58 to 75%]) but also with a high recurrence rate (RS, 32% [95% CI, 16 to 60%]; RT, 26% [95% CI, 14 to 48%]). Remission after RS was higher at short-term follow-up (≤2 years) and with high-dose radiation, while recurrence was higher in women and with lower-dose radiation. Remission was after RT in adults who received TSS prior to RT, and with lower radiation doses. There was heterogeneity (nonstandardization) in the criteria and cutoff points used to define biochemical remission and recurrence. First-line TSS is associated with high remission and low recurrence, while RS and RT are associated with reasonable remission rates but important recurrence rates. The current evidence warrants low confidence due to the noncomparative nature of the studies, high heterogeneity, and imprecision.

Racial Disparities in Intravenous Recombinant Tissue Plasminogen Activator Use Persist at Primary Stroke Centers.

PubMed

Aparicio, Hugo J; Carr, Brendan G; Kasner, Scott E; Kallan, Michael J; Albright, Karen C; Kleindorfer, Dawn O; Mullen, Michael T

2015-10-14

Primary stroke centers (PSCs) utilize more recombinant tissue plasminogen activator (rt-PA) than non-PSCs. The impact of PSCs on racial disparities in rt-PA use is unknown. We used data from the Nationwide Inpatient Sample from 2004 to 2010, limited to states that publicly reported hospital identity and race. Hospitals certified as PSCs by The Joint Commission were identified. Adults with a diagnosis of ischemic stroke were analyzed. Rt-PA use was defined by the International Classification of Diseases, 9th Revision procedure code 99.10. Discharges (304 152 patients) from 26 states met eligibility criteria, and of these 71.5% were white, 15.0% black, 7.9% Hispanic, and 5.6% other. Overall, 24.7% of white, 27.4% of black, 16.2% of Hispanic, and 29.8% of other patients presented to PSCs. A higher proportion received rt-PA at PSCs than non-PSCs in all race/ethnic groups (white 7.6% versus 2.6%, black 4.8% versus 2.0%, Hispanic 7.1% versus 2.4%, other 7.2% versus 2.5%, all P<0.001). In a multivariable model adjusting for year, age, sex, insurance, medical comorbidities, a diagnosis-related group-based mortality risk indicator, ZIP code median income, and hospital characteristics, blacks were less likely to receive rt-PA than whites at non-PSCs (odds ratio=0.58, 95% CI 0.50 to 0.67) and PSCs (odds ratio=0.63, 95% CI 0.54 to 0.74) and Hispanics were less likely than whites to receive rt-PA at PSCs (odds ratio=0.77, 95% CI: 0.63 to 0.95). In the fully adjusted model, interaction between race and presentation to a PSC for likelihood of receiving rt-PA did not reach significance (P=0.98). Racial disparities in intravenous rt-PA use were not reduced by presentation to PSCs. Black patients were less likely to receive thrombolytic treatment than white patients at both non-PSCs and PSCs. Hispanic patients were less likely to be seen at PSCs relative to white patients and were less likely to receive intravenous rt-PA in the fully adjusted model. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Risk-Seeking Versus Risk-Avoiding Investments in Noisy Periodic Environments

NASA Astrophysics Data System (ADS)

Navarro-Barrientos, J. Emeterio; Walter, Frank E.; Schweitzer, Frank

We study the performance of various agent strategies in an artificial investment scenario. Agents are equipped with a budget, x(t), and at each time step invest a particular fraction, q(t), of their budget. The return on investment (RoI), r(t), is characterized by a periodic function with different types and levels of noise. Risk-avoiding agents choose their fraction q(t) proportional to the expected positive RoI, while risk-seeking agents always choose a maximum value qmax if they predict the RoI to be positive ("everything on red"). In addition to these different strategies, agents have different capabilities to predict the future r(t), dependent on their internal complexity. Here, we compare "zero-intelligent" agents using technical analysis (such as moving least squares) with agents using reinforcement learning or genetic algorithms to predict r(t). The performance of agents is measured by their average budget growth after a certain number of time steps. We present results of extensive computer simulations, which show that, for our given artificial environment, (i) the risk-seeking strategy outperforms the risk-avoiding one, and (ii) the genetic algorithm was able to find this optimal strategy itself, and thus outperforms other prediction approaches considered.

Clinical Impact of Re-irradiation with Carbon-ion Radiotherapy for Lymph Node Recurrence of Gynecological Cancers.

PubMed

Shiba, Shintaro; Okonogi, Noriyuki; Kato, Shingo; Wakatsuki, Masaru; Kobayashi, Daijiro; Kiyohara, Hiroki; Ohno, Tatsuya; Karasawa, Kumiko; Nakano, Takashi; Kamada, Tadashi

2017-10-01

To evaluate the safety and efficacy of re-irradiation with carbon-ion radiotherapy (C-ion RT) for lymph node recurrence of gynecological cancers after definitive radiotherapy. Data regarding patients with unresectable and isolated recurrent lymph node from gynecological cancer after definitive radiotherapy were analyzed. Total dose of C-ion RT was 48-57.6 Gy (RBE) in 12 or 16 fractions. Sixteen patients received re-irradiation by C-ion RT were analyzed. Median follow-up was 37 months. Median tumor size was 27 mm. None developed Grade 1 or higher acute toxicities and Grade 3 or higher late toxicities. The 3-year overall survival, local control and disease-free survival rates after C-ion RT were 74%, 94% and 55%, respectively. Re-irradiation with C-ion RT for lymph node recurrence of gynecological cancers after definitive radiotherapy can be safe and effective. This result suggested that C-ion RT could be a curative treatment option for conventionally difficult-to-cure patients. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

WE-E-BRE-05: Ensemble of Graphical Models for Predicting Radiation Pneumontis Risk

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

Lee, S; Ybarra, N; Jeyaseelan, K

Purpose: We propose a prior knowledge-based approach to construct an interaction graph of biological and dosimetric radiation pneumontis (RP) covariates for the purpose of developing a RP risk classifier. Methods: We recruited 59 NSCLC patients who received curative radiotherapy with minimum 6 month follow-up. 16 RP events was observed (CTCAE grade ≥2). Blood serum was collected from every patient before (pre-RT) and during RT (mid-RT). From each sample the concentration of the following five candidate biomarkers were taken as covariates: alpha-2-macroglobulin (α2M), angiotensin converting enzyme (ACE), transforming growth factor β (TGF-β), interleukin-6 (IL-6), and osteopontin (OPN). Dose-volumetric parameters were alsomore » included as covariates. The number of biological and dosimetric covariates was reduced by a variable selection scheme implemented by L1-regularized logistic regression (LASSO). Posterior probability distribution of interaction graphs between the selected variables was estimated from the data under the literature-based prior knowledge to weight more heavily the graphs that contain the expected associations. A graph ensemble was formed by averaging the most probable graphs weighted by their posterior, creating a Bayesian Network (BN)-based RP risk classifier. Results: The LASSO selected the following 7 RP covariates: (1) pre-RT concentration level of α2M, (2) α2M level mid- RT/pre-RT, (3) pre-RT IL6 level, (4) IL6 level mid-RT/pre-RT, (5) ACE mid-RT/pre-RT, (6) PTV volume, and (7) mean lung dose (MLD). The ensemble BN model achieved the maximum sensitivity/specificity of 81%/84% and outperformed univariate dosimetric predictors as shown by larger AUC values (0.78∼0.81) compared with MLD (0.61), V20 (0.65) and V30 (0.70). The ensembles obtained by incorporating the prior knowledge improved classification performance for the ensemble size 5∼50. Conclusion: We demonstrated a probabilistic ensemble method to detect robust associations between RP covariates and its potential to improve RP prediction accuracy. Our Bayesian approach to incorporate prior knowledge can enhance efficiency in searching of such associations from data. The authors acknowledge partial support by: 1) CREATE Medical Physics Research Training Network grant of the Natural Sciences and Engineering Research Council (Grant number: 432290) and 2) The Terry Fox Foundation Strategic Training Initiative for Excellence in Radiation Research for the 21st Century (EIRR21)« less

Comparison of 36 Gy, 20 Gy, or No Radiation Therapy After 6 Cycles of EBVP Chemotherapy and Complete Remission in Early-Stage Hodgkin Lymphoma Without Risk Factors: Results of the EORT-GELA H9-F Intergroup Randomized Trial.

PubMed

Thomas, José; Fermé, Christophe; Noordijk, Evert M; Morschhauser, Franck; Girinsky, Théodore; Gaillard, Isabelle; Lugtenburg, Pieternella J; André, Marc; Lybeert, Marnix L M; Stamatoullas, Aspasia; Beijert, Max; Hélias, Philippe; Eghbali, Houchingue; Gabarre, Jean; van der Maazen, Richard W M; Jaubert, Jérôme; Bouabdallah, Krimo; Boulat, Olivier; Roesink, Judith M; Christian, Bernard; Ong, Francisca; Bordessoule, Dominique; Tertian, Gérard; Gonzalez, Hugo; Vranovsky, Andrej; Quittet, Philippe; Tirelli, Umberto; de Jong, Daphne; Audouin, Josée; Aleman, Berthe M P; Henry-Amar, Michel

2018-04-01

While patients with early-stage Hodgkin lymphoma (HL) have an excellent outcome with combined treatment, the radiation therapy (RT) dose and treatment with chemotherapy alone remain questionable. This noninferiority trial evaluates the feasibility of reducing the dose or omitting RT after chemotherapy. Patients with untreated supradiaphragmatic HL without risk factors (age ≥ 50 years, 4 to 5 nodal areas involved, mediastinum-thoracic ratio ≥ 0.35, and erythrocyte sedimentation rate ≥ 50 mm in first hour without B symptoms or erythrocyte sedimentation rate ≥ 30 mm in first hour with B symptoms) were eligible for the trial. Patients in complete remission after chemotherapy were randomized to no RT, low-dose RT (20 Gy in 10 fractions), or standard-dose involved-field RT (36 Gy in 18 fractions). The limit of noninferiority was 10% for the difference between 5-year relapse-free survival (RFS) estimates. From September 1998 to May 2004, 783 patients received 6 cycles of epirubicin, bleomycin, vinblastine, and prednisone; 592 achieved complete remission or unconfirmed complete remission, of whom 578 were randomized to receive 36 Gy (n=239), 20 Gy of involved-field RT (n=209), or no RT (n=130). Randomization to the no-RT arm was prematurely stopped (≥20% rate of inacceptable events: toxicity, treatment modification, early relapse, or death). Results in the 20-Gy arm (5-year RFS, 84.2%) were not inferior to those in the 36-Gy arm (5-year RFS, 88.6%) (difference, 4.4%; 90% confidence interval [CI] -1.2% to 9.9%). A difference of 16.5% (90% CI 8.0%-25.0%) in 5-year RFS estimates was observed between the no-RT arm (69.8%) and the 36-Gy arm (86.3%); the hazard ratio was 2.55 (95% CI 1.44-4.53; P<.001). The 5-year overall survival estimates ranged from 97% to 99%. In adult patients with early-stage HL without risk factors in complete remission after epirubicin, bleomycin, vinblastine, and prednisone chemotherapy, the RT dose may be limited to 20 Gy without compromising disease control. Omitting RT in these patients may jeopardize the treatment outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

Symptoms of ADHD Affect Intrasubject Variability in Youths with Autism Spectrum Disorder: An Ex-Gaussian Analysis.

PubMed

Hwang-Gu, Shoou-Lian; Lin, Hsiang-Yuan; Chen, Yu-Chi; Tseng, Yu-Han; Hsu, Wen-Yau; Chou, Miao-Chun; Chou, Wen-Jun; Wu, Yu-Yu; Gau, Susan Shur-Fen

2018-05-30

Increased intrasubject variability in reaction times (RT-ISV) is frequently found in individuals with autism spectrum disorder (ASD). However, how dimensional attention deficit/hyperactivity disorder (ADHD) symptoms impact RT-ISV in individuals with ASD remains elusive. We assessed 97 high-functioning youths with co-occurring ASD and ADHD (ASD+ADHD), 124 high-functioning youths with ASD only, 98 youths with ADHD only, and 249 typically developing youths, 8-18 years of age, using the Conners Continuous Performance Test (CCPT). We compared the conventional CCPT parameters (omission errors, commission errors, mean RT and RT standard error (RTSE) as well as the ex-Gaussian parameters of RT (mu, sigma, and tau) across the four groups. We also conducted regression analyses to assess the relationships between RT indices and symptoms of ADHD and ASD in the ASD group (i.e., the ASD+ADHD and ASD-only groups). The ASD+ADHD and ADHD-only groups had higher RT-ISV than the other two groups. RT-ISV, specifically RTSE and tau, was significantly associated with ADHD symptoms rather than autistic traits in the ASD group. Regression models also revealed that sex partly accounted for RT-ISV variance in the ASD group. A post hoc analysis showed girls with ASD had higher tau and RTSE values than their male counterparts. Our results suggest that RT-ISV is primarily associated with co-occurring ADHD symptoms/diagnosis in children and adolescents with ASD. These results do not support the hypothesis of response variability as a transdiagnostic phenotype for ASD and ADHD and warrant further validation at a neural level.

Balancing risk and benefit in early-stage classical Hodgkin lymphoma.

PubMed

Bröckelmann, Paul J; Sasse, Stephanie; Engert, Andreas

2018-04-12

With defined chemotherapy and radiotherapy (RT) and risk-adapted treatment, early-stage classical Hodgkin lymphoma (HL) has become curable in a majority of patients. Hence, a major current goal is to reduce treatment-related toxicity while maintaining long-term disease control. Patients with early-stage favorable disease (ie, limited stage without risk factors [RFs]) are frequently treated with 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (2×ABVD) followed by 20-Gy involved-field or involved-site RT (IF/ISRT). In patients with early-stage unfavorable disease (ie, limited stage with RFs), 4 cycles of chemotherapy are usually consolidated with 30-Gy IF/ISRT. Compared with 4×ABVD, 2 cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (2×BEACOPP escalated ) followed by 2×ABVD improved 5-year progression-free survival (PFS), with similar 5-year overall survival. Recently, treatment strategies based on [ 18 F]fluorodeoxyglucose positron emission tomography (PET) response were evaluated. In early-stage unfavorable HL, a majority of patients achieved a negative interim PET after 2×ABVD and an excellent outcome after 4×ABVD, whereas in those with a positive interim PET, 2×BEACOPP escalated improved 5-year PFS. Furthermore, a PET-guided RT approach was evaluated to decrease long-term toxicity. Although both the RAPID and H10 trials reported poorer disease control without RT, PET-guided omission of RT can constitute a valid therapeutic option in patients with an increased risk of RT-associated toxicity (eg, because of sex, age, or disease localization). Implementation of drugs such as the anti-CD30 antibody-drug conjugate brentuximab vedotin or the anti-programmed death 1 antibodies nivolumab or pembrolizumab might allow further reduction of overall mortality and improve quality of life in affected patients. © 2018 by The American Society of Hematology.

Risk stratification for death and all-cause hospitalization in heart failure clinic outpatients.

PubMed

Hummel, Scott L; Ghalib, Hussam H; Ratz, David; Koelling, Todd M

2013-11-01

Most heart failure (HF) risk stratification models were developed for inpatient use, and available outpatient models use a complex set of variables. We hypothesized that routinely collected clinical data could predict the 6-month risk of death and all-cause medical hospitalization in HF clinic outpatients. Using a quality improvement database and multivariable Cox modeling, we derived the Heart Failure Patient Severity Index (HFPSI) in the University of Michigan HF clinic (UM cohort, n = 1,536; 314 reached primary outcome). We externally validated the HFPSI in the Ann Arbor Veterans' Affairs HF clinic (VA cohort, n = 445; 106 outcomes) and explored "real-time" HFPSI use (VA-RT cohort, n = 486; 141 outcomes) by tracking VA patients for 6 months from their most recently calculated HFPSI, rather than using an arbitrary start date for the cohort. The HFPSI model included blood urea nitrogen, B-type natriuretic peptide, New York Heart Association class, diabetes status, history of atrial fibrillation/flutter, and all-cause hospitalization within the prior 1 and 2 to 6 months. The concordance c statistics in the UM/VA/VA-RT cohorts were 0.71/0.68/0.74. Kaplan-Meier curves and log-rank testing demonstrated excellent risk stratification, particularly between a large, low-risk group (40% of patients, 6-month event rates in the UM/VA/VA-RT cohorts 8%/12%/12%) and a small, high-risk group (10% of patients, 6-month event rates in the UM/VA/VA-RT cohorts 57%/58%/79%). The HFPSI uses readily available data to predict the 6-month risk of death and/or all-cause medical hospitalization in HF clinic outpatients and could potentially help allocate specialized HF resources within health systems. © 2013.

Adjuvant Therapy in Early-Stage Endometrial Cancer: A Systematic Review of the Evidence, Guidelines, and Clinical Practice in the U.S.

PubMed Central

Latif, Nawar A.; Haggerty, Ashley; Jean, Stephanie; Lin, Lilie

2014-01-01

Endometrial cancer is the most common gynecologic malignancy in the U.S., with an increasing incidence likely secondary to the obesity epidemic. Surgery is usually the primary treatment for early stage endometrial cancer, followed by adjuvant therapy in selected cases. This includes radiation therapy [RT] with or without chemotherapy, based on stratification of patients into categories dependent on their future recurrence risk. Several prospective trials (PORTEC-1, GOG#99, and PORTEC-2) have shown that the use of adjuvant RT in the intermediate risk (IR) and the high-intermediate risk (HIR) groups decreases locoregional recurrence (LRR) but has no effect on overall survival. The ad hoc analyses from these studies have shown that an even larger LRR risk reduction was seen within the HIR group compared with the IR group. Vaginal brachytherapy is as good as external beam radiotherapy in controlling vaginal relapse where the majority of recurrence occur, and with less toxicity. In the high-risk group, multimodality therapy (chemotherapy and RT) may play a significant role. Although adjuvant RT has been evaluated in many cost-effectiveness studies, high-quality data in this area are still lacking. The uptake of the above prospective trial results in the U.S. has not been promising. Factors that are driving current practices and defining quality-of-care measures for patients with early-stage disease are what future studies need to address. PMID:24821823

A UK survey of driving behaviour, fatigue, risk taking and road traffic accidents

PubMed Central

Smith, Andrew P

2016-01-01

Objective The aim of the present research was to examine associations between poor driving behaviour (DB), driving when fatigued (DF), risk taking (RT) and road traffic accidents (RTAs). Design The study involved a cross-sectional online survey of clients of an insurance company. The survey measured DB (speeding, distraction, lapses of attention and aggression), RT and frequency of driving when fatigued (DF, driving late at night, prolonged driving, driving after a demanding working day and driving with a cold). Demographic, lifestyle, job characteristics and psychosocial factors were also measured and used as covariates. Setting Cardiff, UK. Sample 3000 clients of an insurance company agreed to participate in the study, and 2856 completed the survey (68% woman, 32% man; mean age: 34 years, range 18–74 years). Main outcome measures The outcomes were RTAs (requiring medical attention; not requiring medical attention), where the person was the driver. Results Factor analyses showed that DB, RT and fatigue loaded on independent factors. Logistic regressions showed that poor DB, frequently DF and taking risks predicted medical and non-medical RTAs. These effects were additive and those who reported poor DB, driving when fatigue and taking risks were twice as likely to have an RTA. These effects remained significant when demographic, lifestyle, medical, driving, work and psychosocial factors were covaried. Conclusions Poor DB, DF and RT predict RTAs. There are now short measuring instruments that can assess these, and driver education programmes must increase awareness of these risk factors. PMID:27540100

The effect of preventive oral care on treatment outcomes of a cohort of oral cancer patients.

PubMed

Morais, Marilia Oliveira; Elias, Marcela Ramos Abrahão; Leles, Cláudio Rodrigues; Dourado Pinezi, Juliana Castro; Mendonça, Elismauro Francisco

2016-04-01

The purpose of this study was to assess patient adherence to an oral preventive measures (OPM) protocol and its impact on cancer treatment outcomes. A retrospective cohort of oral cancer of 133 patients submitted to radiotherapy (RT) was selected, excluding those with metastasis. Patients were grouped according to their local tumor response after finishing RT (favorable or unfavorable) and adherence to an OPM (none, ≤6 months, and >6 months). OPM included education and counseling about adverse effects, elimination of infection foci, restorative procedures, fluoride therapy, oral rehydration, and maintenance and supervision of oral hygiene throughout treatment. Clinical and pathological characteristics were recorded, and patient outcomes (frequency of adverse effects, RT interruption, and overall survival) were analyzed. Patients with higher adherence to the OPM had greater occurrence of RT interruption as a consequence of symptoms (p = 0.01); however, these patients were more likely to complete the established RT protocol (p = 0.02). Overall survival (p = 0.01) was higher in the group with higher adherence. This study suggests that the implementation of oral preventive measures may contribute to improving the prognosis of squamous cell carcinoma (SCC) treatment by reducing the negative impact of oral complications.

Railway train versus motor vehicle collisions: a comparative study of injury severity and patterns.

PubMed

Kligman, M D; Knotts, F B; Buderer, N M; Kerwin, A J; Rodgers, J F

1999-11-01

This study compares the demographics, injury severity, resource use, and injury patterns of patients involved in railway train-motor vehicle (RT-MV) to motor vehicle-motor vehicle (MV-MV) collisions. Retrospective trauma registry review of 74 RT-MV and 1,931 MV-MV consecutive patients, age more than 14 years, presenting to two Level I trauma centers, January of 1991 to May of 1998. Compared with MV-MV, RT-MV had significantly more males (72% vs. 54%), higher mortality (15% vs. 7%), higher Injury Severity Score (median, 20 vs. 9), longer intensive care unit length of stay (1.7 vs. 0.04 days), and longer hospital length of stay (7.5 vs. 4 days). RT-MV patients had a higher percentage of scalp/facial lacerations; intracranial hemorrhage; hemothorax and pneumothorax; fractures of the rib/sternum, upper extremity, skull, and face; and lung, splenic, and renal injuries. After adjusting for the difference in Injury Severity Score between groups, the only remaining significant group difference was the odds of a scalp/facial laceration. RT-MV collisions are a marker for more severe injuries, but not a different pattern of injury, compared with MV-MV collisions.

Impact of initial local therapy on survival in men later receiving chemotherapy for prostate cancer: a population-based, propensity-weighted multivariable analysis.

PubMed

Zabell, Joseph R; Adejoro, Oluwakayode; Jarosek, Stephanie L; Elliott, Sean P; Konety, Badrinath R

2016-10-01

Prostate cancer remains a common disease that is frequently treated with multimodal therapy. The goal of this study was to assess the impact of treatment of the primary tumor on survival in men who go onto receive chemotherapy for prostate cancer. Using surveillance, epidemiology and end results (SEER)-Medicare data from 1992 to 2009, we identified a cohort of 1614 men who received chemotherapy for prostate cancer. Primary outcomes were prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM). We compared survival among men who had previously undergone radical prostatectomy (RP), radiation therapy (RT), or neither of these therapies. Propensity score adjusted Cox proportional hazard models and weighted Kaplan-Meier curves were used to assess survival. Compared to men who received no local treatment, PCSM was lower for men who received RP ± RT (HR 0.65, p < 0.01) and for those who received RT only (HR 0.79, p < 0.05). Patients receiving neither RP nor RT demonstrated higher PCSM and ACM than those receiving treatment in a weighted time-to-event analysis. Men who received RP + RT had longer mean time from diagnosis to initiation of chemotherapy (100.7 ± 47.7 months) than men with no local treatment (48.8 ± 35.0 months, p < 0.05). In patients who go on to receive chemotherapy, treatment of the primary tumor for prostate cancer appears to confer a survival advantage over those who do not receive primary treatment. These data suggest continued importance for local treatment of prostate cancer, even in patients at high risk of failing local therapy.

Multicenter, Phase 3 Trial Comparing Selenium Supplementation With Observation in Gynecologic Radiation Oncology

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

Muecke, Ralph; Schomburg, Lutz; Glatzel, Michael

Purpose: We assessed whether adjuvant supplementation with selenium improves the selenium status and reduces side effects of patients treated by radiotherapy (RT) for cervical and uterine cancer. Methods and Materials: Whole-blood selenium concentrations were measured in patients with cervical cancer (n = 11) and uterine cancer (n = 70) after surgical treatment, during RT, at the end of RT, and 6 weeks after RT. Patients with initial selenium concentrations of less than 84{mu}g/L were randomized before RT either to receive 500 {mu}g of selenium (in the form of sodium selenite [selenase (registered) , biosyn Arzneimittel GmbH, Fellbach, Germany]) by mouthmore » on the days of RT and 300 {mu}g of selenium on the days without RT or to receive no supplement during RT. The primary endpoint of this multicenter Phase 3 study was to assess the efficiency of selenium supplementation during RT; the secondary endpoint was to decrease radiation-induced diarrhea and other RT-dependent side effects. Results: A total of 81 patients were randomized. We enrolled 39 in the selenium group (SG) and 42 in the control group (CG). Selenium levels did not differ between the SG and CG upon study initiation but were significantly higher in the SG at the end of RT. The actuarial incidence of diarrhea of Grade 2 or higher according to Common Toxicity Criteria (version 2) in the SG was 20.5% compared with 44.5% in the CG (p = 0.04). Other blood parameters, Eastern Cooperative Oncology Group performance status, and self-reported quality of life were not different between the groups. Conclusions: Selenium supplementation during RT is effective in improving blood selenium status in selenium-deficient cervical and uterine cancer patients and reduces the number of episodes and severity of RT-induced diarrhea.« less

Toxoplasma gondii infections in chickens - performance of various antibody detection techniques in serum and meat juice relative to bioassay and DNA detection methods.

PubMed

Schares, G; Koethe, M; Bangoura, B; Geuthner, A-C; Randau, F; Ludewig, M; Maksimov, P; Sens, M; Bärwald, A; Conraths, F J; Villena, I; Aubert, D; Opsteegh, M; Van der Giessen, J

2018-05-19

Chickens, especially if free-range, are frequently exposed to Toxoplasma gondii, and may represent an important reservoir for T. gondii. Poultry products may pose a risk to humans, when consumed undercooked. In addition, chickens are regarded as sensitive indicators for environmental contamination with T. gondii oocysts and have been used as sentinels. The aim of the present study was to determine the suitability of commonly used antibody detection methods, i.e. the modified agglutination test (MAT), IFAT and ELISA to detect T. gondii-infected chickens. Samples of experimentally and naturally infected chickens were used. The infection state of all chickens was determined by Magnetic-Capture (MC-) real-time PCR (RT PCR). Naturally exposed chickens were additionally examined by mouse bioassay and conventional RT PCR on acidic pepsin digests (PD-RT PCR). Blood serum and meat juice of various sources were tested for antibodies to T. gondii. In naturally infected chickens, there was substantial agreement between the mouse bioassay and MC-RT PCR or the mouse bioassay and conventional PD-RT PCR. PD-RT PCR was slightly more sensitive than MC-RT PCR, as all (26/26) bioassay-positive chickens also tested positive in at least one of the tissues tested (heart, drumstick). By MC-RT PCR, 92.3% (24/26) of the naturally infected bioassay-positive chickens were positive. The diagnostic sensitivity of MC-RT PCR was clearly related to the organ examined. Based on a quantitative assessment of the MC-RT PCR results in experimentally infected chickens, brain and heart tissues harbored an at least 100 times higher parasite concentration than breast, thigh or drumstick musculature. In naturally infected chickens, only three out of 24 birds, which were MC-RT PCR-positive in heart samples, also tested positive in drumstick musculature. Under experimental conditions, the agreement between MC-RT PCR and the serological techniques revealed 100% diagnostic sensitivity and specificity. Under field conditions, examinations of sera by ELISA, IFAT and MAT showed good performance in identifying chickens that were positive in either a mouse bioassay, MC-RT PCR, or PD-RT PCR as illustrated by diagnostic sensitivities of 87.5%, 87.5% and 65.2%, respectively, and diagnostic specificities of 86.2%, 82.8% and 100%, respectively. The examination of meat juice samples from breast, drumstick or heart musculature revealed similar or even better results in the ELISA. The results in the MAT with meat juice from breast musculature were less consistent than those of ELISA and IFAT because a number of negative chickens tested false-positive in the MAT. The MAT performed similar to ELISA and IFAT when applied to test meat juice samples collected from heart, thigh or drumstick musculature. Copyright © 2018 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

Perineural invasion is associated with increased relapse after external beam radiotherapy for men with low-risk prostate cancer and may be a marker for occult, high-grade cancer.

PubMed

Beard, C J; Chen, M H; Cote, K; Loffredo, M; Renshaw, A A; Hurwitz, M; D'Amico, A V

2004-01-01

To investigate the risk of postradiotherapy prostate-specific antigen (PSA) failure on the basis of pretreatment risk factors in prostate cancer patients with and without perineural invasion (PNI) in prostate biopsy specimens and to explain the observation that otherwise low-risk patients with PNI experience decreased freedom from PSA failure after external beam radiotherapy (RT). The study cohort consisted of 381 patients who underwent RT between 1989 and 2000 for clinically localized prostate cancer. A single genitourinary pathologist scored the absence or presence of PNI on all prostate biopsy specimens. Patients were divided into low-, intermediate- and high-risk subgroups on the basis of their 1992 American Joint Committee on Cancer T-stage, pretreatment PSA level, and Gleason score. Cox regression uni- and multivariate analyses were performed to evaluate whether the presence or absence of PNI in the biopsy specimen was a predictor of the time to post-RT PSA failure for patients in each pretreatment risk group. PSA failure was defined using the American Society for Therapeutic Radiology and Oncology consensus definition. Actuarial PSA failure-free survival was estimated using the Kaplan-Meier method, and comparisons were performed using the log-rank test. Cox regression univariate analysis revealed that PNI was a significant predictor of the time to PSA failure in the low-risk (p = 0.04) and high-risk (p = 0.03) cohorts. The 5-year PSA failure-free survival rate was 50% vs. 80% (p = 0.04) in low-risk patients, 70% vs. 75% (p = 0.72) in intermediate-risk patients, and 29% vs. 53% (p = 0.03) in high-risk patients with and without PNI, respectively. Cox regression multivariate analysis within the high-risk group revealed that a PSA level > or =20 ng/mL (p = 0.01) and Gleason score > or =8 (p = 0.02), but not PNI, were the only significant predictors of the time to PSA failure after RT. However, an association was found between the presence of PNI in the needle biopsy specimen and a biopsy Gleason score of 8-10 (p = 0.06). The association was stronger between the presence of PNI in the needle biopsy specimen and a biopsy Gleason score of 7-10 (p = 0. 033). A decrement in PSA outcome after RT for low-risk patients with PNI-positive biopsy specimens was found. The association between PNI and high Gleason score provides a possible explanation for the loss of statistical significance of PNI in the Cox regression multivariate analysis of the high-risk cohort. The data suggest that PNI found in the biopsy specimen of an otherwise low-risk patient predicts for occult high-grade disease that is missed owing to the sampling error associated with prostate biopsy. The association between PNI and a high Gleason score argues for the use of more aggressive therapy, such as hormonal therapy with RT and/or dose escalation, in these select patients.

Second Malignant Neoplasms and Cause of Death in Patients With Germ Cell Cancer: A Danish Nationwide Cohort Study.

PubMed

Kier, Maria G; Hansen, Merete K; Lauritsen, Jakob; Mortensen, Mette S; Bandak, Mikkel; Agerbaek, Mads; Holm, Niels V; Dalton, Susanne O; Andersen, Klaus K; Johansen, Christoffer; Daugaard, Gedske

2016-12-01

Patients given systemic treatment for testicular germ cell cancer (GCC) are at increased risk for a second malignant neoplasm (SMN). Previous studies on SMN and causes of death lacked information on the exact treatment applied or were based on patients receiving former treatment options. To evaluate the treatment-specific risks for SMN and death in a nationwide population-based cohort of patients with GCC treated with current standard regimens. This study examined a Danish nationwide cohort of 5190 men with GCC who entered the Danish Testicular Cancer database between January 1, 1984, and December 31, 2007. Treatment results were compared with a randomly sampled, age-stratified, population-based control group. Cases of gonadal and extragonadal primary were included in the nationwide cohort. The treatments were surveillance only; retroperitoneal radiotherapy (RT); bleomycin, etoposide, and cisplatin (BEP); or more than 1 line of treatment (MTOL). Cumulative incidence and hazard ratios (HRs) for SMN and death calculated by the Cox proportional hazards model were compared with those of age-matched controls. The study population comprised 2804 patients with seminoma and 2386 with nonseminoma. The median follow-up was 14.4 years (interquartile range, 8.6-20.5 years). The 20-year cumulative incidence of SMN with death as a competing risk was 7.8% (surveillance), 7.6% (BEP), 13.5% (RT), 9.2% (MTOL), and 7.0% (controls). We found no increased risk for SMN after surveillance, while the HRs were 1.7 (95% CI, 1.4-2.0), 1.8 (95% CI, 1.5-2.3), and 3.7 (95% CI, 2.5-5.5), respectively, after BEP, RT, and MTOL. Mortality owing to non-GCC causes was decreased after surveillance, but increased by 1.3 times after BEP and RT and by 2.6 times after MTOL. Excess mortality due to SMN was found after BEP (HR, 1.6; 95% CI, 1.2-2.2), RT (HR, 2.1; 95% CI, 1.5-2.9), and MTOL (HR, 5.8; 95% CI, 3.6-9.6). We found no increased risk for SMN or death among patients undergoing surveillance only. The risks for SMN and death due to SMN were increased after BEP alone, RT alone, and MTOL. Approaches to define patients who might benefit from less intensive treatment are needed.

Clinical outcome after high-precision radiotherapy for skull base meningiomas: Pooled data from three large German centers for radiation oncology.

PubMed

Combs, Stephanie E; Farzin, Mostafa; Boehmer, Julia; Oehlke, Oliver; Molls, Michael; Debus, Jürgen; Grosu, Anca-Ligia

2018-05-01

To evaluate outcome in patients with base of skull meningiomas treated with modern high precision radiation therapy (RT) techniques. 927 patients from three centers were treated with either radiosurgery or fractionated high-precision RT for meningiomas. Treatment planning was based on CT and MRI following institutional guidelines. For radiosurgery, a median dose of 13 Gy was applied, for fractionated treatments, a median dose of 54 Gy in 1.8 Gy single fractions was prescribed. Follow-up included a clinical examination as well as contrast-enhanced imaging. All patients were followed up prospectively after radiotherapy in the three departments within a strict follow-up regimen. The median follow-up time was 81 months (range 1-348 months). Median local control was 79 months (range 1-348 months). Local control (LC) was 98% at 1 year, 94% at 3 years, 92% at 5 years and 86% at 10 years. There was no difference between radiosurgery and fractionated RT. We analyzed the influence of higher doses on LC and could show that dose did not impact LC. Moreover, there was no difference between 54 Gy and 57.6 Gy in the fractionated group. Side effects were below 5% in both groups without any severe treatment-related complications. Based on the pooled data analysis this manuscript provides a large series of meningiomas of the skull base treated with modern high precision RT demonstrating excellent local control and low rates of side effects. Such data support the recommendation of RT for skull base meningiomas in the interdisciplinary tumor board discussions. The strong role of RT must influence treatment recommendations keeping in mind the individual risk-benefit profile of treatment alternatives. Copyright © 2018 Elsevier B.V. All rights reserved.

Neoadjuvant Radiotherapy: A Risk Factor for Short-Term Wound Complications after Radical Resection for Rectal Cancer?

PubMed

Holubar, Stefan D; Brickman, Rachel K; Greaves, Spencer W; Ivatury, S Joga

2016-08-01

Neoadjuvant radiotherapy (RT) for rectal cancer may increase wound complications after oncologic proctectomy. We aimed to assess the relationship between neoadjuvant RT and 30-day wound complications after radical surgery for rectal cancer. We identified rectal cancer patients (International Classification of Diseases, revision-9 [ICD-9] code 154.1) who underwent radical resection, using NSQIP from 2005 to 2010. Patients were stratified into preoperative radiation vs no radiation groups. Our primary outcome was any wound complication. The association between preoperative RT and postoperative wound complication rate was assessed by univariate, multivariable, and propensity score analyses. Of 242,670 colorectal cases, 6,297 patients were included. Of these, 2,476 (39%) received RT within 90 days preoperatively. The RT group, compared with the no RT group, received more chemotherapy within 30 days preoperatively (15.0% vs 2.5%, p < 0.0001), and had less laparoscopic (18.9% vs 25.1%, p < 0.0001) or sphincter-preserving surgery (61.8% vs 67.1%, p < 0.0001). In the univariate analyses, there was no difference in wound complications (19.6% vs 18.7%, p = 0.42) between groups. Similarly, there was no difference in overall complications (29.6% vs 29.8%, p = 0.89), return to operating room (6.7% vs 6.7%, p = 0.96), or length of stay (8.4 vs 8.4 days, p = 0.72) between the RT and no RT groups, respectively. The mortality rate in the RT group was lower on univariate analysis (0.7% vs 1.4%, p = 0.008), but was not significantly different in the multivariable analyses. Multivariable and propensity score analyses were consistent with the lack of association between preoperative RT and postoperative wound complications. Neoadjuvant radiotherapy does not appear to be an independent risk factor for wound complications after radical surgery for rectal cancer. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

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

Extreme-Risk Prostate Adenocarcinoma Presenting With Prostate-Specific Antigen (PSA) >40 ng/ml: Prognostic Significance of the Preradiation PSA Nadir

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

Alexander, Abraham S.; University of British Columbia, Vancouver, British Columbia; Mydin, Aminudin

2011-12-01

Purpose: To examine the impact of patient, disease, and treatment characteristics on survival outcomes in patients treated with neoadjuvant androgen deprivation therapy (ADT) and radical external-beam radiotherapy (RT) for clinically localized, extreme-risk prostate adenocarcinoma with a presenting prostate-specific antigen (PSA) concentration of >40 ng/ml. Methods and Materials: A retrospective chart review was conducted of 64 patients treated at a single institution between 1991 and 2000 with ADT and RT for prostate cancer with a presenting PSA level of >40 ng/ml. The effects of patient age, tumor (presenting PSA level, Gleason score, and T stage), and treatment (total ADT duration andmore » pre-RT PSA level) characteristics on rates of biochemical disease-free survival (bDFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were examined. Results: Median follow-up time was 6.45 years (range, 0.09-15.19 years). Actuarial bDFS, PCSS, and OS rates at 5 years were 39%, 87%, and 78%, respectively, and 17%, 64%, and 45%, respectively, at 10 years. On multivariate analysis, the pre-RT PSA level ({<=}0.1 versus >0.1 ng/ml) was the single most significant prognostic factor for bDFS (p = 0.033) and OS (p = 0.018) rates, whereas age, T stage, Gleason score, and ADT duration ({<=}6 versus >6 months) were not predictive of outcomes. Conclusion: In prostate cancer patients with high presenting PSA levels, >40 ng/ml, treated with combined modality, neoadjuvant ADT, and RT, the pre-RT PSA nadir, rather than ADT duration, was significantly associated with improved survival. This observation supports the use of neoadjuvant ADT to drive PSA levels to below 0.1 ng/ml before initiation of RT, to optimize outcomes for patients with extreme-risk disease.« less

The Effects of 6 Months of Progressive High Effort Resistance Training Methods upon Strength, Body Composition, Function, and Wellbeing of Elderly Adults.

PubMed

Steele, James; Raubold, Kristin; Kemmler, Wolfgang; Fisher, James; Gentil, Paulo; Giessing, Jürgen

2017-01-01

The present study examined the progressive implementation of a high effort resistance training (RT) approach in older adults over 6 months and through a 6-month follow-up on strength, body composition, function, and wellbeing of older adults. Twenty-three older adults (aged 61 to 80 years) completed a 6-month supervised RT intervention applying progressive introduction of higher effort set end points. After completion of the intervention participants could choose to continue performing RT unsupervised until 6-month follow-up. Strength, body composition, function, and wellbeing all significantly improved over the intervention. Over the follow-up, body composition changes reverted to baseline values, strength was reduced though it remained significantly higher than baseline, and wellbeing outcomes were mostly maintained. Comparisons over the follow-up between those who did and those who did not continue with RT revealed no significant differences for changes in any outcome measure. Supervised RT employing progressive application of high effort set end points is well tolerated and effective in improving strength, body composition, function, and wellbeing in older adults. However, whether participants continued, or did not, with RT unsupervised at follow-up had no effect on outcomes perhaps due to reduced effort employed during unsupervised RT.

Intraoperative Spillage of Favorable Histology Wilms Tumor Cells: Influence of Irradiation and Chemotherapy Regimens on Abdominal Recurrence. A Report From the National Wilms Tumor Study Group

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

Kalapurakal, John A., E-mail: j-kalapurakal@northwestern.ed; Li, Sierra M.; Breslow, Norman E.

Purpose: We undertook this study to determine (1) the frequency with which spilled tumor cells of favorable histology produced intra-abdominal disease in patients treated with differing chemotherapy regimens and abdominal radiation therapy (RT) and (2) the patterns of relapse and outcomes in such patients. Methods and Materials: The influence of RT dose (0, 10, and 20 Gy), RT fields (flank, whole abdomen), and chemotherapy with dactinomycin and vincristine (2 drugs) vs. added doxorubicin (three drugs) on intra-abdominal tumor recurrence rates was analyzed by logistic regression in 450 patients. Each patient was considered at risk for two types of failure: flankmore » and subdiaphragmatic beyond-flank recurrence, with the correlation between the two outcomes accounted for in the analyses. Results: The crude odds ratio for the risk of recurrence relative to no RT was 0.35 (0.15-0.78) for 10Gy and 0.08 (0.01-0.58) for 20Gy. The odds ratio for the risk of recurrence for doxorubicin to two drugs after adjusting for RT was not significant. For Stage II patients (NWTS-4), the 8-year event rates with and without spillage, respectively, were 79% and 87% for relapse-free survival (p = 0.07) and 90% and 95% for overall survival (p = 0.04). Conclusions: Irradiation (10 Gy or 20 Gy) reduced abdominal tumor recurrence rates after tumor spillage. Tumor spillage in Stage II patients reduced relapse-free survival and overall survival, but only the latter was of statistical significance. These data provide a basis for assessing the risks vs. benefits when considering treatment for children with favorable histology Wilms tumor and surgical spillage.« less

Cardiac risk index as a simple geometric indicator to select patients for the heart-sparing radiotherapy of left-sided breast cancer.

PubMed

Sung, KiHoon; Choi, Young Eun; Lee, Kyu Chan

2017-06-01

This is a dosimetric study to identify a simple geometric indicator to discriminate patients who meet the selection criterion for heart-sparing radiotherapy (RT). The authors proposed a cardiac risk index (CRI), directly measurable from the CT images at the time of scanning. Treatment plans were regenerated using the CT data of 312 consecutive patients with left-sided breast cancer. Dosimetric analysis was performed to estimate the risk of cardiac mortality using cardiac dosimetric parameters, such as the relative heart volumes receiving ≥25 Gy (heart V 25 ). For each CT data set, in-field heart depth (HD) and in-field heart width (HW) were measured to generate the geometric parameters, including maximum HW (HW max ) and maximum HD (HD max ). Seven geometric parameters were evaluated as candidates for CRI. Receiver operating characteristic (ROC) curve analyses were used to examine the overall discriminatory power of the geometric parameters to select high-risk patients (heart V 25  ≥ 10%). Seventy-one high-risk (22.8%) and 241 low-risk patients (77.2%) were identified by dosimetric analysis. The geometric and dosimetric parameters were significantly higher in the high-risk group. Heart V 25 showed the strong positive correlations with all geometric parameters examined (r > 0.8, p < 0.001). The product of HD max and HW max (CRI) revealed the largest area under the curve (AUC) value (0.969) and maintained 100% sensitivity and 88% specificity at the optimal cut-off value of 14.58 cm 2 . Cardiac risk index proposed as a simple geometric indicator to select high-risk patients provides useful guidance for clinicians considering optimal implementation of heart-sparing RT. © 2016 The Royal Australian and New Zealand College of Radiologists.

Adoption of Hypofractionated Radiation Therapy for Breast Cancer After Publication of Randomized Trials

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

Jagsi, Reshma, E-mail: rjagsi@med.umich.edu; Falchook, Aaron D.; Hendrix, Laura H.

2014-12-01

Purpose: Large randomized trials have established the noninferiority of shorter courses of “hypofractionated” radiation therapy (RT) to the whole breast compared to conventional courses using smaller daily doses in the adjuvant treatment of selected breast cancer patients undergoing lumpectomy. Hypofractionation is more convenient and less costly. Therefore, we sought to determine uptake of hypofractionated breast RT over time. Methods and Materials: In the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database, we identified 16,096 women with node-negative breast cancer and 4269 with ductal carcinoma in situ (DCIS) who received lumpectomy followed by more than 12 fractions of RT between 2004 andmore » 2010. Based on Medicare claims, we determined the number of RT treatments given and grouped patients into those receiving hypofractionation (13-24) or those receiving conventional fractionation (≥25). We also determined RT technique (intensity modulated RT or not) using Medicare claims. We evaluated patterns and correlates of hypofractionation receipt using bivariate and multivariable analyses. Results: Hypofractionation use was similar in patients with DCIS and those with invasive disease. Overall, the use of hypofractionation increased from 3.8% in 2006 to 5.4% in 2007, to 9.4% in 2008, and to 13.6% in 2009 and 2010. Multivariable analysis showed increased use of hypofractionation in recent years and in patients with older age, smaller tumors, increased comorbidity, higher regional education, and Western SEER regions. However, even in patients over the age of 80, the hypofractionation rate in 2009 to 2010 was only 25%. Use of intensity modulated RT (IMRT) also increased over time (from 9.4% in 2004 to 22.7% in 2009-2010) and did not vary significantly between patients receiving hypofractionation and those receiving traditional fractionation. Conclusions: Hypofractionation use increased among low-risk older US breast cancer patients with publication and maturation of evidence from randomized trials, but overall use of this cost-saving approach remained low. This contrasts with the more rapid rate of adoption of IMRT in the same time period, a costly innovation supported by less strong evidence of benefit.« less

Development of NTCP models for head and neck cancer patients treated with three-dimensional conformal radiotherapy for xerostomia and sticky saliva: the role of dosimetric and clinical factors.

PubMed

Beetz, Ivo; Schilstra, Cornelis; Burlage, Fred R; Koken, Phil W; Doornaert, Patricia; Bijl, Henk P; Chouvalova, Olga; Leemans, C René; de Bock, Geertruida H; Christianen, Miranda E M C; van der Laan, Bernard F A M; Vissink, Arjan; Steenbakkers, Roel J H M; Langendijk, Johannes A

2012-10-01

The purpose of this multicentre prospective study was to investigate the significance of the radiation dose in the major and minor salivary glands, and other pre-treatment and treatment factors, with regard to the development of patient-rated xerostomia and sticky saliva among head and neck cancer (HNC) patients treated with primary (chemo-) radiotherapy ((CH)RT). The study population was composed of 167 consecutive HNC patients treated with three-dimensional conformal (3D-CRT) (CH) RT. The primary endpoint was moderate to severe xerostomia (XER6m) as assessed by the EORTC QLQ-H&N35 at 6 months after completing (CH)RT. The secondary endpoint was moderate to severe sticky saliva at 6 months (STIC6m). All organs at risk (OARs) potentially involved in salivary function were delineated on planning-CT, including the parotid, submandibular and sublingual glands and the minor glands in the soft palate, cheeks and lips. Patients with moderate to severe xerostomia or sticky saliva at baseline were excluded. The optimum number of variables for a multivariate logistic regression model was determined using a bootstrapping method. The multivariate analysis showed the mean parotid dose, age and baseline xerostomia (none versus a bit) to be the most important predictors for XER6m. The risk of developing xerostomia increased with age and was higher when minor baseline xerostomia was present in comparison with patients without any xerostomia complaints at baseline. Model performance was good with an area under the curve (AUC) of 0.82. For STIC6m, the mean submandibular dose, age, the mean sublingual dose and baseline sticky saliva (none versus a bit) were most predictive for sticky saliva. The risk of developing STIC6m increased with age and was higher when minor baseline sticky saliva was present in comparison with patients without any sticky saliva complaints at baseline. Model performance was good with an AUC of 0.84. Dose distributions in the minor salivary glands in patients receiving 3D-CRT have limited significance with regard to patient-rated symptoms related to salivary dysfunction. Besides the parotid and submandibular glands, only the sublingual glands were significantly associated with sticky saliva. In addition, reliable risk estimation also requires information from other factors such as age and baseline subjective scores. When these selected factors are included in predictive models, instead of only dose volume histogram parameters, model performance can be improved significantly. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

A polymeric micelle magnetic resonance imaging (MRI) contrast agent reveals blood-brain barrier (BBB) permeability for macromolecules in cerebral ischemia-reperfusion injury.

PubMed

Shiraishi, Kouichi; Wang, Zuojun; Kokuryo, Daisuke; Aoki, Ichio; Yokoyama, Masayuki

2017-05-10

Blood-brain barrier (BBB) opening is a key phenomenon for understanding ischemia-reperfusion injuries that are directly linked to hemorrhagic transformation. The recombinant human tissue-type plasminogen activator (rtPA) increases the risk of symptomatic intracranial hemorrhages. Recent imaging technologies have advanced our understanding of pathological BBB disorders; however, an ongoing challenge in the pre-"rtPA treatment" stage is the task of developing a rigorous method for hemorrhage-risk assessments. Therefore, we examined a novel method for assessment of rtPA-extravasation through a hyper-permeable BBB. To examine the image diagnosis of rtPA-extravasation for a rat transient occlusion-reperfusion model, in this study we used a polymeric micelle MRI contrast-agent (Gd-micelles). Specifically, we used two MRI contrast agents at 1h after reperfusion. Gd-micelles provided very clear contrast images in 15.5±10.3% of the ischemic hemisphere at 30min after i.v. injection, whereas a classic gadolinium chelate MRI contrast agent provided no satisfactorily clear images. The obtained images indicate both the hyper-permeable BBB area for macromolecules and the distribution area of macromolecules in the ischemic hemisphere. Owing to their large molecular weight, Gd-micelles remained in the ischemic hemisphere through the hyper-permeable BBB. Our results indicate the feasibility of a novel clinical diagnosis for evaluating rtPA-related hemorrhage risks. Copyright © 2017 Elsevier B.V. All rights reserved.

The addition of low-dose-rate brachytherapy and androgen-deprivation therapy decreases biochemical failure and prostate cancer death compared with dose-escalated external-beam radiation therapy for high-risk prostate cancer.

PubMed

Shilkrut, Mark; Merrick, Gregory S; McLaughlin, P William; Stenmark, Matthew H; Abu-Isa, Eyad; Vance, Sean M; Sandler, Howard M; Feng, Felix Y; Hamstra, Daniel A

2013-02-01

The objective of this study was to determine whether the addition of low-dose-rate brachytherapy or androgen-deprivation therapy (ADT) improves clinical outcome in patients with high-risk prostate cancer (HiRPCa) who received dose-escalated radiotherapy (RT). Between 1995 and 2010, 958 patients with HiRPCa were treated at Schiffler Cancer Center (n = 484) or at the University of Michigan (n = 474) by receiving either dose-escalated external-beam RT (EBRT) (n = 510; minimum prescription dose, 75 grays [Gy]; median dose, 78 Gy) or combined-modality RT (CMRT) consisting of (103) Pd implants (n = 369) or (125) I implants (n = 79) both with pelvic irradiation (median prescription dose, 45 Gy). The cumulative incidences of biochemical failure (BF) and prostate cancer-specific mortality (PCSM) were estimated by using the Kaplan-Meier method and Fine and Gray regression analysis. The median follow-up was 63.2 months (interquartile range, 35.4-99.0 months), and 250 patients were followed for >8 years. Compared with CMRT, patients who received EBRT had higher prostate-specific antigen levels, higher tumor classification, lower Gleason sum, and more frequent receipt of ADT for a longer duration. The 8-year incidence BF and PCSM among patients who received EBRT was 40% (standard error, 38%-44%) and 13% (standard error, 11%-15%) compared with 14% (standard error, 12%-16%; P < .0001) and 7% (standard error 6%-9%; P = .003) among patients who received CMRT. On multivariate analysis, the hazard ratios (HRs) for BF and PCSM were 0.35 (95% confidence interval [CI], 0.23-0.52; P < .0001) and 0.41 (95% CI, 0.23-0.75; P < .003), favoring CMRT. Increasing duration of ADT predicted decreased BF (P = .04) and PCSM (P = .001), which was greatest with long-term ADT (BF: HR, 0.33; P < .0001; 95% CI, 0.21-0.52; PCSM: HR, 0.30; P = .001; 95% CI, 0.15-0.6) even in the subgroup that received CMRT. In this retrospective comparison, both low-dose-rate brachytherapy boost and ADT were associated with decreased risks of BF and PCSM compared with EBRT. Copyright © 2012 American Cancer Society.

Incidence, Causative Mechanisms, and Anatomic Localization of Stroke in Pituitary Adenoma Patients Treated With Postoperative Radiation Therapy Versus Surgery Alone

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

Sattler, Margriet G.A., E-mail: g.a.sattler@umcg.nl; Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON; Vroomen, Patrick C.

Purpose: To assess and compare the incidence of stroke and stroke subtype in pituitary adenoma patients treated with postoperative radiation therapy (RT) and surgery alone. Methods and Materials: A cohort of 462 pituitary adenoma patients treated between 1959 and 2008 at the University Medical Center Groningen in The Netherlands was studied. Radiation therapy was administered in 236 patients. The TOAST (Trial of ORG 10172 in Acute Stroke Treatment) and the Oxfordshire Community Stroke Project classification methods were used to determine causative mechanism and anatomic localization of stroke. Stroke incidences in patients treated with RT were compared with that observed aftermore » surgery alone. Risk factors for stroke incidence were studied by log–rank test, without and with stratification for other significant risk factors. In addition, the stroke incidence was compared with the incidence rate in the general Dutch population. Results: Thirteen RT patients were diagnosed with stroke, compared with 12 surgery-alone patients. The relative risk (RR) for stroke in patients treated with postoperative RT was not significantly different compared with surgery-alone patients (univariate RR 0.62, 95% confidence interval [CI] 0.28-1.35, P=.23). Stroke risk factors were coronary or peripheral artery disease (univariate and multivariate RR 10.4, 95% CI 4.7-22.8, P<.001) and hypertension (univariate RR 3.9, 95% CI 1.6-9.8, P=.002). There was no difference in TOAST and Oxfordshire classification of stroke. In this pituitary adenoma cohort 25 strokes were observed, compared with 16.91 expected (standard incidence ratio 1.48, 95% CI 1.00-1.96, P=.049). Conclusions: In pituitary adenoma patients, an increased incidence of stroke was observed compared with the general population. However, postoperative RT was not associated with an increased incidence of stroke or differences in causative mechanism or anatomic localization of stroke compared with surgery alone. The primary stroke risk factor was pre-existent coronary or peripheral artery disease.« less

The effect on esophagus after different radiotherapy techniques for early stage Hodgkin's lymphoma.

PubMed

Jørgensen, Anni Y S; Maraldo, Maja V; Brodin, Nils Patrik; Aznar, Marianne C; Vogelius, Ivan R; Rosenschöld, Per Munck Af; Petersen, Peter M; Specht, Lena

2013-10-01

The cure rate of early stage Hodgkin's lymphoma (HL) is excellent; investigating the late effects of treatment is thus important. Esophageal toxicity is a known side effect in patients receiving radiotherapy (RT) to the mediastinum, although little is known of this in HL survivors. This study investigates the dose to the esophagus in the treatment of early stage HL using different RT techniques. Estimated risks of early esophagitis, esophageal stricture and cancer are compared between treatments. We included 46 patients ≥ 15 years with supradiaphragmatic, clinical stage I-II HL, who received chemotherapy followed by involved node RT (INRT) to 30.6 Gy at our institution. INRT was planned with three-dimensional conformal RT (3DCRT). For each patient a volumetric modulated arc therapy (VMAT), proton therapy (PT) and mantle field (MF) treatment plan was simulated. Mean, maximum and minimum dose to the esophagus were extracted from the treatment plans. Risk estimates were based on dose-response models from clinical series with long-term follow-up. Statistical analyses were performed with repeated measures ANOVA using Bonferroni corrections. Mean dose to the esophagus was 16.4, 16.4, 14.7 and 34.2 Gy (p < 0.001) with 3DCRT, VMAT, PT and MF treatment, respectively. No differences were seen in the estimated risk of developing esophagitis, stricture or cancer with 3DCRT compared to VMAT (p = 1.000, p = 1.000, p = 0.356). PT performed significantly better with the lowest risk estimates on all parameters compared to the photon treatments, except compared to 3DCRT for stricture (p = 0.066). On all parameters the modern techniques were superior to MF treatment (p < 0.001). The estimated dose to the esophagus and the corresponding estimated risks of esophageal complications are decreased significantly with highly conformal RT compared to MF treatment. The number of patients presenting with late esophageal side effects will, thus, likely be minimal in the future.

259 Patients with DCIS of the breast applying USC/Van Nuys prognostic index: a retrospective review with long term follow up.

PubMed

Di Saverio, Salomone; Catena, Fausto; Santini, Donatella; Ansaloni, Luca; Fogacci, Tommaso; Mignani, Stefano; Leone, Antonio; Gazzotti, Filippo; Gagliardi, Stefano; De Cataldis, Angelo; Taffurelli, Mario

2008-06-01

The Van Nuys Prognostic Index (VNPI) is a simple score for predicting the risk of local recurrence (LR) in patients with Ductal Carcinoma In Situ (DCIS) conservatively treated. This score combines three independent predictors of Local Recurrence. The VNPI has recently been updated with the addition of age as a fourth parameter into the scoring system (University of Southern California/ VNPI). Our database consisted of 408 women with DCIS. Applying the USC/VNPI we reviewed retrospectively 259 patients who were treated with breast conserving surgery with or without radiotherapy (RT). Of these patients 63.5% had a low VNPI score, 32% intermediate and 4.5% a high score. In the low score group, the majority of the patients underwent Conservative Surgery (CS) without RT while in the intermediate group, almost half of the patients received RT. Eighty-three percent (83%) of the patients with high VNPI were treated with Conservative Surgery plus RT. Nodal assessment by Sentinel Lymph Node Biopsy was obtained in 32 patients since 2002. Twenty-one Local Recurrences were observed (8%) with a mean follow up of 130 months: sixteen were invasive. No statistically significant differences in Disease Free Survival were reached in all groups of VNPI score between patients treated with Conservative Surgery or Conservative Surgery plus RT. However it was noted that the higher the VNPI score, the lower was the risk of local recurrence in the group treated additionally with RT, even though it was not statistically significant. Further analysis included those patients treated with Conservative Surgery alone and followed up. Disease-free survival (DFS) at 10 years was 94% with low VNPI and 83% in both intermediate and high score (P < 0.05). No significant differences were observed in the subgroups of VNPI. The Local Relapse rate after Conservative Surgery alone, increased with tumor size, margin width, and pathology classification (P < 0,05), while age was not found to be a significant factor. Lesions with only mammographic appearances are associated with lower DFS but it did not reach significance (P = ns), while assumption of estrogenic hormones and familial history of breast cancer are significant factors associated with a higher risk of local recurrence. After multivariate analysis including seven clinical and pathological factors, the only significant predictors of local recurrence remained margin width of surgical excision, previous therapy with estrogens (contraceptives or Hormone Replacement Therapy) and the Van Nuys pathologic classification. The overall survival breast cancer specific was 99% and no differences were observed between groups (P = ns). The comparison of patients treated with a total mastectomy and those conservatively treated showed a significantly better local relapse free survival rate obtained with mastectomy (98.2% vs. 89.7% at 10 years P = 0.02). However, the overall cause-specific survival did not prove any better outcome (98.7% in both groups). Of the 32 patients who underwent a Sentinel Lymph Node Biopsy, four were found to have micrometastases and all of them had a previous Directional Vacuum Assisted Biopsy. Although in our series there is not a significant difference in LR rates by the parameter of age, the new USC/VNPI is still a simple and reliable scoring system for therapeutic management of DCIS. We did not find any statistically significant advantage in groups treated with the addition of RT. Obtaining wide surgical margins appears to be the strongest prognostic factor for local recurrence, regardless of other pathological factors or the addition of adjuvant radiation therapy. However, only prospective randomized studies can precisely predict the risk of LR of conservatively treated DCIS. The clinical significance of Sentinel Lymph Nodes micrometastases Immuno-Histo-Chemistry-detected found in DCIS patients remains uncertain. However, we hypothesize that the anatomical disruption after preoperative biopsy procedures increases the likelihood of epithelial cell displacement and the frequency of IHC-positive Sentinel Lymph Nodes, both of which are directly proportional to the degree of manipulation.

A non-discrete method for computation of residence time in fluid mechanics simulations.

PubMed

Esmaily-Moghadam, Mahdi; Hsia, Tain-Yen; Marsden, Alison L

2013-11-01

Cardiovascular simulations provide a promising means to predict risk of thrombosis in grafts, devices, and surgical anatomies in adult and pediatric patients. Although the pathways for platelet activation and clot formation are not yet fully understood, recent findings suggest that thrombosis risk is increased in regions of flow recirculation and high residence time (RT). Current approaches for calculating RT are typically based on releasing a finite number of Lagrangian particles into the flow field and calculating RT by tracking their positions. However, special care must be taken to achieve temporal and spatial convergence, often requiring repeated simulations. In this work, we introduce a non-discrete method in which RT is calculated in an Eulerian framework using the advection-diffusion equation. We first present the formulation for calculating residence time in a given region of interest using two alternate definitions. The physical significance and sensitivity of the two measures of RT are discussed and their mathematical relation is established. An extension to a point-wise value is also presented. The methods presented here are then applied in a 2D cavity and two representative clinical scenarios, involving shunt placement for single ventricle heart defects and Kawasaki disease. In the second case study, we explored the relationship between RT and wall shear stress, a parameter of particular importance in cardiovascular disease.

A non-discrete method for computation of residence time in fluid mechanics simulations

NASA Astrophysics Data System (ADS)

Esmaily-Moghadam, Mahdi; Hsia, Tain-Yen; Marsden, Alison L.

2013-11-01

Cardiovascular simulations provide a promising means to predict risk of thrombosis in grafts, devices, and surgical anatomies in adult and pediatric patients. Although the pathways for platelet activation and clot formation are not yet fully understood, recent findings suggest that thrombosis risk is increased in regions of flow recirculation and high residence time (RT). Current approaches for calculating RT are typically based on releasing a finite number of Lagrangian particles into the flow field and calculating RT by tracking their positions. However, special care must be taken to achieve temporal and spatial convergence, often requiring repeated simulations. In this work, we introduce a non-discrete method in which RT is calculated in an Eulerian framework using the advection-diffusion equation. We first present the formulation for calculating residence time in a given region of interest using two alternate definitions. The physical significance and sensitivity of the two measures of RT are discussed and their mathematical relation is established. An extension to a point-wise value is also presented. The methods presented here are then applied in a 2D cavity and two representative clinical scenarios, involving shunt placement for single ventricle heart defects and Kawasaki disease. In the second case study, we explored the relationship between RT and wall shear stress, a parameter of particular importance in cardiovascular disease.

A non-discrete method for computation of residence time in fluid mechanics simulations

PubMed Central

Esmaily-Moghadam, Mahdi; Hsia, Tain-Yen; Marsden, Alison L.

2013-01-01

Cardiovascular simulations provide a promising means to predict risk of thrombosis in grafts, devices, and surgical anatomies in adult and pediatric patients. Although the pathways for platelet activation and clot formation are not yet fully understood, recent findings suggest that thrombosis risk is increased in regions of flow recirculation and high residence time (RT). Current approaches for calculating RT are typically based on releasing a finite number of Lagrangian particles into the flow field and calculating RT by tracking their positions. However, special care must be taken to achieve temporal and spatial convergence, often requiring repeated simulations. In this work, we introduce a non-discrete method in which RT is calculated in an Eulerian framework using the advection-diffusion equation. We first present the formulation for calculating residence time in a given region of interest using two alternate definitions. The physical significance and sensitivity of the two measures of RT are discussed and their mathematical relation is established. An extension to a point-wise value is also presented. The methods presented here are then applied in a 2D cavity and two representative clinical scenarios, involving shunt placement for single ventricle heart defects and Kawasaki disease. In the second case study, we explored the relationship between RT and wall shear stress, a parameter of particular importance in cardiovascular disease. PMID:24046509

An audit of referral and treatment patterns of high-risk prostate cancer patients in Alberta.

PubMed

Alghamdi, Majed; Taggar, Amandeep; Tilley, Derek; Kerba, Marc; Kostaras, Xanthoula; Gotto, Geoffrey; Sia, Michael

2016-01-01

We aimed to determine the impact of clinical practice guidelines (CPG) on rates of radiation oncologist (RO) referral, androgen-deprivation therapy (ADT), radiation therapy (RT), and radical prostatectomy (RP) in patients with high-risk prostate cancer (HR-PCa). All men >18 years, diagnosed with PCa in 2005 and 2012 were identified from the Alberta Cancer Registry. Patient age, aggregated clinical risk group (ACRG) score, Gleason score (GS), pre-treatment prostate-specific antigen (PSA), RO referral, and treatment received were extracted from electronic medical records. Logistic regression modelling was used to examine associations between RO referral rates and relevant factors. HR-PCa was diagnosed in 261 of 1792 patients in 2005 and 435 of 2148 in 2012. Median age and ACRG scores were similar in both years (p>0.05). The rate of patients with PSA >20 were 67% and 57% in 2005 and 2012, respectively (p=0.004). GS ≤6 was found in 13% vs. 5% of patients, GS 7 in 27% vs. 24%, and GS ≥8 in 59% vs. 71% in 2005 and 2012, respectively (p<0.001). In 2005, RO referral rate was 68% compared to 56% in 2012 (p=0.001), use of RT + ADT was 53% compared to 32% (p<0.001), and RP rate was 9% vs. 17% (p=0.002). On regression analysis, older age, 2012 year of diagnosis and higher PSA were associated with decreased RO referral rates (odds ratios [OR] 0.49, 95% confidence interval [CI] 0.39-0.61; OR 0.51, 95% CI 0.34-0.76; and OR 0.64, 95% CI 0.39-0.61), respectively [p<0.001]). Since CPG creation in 2005, RO referral rates and ADT + RT use declined and RP rates increased, which demonstrates a need to improve adherence to CPG in the HR-PCa population.

The risk of carotid stenosis in head and neck cancer patients after radiation therapy.

PubMed

Carpenter, David J; Mowery, Yvonne M; Broadwater, Gloria; Rodrigues, Anna; Wisdom, Amy J; Dorth, Jennifer A; Patel, Pretesh R; Shortell, Cynthia K; Clough, Robert; Brizel, David M

2018-05-01

Head and neck radiotherapy (RT) is a risk factor for cerebrovascular disease. We performed a retrospective cohort study to evaluate carotid artery stenosis (CAS) incidence in head and neck cancer (HNC) patients undergoing RT, characterizing associated risk factors. Records were retrospectively reviewed for HNC patients undergoing carotid ultrasound screening after definitive or adjuvant RT between January 2000 and May 2016. CAS was defined as ≥50% stenosis on imaging, stroke, or transient ischemic attack. Actuarial CAS rates were calculated by Kaplan-Meier method. Univariate and multivariate analyses predicted CAS risk based on carotid dosimetric and clinical parameters. 366 patients met inclusion criteria. Median time from RT completion to last follow-up was 4.1 yr. Actuarial risk for CAS was 29% (95% CI 22-36%) at 8 years. Univariate analysis showed that smoking (HR 1.7; 95% CI 1.1-2.7), hyperlipidemia (HR 1.6; 95% CI 1.03-2.6), diabetes (HR 2.8; 95% CI 1.6-4.8), coronary artery disease (HR 2.4; 95% CI 1.4-4.2), and peripheral artery disease (HR 3.6; 95% CI 1.1-11.6) were significantly associated with increased CAS. In multivariate analysis, diabetes was predictive of time to CAS (HR 1.9; 95% CI 1.1-3.4). Carotid dose parameters were not significantly associated with CAS. CAS incidence is high after head and neck radiotherapy, gradually rising over time. No clear dose-response effect between carotid dose and CAS was identified for HNC patients. Carotid artery screening and preventative strategies should be employed in this high-risk patient population. Copyright © 2018 Elsevier Ltd. All rights reserved.

Avascular Necrosis of the Femoral Head After Palliative Radiotherapy in Metastatic Prostate Cancer: Absence of a Dose Threshold?

PubMed

Daoud, Alia M; Hudson, Mack; Magnus, Kenneth G; Huang, Fleur; Danielson, Brita L; Venner, Peter; Saluja, Ronak; LeGuerrier, Bronwen; Daly, Helene; Emmenegger, Urban; Fairchild, Alysa

2016-03-06

Avascular necrosis (AVN) is the final common pathway resulting from insufficient blood supply to bone, commonly the femoral head. There are many postulated etiologies of non-traumatic AVN, including corticosteroids, bisphosphonates, and radiotherapy (RT). However, it is unclear whether there is a dose threshold for the development of RT-induced AVN. In this case report, we describe a patient with prostate cancer metastatic to bone diagnosed with AVN after receiving single-fraction palliative RT to the left femoral head. Potential contributing factors are discussed, along with a review of other reported cases. At present, the RT dose threshold below which there is no risk for AVN is unknown, and therefore detrimental impact from the RT cannot be excluded. Given the possibility that RT-induced AVN is a stochastic effect, it is important to be aware of the possibility of this diagnosis in any patient with a painful hip who has received RT to the femoral head.

Integrated skin flash planning technique for intensity-modulated radiation therapy for vulvar cancer prevents marginal misses and improves superficial dose coverage.

PubMed

Dyer, Brandon A; Jenshus, Abriel; Mayadev, Jyoti S

2018-02-28

Radiation therapy (RT) plays a definitive role in locally advanced vulvar cancer, and in the adjuvant setting with high risk postoperative features after wide local excision. There is significant morbidity associated with traditional, large RT fields using 2D or 3D techniques, and the use of intensity-modulated radiation therapy (IMRT) in vulvar cancer is increasing. However, there remains a paucity of technical information regarding the prevention of a marginal miss during the treatment planning process. The use of an integrated skin flash (ISF) during RT planning can be used to account for anatomic variation, and intra- and interfraction motion seen during treatment. Herein we present the case of a patient with a T1aN0M0, Stage IA vulva cancer to illustrate the progressive vulvar swelling and lymph edema seen during treatment and retrospectively evaluate the dosimetric effects of using an ISF RT plan vs standard RT planning techniques. Standard planning techniques to treat vulvar cancer patients with IMRT do not sufficiently account for the change in patient anatomy and can lead to a marginal miss. ISF is an RT planning technique that can decrease the risk of a marginal miss and the technique is easily implemented during the planning stages of RT treatment. Furthermore, use of an ISF technique can improve vulvar clinical target volume coverage and plan homogeneity. Based on our experience, and this study, a 2-cm ISF is suggested to account for variations in daily clinical setup and changes in patient anatomy during treatment. Published by Elsevier Inc.

Evaluation of Biologic Effective Dose and Schedule of Fractionation for Preoperative Radiotherapy for Rectal Cancer: Meta-Analyses and Meta-Regression;Rectal cancer; Preoperative radiotherapy; Biologic effective dose; Meta-analysis

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

Arruda Viani, Gustavo, E-mail: gusviani@gmail.com; Stefano, Eduardo Jose; Vendito Soares, Francisco

2011-07-15

Purpose: To evaluate whether the risk of local recurrence depends on the biologic effective dose (BED) or fractionation dose in patients with resectable rectal cancer undergoing preoperative radiotherapy (RT) compared with surgery alone. Methods and Materials: A meta-analysis of randomized controlled trials (RCTs) was performed. The MEDLINE, Embase, CancerLit, and Cochrane Library databases were systematically searched for evidence. To evaluate the dose-response relationship, we conducted a meta-regression analysis. Four subgroups were created: Group 1, RCTs with a BED >30 Gy{sub 10} and a short RT schedule; Group 2, RCTs with BED >30 Gy{sub 10} and a long RT schedule; Groupmore » 3, RCTs with BED {<=}30 Gy{sub 10} and a short RT schedule; and Group 4, RCTs with BED {<=}30 Gy{sub 10} and a long RT schedule. Results: Our review identified 21 RCTs, yielding 9,097 patients. The pooled results from these 21 randomized trials of preoperative RT showed a significant reduction in mortality for groups 1 (p = .004) and 2 (p = .03). For local recurrence, the results were also significant in groups 1 (p = .00001) and 2 (p = .00001).The only subgroup that showed a greater sphincter preservation (SP) rate than surgery was group 2 (p = .03). The dose-response curve was linear (p = .006), and RT decreased the risk of local recurrence by about 1.7% for each Gy{sub 10} of BED. Conclusion: Our data have shown that RT with a BED of >30 Gy{sub 10} is more efficient in reducing local recurrence and mortality rates than a BED of {<=}30 Gy{sub 10}, independent of the schedule of fractionation used. A long RT schedule with a BED of >30 Gy{sub 10} should be recommended for sphincter preservation.« less

Evaluation of particle radiotherapy for the re-irradiation of recurrent intracranial meningioma.

PubMed

El Shafie, Rami A; Czech, Maja; Kessel, Kerstin A; Habermehl, Daniel; Weber, Dorothea; Rieken, Stefan; Bougatf, Nina; Jäkel, Oliver; Debus, Jürgen; Combs, Stephanie E

2018-05-08

With the advance of modern irradiation techniques, the role of radiotherapy (RT) for intracranial meningioma has increased significantly throughout the past years. Despite that tumor's generally favorable outcome with local control rates of up to 90% after ten years, progression after RT does occur. In those cases, re-irradiation is often difficult due to the limited radiation tolerance of the surrounding tissue. The aim of this analysis is to determine the value of particle therapy with its better dose conformity and higher biological efficacy for re-irradiating recurrent intracranial meningioma. It was performed within the framework of the "clinical research group heavy ion therapy" and funded by the German Research Council (DFG, KFO 214). Forty-two patients treated with particle RT (protons (n = 8) or carbon ions (n = 34)) for recurrent intracranial meningioma were included in this analysis. Location of the primary lesion varied, including skull base (n = 31), convexity (n = 5) and falx (n = 6). 74% of the patients were categorized high-risk according to histology with a WHO grading of II (n = 25) or III (n = 6), in the remaining cases histology was either WHO grade I (n = 10) or unknown (n = 1). Median follow-up was 49,7 months. In all patients, re-irradiation could be performed safely without interruptions due to side effects. No grade IV or V toxicities according to CTCAE v4.0 were observed. Particle RT offered good overall local control rates with 71% progression-free survival (PFS) after 12 months, 56,5% after 24 months and a median PFS of 34,3 months (95% CI 11,7-56,9). Histology had a significant impact on PFS yielding a median PFS of 25,7 months (95% CI 5,8-45,5) for high-risk histology (WHO grades II and III) while median PFS was not reached for low-risk tumors (WHO grade I) (p = 0,03). Median time to local progression was 15,3 months (Q1-Q3 8,08-34,6). Overall survival (OS) after re-irradiation was 89,6% after 12 months and 71,4% after 24 months with a median OS of 61,0 months (95% CI 34,2-87,7). Again, WHO grading had an effect, as median OS for low-risk patients was not reached whereas for high-risk patients it was 45,5 months (95% CI 35,6-55,3). Re-irradiation using particle therapy is an effective method for the treatment of recurrent meningiomas. Interdisciplinary decision making is necessary to guarantee best treatment for every patient.

Template-independent DNA synthesis activity associated with the reverse transcriptase of the long terminal repeat retrotransposon Tf1.

PubMed

Oz-Gleenberg, Iris; Herzig, Eytan; Hizi, Amnon

2012-01-01

Reverse transcriptases (RTs) possess a non-templated addition (NTA) activity while synthesizing DNA with blunt-ended DNA primer/templates. Interestingly, the RT of the long terminal repeat retrotransposon Tf1 has an NTA activity that is substantially higher than that of HIV-1 or murine leukemia virus RTs. By performing steady state kinetics, we found that the differences between the NTA activities of Tf1 and HIV-1 RTs can be explained by the substantially lower K(M) value for the incoming dNTP of Tf1 RT (while the differences between the apparent k(cat) values of these two RTs are relatively small). Furthermore, the K(M) values, calculated for both RTs with the same dNTP, are much lower for the template-dependent synthesis (TDS) than those of NTA. However, TDS of HIV-1 RT is higher than that of Tf1 RT. The overall relative order of the apparent k(cat)/K(M) values for dATP is: HIV-1 RT (TDS) > Tf1 RT (TDS) > Tf1 RT (NTA) > HIV-1 RT (NTA). Under the employed conditions, Tf1 RT can add up to seven nucleotides to the blunt-ended substrate, while the other RTs add mostly a single nucleotide. The NTA activity of Tf1 RT is restricted to DNA primers. Furthermore, the NTA activity of Tf1 and HIV-1 RTs is suppressed by ATP, as it competes with the incoming dATP (although ATP is not incorporated by the NTA activity of the RTs). The unusually high NTA activity of Tf1 RT can explain why, after completing cDNA synthesis, the in vivo generated Tf1 cDNA has relatively long extra sequences beyond the highly conserved CA at its 3'-ends. © 2011 The Authors Journal compilation © 2011 FEBS.

Annual Glyphosate Treatments Alter Growth of Unaffected Bentgrass (Agrostis) Weeds and Plant Community Composition

PubMed Central

Ahrens, Collin W.; Auer, Carol A.

2012-01-01

Herbicide resistance is becoming more common in weed ecotypes and crop species including turfgrasses, but current gaps in knowledge limit predictive ecological risk assessments and risk management plans. This project examined the effect of annual glyphosate applications on the vegetative growth and reproductive potential of two weedy bentgrasses, creeping bentgrass (CB) and redtop (RT), where the glyphosate resistance (GR) trait was mimicked by covering the bentgrass plants during glyphosate application. Five field plots were studied in habitats commonly inhabited by weedy bentgrasses including an agricultural hayfield, natural meadow, and wasteland. Results showed that annual glyphosate treatment improved bentgrass survivorship, vegetative growth, and reproductive potential compared with bentgrass in unsprayed subplots. In the second year of growth, RT plants had an 86-fold increase in flower number in glyphosate-treated subplots versus controls, while CB plants had a 20-fold increase. At the end of the three year study, plant community composition had changed in glyphosate-treated subplots in hayfield and meadow plots compared to controls. Soils in subplots receiving glyphosate had higher nitrate concentrations than controls. This is the first study to mimic the GR trait in bentgrass plants with the goal of quantifying bentgrass response to glyphosate selection pressure and understanding the impacts on surrounding plant communities. PMID:23226530

The role of helical tomotherapy in the treatment of bone plasmacytoma.

PubMed

Chargari, Cyrus; Hijal, Tarek; Bouscary, Didier; Caussa, Lucas; Dendale, Remi; Zefkili, Sofia; Fourquet, Alain; Kirova, Youlia M

2012-01-01

We evaluated the early clinical outcome of patients with solitary bone plasmacytoma (SP) or a solitary lesion of multiple myeloma (MM) treated with helical tomotherapy (HT) compared with 3D conformal radiotherapy (3D-CRT), in terms of target coverage and exposure of critical organs. Ten patients with SP and 3 patients with a solitary lesion of MM underwent radiation therapy (RT) delivered by HT, to a dose of 40 Gy in 20 fractions. Treatment planning was then performed with 3D-CRT and the dosimetric parameters of both techniques were compared. Patients were also assessed for response to treatment and acute toxicities. With a median follow-up of 13 months, 78% of patients with pain before RT had resolution of their symptoms. Coverage of target lesion was adequate with both techniques in 12 of 13 patients. Target coverage was significantly lower for HT (V(95%) = 98.55% vs. 97.15%; p = 0.04, for 3D-CRT and HT, respectively). Target overdoses were also lower with HT (V(105%) = 2.01% vs. 0.19%; p= 0.16), although nonsignificant. Finally, there were no significant differences in organs-at-risk irradiation between both techniques. The early treatment tolerance was excellent, with no toxicity higher than grade I. RT of SP and MM with a solitary lesion can be safely delivered with HT, with no major acute side effects and good symptomatic control. Finally, HT provides a dosimetry similar to that of 3D-CRT in terms of organs-at-risk sparing and target volume coverage. Copyright © 2012 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Epidemiological aspects of astrovirus and coronavirus in poults in the South Eastern Region of Brazil

PubMed Central

da Silva, S.E.L.; Bonetti, A.M.; Petrocelli, A.; Ferrari, H.F.; Luvizotto, M.C.R.; Cardoso, T.C.

2009-01-01

A survey of Turkey Coronavirus (TCoV) and Astrovirus (TAstV-2) prevalence was carried out from February to December during 2006 year in semiarid region of Brazil, from a turkey producer area, localized in South Eastern of Brazil. To asses the risk factor related to clinical material, climatic condition and type of RT-PCR applied, cloacal swabs (CS), faeces, sera, bursa of Fabricius (BF), thymus (TH) and spleen (SP) and ileum-caeca region were collected from 30-day-old poults suffering of enteritis episode characterized as poult enteritis mortality syndrome (PEMS). The PEMS clinical features were characterized by watery to foamy faeces, light brown-yellow in colour and low mortality rate. Meteorological data (rainfall and relative humidity) observed during along the study presented monthly average temperature ranging from 39.3 and 31.2ºC, precipitation in rainy season from 40 to 270.3 mm/month, and no rain during dry season. Simplex RT-PCR gave odds ratio (OR) values suggesting that ileum-caeca region is at higher chance (OR=1.9; p=0.9741) to have both viral RNA than faeces (OR=1.5; p=0.7319). However, multiplex RT-PCR showed 3.98 (p=0.89982) more chance to give positive results in faeces than CS at dry season. The major risk factors seem to be low rate of humidity and high temperatures at winter, probably responsible for spread, easily, the TCoV and TAstv-2 among the flocks. The positive results of both virus suggested that they can play an important role in enteric disorders, associated to low humidity and high temperatures frequently found in tropical countries. PMID:24031353

Image quality and diagnostic performance of free-breathing diffusion-weighted imaging for hepatocellular carcinoma.

PubMed

Takayama, Yukihisa; Nishie, Akihiro; Asayama, Yoshiki; Ishigami, Kousei; Kakihara, Daisuke; Ushijima, Yasuhiro; Fujita, Nobuhiro; Shirabe, Ken; Takemura, Atsushi; Honda, Hiroshi

2017-05-18

To retrospectively evaluate the diagnostic performance of free-breathing diffusion-weighted imaging (FB-DWI) with modified imaging parameter settings for detecting hepatocellular carcinomas (HCCs). Fifty-one patients at risk for HCC were scanned with both FB-DWI and respiratory-triggered DWI with the navigator echo respiratory-triggering technique (RT-DWI). Qualitatively, the sharpness of the liver contour, the image noise and the chemical shift artifacts on each DWI with b -values of 1000 s/mm 2 were independently evaluated by three radiologists using 4-point scoring. We compared the image quality scores of each observer between the two DWI methods, using the Wilcoxon signed-rank test. Quantitatively, we compared the signal-to-noise ratios (SNRs) of the liver parenchyma and lesion-to-nonlesion contrast-to-noise ratios (CNRs) after measuring the signal intensity on each DWI with a b-factor of 1000 s/mm 2 . The average SNRs and CNRs between the two DWI methods were compared by the paired t-test. The detectability of HCC on each DWI was also analyzed by three radiologists. The detectability provided by the two DWI methods was compared using McNemar's test. For all observers, the averaged image quality scores of FB-DWI were: Sharpness of the liver contour [observer (Obs)-1, 3.08 ± 0.81; Obs-2, 2.98 ± 0.73; Obs-3, 3.54 ± 0.75], those of the distortion (Obs-1, 2.94 ± 0.50; Obs-2, 2.71 ± 0.70; Obs-3, 3.27 ± 0.53), and the chemical shift artifacts (Obs-1, 3.38 ± 0.60; Obs-2, 3.15 ± 1.07; Obs-3, 3.21 ± 0.85). The averaged image quality scores of RT-DWI were: Sharpness of the liver contour (Obs-1, 2.33 ± 0.65; Obs-2, 2.37 ± 0.74; Obs-3, 2.75 ± 0.81), distortion (Obs-1, 2.81 ± 0.56; Obs-2, 2.25 ± 0.74; Obs-3, 2.96 ± 0.71), and the chemical shift artifacts (Obs-1, 2.92 ± 0.59; Obs-2, 2.21 ± 0.85; Obs-3, 2.77 ± 1.08). All image quality scores of FB-DWI were significantly higher than those of RT-DWI ( P < 0.05). The average SNR of the normal liver parenchyma by FB-DWI (11.0 ± 4.8) was not significantly different from that shown by RT-DWI (11.0 ± 5.0); nor were the lesion-to-nonlesion CNRs significantly different (FB-DWI, 21.4 ± 17.7; RT-DWI, 20.1 ± 15.1). For all three observers, the detectability of FB-DWI (Obs-1, 43.6%; Obs-2, 53.6%; and Obs-3, 45.0%) was significantly higher than that of RT-DWI (Obs-1, 29.1%; Obs-2, 43.6%; and Obs-3, 34.5%) ( P < 0.05). FB-DWI showed better image quality and higher detectability of HCC compared to RT-DWI, without significantly reducing the SNRs of the liver parenchyma and lesion-to-nonlesion CNRs.

Image quality and diagnostic performance of free-breathing diffusion-weighted imaging for hepatocellular carcinoma

PubMed Central

Takayama, Yukihisa; Nishie, Akihiro; Asayama, Yoshiki; Ishigami, Kousei; Kakihara, Daisuke; Ushijima, Yasuhiro; Fujita, Nobuhiro; Shirabe, Ken; Takemura, Atsushi; Honda, Hiroshi

2017-01-01

AIM To retrospectively evaluate the diagnostic performance of free-breathing diffusion-weighted imaging (FB-DWI) with modified imaging parameter settings for detecting hepatocellular carcinomas (HCCs). METHODS Fifty-one patients at risk for HCC were scanned with both FB-DWI and respiratory-triggered DWI with the navigator echo respiratory-triggering technique (RT-DWI). Qualitatively, the sharpness of the liver contour, the image noise and the chemical shift artifacts on each DWI with b-values of 1000 s/mm2 were independently evaluated by three radiologists using 4-point scoring. We compared the image quality scores of each observer between the two DWI methods, using the Wilcoxon signed-rank test. Quantitatively, we compared the signal-to-noise ratios (SNRs) of the liver parenchyma and lesion-to-nonlesion contrast-to-noise ratios (CNRs) after measuring the signal intensity on each DWI with a b-factor of 1000 s/mm2. The average SNRs and CNRs between the two DWI methods were compared by the paired t-test. The detectability of HCC on each DWI was also analyzed by three radiologists. The detectability provided by the two DWI methods was compared using McNemar’s test. RESULTS For all observers, the averaged image quality scores of FB-DWI were: Sharpness of the liver contour [observer (Obs)-1, 3.08 ± 0.81; Obs-2, 2.98 ± 0.73; Obs-3, 3.54 ± 0.75], those of the distortion (Obs-1, 2.94 ± 0.50; Obs-2, 2.71 ± 0.70; Obs-3, 3.27 ± 0.53), and the chemical shift artifacts (Obs-1, 3.38 ± 0.60; Obs-2, 3.15 ± 1.07; Obs-3, 3.21 ± 0.85). The averaged image quality scores of RT-DWI were: Sharpness of the liver contour (Obs-1, 2.33 ± 0.65; Obs-2, 2.37 ± 0.74; Obs-3, 2.75 ± 0.81), distortion (Obs-1, 2.81 ± 0.56; Obs-2, 2.25 ± 0.74; Obs-3, 2.96 ± 0.71), and the chemical shift artifacts (Obs-1, 2.92 ± 0.59; Obs-2, 2.21 ± 0.85; Obs-3, 2.77 ± 1.08). All image quality scores of FB-DWI were significantly higher than those of RT-DWI (P < 0.05). The average SNR of the normal liver parenchyma by FB-DWI (11.0 ± 4.8) was not significantly different from that shown by RT-DWI (11.0 ± 5.0); nor were the lesion-to-nonlesion CNRs significantly different (FB-DWI, 21.4 ± 17.7; RT-DWI, 20.1 ± 15.1). For all three observers, the detectability of FB-DWI (Obs-1, 43.6%; Obs-2, 53.6%; and Obs-3, 45.0%) was significantly higher than that of RT-DWI (Obs-1, 29.1%; Obs-2, 43.6%; and Obs-3, 34.5%) (P < 0.05). CONCLUSION FB-DWI showed better image quality and higher detectability of HCC compared to RT-DWI, without significantly reducing the SNRs of the liver parenchyma and lesion-to-nonlesion CNRs. PMID:28588750

Patterns of Care Among Patients Receiving Radiation Therapy for Bone Metastases at a Large Academic Institution

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

Ellsworth, Susannah G.; Alcorn, Sara R., E-mail: salcorn2@jhmi.edu; Hales, Russell K.

Purpose: This study evaluates outcomes and patterns of care among patients receiving radiation therapy (RT) for bone metastases at a high-volume academic institution. Methods and Materials: Records of all patients whose final RT course was for bone metastases from April 2007 to July 2012 were identified from electronic medical records. Chart review yielded demographic and clinical data. Rates of complicated versus uncomplicated bone metastases were not analyzed. Results: We identified 339 patients whose final RT course was for bone metastases. Of these, 52.2% were male; median age was 65 years old. The most common primary was non-small-cell lung cancer (29%). Most patientsmore » (83%) were prescribed ≤10 fractions; 8% received single-fraction RT. Most patients (52%) had a documented goals of care (GOC) discussion with their radiation oncologist; hospice referral rates were higher when patients had such discussions (66% with vs 50% without GOC discussion, P=.004). Median life expectancy after RT was 96 days. Median survival after RT was shorter based on inpatient as opposed to outpatient status at the time of consultation (35 vs 136 days, respectively, P<.001). Hospice referrals occurred for 56% of patients, with a median interval between completion of RT and hospice referral of 29 days and a median hospice stay of 22 days. Conclusions: These data document excellent adherence to American Society for Radiation Oncolology Choosing Wisely recommendation to avoid routinely using >10 fractions of palliative RT for bone metastasis. Nonetheless, single-fraction RT remains relatively uncommon. Participating in GOC discussions with a radiation oncologist is associated with higher rates of hospice referral. Inpatient status at consultation is associated with short survival.« less

Prognostic Significance of Clinicopathologic Features in Patients With Breast Ductal Carcinoma-in-Situ Who Received Breast-Conserving Surgery.

PubMed

Kuo, Sung-Hsin; Lo, Chiao; Chen, Yu-Hsuan; Lien, Huang-Chun; Kuo, Wen-Hung; Wang, Ming-Yang; Lee, Yi-Hsuan; Huang, Chiun-Sheng

2018-04-10

To identify whether a certain group of breast ductal carcinoma-in-situ (DCIS) patients can be treated with breast-conserving surgery (BCS) alone; to analyze the clinicopathologic features of DCIS and tamoxifen administration in patients treated with BCS who developed ipsilateral breast tumor recurrence (IBTR). Data for 375 women with breast DCIS who underwent BCS at our institute between June 2003 and October 2010 were analyzed. The patients were divided into different categories according to the recurrence risk predicted using the California/Van Nuys Prognostic Index (USC/VNPI) score (4-6, 7-9, and 10-12), Eastern Cooperative Oncology Group (ECOG) E5194 criteria, or combined risk features with USC/VNPI score and ECOG E5194 criteria. The IBTR and disease-free survival (DFS) rates were calculated by the Kaplan-Meier method. The prognostic effects of age, tumor size, tumor grade, margin width, estrogen receptor status, USC/VNPI score, low-risk characteristics, and tamoxifen use were evaluated by log-rank tests. Of the patients, 168 were treated with breast irradiation after BCS and 207 were not. The patients who were treated with radiotherapy (RT) tended to be younger (< 40 years), to have higher USC/VNPI scores (7-9), and to meet the ECOG E5194 non-cohort 1 criteria. The 7-year risk of IBTR was 6.2% (n = 11) in the patients who received irradiation and 9.0% (n = 22) in those who did not. DFS rates were better in the patients who underwent RT than in those who did not (93.3% vs. 88.5%, P = .056). Among the patients who underwent BCS alone, age ≥ 40 years, margin width > 10 mm, USC/VNPI scores 4-6, ECOG E5194 cohort 1 criteria, estrogen receptor-positive status, and tamoxifen use predicted lower IBTR and better DFS rates. In the multivariate analysis, combined low-risk characteristics (USC/VNPI scores 4-6 and meeting the ECOG E5194 cohort 1 criteria) were identified as an independent prognostic factor of lower IBTR (P = .028) and better DFS (P = .005). RT reduces the risk of IBTR after BCS for DCIS of the breast. Patients with combined low-risk characteristics (USC/VNPI scores 4-6 and meeting the ECOG E5194 cohort 1 criteria) may be adequately treated with BCS alone. Copyright © 2018 Elsevier Inc. All rights reserved.

Anxiety at the first radiotherapy session for non-metastatic breast cancer: key communication and communication-related predictors.

PubMed

Lewis, Florence; Merckaert, Isabelle; Liénard, Aurore; Libert, Yves; Etienne, Anne-Marie; Reynaert, Christine; Slachmuylder, Jean-Louis; Scalliet, Pierre; Van Houtte, Paul; Coucke, Philippe; Salamon, Emile; Razavi, Darius

2015-01-01

Patients may experience clinically relevant anxiety at their first radiotherapy (RT) sessions. To date, studies have not investigated during/around the RT simulation the key communication and communication-related predictors of this clinically relevant anxiety. Breast cancer patients (n=227) completed visual analog scale (VAS) assessments of anxiety before and after their first RT sessions. Clinically relevant anxiety was defined as having pre- and post-first RT session VAS scores ⩾4 cm. Communication during RT simulation was assessed with content analysis software (LaComm), and communication-related variables around the RT simulation were assessed with questionnaires. Clinically relevant anxiety at the first RT session was predicted by lower self-efficacy to communicate with the RT team (OR=0.65; p=0.020), the perception of lower support received from the RT team (OR=0.70; p=0.020), lower knowledge of RT-associated side effects (OR=0.95; p=0.057), and higher use of emotion-focused coping (OR=1.09; p=0.013). This study provides RT team members with information about potential communication strategies, which may be used to reduce patient anxiety at the first RT session. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Updated Systematic Review and Meta-analysis of the Comparative Data on Colposuspensions, Pubovaginal Slings, and Midurethral Tapes in the Surgical Treatment of Female Stress Urinary Incontinence.

PubMed

Fusco, Ferdinando; Abdel-Fattah, Mohamed; Chapple, Christopher R; Creta, Massimiliano; La Falce, Sabrina; Waltregny, David; Novara, Giacomo

2017-10-01

Retropubic (RP-TVT) and transobturator miurethral (TO-TVT) midurethral sling (MUS) are popular surgical treatments for female stress urinary incontinence. The long-term efficacy and safety of the procedures is still a topic of intense clinical research and several randomised controlled trials (RCTs) have been published in the last years OBJECTIVE: To evaluate the efficacy and safety of MUS compared with other surgical treatments for female stress urinary incontinence. A systematic review and meta-analysis of the literature was performed using the Medline, Scopus, and Web of Science databases to update our previously published analyses. Twenty-eight RCTs were identified. In total, the meta-analyses included 15 855 patients. Patients receiving MUS had significantly higher overall (odds ratio [OR]: 0.59, p=0.0003) and objective (OR: 0.51, p=0.001) cure rates than those receiving Burch colposuspension. Patients undergoing MUS and pubovaginal slings had similar cure rates. Patients treated with RT-TVT had higher subjective (OR: 0.83, p=0.03) and objective (OR: 0.82, p=0.01) cure rates than those receiving TO-TVT. However, the latter had a lower risk of intraoperative bladder or vaginal perforation (OR: 2.4, p=0.0002), pelvic haematoma (OR: 2.61, p=0.002), urinary tract infections (OR: 1.31, p=0.04) and voiding lower urinary tract symptoms (OR: 1.66, p=0.002). Sensitivity analyses limited to RCTs with follow-up durations >60 mo demonstrated similar outcomes for RP-TVT and TO-TVT. No significant differences in efficacy were identified comparing inside-to-out and outside-to-in TO-TVT but vaginal perforations were less common with the former (OR: 0.21, p=0.0002). The present analysis confirms the superiority of MUS over Burch colposuspension. The studies comparing insertion of RT-TVT and TO-TVT showed higher subjective and objective cure rates for the RP-TVT but at the cost of higher risks of some complications and voiding lower urinary tract symptoms. Efficacy of inside-out and outside-in techniques of TO-TVT insertion was similar, although the risk of vaginal perforation was lower in the inside-to-out TO-TVT. Retropubic and transobturator midurethral slings are a popular treatment for female stress urinary incontinence. The available literature suggest that those slings are either more effective or safer than other older surgical procedures. Retropubic tapes are followed with slightly higher continence rates as compared with the transobturator tapes but are associated with higher risk of intra- and postoperative complications. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Clinical equipoise: Protons and the child with craniopharyngioma.

PubMed

Conroy, Ruth; Gomes, Lavier; Owen, Catherine; Buchsbaum, Jeffrey; Ahern, Verity

2015-06-01

Childhood craniopharyngioma is a complex condition to manage. Survival figures are high but the potential for long-term morbidity is great. There is much debate regarding the best management for these tumours with increasing interest in the use of proton beam therapy. We have therefore reviewed our radiotherapy (RT) practice at Westmead Hospital and the literature regarding the use of protons for these children. Three children have received fractionated stereotactic RT for craniopharyngioma at Westmead Hospital since 2007. Each RT plan was reviewed and additional organs at risk were contoured to enable comparison with published proton data. Planning target volume coverage was similar with all modalities: with the conformity index ranging from 0.70 to 0.78 in our patients compared with 0.50-0.84 in the published data. RT dose to temporal lobes, hippocampi and whole brain was also similar with protons and photons. Proton beam therapy may give lower dose to the Circle of Willis than stereotactic RT. Currently there is no clear evidence that proton beam therapy will improve survival or reduce morbidity for children with craniopharyngioma. However, proton therapy has the potential to reduce RT dose to the Circle of Willis, which may reduce the risk of future cerebrovascular complications. We propose that more resources should be allocated to ensuring these patients are managed by experienced multidisciplinary teams through the continuum from diagnosis to long-term follow-up. © 2014 The Royal Australian and New Zealand College of Radiologists.

Diabetes increases the risk of recent-transmission tuberculosis in household contacts in São Paulo, Brazil.

PubMed

Rajan, J V; Ferrazoli, L; Waldman, E A; Simonsen, V; Ferreira, P; Telles, M A; Riley, L W

2017-08-01

A cohort of household contacts of tuberculosis (TB) index cases from four public health clinics in São Paulo, Brazil. To measure the association between diabetes mellitus (DM) among household contacts and recent-transmission TB (RT TB). Index TB cases (n = 263) identified from 2001 to 2002 in São Paulo, whose household contacts (n = 1383) were monitored for active TB until December 2010. From 2001 to 2010, there were 29 cases of RT TB among household contacts (cumulative incidence 2.1%, 95%CI 1.4-2.9). DM in household contacts was associated with RT TB (OR 3.96, 95%CI 1.33-11.79) even after adjustment for human immunodeficiency virus (HIV) status, smoking and alcohol use (adjusted OR [aOR] 3.21, 95%CI 1.01-10.19). HIV infection was also associated with RT TB (OR 6.40, 95%CI 1.40-29.40; aOR 4.81, 95%CI 0.96-24.18). Household contact DM was not associated with non-RT TB (OR 1.27, 95%CI 0.30-5.40). The time to diagnosis of TB was shorter in household contacts with and without DM (P = 0.035) and in household contacts with and without HIV (P = 0.0002). Household contact DM was associated with an increased risk of RT TB in a cohort in Brazil, lending support to the active screening of household contacts with DM for TB in Brazil.

Whole transcriptome RNA-Seq analysis of breast cancer recurrence risk using formalin-fixed paraffin-embedded tumor tissue.

PubMed

Sinicropi, Dominick; Qu, Kunbin; Collin, Francois; Crager, Michael; Liu, Mei-Lan; Pelham, Robert J; Pho, Mylan; Dei Rossi, Andrew; Jeong, Jennie; Scott, Aaron; Ambannavar, Ranjana; Zheng, Christina; Mena, Raul; Esteban, Jose; Stephans, James; Morlan, John; Baker, Joffre

2012-01-01

RNA biomarkers discovered by RT-PCR-based gene expression profiling of archival formalin-fixed paraffin-embedded (FFPE) tissue form the basis for widely used clinical diagnostic tests; however, RT-PCR is practically constrained in the number of transcripts that can be interrogated. We have developed and optimized RNA-Seq library chemistry as well as bioinformatics and biostatistical methods for whole transcriptome profiling from FFPE tissue. The chemistry accommodates low RNA inputs and sample multiplexing. These methods both enable rediscovery of RNA biomarkers for disease recurrence risk that were previously identified by RT-PCR analysis of a cohort of 136 patients, and also identify a high percentage of recurrence risk markers that were previously discovered using DNA microarrays in a separate cohort of patients, evidence that this RNA-Seq technology has sufficient precision and sensitivity for biomarker discovery. More than two thousand RNAs are strongly associated with breast cancer recurrence risk in the 136 patient cohort (FDR <10%). Many of these are intronic RNAs for which corresponding exons are not also associated with disease recurrence. A number of the RNAs associated with recurrence risk belong to novel RNA networks. It will be important to test the validity of these novel associations in whole transcriptome RNA-Seq screens of other breast cancer cohorts.

Whole Transcriptome RNA-Seq Analysis of Breast Cancer Recurrence Risk Using Formalin-Fixed Paraffin-Embedded Tumor Tissue

PubMed Central

Sinicropi, Dominick; Qu, Kunbin; Collin, Francois; Crager, Michael; Liu, Mei-Lan; Pelham, Robert J.; Pho, Mylan; Rossi, Andrew Dei; Jeong, Jennie; Scott, Aaron; Ambannavar, Ranjana; Zheng, Christina; Mena, Raul; Esteban, Jose; Stephans, James; Morlan, John; Baker, Joffre

2012-01-01

RNA biomarkers discovered by RT-PCR-based gene expression profiling of archival formalin-fixed paraffin-embedded (FFPE) tissue form the basis for widely used clinical diagnostic tests; however, RT-PCR is practically constrained in the number of transcripts that can be interrogated. We have developed and optimized RNA-Seq library chemistry as well as bioinformatics and biostatistical methods for whole transcriptome profiling from FFPE tissue. The chemistry accommodates low RNA inputs and sample multiplexing. These methods both enable rediscovery of RNA biomarkers for disease recurrence risk that were previously identified by RT-PCR analysis of a cohort of 136 patients, and also identify a high percentage of recurrence risk markers that were previously discovered using DNA microarrays in a separate cohort of patients, evidence that this RNA-Seq technology has sufficient precision and sensitivity for biomarker discovery. More than two thousand RNAs are strongly associated with breast cancer recurrence risk in the 136 patient cohort (FDR <10%). Many of these are intronic RNAs for which corresponding exons are not also associated with disease recurrence. A number of the RNAs associated with recurrence risk belong to novel RNA networks. It will be important to test the validity of these novel associations in whole transcriptome RNA-Seq screens of other breast cancer cohorts. PMID:22808097

Gene Profiling Technique to Accelerate Stem Cell Therapies for Eye Diseases

MedlinePlus

... like RPE. They also use a technique called quantitative RT-PCR to measure the expression of genes ... higher in iPS cells than mature RPE. But quantitative RT-PCR only permits the simultaneous measurement of ...

A UK survey of driving behaviour, fatigue, risk taking and road traffic accidents.

PubMed

Smith, Andrew P

2016-08-18

The aim of the present research was to examine associations between poor driving behaviour (DB), driving when fatigued (DF), risk taking (RT) and road traffic accidents (RTAs). The study involved a cross-sectional online survey of clients of an insurance company. The survey measured DB (speeding, distraction, lapses of attention and aggression), RT and frequency of driving when fatigued (DF, driving late at night, prolonged driving, driving after a demanding working day and driving with a cold). Demographic, lifestyle, job characteristics and psychosocial factors were also measured and used as covariates. Cardiff, UK. 3000 clients of an insurance company agreed to participate in the study, and 2856 completed the survey (68% woman, 32% man; mean age: 34 years, range 18-74 years). The outcomes were RTAs (requiring medical attention; not requiring medical attention), where the person was the driver. Factor analyses showed that DB, RT and fatigue loaded on independent factors. Logistic regressions showed that poor DB, frequently DF and taking risks predicted medical and non-medical RTAs. These effects were additive and those who reported poor DB, driving when fatigue and taking risks were twice as likely to have an RTA. These effects remained significant when demographic, lifestyle, medical, driving, work and psychosocial factors were covaried. Poor DB, DF and RT predict RTAs. There are now short measuring instruments that can assess these, and driver education programmes must increase awareness of these risk factors. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Resistance exercise and aerobic exercise when paired with dietary energy restriction both reduce the clinical components of metabolic syndrome in previously physically inactive males.

PubMed

Potteiger, Jeffrey A; Claytor, Randal P; Hulver, Mathew W; Hughes, Michael R; Carper, Michael J; Richmond, Scott; Thyfault, John P

2012-06-01

The purpose of this study was to compare resistance exercise training (RT) to aerobic exercise training (AE) on the clinical risk factors for metabolic syndrome (MetSyn) in physically inactive overweight males (age 27-48 years). Subjects with at least one risk factor for MetSyn performed RT (n = 13, age 35.1 ± 4.7 years, BMI 31.2 ± 2.7 kg/m(2)) or AE (n = 9, age 37.6 ± 4.9 years, BMI, 31.2 ± 3.2 kg/m(2)) for 6 months. Training frequency and exercise session duration were equal and by 3 months the subjects exercised 4 day/week for 45 min/session. Blood lipids and glucose, waist circumference, and mean arterial blood pressure (MAP) were measured at 0, 3, and 6 months. A MetSyn z score was calculated for each subject from triglycerides, HDL cholesterol, fasting glucose, waist circumference, and MAP. Statistical significance was set at p ≤ 0.05. No significant differences existed between RT and AE groups at 0 month. AE showed a significant reduction in MetSyn z score from 0 (0.91 ± 3.57) to 6 months (-1.35 ± 2.95), while RT approached significance (p = 0.07) from 0 (0.09 ± 2.62) to 6 months (-1.30 ± 2.22). Triglycerides (mmol/L) significantly decreased in AE from 0 (1.93 ± 0.90) to 6 months (1.41 ± 0.70). Waist circumference (cm) significantly decreased in AE from 0 (106.8 ± 7.3) to 6 months (101.2 ± 6.5), and in RT from 0 (108.4 ± 9.0) to 6 months (105.7 ± 7.0). MAP (mmHg) decreased in RT from 0 (93.8 ± 5.8) to 6 months (87.5 ± 6.1) and in AE from 0 (97.6 ± 7.0) to 6 months (91.3 ± 6.8). With equal training frequency and exercise session duration, both RT and AE training, when paired with energy restriction improve the clinical risk factor profile for MetSyn.

The impact of HPV status on weight loss and feeding tube use in oropharyngeal carcinoma.

PubMed

Vangelov, Belinda; Kotevski, Damian P; Williams, Janet R; Smee, Robert I

2018-04-01

It has been well established that patients with oropharyngeal carcinoma are at high nutritional risk, with significant weight loss and tube feeding common. Human papillomavirus (HPV)-associated disease has led to a change in the "typical" presentation and nutritional profile of this population. The aim of our study was to determine whether the need for a feeding tube, and weight loss during radiotherapy (RT) in patients with oropharyngeal carcinoma differed with HPV status. Patients who received curative RT ± chemotherapy from January 2011 to January 2016 were included (n = 100). We retrospectively evaluated feeding tube use and timing of insertion (prophylactic vs reactive), percentage weight loss during RT and the prevalence of critical weight loss (CWL) ≥5%. HPV-positive patients had significantly higher weight loss during RT compared to the rest of the cohort (8.4% vs 6.1%, 95%CI 0.8-3.9, p = 0.003). CWL was observed in 86% and in a higher proportion with HPV-positive disease (93%, p = 0.011). Conditional probability modelling analysis revealed, with 74% accuracy, concurrent chemoradiotherapy and HPV-positive status were predictors of CWL when comparing HPV-positive patients to HPV-negative (96%, p = 0.001 and 98%, p = 0.012 respectively). More HPV-positive patients required feeding tubes (n = 43, 63%, p = 0.05), most being reactive (n = 27, 63%). All patients with reactive tubes experienced CWL. The high incidence of CWL in patients with HPV-positive oropharyngeal carcinoma is of concern. Tube feeding continues to be a necessary nutritional intervention in this population and predicting who will require a tube is challenging. Larger, prospective cohort studies are required. Copyright © 2018 Elsevier Ltd. All rights reserved.

Does Specialty Bias Trump Evidence in the Management of High-risk Prostate Cancer?

PubMed

Kishan, Amar U; Duchesne, Gillian; Wang, Pin-Chieh; Rwigema, Jean-Claude M; Saigal, Christopher; Rettig, Matthew; Steinberg, Michael L; King, Christopher R

2018-06-01

The objective was to query how specialty influences treatment recommendations for high-risk prostate cancer in 3 clinical settings: upfront management, postoperative management, and management of biochemical recurrences (BCRs) after radiotherapy (RT). We hypothesized that specialty bias would manifest in all settings, trumping available evidence. A survey of practicing urologists and radiation oncologists was distributed through electronic mail. Questions pertained to upfront management, postoperative treatment, and local salvage for postradiation BCRs. The associations between 26 selected categorical responses and specialty were assessed using multivariate logistic regression. Training level/expertise, practice setting, percentage of consultation caseload consisting of prostate cancer, and nationality were set as effect modifiers. One thousand two hundred fifty-three physicians (846 radiation oncologists and 407 urologists) completed the survey. Radiation oncologists were more likely to recommend adjuvant RT and consider it to be underutilized, and more likely to recommend salvage RT at lower prostate-specific antigen thresholds (P<0.0001). Urologists were more likely to recommend salvage radical prostatectomy or cryoablation for local salvage after RT, whereas radiation oncologists were more likely to recommend RT-based modalities and more likely to report that local salvage was underutilized after RT (P<0.0001). Urologists were more likely to report that upfront radical prostatectomy was a better definitive treatment (P<0.0001), whereas radiation oncologists were more likely to report the opposite (P=0.005). Specialty biases permeate recommendations for upfront management and management in the postoperative and post-RT BCR setting, irrespective of available evidence. These data reveal the critical need for multidisciplinary clinics and cross-specialty training as potential solutions for overcoming specialty bias.

Pre-Radiation Therapy Fluorine 18 Fluorodeoxyglucose PET Helps Identify Patients with Esophageal Cancer at High Risk for Radiation Pneumonitis.

PubMed

Castillo, Richard; Pham, Ngoc; Castillo, Edward; Aso-Gonzalez, Samantha; Ansari, Sobiya; Hobbs, Brian; Palacio, Diana; Skinner, Heath; Guerrero, Thomas M

2015-06-01

To examine the association between pre-radiation therapy (RT) fluorine 18 fluorodeoxyglucose (FDG) uptake and post-RT symptomatic radiation pneumonitis (RP). In accordance with the retrospective study protocol approved by the institutional review board, 228 esophageal cancer patients who underwent FDG PET/CT before chemotherapy and RT were examined. RP symptoms were evaluated by using the Common Terminology Criteria for Adverse Events, version 4.0, from the consensus of five clinicians. By using the cumulative distribution of standardized uptake values (SUVs) within the lungs, those values greater than 80%-95% of the total lung voxels were determined for each patient. The effect of pre-chemotherapy and RT FDG uptake, dose, and patient or treatment characteristics on RP toxicity was studied by using logistic regression. The study subjects were treated with three-dimensional conformal RT (n = 36), intensity-modulated RT (n = 135), or proton therapy (n = 57). Logistic regression analysis demonstrated elevated FDG uptake at pre-chemotherapy and RT was related to expression of RP symptoms. Study subjects with elevated 95% percentile of the SUV (SUV95) were more likely to develop symptomatic RP (P < .000012); each 0.1 unit increase in SUV95 was associated with a 1.36-fold increase in the odds of symptomatic RP. Receiver operating characteristic (ROC) curve analysis resulted in area under the ROC curve of 0.676 (95% confidence interval: 0.58, 0.77), sensitivity of 60%, and specificity of 71% at the 1.17 SUV95 threshold. CT imaging and dosimetric parameters were found to be poor predictors of RP symptoms. The SUV95, a biomarker of pretreatment pulmonary metabolic activity, was shown to be prognostic of symptomatic RP. Elevation in this pretreatment biomarker identifies patients at high risk for posttreatment symptomatic RP. RSNA, 2015

Long-term tillage and crop rotation effects on residual nitrate in the crop root zone and nitrate accumulation in the intermediate vadose zone

USGS Publications Warehouse

Katupitiya, A.; Eisenhauer, D.E.; Ferguson, R.B.; Spalding, R.F.; Roeth, F.W.; Bobier, M.W.

1997-01-01

Tillage influences the physical and biological environment of soil. Rotation of crops with a legume affects the soil N status. A furrow irrigated site was investigated for long-term tillage and crop rotation effects on leaching of nitrate from the root zone and accumulation in the intermediate vadose zone (IVZ). The investigated tillage systems were disk-plant (DP), ridge-till (RT) and slot-plant (SP). These tillage treatments have been maintained on the Hastings silt loam (Udic Argiustoll) and Crete silt loam (Pachic Argiustoll) soils since 1976. Continuous corn (CC) and corn soybean (CS) rotations were the subtreatments. Since 1984, soybeans have been grown in CS plots in even calendar years. All tillage treatments received the same N rate. The N rate varied annually depending on the root zone residual N. Soybeans were not fertilized with N-fertilizer. Samples for residual nitrate in the root zone were taken in 8 of the 15 year study while the IVZ was only sampled at the end of the study. In seven of eight years, root zone residual soil nitrate-N levels were greater with DP than RT and SP. Residual nitrate-N amounts were similar in RT and SP in all years. Despite high residual nitrate-N with DP and the same N application rate, crop yields were higher in RT and SP except when DP had an extremely high root zone nitrate level. By applying the same N rates on all tillage treatments, DP may have been fertilized in excess of crop need. Higher residual nitrate-N in DP was most likely due to a combination of increased mineralization with tillage and lower yield compared to RT and SP. Because of higher nitrate availability with DP, the potential for nitrate leaching from the root zone was greater with DP as compared to the RT and SP tillage systems. Spring residual nitrate-N contents of DP were larger than RT and SP in both crop rotations. Ridge till and SP systems had greater nitrate-N with CS than CC rotations. Nitrate accumulation in IVZ at the upstream end of the field was twice as high with DP compared to RT and SP. At the downstream end, it was 2.4 and 1.6 times greater with DP than RT and SP, respectively. Nitrate concentration was greater in the IVZ of DP compared to RT and SP tillage systems. Nitrate accumulations in IVZ of RT and SP were not different. Continuous corn had slightly higher nitrate levels in IVZ than CS. The depth of nitrate penetration at the upstream end was greater than that of the downstream end. Estimated rates of nitrate movement ranged from 0.87 to 0.92 m yr-1 at the upstream end and 0.73 to 0.78 m yr-1 at the downstream end.

Pretreatment risk stratification of feeding tube use in patients treated with intensity-modulated radiotherapy for head and neck cancer.

PubMed

Anderson, Nigel J; Jackson, James E; Smith, Jennifer G; Wada, Morikatsu; Schneider, Michal; Poulsen, Michael; Rolfo, Maureen; Fahandej, Maziar; Gan, Hui; Joon, Daryl Lim; Khoo, Vincent

2018-05-13

The purpose of this study was to establish a risk stratification model for feeding tube use in patients who undergo intensity-modulated radiotherapy (IMRT) for head and neck cancers. One hundred thirty-nine patients treated with definitive IMRT (+/- concurrent chemotherapy) for head and neck mucosal cancers were included in this study. Patients were recommended a prophylactic feeding tube and followed up by a dietician for at least 8 weeks postradiotherapy (post-RT). Potential prognostic factors were analyzed for risk and duration of feeding tube use for at least 25% of dietary requirements. Many variables had significant effects on risk and/or duration of feeding tube use in univariate analyses. Subsequent multivariable analysis showed that T classification ≥3 and level 2 lymphadenopathy were the best independent significant predictors of higher risk and duration of feeding tube use, respectively, in oral cavity, pharyngeal, and supraglottic primaries. In patients treated with definitive IMRT, T classification ≥3 and level 2 lymphadenopathy can potentially stratify patients into 4 risk groups for developing severe dysphagia requiring feeding tube use. © 2018 Wiley Periodicals, Inc.

Examining multi-session brief intervention for substance use in primary care: research methods of a randomized controlled trial.

PubMed

Chambers, Jaclyn E; Brooks, Adam C; Medvin, Rachel; Metzger, David S; Lauby, Jennifer; Carpenedo, Carolyn M; Favor, Kevin E; Kirby, Kimberly C

2016-04-18

Brief interventions such as Screening, a single session of Brief Intervention, and Referral to Treatment (SBIRT) have shown mixed effectiveness in primary care. However, there are indications that multi-session brief interventions may demonstrate more consistently positive outcomes, and perhaps a more intensive approach would be of benefit in addressing substance use in primary care. This study compared the effectiveness of SBIRT with a single BI session (BI/RT) to a multi-session brief-treatment intervention (BI/RT+) in primary care. We also developed easy-to-use, evidence-based materials to assist clinicians in delivering these interventions. This study was conducted in three Federally Qualified Healthcare Centers (FQHCs). A total of 10,935 patients were screened, and 600 individuals were recruited. The sample was primarily Black/African American (82 %) with a mean age of 40. Patients who attended a healthcare appointment were screened for substance use via the AUDIT and DAST. Patients were eligible for the study if they scored 8 or higher on the AUDIT, were using only marijuana and scored 2 or higher on the DAST, or were using other illicit drugs and scored 1 or higher on the DAST. Participants were randomly assigned to receive one-session BI/RT, or two to six sessions of brief intervention that incorporated elements of motivational enhancement therapy and cognitive-behavioral therapy (BI/RT+). Both interventions were delivered by behavioral health consultants at the FQHCs. Participants completed follow-up assessments every 3 months for 1 year. Primary outcome variables included substance use treatment sessions attended and days of substance use. Secondary outcomes included measures of health, employment, legal, and psychiatric functioning and HIV risk behaviors. Additionally, we will conduct an economic evaluation examining cost-effectiveness and will analyze outcomes from a process evaluation examining patient and provider experiences. The ability of brief interventions to impact substance use has great potential, but research findings have been mixed. By conducting a large-scale randomized controlled trial in real-world health centers, this study will answer important questions about the effectiveness of expanded BIs for patients who screen positive for risky substance use in primary care. Trial registration NCT01751672.

Validation of the RT3 triaxial accelerometer for the assessment of physical activity.

PubMed

Rowlands, Ann V; Thomas, Philip W M; Eston, Roger G; Topping, Rodney

2004-03-01

The aims of this study were to assess and compare the validity of the RT3 accelerometer for the assessment of physical activity in boys and men, to compare RT3 and Tritrac accelerometer counts, and to determine count cut-off values for moderate (> or =3 < 6 METs) and vigorous (> or =6 METs) activity. Nineteen boys (age: 9.5 +/- 0.8 yr) and 15 men (age: 20.7 +/- 1.4 yr) walked and ran on a treadmill, kicked a ball to and fro, played hopscotch, and sat quietly. An RT3 was worn on the right hip; boys also wore a Tritrac on the left hip. Oxygen consumption was expressed as a ratio of body mass raised to the power of 0.75 (S VO2). RT3 counts correlated significantly with S VO2 in boys (r = 0.87, P < 0.01) and men (r = 0.85, P < 0.01). However, during treadmill activities, RT3 counts were significantly higher for boys (P < 0.05). RT3 counts corresponding to "moderate" and "vigorous" activity were similar for boys and men for all activities (moderate = 970.2 for boys and 984.0 for men; vigorous = 2333.0 for boys and 2340.8 for men) but approximately 400 counts lower in men when only treadmill activities were considered. Tritrac counts correlated significantly with S VO2 in boys (r = 0.87, P < 0.01), but were significantly lower than RT3 counts across most activities (P < 0.05). The RT3 accelerometer is a good measure of physical activity for boys and men. However, moderate and vigorous intensity count thresholds differ for boys and men when the predominant activities are walking and running. RT3 counts are significantly higher than Tritrac counts for a number of activities. These findings have implications when comparing activity counts between studies using the different instruments.

For-Profit Hospital Ownership Status and Use of Brachytherapy after Breast-Conserving Surgery

PubMed Central

Sen, Sounok; Soulos, Pamela R.; Herrin, Jeph; Roberts, Kenneth B.; Yu, James B.; Lesnikoski, Beth-Ann; Ross, Joseph S.; Krumholz, Harlan M.; Gross, Cary P.

2014-01-01

BACKGROUND Little is known about the relation between surgical care for breast cancer at for-profit hospitals and subsequent use of adjuvant radiation therapy (RT). Among Medicare beneficiaries, we examined whether hospital ownership status is associated with the use of breast brachytherapy – a newer and more expensive modality – as well as overall RT. METHODS We conducted a retrospective study of female Medicare beneficiaries receiving breast-conserving surgery for invasive breast cancer in 2008 and 2009. We assessed the relationship between hospital ownership and receipt of brachytherapy or overall RT using hierarchical generalized linear models. RESULTS The sample consisted of 35,118 women, 8.0% of whom had surgery at for-profit hospitals. Among patients who received RT, those who underwent surgery at for-profit hospitals were significantly more likely to receive brachytherapy (20.2%) than patients treated at not-for-profit hospitals (15.2%; OR for for-profit vs. not-for-profit: 1.50; 95%CI: 1.23–1.84; p<0.001). Among women aged 66–79, there was no relation between hospital ownership status and overall RT use. Among women aged 80–94 years old – the group least likely to benefit from RT due to shorter life expectancy – receipt of surgery at a for-profit hospital was significantly associated with higher overall RT use (OR: 1.22; 95%CI: 1.03–1.45, p=0.03) and brachytherapy use (OR: 1.66; 95%CI: 1.18–2.34, p=0.003). CONCLUSIONS Surgical care at for-profit hospitals was associated with increased use of the newer and more expensive RT modality, brachytherapy. Among the oldest women, who are least likely to benefit from RT, surgical care at a for-profit hospital was associated with higher overall RT use, with this difference largely driven by the use of brachytherapy. PMID:24787104

One-Year Longitudinal Study of Fatigue, Cognitive Functions, and Quality of Life After Adjuvant Radiotherapy for Breast Cancer

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

Noal, Sabine; Clinical Research Department, Centre Francois Baclesse, Caen; Levy, Christelle

Purpose: Most patients with localized breast cancer (LBC) who take adjuvant chemotherapy (CT) complain of fatigue and a decrease in quality of life during or after radiotherapy (RT). The aim of this longitudinal study was to compare the impact of RT alone with that occurring after previous CT on quality of life. Methods and Materials: Fatigue (the main endpoint) and cognitive impairment were assessed in 161 CT-RT and 141 RT patients during RT and 1 year later. Fatigue was assessed with Functional Assessment of Cancer Therapy-General questionnaires, including breast and fatigue modules. Results: At baseline, 60% of the CT-RT patientsmore » expressed fatigue vs. 33% of the RT patients (p <0.001). Corresponding values at the end of RT were statistically similar (61% and 53%), and fatigue was still reported at 1 year by more than 40% of patients in both groups. Risk factors for long-term fatigue included depression (odds ratio [OR] = 6), which was less frequent in the RT group at baseline (16% vs. 28 %, respectively, p = 0.01) but reached a similar value at the end of RT (25% in both groups). Initial mild cognitive impairments were reported by RT (34 %) patients and CT-RT (24 %) patients and were persistent at 1 year for half of them. No biological disorders were associated with fatigue or cognitive impairment. Conclusions: Fatigue was the main symptom in LBC patients treated with RT, whether they received CT previously or not. The correlation of persistent fatigue with initial depressive status favors administering medical and psychological programs for LBC patients treated with CT and/or RT, to identify and manage this main quality-of-life-related symptom.« less

Risk of radiation-induced malignancy with heterotopic ossification prophylaxis: a case-control analysis.

PubMed

Sheybani, Arshin; TenNapel, Mindi J; Lack, William D; Clerkin, Patrick; Hyer, Daniel E; Sun, Wenqing; Jacobson, Geraldine M

2014-07-01

To determine the risk of radiation-induced malignancy after prophylactic treatment for heterotopic ossification (HO). A matched case-control study was conducted within a population-based cohort of 3489 patients treated either for acetabular fractures with acetabular open reduction internal fixation or who underwent total hip arthroplasty from 1990 to 2009. Record-linkage techniques identified patients who were diagnosed with a malignancy from our state health registry. Patients with a prior history of malignancy were excluded from the cohort. For each documented case of cancer, 2 controls were selected by stratified random sampling from the cohort that did not develop a malignancy. Matching factors were sex, age at time of hip treatment, and duration of follow-up. A total of 243 patients were diagnosed with a malignancy after hip treatment. Five patients were excluded owing to inadequate follow-up time in the corresponding control cohort. A cohort of 238 cases (control, 476 patients) was included. Mean follow-up was 10 years, 12 years in the control group. In the cancer cohort, 4% of patients had radiation therapy (RT), compared with 7% in the control group. Of the 9 patients diagnosed with cancer after RT, none occurred within the field. The mean latency period was 5.9 years in the patients who received RT and 6.6 years in the patients who did not. Median (range) age at time of cancer diagnosis in patients who received RT was 62 (43-75) years, compared with 70 (32-92) years in the non-RT patients. An ad hoc analysis was subsequently performed in all 2749 patients who were not matched and found neither an increased incidence of malignancy nor a difference in distribution of type of malignancy. We were unable to demonstrate an increased risk of malignancy in patients who were treated with RT for HO prophylaxis compared with those who were not. Copyright © 2014 Elsevier Inc. All rights reserved.

Risk of Radiation-Induced Malignancy With Heterotopic Ossification Prophylaxis: A Case–Control Analysis

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

Sheybani, Arshin, E-mail: arshin-sheybani@uiowa.edu; TenNapel, Mindi J.; Lack, William D.

2014-07-01

Purpose: To determine the risk of radiation-induced malignancy after prophylactic treatment for heterotopic ossification (HO). Methods and Materials: A matched case–control study was conducted within a population-based cohort of 3489 patients treated either for acetabular fractures with acetabular open reduction internal fixation or who underwent total hip arthroplasty from 1990 to 2009. Record-linkage techniques identified patients who were diagnosed with a malignancy from our state health registry. Patients with a prior history of malignancy were excluded from the cohort. For each documented case of cancer, 2 controls were selected by stratified random sampling from the cohort that did not developmore » a malignancy. Matching factors were sex, age at time of hip treatment, and duration of follow-up. Results: A total of 243 patients were diagnosed with a malignancy after hip treatment. Five patients were excluded owing to inadequate follow-up time in the corresponding control cohort. A cohort of 238 cases (control, 476 patients) was included. Mean follow-up was 10 years, 12 years in the control group. In the cancer cohort, 4% of patients had radiation therapy (RT), compared with 7% in the control group. Of the 9 patients diagnosed with cancer after RT, none occurred within the field. The mean latency period was 5.9 years in the patients who received RT and 6.6 years in the patients who did not. Median (range) age at time of cancer diagnosis in patients who received RT was 62 (43-75) years, compared with 70 (32-92) years in the non-RT patients. An ad hoc analysis was subsequently performed in all 2749 patients who were not matched and found neither an increased incidence of malignancy nor a difference in distribution of type of malignancy. Conclusion: We were unable to demonstrate an increased risk of malignancy in patients who were treated with RT for HO prophylaxis compared with those who were not.« less

Investigating the role of feedback and motivation in clinical reaction time assessment.

PubMed

Eckner, James T; Chandran, Srikrishna; Richardson, James K

2011-12-01

To investigate the influence of performance feedback and motivation during 2 tests of simple visuomotor reaction time (RT). Cross-sectional, observational study. Outpatient academic physiatry clinic. Thirty-one healthy adults (mean [SD], 54 ± 15 years). Participants completed a clinical test of RT (RT(clin)) and a computerized test of RT with and without performance feedback (RT(compFB) and RT(compNoFB), respectively) in randomly assigned order. They then ranked their degree of motivation during each test. RT(clin) measured the time required to catch a suspended vertical shaft by hand closure after release of the shaft by the examiner. RT(compFB) and RT(compNoFB) both measured the time required to press a computer key in response to a visual cue displayed on a computer monitor. Performance feedback (visual display of the previous trial and summary results) was provided for RT(compFB), but not for RT(compNoFB). Means and standard deviations of RT(clin), RT(compFB), and RT(compNoFB) and participants' self-reported motivation on a 5-point Likert scale for each test. There were significant differences in both the means and standard deviations of RT(clin), RT(compFB), and RT(compNoFB) (F(2,60) = 81.66, P < .0001; F(2,60) = 32.46, P < .0001, respectively), with RT(clin) being both the fastest and least variable of the RT measurements. RT(clin) was more strongly correlated with RT(compFB) (r = 0.449, P = .0011) than with RT(compNoFB) (r = 0.314, P = .086). The participants reported similar levels of motivation between RT(clin) and RT(compFB), both of which were reported to be more motivating than RT(compNoFB). The stronger correlation between RT(clin) and RT(compFB) as well as the higher reported motivation during RT(clin) and RT(compFB) testing suggest that performance feedback is a positive motivating factor that is inherent to RT(clin) testing. RT(clin) is a simple, inexpensive technique for measuring RT and appears to be an intrinsically motivating task. This motivation may promote faster, more consistent RT performance compared with currently available computerized programs, which do not typically provide performance feedback. Copyright © 2011 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

The Potential Cost Implications of Averting Severe Hypoglycemic Events Requiring Hospitalization in High-Risk Adults With Type 1 Diabetes Using Real-Time Continuous Glucose Monitoring

PubMed Central

Bronstone, Amy; Graham, Claudia

2016-01-01

Background: Severe hypoglycemia remains a major barrier to optimal diabetes management and places a high burden on the US health care system due to the high costs of hypoglycemia-related emergency visits and hospitalizations. Patients with type 1 diabetes (T1DM) who have hypoglycemia unawareness are at a particularly high risk for severe hypoglycemia, the incidence of which may be reduced by the use of real-time continuous glucose monitoring (RT-CGM). Methods: We performed a cost calculation using values of key parameters derived from various published sources to examine the potential cost implications of standalone RT-CGM as a tool for reducing rates of severe hypoglycemia requiring hospitalization in adult patients with T1DM who have hypoglycemia unawareness. Results: In a hypothetical commercial health plan with 10 million members aged 18-64 years, 9.3% (930 000) are expected to have diagnosed diabetes, with approximately 5% (46 500) having T1DM, of whom approximately 20% (9300) have hypoglycemia unawareness. RT-CGM was estimated to reduce the cost of annual hypoglycemia-related hospitalizations in this select population by $54 369 000, yielding an estimated net cost savings of $8 799 000 to $12 519 000 and a savings of $946 to $1346 per patient. Conclusion: This article presents a cost calculation based on available data from multiple sources showing that RT-CGM has the potential to reduce short-term health care costs by averting severe hypoglycemic events requiring hospitalization in a select high-risk population. Prospective, randomized studies that are adequately powered and specifically enroll patients at high risk for severe hypoglycemia are needed to confirm that RT-CGM significantly reduces the incidence of these costly events. PMID:26880392

Postoperative Concurrent Chemoradiotherapy Versus Postoperative Radiotherapy in High-Risk Cutaneous Squamous Cell Carcinoma of the Head and Neck: The Randomized Phase III TROG 05.01 Trial.

PubMed

Porceddu, Sandro Virgilio; Bressel, Mathias; Poulsen, Michael Geoffrey; Stoneley, Adam; Veness, Michael John; Kenny, Lizbeth Moira; Wratten, Chris; Corry, June; Cooper, Stephen; Fogarty, Gerald Blaise; Collins, Marnie; Collins, Michael Kevin; Macann, Andrew Martin John; Milross, Christopher Gerard; Penniment, Michael Gordon; Liu, Howard Yu-Hao; King, Madeleine Trudy; Panizza, Benedict James; Rischin, Danny

2018-05-01

Purpose To report the results of the Trans Tasman Radiation Oncology Group randomized phase III trial designed to determine whether the addition of concurrent chemotherapy to postoperative radiotherapy (CRT) improved locoregional control in patients with high-risk cutaneous squamous cell carcinoma of the head and neck. Patients and Methods The primary objective was to determine whether there was a difference in freedom from locoregional relapse (FFLRR) between 60 or 66 Gy (6 to 6.5 weeks) with or without weekly carboplatin (area under the curve 2) after resection of gross disease. Secondary efficacy objectives were to compare disease-free survival and overall survival. Results Three hundred twenty-one patients were randomly assigned, with 310 patients commencing allocated treatment (radiotherapy [RT] alone, n = 157; CRT, n = 153). Two hundred thirty-eight patients (77%) had high-risk nodal disease, 59 (19%) had high-risk primary or in-transit disease, and 13 (4%) had both. Median follow-up was 60 months. Median RT dose was 60 Gy, with 84% of patients randomly assigned to CRT completing six cycles of carboplatin. The 2- and 5-year FFLRR rates were 88% (95% CI, 83% to 93%) and 83% (95% CI, 77% to 90%), respectively, for RT and 89% (95% CI, 84% to 94%) and 87% (95% CI, 81% to 93%; hazard ratio, 0.84; 95% CI, 0.46 to 1.55; P = .58), respectively, for CRT. There were no significant differences in disease-free or overall survival. Locoregional failure was the most common site of first treatment failure, with isolated distant metastases as the first site of failure seen in 7% of both arms. Treatment was well tolerated in both arms, with no observed enhancement of RT toxicity with carboplatin. Grade 3 or 4 late toxicities were infrequent. Conclusion Although surgery and postoperative RT provided excellent FFLRR, there was no observed benefit with the addition of weekly carboplatin.

Diffusion-Weighted Magnetic Resonance Imaging to Evaluate Major Salivary Gland Function Before and After Radiotherapy

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

Dirix, Piet; Keyzer, Frederik de; Vandecaveye, Vincent

2008-08-01

Purpose: To evaluate diffusion-weighted (DW)-MRI as a noninvasive tool to investigate major salivary gland function before and after radiotherapy (RT) for head and neck cancer (HNC). Methods and Materials: DW-MRI was performed in 8 HNC patients before and after parotid-sparing RT (mean dose to the contralateral parotid gland <26 Gy). A DW sequence was performed once at rest and then repeated continuously during salivary stimulation. Apparent diffusion coefficient (ADC) maps for both parotid and submandibular glands were calculated. Findings were compared with salivary gland scintigraphy. Results: Before RT, the mean ADC value at rest was significantly lower in the parotidmore » than in the submandibular glands. During the first 5 min of stimulation, the ADC value of the salivary glands showed a decrease, followed by a steady increase until a peak ADC, significantly higher than the baseline value, was reached after a median of 17 min. The baseline ADC value at rest was significantly higher after RT than before RT in the nonspared salivary glands but not in the spared parotid glands. In the contralateral parotid glands, the same response was seen as before RT. This pattern was completely lost in the nonspared glands. These results corresponded with remaining or loss of salivary function, respectively, as confirmed by salivary gland scintigraphy. Conclusions: Diffusion-weighted-MRI allows noninvasive evaluation of functional changes in the major salivary glands after RT and is a promising tool for investigating radiation-induced xerostomia.« less

Acid-producing capacity from sugars and sugar alcohols among Lactobacillus isolates collected in connection with radiation therapy.

PubMed

Almståhl, Annica; Rudbäck, Helena; Basic, Amina; Carlén, Anette; Alstad, Torgny

2017-12-01

To investigate the acid-producing capacity from sugars and sugar alcohols of oral Lactobacillus collected in connection with radiation therapy (RT) to the head and neck region. Lactobacillus were collected from the tongue, buccal mucosa and supragingival plaque in 24 patients before, during, and after RT. The acid-producing capacity of Lactobacillus isolates (n=211) was analyzed using a colorimetric fermentation test in microtiter plates. Solutions containing 2% sugars (sucrose, glucose, fructose, lactose) or sugar-alcohols (sorbitol and xylitol) were used. After 24h of incubation, bacterial acid-producing capacity was determined as strong (pH<5), weak (pH  ≥5-≤ 6) or low/absent (pH>6). Data regarding intake frequency of sugar-rich products and products with sugar-alcohols was collected. The highest acid-producing capacity using the sugars was seen for isolates collected during RT. Sorbitol was fermented to a higher extent during and post RT, especially among isolates from plaque. Lactobacillus fermenting xylitol showed the highest acid-producing capacity during RT (p<0.05). No statistically significant correlations between stimulated whole salivary secretion rate and acid-producing capacity, or between the intake frequency of sugar-rich products or sugar-alcohol containing products and Lactobacillus acid-producing capacity, were found. The results suggest that Lactobacillus isolates, collected from the tongue, buccal mucosa and supragingival plaque, have a higher acid-producing capacity using sugars and sugar-alcohols during RT than one year post RT. Copyright © 2017 Elsevier Ltd. All rights reserved.

A higher body temperature is associated with haemorrhagic transformation in patients with acute stroke untreated with recombinant tissue-type plasminogen activator (rtPA).

PubMed

Leira, Rogelio; Sobrino, Tomás; Blanco, Miguel; Campos, Francisco; Rodríguez-Yáñez, Manuel; Castellanos, Mar; Moldes, Octavio; Millán, Mónica; Dávalos, Antoni; Castillo, José

2012-02-01

Higher body temperature is a prognostic factor of poor outcome in acute stroke. Our aim was to study the relationship between body temperature, HT (haemorrhagic transformation) and biomarkers of BBB (blood-brain barrier) damage in patients with acute ischaemic stroke untreated with rtPA (recombinant tissue-type plasminogen activator). We studied 229 patients with ischaemic stroke <12 h from symptom onset. Body temperature was determined at admission and every 6 h during the first 3 days. HT was evaluated according to ECASS II (second European Co-operative Acute Stroke Study) criteria in a multimodal MRI (magnetic resonance imaging) at 72 h. We found that 55 patients (34.1%) showed HT. HT was associated with cardioembolic stroke (64.2% against 23.0%; P<0.0001), higher body temperature during the first 24 h (36.9°C compared with 36.5°C; P<0.0001), more severe stroke [NIHSS (National Institutes of Health Stroke Scale) score, 14 (9-20) against 10 (7-15); P=0.002], and greater DWI (diffusion-weighted imaging) lesion volume at admission (23.2 cc compared with 13.2 cc; P<0.0001). Plasma MMP-9 (matrix metalloproteinase 9) (187.3 ng/ml compared with 44.2 ng/ml; P<0.0001) and cFn (cellular fibronectin) levels (16.3 μg/ml compared with 7.1 μg/ml; P=0.001) were higher in patients with HT. Body temperature within the first 24 h was independently associated with HT {OR (odds ratio), 7.3 [95% CI (confidence interval), 2.4-22.6]; P<0.0001} after adjustment for cardioembolic stroke subtype, baseline NIHSS score and DWI lesion volume. This effect remained unchanged after controlling for MMP-9 and cFn. In conclusion, high body temperature within the first 24 h after ischaemic stroke is a risk factor for HT in patients untreated with rtPA. This effect is independent of some biological signatures of BBB damage.

Cytomegalovirus Urinary Shedding in HIV-infected Pregnant Women and Congenital Cytomegalovirus Infection.

PubMed

Adachi, Kristina; Xu, Jiahong; Ank, Bonnie; Watts, D Heather; Mofenson, Lynne M; Pilotto, Jose Henrique; Joao, Esau; Santos, Breno; Fonseca, Rosana; Kreitchmann, Regis; Pinto, Jorge; Mussi-Pinhata, Marisa M; Gray, Glenda; Theron, Gerhard; Morgado, Mariza G; Bryson, Yvonne J; Veloso, Valdilea G; Klausner, Jeffrey D; Moye, Jack; Nielsen-Saines, Karin

2017-08-01

Cytomegalovirus (CMV) urinary shedding in pregnant women infected with human immunodeficiency virus (HIV) was evaluated to determine whether it poses an increased risk for congenital CMV infection (cCMV). A subset of mother-infant pairs enrolled in the perinatal NICHD HPTN 040 study (distinguished by no antiretroviral use before labor) was evaluated. Maternal and infant urines were tested by qualitative real-time polymerase chain reaction (RT-PCR) for CMV DNA with quantitative RT-PCR performed on positive specimens. Urine specimens were available for 260 women with 85.4% from the Americas and 14.6% from South Africa. Twenty-four women (9.2%) had detectable CMV viruria by qualitative PCR. Maternal CMV viruria was not associated with mean CD4 cell counts or HIV viral load but was associated with younger maternal age (P = .02). Overall, 10 of 260 infants (3.8%) had cCMV. Women with detectable peripartum CMV viruria were more likely to have infants with cCMV than those without: 20.8% (5/24) versus 2.1% (5/236), (P = .0001). Women with CMV viruria had significantly higher rates of HIV perinatal transmission (29.2% vs. 8.1%, P = .002). They were 5 times (adjusted odds ratio [aOR] = 5.6, 95% confidence interval [CI] 1.9-16.8) and nearly 30 times (aOR, 29.7; 95% CI, 5.4-164.2) more likely to transmit HIV and CMV to their infants, respectively. Maternal gonorrhea (aOR, 19.5; 95% CI, 2.5-151.3) and higher maternal HIV log10 viral load (OR, 2.8; 95% CI, 1.3-6.3) were also significant risk factors for cCMV. In this cohort of HIV-infected pregnant women not on antiretrovirals, urinary CMV shedding was a significant risk factor for CMV and HIV transmission to infants. NCT00099359. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com

Improved Survival Endpoints With Adjuvant Radiation Treatment in Patients With High-Risk Early-Stage Endometrial Carcinoma

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

Elshaikh, Mohamed A., E-mail: melshai1@hfhs.org; Vance, Sean; Suri, Jaipreet S.

2014-02-01

Purpose/Objective(s): To determine the impact of adjuvant radiation treatment (RT) on recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) in patients with high-risk 2009 International Federation of Gynecology and Obstetrics stage I-II endometrial carcinoma. Methods and Materials: We identified 382 patients with high-risk EC who underwent hysterectomy. RFS, DSS, and OS were calculated from the date of hysterectomy by use of the Kaplan-Meier method. Cox regression modeling was used to explore the risks associated with various factors on survival endpoints. Results: The median follow-up time for the study cohort was 5.4 years. The median age was 71 years.more » All patients underwent hysterectomy and salpingo-oophorectomy, 93% had peritoneal cytology, and 85% underwent lymphadenectomy. Patients with endometrioid histology constituted 72% of the study cohort, serous in 16%, clear cell in 7%, and mixed histology in 4%. Twenty-three percent of patients had stage II disease. Adjuvant management included RT alone in 220 patients (57%), chemotherapy alone in 25 patients (7%), and chemoradiation therapy in 27 patients (7%); 110 patients (29%) were treated with close surveillance. The 5-year RFS, DSS, and OS were 76%, 88%, and 73%, respectively. On multivariate analysis, adjuvant RT was a significant predictor of RFS (P<.001) DSS (P<.001), and OS (P=.017). Lymphovascular space involvement was a significant predictor of RFS and DSS (P<.001). High tumor grade was a significant predictor for RFS (P=.038) and DSS (P=.025). Involvement of the lower uterine segment was also a predictor of RFS (P=.049). Age at diagnosis and lymphovascular space involvement were significant predictors of OS: P<.001 and P=.002, respectively. Conclusion: In the treatment of patients with high-risk features, our study suggests that adjuvant RT significantly improves recurrence-free, disease-specific, and overall survival in patients with early-stage endometrial carcinoma. Furthermore, adjuvant RT is an independent predictor for RFS, DSS, and OS in this group of patients. These findings need validation from a prospective randomized study.« less

Comparison of electron microscopy, ELISA, real time RT-PCR and insulated isothermal RT-PCR for the detection of Rotavirus group A (RVA) in feces of different animal species.

PubMed

Soltan, Mohamed A; Tsai, Yun-Long; Lee, Pei-Yu A; Tsai, Chuan-Fu; Chang, Hsiao-Fen G; Wang, Hwa-Tang T; Wilkes, Rebecca P

2016-09-01

There is no gold standard for detection of Rotavirus Group A (RVA), one of the main causes of diarrhea in neonatal animals. Sensitive and specific real-time RT-PCR (rtRT-PCR) assays are available for RVA but require submission of the clinical samples to diagnostic laboratories. Patient-side immunoassays for RVA protein detection have shown variable results, particularly with samples from unintended species. A sensitive and specific test for detection of RVA on the farm would facilitate rapid management decisions. The insulated isothermal RT-PCR (RT-iiPCR) assay works in a portable machine to allow sensitive and specific on-site testing. The aim of this investigation was to evaluate a commercially available RT-iiPCR assay for RVA detection in feces from different animal species. This assay was compared to an in-house rtRT-PCR assay and a commercially available rtRT-PCR kit, as well as an ELISA and EM for RVA detection. All three PCR assays targeted the well-conserved NSP5 gene. Clinical fecal samples from 108 diarrheic animals (mainly cattle and horses) were tested. The percentage of positive samples by ELISA, EM, in-house rtRT-PCR, commercial rtRT-PCR, and RT-iiPCR was 29.4%, 31%, 36.7%, 51.4%, 56.9%, respectively. The agreement between different assays was high (81.3-100%) in samples containing high viral loads. The sensitivity of the RT-iiPCR assay appeared to be higher than the commercially available rtRT-PCR assay, with a limit of detection (95% confidence index) of 3-4 copies of in vitro transcribed dsRNA. In conclusion, the user-friendly, field-deployable RT-iiPCR system holds substantial promise for on-site detection of RVA. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Predicting Future Reading Problems Based on Pre-reading Auditory Measures: A Longitudinal Study of Children with a Familial Risk of Dyslexia

PubMed Central

Law, Jeremy M.; Vandermosten, Maaike; Ghesquière, Pol; Wouters, Jan

2017-01-01

Purpose: This longitudinal study examines measures of temporal auditory processing in pre-reading children with a family risk of dyslexia. Specifically, it attempts to ascertain whether pre-reading auditory processing, speech perception, and phonological awareness (PA) reliably predict later literacy achievement. Additionally, this study retrospectively examines the presence of pre-reading auditory processing, speech perception, and PA impairments in children later found to be literacy impaired. Method: Forty-four pre-reading children with and without a family risk of dyslexia were assessed at three time points (kindergarten, first, and second grade). Auditory processing measures of rise time (RT) discrimination and frequency modulation (FM) along with speech perception, PA, and various literacy tasks were assessed. Results: Kindergarten RT uniquely contributed to growth in literacy in grades one and two, even after controlling for letter knowledge and PA. Highly significant concurrent and predictive correlations were observed with kindergarten RT significantly predicting first grade PA. Retrospective analysis demonstrated atypical performance in RT and PA at all three time points in children who later developed literacy impairments. Conclusions: Although significant, kindergarten auditory processing contributions to later literacy growth lack the power to be considered as a single-cause predictor; thus results support temporal processing deficits' contribution within a multiple deficit model of dyslexia. PMID:28223953

Foliar carbon dynamics of piñon and juniper in response to experimental drought and heat

NASA Astrophysics Data System (ADS)

Collins, A.; Ryan, M. G.; Adams, H. D.; Dickman, L. T.; Garcia-Forner, N.; Grossiord, C.; Powers, H. H.; Sevanto, S.; McDowell, N. G.

2015-12-01

Plant respiration (R) is generally well-coupled with temperature and in the absence of thermal acclimation, respiration is expected to increase as climate change brings higher temperatures. Increased drought is also predicted for future climate, which could drive respiration higher if the carbon (C) cost to maintain tissues (Rm) or grow increases, or lower if substrate or other factors become limiting. We examined the effects of temperature and drought on R as well as photosynthesis, growth, and carbohydrate storage of mature individuals of two co-dominant tree species. Three mature, in-situ piñon (Pinus edulis) and juniper (Juniperus monosperma) trees were assigned to each of the following treatments: +4.8 °C; 45% reduced precipitation; a combination of both (heat + drought); along with ambient control and treatment controls. Rm measured prior to foliar and twig growth was far more sensitive to drought in piñon, and heat in juniper. Total respiration (Rt, R not partitioned) acclimated to temperature in piñon such that elevated temperature had minimal impacts on Rt; however, juniper exhibited higher Rt with elevated temperature, thus juniper did not display any thermal acclimation. Rt in both species was weakly associated with temperature, but strongly correlated with pre-dawn water potential, photosynthetic assimilation (A) rates, and in piñon, foliar carbohydrates. For both species, heat caused far more days where A-R was negative than did drought. The consequences of drought alone and heat alone in piñon included higher Rt per unit growth, indicating that each abiotic stress forces a greater allocation of Rt to maintenance costs, and both drought + heat in combination results in far fewer days that foliar carbohydrates could sustain R in both species. Notably, the much higher A and R of juniper than piñon is consistent with predicted superior carbon budget regulation of juniper than piñon during drought; however, juniper's lack of temperature acclimation in contrast to piñon suggests climate warming may have a greater deleterious impact on juniper carbon balance than piñon.

The impact of dietary regimen compliance on outcomes for HNSCC patients treated with radiation therapy.

PubMed

Kabarriti, Rafi; Bontempo, Amanda; Romano, Maria; McGovern, Kevin P; Asaro, Alyssa; Viswanathan, Shankar; Kalnicki, Shalom; Garg, Madhur K

2018-04-18

To analyze nutritional factors and compliance with dietary recommendations for associations with overall survival (OS) and progression-free survival (PFS) in patients receiving definitive RT for laryngeal and oropharyngeal cancers. We identified 352 patients with non-metastatic laryngeal (146) and oropharyngeal (206) cancer treated with definitive RT between 2004 and 2013. Disease and patient characteristics, treatment information, sarcopenia based on muscle areas at L3 level on CT, compliance with the nutritional program, and clinical outcomes data were tabulated. Descriptive statistics, Kaplan-Meier survival analysis, and log rank tests were performed, and Cox regression models were used to examine predictors of OS and PFS. The median follow-up for the entire cohort was 22.86 months. The actuarial rates for OS were 91, 86, and 73% at years 1, 2, and 5, respectively. Of patients with abdominal CT prior to starting RT, 70.9% (112/158) were sarcopenic with a median muscle mass index of 48.2 (range 30.4-70.9) for males and 35.9 (range 24.6-53.2) for females. The majority (85.8%) of patients met with a dietitian during their course of RT and 62.6% of these patients were compliant with the nutritional program. Compliance with the nutritional program resulted in 27% (HR 0.73, 95% CI 0.43-1.26) protection from death (did not reach significance) and 31% (HR 0.69, 95% CI 0.50-0.94) significant protection from disease progression. Higher pretreatment BMI was associated with a lower risk of death (HR 0.94, 95% CI 0.90-0.99) and disease progression (HR 0.96, 95% CI 0.93-0.99). Laryngeal and oropharyngeal cancer patients treated with definitive RT who are compliant with regular dietetic counseling and contact appear to have improved outcomes. Not applicable.

Salvage Radiation Therapy Dose Response for Biochemical Failure of Prostate Cancer After Prostatectomy—A Multi-Institutional Observational Study

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

Pisansky, Thomas M., E-mail: pisansky.thomas@mayo.edu; Agrawal, Shree; Hamstra, Daniel A.

Purpose: To determine whether a dose-response relationship exists for salvage radiation therapy (RT) of biochemical failure after prostatectomy for prostate cancer. Methods and Materials: Individual data from 1108 patients who underwent salvage RT at 10 academic centers were pooled. The cohort was enriched for selection criteria more likely associated with tumor recurrence in the prostate bed (margin positive and pre-RT prostate-specific antigen [PSA] level of ≤2.0 ng/mL) and without the confounding of planned androgen suppression. The cumulative incidence of biochemical failure and distant metastasis over time was computed, and competing risks hazard regression models were used to investigate the association betweenmore » potential predictors and these outcomes. The association of radiation dose with outcomes was the primary focus. Results: With a 65.2-month follow-up duration, the 5- and 10-year estimates of freedom from post-RT biochemical failure (PSA level >0.2 ng/mL and rising) was 63.5% and 49.8%, respectively, and the cumulative incidence of distant metastasis was 12.4% by 10 years. A Gleason score of ≥7, higher pre-RT PSA level, extraprostatic tumor extension, and seminal vesicle invasion were associated with worse biochemical failure and distant metastasis outcomes. A salvage radiation dose of ≥66.0 Gy was associated with a reduced cumulative incidence of biochemical failure, but not of distant metastasis. Conclusions: The use of salvage radiation doses of ≥66.0 Gy are supported by evidence presented in the present multicenter pooled analysis of individual patient data. The observational reporting method, limited sample size, few distant metastasis events, modest follow-up duration, and elective use of salvage therapy might have diminished the opportunity to identify an association between the radiation dose and this endpoint.« less

A relative difference in systolic blood pressure between arms by synchronal measurement and conventional cardiovascular risk factors are associated with the severity of coronary atherosclerosis.

PubMed

Yamamoto, Tomohiko; Miura, Shin-Ichiro; Suematsu, Yasunori; Kuwano, Takashi; Sugihara, Makoto; Ike, Amane; Iwata, Atsushi; Nishikawa, Hiroaki; Saku, Keijiro

2016-06-01

It is not known the relationships between a difference in systolic blood pressure (SBP) or diastolic BP (DBP) between arms by synchronal measurement and the presence of coronary artery disease (CAD), and between a difference in BP between arms and the severity of coronary atherosclerosis. We enrolled 425 consecutive patients (M/F = 286/139, 67 ± 13 year) who were admitted to our University Hospital and in whom we could measure the absolute (|rt. BP - lt. BP|) and relative (rt. BP - lt. BP) differences in SBP and DBP using a nico PS-501(®) (Parama-Tech). We divided all patients into those who did and did not have CAD. The relative differences in SBP between arms in patients with CAD were significantly lower than those in patients without CAD. However, the relative difference in SBP between arms was not a predictor of the presence of CAD. We also divided 267 patients who underwent coronary angiography into tertiles according to the Gensini score (low, middle, and high score groups). Interestingly, the middle + high score groups showed significantly lower relative differences in SBP between arms than the low score group. The mean Korotkoff sound graph in the middle + high Gensini score group was significantly higher than that in the low Gensini score group. Among conventional cardiovascular risk factors and nico parameters, the relative difference in SBP between arms in addition to the risk factors (age, gender, body mass index, hypertension, dyslipidemia, and diabetes mellitus) was associated with the score by a logistic regression analysis. In conclusion, the relative difference in SBP between arms as well as conventional risk factors may be associated with the severity of coronary arteriosclerosis.

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

Hughes, Michael A.; Parisi, Michele; Grossman, Stuart

Purpose: Patients with primary brain tumors are often treated with high doses of corticosteroids for prolonged periods to reduce intracranial swelling and alleviate symptoms such as headaches. This treatment may lead to immunosuppression, placing the patient at risk of life-threatening opportunistic infections, such as Pneumocystis carinii pneumonia. The risk of contracting some types of infection may be reduced with prophylactic antibiotics. The purpose of this study was to determine the occurrence of low CD4 counts and whether monitoring CD4 counts during and after radiotherapy (RT) is warranted. Methods and Materials: CD4 counts were measured during RT in 70 of 76more » consecutive patients with newly diagnosed Grade III and IV astrocytoma and anaplastic oligodendroglioma treated with corticosteroids and seen at the Johns Hopkins Hospital. Weekly CD4 measurements were taken in the most recent 25 patients. Prophylactic trimethoprim-sulfamethoxazole (160 mg/800 mg p.o. every Monday, Wednesday, and Friday) or dapsone (100 mg p.o. daily) in those with sulfa allergy was prescribed only if patients developed a low CD4 count. Carmustine chemotherapy wafers were placed at surgery in 23% of patients, evenly distributed between the groups. No patient received any other chemotherapy concurrent with RT. Results: CD4 counts decreased to <200/mm{sup 3} in 17 (24%) of 70 patients. For the 25 patients with weekly CD4 counts, all CD4 counts were >450/mm{sup 3} before RT, but 6 (24%) of 25 fell to <200/mm{sup 3} during RT. Patients with counts <200/mm{sup 3} were significantly more likely to be hospitalized (41% vs. 9%, p <0.01) and be hospitalized for infection (23% vs. 4%, p <0.05) during RT. Overall survival was not significantly different between the groups. All patients with low CD4 counts were treated with prophylactic antibiotics, and no patient developed Pneumocystis carinii pneumonia. No patients developed a serious adverse reaction to antibiotic therapy. The mean dose of steroids, mean minimal white blood cell count, and number of patients treated with Gliadel wafers were not significantly different between the groups. Conclusion: The results of this study have confirmed the clinical impression that the use of high-dose corticosteroids and RT in patients with primary brain cancer is sufficient to result in severe immunosuppression and place these patients at risk of life-threatening opportunistic infections. A protocol of prophylactic antibiotics for those at risk may help prevent a potentially fatal side effect of treatment. A prospective study is underway to determine the frequency, depth, and prognostic implications of this finding.« less

Prostate-Specific Antigen Halving Time While on Neoadjuvant Androgen Deprivation Therapy Is Associated With Biochemical Control in Men Treated With Radiation Therapy for Localized Prostate Cancer

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

Malik, Renuka; Jani, Ashesh B.; Liauw, Stanley L., E-mail: sliauw@radonc.uchicago.ed

2011-03-15

Purpose: To assess whether the PSA response to neoadjuvant androgen deprivation therapy (ADT) is associated with biochemical control in men treated with radiation therapy (RT) for prostate cancer. Methods and Materials: In a cohort of men treated with curative-intent RT for localized prostate cancer between 1988 and 2005, 117 men had PSA values after the first and second months of neoadjuvant ADT. Most men had intermediate-risk (45%) or high-risk (44%) disease. PSA halving time (PSAHT) was calculated by first order kinetics. Median RT dose was 76 Gy and median total duration of ADT was 4 months. Freedom from biochemical failuremore » (FFBF, nadir + 2 definition) was analyzed by PSAHT and absolute PSA nadir before the start of RT. Results: Median follow-up was 45 months. Four-year FFBF was 89%. Median PSAHT was 2 weeks. A faster PSA decline (PSAHT {<=}2 weeks) was associated with greater FFBF (96% vs. 81% for a PSAHT >2 weeks, p = 0.0110). Those within the fastest quartile of PSAHTs ({<=} 10 days) achieved a FFBF of 100%. Among high-risk patients, a PSAHT {<=}2 weeks achieved a 4-yr FFBF of 93% vs. 70% for those with PSAHT >2 weeks (p = 0.0508). Absolute PSA nadir was not associated with FFBF. On multivariable analysis, PSAHT (p = 0.0093) and Gleason score (p = 0.0320) were associated with FFBF, whereas T-stage (p = 0.7363) and initial PSA level (p = 0.9614) were not. Conclusions: For men treated with combined ADT and RT, PSA response to the first month of ADT may be a useful criterion for prognosis and treatment modification.« less

Phase 1 trial of neoadjuvant radiation therapy before prostatectomy for high-risk prostate cancer.

PubMed

Koontz, Bridget F; Quaranta, Brian P; Pura, John A; Lee, W R; Vujaskovic, Zeljko; Gerber, Leah; Haake, Michael; Anscher, Mitchell S; Robertson, Cary N; Polascik, Thomas J; Moul, Judd W

2013-09-01

To evaluate, in a phase 1 study, the safety of neoadjuvant whole-pelvis radiation therapy (RT) administered immediately before radical prostatectomy in men with high-risk prostate cancer. Twelve men enrolled and completed a phase 1 single-institution trial between 2006 and 2010. Eligibility required a previously untreated diagnosis of localized but high-risk prostate cancer. Median follow-up was 46 months (range, 14-74 months). Radiation therapy was dose-escalated in a 3 × 3 design with dose levels of 39.6, 45, 50.4, and 54 Gy. The pelvic lymph nodes were treated up to 45 Gy with any additional dose given to the prostate and seminal vesicles. Radical prostatectomy was performed 4-8 weeks after RT completion. Primary outcome measure was intraoperative and postoperative day-30 morbidity. Secondary measures included late morbidity and oncologic outcomes. No intraoperative morbidity was seen. Chronic urinary grade 2+ toxicity occurred in 42%; 2 patients (17%) developed a symptomatic urethral stricture requiring dilation. Two-year actuarial biochemical recurrence-free survival was 67% (95% confidence interval 34%-86%). Patients with pT3 or positive surgical margin treated with neoadjuvant RT had a trend for improved biochemical recurrence-free survival compared with a historical cohort with similar adverse factors. Neoadjuvant RT is feasible with moderate urinary morbidity. However, oncologic outcomes do not seem to be substantially different from those with selective postoperative RT. If this multimodal approach is further evaluated in a phase 2 setting, 54 Gy should be used in combination with neoadjuvant androgen deprivation therapy to improve biochemical outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

Mouth opening in patients irradiated for head and neck cancer: a prospective repeated measures study.

PubMed

Kamstra, J I; Dijkstra, P U; van Leeuwen, M; Roodenburg, J L N; Langendijk, J A

2015-05-01

Aims of this prospective cohort study were (1) to analyze the course of mouth opening up to 48months post-radiotherapy (RT), (2) to assess risk factors predicting decrease in mouth opening, and (3) to develop a multivariable prediction model for change in mouth opening in a large sample of patients irradiated for head and neck cancer. Mouth opening was measured prior to RT (baseline) and at 6, 12, 18, 24, 36, and 48months post-RT. The primary outcome variable was mouth opening. Potential risk factors were entered into a linear mixed model analysis (manual backward-stepwise elimination) to create a multivariable prediction model. The interaction terms between time and risk factors that were significantly related to mouth opening were explored. The study population consisted of 641 patients: 70.4% male, mean age at baseline 62.3years (sd 12.5). Primary tumors were predominantly located in the oro- and nasopharynx (25.3%) and oral cavity (20.6%). Mean mouth opening at baseline was 38.7mm (sd 10.8). Six months post-RT, mean mouth opening was smallest, 36.7mm (sd 10.0). In the linear mixed model analysis, mouth opening was statistically predicted by the location of the tumor, natural logarithm of time post-RT in months (Ln (months)), gender, baseline mouth opening, and baseline age. All main effects interacted with Ln (months). The mean mouth opening decreased slightly over time. Mouth opening was predicted by tumor location, time, gender, baseline mouth opening, and age. The model can be used to predict mouth opening. Copyright © 2015 Elsevier Ltd. All rights reserved.

Respiratory Therapist Job Perceptions: The Impact of Protocol Use.

PubMed

Metcalf, Ashley Y; Stoller, James K; Habermann, Marco; Fry, Timothy D

2015-11-01

Demand for respiratory care services and staffing levels of respiratory therapists (RTs) is expected to increase over the next several years. Hence, RT job satisfaction will be a critical factor in determining recruitment and retention of RTs. Determinants of RT job satisfaction measures have received little attention in the literature. This study examines the use of respiratory care protocols and associated levels of RT job satisfaction, turnover intentions, and job stress. Four-hundred eighty-one RTs at 44 hospitals responded to an online survey regarding job satisfaction, turnover intentions, and job stress. Random coefficient modeling was used for analysis and to account for the nested structure of the data. Higher levels of RT protocol use were associated with higher levels of job satisfaction, lower rates of turnover intentions, and lower levels of job stress. In addition, RTs with greater experience had higher levels of job satisfaction, and RTs working at teaching hospitals had lower rates of turnover intentions. The study extends prior research by examining how the use of respiratory care protocols favorably affects RTs' perceptions of job satisfaction, turnover intention, and job stress. In a time of increasing demand for respiratory care services, protocols may enhance retention of RTs. Copyright © 2015 by Daedalus Enterprises.

Does Radiation Have a Role in Advanced Stage Hodgkin's or Non-Hodgkin Lymphoma?

PubMed

Specht, Lena

2016-01-01

Radiation therapy (RT) is one of the most effective agents available in the treatment of lymphomas. However, it is a local treatment, and today, with systemic treatments assuming a primary role for induction of response, RT is primarily used for consolidation. For advanced stage lymphomas, the indications for the use of RT have been questioned and debated, and proper randomized evidence is sparse. RT has significant long-term side effects, and the very extended RT fields of the past yielded unacceptable toxicity in many patients. Modern advanced imaging and conformal RT techniques now enable treatment of larger and anatomically more challenging target volumes with much less radiation to normal tissues and consequently much lower risks of long-term complications. The modern concept of involved site radiation therapy (ISRT) has now been accepted as standard in lymphomas. In advanced Hodgkin lymphoma (HL), RT to residual disease and/or initial bulk benefits some patients, depending on the chemotherapy regimen used. The more intensive the chemotherapy regimen, the fewer patients benefit from RT. In advanced aggressive non-Hodgkin lymphoma (NHL), most of the evidence comes from the most common type, the diffuse large B cell lymphoma (DLBCL). In patients treated with modern immunochemotherapy, RT to initial bulky disease or extralymphatic involvement is beneficial. For both HL and aggressive NHL, RT to residual masses after systemic treatment is of benefit. The role of PET in the evaluation and indication for RT to residual masses has not been tested in randomized trials. In advanced indolent NHL, very low dose RT offers excellent palliation with very few side effects. Modern RT in advanced lymphomas warrants further evaluation in randomized trials.

Evaluation of erectile dysfunction risk factors in young male survivors of colorectal cancer.

PubMed

Sendur, Mehmet A N; Aksoy, Sercan; Ozdemir, Nuriye Y; Yaman, Sebnem; Yazici, Ozan; Bulent Akinci, Muhammed; Uncu, Dogan; Zengin, Nurullah; Altundag, Kadri

2014-01-01

Improved long-term survival of colorectal cancer patients (CRC) treated with surgery and/or chemotherapy ± radiotherapy (RT) has led to increased awareness of long-term side effects, including effecting sexual life, which can ultimately affect the quality of life in these patients. Because the absolute risk factors of erectile dysfunction (ED) have not been defined in CRC patients, the aim of this research was to identify the severity and the absolute risk factors of ED in male CRC survivors. The medical records of 61 male survivors of CRC treated with surgery and/or chemotherapy ± RT were retrieved from the medical oncology outpatient clinics during routine follow-up visits in 2011-2012. Patients older than 55 years and those with ED history before diagnosis were excluded. International Index of Erectile Function (IIEF) questionnaire was filled in by the patients. The patient mean age was 47.6±6.7 years (range 18-55) at the time of filling in the questionnaire. According to the International Index of Erectile Function (IIEF) score, 83.6% of the patients had some degree of ED. The risk factors of erectile dysfunction were advancing age (p=0.01), tumor location (p=0.01), type of surgery (p=0.02), presence of stoma (p=0.03)) and RT (p=0.005). Chemotherapy didn't impact ED (p=0.46). Also, there was no significant correlation between smoking status, hypertension, diabetes mellitus, cardiovascular disease, stage of the tumor and ED. Also hormonal disturbances such as serum FSH, LH and testesterone levels did not affect the presence of ED. Overall, 83.6% of the male CRC survivors had some degree of ED according to the IIEF. The risk factors of ED were advancing age, tumor location, type of operation, presence of stoma and RT. Clinicians should be aware of these risk factors to offer their patients adequate treatment options and also come up with new treatment strategies necessary to reduce further ED in CRC survivors.

SU-E-J-264: Using Magnetic Resonance Imaging-Derived Features to Quantify Radiotherapy-Induced Normal Tissue Morbidity

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

Thor, M; Tyagi, N; Deasy, J

2015-06-15

Purpose: The aim of this study was to explore the use of Magnetic Resonance Imaging (MRI)-derived features as indicators of Radiotherapy (RT)-induced normal tissue morbidity. We also investigate the relationship between these features and RT dose in four critical structures. Methods: We demonstrate our approach for four patients treated with RT for base of tongue cancer in 2005–2007. For each patient, two MRI scans (T1-weighted pre (T1pre) and post (T1post) gadolinium contrast-enhancement) were acquired within the first six months after RT. The assessed morbidity endpoint observed in 2/4 patients was Grade 2+ CTCAEv.3 trismus. Four ipsilateral masticatory-related structures (masseter, lateralmore » and medial pterygoid, and the temporal muscles) were delineated on both T1pre and T1post and these scans were co-registered to the treatment planning CT using a deformable demons algorithm. For each structure, the maximum and mean RT dose, and six MRI-derived features (the second order texture features entropy and homogeneity, and the first order mean, median, kurtosis, and skewness) were extracted and compared structure-wise between patients with and without trismus. All MRI-derived features were calculated as the difference between T1pre and T1post, ΔS. Results: For 5/6 features and all structures, ΔS diverged between trismus and non-trismus patients particularly for the masseter, lateral pterygoid, and temporal muscles using the kurtosis feature (−0.2 vs. 6.4 for lateral pterygoid). Both the maximum and mean RT dose in all four muscles were higher amongst the trismus patients (with the maximum dose being up to 25 Gy higher). Conclusion: Using MRI-derived features to quantify RT-induced normal tissue complications is feasible. We showed that several features are different between patients with and without morbidity and that the RT dose in all investigated structures are higher amongst patients with morbidity. MRI-derived features, therefore, has the potential to improve predictions of normal tissue morbidity.« less

Prevention of Gynecomastia and Breast Pain Caused by Androgen Deprivation Therapy in Prostate Cancer: Tamoxifen or Radiotherapy?

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

Arruda Viani, Gustavo, E-mail: gusviani@gmail.com; Bernardes da Silva, Lucas Godoi; Stefano, Eduardo Jose

Purpose: To determine, in a meta-analysis, whether gynecomastia and breast pain rates in men with prostate cancer treated with androgen deprivation therapy (ADT) are reduced if treated with prophylactic radiotherapy (RT) or tamoxifen (TMX). Methods and Materials: The MEDLINE, EMBASE, CANCERLIT, and Cochrane Library databases, as well as proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing RT or TMX with observation for men with prostate cancer using ADT. Results: Six RCTs (three RT trials and three TMX trials, N = 777 patients total) were identified that met the study criteria. Pooled results from these RCTsmore » comparing RT vs. observation showed a significant reduction in the incidence of gynecomastia and breast pain rates in patients treated with RT (odds ratio [OR] = 0.21, 95% confidence interval [CI] = 0.12-0.37, p < 0.0001, and OR = 0.34, 95% CI 0.20-0.57, p < 0.0001, respectively). Use of RT resulted in an absolute risk reduction (ARR) of 29.4% and 19.9%, with a number needed to treat (NNT) of 3.4 and 5 to avoid one case of gynecomastia and breast pain, respectively. Pooled results from trials comparing TMX vs. observation showed a statistical benefit for breast pain and gynecomastia in favor of TMX arms (OR = 0.04, 95% CI = 0.02-0.08, p < 0.0001 and OR = 0.07, 95% CI = 0.0-0.14, p < 0.00001). TMX resulted in an ARR = 64.1% and 47.6%, with an NNT of 1.56 and 2.1 to avoid one case of gynecomastia and breast pain, respectively. Considering adverse effects, TMX was 6 times more adverse effects than RT. Conclusions: Our data have shown that both TMX and RT prevented gynecomastia and breast pain in patients with prostate cancer receiving ADT for prostate cancer. Although TMX was two times more effective in preventing gynecomastia, RT should represent an effective and safe treatment option, to take into account mainly in patients with cardiovascular risk factors or thrombotic diathesis.« less

Pro-community altruism and social status in a Shuar village.

PubMed

Price, Michael E

2003-06-01

Reciprocity theory (RT) and costly signaling theory (CST) provide different explanations for the high status of pro-community altruists: RT proposes that altruists are positively and negatively sanctioned by others, whereas CST proposes that altruists are attractive to others. Only RT, however, is beset by first- and higher-order free rider problems, which must be solved in order for RT to explain status allocations. In this paper, several solutions to RT's free rider problems are proposed, and data about status allocations to Ecuadorian Shuar pro-community altruists are analyzed in light of RT and CST. These data confirm that perceived pro-community altruists are indeed high status and suggest that (1) community residents skillfully monitor the altruism of coresidents, (2) residents who engage in opportunities to broadcast desirable qualities are high status only to the extent that they are considered altruistic, and (3) individuals who sanction coresidents based on coresidents' contributions to the community are themselves relatively high status. To a greater extent than CST, RT straightforwardly predicts all of these results.

Breast-conserving therapy after previous irradiation for lymphoma.

PubMed

Nguyen, Sonia K A; Dagnault, Anne

2010-12-01

There is an increased risk of breast cancer in patients who have undergone radiation treatment for lymphoma. While this usually precludes further radiotherapy (RT), we report five women who received irradiation for lymphoma and who subsequently received breast-conserving therapy between 1995 and 2007 for early-stage breast cancer. There was an overlap between the two treatment fields in all patients. RT for lymphoma ranged between 29.8 and 40 grays (Gy). The interval between lymphoma and the diagnosis of breast cancer was 11-24 years. All five patients had lumpectomy and received subsequent RT (45 Gy in four patients, 50 Gy in the other). All tolerated breast RT well, and toxicity was limited to grade 1 events. All five patients were alive at last follow-up, and there was no local recurrence in the irradiated breast in any patient. We conclude that previous RT for lymphoma is not necessarily an absolute contraindication to breast-conserving therapy.

Thrombolysis with Intravenous Tissue Plasminogen Activator (rt-PA) Predicts Favorable Discharge Disposition in Patients with Acute Ischemic Stroke

PubMed Central

Ifejika-Jones, Nneka L.; Harun, Nusrat; Mohammed-Rajput, Nareesa A.; Noser, Elizabeth A.; Grotta, James C.

2011-01-01

Background and Purpose Acute ischemic stroke patients receiving IV tissue plasminogen activator (rt-PA) within 3 hours of symptom onset are 30% more likely to have minimal disability at three months. During hospitalization, short-term disability is subjectively measured by discharge disposition, whether to home, Inpatient Rehabilitation (IR), Skilled Nursing Facility (SNF) or Subacute Care (Sub). There are no studies assessing the role of rt-PA use as a predictor of post-stroke disposition. Methods Retrospective analysis of all ischemic stroke patients admitted to the University of Texas Houston Medical School (UTHMS) Stroke Service between Jan 2004 and Oct 2009. Baseline demographics and National Institute of Health Stroke Scale (NIHSS) score were collected. Cerebrovascular disease risk factors were used for risk stratification. Results Home vs. IR, SNF, Sub Of 2225 acute ischemic stroke patients, 1019 were discharged home, 1206 to another level of care. Patients who received rt-PA therapy were 1.9 times more likely to be discharged home (P = <0.0001; OR 1.945, 95% CI 1.538 to 2.459). IR vs. SNF, Sub / SNF vs. Sub Of 1206 acute ischemic stroke patients, 719 patients were discharged to acute IR, 371 were discharged to SNF, 116 to Sub. There were no differences in disposition between patients who received rt-PA therapy. Conclusions Stroke patients who receive IV rt-PA for acute ischemic stroke are more 1.9 times more likely to be discharged directly home after hospitalization. This study is limited by its retrospective nature and the undetermined role of psychosocial factors related to discharge. PMID:21293014

Designing cylindrical implosion experiments on NIF to study deceleration phase of Rayleigh-Taylor

NASA Astrophysics Data System (ADS)

Vazirani, N.; Kline, J. L.; Loomis, E.; Sauppe, J. P.; Palaniyappan, S.; Flippo, K.; Srinivasan, B.; Malka, E.; Bose, A.; Shvarts, D.

2017-10-01

The Rayleigh-Taylor (RT) hydrodynamic instability occurs when a lower density fluid pushes on a higher density fluid. This occurs in inertial confinement fusion (ICF) implosions at each of the capsule interfaces during the initial acceleration and the deceleration as it stagnates. The RT instabilities mix capsule material into the fusion fuel degrading the Deuterium-Tritium reactivity and ultimately play a key role in limiting target performance. While significant effort has focused on understanding RT at the outer capsule surface, little work has gone into understanding the inner surface RT instability growth during the deceleration phase. Direct measurements of the RT instability are difficult to make at high convergence in a spherical implosion. Here we present the design of a cylindrical implosion system for the National Ignition Facility for studying deceleration phase RT. We will discuss the experimental design, the estimated instability growth, and our outstanding concerns.

Outcomes After Radiation Therapy to Metastatic Sites in Patients With Stage 4 Neuroblastoma

PubMed Central

Kandula, Shravan; Prabhu, Roshan S.; Nanda, Ronica; Switchenko, Jeffrey M.; Cash, Thomas; Qayed, Muna; Katzenstein, Howard; Esiashvili, Natia

2016-01-01

Summary In patients with high-risk metastatic neuroblastoma, the benefit of radiation therapy (RT) to metastatic sites as part of primary treatment has not been fully investigated. The purpose of this single-institution study was to evaluate local control of irradiated metastatic sites, and characterize metastatic disease burden and anatomic distribution in patients with high-risk metastatic neuroblastoma. The records of all patients diagnosed with stage 4 neuroblastoma between August 2000 and January 2010 were reviewed. Exclusion criteria included: bone-marrow only metastatic site, total body irradiation, or no imaging follow-up. A total of 37 patients met eligibility criteria. Median follow-up period for patients without relapse was 61 months. Five-year overall survival for all patients was 67%. Thirteen patients (35%) received RT to a metastatic site as part of their primary treatment. Among these patients, in-field recurrence occurred in three patients (23%), including two of three treated calvarial sites. In patients treated with or without RT to a metastatic site, respectively, there was no significant difference in 5-year overall survival (73% vs. 63%, P = 0.84) or relapse-free survival (46% and 55%, P = 0.48). Current metastatic site RT dose may be suboptimal, and certain locations may predict for a poor response. Further studies are necessary to elucidate the optimal role of RT to metastatic sites. PMID:25238225

Evaluation of a duplex reverse-transcription real-time PCR assay for the detection of encephalomyocarditis virus.

PubMed

Qin, Shaomin; Underwood, Darren; Driver, Luke; Kistler, Carol; Diallo, Ibrahim; Kirkland, Peter D

2018-06-01

We evaluated a fluorogenic probe-based assay for the detection of encephalomyocarditis virus (EMCV) by comparing a set of published primers and probe to a new set of primers and probe. The published reagents failed to amplify a range of Australian isolates and an Italian reference strain of EMCV. In contrast, an assay based on 2 new sets of primers and probes that were run in a duplex reverse-transcription real-time PCR (RT-rtPCR) worked well, with high amplification efficiency. The analytical sensitivity was ~100-fold higher than virus isolation in cell culture. The intra-assay variation was 0.21-4.90%. No cross-reactivity was observed with a range of other porcine viruses. One hundred and twenty-two clinical specimens were tested simultaneously by RT-rtPCR and virus isolation in cell culture; 72 specimens gave positive results by RT-rtPCR, and 63 of these were also positive by virus isolation. Of 245 archived cell culture isolates of EMCV that were tested in the RT-rtPCR, 242 samples were positive. The new duplex RT-rtPCR assay is a reliable tool for the detection of EMCV in clinical specimens and for use in epidemiologic investigations.

Cardiotoxicity and cancer therapy: treatment-related cardiac morbidity in patients presenting with symptoms suggestive of heart or lung disease.

PubMed

Wieshammer, Siegfried; Dreyhaupt, Jens; Müller, Dirk; Momm, Felix; Jakob, Andreas; Freund, Ulrich

2013-01-01

Cardiac injury is one of the complications of cancer treatment. This study aimed to investigate the relationships between the types of radiotherapy of the chest (RT), chemotherapy (CT), cancer surgery (CS) and endocrine therapy (ET), and the presence of heart disease, and their associations with the serum level of N-terminal pro-B-type natriuretic peptide (NT-proBNP). A consecutive series of 374 patients with cancer who were referred because of symptoms suggestive of heart or lung disease prospectively underwent a diagnostic workup. The prevalence of heart disease was 36.9%. RT administered before 1995 (n = 19) was associated with both increased odds of heart disease [adjusted odds ratio 10.3, 95% confidence interval 3.1-34.0] and higher ln-transformed NT-proBNP values (p < 0.01) compared to the control group (no RT or RT for right-sided breast cancer from 1995 onwards; n = 311). Anthracycline-treated patients (n = 54) had higher adjusted values for ln(NT-proBNP) compared to the control group (no CT; n = 243; p < 0.01) but no increased odds of heart disease. While pre-1995 RT and anthracycline-containing CT were associated with cardiac effects, there was no evidence that RT using modern cardioprotective techniques, CT in the absence of anthracyclines, CS or ET had detrimental effects on the heart. Copyright © 2013 S. Karger AG, Basel.

Are levels of NT-proBNP and SDMA useful to determine diastolic dysfunction in chronic kidney disease and renal transplant patients?

PubMed

Memon, Lidija; Spasojevic-Kalimanovska, Vesna; Stanojevic, Natasa Bogavac; Kotur-Stevuljevic, Jelena; Simic-Ogrizovic, Sanja; Giga, Vojislav; Dopsaj, Violeta; Jelic-Ivanovic, Zorana; Spasic, Slavica

2013-11-01

The aim of the study was to determine the clinical usefulness of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and symmetric dimethylarginine (SDMA) for detection of renal and left ventricular (LV) diastolic dysfunction in chronic kidney disease (CKD) patients and renal transplant (RT) recipients. We included 98 CKD and 44 RT patients. We assessed LV function using pulsed-wave Doppler ultrasound. Diastolic dysfunction was defined when the E:A ratio was <1. Independent predictors of NT-proBNP levels were age, creatinine, and albumin in CKD patients and age and urea in RT patients. Determinants of SDMA in CKD patients were glomerular filtration rate (GFR) and NT-proBNP and creatinine in RT patients. In RT patients with diastolic dysfunction, NT-proBNP and SDMA were significantly higher than in patients without diastolic dysfunction (F = 7.478, P < 0.011; F = 2.631, P < 0.017). After adjustment for GFR, the differences were not seen. In CKD patients adjusted NT-proBNP and SDMA values for GFR were not significantly higher in patients with diastolic dysfunction than in patients without diastolic dysfunction. NT-proBNP is useful for detection of LV diastolic dysfunction in RT recipients. When evaluating both NT-proBNP and SDMA it is necessary to consider GFR as a confounding factor. © 2013 Wiley Periodicals, Inc.

Value of apparent diffusion coefficient (ADC) in assessing radiotherapy and chemotherapy success in cervical cancer.

PubMed

Fu, Zhan-Zhao; Peng, Yong; Cao, Li-Yan; Chen, Yan-Sheng; Li, Kun; Fu, Bao-Hong

2015-06-01

We investigated the clinical significance of apparent diffusion coefficient (ADC) values in diffusion-weighted magnetic resonance imaging (DWI) in monitoring the efficacy of radiotherapy (RT) and chemotherapy (CT) treatments in cervical cancer. In order to identify relevant high quality clinical cohort studies reporting the use of DWI in cervical cancers, the following electronic databases in English and Chinese languages were comprehensively searched: MEDLINE, Science Citation Index database, Cochrane Library Database, PubMed, Embase, CINAHL, and Current Contents Index; Chinese Biomedical Database, Chinese Journal Full-Text Database. All selected studies were published prior to March 2014, and data extracted from these studies were analyzed using STATA 12.0 statistical software. We initially retrieved 196 articles (79 Chinese articles and 117 English articles) through database searches and finally selected sixteen cohort studies for this meta-analysis. The 16 studies contained a combined total of 517 subjects, and all selected studies reported the mean ADC value (10(-3) mm(2)/s) in DWI in cervical cancer patients treated with RT and CT. Combined standardized mean difference (SMD) suggested that the mean post-RT and mean post-CT ADC values were significantly higher than the mean pre-RT and mean pre-CT ADC values, respectively, in cervical cancer patients (SMD=2.95, 95% CI=2.19-3.72, P<0.001). Ethnicity-stratified analysis revealed that increased ADC values were observed post-RT and post-CT in both Caucasian (SMD=1.44, 95% CI=0.93-1.95, P<0.001) and Asian populations (SMD=3.32, 95% CI=2.42-4.22, P<0.001), compared with the mean ADC values before RT and CT, respectively, in the two subgroups. Further, subgroup analysis based on b-value revealed that higher ADC values were found in cervical cancer patients after RT and CT, compared to before RT and CT treatment, with both b value≤900 (SMD=3.71, 95% CI=2.35-5.07, P<0.001) and >900 (SMD=2.55, 95% CI=1.78-3.32, P<0.001). The mean ADC value in patients without residual tumor post-RT and post-CT treatment was significantly higher than seen in patients with residual tumors (SMD=0.80, 95% CI=0.49-1.12, P<0.001). Our meta-analysis revealed a significant correlation between mean ADC values and the clinical response to RT and CT treatment. Thus, ADC values in DWI may be effective in evaluating the clinical outcome of treatments in cervical cancer patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Esthesioneuroblastoma of the nasal cavity.

PubMed

Hollen, Tyler R; Morris, Christopher G; Kirwan, Jessica M; Amdur, Robert J; Werning, John W; Vaysberg, Mikhail; Mendenhall, William M

2015-06-01

Esthesioneuroblastoma is an uncommon cancer of the nasal cavity. We describe the outcomes for 26 patients treated with curative intent with photon radiotherapy (RT) at the University of Florida. Between May 1972 and June 2007, 26 patients received RT for previously untreated esthesioneuroblastoma of the nasal cavity. Sixteen patients were males and 10 were females with a median age of 55 years (range, 3 to 82 y). The modified Kadish stage distribution was: B, 7 patients; C, 17 patients; and D, 2 patients. Treatment modalities included the following: definitive RT, 5 patients; preoperative RT, 2 patients; and postoperative RT after resection, 19 patients. Elective neck irradiation (ENI) was performed in 17 (71%) of 24 N0 patients. Rates of local control, cause-specific survival, and absolute overall survival at 5 years were 79%, 72%, and 69%, respectively. Overall survival among patients treated with definitive RT was 20% at 5 years, compared with 81% among those who underwent surgery and adjuvant RT (P=0.01). One (6%) of 17 patients who received ENI developed a recurrence in the neck and was successfully salvaged. Ultimate neck control was 100% at 5 years for patients who received ENI versus 69% among those not receiving ENI (P=0.0173). Resection combined with adjuvant RT is more effective than surgery or RT alone in the treatment of esthesioneuroblastoma. ENI reduces the risk of regional relapse in patients with Kadish stage B and C cancers.

Intensity modulated radiation-therapy for preoperative posterior abdominal wall irradiation of retroperitoneal liposarcomas

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

Bossi, Alberto; De Wever, Ivo; Van Limbergen, Erik

2007-01-01

Purpose: Preoperative external-beam radiation therapy (preop RT) in the management of Retroperitoneal Liposarcomas (RPLS) typically involves the delivery of radiation to the entire tumor mass: yet this may not be necessary. The purpose of this study is to evaluate a new strategy of preop RT for RPLS in which the target volume is limited to the contact area between the tumoral mass and the posterior abdominal wall. Methods and Materials: Between June 2000 and Jan 2005, 18 patients with the diagnosis of RPLS have been treated following a pilot protocol of pre-op RT, 50 Gy in 25 fractions of 2more » Gy/day. The Clinical Target Volume (CTV) has been limited to the posterior abdominal wall, region at higher risk for local relapse. A Three-Dimensional conformal (3D-CRT) and an Intensity Modulated (IMRT) plan were generated and compared; toxicity was reported following the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events v3.0. Results: All patients completed the planned treatment and the acute toxicity was tolerable: 2 patients experienced Grade 3 and 1 Grade 2 anorexia while 2 patients developed Grade 2 nausea. IMRT allows a better sparing of the ipsilateral and the contralateral kidney. All tumors were successfully resected without major complications. At a median follow-up of 27 months 2 patients developed a local relapse and 1 lung metastasis. Conclusions: Our strategy of preop RT is feasible and well tolerated: the rate of resectability is not compromised by limiting the preop CTV to the posterior abdominal wall and a better critical-structures sparing is obtained with IMRT.« less

Modern Radiation Therapy for Nodal Non-Hodgkin Lymphoma—Target Definition and Dose Guidelines From the International Lymphoma Radiation Oncology Group

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

Illidge, Tim, E-mail: Tim.Illidge@ics.manchester.ac.uk; Specht, Lena; Yahalom, Joachim

2014-05-01

Radiation therapy (RT) is the most effective single modality for local control of non-Hodgkin lymphoma (NHL) and is an important component of therapy for many patients. Many of the historic concepts of dose and volume have recently been challenged by the advent of modern imaging and RT planning tools. The International Lymphoma Radiation Oncology Group (ILROG) has developed these guidelines after multinational meetings and analysis of available evidence. The guidelines represent an agreed consensus view of the ILROG steering committee on the use of RT in NHL in the modern era. The roles of reduced volume and reduced doses aremore » addressed, integrating modern imaging with 3-dimensional planning and advanced techniques of RT delivery. In the modern era, in which combined-modality treatment with systemic therapy is appropriate, the previously applied extended-field and involved-field RT techniques that targeted nodal regions have now been replaced by limiting the RT to smaller volumes based solely on detectable nodal involvement at presentation. A new concept, involved-site RT, defines the clinical target volume. For indolent NHL, often treated with RT alone, larger fields should be considered. Newer treatment techniques, including intensity modulated RT, breath holding, image guided RT, and 4-dimensional imaging, should be implemented, and their use is expected to decrease significantly the risk for normal tissue damage while still achieving the primary goal of local tumor control.« less

Novel HBV recombinants between genotypes B and C in 3'-terminal reverse transcriptase (RT) sequences are associated with enhanced viral DNA load, higher RT point mutation rates and place of birth among Chinese patients.

PubMed

Liu, Baoming; Yang, Jing-Xian; Yan, Ling; Zhuang, Hui; Li, Tong

2018-01-01

As one of the major global public health concerns, hepatitis B virus (HBV) can be divided into at least eight genotypes, which may be related to disease severity and treatment response. We previously demonstrated that genotypes B and C HBV, with distinct geographical distribution in China, had divergent genotype-dependent amino acid polymorphisms and variations in reverse transcriptase (RT) gene region, a target of antiviral therapy using nucleos(t)ide analogues. Recently recombination between HBV genotypes B and C was reported to occur in the RT region. However, their frequency and clinical significance is poorly understood. Here full-length HBV RT sequences from 201 Chinese chronic hepatitis B (CHB) patients were amplified and sequenced, among which 31.34% (63/201) were genotype B whereas 68.66% (138/201) genotype C. Although no intergenotypic recombination was detected among C-genotype HBV, 38.10% (24/63) of B-genotype HBV had recombination with genotype C in the 3'-terminal RT sequences. The patients with B/C intergenotypic recombinants had significantly (P<0.05) higher serum HBV DNA level than the "pure" B-genotype cohort did. Moreover, the B/C intergenotypic recombinants were prone to more substitutions at several specific residues in the RT region than genotype B or C. Besides, unlike their parental genotypes, the recombinant HBV appeared to display an altered geographic distribution feature in China. Our findings provide novel insight into the virological, clinical and epidemiological features of new HBV B/C intergenotypic recombinants at the 3' end of RT sequences among Chinese CHB patients. The highly complex genetic background of the novel recombinant HBV carrying new mutations affecting RT protein may contribute to an enhanced heterogeneity in treatment response or prognosis among CHB patients. Published by Elsevier B.V.

Resistance Training Improves Muscle Function and Cardiometabolic Risks But Not Quality of Life in Older People With Type 2 Diabetes Mellitus: A Randomized Controlled Trial.

PubMed

Hsieh, Ping-Lun; Tseng, Chin-Hsiao; Tseng, Yufeng Jane; Yang, Wei-Shiung

In older people with type 2 diabetes mellitus (T2DM), the effects of aging and T2DM may compromise the function of skeletal muscle, deteriorate metabolic status, and jeopardize physical performance, aerobic capacity, and quality of life (QoL). The purpose of this study was to investigate the effects of 12 weeks of resistance training (RT) on muscle function, physical performance, cardiometabolic risks, and QoL in older people with T2DM. This study was a randomized controlled trial that employed block randomization, assessor blinding, and the intention-to-treat principle. Thirty people 65 years or older with a diagnosis of T2DM were randomly assigned to either an exercise group or a control group and were further stratified by gender. The exercise group performed 8 RT exercises in 3 sets of 8 to 12 repetitions at 75% 1-repetition maximum (1-RM) 3 times per week for 12 weeks. The control group received usual care and maintained their daily activities and lifestyle. Muscle function (1-RM and muscle oxygenation responses), physical performance (5-repetition sit-to-stand test and Timed Up and Go test), cardiometabolic risks (aerobic capacity, blood pressure, body composition, glycemic control, lipids levels, and high-sensitivity C-reactive protein levels), and QoL (Audit of Diabetes-Dependent Quality of Life 19) were assessed at baseline (week 0) and after the 12-week interventions (week 12). The 1-RM chest-press and leg-press strength and physical performance in 5-repetition sit-to-stand test were significantly improved in the exercise group compared with the controls after the interventions. The exercise group had significantly lower resting systolic blood pressure (by -12.1 mm Hg, P = 0.036) than did the controls after 12 weeks of RT, without any significant within-group change in either group after intervention. The waist circumference, fasting glucose levels, and peak diastolic blood pressure tended to favor RT over usual care after the interventions. Twelve weeks of RT increased the maximal strength in chest-press and leg-press tests, and improved 5-repetition sit-to-stand performance in older people with T2DM. Our study demonstrated that supervised, structured RT was able to promote muscle function and alleviate cardiometabolic risks in people with T2DM 65 years or older.

Aberrant Methylation-Mediated Suppression of APAF1 in Myelodysplastic Syndrome.

PubMed

Zaker, Farhad; Nasiri, Nahid; Amirizadeh, Naser; Razavi, Seyed Mohsen; Yaghmaie, Marjan; Teimoori-Toolabi, Ladan; Maleki, Ali; Bakhshayesh, Masoumeh

2017-04-01

Background: Myelodysplastic syndromes (MDSs) include a diverse group of clonal bone marrow disorders characterized by ineffective hematopoiesis and pancytopenia. It was found that down regulation of APAF1, a putative tumor suppressor gene (TSG), leads to resistance to chemotherapy and disease development in some cancers. In this study, we investigated the relation of APAF1 methylation status with its expression and clinicopathological factors in myelodysplastic syndrome (MDS) patients. Materials and Methods: Methylation Sensitive-High Resolution Melting Curve Analysis (MS-HRM) was employed in studying the methylation of CpG islands in the APAF1promoter region in MDS. Gene expression was analyzed by using real time RT-PCR. Results: 42.6% of patient samples were methylated in promoter region of APAF1analyzed, while methylation of the gene was not seen in controls (P<0.05). Methylation of APAF1was significantly associated with the suppression of its mRNA expression (P=0.00). The methylation status of APAF1in advanced-stage MDS patients (80%) was significantly higher than that of the early-stage MDS patients (28.2%) (P=0.001). The difference in frequency of hypermethylatedAPAF1 gene was significant between good (37.5%) and poor (85.71%) cytogenetic risk groups (P=0.043). In addition, a higher frequency of APAF1hypermethylation was observed in higher-risk MDS group (69.2%) compared to lower-risk MDS group (34.14%) (P=0.026). Conclusion: Our study indicated that APAF1hypermethylation in MDS was associated to high-risk disease classified according to the IPSS, WHO and cytogenetic risk.

Simplest chronoscope. III. Further comparisons between reaction times obtained by meterstick versus machine.

PubMed

Montare, Alberto

2013-06-01

The three classical Donders' reaction time (RT) tasks (simple, choice, and discriminative RTs) were employed to compare reaction time scores from college students obtained by use of Montare's simplest chronoscope (meterstick) methodology to scores obtained by use of a digital-readout multi-choice reaction timer (machine). Five hypotheses were tested. Simple RT, choice RT, and discriminative RT were faster when obtained by meterstick than by machine. The meterstick method showed higher reliability than the machine method and was less variable. The meterstick method of the simplest chronoscope may help to alleviate the longstanding problems of low reliability and high variability of reaction time performances; while at the same time producing faster performance on Donders' simple, choice and discriminative RT tasks than the machine method.

Comparison of academic and practice outcomes of rural and traditional track graduates of a family medicine residency program.

PubMed

Petrany, Stephen M; Gress, Todd

2013-06-01

The Marshall University Family Medicine Residency (MUFMR) implemented its rural track (RT) in 1994 to help achieve its mission of producing primary care physicians for practice in rural areas and West Virginia. This study examined the impact of the RT on the program's training outcomes and assessed the academic equivalence of the RT and traditional track (TT) curricula. The authors analyzed academic outcomes (in-training examination [ITE] scores, board certification rates) and practice outcomes (location and type following graduation) for the 174 MUFMR graduates who entered the program from 1984 through 2006. They compared RT and TT graduates who entered after RT implementation (1994-2006) with each other and with graduates who entered during the decade before implementation (1984-1993). There were differences between the 12 RT and 94 TT graduates in rural practice upon graduation (RT: 83% versus TT: 40%; P<.01) and practice in West Virginia (RT 83% versus TT 68%; P=.34). RT and TT graduates had similar mean increases in ITE scores and board certification rates. The 106 post-implementation graduates had a significantly higher rate of West Virginia practice than did the 68 pre-implementation graduates (70% versus 52%; P=.02). RT development was associated with a substantial increase in MUFMR graduates practicing in West Virginia. RT graduates were more likely than TT graduates to practice in rural areas and in the state upon graduation. RT graduates seem to advance academically as well as their TT counterparts.

The effects of aerobic, resistance, and combination training on insulin sensitivity and secretion in overweight adults from STRRIDE AT/RT: a randomized trial.

PubMed

AbouAssi, Hiba; Slentz, Cris A; Mikus, Catherine R; Tanner, Charles J; Bateman, Lori A; Willis, Leslie H; Shields, A Tamlyn; Piner, Lucy W; Penry, Lorrie E; Kraus, Erik A; Huffman, Kim M; Bales, Connie W; Houmard, Joseph A; Kraus, William E

2015-06-15

Most health organizations recommend a combination of aerobic training (AT) and resistance training (RT), yet few studies have compared their acute (within 24 h of the last exercise bout) and sustained (after 14 days of no exercise training) effects alone and in combination on glucose metabolism. The present study (Studies Targeting Risk Reduction Interventions through Defined Exercise-Aerobic Training and/or Resistance Training) compared the effects of AT, RT, and the combination (AT/RT) on insulin action at both acute and sustained phases. Subjects (N = 196) were 18-70 yr old (mean age = 50 yr), overweight (mean body mass index = 30 kg/m2), sedentary with moderate dyslipidemia, and were randomized into one of three 8-mo exercise groups: 1) RT: 3 days/wk, 8 exercises, 3 sets/exercise, 8-12 repetitions/set; 2) AT: equivalent to ∼19.2 km/wk (12 miles/wk) at 75% peak O2 consumption; 3) AT/RT: the combination of AT and RT. One hundred forty-four subjects completed the intervention. Eighty-eight subjects completed all pre- and postintervention testing visits. Insulin sensitivity, glucose effectiveness, and disposition index were measured via a frequently sampled intravenous glucose tolerance test with subsequent minimal model analyses. AT/RT resulted in greater improvements in insulin sensitivity, β-cell function (disposition index), and glucose effectiveness than either AT or RT alone (all P < 0.05). Approximately 52% of the improvement in insulin sensitivity by AT/RT was retained 14 days after the last exercise training bout. Neither AT or RT led to acute or chronic improvement in sensitivity index. In summary, only AT/RT (which required twice as much time as either alone) led to significant acute and sustained benefits in insulin sensitivity

Epigastric Distress Caused by Esophageal Candidiasis in 2 Patients Who Received Sorafenib Plus Radiotherapy for Hepatocellular Carcinoma: Case Report.

PubMed

Chen, Kuo-Hsin; Weng, Meng-Tzu; Chou, Yueh-Hung; Lu, Yueh-Feng; Hsieh, Chen-Hsi

2016-03-01

Sorafenib followed by fractionated radiotherapy (RT) has been shown to decrease the phagocytic and candidacidal activities of antifungal agents due to radiosensitization. Moreover, sorafenib has been shown to suppress the immune system, thereby increasing the risk for candida colonization and infection. In this study, we present the 2 hepatocellular carcinoma (HCC) patients suffered from epigastric distress caused by esophageal candidiasis who received sorafenib plus RT. Two patients who had received sorafenib and RT for HCC with bone metastasis presented with hiccups, gastric ulcer, epigastric distress, anorexia, heart burn, and fatigue. Empiric antiemetic agents, antacids, and pain killers were ineffective at relieving symptoms. Panendoscopy revealed diffuse white lesions in the esophagus. Candida esophagitis was suspected. Results of periodic acid-Schiff staining were diagnostic of candidiasis. Oral fluconazole (150 mg) twice daily and proton-pump inhibitors were prescribed. At 2-weak follow-up, esophagitis had resolved and both patients were free of gastrointestinal symptoms. Physicians should be aware that sorafenib combined with RT may induce an immunosuppressive state in patients with HCC, thereby increasing their risk of developing esophagitis due to candida species.

Patterns of local-regional recurrence following parotid-sparing conformal and segmental intensity-modulated radiotherapy for head and neck cancer.

PubMed

Dawson, L A; Anzai, Y; Marsh, L; Martel, M K; Paulino, A; Ship, J A; Eisbruch, A

2000-03-15

To analyze the patterns of local-regional recurrence in patients with head and neck cancer treated with parotid-sparing conformal and segmental intensity-modulated radiotherapy (IMRT). Fifty-eight patients with head and neck cancer were treated with bilateral neck radiation (RT) using conformal or segmental IMRT techniques, while sparing a substantial portion of one parotid gland. The targets for CT-based RT planning included the gross tumor volume (GTV) (primary tumor and lymph node metastases) and the clinical target volume (CTV) (postoperative tumor bed, expansions of the GTVs and lymph node groups at risk of subclinical disease). Lymph node targets at risk of subclinical disease included the bilateral jugulodigastric and lower jugular lymph nodes, bilateral retropharyngeal lymph nodes at risk, and high jugular nodes at the base of skull in the side of the neck at highest risk (containing clinical neck metastases and/or ipsilateral to the primary tumor). The CTVs were expanded by 5 mm to yield planning target volumes (PTVs). Planning goals included coverage of all PTVs (with a minimum of 95% of the prescribed dose) and sparing of a substantial portion of the parotid gland in the side of the neck at less risk. The median RT doses to the gross tumor, the operative bed, and the subclinical disease PTVs were 70.4 Gy, 61.2 Gy, and 50.4 Gy respectively. All recurrences were defined on CT scans obtained at the time of recurrence, transferred to the pretreatment CT dataset used for RT planning, and analyzed using dose-volume histograms. The recurrences were classified as 1) "in-field," in which 95% or more of the recurrence volume (V(recur)) was within the 95% isodose; 2) "marginal," in which 20% to 95% of V(recur) was within the 95% isodose; or 3) "outside," in which less than 20% of V(recur) was within the 95% isodose. With a median follow-up of 27 months (range 6 to 60 months), 10 regional recurrences, 5 local recurrences (including one noninvasive recurrence) and 1 stomal recurrence were seen in 12 patients, for a 2-year actuarial local-regional control rate of 79% (95% confidence interval 68-90%). Ten patients (80%) relapsed in-field (in areas of previous gross tumor in nine patients), and two patients developed marginal recurrences in the side of the neck at highest risk (one in the high retropharyngeal nodes/base of skull and one in the submandibular nodes). Four regional recurrences extended superior to the jugulodigastric node, in the high jugular and retropharyngeal nodes near the base of skull of the side of the neck at highest risk. Three of these were in-field, in areas that had received the dose intended for subclinical disease. No recurrences were seen in the nodes superior to the jugulodigastric nodes in the side of the neck at less risk, where RT was partially spared. The majority of local-regional recurrences after conformal and segmental IMRT were "in-field," in areas judged to be at high risk at the time of RT planning, including the GTV, the operative bed, and the first echelon nodes. These findings motivate studies of dose escalation to the highest risk regions.

Locally targeted delivery of a micron-size radiation therapy source using temperature-sensitive hydrogel.

PubMed

Kim, Yusung; Seol, Dong Rim; Mohapatra, Sucheta; Sunderland, John J; Schultz, Michael K; Domann, Frederick E; Lim, Tae-Hong

2014-04-01

To propose a novel radiation therapy (RT) delivery modality: locally targeted delivery of micron-size RT sources by using temperature-sensitive hydrogel (RT-GEL) as an injectable vehicle. Hydrogel is a water-like liquid at room temperature but gels at body temperature. Two US Food and Drug Administration-approved polymers were synthesized. Indium-111 (In-111) was used as the radioactive RT-GEL source. The release characteristics of In-111 from polymerized RT-GEL were evaluated. The injectability and efficacy of RT-GEL delivery to human breast tumor were tested using animal models with control datasets of RT-saline injection. As proof-of-concept studies, a total of 6 nude mice were tested by injecting 4 million tumor cells into their upper backs after a week of acclimatization. Three mice were injected with RT-GEL and 3 with RT-saline. Single-photon emission computed tomography (SPECT) and CT scans were performed on each mouse at 0, 24, and 48 h after injection. The efficacy of RT-GEL was determined by comparison with that of the control datasets by measuring kidney In-111 accumulation (mean nCi/cc), representing the distant diffusion of In-111. RT-GEL was successfully injected into the tumor by using a 30-gauge needle. No difficulties due to polymerization of hydrogel during injection and intratumoral pressure were observed during RT-GEL injection. No back flow occurred for either RT-GEL or RT-saline. The residual tumor activities of In-111 were 49% at 24 h (44% at 48 h, respectively) for RT-GEL and 29% (22%, respectively) for RT-saline. Fused SPECT-CT images of RT-saline showed considerable kidney accumulation of In-111 (2886%, 261%, and 262% of RT-GEL at 0, 24, and 48 h, respectively). RT-GEL was successfully injected and showed much higher residual tumor activity: 170% (200%, respectively), than that of RT-saline at 24 h (48 h, respectively) after injection with a minimal accumulation of In-111 to the kidneys. Preliminary data of RT-GEL as a delivery modality of a radiation source to a local tumor are promising. Published by Elsevier Inc.

Close Margins Less Than 2 mm Are Not Associated With Higher Risks of 10-Year Local Recurrence and Breast Cancer Mortality Compared With Negative Margins in Women Treated With Breast-Conserving Therapy.

PubMed

Tyler, Susan; Truong, Pauline T; Lesperance, Mary; Nichol, Alan; Baliski, Chris; Warburton, Rebecca; Tyldesley, Scott

2018-03-13

The 2014 Society of Surgical Oncology-American Society for Radiation Oncology consensus suggested "no ink on tumor" is a sufficient surgical margin for invasive breast cancer treated with breast-conserving surgery (BCS). Whether close margins <2 mm are associated with inferior outcomes remains controversial. This study evaluated 10-year outcomes by margin status in a population-based cohort treated with BCS and adjuvant radiation therapy (RT). The subjects were 10,863 women with invasive cancer categorized as pT1 to T3, any N, and M0 referred from 2001 to 2011, an era in which the institutional policy was to re-excise close or positive margins, except in select cases. All women underwent BCS and whole-breast RT with or without boost RT. Local recurrence (LR) and breast cancer-specific survival (BCSS) were examined using competing-risk analysis in cohorts with negative (≥2 mm; n = 9241, 85%), close (<2 mm; n = 1310, 12%), or positive (tumor touching ink; n = 312, 3%) margins. Multivariable analysis and matched-pair analysis were performed. The median follow-up period was 8 years. Systemic therapy was used in 87% of patients. Boost RT was used in 34.1%, 76.9%, and 79.5% of patients with negative, close, and positive margins, respectively. In the negative, close, and positive margin cohorts, the 10-year cumulative incidence of LR was 1.8%, 2.0%, and 1.1%, respectively (P = .759). Corresponding BCSS estimates were 93.9%, 91.8%, and 87.9%, respectively (P < .001). On multivariable analysis, close margins were not associated with increased LR (hazard ratio, 1.25; 95% confidence interval 0.79-1.97; P = .350) or reduced BCSS (hazard ratio, 1.25; 95% confidence interval 0.98-1.58, P = .071) relative to negative margins. On matched-pair analysis, close margin cases had similar LR (P = .114) and BCSS (P = .100) to negative margin controls. Select cases with close or positive margins in this population-based analysis had similar LR and BCSS to cases with negative margins. While these findings do not endorse omitting re-excision for all cases, the data support a policy of accepting carefully selected cases with close margins for adjuvant RT without re-excision. Copyright © 2018 Elsevier Inc. All rights reserved.

Percentage of Positive Biopsy Cores: A Better Risk Stratification Model for Prostate Cancer?

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

Huang Jiayi; Vicini, Frank A.; Williams, Scott G.

2012-07-15

Purpose: To assess the prognostic value of the percentage of positive biopsy cores (PPC) and perineural invasion in predicting the clinical outcomes after radiotherapy (RT) for prostate cancer and to explore the possibilities to improve on existing risk-stratification models. Methods and Materials: Between 1993 and 2004, 1,056 patients with clinical Stage T1c-T3N0M0 prostate cancer, who had four or more biopsy cores sampled and complete biopsy core data available, were treated with external beam RT, with or without a high-dose-rate brachytherapy boost at William Beaumont Hospital. The median follow-up was 7.6 years. Multivariate Cox regression analysis was performed with PPC, Gleasonmore » score, pretreatment prostate-specific antigen, T stage, PNI, radiation dose, androgen deprivation, age, prostate-specific antigen frequency, and follow-up duration. A new risk stratification (PPC classification) was empirically devised to incorporate PPC and replace the T stage. Results: On multivariate Cox regression analysis, the PPC was an independent predictor of distant metastasis, cause-specific survival, and overall survival (all p < .05). A PPC >50% was associated with significantly greater distant metastasis (hazard ratio, 4.01; 95% confidence interval, 1.86-8.61), and its independent predictive value remained significant with or without androgen deprivation therapy (all p < .05). In contrast, PNI and T stage were only predictive for locoregional recurrence. Combining the PPC ({<=}50% vs. >50%) with National Comprehensive Cancer Network risk stratification demonstrated added prognostic value of distant metastasis for the intermediate-risk (hazard ratio, 5.44; 95% confidence interval, 1.78-16.6) and high-risk (hazard ratio, 4.39; 95% confidence interval, 1.70-11.3) groups, regardless of the use of androgen deprivation and high-dose RT (all p < .05). The proposed PPC classification appears to provide improved stratification of the clinical outcomes relative to the National Comprehensive Cancer Network classification. Conclusions: The PPC is an independent and powerful predictor of clinical outcomes of prostate cancer after RT. A risk model replacing T stage with the PPC to reduce subjectivity demonstrated potentially improved stratification.« less

Progressive Resistance Training Improves Overall Physical Activity Levels in Patients With Early Osteoarthritis of the Knee: A Randomized Controlled Trial

PubMed Central

Going, Scott B.; McKnight, Patrick E.; Kasle, Shelley; Cussler, Ellen C.; Cornett, Michelle

2010-01-01

Background Prescription of resistance training (RT) exercises is an essential aspect of management for knee osteoarthritis (OA). However, whether patients with knee OA who are randomly assigned to receive RT simply substitute RT for other modes of physical activity remains unclear. Objective The aim of this study was to determine the effect of a structured RT intervention on overall levels of moderate- and vigorous-intensity physical activity (MVPA) in patients with early-onset knee OA. The study compared patients with early-onset OA who participated in an RT program, those who participated in a self-management (SM) program, and those who participated in both RT and SM. Because participants randomly assigned to receive the RT intervention may simply switch activity modes, resulting in little net effect, we assessed total MVPA in addition to tracking changes in strength (force-generating capacity). Design and Intervention This study was a randomized controlled trial comparing the effectiveness of SM alone, RT alone, and combined RT+SM on MVPA in patients with early OA of the knee. Setting The study was conducted on a university campus, with patient recruitment from the local community. Participants The participants in this study were 171 patients (74% women, 26% men) with knee OA. They had a mean age of 55.1 (SD=7.1) years, a mean body mass index of 27.6 (SD=4.2) kg/m2, and radiographic status of grade II OA (and no higher) in at least one knee, as defined by the Kellgren and Lawrence classification. They wore an accelerometer while awake (X̄=14.2 [SD=2.2] hours) for 5 to 7 contiguous days (X̄=6.8 [SD=0.5] days) at baseline and at 3 and 9 months of intervention. Results The participants engaged in MVPA a mean of 26.2 (SD=19.3) minutes per day at baseline. Both groups significantly increased their MVPA from baseline to 3 months (RT group by 18% [effect size (d)=0.26]; SM group by 22% [effect size (d)=0.25]), but only the RT group sustained those changes at 9 months (RT group maintained a 10% increase [effect size (d)=0.15]; SM group maintained a 2% increase [effect size (d)=0.03]). A significant group × time interaction for MVPA indicated that the RT group maintained higher MVPA levels than the SM group. Limitations. Lack of direct measures of energy expenditure and physical function was a limitation of the study. Conclusions Patients with early-onset OA of the knee can engage in an RT program without sacrificing their overall MVPA levels. These results support the value of RT for management of knee OA. PMID:20056719

Effects of the dietary amount and source of protein, resistance training and anabolic-androgenic steroids on body weight and lipid profile of rats.

PubMed

Aparicio, V A; Sánchez, C; Ortega, F B; Nebot, E; Kapravelou, G; Porres, J M; Aranda, P

2013-01-01

Dietary protein amount and source, hypertrophy resistance training (RT) and anabolicandrogenic steroids (AAS) may affect body weight and plasma and hepatic lipid profile. 157 adult male Wistar rats were randomly distributed in 16 experimental groups resulting in: normal-protein (NP) or high-protein (HP) diets, whey or soy-protein diets, with or without RT and with or without AAS, for 3 months. Final body weight was lower in the RT and AAS groups compared to sedentary and non- AAS groups, respectively (all, p<0.001). Plasma total cholesterol (TC) was lower for the HP compared to the NP diets, for the whey compared to the soy-protein diets and for the AAS compared to the non-AAS groups (all, p<0.001). Plasma HDL-cholesterol was higher in the RT groups (p<0.05) but lower for the AAS groups (p<0.001), the HP and the soy-protein diets (p<0.05). Plasma triglycerides (TAG) were lower for the HP diet (p<0.001), for the RT (p=0.002) and the non-AAS groups (p=0.001). Liver TC was lower for the NP (p<0.01), for the soyprotein (p<0.05) and for the AAS groups (p<0.001). Liver TAG were lower for the whey-protein diet (p<0.001), RT and non-AAS groups (both, p<0.05). Some interactions were found, such as the greater effect of AAS on reducing body weight of rats that performed RT or ingested a HP diet (all, p<0.05). HDL-cholesterol was higher when RT was combined with HP diets (p=0.010) or non-AAS and when HP diets were combined with non-AAS (both,p<0.001). Groups that combined RT with non-AAS administration obtained the lowest hepatic TAG (p<0.05). Among all the interventions tested, AAS was the factor that most negatively affected plasma and hepatic lipid profile, whereas HP diets and RT could benefit lipid profile, especially when combined. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

Bridging Therapy with i. v. rtPA in MCA Occlusion Prior to Endovascular Thrombectomy: a Double-Edged Sword?

PubMed

Kaesmacher, Johannes; Kleine, Justus F

2018-03-01

Recent studies suggested that preinterventional intravenous (i. v.) recombinant tissue plasminogen activator (rtPA) as bridging therapy facilitates successful and fast vessel recanalization in endovascular stroke treatment (EST); however, data on this effect and the associated clinical value are discrepant. This study examined if this discrepancy could be related to an effect-modifying variable, specifically to the exact occlusion site. Retrospective analysis of 239 patients with acute occlusion of the middle cerebral artery (MCA) treated with up to date endovascular techniques. Effects of i. v.-rtPA bridging on clinical outcomes and safety/efficacy of EST, defined as the respective rates of successful, first pass and thrombolysis in cerebral infarction (TICI) scale 3 recanalization, were evaluated and stratified according to distal versus proximal occlusion sites. Overall, i. v.-rtPA bridging was associated with a significantly higher rate of successful recanalization (86.9 % vs. 75.7 %, p = 0.028). i. v.-rtPA bridging-related effects, however, were observable only in distal, but not in proximal MCA-occlusions. In distal occlusions, i. v.-rtPA clearly favored successful recanalization (adj. OR 4.6, 95 %-CI 1.5-13.6, p = 0.006) and first-pass successes (adj. OR 2.8, 95 %-CI 1.0-7.6, p = 0.042), but tended to be associated with lower rates of complete (TICI-3) reperfusion (adj. OR 0.4, 95 %-CI 0.2-1.1, p = 0.068). The net effect was a small clinical benefit, reflected in higher rates of strong neurological improvement (adj. OR: 2.8, 95 %-CI: 1.1-6.9, p = 0.03). i. v.-rtPA-bridging-related effects are occlusion site-dependent, paralleling similar effects of systemic i. v.-rtPA when applied without subsequent endovascular therapy. In distal occlusions, i. v.-rtPA facilitates thrombectomy, but may also promote distal embolization, with a small clinical benefit as overall net effect. Randomized trials assessing i.v-rtPA bridging need to be stratified according to occlusions sites.

Reducing late effects of radiotherapy in average risk medulloblastoma.

PubMed

Ibrahim, Noha Yehia; Abdel Aal, Hisham H; Abdel Kader, Mohamed S; Makaar, Wael S; Shaaban, Ahmed H

2014-03-01

To assess the efficacy and safety in average-risk pediatric medulloblastoma (MB) receiving tumor bed boost irradiation compared to a posterior fossa (PF) boost. Thirty patients were enrolled in the study and divided evenly into two treatment arms of 15. Both arms received 23.4 Gy craniospinal irradiation (CS) and a 32.4 Gy boost. Patients in arm 1 were given PF boosts, and those in arm 2 were given boosts to the gross target volume (GTV). Weekly oncovin was given throughout all radiotherapy (RT). Eight cycles of adjuvant chemotherapy of CCNU, oncovin and platinol were given to all patients after RT. MRI, pure tone audiogram (PTA) and intelligence quotient (IQ) tests were performed before and after RT and every three months thereafter. There were significant differences in the sparing dose to the cochlea and brain stem as well as the volume of the normal brain receiving a 100% dose. There was a significant initial improvement of hearing function in patients given the target volume boost after RT, which was lost after chemotherapy. With a median follow up of 23 months, there was no difference in progression free survival or overall survival between the two arms. Irradiation of the tumor bed after 23.4 Gy craniospinal irradiation for average-risk MB results in similar disease control as a PF boost. Dosimetric sparing for the cochleae and normal tissue is evident in patients receiving tumor bed boosts. The hearing improvement and cognitive function preservation effects of the treatment need more follow up.

What does postradiotherapy PSA nadir tell us about freedom from PSA failure and progression-free survival in patients with low and intermediate-risk localized prostate cancer?

PubMed

DeWitt, K D; Sandler, H M; Weinberg, V; McLaughlin, P W; Roach, M

2003-09-01

To determine whether the post-external beam radiotherapy (RT) prostate-specific antigen nadir (nPSA) improves our ability to predict freedom from PSA failure, progression-free survival (PFS), and overall survival. Controversy regarding the importance of nPSA after external beam RT as a prognostic indicator for patients with localized prostate cancer has continued. This analysis was based on the data from 748 patients with low and intermediate-risk localized prostate cancer treated with external beam RT alone. Patients were categorized by nPSA quartile groups with cutpoints of less than 0.3, 0.3 to less than 0.6, 0.6 to less than 1.2, and 1.2 ng/mL or greater. Both univariate and multivariate analyses were used to determine the significance of nPSA on PSA failure (American Society for Therapeutic Radiology Oncology consensus definition), PFS (death after PSA failure), and overall survival (death from any cause). Freedom from PSA failure was strongly associated with nadir quartile groups (P <0.0001). PFS was also significantly different statistically among nadir quartile groups (P = 0.02). No statistically significant difference was found in overall survival associated with nPSA at this point. nPSA is a strong independent predictor of freedom from PSA failure and PFS in patients with low and intermediate-risk localized prostate cancer treated with RT alone. Longer follow-up and larger patient numbers are required to confirm these observations.

PET/CT in Radiation Therapy Planning.

PubMed

Specht, Lena; Berthelsen, Anne Kiil

2018-01-01

Radiation therapy (RT) is an important component of the management of lymphoma patients. Most lymphomas are metabolically active and accumulate 18 F-fluorodeoxyglucose (FDG). Positron emission tomography with computer tomography (PET/CT) imaging using FDG is used routinely in staging and treatment evaluation. FDG-PET/CT imaging is now also used routinely for contouring the target for RT, and has been shown to change the irradiated volume significantly compared with CT imaging alone. Modern advanced imaging techniques with image fusion and motion management in combination with modern highly conformal RT techniques have increased the precision of RT, and have made it possible to reduce dramatically the risks of long-term side effects of treatment while maintaining the high cure rates for these diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Probabilistic Health Risk Assessment of Chemical Mixtures: Importance of Travel Times and Connectivity

NASA Astrophysics Data System (ADS)

Henri, Christopher V.; Fernàndez-Garcia, Daniel; de Barros, Felipe P. J.

2014-05-01

Subsurface contamination cases giving rise to groundwater pollutions are extensively found in all industrialized countries. Under this pressure, risk assessment methods play an important role in population protection by (1) quantifying the potential impact on human health of an aquifer contamination and (2) helping and driving decisions of groundwater-resource managers. Many reactive components such as chlorinated solvents or nitrates potentially experience attenuation processes under common geochemical conditions. This represents an attractive and extensively used remediation solution but leads often to the production of by-products before to reach a harmless chemical form. This renders mixtures of contaminants a common issue for groundwater resources managers. In this case, the threat posed by these contaminants to human health at a given sensitive location greatly depends on the competition between reactive and advective-dispersive characteristic times. However, hydraulic properties of the aquifer are known to be spatially variable, which can lead to the formation of preferential flow channels and fast contamination pathways. Therefore, the uncertainty on the spatial distribution of the aquifer properties controlling the plume travel time may then play a particular role in the human health risk assessment of chemical mixtures. We investigate here the risk related to a multispecies system in response to different degrees of heterogeneity of the hydraulic conductivity (K or Y =ln(K)). This work focuses on a Perchloroethylene (PCE) contamination problem followed by the sequential first-order production/biodegradation of its daughter species Trichloroethylene (TCE), Dichloroethylene (DCE) and Vinyl Chlorine (VC). For this specific case, VC is known to be a highly toxic contaminant. By performing numerical experiments, we evaluate transport through three-dimensional mildly (σY 2=1.0) and highly (σY 2=4.0) heterogeneous aquifers. Uncertainty on the hydraulic conductivity field is considered through a Monte Carlo scheme, and statistics of the total risk for human health (RT) related to the mixtures of the four carcinogenic plumes are evaluated. Results show two distinct spatiotemporal behavior of the RT estimation. Simulations in highly heterogeneous aquifers display a lower mean of RT close to the injection and higher further away. We explain this by the distinct ranges of travel times and connectivity metrics related to the two sets of aquifers. A high σY 2 trends to decrease the travel time (and increase the connectivity). Early travel times, associated to channeling effects, are intuitively perceived as an indicator for high risk. However, in our case, early travel times lead a limited production of highly toxic daughter species and a lower total risk. Our results reflect then the interplay between the characteristic reactive time for each component and the characteristic travel time of the plume since the production of VC depends on these factors.

Radiation Therapy Risk Factors for Development of Lymphedema in Patients Treated With Regional Lymph Node Irradiation for Breast Cancer

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

Chandra, Ravi A.; Miller, Cynthia L.; Skolny, Melissa N.

2015-03-15

Purpose: We previously evaluated the risk of breast cancer-related lymphedema (LE) with the addition of regional lymph node irradiation (RLNR) and found an increased risk when RLNR is used. Here we analyze the association of technical radiation therapy (RT) factors in RLNR patients with the risk of LE development. Methods and Materials: From 2005 to 2012, we prospectively screened 1476 women for LE who underwent surgery for breast cancer. Among 1507 breasts treated, 172 received RLNR and had complete technical data for analysis. RLNR was delivered as supraclavicular (SC) irradiation (69% [118 of 172 patients]) or SC plus posterior axillarymore » boost (PAB) (31% [54 of 172]). Bilateral arm volume measurements were performed pre- and postoperatively. Patients' RT plans were analyzed for SC field lateral border (relative to the humeral head), total dose to SC, RT fraction size, beam energy, and type of tangent (normal vs wide). Cox proportional hazards models were used to analyze associated risk factors for LE. Results: Median postoperative follow-up was 29.3 months (range: 4.9-74.1 months). The 2-year cumulative incidence of LE was 22% (95% confidence interval [CI]: 15%-32%) for SC and 20% (95% CI: 11%-37%) for SC plus PAB (SC+PAB). None of the analyzed variables was significantly associated with LE risk (extent of humeral head: P=.74 for <1/3 vs >2/3, P=.41 for 1/3 to 2/3 vs >2/3; P=.40 for fraction size of 1.8 Gy vs 2.0 Gy; P=.57 for beam energy 6 MV vs 10 MV; P=.74 for tangent type wide vs regular; P=.66 for SC vs SC+PAB). Only pretreatment body mass index (hazard ratio [HR]: 1.09; 95% CI: 1.04-1.15, P=.0007) and the use of axillary lymph node dissection (HR: 7.08, 95% CI: 0.98-51.40, P=.05) were associated with risk of subsequent LE development. Conclusions: Of the RT parameters tested, none was associated with an increased risk of LE development. This study underscores the need for future work investigating alternative RLNR risk factors for LE.« less

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

Krayenbuehl, Jerome Dipl.Phys. E.T.H.; Oertel, Susanne; Davis, J. Bernard

Purpose: The optimal technique for postoperative radiotherapy (RT) after extrapleural pleuropneumonectomy (EPP) of malignant pleural mesothelioma (MPM) remains debated. Methods and Materials: The data from 8 right-sided and 9 left-sided consecutive cases of MPM treated with RT after radical EPP were reviewed. Of the 17 patients, 8 had been treated with three-dimensional (3D) conformal RT (3D-CRT) and 9 with intensity-modulated RT (IMRT) with 6-MV photons. The clinical outcome and adverse events were assessed. For comparative planning, each case was replanned with 3D-CRT using photons and electrons or with IMRT. Homogeneity, doses to the organs at risk, and target volume coveragemore » were analyzed. Results: Both techniques yielded acceptable plans. The dose coverage and homogeneity of IMRT increased by 7.7% for the first planning target volume and 9.7% for the second planning target volume, ensuring {>=}95% of the prescribed dose compared with 3D-CRT (p < 0.01). Compared with 3D-CRT, IMRT increased the dose to the contralateral lung, with an increase in the mean lung dose of 7.8 Gy and an increase in the volume receiving 13 Gy and 20 Gy by 20.5% and 7.2%, respectively (p < 0.01). A negligible dose increase to the contralateral kidney and liver was observed. No differences were seen for the spinal cord and ipsilateral kidney. Two adverse events of clinical relevant lung toxicity were observed with IMRT. Conclusion: Intensity-modulated RT and 3D-CRT are both suitable for adjuvant RT. IMRT improves the planning target volume coverage but delivered greater doses to the organs at risk. Rigid dose constraints for the lung should be respected.« less

Renal Atrophy Secondary to Chemoradiotherapy of Abdominal Malignancies

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

Yang, Gary Y., E-mail: Gary.Yang@RoswellPark.or; May, Kilian Salerno; Iyer, Renuka V.

2010-10-01

Purpose: To identify factors predictive of renal atrophy after chemoradiotherapy of gastrointestinal malignancies. Methods and Materials: Patients who received chemotherapy and abdominal radiotherapy (RT) between 2002 and 2008 were identified for this study evaluating change in kidney size and function after RT. Imaging and biochemical data were obtained before and after RT in 6-month intervals. Kidney size was defined by craniocaudal measurement on CT images. The primarily irradiated kidney (PK) was defined as the kidney that received the greater mean kidney dose. Receiver operating characteristic (ROC) curves were generated to predict risk for renal atrophy. Results: Of 130 patients, medianmore » age was 64 years, and 51.5% were male. Most primary disease sites were pancreas and periampullary tumors (77.7%). Median follow-up was 9.4 months. Creatinine clearance declined 20.89%, and size of the PK decreased 4.67% 1 year after completion of chemoradiation. Compensatory hypertrophy of the non-PK was not seen. Percentage volumes of the PK receiving {>=}10 Gy (V{sub 10}), 15 Gy (V{sub 15}), and 20 Gy (V{sub 20}) were significantly associated with renal atrophy 1 year after RT (p = 0.0030, 0.0029, and 0.0028, respectively). Areas under the ROC curves for V{sub 10}, V{sub 15}, and V{sub 20} to predict >5% decrease in PK size were 0.760, 0.760, and 0.762, respectively. Conclusions: Significant detriments in PK size and renal function were seen after abdominal RT. The V{sub 10}, V{sub 15}, and V{sub 20} were predictive of risk for PK atrophy 1 year after RT. Analyses suggest the association of lower-dose renal irradiation with subsequent development of renal atrophy.« less

Impact of Cranial Irradiation Added to Intrathecal Conditioning in Hematopoietic Cell Transplantation in Adult Acute Myeloid Leukemia With Central Nervous System Involvement

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

Mayadev, Jyoti S.; Department of Radiation Oncology University of California-Davis Medical Center, Davis, CA; Douglas, James G., E-mail: drjay@u.washington.ed

Purpose: Neither the prognostic importance nor the appropriate management of central nervous system (CNS) involvement is known for patients with acute myeloid leukemia (AML) undergoing hematopoietic cell transplantation (HCT). We examined the impact of a CNS irradiation boost to standard intrathecal chemotherapy (ITC). Methods and Materials: From 1995 to 2005, a total of 648 adult AML patients received a myeloablative HCT: 577 patients were CNS negative (CNS-), and 71 were CNS positive (CNS+). Of the 71 CNS+ patients, 52 received intrathecal chemotherapy alone (CNS+ITC), and 19 received ITC plus an irradiation boost (CNS+RT). Results: The CNS-, CNS+ITC, and CNS+RT patientsmore » had 1- and 5-year relapse-free survivals (RFS) of 43% and 35%, 15% and 6%, and 37% and 32%, respectively. CNS+ITC patients had a statistically significant worse RFS compared with CNS- patients (hazard ratio [HR], 2.65; 95% confidence interval [CI], 2.0-3.6; p < 0.0001). CNS+RT patients had improved relapse free survival over that of CNS+ITC patients (HR, 0.45; 95% CI, 0.2-0.8; p = 0.01). The 1- and 5-year overall survivals (OS) of patients with CNS-, CNS+ITC, and CNS+RT, were 50% and 38%, 21% and 6%, and 53% and 42%, respectively. The survival of CNS+RT were significantly better than CNS+ITC patients (p = 0.004). After adjusting for known risk factors, CNS+RT patients had a trend toward lower relapse rates and reduced nonrelapse mortality. Conclusions: CNS+ AML is associated with a poor prognosis. The role of a cranial irradiation boost to intrathecal chemotherapy appears to mitigate the risk of CNS disease, and needs to be further investigated to define optimal treatment strategies.« less

Evaluation of the clinical performance of the Abbott RealTime High-Risk HPV for carcinogenic HPV detection.

PubMed

Halfon, Philippe; Benmoura, Dominique; Agostini, Aubert; Khiri, Hacene; Penaranda, Guillaume; Martineau, Agnes; Blanc, Bernard

2010-08-01

Abbott RealTime (RT) High-Risk (HR) HPV assay is a new qualitative real-time polymerase chain reaction (PCR) based assay for the detection of 14 HR HPV DNA. The assay can differentiate between the infection by HPV 16, HPV 18 and non-HPV 16/18 types through the distinct fluorescent labels on the type specific probes. To evaluate the clinical performance of the Abbott RT HR HPV test, in comparison with biopsy, Hybrid Capture II (HCII), and Linear Array (LA), for detection of high-grade disease (CIN2+). The study population consisted of 143 women who were included in three referral gynecology clinics in Marseilles (France) between March 2007 and June 2008. The clinical performance of the RT HR HPV assay, performed on the fully automated m2000 system, was compared with HCII and LA. HR HPV positivity rate was similar for all tests (Abbott RT HR HPV and HCII, 62%, and LA 63%). All tests had high sensitivities and negative predictive values for CIN2+ detection (>90%). The agreement between HCII and Abbott RT HR HPV, and between HCII and LA were 93% (k=0.85) and 96% (k=0.91) respectively. As expected, HPV16 or HPV18 positivity was greater in advanced grades of disease, especially in CIN2+ patients: 85% in CIN2+ vs. 33% in

Clinical validation and applications for CT-based atlas for contouring the lower cranial nerves for head and neck cancer radiation therapy.

PubMed

Mourad, Waleed F; Young, Brett M; Young, Rebekah; Blakaj, Dukagjin M; Ohri, Nitin; Shourbaji, Rania A; Manolidis, Spiros; Gámez, Mauricio; Kumar, Mahesh; Khorsandi, Azita; Khan, Majid A; Shasha, Daniel; Blakaj, Adriana; Glanzman, Jonathan; Garg, Madhur K; Hu, Kenneth S; Kalnicki, Shalom; Harrison, Louis B

2013-09-01

Radiation induced cranial nerve palsy (RICNP) involving the lower cranial nerves (CNs) is a serious complication of head and neck radiotherapy (RT). Recommendations for delineating the lower CNs on RT planning studies do not exist. The aim of the current study is to develop a standardized methodology for contouring CNs IX-XII, which would help in establishing RT limiting doses for organs at risk (OAR). Using anatomic texts, radiologic data, and guidance from experts in head and neck anatomy, we developed step-by-step instructions for delineating CNs IX-XII on computed tomography (CT) imaging. These structures were then contoured on five consecutive patients who underwent definitive RT for locally-advanced head and neck cancer (LAHNC). RT doses delivered to the lower CNs were calculated. We successfully developed a contouring atlas for CNs IX-XII. The median total dose to the planning target volume (PTV) was 70Gy (range: 66-70Gy). The median CN (IX-XI) and (XII) volumes were 10c.c (range: 8-12c.c) and 8c.c (range: 7-10c.c), respectively. The median V50, V60, V66, and V70 of the CN (IX-XI) and (XII) volumes were (85, 77, 71, 65) and (88, 80, 74, 64) respectively. The median maximal dose to the CN (IX-XI) and (XII) were 72Gy (range: 66-77) and 71Gy (range: 64-78), respectively. We have generated simple instructions for delineating the lower CNs on RT planning imaging. Further analyses to explore the relationship between lower CN dosing and the risk of RICNP are recommended in order to establish limiting doses for these OARs. Published by Elsevier Ltd.

Hyperfractionated Low-Dose (21 Gy) Radiotherapy for Cranial Skeletal Metastases in Patients With High-Risk Neuroblastoma

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

Kushner, Brian H., E-mail: kushnerb@mskcc.or; Cheung, Nai-Kong V.; Barker, Christopher A.

2009-11-15

Purpose: To present a large experience (73 patients) using a standard radiotherapy (RT) protocol to prevent relapse in cranial sites where measurable metastatic neuroblastoma (NB), an adverse prognostic marker, is common. Methods and Materials: High-risk NB patients with measurable cranial disease at diagnosis or residual cranial disease after induction therapy had those sites irradiated with hyperfractionated 21 Gy; a brain-sparing technique was used for an extensive field. The patients were grouped according to the response to systemic therapy. Thus, when irradiated, Group 1 patients were in complete remission and Group 2 patients had primary refractory disease. Follow-up was from themore » start of cranial RT. Results: At 3 years, the 39 Group 1 patients had a progression-free survival rate of 51%; control of cranial disease was 79%. Two relapses involved irradiated cranial sites. Two other patients relapsed in the irradiated cranial sites 6 and 12 months after a systemic relapse. At 3 years, the 34 Group 2 patients had a progression-free survival rate of 33%; control of cranial disease was 52%. Group 2 included 19 patients who had residual cranial (with or without extracranial) disease. The cranial sites showed major (n = 13), minor (n = 2), or no response (n = 4) to RT. Five patients had progression in the cranial RT field at 10-27 months. Group 2 also included 15 patients who had persistent NB in extracranial, but not cranial, sites. Of these 15 patients, 2 relapsed in the irradiated cranial sites and elsewhere at 8 and 14 months. Cranial RT was well tolerated, with no Grade 2 or greater toxicity. Conclusion: Hyperfractionated 21-Gy cranial RT might help control NB and is feasible without significant toxicity in children.« less

Harsh Corporal Punishment Is Associated With Increased T2 Relaxation Time in Dopamine-Rich Regions

PubMed Central

Sheu, Yi-Shin; Polcari, Ann; Anderson, Carl M.; Teicher, Martin H.

2010-01-01

Harsh corporal punishment (HCP) was defined as frequent parental administration of corporal punishment (CP) for discipline, with occasional use of objects such as straps, or paddles. CP is linked to increased risk for depression and substance abuse. We examine whether long-term exposure to HCP acts as sub-traumatic stressor that contributes to brain alterations, particularly in dopaminergic pathways, which may mediate their increased vulnerability to drug and alcohol abuse. Nineteen young adults who experienced early HCP but no other forms of maltreatment and twenty-three comparable controls were studied. T2 relaxation time (T2-RT) measurements were performed with an echo planar imaging TE stepping technique and T2 maps were calculated and analyzed voxel-by-voxel to locate regional T2-RT differences between groups. Previous studies indicated that T2-RT provides an indirect index of resting cerebral blood volume. Region of interest (ROI) analyses were also conducted in caudate, putamen, nucleus accumbens, anterior cingulate cortex, dorsolateral prefrontal cortex, thalamus, globus pallidus and cerebellar hemispheres. Voxel-based relaxometry showed that HCP was associated with increased T2-RT in right caudate and putamen. ROI analyses also revealed increased T2-RT in dorsolateral prefrontal cortex, substantia nigra, thalamus and accumbens but not globus pallidus or cerebellum. There were significant associations between T2-RT measures in dopamine target regions and use of drugs and alcohol, and memory performance. Alteration in the paramagnetic or hemodynamic properties of dopaminergic cell body and projection regions were observed in subjects with HCP, and these findings may relate to their increased risk for drug and alcohol abuse. PMID:20600981

Intensity Modulated Radiation Therapy With Dose Painting to Treat Rhabdomyosarcoma

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

Yang, Joanna C.; Dharmarajan, Kavita V.; Wexler, Leonard H.

Purpose: To examine local control and patterns of failure in rhabdomyosarcoma patients treated with intensity modulated radiation therapy (RT) with dose painting (DP-IMRT). Patients and Methods: A total of 41 patients underwent DP-IMRT with chemotherapy for definitive treatment. Nineteen also underwent surgery with or without intraoperative RT. Fifty-six percent had alveolar histologic features. The median interval from beginning chemotherapy to RT was 17 weeks (range, 4-25). Very young children who underwent second-look procedures with or without intraoperative RT received reduced doses of 24-36 Gy in 1.4-1.8-Gy fractions. Young adults received 50.4 Gy to the primary tumor and lower doses ofmore » 36 Gy in 1.8-Gy fractions to at-risk lymph node chains. Results: With 22 months of median follow-up, the actuarial local control rate was 90%. Patients aged {<=}7 years who received reduced overall and fractional doses had 100% local control, and young adults had 79% (P=.07) local control. Three local failures were identified in young adults whose primary target volumes had received 50.4 Gy in 1.8-Gy fractions. Conclusions: DP-IMRT with lower fractional and cumulative doses is feasible for very young children after second-look procedures with or without intraoperative RT. DP-IMRT is also feasible in adolescents and young adults with aggressive disease who would benefit from prophylactic RT to high-risk lymph node chains, although dose escalation might be warranted for improved local control. With limited follow-up, it appears that DP-IMRT produces local control rates comparable to those of sequential IMRT in patients with rhabdomyosarcoma.« less

Harsh corporal punishment is associated with increased T2 relaxation time in dopamine-rich regions.

PubMed

Sheu, Yi-Shin; Polcari, Ann; Anderson, Carl M; Teicher, Martin H

2010-11-01

Harsh corporal punishment (HCP) was defined as frequent parental administration of corporal punishment (CP) for discipline, with occasional use of objects such as straps, or paddles. CP is linked to increased risk for depression and substance abuse. We examine whether long-term exposure to HCP acts as sub-traumatic stressor that contributes to brain alterations, particularly in dopaminergic pathways, which may mediate their increased vulnerability to drug and alcohol abuse. Nineteen young adults who experienced early HCP but no other forms of maltreatment and twenty-three comparable controls were studied. T2 relaxation time (T2-RT) measurements were performed with an echo planar imaging TE stepping technique and T2 maps were calculated and analyzed voxel-by-voxel to locate regional T2-RT differences between groups. Previous studies indicated that T2-RT provides an indirect index of resting cerebral blood volume. Region of interest (ROI) analyses were also conducted in caudate, putamen, nucleus accumbens, anterior cingulate cortex, dorsolateral prefrontal cortex, thalamus, globus pallidus and cerebellar hemispheres. Voxel-based relaxometry showed that HCP was associated with increased T2-RT in right caudate and putamen. ROI analyses also revealed increased T2-RT in dorsolateral prefrontal cortex, substantia nigra, thalamus and accumbens but not globus pallidus or cerebellum. There were significant associations between T2-RT measures in dopamine target regions and use of drugs and alcohol, and memory performance. Alteration in the paramagnetic or hemodynamic properties of dopaminergic cell body and projection regions were observed in subjects with HCP, and these findings may relate to their increased risk for drug and alcohol abuse. Copyright 2010 Elsevier Inc. All rights reserved.

Consideration of Dose Limits for Organs at Risk of Thoracic Radiotherapy: Atlas for Lung, Proximal Bronchial Tree, Esophagus, Spinal Cord, Ribs, and Brachial Plexus

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

Kong, Feng-Ming, E-mail: fengkong@med.umich.edu; Ritter, Timothy; Quint, Douglas J.

2011-12-01

Purpose: To review the dose limits and standardize the three-dimenional (3D) radiographic definition for the organs at risk (OARs) for thoracic radiotherapy (RT), including the lung, proximal bronchial tree, esophagus, spinal cord, ribs, and brachial plexus. Methods and Materials: The present study was performed by representatives from the Radiation Therapy Oncology Group, European Organization for Research and Treatment of Cancer, and Soutwestern Oncology Group lung cancer committees. The dosimetric constraints of major multicenter trials of 3D-conformal RT and stereotactic body RT were reviewed and the challenges of 3D delineation of these OARs described. Using knowledge of the human anatomy andmore » 3D radiographic correlation, draft atlases were generated by a radiation oncologist, medical physicist, dosimetrist, and radiologist from the United States and reviewed by a radiation oncologist and medical physicist from Europe. The atlases were then critically reviewed, discussed, and edited by another 10 radiation oncologists. Results: Three-dimensional descriptions of the lung, proximal bronchial tree, esophagus, spinal cord, ribs, and brachial plexus are presented. Two computed tomography atlases were developed: one for the middle and lower thoracic OARs (except for the heart) and one focusing on the brachial plexus for a patient positioned supine with their arms up for thoracic RT. The dosimetric limits of the key OARs are discussed. Conclusions: We believe these atlases will allow us to define OARs with less variation and generate dosimetric data in a more consistent manner. This could help us study the effect of radiation on these OARs and guide high-quality clinical trials and individualized practice in 3D-conformal RT and stereotactic body RT.« less

Local Failure in Parameningeal Rhabdomyosarcoma Correlates With Poor Response to Induction Chemotherapy

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

Ladra, Matthew M.; Mandeville, Henry C.; Niemierko, Andrzej

2015-06-01

Background: Local control remains a challenge in pediatric parameningeal rhabdomyosarcoma (PM-RMS), and survival after local failure (LF) is poor. Identifying patients with a high risk of LF is of great interest to clinicians. In this study, we examined whether tumor response to induction chemotherapy (CT) could predict LF in embryonal PM-RMS. Methods: We identified 24 patients with embryonal PM-RMS, age 2 to 18 years, with complete magnetic resonance imaging and gross residual disease after surgical resection. All patients received proton radiation therapy (RT), median dose 50.4 Gy{sub RBE} (50.4-55.8 Gy{sub RBE}). Tumor size was measured before initial CT and before RT. Results:more » With a median follow-up time of 4.1 years for survivors, LF was seen in 9 patients (37.5%). The median time from the initiation of CT to the start of RT was 4.8 weeks. Patients with LF had a similar initial (pre-CT) tumor volume compared with patients with local controlled (LC) (54 cm{sup 3} vs 43 cm{sup 3}, P=.9) but a greater median volume before RT (pre-RT) (40 cm{sup 3} vs 7 cm{sup 3}, P=.009) and a smaller median relative percent volume reduction (RPVR) in tumor size (0.4% vs 78%, P<.001). Older age (P=.05), larger pre-RT tumor volume (P=.03), and smaller RPVR (P=.003) were significantly associated with actuarial LF on univariate Cox analysis. Conclusions: Poor response to induction CT appears to be associated with an increased risk of LF in pediatric embryonal PM-RMS.« less

Predictive Models for Regional Hepatic Function Based on 99mTc-IDA SPECT and Local Radiation Dose for Physiologic Adaptive Radiation Therapy

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

Wang, Hesheng, E-mail: hesheng@umich.edu; Feng, Mary; Frey, Kirk A.

2013-08-01

Purpose: High-dose radiation therapy (RT) for intrahepatic cancer is limited by the development of liver injury. This study investigated whether regional hepatic function assessed before and during the course of RT using 99mTc-labeled iminodiacetic acid (IDA) single photon emission computed tomography (SPECT) could predict regional liver function reserve after RT. Methods and Materials: Fourteen patients treated with RT for intrahepatic cancers underwent dynamic 99mTc-IDA SPECT scans before RT, during, and 1 month after completion of RT. Indocyanine green (ICG) tests, a measure of overall liver function, were performed within 1 day of each scan. Three-dimensional volumetric hepatic extraction fraction (HEF)more » images of the liver were estimated by deconvolution analysis. After coregistration of the CT/SPECT and the treatment planning CT, HEF dose–response functions during and after RT were generated. The volumetric mean of the HEFs in the whole liver was correlated with ICG clearance time. Three models, dose, priori, and adaptive models, were developed using multivariate linear regression to assess whether the regional HEFs measured before and during RT helped predict regional hepatic function after RT. Results: The mean of the volumetric liver HEFs was significantly correlated with ICG clearance half-life time (r=−0.80, P<.0001), for all time points. Linear correlations between local doses and regional HEFs 1 month after RT were significant in 12 patients. In the priori model, regional HEF after RT was predicted by the planned dose and regional HEF assessed before RT (R=0.71, P<.0001). In the adaptive model, regional HEF after RT was predicted by regional HEF reassessed during RT and the remaining planned local dose (R=0.83, P<.0001). Conclusions: 99mTc-IDA SPECT obtained during RT could be used to assess regional hepatic function and helped predict post-RT regional liver function reserve. This could support individualized adaptive radiation treatment strategies to maximize tumor control and minimize the risk of liver damage.« less

Predictive models for regional hepatic function based on 99mTc-IDA SPECT and local radiation dose for physiologic adaptive radiation therapy.

PubMed

Wang, Hesheng; Feng, Mary; Frey, Kirk A; Ten Haken, Randall K; Lawrence, Theodore S; Cao, Yue

2013-08-01

High-dose radiation therapy (RT) for intrahepatic cancer is limited by the development of liver injury. This study investigated whether regional hepatic function assessed before and during the course of RT using 99mTc-labeled iminodiacetic acid (IDA) single photon emission computed tomography (SPECT) could predict regional liver function reserve after RT. Fourteen patients treated with RT for intrahepatic cancers underwent dynamic 99mTc-IDA SPECT scans before RT, during, and 1 month after completion of RT. Indocyanine green (ICG) tests, a measure of overall liver function, were performed within 1 day of each scan. Three-dimensional volumetric hepatic extraction fraction (HEF) images of the liver were estimated by deconvolution analysis. After coregistration of the CT/SPECT and the treatment planning CT, HEF dose-response functions during and after RT were generated. The volumetric mean of the HEFs in the whole liver was correlated with ICG clearance time. Three models, dose, priori, and adaptive models, were developed using multivariate linear regression to assess whether the regional HEFs measured before and during RT helped predict regional hepatic function after RT. The mean of the volumetric liver HEFs was significantly correlated with ICG clearance half-life time (r=-0.80, P<.0001), for all time points. Linear correlations between local doses and regional HEFs 1 month after RT were significant in 12 patients. In the priori model, regional HEF after RT was predicted by the planned dose and regional HEF assessed before RT (R=0.71, P<.0001). In the adaptive model, regional HEF after RT was predicted by regional HEF reassessed during RT and the remaining planned local dose (R=0.83, P<.0001). 99mTc-IDA SPECT obtained during RT could be used to assess regional hepatic function and helped predict post-RT regional liver function reserve. This could support individualized adaptive radiation treatment strategies to maximize tumor control and minimize the risk of liver damage. Published by Elsevier Inc.

Is a reduction in radiation lung volume and dose necessary with paclitaxel chemotherapy for node-positive breast cancer?

PubMed

Taghian, Alphonse G; Assaad, Sherif I; Niemierko, Andrzej; Floyd, Scott R; Powell, Simon N

2005-06-01

To evaluate and quantify the effect of irradiated lung volume, radiation dose, and paclitaxel chemotherapy on the development of radiation pneumonitis (RP) in breast cancer patients with positive lymph nodes. We previously reported the incidence of RP among 41 patients with breast cancer treated with radiotherapy (RT) and adjuvant paclitaxel-containing chemotherapy. We recorded the central lung distance, a measure of the extent of lung included in the RT volume, in these patients. We used this measure and the historical and observed rates of RP in our series to model the lung tolerance to RT in patients receiving chemotherapy (CHT) both with and without paclitaxel. To evaluate the risk factors for the development of RP, we performed a case-control study comparing paclitaxel-treated patients who developed RP with those who did not, and a second case-control study comparing patients receiving paclitaxel in addition to standard CHT/RT (n = 41) and controls receiving standard CHT/RT alone (n = 192). The actuarial rate of RP in the paclitaxel-treated group was 15.4% compared with 0.9% among breast cancer patients treated with RT and non-paclitaxel-containing CHT. Our mathematical model found that the effective lung tolerance for patients treated with paclitaxel was reduced by approximately 24%. No statistically significant difference was found with regard to the dose delivered to specific radiation fields, dose per fraction, central lung distance, or percentage of lung irradiated in the case-control study of paclitaxel-treated patients who developed RP compared with those who did not. In the comparison of 41 patients receiving RT and CHT with paclitaxel and 192 matched controls receiving RT and CHT without paclitaxel, the only significant differences identified were the more frequent use of a supraclavicular radiation field and a decrease in the RT lung dose among the paclitaxel-treated patients. This finding indicates that the major factor associated with development of RP was paclitaxel treatment. The use of paclitaxel chemotherapy and RT in the primary treatment of node-positive breast cancer is likely to increase the incidence of RP. In patients treated with paclitaxel, reducing the percentage of lung irradiated by 24% should reduce the risk of RP to 1%, according to our calculations of lung tolerance. Future clinical trials using combination CHT that includes paclitaxel and RT should carefully evaluate the incidence and severity of RP and should also accurately monitor the extent of lung included within the RT volume to develop safe guidelines for the delivery of what is becoming standard therapy for node-positive breast cancer.

Primary surgery results in no survival benefit compared to primary radiation for oropharyngeal cancer patients stratified by high-risk human papilloma virus status.

PubMed

Lybak, Stein; Ljøkjel, Borghild; Haave, Hilde; Karlsdottir, Àsa; Vintermyr, Olav K; Aarstad, Hans Jørgen

2017-01-01

We changed the primary oropharynx squamous cell carcinoma (OPSCC) treatment recommendation from primary radiation therapy (RT) to tumor surgery and neck dissection, followed by RT around the year 2000 with apparently improved survival. However, high-risk human papilloma virus (hr-HPV)-16-caused OPSCCs have increased during this period. Furthermore, hr-HPV+ OPSCC carry a better prognosis than hr-HPV-negative patients. We have, therefore, evaluated the 5-year survival in the period from 1992 to 1999 versus 2000 to 2008 stratified by hr-HPV tumor infection status. Ninety-six OPSCC patients were treated from 1992 to 1999 compared with 136 patients from 2000 to 2008. The 5-year disease-specific survival (DDS) and overall survival (OS) were recorded, while the health-related quality of life (HRQoL) scores were obtained from some of the cured patients. Thirty-eight (40 %) in the first period and 86 OPSCCs (63 %) in the second period were hr-HPV+. In the first period, 16 versus 62 patients in the last period were treated by neck dissection, primary tumor surgery, and RT. DSS among all the hr-HPV-negative patients in the first period was 51 versus 55 % in the second period, and the corresponding OS was 33 versus 31 %, respectively. The DSS among all the hr-HPV+ patients was 78 % in the first period versus 77 % in the second period, while the OS was 71 versus 69 %, respectively. The HRQoL scores among successfully treated patients were worse following surgery, plus RT than RT only. The hr-HPV-adjusted 5-year survival in OPSCC patients was similar between the two time periods. A decreased HRQoL was associated with surgical therapy, which indicates that hr-HPV+ OPSCC patients may be treated by primary RT followed by major surgery only if RT treatment fails.

Pre–Radiation Therapy Fluorine 18 Fluorodeoxyglucose PET Helps Identify Patients with Esophageal Cancer at High Risk for Radiation Pneumonitis

PubMed Central

Castillo, Richard; Pham, Ngoc; Castillo, Edward; Aso-Gonzalez, Samantha; Ansari, Sobiya; Hobbs, Brian; Palacio, Diana; Skinner, Heath

2015-01-01

Purpose To examine the association between pre–radiation therapy (RT) fluorine 18 fluorodeoxyglucose (FDG) uptake and post-RT symptomatic radiation pneumonitis (RP). Materials and Methods In accordance with the retrospective study protocol approved by the institutional review board, 228 esophageal cancer patients who underwent FDG PET/CT before chemotherapy and RT were examined. RP symptoms were evaluated by using the Common Terminology Criteria for Adverse Events, version 4.0, from the consensus of five clinicians. By using the cumulative distribution of standardized uptake values (SUVs) within the lungs, those values greater than 80%–95% of the total lung voxels were determined for each patient. The effect of pre-chemotherapy and RT FDG uptake, dose, and patient or treatment characteristics on RP toxicity was studied by using logistic regression. Results The study subjects were treated with three-dimensional conformal RT (n = 36), intensity-modulated RT (n = 135), or proton therapy (n = 57). Logistic regression analysis demonstrated elevated FDG uptake at pre-chemotherapy and RT was related to expression of RP symptoms. Study subjects with elevated 95% percentile of the SUV (SUV95) were more likely to develop symptomatic RP (P < .000012); each 0.1 unit increase in SUV95 was associated with a 1.36-fold increase in the odds of symptomatic RP. Receiver operating characteristic (ROC) curve analysis resulted in area under the ROC curve of 0.676 (95% confidence interval: 0.58, 0.77), sensitivity of 60%, and specificity of 71% at the 1.17 SUV95 threshold. CT imaging and dosimetric parameters were found to be poor predictors of RP symptoms. Conclusion The SUV95, a biomarker of pretreatment pulmonary metabolic activity, was shown to be prognostic of symptomatic RP. Elevation in this pretreatment biomarker identifies patients at high risk for posttreatment symptomatic RP. © RSNA, 2015 PMID:25584706

[Effects of functional training combined with self-made hand flexing training band in treatment of scar contracture after burn injury of dorsal hand].

PubMed

Zhu, C; Yi, N; Shi, M N; Liang, Y Y; Zhou, Y B; Dang, R; Qi, Z S; Zhao, H Y

2017-07-20

Objective: To observe the effects of functional training combined with self-made hand flexing training band in treatment of scar contracture after burn injury of dorsal hand. Methods: Forty-six patients with scar contracture after deep partial-thickness or full-thickness burn injury of dorsal hand hospitalized in our department from March 2013 to February 2015 were divided into routine training group (RT, n =18) and comprehensive training group (CT, n =28) according to their willingness. Two weeks after the wounds were healed, patients in group RT were treated with functional training of hands and self-made pressure gloves, while patients in group CT were treated with self-made hand flexing training band (consisting of nylon strap, flexing band, and velcro) on the basis of those in group RT. All patients were treated for 3 months. Before and after treatment, scar condition of affected hands was assessed with Vancouver Scar Scale (VSS). The range of motion of joints of affected hands was measured by Total Active Movement (TAM) Scale. The function of affected hands was evaluated by Carroll Upper Extremity Function Test. Data were processed with t test, chi-square test, and Mann-Whitney U test. Results: (1) The score of VSS in patients of group RT was (10.0±1.9) points before treatment and (4.4±1.4) points after treatment, with the improved score of (5.6±1.0) points. The score of VSS in patients of group CT was (10.5±1.8) points before treatment and (4.6±1.4) points after treatment, with the improved score of (5.9±1.2) points. There was no statistically significant difference in the improved score of patients between the two groups ( t =0.834, P >0.05). The score of VSS in patients of groups RT and CT after treatment was significantly lower than that before treatment (with t values respectively 14.014 and 10.003, P values below 0.01). (2) Before treatment, the ratios of excellent and good results according to TAM were 2/9 in patients of group RT and 3/14 in group CT, with no statistical differences between them ( χ (2)=2.140, P >0.05). After treatment, the ratio of excellent and good results according to TAM in patients of group CT (6/7) was higher than that in group RT (5/9, χ (2)=0.023, P =0.038). The ratios of excellent and good results according to TAM in patients of groups RT and CT after treatment were significantly higher than those before treatment (with Z values respectively -2.023 and -4.780, P values below 0.05). (3) The improved score of hand function in patients of group CT was (26±12) points, which was higher than (15±7) points in group RT ( t =3.278, P =0.002). The score of hand function in patients of groups RT and CT after treatment was significantly higher than that before treatment (with t values respectively 2.628 and 6.125, P values below 0.05). There were no significant differences in grades of hand function of patients between the two groups before treatment ( Z =-0.286, P >0.05). After treatment, the grade of hand function in patients of group CT was higher than that in group RT( Z =-1.993, P =0.046). The grades of hand function in patients of groups RT and CT after treatment were significantly higher than those before treatment (with Z values respectively -2.717 and -4.998, P values below 0.01). Conclusions: For patients with scar contracture after burn injury of dorsal hand, early functional training combined with hand flexing training band can improve the range of motion of hand joints and functional recovery of hand, and the result was better than functional training alone.

TU-F-18C-09: Mammogram Surveillance Using Texture Analysis for Breast Cancer Patients After Radiation Therapy

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

Kuo, H; Tome, W; FOX, J

2014-06-15

Purpose: To study the feasibility of applying cancer risk model established from treated patients to predict the risk of recurrence on follow-up mammography after radiation therapy for both ipsilateral and contralateral breast. Methods: An extensive set of textural feature functions was applied to a set of 196 Mammograms from 50 patients. 56 Mammograms from 28 patients were used as training set, 44 mammograms from 22 patients were used as test set and the rest were used for prediction. Feature functions include Histogram, Gradient, Co-Occurrence Matrix, Run-Length Matrix and Wavelet Energy. An optimum subset of the feature functions was selected bymore » Fisher Coefficient (FO) or Mutual Information (MI) (up to top 10 features) or a method combined FO, MI and Principal Component (FMP) (up to top 30 features). One-Nearest Neighbor (1-NN), Linear Discriminant Analysis (LDA) and Nonlinear Discriminant Analysis (NDA) were utilized to build a risk model of breast cancer from the training set of mammograms at the time of diagnosis. The risk model was then used to predict the risk of recurrence from mammogram taken one year and three years after RT. Results: FPM with NDA has the best classification power in classifying the training set of the mammogram with lesions versus those without lesions. The model of FPM with NDA achieved a true positive (TP) rate of 82% compared to 45.5% of using FO with 1-NN. The best false positive (FP) rates were 0% and 3.6% in contra-lateral breast of 1-year and 3-years after RT, and 10.9% in ipsi-lateral breast of 3-years after RT. Conclusion: Texture analysis offers high dimension to differentiate breast tissue in mammogram. Using NDA to classify mammogram with lesion from mammogram without lesion, it can achieve rather high TP and low FP in the surveillance of mammogram for patient with conservative surgery combined RT.« less

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

Genetic Variants of NPAT-ATM and AURKA are Associated With an Early Adverse Reaction in the Gastrointestinal Tract of Patients With Cervical Cancer Treated With Pelvic Radiation Therapy

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

Ishikawa, Atsuko; Suga, Tomo; Shoji, Yoshimi

2011-11-15

Purpose: This study sought to associate polymorphisms in genes related to cell cycle regulation or genome maintenance with radiotherapy (RT)-induced an early adverse reaction (EAR) in patients with cervical cancer. Methods and Materials: This study enrolled 243 cervical cancer patients who were treated with pelvic RT. An early gastrointestinal reaction was graded using the National Cancer Institute Common Toxicity Criteria, version 2. Clinical factors of the enrolled patients were analyzed, and 208 patients were grouped for genetic analysis according to their EAR (Grade {<=}1, n = 150; Grade {>=}2, n = 58). Genomic DNA was genotyped, and association with themore » risk of EAR for 44 functional single-nucleotide polymorphisms (SNPs) of 19 candidate genes was assessed by single-locus, haplotype, and multilocus analyses. Results: Our analysis revealed two haplotypes to be associated with an increased risk of EAR. The first, comprising rs625120C, rs189037T, rs228589A, and rs183460G, is located between the 5' ends of NPAT and ATM (OR = 1.86; 95% CI, 1.21-2.87), whereas the second is located in the AURKA gene and comprises rs2273535A and rs1047972G (OR = 1.75; 95% CI, 1.10-2.78). A third haplotype, rs2273535T and rs1047972A in AURKA, was associated with a reduced EAR risk (OR = 0.42; 95% CI, 0.20-0.89). The risk of EAR was significantly higher among patients with both risk diplotypes than in those possessing the other diplotypes (OR = 3.24; 95% CI, 1.52-6.92). Conclusions: Individual radiosensitivity of intestine may be determined by haplotypes in the NPAT-ATM and AURKA genes. These variants should be explored in larger association studies in cervical cancer patients.« less

The Effects of Tier 2 Intervention on the Mathematics Performance of First-Grade Students Who Are at Risk for Mathematics Difficulties

ERIC Educational Resources Information Center

Bryant, Diane Pedrotty; Bryant, Brian R.; Gersten, Russell M.; Scammacca, Nancy N.; Funk, Catherine; Winter, Amanda; Shih, Minyi; Pool, Cathy

2008-01-01

Responsiveness to Intervention (RtI) is recommended both as an essential step before identifying learning disabilities (LD) and as a mechanism for preventing learning difficulties. The use of evidence-based multi-tiered interventions is of critical importance when implementing RtI. This article presents the results of a study that examined the…

The impact of radiation therapy sequencing on survival and cardiopulmonary mortality in the combined modality treatment of patients with esophageal cancer.

PubMed

Wojcieszynski, Andrzej P; Berman, Abigail T; Wan, Fei; Plastaras, John P; Metz, James M; Mitra, Nandita; Apisarnthanarax, Smith

2013-06-01

The addition of chemoradiation (CRT) to surgery has been shown to improve survival in patients with esophageal cancer. In the current study, the authors determined whether the sequencing of CRT has an effect on survival and cardiopulmonary mortality in patients with esophageal cancer. Patients with the following inclusion criteria were identified within 17 Surveillance, Epidemiology, and End Results registries from 1988 through 2007: adenocarcinoma or squamous cell carcinoma of the esophagus and having undergone esophagectomy. Patients who died within 90 days of surgery were excluded. Demographic, tumor, and survival data were compared between patients receiving preoperative and postoperative RT. Cox proportional hazards regression models were calculated to identify parameters associated with cause-specific survival and overall survival. A competing risk analysis was performed to account for death due to esophageal cancer in the calculation of cardiopulmonary mortality. Of 5512 patients, 1881 received preoperative RT, 901 received postoperative RT, and 2730 did not receive RT. Patients receiving preoperative RT had improved 5-year cause-specific survival (41% vs 31%; P < .0001) and overall survival (33% vs 23%; P < .0001) compared with those receiving postoperative RT. No differences in adjusted cardiopulmonary mortality were found between patients who received RT versus those who did not (8% vs 10% at 10 years; hazards ratio [HR], 0.84 [95% confidence interval (95% CI), 0.64-1.12] [P = .24]) or between those treated with preoperative RT versus those treated with postoperative RT (HR, 0.70; 95% CI, 0.46-1.08 [P = .11]). These population-based data support the use of preoperative RT in patients with locally advanced esophageal cancer. RT should not be withheld out of concern for cardiopulmonary mortality. Copyright © 2013 American Cancer Society.

Radiation Therapy Field Extent for Adjuvant Treatment of Axillary Metastases From Malignant Melanoma

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

Beadle, Beth M.; Guadagnolo, B. Ashleigh; Ballo, Matthew T.

2009-04-01

Purpose: To compare treatment-related outcomes and toxicity for patients with axillary lymph node metastases from malignant melanoma treated with postoperative radiation therapy (RT) to either the axilla only or both the axilla and supraclavicular fossa (extended field [EF]). Methods and Materials: The medical records of 200 consecutive patients treated with postoperative RT for axillary lymph node metastases from malignant melanoma were retrospectively reviewed. All patients received postoperative hypofractionated RT for high-risk features; 95 patients (48%) received RT to the axilla only and 105 patients (52%) to the EF. Results: At a median follow-up of 59 months, 111 patients (56%) hadmore » sustained relapse, and 99 patients (50%) had died. The 5-year overall survival, disease-free survival, and distant metastasis-free survival rates were 51%, 43%, and 46%, respectively. The 5-year axillary control rate was 88%. There was no difference in axillary control rates on the basis of the treated field (89% for axilla only vs. 86% for EF; p = 0.4). Forty-seven patients (24%) developed treatment-related complications. On both univariate and multivariate analyses, only treatment with EF irradiation was significantly associated with increased treatment-related complications. Conclusions: Adjuvant hypofractionated RT to the axilla only for metastatic malignant melanoma with high-risk features is an effective method to control axillary disease. Limiting the radiation field to the axilla only produced equivalent axillary control rates to EF and resulted in lower treatment-related complication rates.« less

Second Malignancies After Adjuvant Radiation Therapy for Early Stage Breast Cancer: Is There Increased Risk With Addition of Regional Radiation to Local Radiation?

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

Hamilton, Sarah Nicole; Department of Radiation Oncology, British Columbia Cancer Agency-Vancouver Centre, Vancouver, British Columbia; Tyldesley, Scott, E-mail: styldesl@bccancer.bc.ca

2015-04-01

Purpose: This study was undertaken to determine whether there was an increased risk of second malignancies (SM), particularly lung cancer, in early stage breast cancer patients treated with the addition of nodal fields to breast and/or chest wall radiation therapy (RT). Materials and Methods: Subjects were stage I/II female breast cancer patients 20 to 79 years of age, diagnosed between 1989 and 2005 and treated with adjuvant RT at our institution. Patients were included if they survived and did not have SM within 3 years of diagnosis. Standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated to compare SM incidencemore » to cancer incidence in the general sex- and age-matched populations. Secondary malignancy risks in patients treated with local RT (LRT) to the breast/chest wall were compared to those in patients treated with locoregional RT (LRRT) to the breast/chest wall and regional nodes, using multivariate regression analysis (MVA) to account for covariates. Results: The cohort included 12,836 patients with a median follow-up of 8.4 years. LRRT was used in 18% of patients. The SIR comparing patients treated with LRT to the general population was 1.29 (CI: 1.21-1.38). No statistically significant increased incidence of in-field malignancies (SIR, 1.04; CI: 0.87-1.23) and lung cancers (SIR, 1.06; CI: 0.88-1.26) was detected. The SIR comparing patients treated with LRRT to the general population was 1.39 (CI: 1.17-1.64). No statistically significant increased incidence of in-field malignancies (SIR, 1.26; CI: 0.77-1.94) and lung cancers (SIR, 1.27; CI: 0.76-1.98) was detected. On MVA comparing LRRT to LRT, the adjusted hazard ratio was 1.20 for in-field malignancies (CI: 0.68-2.16) and 1.26 for lung cancer (CI: 0.67-2.36). The excess attributable risk (EAR) to regional RT was 3.1 per 10,000 person years (CI: −8.7 to 9.9). Conclusions: No statistically significant increased risk of second malignancy was detected after LRRT relative to that for LRT. The upper limit of the EAR was approximately 1% at 10 years.« less

Development of a rapid and sensitive one-step reverse transcription-nested polymerase chain reaction in a single tube using the droplet-polymerase chain reaction machine.

PubMed

Yamaguchi, Akemi; Matsuda, Kazuyuki; Sueki, Akane; Taira, Chiaki; Uehara, Masayuki; Saito, Yasunori; Honda, Takayuki

2015-08-25

Reverse transcription (RT)-nested polymerase chain reaction (PCR) is a time-consuming procedure because it has several handling steps and is associated with the risk of cross-contamination during each step. Therefore, a rapid and sensitive one-step RT-nested PCR was developed that could be performed in a single tube using a droplet-PCR machine. The K562 BCR-ABL mRNA-positive cell line as well as bone marrow aspirates from 5 patients with chronic myelogenous leukemia (CML) and 5 controls without CML were used. We evaluated one-step RT-nested PCR using the droplet-PCR machine. One-step RT-nested PCR performed in a single tube using the droplet-PCR machine enabled the detection of BCR-ABL mRNA within 40min, which was 10(3)-fold superior to conventional RT nested PCR using three steps in separate tubes. The sensitivity of the one-step RT-nested PCR was 0.001%, with sample reactivity comparable to that of the conventional assay. One-step RT-nested PCR was developed using the droplet-PCR machine, which enabled all reactions to be performed in a single tube accurately and rapidly and with high sensitivity. This one-step RT-nested PCR may be applicable to a wide spectrum of genetic tests in clinical laboratories. Copyright © 2015 Elsevier B.V. All rights reserved.

Phase Measurement of Cognitive Impairment Specific to Radiotherapy

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

Armstrong, Carol L., E-mail: armstrongc@email.chop.edu; Department of Pediatrics, Division of Neuro-Oncology, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania; Shera, David M.

Purpose: Memory impairment is an early-delayed effect of radiotherapy (RT). The prospective longitudinal measurement of the cognitive phase effects from RT was conducted on treated and untreated brain tumor patients. The study design investigated semantic vs. perceptual and visual vs. verbal memory to determine the most disease-specific measure of RT-related changes and understanding of the neurotoxicity from RT to the brain. Methods and Materials: Tests of memory that had previously shown RT-related phasic changes were compared with experimental tests of memory to test hypotheses about cognition targeted to the neural toxicity of RT. The results from 41 irradiated and 29more » nonirradiated patients with low-grade, supratentorial tumors were analyzed. The methods controlled for comorbid white matter risk, recurrence, interval after treatment, and age (18-69 years). The effects were examined before RT and at three points after RT to 1 year using a mixed effects model that included interval, group, surgical status, medication use, practice, and individual random effects. Four new tests of memory and other candidate cognitive tests were investigated, and a post hoc analysis of a comprehensive battery of tests was performed to identify the cognitive processes most specific to RT. Results: The RT effects on memory were identified in the treated group only; among the new tests of memory and the complete neurocognitive battery, the RT effects were significant only for delayed recall (p < 0.009) and interval to recognize (p < 0.002). Tumor location was not related to the treatment effect. Memory decline was specific to retrieval of semantic memories; a double dissociation of semantic from perceptual visual memory was demonstrated in the RT group. Conclusions: These results implicate memory dependent on the semantic cortex and the hippocampal memory system. A cognitive measurement that is brief but specific to neural mechanisms is effective and feasible for studies of RT damage.« less

Brainstem dose is associated with patient-reported acute fatigue in head and neck cancer radiation therapy.

PubMed

Ferris, Matthew J; Zhong, Jim; Switchenko, Jeffrey M; Higgins, Kristin A; Cassidy, Richard J; McDonald, Mark W; Eaton, Bree R; Patel, Kirtesh R; Steuer, Conor E; Baddour, H Michael; Miller, Andrew H; Bruner, Deborah W; Xiao, Canhua; Beitler, Jonathan J

2018-01-01

Radiation (RT) dose to the central nervous system (CNS) has been implicated as a contributor to treatment-related fatigue in head and neck cancer (HNC) patients undergoing radiation therapy (RT). This study evaluates the association of RT dose to CNS structures with patient-reported (PRO) fatigue scores in a population of HNC patients. At pre-RT (baseline), 6th week of RT, and 1-month post-RT time points, Multidimensional Fatigue Inventory (MFI-20) scores were prospectively obtained from 124 patients undergoing definitive treatment for HNC. Medulla, pons, midbrain, total brainstem, cerebellum, posterior fossa, and pituitary dosimetry were evaluated using summary statistics and dose-volume histograms, and associations with MFI-20 scores were analyzed. Maximum dose (Dmax) to the brainstem and medulla was significantly associated with MFI-20 scores at 6th week of RT and 1-month post-RT time points, after controlling for baseline scores (p<0.05). Each 1Gy increase in medulla Dmax resulted in an increase in total MFI-20 score over baseline of 0.30 (p=0.026), and 0.25 (p=0.037), at the 6th week of RT and 1-month post-RT, respectively. Each 1Gy increase in brainstem Dmax resulted in an increase in total MFI-20 score over baseline of 0.30 (p=0.027), and 0.25 (p=0.037) at the 6th week of RT, 1-month post-RT, respectively. Statistically significant associations were not found between dosimetry for the other CNS structures and MFI-20 scores. In this analysis of PRO fatigue scores from a population of patients undergoing definitive RT for HNC, maximum dose to the brainstem and medulla was associated with a significantly increased risk of acute patient fatigue. Copyright © 2017 Elsevier B.V. All rights reserved.

Investigation of the deformation mechanisms of core-shell rubber-modified epoxy at cryogenic temperatures

NASA Astrophysics Data System (ADS)

Brown, Hayley Rebecca

The industrial demand for high strength-to-weight ratio materials is increasing due to the need for high performance components. Epoxy polymers, although often used in fiber-reinforced polymeric composites, have an inherent low toughness that further decreases with decreasing temperatures. Second-phase additives have been effective in increasing the toughness of epoxies at room temperature; however, the mechanisms at low temperatures are still not understood. In this study, the deformation mechanisms of a DGEBA epoxy modified with MX960 core-shell rubber (CSR) particles were investigated under quasi-static tensile and impact loads at room temperature (RT) and liquid nitrogen (LN 2) temperature. Overall, the CSR had little effect on the tensile properties at RT and LN2 temperature. The impact strength decreased from neat to 3 wt% but increased from neat to 5 wt% at RT and LN2 temperature, with a higher impact strength at RT at all CSR loadings. The CSR particles debonded in front of the crack tip, inducing voids into the matrix. It was found that an increase in shear deformation and void growth likely accounted for the higher impact strength at 5 wt% CSR loading at RT while the thermal stress fields due to the coefficient of thermal expansion mismatch between rubber and epoxy and an increase in secondary cracking is likely responsible for the higher impact strength at 5 wt% tested at LN2 temperature. While a large toughening effect was not seen in this study, the mechanisms analyzed herein will likely be of use for further material investigations at cryogenic temperatures.

Intraocular pressure measurement over soft contact lens by rebound tonometer: a comparative study

PubMed Central

Nacaroglu, Senay Asik; Un, Emine Seker; Ersoz, Mehmet Giray; Tasci, Yelda

2015-01-01

AIM To evaluate the intraocular pressure (IOP) measurements by Icare rebound tonometer over a contact lens in comparison with Goldmann applanation tonometry (GAT). METHODS Fifty patients using contact lens were included in this study. One of the eyes of the patients was selected randomly and their IOP were measured by rebound tonometer with and without contact lens (RTCL, RT respectively) and by GAT, as well as their central corneal thickness (CCT) by optical pachymeter. The results of both methods were compared by correlation analysis, general linear method repeated measure and Bland-Altman analysis. RESULTS Mean IOP values measured by RTCL, RT and GAT were 15.68±3.7, 14.50±3.4 and 14.16±2.8 (P<0.001), respectively. Mean IOP by RTCL was significantly higher than the measurements implemented by RT and GAT (P<0.001), while there was no difference between the measurements by GAT and RT (P=0.629). There was a good level of positive correlation between GAT and RTCL as well as RT (r=0.786 P<0.001, r=0.833 P<0.001, respectively). We have observed that CCT increase did not show any correlation with the differences of the measurements between RTCL and RT (P=0.329), RTCL and GAT (P=0.07) as well as RT and GAT (P=0.189) in linear regression model. CONCLUSION The average of the measurements over contact lens by rebound tonometer was found to be higher than what was measured by GAT. Although this difference is statistically significant, it may be clinically negligible in the normal population. PMID:26086004

In Vitro Stability of Free and Glucuronidated Cannabinoids in Urine Following Controlled Smoked Cannabis

PubMed Central

Desrosiers, Nathalie A.; Lee, Dayong; Scheidweiler, Karl B.; Concheiro-Guisan, Marta; Gorelick, David A.; Huestis, Marilyn A.

2014-01-01

Analyte stability is an important factor in urine test interpretation, yet cannabinoid stability data are limited. A comprehensive study of Δ9-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol, cannabinol, THC-glucuronide, and THCCOOH-glucuronide stabilities in authentic urine was completed. Urine samples after ad libitum cannabis smoking were pooled to prepare low and high pools for each study participant; baseline concentrations were measured within 24h at room temperature (RT), 4°C and −20°C. Stability at RT, 4°C and −20°C was evaluated by Friedman tests for up to 1 year. THCCOOH, THC-glucuronide, and THCCOOH-glucuronide were quantified in baseline pools. RT THCCOOH baseline concentrations were significantly higher than −20°C, but not 4°C baseline concentrations. After 1 week at RT, THCCOOH increased, THCCOOH-glucuronide decreased, but THC-glucuronide was unchanged. In RT low pool, total THCCOOH (THCCOOH+THCCOOH-glucuronide) was significantly lower after 1 week. At 4°C, THCCOOH was stable 2 weeks, THCCOOH-glucuronide 1 month and THC-glucuronide for at least 6 months. THCCOOH was stable frozen for 1 year, but 6 months high pool results were significantly higher than baseline; THC-glucuronide and THCCOOH-glucuronide were stable for 6 months. Total THCCOOH was stable 6 months at 4°C, and frozen 6 months (low) and 1 year (high). THC, cannabidiol and cannabinol were never detected in urine; although not detected initially, 11-OH-THC was detected in 2 low and 3 high pools after one week at RT. Substantial THCCOOH-glucuronide deconjugation was observed at RT and 4°C. Analysis should be conducted within 3 months if non-hydrolyzed THCCOOH or THCCOOH-glucuronide quantification is required. PMID:24292435

Effects of Different Types of Exercise on Body Composition, Muscle Strength, and IGF-1 in the Elderly with Sarcopenic Obesity.

PubMed

Chen, Hung-Ting; Chung, Yu-Chun; Chen, Yu-Jen; Ho, Sung-Yen; Wu, Huey-June

2017-04-01

To investigate the influence of resistance training (RT), aerobic training (AT), or combination training (CT) interventions on the body composition, muscle strength performance, and insulin-like growth factor 1 (IGF-1) of patients with sarcopenic obesity. Randomized controlled trial. Community center and research center. Sixty men and women aged 65-75 with sarcopenic obesity. Participants were randomly assigned to RT, AT, CT, and control (CON) groups. After training twice a week for 8 weeks, the participants in each group ceased training for 4 weeks before being examined for the retention effects of the training interventions. The body composition, grip strength, maximum back extensor strength, maximum knee extensor muscle strength, and blood IGF-1 concentration were measured. The skeletal muscle mass (SMM), body fat mass, appendicular SMM/weight %, and visceral fat area (VFA) of the RT, AT, and CT groups were significantly superior to those of the CON group at both week 8 and week 12. Regarding muscle strength performance, the RT group exhibited greater grip strength at weeks 8 and 12 as well as higher knee extensor performance at week 8 than that of the other groups. At week 8, the serum IGF-1 concentration of the RT group was higher than the CON group, whereas the CT group was superior to the AT and CON groups. Older adults with sarcopenic obesity who engaged in the RT, AT, and CT interventions demonstrated increased muscle mass and reduced total fat mass and VFA compared with those without training. The muscle strength performance and serum IGF-1 level in trained groups, especially in the RT group, were superior to the control group. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Comparison of clinicopathologic characteristics of urothelial carcinoma between patients after renal transplantation and on dialysis.

PubMed

Zhang, Bo; Shen, Cheng; Han, Wen-ke; Yu, Wei

2014-09-15

Urothelial carcinoma (UC) is a common complication after renal replacement therapy (RRT) among Chinese end-stage renal disease (ESRD) patients. It is unclear whether there are any differences in the clinicopathologic characteristics of UC between renal transplantation (RT) and dialysis patients; such differences could impact RRT modality selection. We retrospectively reviewed clinicopathologic data for 27 RT patients and 40 dialysis patients who were diagnosed with UC in our center to explore differences in the clinicopathologic characteristics of UC and prognoses between the two groups. The median follow-up period was 92 months (2-137) for the RT group and 71 months (18-155) for the dialysis group. The demographic and baseline data showed no significant differences between the two groups. Upper urinary tract UC (UUC) occurred more frequently in the RT group (22 UUCs in 39 UCs), whereas bladder UC (BUC) predominated in the dialysis group (33 BUCs in 49 UCs) (P=0.025). The pathologic grading in the RT group was significantly higher than that in the dialysis group (P=0.046 for WHO1973 grading, P=0.026 for WHO2004 grading), whereas the difference in tumor stage was not significant (P=0.089). The RT group manifested a higher recurrence rate than the dialysis group (P=0.024). However, the overall and cancer-specific survival rates between the two groups were not significantly different (P=0.239 and P=0.818, respectively). Certain traits of UC, including tumor site, pathologic grading, and recurrence-free survival, were notably different between RT and dialysis patients, but the overall and cancer-specific survival rates were similar.

Movement is the glue connecting home ranges and habitat selection.

PubMed

Van Moorter, Bram; Rolandsen, Christer M; Basille, Mathieu; Gaillard, Jean-Michel

2016-01-01

Animal space use has been studied by focusing either on geographic (e.g. home ranges, species' distribution) or on environmental (e.g. habitat use and selection) space. However, all patterns of space use emerge from individual movements, which are the primary means by which animals change their environment. Individuals increase their use of a given area by adjusting two key movement components: the duration of their visit and/or the frequency of revisits. Thus, in spatially heterogeneous environments, animals exploit known, high-quality resource areas by increasing their residence time (RT) in and/or decreasing their time to return (TtoR) to these areas. We expected that spatial variation in these two movement properties should lead to observed patterns of space use in both geographic and environmental spaces. We derived a set of nine predictions linking spatial distribution of movement properties to emerging space-use patterns. We predicted that, at a given scale, high variation in RT and TtoR among habitats leads to strong habitat selection and that long RT and short TtoR result in a small home range size. We tested these predictions using moose (Alces alces) GPS tracking data. We first modelled the relationship between landscape characteristics and movement properties. Then, we investigated how the spatial distribution of predicted movement properties (i.e. spatial autocorrelation, mean, and variance of RT and TtoR) influences home range size and hierarchical habitat selection. In landscapes with high spatial autocorrelation of RT and TtoR, a high variation in both RT and TtoR occurred in home ranges. As expected, home range location was highly selective in such landscapes (i.e. second-order habitat selection); RT was higher and TtoR lower within the selected home range than outside, and moose home ranges were small. Within home ranges, a higher variation in both RT and TtoR was associated with higher selectivity among habitat types (i.e. third-order habitat selection). Our findings show how patterns of geographic and environmental space use correspond to the two sides of a coin, linked by movement responses of individuals to environmental heterogeneity. By demonstrating the potential to assess the consequences of altering RT or TtoR (e.g. through human disturbance or climatic changes) on home range size and habitat selection, our work sets the basis for new theoretical and methodological advances in movement ecology. © 2015 The Authors. Journal of Animal Ecology © 2015 British Ecological Society.

Respiratory Viruses and Treatment Failure in Children With Asthma Exacerbation.

PubMed

Merckx, Joanna; Ducharme, Francine M; Martineau, Christine; Zemek, Roger; Gravel, Jocelyn; Chalut, Dominic; Poonai, Naveen; Quach, Caroline

2018-06-04

: media-1vid110.1542/5771275574001PEDS-VA_2017-4105 Video Abstract OBJECTIVES: Respiratory pathogens commonly trigger pediatric asthma exacerbations, but their impact on severity and treatment response remains unclear. We performed a secondary analysis of the Determinants of Oral Corticosteroid Responsiveness in Wheezing Asthmatic Youth (DOORWAY) study, a prospective cohort study of children (aged 1-17 years) presenting to the emergency department with moderate or severe exacerbations. Nasopharyngeal specimens were analyzed by RT-PCR for 27 respiratory pathogens. We investigated the association between pathogens and both exacerbation severity (assessed with the Pediatric Respiratory Assessment Measure) and treatment failure (hospital admission, emergency department stay >8 hours, or relapse) of a standardized severity-specific treatment. Logistic multivariate regressions were used to estimate average marginal effects (absolute risks and risk differences [RD]). Of 958 participants, 61.7% were positive for ≥1 pathogen (rhinovirus was the most prevalent [29.4%]) and 16.9% experienced treatment failure. The presence of any pathogen was not associated with higher baseline severity but with a higher risk of treatment failure (20.7% vs 12.5%; RD = 8.2% [95% confidence interval: 3.3% to 13.1%]) compared to the absence of a pathogen. Nonrhinovirus pathogens were associated with an increased absolute risk (RD) of treatment failure by 13.1% (95% confidence interval: 6.4% to 19.8%), specifically, by 8.8% for respiratory syncytial virus, 24.9% for influenza, and 34.1% for parainfluenza. Although respiratory pathogens were not associated with higher severity on presentation, they were associated with increased treatment failure risk, particularly in the presence of respiratory syncytial virus, influenza, and parainfluenza. This supports influenza prevention in asthmatic children, consideration of pathogen identification on presentation, and exploration of treatment intensification for infected patients at higher risk of treatment failure. Copyright © 2018 by the American Academy of Pediatrics.

Pretreatment anemia is correlated with the reduced effectiveness of radiation and concurrent chemotherapy in advanced head and neck cancer

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

Prosnitz, Robert G.; Yao, Bin M.S.; Farrell, Catherine L.

2005-03-15

Purpose: Pretreatment anemia is an adverse prognostic variable in squamous cell head-and-neck cancer (HNC) patients treated with radiotherapy (RT) alone. Tumor hypoxia is an adverse parameter for treatment with RT alone or with RT and concurrent chemotherapy (CCT). Tumor hypoxia is more prevalent in patients who present with pretreatment hemoglobin (Hgb) concentrations less than 13 g/dL. RT/CCT improves survival over RT alone in advanced HNC, and its use is becoming more widespread. This study was performed to evaluate whether pretreatment Hgb less than 13 g/dL was correlated with treatment outcome in patients with advanced HNC treated with a uniform regimenmore » of RT/CCT. Methods and materials: The study population consisted of patients with AJCC Stage III or IV, M0 HNC who were treated with 70 to 72.5 Gy accelerated hyperfractionated RT (1.25 Gy b.i.d.) and CCT consisting of 2 cycles of CDDP (12-20 mg/m{sup 2}/d x 5 days) and continuous infusion 5-FU (600 mg/m{sup 2}/d x 5 days) during Week 1 and Week 6. A planned break in RT occurred during Week 4. These patients were enrolled on the experimental arm of a prospective randomized trial that compared this regimen to hyperfractionated irradiation alone from 1990 to 1996. RT/CCT was delivered as standard therapy from 1996 to 2000. The primary endpoint was failure-free survival (FFS). Secondary endpoints included local-regional control and overall survival. Results: One hundred and fifty-nine patients were treated from 1990 to 2000. The median (25-75%) pretreatment Hgb was 13.6 (12.2-13.5) g/dL. Hgb was 13 g/dL or higher in 105 patients and less than 13 g/dL in 54 patients. Primary tumor sites included oropharynx (43%), hypopharynx/larynx (36%), oral cavity (9%), and nasopharynx (6%). Seventy-eight percent of the patients with Hgb 13 g/dL or higher and 92% of the patients with Hgb less than 13 g/dL had a primary tumor stage of T3 or T4 (p = 0.01). Node-positive disease was present in 74 of 105 (70%) of patients with Hgb 13 g/dL or higher patients and in 36/54 (67%) of patients with Hgb less than 13 g/dL patients. Median follow-up of surviving patients was 42 months (range, 4-128 months). Five-year FFS was 75% for patients with Hgb 13 g/dL or higher vs. 50% for patients with Hgb less than 13 g/dL had a (p < 0.01). A total of 49 failures occurred in both patient cohorts. The median (25-75%) decrease in Hgb during RT/CCT was 2.2 (1.3-3.1) g/dL, both in patients who failed and in those who remained disease-free. Conclusion: Pretreatment Hgb less than 13 g/dL is correlated with adverse outcomes in advanced HNC patients treated with RT/CCT. Whether anemia actually causes poor outcomes remains unknown. The therapeutic effect of anemia correction is being evaluated in prospective trials.« less

Relationship Between Radiation Therapy Dose and Outcome in Patients Treated With Neoadjuvant Chemoradiation Therapy and Surgery for Stage IIIA Non-Small Cell Lung Cancer: A Population-Based, Comparative Effectiveness Analysis

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

Sher, David J., E-mail: david_sher@rush.edu; Fidler, Mary Jo; Seder, Christopher W.

Purpose: To compare, using the National Cancer Database, survival, pathologic, and surgical outcomes in patients with stage IIIA non-small cell lung cancer treated with differential doses of neoadjuvant chemoradiation therapy, with the aim to discern whether radiation dose escalation was associated with a comparative effectiveness benefit and/or toxicity risk. Methods and Materials: Patients in the National Cancer Database with stage IIIA non-small cell lung cancer treated with neoadjuvant chemoradiation therapy and surgery between 1998 and 2005 were analyzed. Dose strata were divided between 36 to 45 Gy (low-dose radiation therapy, LD-RT), 45 to 54 Gy (inclusive, standard-dose, SD-RT), and 54 to 74 Gymore » (high-dose, HD-RT). Outcomes included overall survival, residual nodal disease, positive surgical margin status, hospital length of stay, and adverse surgical outcomes (30-day mortality or readmission). Results: The cohort consisted of 1041 patients: 233 (22%) LD-RT, 584 (56%) SD-RT, and 230 (22%) HD-RT. The median, 3-year, and 5-year overall survival outcomes were 34.9 months, 48%, and 37%, respectively. On univariable analysis, patients treated with SD-RT experienced prolonged overall survival (median 38.3 vs 31.8 vs 29.0 months for SD-RT, LD-RT, and HD-RT, respectively, P=.0089), which was confirmed on multivariable analysis (hazard ratios 0.77 and 0.81 vs LD and HD, respectively). Residual nodal disease was seen less often after HD-RT (25.5% vs 31.8% and 37.5% for HD-RT, LD-RT, and SD-RT, respectively, P=.0038). Patients treated with SD-RT had fewer prolonged hospital stays. There were no differences in positive surgical margin status or adverse surgical outcomes between the cohorts. Conclusions: Neoadjuvant chemoradiation therapy between 45 and 54 Gy was associated with superior survival in comparison with doses above and below this threshold. Although this conclusion is limited by selection bias, clear candidates for trimodality therapy do not seem to achieve additional benefit with dose escalation.« less

Severity of Oral Mucositis in Children following Chemotherapy and Radiotherapy and Its Implications at a Single Oncology Centre in Durango State, Mexico.

PubMed

Carreón-Burciaga, Ramón G; Castañeda-Castaneira, Enrique; González-González, Rogelio; Molina-Frechero, Nelly; Gaona, Enrique; Bologna-Molina, Ronell

2018-01-01

Mucositis is an adverse effect of chemotherapy (QT) and/or radiotherapy (RT). The purpose of this study was to investigate the occurrence of oral mucositis in children undergoing cancer treatment. Fifty-one children with cancer who had received QT, RT, or both (QT-RT) underwent clinical evaluations; World Health Organization criteria were used to establish the degree and severity of mucositis. The correlations between the clinical data, type of cancer, and therapy were statistically analysed. Mucositis was present in 88.23% of the patients; 57.78%, 7.78%, and 24.44% received QT, RT, and QT-RT, respectively. Severity scores of 1 and 2 were the most common; scores of 3-4 were observed in patients who received QT-RT or more than 7 treatment cycles. There was a significant association between mucositis, the type of treatment, and the number of cycles received ( p < 0.05). It is important to implement therapeutic protocols that help maintain excellent oral health and reduce the risk of oral mucositis. Stomatologists should be consulted to assess patients' oral cavities and provide preventive treatment prior to QT and/or RT administration. It is important to integrate a stomatologist into the oncological working group to focus on preventing and managing oral mucositis.

Prostate Cancer Radiation Therapy: What Do Clinicians Have to Know?

PubMed Central

Van Limbergen, Evert J.; van Lin, Emile N.; van Roermund, Joep G. H.; Lambin, Philippe

2016-01-01

Radiotherapy (RT) for prostate cancer (PC) has steadily evolved over the last decades, with improving biochemical disease-free survival. Recently population based research also revealed an association between overall survival and doses ≥ 75.6 Gray (Gy) in men with intermediate- and high-risk PC. Examples of improved RT techniques are image-guided RT, intensity-modulated RT, volumetric modulated arc therapy, and stereotactic ablative body RT, which could facilitate further dose escalation. Brachytherapy is an internal form of RT that also developed substantially. New devices such as rectum spacers and balloons have been developed to spare rectal structures. Newer techniques like protons and carbon ions have the intrinsic characteristics maximising the dose on the tumour while minimising the effect on the surrounding healthy tissue, but clinical data are needed for confirmation in randomised phase III trials. Furthermore, it provides an overview of an important discussion issue in PC treatment between urologists and radiation oncologists: the comparison between radical prostatectomy and RT. Current literature reveals that all possible treatment modalities have the same cure rate, but a different toxicity pattern. We recommend proposing the possible different treatment modalities with their own advantages and side-effects to the individual patient. Clinicians and patients should make treatment decisions together (shared decision-making) while using patient decision aids. PMID:28116302

Recommendations for the referral of patients for proton-beam therapy, an Alberta Health Services report: a model for Canada?

PubMed Central

Patel, S.; Kostaras, X.; Parliament, M.; Olivotto, I.A.; Nordal, R.; Aronyk, K.; Hagen, N.

2014-01-01

Background Compared with photon therapy, proton-beam therapy (pbt) offers compelling advantages in physical dose distribution. Worldwide, gantry-based proton facilities are increasing in number, but no such facilities exist in Canada. To access pbt, Canadian patients must travel abroad for treatment at high cost. In the face of limited access, this report seeks to provide recommendations for the selection of patients most likely to benefit from pbt and suggests an out-of-country referral process. Methods The medline, embase, PubMed, and Cochrane databases were systematically searched for studies published between January 1990 and May 2014 that evaluated clinical outcomes after pbt. A draft report developed through a review of evidence was externally reviewed and then approved by the Alberta Health Services Cancer Care Proton Therapy Guidelines steering committee. Results Proton therapy is often used to treat tumours close to radiosensitive tissues and to treat children at risk of developing significant late effects of radiation therapy (rt). In uncontrolled and retrospective studies, local control rates with pbt appear similar to, or in some cases higher than, photon rt. Randomized trials comparing equivalent doses of pbt and photon rt are not available. Summary Referral for pbt is recommended for patients who are being treated with curative intent and with an expectation for long-term survival, and who are able and willing to travel abroad to a proton facility. Commonly accepted indications for referral include chordoma and chondrosarcoma, intraocular melanoma, and solid tumours in children and adolescents who have the greatest risk for long-term sequelae. Current data do not provide sufficient evidence to recommend routine referral of patients with most head-and-neck, breast, lung, gastrointestinal tract, and pelvic cancers, including prostate cancer. It is recommended that all referrals be considered by a multidisciplinary team to select appropriate cases. PMID:25302033

Pulmonary embolism in a stroke patient after systemic thrombolysis: clinical decisions and literature review.

PubMed

Pilato, Fabio; Calandrelli, Rosalinda; Profice, Paolo; Della Marca, Giacomo; Broccolini, Aldobrando; Bello, Giuseppe; Bocci, Maria Grazia; Distefano, Marisa; Colosimo, Cesare; Rossini, Paolo Maria

2013-11-01

Pulmonary embolism can be a catastrophic event that can result in early death or serious hemodynamic dysfunction. The dehydration, immobility, and infections occurring in acute stroke patients puts these patients at risk of developing deep vein thrombosis and pulmonary embolism. Recombinant tissue-type plasminogen activator (rt-PA) is the established therapy for acute ischemic stroke, and its prompt administration results in a better outcome in stroke patients. We describe a 73-year-old man who arrived at the emergency room within 2 hours of acute onset of left hemiparesis who was treated with rt-PA and suffered a pulmonary embolism 3 days after acute stroke therapy. rt-PA is also a current therapy for pulmonary embolism, but an ischemic stroke in the previous 3 months is an absolute contraindication to thrombolysis because of the high risk of intracranial hemorrhage. We discuss clinical and therapeutic decisions and review the current literature. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Rehabilitation technology services and employment outcomes among consumers using division of rehabilitation services.

PubMed

Sprong, Matthew Evan; Dallas, Bryan; Paul, Erina; Xia, Michelle

2018-05-03

The primary goal of the study was to evaluate how the use of rehabilitation technology impacted closure status for consumers receiving services in fiscal year (FY) 2014. Rehabilitation Service Administration (RSA-911) Case Service Report FY 2014 archival dataset was obtained from the U.S. Department of Education (2014) and secondary analyses was performed for this study. RSA-911 archival data is updated on an annual basis and consists of all state-federal rehabilitation consumers who were served in the specific fiscal year. The dataset contains information related to each consumer's demographic information (e.g. age, gender, race) and other supplemental information (e.g. weekly earnings at closure, cause of disability, services provided). A multiple logistic regression analysis was utilized and revealed that white consumers receiving rehabilitation technology (RT) services have significantly higher closure rate than consumers of other races, RT services differ by the employment status at application, RT services differ by the type of disability, educational level at application for people receiving RT services did predict closure status (i.e. exiting with an employment outcome), IEP status did not predict closure status, weekly earnings at application did predict closure status and the interaction effect between IEP and RT services is statistically significant. The odds ratio (ORs) were presented at the 95% confidence interval (CI). Vocational rehabilitation counselors needs training to correctly identify appropriate RT services for consumers, so that the likelihood of exiting with an employment outcome is obtained. Implications for Rehabilitation RT services significantly improved their chances of successful employment compared to those who did not receive RT services. Education at closure would also have some significant impact on employment outcomes. Training in Assistive Technology (AT) for Vocational Rehabilitation counselors will assist in the proper identification of AT requirements, which may lead to a higher likelihood of consumers exiting with an employment outcome.

Novel concepts in radiation-induced cardiovascular disease

PubMed Central

Cuomo, Jason R; Sharma, Gyanendra K; Conger, Preston D; Weintraub, Neal L

2016-01-01

Radiation-induced cardiovascular disease (RICVD) is the most common nonmalignant cause of morbidity and mortality among cancer survivors who have undergone mediastinal radiation therapy (RT). Cardiovascular complications include effusive or constrictive pericarditis, cardiomyopathy, valvular heart disease, and coronary/vascular disease. These are pathophysiologically distinct disease entities whose prevalence varies depending on the timing and extent of radiation exposure to the heart and great vessels. Although refinements in RT dosimetry and shielding will inevitably limit future cases of RICVD, the increasing number of long-term cancer survivors, including those treated with older higher-dose RT regimens, will ensure a steady flow of afflicted patients for the foreseeable future. Thus, there is a pressing need for enhanced understanding of the disease mechanisms, and improved detection methods and treatment strategies. Newly characterized mechanisms responsible for the establishment of chronic fibrosis, such as oxidative stress, inflammation and epigenetic modifications, are discussed and linked to potential treatments currently under study. Novel imaging modalities may serve as powerful screening tools in RICVD, and recent research and expert opinion advocating their use is introduced. Data arguing for the aggressive use of percutaneous interventions, such as transcutaneous valve replacement and drug-eluting stents, are examined and considered in the context of prior therapeutic approaches. RICVD and its treatment options are the subject of a rich and dynamic body of research, and patients who are at risk or suffering from this disease will benefit from the care of physicians with specialty expertise in the emerging field of cardio-oncology. PMID:27721934

Proton Beam Reirradiation for Recurrent Head and Neck Cancer: Multi-institutional Report on Feasibility and Early Outcomes

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

Romesser, Paul B.; Cahlon, Oren; ProCure Proton Therapy Center, Somerset, New Jersey

Purpose: Reirradiation therapy (re-RT) is the only potentially curative treatment option for patients with locally recurrent head and neck cancer (HNC). Given the significant morbidity with head and neck re-RT, interest in proton beam radiation therapy (PBRT) has increased. We report the first multi-institutional clinical experience using curative-intent PBRT for re-RT in recurrent HNC. Methods and Materials: A retrospective analysis of ongoing prospective data registries from 2 hybrid community practice and academic proton centers was conducted. Patients with recurrent HNC who underwent at least 1 prior course of definitive-intent external beam radiation therapy (RT) were included. Acute and late toxicitiesmore » were assessed with the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 and the Radiation Therapy Oncology Group late radiation morbidity scoring system, respectively. The cumulative incidence of locoregional failure was calculated with death as a competing risk. The actuarial 12-month freedom–from–distant metastasis and overall survival rates were calculated with the Kaplan-Meier method. Results: Ninety-two consecutive patients were treated with curative-intent re-RT with PBRT between 2011 and 2014. Median follow-up among surviving patients was 13.3 months and among all patients was 10.4 months. The median time between last RT and PBRT was 34.4 months. There were 76 patients with 1 prior RT course and 16 with 2 or more courses. The median PBRT dose was 60.6 Gy (relative biological effectiveness, [RBE]). Eighty-five percent of patients underwent prior HNC RT for an oropharynx primary, and 39% underwent salvage surgery before re-RT. The cumulative incidence of locoregional failure at 12 months, with death as a competing risk, was 25.1%. The actuarial 12-month freedom–from–distant metastasis and overall survival rates were 84.0% and 65.2%, respectively. Acute toxicities of grade 3 or greater included mucositis (9.9%), dysphagia (9.1%), esophagitis (9.1%), and dermatitis (3.3%). There was 1 death during PBRT due to disease progression. Grade 3 or greater late skin and dysphagia toxicities were noted in 6 patients (8.7%) and 4 patients (7.1%), respectively. Two patients had grade 5 toxicity due to treatment-related bleeding. Conclusions: Proton beam re-RT of the head and neck can provide effective tumor control with acceptable acute and late toxicity profiles likely because of the decreased dose to the surrounding normal, albeit previously irradiated, tissue, although longer follow-up is needed to confirm these findings.« less

Risk factors for scoliosis in children with neuroblastoma

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

Paulino, Arnold C.; Fowler, B. Zach

2005-03-01

Purpose: To determine the risk factors for scoliosis in children treated for neuroblastoma. Methods and materials: From 1957 to 1997, 58 children with neuroblastoma were treated at one institution and have survived a minimum of 5 years. There were 35 boys and 23 girls with a median age of 6 months (range, 2 weeks to 15 years) at initial diagnosis. Primary site was located in the adrenal gland in 25 (43.1%), abdominal/nonadrenal in 16 (27.6%), thoracic in 12 (20.7%), cervical in 3 (5.3%), and pelvic region in 2 (3.5%). The International Neuroblastoma Staging System (INSS) stage was Stage 1 inmore » 10 (17.2%), Stage 2A in 7 (12.1%), Stage 2B in 5 (8.6%), Stage 3 in 22 (37.9%), Stage 4 in 4 (6.9%), and Stage 4S in 10 (17.2%). Thirty-three (56.9%) received chemotherapy whereas 5 (8.6%) had a laminectomy as part of the surgical procedure. Twenty-seven (46.6%) received radiotherapy (RT). Beam energy was 1.25 MV in 11 (41%), 250 kV in 10 (37%), 4 MV in 4 (15%), and 6-MV photons in 1 patient. One patient received 300 cGy in 1 fraction total skin RT using 6-MeV electrons. For the remaining patients, fraction size was 100 cGy in 6 (22%), 150-180 cGy in 11 (41%), 200 cGy in 4 (15%), and 250-300 cGy in 3. Three patients had total body irradiation at 333 cGy for 3 fractions. For all children who received RT, median total dose was 2000 cGy (range, 300-3900 cGy). Patients who were treated with RT had plain films of the irradiated area every 1 to 2 years until at least the age of puberty. Median follow-up was 10 years (range, 5-46 years). Results: The overall 5-, 10-, and 15-year scoliosis-free rates were 87.6%, 79.0%, and 76.0% respectively. Twelve (21%) developed scoliosis at a median time of 51 months (range, 8-137 months). The degree of scoliosis was mild ({<=}20 deg ) in 8 (67%). Four had scoliosis ranging from 30 deg to 66 deg ; 3 of these patients required surgical intervention, whereas 1 had an underlying Duchenne muscular dystrophy which manifested itself 8 years after diagnosis of neuroblastoma. Median time to scoliosis was 23 months (range, 8-54 months) in children who had a laminectomy. On multivariate analysis, both history of laminectomy (p = 0.0005) and use of RT (p = 0.0284) were found to be risk factors for development of scoliosis. Gender, age at diagnosis, INSS stage, primary site, and use of chemotherapy were not found to be significant. Both RT fraction size and beam energy were also not significant, but increasing total RT dose was found to be significant (p = 0.0039). The 15-year scoliosis-free rates were 20% for children who had a laminectomy and 81.3% for those who did not have a laminectomy. The 15-year scoliosis-free rates for children treated with RT doses 0 cGy, 1-1750 cGy, 1751-2300 cGy, and >2300 cGy were 91.7%, 87.5%, 51.4%, and 44.4% respectively. Conclusions: Treatment-related factors, namely laminectomy and radiotherapy, were found to increase the risk of scoliosis in patients with neuroblastoma. Children who had a laminectomy were more likely to manifest scoliosis earlier. Increasing RT dose was found to impact adversely on the development of scoliosis.« less

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

Pinnix, Chelsea C.; Dabaja, Bouthaina, E-mail: bdabaja@mdanderson.org; Ahmed, Mohamed Amin

Purpose: Excellent outcomes obtained after infusional dose-adjusted etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and rituximab (R-EPOCH) alone have led some to question the role of consolidative radiation therapy (RT) in the treatment of primary mediastinal B cell lymphoma (PMBL). We reviewed the outcomes in patients treated with 1 of 3 rituximab-containing regimens (cyclophosphamide, doxorubicin, vincristine, prednisone [R-CHOP]; hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone [R-HCVAD], or R-EPOCH) with or without RT. We also evaluated the ability of positron emission tomography–computed tomography (PET-CT) to identify patients at risk of relapse. Methods and Materials: We retrospectively identified 97 patients with diagnoses of stage I/IImore » PMBCL treated at our institution between 2001 and 2013. The clinical characteristics, treatment outcomes, and toxicity were assessed. We analyzed whether postchemotherapy PET-CT could identify patients at risk for progressive disease according to a 5 point scale (5PS) Deauville score assigned. Results: Among 97 patients (median follow-up time, 57 months), the 5-year overall survival rate was 99%. Of patients treated with R-CHOP, 99% received RT; R-HCVAD, 82%; and R-EPOCH, 36%. Of 68 patients with evaluable end-of-chemotherapy PET-CT scans, 62% had a positive scan (avidity above that of the mediastinal blood pool [Deauville 5PS = 3]), but only 9 patients experienced relapse (n=1) or progressive disease (n=8), all with a 5PS of 4 to 5. Of the 25 patients who received R-EPOCH, 4 experienced progression, all with 5PS of 4 to 5; salvage therapy (RT and autologous stem cell transplantation) was successful in all cases. Conclusion: Combined modality immunochemotherapy and RT is well tolerated and effective for treatment of PMBCL. A postchemotherapy 5PS of 4 to 5, rather than 3 to 5, can identify patients at high risk of progression who should be considered for therapy beyond chemotherapy alone after R-EPOCH.« less

Rapid and sensitive detection of Lily symptomless virus by reverse transcription loop-mediated isothermal amplification.

PubMed

He, Xiangfeng; Xue, Fei; Xu, Shufa; Wang, Wenhe

2016-12-01

Lily symptomless virus (LSV) is one of the most prevalent viruses that infect lily plants worldwide. A rapid and sensitive reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed for detection of LSV, using two primer pairs that specifically amplified the conserved sequence of LSV coat protein. The optimum reaction conditions were as follows: 4mM MgCl 2 and 0.8M betaine with incubation at 64°C for 30min. The limit of detection of LSV from infected lily leaves was 10-fold higher for RT-LAMP than for conventional RT-PCR. Moreover, RT-LAMP detected LSV in not only symptomatic, but also in symptomless tissues of infected plants. These findings indicate that our RT-LAMP method for LSV can serve as a low-cost, simple, and rapid alternative to conventional detection assays. Copyright © 2016 Elsevier B.V. All rights reserved.

Validated reverse transcription droplet digital PCR serves as a higher order method for absolute quantification of Potato virus Y strains.

PubMed

Mehle, Nataša; Dobnik, David; Ravnikar, Maja; Pompe Novak, Maruša

2018-05-03

RNA viruses have a great potential for high genetic variability and rapid evolution that is generated by mutation and recombination under selection pressure. This is also the case of Potato virus Y (PVY), which comprises a high diversity of different recombinant and non-recombinant strains. Consequently, it is hard to develop reverse transcription real-time quantitative PCR (RT-qPCR) with the same amplification efficiencies for all PVY strains which would enable their equilibrate quantification; this is specially needed in mixed infections and other studies of pathogenesis. To achieve this, we initially transferred the PVY universal RT-qPCR assay to a reverse transcription droplet digital PCR (RT-ddPCR) format. RT-ddPCR is an absolute quantification method, where a calibration curve is not needed, and it is less prone to inhibitors. The RT-ddPCR developed and validated in this study achieved a dynamic range of quantification over five orders of magnitude, and in terms of its sensitivity, it was comparable to, or even better than, RT-qPCR. RT-ddPCR showed lower measurement variability. We have shown that RT-ddPCR can be used as a reference tool for the evaluation of different RT-qPCR assays. In addition, it can be used for quantification of RNA based on in-house reference materials that can then be used as calibrators in diagnostic laboratories.

Rapid detection of duck hepatitis A virus genotype C using reverse transcription loop-mediated isothermal amplification.

PubMed

Li, Chuanfeng; Chen, Zongyan; Meng, Chunchun; Liu, Guangqing

2014-02-01

A one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was used and optimized to develop a rapid and sensitive detection system for duck hepatitis A virus genotype C (DHAV-C) RNA. A set of four specific primers was designed against highly conserved sequences located within the 3D gene from DHAV (strain GX1201). Under optimal reaction conditions, the sensitivity of DHAV-C-specific RT-LAMP was 100-fold higher than that of reverse transcriptase-polymerase chain reaction (RT-PCR), with a detection limit of 0.3pg (6.59×10(4) copies) per reaction. No cross-reactivity was observed from the samples of other duck viruses, which is in good accordance with RT-PCR. Furthermore, a positive reaction can be visually inspected by observing turbidity or color change after the addition of SYBR green I dye. The DHAV-C-specific RT-LAMP assay was applied to the samples and compared with RT-PCR. The positive-sample ratios were 26.7% (12 of 45) by RT-LAMP and 20% (9 of 45) by RT-PCR. Therefore, the newly developed RT-LAMP assay is a rapid, specific, sensitive, and cost-effective method of DHAV-C detection. This assay has potential applications in both clinical diagnosis and field surveillance of DHAV-C infection. Copyright © 2013. Published by Elsevier B.V.

Preparation, Mechanical and Thermal Properties of Cement Board with Expanded Perlite Based Composite Phase Change Material for Improving Buildings Thermal Behavior

PubMed Central

Ye, Rongda; Fang, Xiaoming; Zhang, Zhengguo; Gao, Xuenong

2015-01-01

Here we demonstrate the mechanical properties, thermal conductivity, and thermal energy storage performance of construction elements made of cement and form-stable PCM-Rubitherm® RT 28 HC (RT28)/expanded perlite (EP) composite phase change materials (PCMs). The composite PCMs were prepared by adsorbing RT28 into the pores of EP, in which the mass fraction of RT28 should be limited to be no more than 40 wt %. The adsorbed RT28 is observed to be uniformly confined into the pores of EP. The phase change temperatures of the RT28/EP composite PCMs are very close to that of the pure RT28. The apparent density and compression strength of the composite cubes increase linearly with the mass fraction of RT28. Compared with the thermal conductivity of the boards composed of cement and EP, the thermal conductivities of the composite boards containing RT28 increase by 15%–35% with the mass fraction increasing of RT28. The cubic test rooms that consist of six boards were built to evaluate the thermal energy storage performance, it is found that the maximum temperature different between the outside surface of the top board with the indoor temperature using the composite boards is 13.3 °C higher than that of the boards containing no RT28. The thermal mass increase of the built environment due to the application of composite boards can contribute to improving the indoor thermal comfort and reducing the energy consumption in the buildings. PMID:28793671

MZC Gel Inhibits SHIV-RT and HSV-2 in Macaque Vaginal Mucosa and SHIV-RT in Rectal Mucosa.

PubMed

Calenda, Giulia; Villegas, Guillermo; Barnable, Patrick; Litterst, Claudia; Levendosky, Keith; Gettie, Agegnehu; Cooney, Michael L; Blanchard, James; Fernández-Romero, José A; Zydowsky, Thomas M; Teleshova, Natalia

2017-03-01

The Population Council's microbicide gel MZC (also known as PC-1005) containing MIV-150 and zinc acetate dihydrate (ZA) in carrageenan (CG) has shown promise as a broad-spectrum microbicide against HIV, herpes simplex virus (HSV), and human papillomavirus. Previous data show antiviral activity against these viruses in cell-based assays, prevention of vaginal and rectal simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) infection, and reduction of vaginal HSV shedding in rhesus macaques and also excellent antiviral activity against HSV and human papillomavirus in murine models. Recently, we demonstrated that MZC is safe and effective against SHIV-RT in macaque vaginal explants. Here we established models of ex vivo SHIV-RT/HSV-2 coinfection of vaginal mucosa and SHIV-RT infection of rectal mucosa in macaques (challenge of rectal mucosa with HSV-2 did not result in reproducible tissue infection), evaluated antiviral activity of MZC, and compared quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay readouts for monitoring SHIV-RT infection. MZC (at nontoxic dilutions) significantly inhibited SHIV-RT in vaginal and rectal mucosas and HSV-2 in vaginal mucosa when present during viral challenge. Analysis of SHIV-RT infection and MZC activity by 1-step simian immunodeficiency virus gag quantitative RT-PCR and p27 enzyme-linked immunosorbent assay demonstrated similar virus growth dynamics and MZC activity by both methods and higher sensitivity of quantitative RT-PCR. Our data provide more evidence that MZC is a promising dual compartment multipurpose prevention technology candidate.

Patterns of care in palliative radiotherapy: a population-based study.

PubMed

Murphy, James D; Nelson, Lorene M; Chang, Daniel T; Mell, Loren K; Le, Quynh-Thu

2013-09-01

Approximately one half of the radiotherapy (RT) prescribed in the United States is delivered with palliative intent. The purpose of this study was to investigate the patterns of delivery of palliative RT across the United States. Using the Surveillance, Epidemiology, and End Results-Medicare linked database, 51,610 patients were identified with incident stage IV breast, prostate, lung, or colorectal cancer diagnosed between 2000 and 2007 and observed through 2009. Multivariate logistic regression determined predictors of palliative RT. Forty-one percent of the study population received palliative RT, including 53% of patients with lung cancer, followed by those with breast (42%), prostate (40%), and colorectal cancers (12%). Multivariate analysis revealed that older patients (P<.001) and those with higher Charlson comorbidity scores (P<.001) were less likely to receive palliative RT. Black patients with prostate cancer were 20% less likely (P<.001), and black patients with colorectal cancer were 28% less likely (P<.001), than white patients to receive palliative RT. Among those treated with RT, 23% of patients with lung cancer died within 2 weeks of completing treatment, followed by those with colorectal (12%), breast (11%), and prostate cancers (8%). In addition to tumor site, significant predictors (P<.05) of death within 2 weeks of receiving RT included increased age, increased comorbidity, and male sex. Inequality in the receipt of palliative RT exists among the elderly and patients with comorbid conditions and varies with race. In addition, a significant number of patients die shortly after receiving RT. Understanding these patterns of care, along with further research into the underlying causes, will improve access and quality of palliative RT.

Analytical validation of a reverse transcriptase droplet digital PCR (RT-ddPCR) for quantitative detection of infectious hematopoietic necrosis virus

USGS Publications Warehouse

Jia, Peng; Purcell, Maureen; Pan, Guang; Wang, Jinjin; Kan, Shifu; Liu, Yin; Zheng, Xiaocong; SHi, Xiujie; He, Junqiang; Yu, Li; Hua, Qunyi; Lu, Tikang; Lan, Wensheng; Winton, James; Jin, Ningyi; Liu, Hong

2017-01-01

Infectious hematopoietic necrosis virus (IHNV) is an important pathogen of salmonid fishes. A validated universal reverse transcriptase quantitative PCR (RT-qPCR) assay that can quantify levels of IHNV in fish tissues has been previously reported. In the present study, we adapted the published set of IHNV primers and probe for use in a reverse-transcriptase droplet digital PCR (RT-ddPCR) assay for quantification of the virus in fish tissue samples. The RT-ddPCR and RT-qPCR assays detected 13 phylogenetically diverse IHNV strains, but neither assay produced detectable amplification when RNA from other fish viruses was used. The RT-ddPCR assay had a limit of detection (LOD) equating to 2.2 plaque forming units (PFU)/μl while the LOD for the RT-qPCR was 0.2 PFU/μl. Good agreement (69.4–100%) between assays was observed when used to detect IHNV RNA in cell culture supernatant and tissues from IHNV infected rainbow trout (Oncorhynchus mykiss) and arctic char (Salvelinus alpinus). Estimates of RNA copy number produced by the two assays were significantly correlated but the RT-qPCR consistently produced higher estimates than the RT-ddPCR. The analytical properties of the N gene RT-ddPCR test indicated that this method may be useful to assess IHNV RNA copy number for research and diagnostic purposes. Future work is needed to establish the within and between laboratory diagnostic performance of the RT-ddPCR assay.

Preparation, Mechanical and Thermal Properties of Cement Board with Expanded Perlite Based Composite Phase Change Material for Improving Buildings Thermal Behavior.

PubMed

Ye, Rongda; Fang, Xiaoming; Zhang, Zhengguo; Gao, Xuenong

2015-11-13

Here we demonstrate the mechanical properties, thermal conductivity, and thermal energy storage performance of construction elements made of cement and form-stable PCM-Rubitherm® RT 28 HC (RT28)/expanded perlite (EP) composite phase change materials (PCMs). The composite PCMs were prepared by adsorbing RT28 into the pores of EP, in which the mass fraction of RT28 should be limited to be no more than 40 wt %. The adsorbed RT28 is observed to be uniformly confined into the pores of EP. The phase change temperatures of the RT28/EP composite PCMs are very close to that of the pure RT28. The apparent density and compression strength of the composite cubes increase linearly with the mass fraction of RT28. Compared with the thermal conductivity of the boards composed of cement and EP, the thermal conductivities of the composite boards containing RT28 increase by 15%-35% with the mass fraction increasing of RT28. The cubic test rooms that consist of six boards were built to evaluate the thermal energy storage performance, it is found that the maximum temperature different between the outside surface of the top board with the indoor temperature using the composite boards is 13.3 °C higher than that of the boards containing no RT28. The thermal mass increase of the built environment due to the application of composite boards can contribute to improving the indoor thermal comfort and reducing the energy consumption in the buildings.

Intensity Modulated Proton and Photon Therapy for Early Prostate Cancer With or Without Transperineal Injection of a Polyethylen Glycol Spacer: A Treatment Planning Comparison Study

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

Weber, Damien C., E-mail: damien.weber@unige.ch; Zilli, Thomas; Vallee, Jean Paul

2012-11-01

Purpose: Rectal toxicity is a serious adverse effect in early-stage prostate cancer patients treated with curative radiation therapy (RT). Injecting a spacer between Denonvilliers' fascia increases the distance between the prostate and the anterior rectal wall and may thus decrease the rectal radiation-induced toxicity. We assessed the dosimetric impact of this spacer with advanced delivery RT techniques, including intensity modulated RT (IMRT), volumetric modulated arc therapy (VMAT), and intensity modulated proton beam RT (IMPT). Methods and Materials: Eight prostate cancer patients were simulated for RT with or without spacer. Plans were computed for IMRT, VMAT, and IMPT using the Eclipsemore » treatment planning system using both computed tomography spacer+ and spacer- data sets. Prostate {+-} seminal vesicle planning target volume [PTV] and organs at risk (OARs) dose-volume histograms were calculated. The results were analyzed using dose and volume metrics for comparative planning. Results: Regardless of the radiation technique, spacer injection decreased significantly the rectal dose in the 60- to 70-Gy range. Mean V{sub 70Gy} and V{sub 60Gy} with IMRT, VMAT, and IMPT planning were 5.3 {+-} 3.3%/13.9 {+-} 10.0%, 3.9 {+-} 3.2%/9.7 {+-} 5.7%, and 5.0 {+-} 3.5%/9.5 {+-} 4.7% after spacer injection. Before spacer administration, the corresponding values were 9.8 {+-} 5.4% (P=.012)/24.8 {+-} 7.8% (P=.012), 10.1 {+-} 3.0% (P=.002)/17.9 {+-} 3.9% (P=.003), and 9.7 {+-} 2.6% (P=.003)/14.7% {+-} 2.7% (P=.003). Importantly, spacer injection usually improved the PTV coverage for IMRT. With this technique, mean V{sub 70.2Gy} (P=.07) and V{sub 74.1Gy} (P=0.03) were 100 {+-} 0% to 99.8 {+-} 0.2% and 99.1 {+-} 1.2% to 95.8 {+-} 4.6% with and without Spacer, respectively. As a result of spacer injection, bladder doses were usually higher but not significantly so. Only IMPT managed to decrease the rectal dose after spacer injection for all dose levels, generally with no observed increase to the bladder dose. Conclusions: Regardless of the radiation technique, a substantial decrease of rectal dose was observed after spacer injection for curative RT to the prostate.« less

De Novo Upper Extremity Lymphedema After Elective Hand Surgery in Breast Cancer Survivors.

PubMed

Baltzer, Heather L; Harvey, Jamison; Fox, Paige M; Moran, Steven L

2017-07-01

The safety of elective hand surgery in breast cancer (BC) survivors is controversial because of concerns of developing upper extremity lymphedema. This study aimed to evaluate the risk of developing lymphedema after elective hand surgery among patients that underwent ipsilateral axillary lymph node dissection (ALND), sentinel lymph node biopsy (SLNB), and/or radiation therapy (RT). A retrospective cohort of BC patients treated with ALND, SLNB, and/or RT was identified (1997-2012). Patients with subsequent ipsilateral elective hand surgery were included if greater than 1 year of follow-up and no preexisting lymphedema. The primary outcome was lymphedema after hand surgery. Comparisons between patients with and without lymphedema were made to identify potential lymphedema risk factors. Dichotomous and continuous variables were compared with Fisher exact and Student t tests, respectively. The analysis included 103 patients, of which 4 (3.8%) had documented lymphedema after hand surgery. Lymphedema developed early and was self-limited. Lymphedema was not related to age and type of hand surgery. Tourniquet time was longer in the nonlymphedema group. The lymphedema group all received adjuvant chemotherapy and RT with either ALND or SLNB. Patients with lymphedema had a shorter interval between hand surgery and completion of BC surgery (2.1 vs 6.2 years) and RT (2.0 vs 3.3 years). Lymphedema is uncommon after elective hand surgery among survivors and was not associated with tourniquet use. The combination of adjuvant therapies and axillary procedures and a short temporal relationship of these to hand surgery may increase lymphedema risk.

Abilities of the mCP Agar Method and CRENAME Alpha Toxin-Specific Real-Time PCR Assay To Detect Clostridium perfringens Spores in Drinking Water

PubMed Central

Maheux, Andrée F.; Bérubé, Ève; Boudreau, Dominique K.; Villéger, Romain; Cantin, Philippe; Boissinot, Maurice; Bissonnette, Luc

2013-01-01

We first determined the analytical specificity and ubiquity (i.e., the ability to detect all or most strains) of a Clostridium perfringens-specific real-time PCR (rtPCR) assay based on the cpa gene (cpa rtPCR) by using a bacterial strain panel composed of C. perfringens and non-C. perfringens Clostridium strains. All non-C. perfringens Clostridium strains tested negative, whereas all C. perfringens strains tested positive with the cpa rtPCR, for an analytical specificity and ubiquity of 100%. The cpa rtPCR assay was then used to confirm the identity of 116 putative C. perfringens isolates recovered after filtration of water samples and culture on mCP agar. Colonies presenting discordant results between the phenotype on mCP agar and cpa rtPCR were identified by sequencing the 16S rRNA and cpa genes. Four mCP−/rtPCR+ colonies were identified as C. perfringens, whereas 3 mCP+/rtPCR− colonies were identified as non-C. perfringens. The cpa rtPCR was negative with all 51 non-C. perfringens strains and positive with 64 of 65 C. perfringens strains. Finally, we compared mCP agar and a CRENAME (concentration and recovery of microbial particles, extraction of nucleic acids, and molecular enrichment) procedure plus cpa rtPCR (CRENAME + cpa rtPCR) for their abilities to detect C. perfringens spores in drinking water. CRENAME + cpa rtPCR detected as few as one C. perfringens CFU per 100 ml of drinking water sample in less than 5 h, whereas mCP agar took at least 25 h to deliver results. CRENAME + cpa rtPCR also allows the simultaneous and sensitive detection of Escherichia coli and C. perfringens from the same potable water sample. In itself, it could be used to assess the public health risk posed by drinking water potentially contaminated with pathogens more resistant to disinfection. PMID:24077714

Prediction of Liver Function by Using Magnetic Resonance-based Portal Venous Perfusion Imaging

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

Cao Yue, E-mail: yuecao@umich.edu; Department of Radiology, University of Michigan, Ann Arbor, Michigan; Wang Hesheng

2013-01-01

Purpose: To evaluate whether liver function can be assessed globally and spatially by using volumetric dynamic contrast-enhanced magnetic resonance imaging MRI (DCE-MRI) to potentially aid in adaptive treatment planning. Methods and Materials: Seventeen patients with intrahepatic cancer undergoing focal radiation therapy (RT) were enrolled in institution review board-approved prospective studies to obtain DCE-MRI (to measure regional perfusion) and indocyanine green (ICG) clearance rates (to measure overall liver function) prior to, during, and at 1 and 2 months after treatment. The volumetric distribution of portal venous perfusion in the whole liver was estimated for each scan. We assessed the correlation betweenmore » mean portal venous perfusion in the nontumor volume of the liver and overall liver function measured by ICG before, during, and after RT. The dose response for regional portal venous perfusion to RT was determined using a linear mixed effects model. Results: There was a significant correlation between the ICG clearance rate and mean portal venous perfusion in the functioning liver parenchyma, suggesting that portal venous perfusion could be used as a surrogate for function. Reduction in regional venous perfusion 1 month after RT was predicted by the locally accumulated biologically corrected dose at the end of RT (P<.0007). Regional portal venous perfusion measured during RT was a significant predictor for regional venous perfusion assessed 1 month after RT (P<.00001). Global hypovenous perfusion pre-RT was observed in 4 patients (3 patients with hepatocellular carcinoma and cirrhosis), 3 of whom had recovered from hypoperfusion, except in the highest dose regions, post-RT. In addition, 3 patients who had normal perfusion pre-RT had marked hypervenous perfusion or reperfusion in low-dose regions post-RT. Conclusions: This study suggests that MR-based volumetric hepatic perfusion imaging may be a biomarker for spatial distribution of liver function, which could aid in individualizing therapy, particularly for patients at risk for liver injury after RT.« less

Impact of Adjuvant External-Beam Radiation Therapy in Early-Stage Uterine Papillary Serous and Clear Cell Carcinoma

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

Kim, Anne, E-mail: akim2@health-quest.org; Schreiber, David; Rineer, Justin

2011-11-15

Purpose: Adjuvant radiation therapy (RT) in early-stage high- to intermediate-risk endometrioid adenocarcinoma is well established and has been shown to improve locoregional control. Its role in the management of early-stage clear cell carcinoma and uterine papillary serous carcinoma (UPSC) remains controversial. Methods and Materials: Using the Surveillance Epidemiology and End Results database, we identified women with American Joint Committee on Cancer Stage Sixth Edition. Stage IA-IIB clear cell carcinoma or UPSC who underwent hysterectomy with or without adjuvant RT between 1988 and 2003. We used Kaplan-Meier and Cox regression analysis to compare overall survival (OS) for all patients. Results: Wemore » identified 1,333 women of whom 451 had clear cell carcinoma and 882 had UPSC. Of those patients, 775 underwent surgery alone and 558 received adjuvant RT as well. For Stages I-IIB disease, the median OS with surgery alone was 106 months, vs. 151 months with adjuvant RT (p = 0.006). On subgroup analysis, we saw the benefit from adjuvant RT only in Stage IB-C patients. For Stage IB disease, patients undergoing surgery alone had a median OS of 117 months, vs. median survival not reached with the addition of RT (p = 0.006). For Stage IC disease, surgery alone had a median OS of 35 months vs. 120 months with RT (p = 0.001). Although the apparent benefit of RT diminished when measured via multivariate analysis, the impact of RT on survival did show a trend toward significance (hazard ration 0.808, confidence interval 95% 0.651-1.002, p = 0.052) Conclusion: In FIGO Stage IB-C papillary serous and clear cell uterine carcinoma, adjuvant RT seems to play an important role in improving survival.« less

The impact of lesion side on acute stroke treatment.

PubMed

Di Legge, Silvia; Fang, Jiming; Saposnik, Gustavo; Hachinski, Vladimir

2005-07-12

Only a small percentage of patients with acute stroke are treated with recombinant tissue plasminogen activator (rt-PA). To investigate why patients with right-hemisphere strokes seem at high risk of not receiving rt-PA. This study includes two phases. Phase 1: the authors compared demographic, clinical, and outcome measures between patients with right- and left-hemisphere strokes in the rt-PA Registry of Southwestern Ontario (RSWO); Phase 2: the authors tested the hypotheses generated in Phase 1 using the Registry of the Canadian Stroke Network (RCSN). A multiple logistic analysis was applied to detect independent predictors of rt-PA administration. Phase 1: of 179 rt-PA-treated patients, 39% had right-hemisphere syndrome. Patients with right-hemisphere strokes had a longer hospital stay (15 vs 9 days; p = 0.03). Phase 2: of 990 stroke patients in the RCSN, 505 (51%) had a right- and 485 (49%) a left-hemisphere syndrome. Of 110 rt-PA-treated patients, 37 (34%) had a right-hemisphere syndrome (p = 0.0001). Negative independent predictors of rt-PA administration were right-hemisphere stroke (OR, 0.55; CI: 0.31 to 0.96; p = 0.037), onset-to-emergency department time (OR, 0.99; CI 0.98 to 0.99; p = 0.04), and CNS score (OR, 0.78; CI 0.71 to 0.86; p < 0.0001). Neglect predicted rt-PA administration (OR, 2.32; CI 1.29 to 4.16; p = 0.004). Patients with right-hemisphere strokes are 45% less likely to be treated with recombinant tissue plasminogen activator (rt-PA) compared to patients with left-hemisphere strokes. The presence of neglect confers a twofold increased likelihood of rt-PA administration. Prehospital delay and lack of standardized scores for the neglect syndrome may limit accessibility of patients with right-hemisphere stroke to thrombolysis.

Barriers to the Implementation of Surveillance for Stage I Testicular Seminoma

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

Arvold, Nils D.; Catalano, Paul J.; Sweeney, Christopher J.

2012-10-01

Purpose: Postorchiectomy adjuvant radiotherapy (RT) for Stage I seminoma can be associated with long-term toxicity, and management strategies with a lower treatment burden achieve the same excellent cure rate. Because studies suggest that radiation oncologists in the United States continue to recommend RT for these patients, we sought to identify factors associated with management recommendations. Methods and Materials: We conducted a one-time internet-based survey among 491 randomly selected American radiation oncologists self-described as specializing in genitourinary oncology. Results: Response rate was 53% (n = 261). Forty-nine percent of respondents worked in university-affiliated practices. Sixty-two percent of respondents always/usually recommended adjuvantmore » RT for patients with Stage I seminoma, whereas 21% always/usually recommended surveillance and 3% always/usually recommended chemotherapy. One third (33%) expressed concerns that patients who experienced relapse during surveillance could not be salvaged. Although 88% of physicians were aware of an increased risk of second malignant neoplasms (SMN) after adjuvant RT, 85% underestimated its magnitude. Compared with physicians not typically recommending RT, physicians who always/usually recommended RT were more likely to believe that patients might not be salvaged at relapse during surveillance (p = 0.008) and were less aware of the association between RT and SMN (p = 0.04). Conclusions: Respondents who always/usually recommend postorchiectomy RT for patients with Stage I seminoma are more likely to underestimate late RT morbidity and to believe that surveillance is associated with increased mortality. Given the equivalent efficacy and reduced morbidity of surveillance compared with RT, our findings underscore the need for ongoing physician education to increase appropriate clinical implementation of surveillance strategies.« less

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

Jebsen, Nina L.; Department of Oncology, Haukeland University Hospital, Bergen; Trovik, Clement S.

Purpose: Adjuvant radiotherapy has during the past decades become increasingly used in the treatment of localized soft tissue sarcoma. We evaluated the effect of radiotherapy (RT) on local recurrence rates (LRRs) in Scandinavia between 1986 and 2005. Methods and Materials: A total of 1,093 adult patients with extremity or trunk wall soft tissue sarcoma treated at four Scandinavian sarcoma centers were stratified according to the treatment period (1986-1991, 1992-1997, and 1998-2005). The use of adjuvant RT, quality of the surgical margin, interval between surgery and RT, and LRR were analyzed. The median follow-up was 5 years. Results: The use ofmore » RT (77% treated postoperatively) increased from 28% to 53%, and the 5-year LRR decreased from 27% to 15%. The rate of wide surgical margins did not increase. The risk factors for local recurrence were histologic high-grade malignancy (hazard ratio [HR], 5), an intralesional (HR, 6) or marginal (HR, 3) surgical margin, and no RT (HR, 3). The effect of RT on the LRR was also significant after a wide margin resection and in low-grade malignant tumors. The LRR was the same after preoperative and postoperative RT. The median interval from surgery to the start of RT was 7 weeks, and 98% started RT within 4 months. The LRR was the same in patients who started treatment before and after 7 weeks. Conclusion: The results of our study have shown that adjuvant RT effectively prevents local recurrence in soft tissue sarcoma, irrespective of the tumor depth, malignancy grade, and surgical margin status. The effect was most pronounced in deep-seated, high-grade tumors, even when removed with a wide surgical margin.« less

[Dengue fever cases in Czech workers returning from the Maldives].

PubMed

Trojánek, Milan; Tomíčková, Dora; Roháčová, Hana; Kosina, Pavel; Gebouský, Jan; Dvořák, Jan; Chmelik, Vaclav; Batistová, Květoslava; Husa, Petr; Maixner, Jan; Sojková, Naděžda; Zelená, Hana; Marešová, Vilma; Stejskal, František

2013-09-01

The objective of this study is to present epidemiological characteristics and clinical symptoms of dengue fever cases in Czech workers who acquired the infection while working on the island of Fushivelavaru, Maldives. Furthermore, the study compares the sensitivity of novel direct detection assays, i.e. Real-Time Polymerase Chain Reaction (RT-PCR) and detection of Dengue NS1 antigen. The retrospective study evaluated the clinical course of dengue fever cases in Czech workers returning from a job in the Maldives who were diagnosed with dengue virus infection from September 1 to October 31, 2012. The laboratory diagnosis of dengue fever was based on the serological detection of IgM and IgG antibodies, detection of dengue NS1 antigen by enzyme-linked immunosobent assay (ELISA), and detection of dengue virus DNA by RT-PCR. The infection with dengue virus was confirmed in 18 males with a median age of 40 years (IQR 36-47) who returned from a job in the Maldives. Only one patient required admission to the hospital while the others were treated on an outpatient basis. The most frequently observed symptoms were fever (18), headache (9), muscle and joint pain (8 and 7, respectively), and rash (9). Typical laboratory findings were leukocytopenia and thrombocytopenia, a low CRP level, and elevated aminotransferase activity. The clinical course was uncomplicated in all patients. The dengue NS1 antigen detection (positive in all 10 patients with acute dengue fever) showed significantly higher sensitivity than the detection of viral RNA using RT-PCR (positive in 4 patients), p = 0.011. Although the vast majority of dengue fever cases are diagnosed among travellers returning from the tropics, the presented study points out the risks posed by dengue fever to long-term workers in endemic areas. The infection in the serologically naïve hosts is usually uncomplicated; however, infected persons are at significant risk of developing a severe complicated clinical course if challenged by another serotype. Furthermore, sick leaves or premature departures cause a considerable economic burden to employers. In the diagnosis of acute dengue fever, preference should be given to highly sensitive and specific tests for the direct detection of dengue virus (NS1 antigen and RT-PCR assays).

Radiotherapy is essential after complete response to asparaginase-containing chemotherapy in early-stage extranodal nasal-type NK/T-cell lymphoma: A multicenter study from the China Lymphoma Collaborative Group (CLCG).

PubMed

Deng, Xiu-Wen; Wu, Jun-Xin; Wu, Tao; Zhu, Su-Yu; Shi, Mei; Su, Hang; Wang, Ying; He, Xia; Xu, Li-Ming; Yuan, Zhi-Yong; Zhang, Li-Ling; Wu, Gang; Qu, Bao-Lin; Qian, Li-Ting; Hou, Xiao-Rong; Zhang, Fu-Quan; Zhang, Yu-Jing; Zhu, Yuan; Cao, Jian-Zhong; Lan, Sheng-Min; Dong, Mei; Qi, Shu-Nan; Yang, Yong; Li, Ye-Xiong

2018-05-05

This study aimed to clarify the benefit of radiotherapy (RT) in patients with early-stage extranodal NK/T-cell lymphoma (NKTCL) who achieve a complete response (CR) after asparaginase-containing chemotherapy (CT). Of 240 patients achieved a CR after asparaginase-containing CT, 202 patients received additional RT (CT + RT), and 38 patients did not (CT alone). Compared to CT alone, CT + RT significantly improved overall survival (OS), disease-free survival (DFS) and locoregional control (LRC). The 5-year OS, DFS and LRC rates were 84.9%, 76.2% and 84.9% for CT + RT, compared to 58.9% (P = 0.006), 43.6% (P = 0.001) and 62.1% (P = 0.026) for CT alone. The 5-year cumulative disease recurrence rate was 18.8% for CT + RT compared to 46.9% (P = 0.003) for CT alone. High-dose RT (≥50 Gy) significantly decreased the risk of locoregional recurrence. The 5-year cumulative locoregional failure rate was 35.5% for patients receiving <50 Gy compared to 8.8% for patients receiving ≥50 Gy (P = 0.028). For patients with early-stage NKTCL who achieve a CR after asparaginase-containing CT, omission of RT results in frequent locoregional recurrence and a poor prognosis; RT is essential to improve locoregional control and survival. Copyright © 2018 Elsevier B.V. All rights reserved.

Analysis of formability of Ca-added magnesium alloy sheets at low temperatures

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

Kim, Se-Jong; Lee, Young-Seon; Kim, Daeyong, E-mail: daeyong@kims.re.kr

The formability of sheets of the Ca-added magnesium alloy AZX311 was analyzed. The parameters affecting the sheet formability, such as the strain-hardening rate and the strain-rate sensitivity, did not seem to be higher in the alloy AZX311 at temperatures of room temperature (RT) and 200 °C. In addition, the critical stress for fracture at RT was lower in AZX311 than in AZ31. However, AZX311 exhibited higher stretchability and formability at low temperatures than AZ31. Electron back-scattered diffraction microscopy revealed that AZX311 had a weaker basal texture as well as broadened basal poles along the transverse direction. Polycrystal plasticity simulations confirmedmore » that this weaker basal texture increases the activity of basal slip over thickness strain, resulting in the higher formability of AZX311. - Highlights: • A weak basal texture with broadening basal poles along the TD in AZX311 • Lower critical stress for fracture at RT in AZX311 than in AZ31 • Lower strain-hardening rates at low temperatures in the AZX311 than in the AZ31 • Higher formability at low temperatures in AZX311 because of the weak basal texture.« less

Adverse Outcomes After Palliative Radiation Therapy for Uncomplicated Spine Metastases: Role of Spinal Instability and Single-Fraction Radiation Therapy

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

Lam, Tai-Chung, E-mail: lamtaichung@gmail.com; Uno, Hajime; Krishnan, Monica

2015-10-01

Purpose: Level I evidence demonstrates equivalent pain response after single-fraction (SF) or multifraction (MF) radiation therapy (RT) for bone metastases. The purpose of this study is to provide additional data to inform the incidence and predictors of adverse outcomes after RT for spine metastases. Methods and Materials: At a single institution, 299 uncomplicated spine metastases (without cord compression, prior RT, or surgery) treated with RT from 2008 to 2013 were retrospectively reviewed. The spinal instability neoplastic score (SINS) was used to assess spinal instability. The primary outcome was time to first spinal adverse event (SAE) at the site, including symptomaticmore » vertebral fracture, hospitalization for site-related pain, salvage surgery, interventional procedure, new neurologic symptoms, or cord compression. Fine and Gray's multivariable model assessed associations of the primary outcome with SINS, SF RT, and other significant baseline factors. Propensity score matched analysis further assessed the relationship of SF RT to first SAEs. Results: The cumulative incidence of first SAE after SF RT (n=66) was 6.8% at 30 days, 16.9% at 90 days, and 23.6% at 180 days. For MF RT (n=233), the incidence was 3.5%, 6.4%, and 9.2%, respectively. In multivariable analysis, SF RT (hazard ratio [HR] = 2.8, 95% confidence interval [CI] 1.5-5.2, P=.001) and SINS ≥11 (HR=2.5 , 95% CI 1.3-4.9, P=.007) were predictors of the incidence of first SAE. In propensity score matched analysis, first SAEs had developed in 22% of patients with SF RT versus 6% of those with MF RT cases (HR=3.9, 95% CI 1.6-9.6, P=.003) at 90 days after RT. Conclusion: In uncomplicated spinal metastases treated with RT alone, spinal instability with SINS ≥11 and SF RT were associated with a higher rate of SAEs.« less

Combination therapy of intravenously injected microglia and radiotherapy prolongs survival in a rat model of spontaneous malignant glioma.

PubMed

Okonogi, Noriyuki; Suzuki, Yoshiyuki; Sato, Hiro; Oike, Takahiro; Yoshimoto, Yuya; Mimura, Kousaku; Noda, Shin-Ei; Okamoto, Masahiko; Tamaki, Tomoaki; Morokoshi, Yukie; Hasegawa, Sumitaka; Ohgaki, Hiroko; Yokoo, Hideaki; Nakano, Takashi

2018-06-18

The aim of this study was to investigate the efficacy of combination therapy with intravenously injected microglia (MI) and radiotherapy (RT) for rat malignant glioma. Transgenic rats expressing v-erbB and spontaneously developing malignant glioma were used. The rats were divided into four groups: control (n = 19), RT alone (n = 10), MI alone (n = 9), and combination of MI and RT (MI+RT) (n = 10). Cranial X-ray irradiation (8 Gy per fraction; once per week) was performed at 50 and 51 weeks of age. Cultured rat microglial cells (5 × 10 6 cells/rat) were intravenously injected via the tail vein within 30 minutes after RT. No evidence of side effects including thrombosis or graft-versus-host disease was noted. Rats treated with RT alone, MI alone, MI+RT, and control survived 60.9, 56.3, 66.0, and 56.1 weeks, respectively. The survival period of MI+RT was significantly longer than that of control (p = 0.014), MI alone (p = 0.027), and RT alone (p = 0.049). Immunohistochemical analysis showed significantly higher number of tumor-infiltrated microglia in the RT alone (p = 0.041) and MI+RT groups (p = 0.014) compared with the control. Significantly more CD8-positive lymphocytes were observed in the MI+RT group (p = 0.049) compared with the control. A positive correlation was found between the number of microglia and CD8-positive lymphocytes (R 2 = 0.556). A positive correlation was also found between CD8-positive lymphocytes and survival periods (R 2 = 0.460). MI+RT increased infiltrated microglia and CD8-positive T cells and prolonged the survival in transgenic rats spontaneously developing malignant glioma. Combined immunocellular therapy and RT may provide a novel treatment strategy for malignant glioma. Copyright © 2018. Published by Elsevier Inc.

A comparative study of digital RT-PCR and RT-qPCR for quantification of Hepatitis A virus and Norovirus in lettuce and water samples.

PubMed

Coudray-Meunier, Coralie; Fraisse, Audrey; Martin-Latil, Sandra; Guillier, Laurent; Delannoy, Sabine; Fach, Patrick; Perelle, Sylvie

2015-05-18

Sensitive and quantitative detection of foodborne enteric viruses is classically achieved by quantitative RT-PCR (RT-qPCR). Recently, digital PCR (dPCR) was described as a novel approach to genome quantification without need for a standard curve. The performance of microfluidic digital RT-PCR (RT-dPCR) was compared to RT-qPCR for detecting the main viruses responsible for foodborne outbreaks (human Noroviruses (NoV) and Hepatitis A virus (HAV)) in spiked lettuce and bottled water. Two process controls (Mengovirus and Murine Norovirus) were used and external amplification controls (EAC) were added to examine inhibition of RT-qPCR and RT-dPCR. For detecting viral RNA and cDNA, the sensitivity of the RT-dPCR assays was either comparable to that of RT-qPCR (RNA of HAV, NoV GI, Mengovirus) or slightly (around 1 log10) decreased (NoV GII and MNV-1 RNA and of HAV, NoV GI, NoV GII cDNA). The number of genomic copies determined by dPCR was always from 0.4 to 1.7 log10 lower than the expected numbers of copies calculated by using the standard qPCR curve. Viral recoveries calculated by RT-dPCR were found to be significantly higher than by RT-qPCR for NoV GI, HAV and Mengovirus in water, and for NoV GII and HAV in lettuce samples. The RT-dPCR assay proved to be more tolerant to inhibitory substances present in lettuce samples. This absolute quantitation approach may be useful to standardize quantification of enteric viruses in bottled water and lettuce samples and may be extended to quantifying other human pathogens in food samples. Copyright © 2015 Elsevier B.V. All rights reserved.

Rapid detection of newly isolated Tembusu-related Flavivirus by reverse-transcription loop-mediated isothermal amplification assay

PubMed Central

2011-01-01

Background From April 2010 to January 2011, a severe new viral disease had devastated most duck-farming regions in China. This disease affected not only laying ducks but also meat ducks, causing huge economic losses for the poultry industry. The objective of this study is to develop a one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for the detection of the new virus related to Tembusu-related Flavivirus. Results The RT-LAMP assay is very simple and rapid, and the amplification can be completed within 50 min under isothermal conditions at 63°C by a set of 6 primers targeting the E gene based on the sequences analysis of the newly isolated viruses and other closely related Flavivirus.The monitoring of gene amplification can also be visualized by using SYBR green I fluorescent dye. In addition, the RT-LAMP assay for newly isolated Tembusu-related Flavivirus showed higher sensitivity with an RNA detection-limit of 2 copies/μL compared with 190 copies/μL of the conventional RT-PCR method. The specificity was identified without cross reaction to other common avian pathogens. By screening a panel of clinical samples this method was more feasible in clinical settings and there was higher positive coincidence rate than conventional RT-PCR and virus isolation. Conclusion The RT-LAMP assay for newly isolated Tembusu-related Flavivirus is a valuable tool for the rapid and real-time detection not only in well-equipped laboratories but also in general conditions. PMID:22185513

Antithymocyte antibody-induced coagulopathy in renal transplant recipients.

PubMed

Siparsky, N F; Klein, R; Kushnir, L F; Gallichio, M H; Conti, D J

2013-05-01

Antithymocyte antibody (ATA) remains the most commonly used induction immunosuppressive agent in renal transplantation (RT). To date, few case reports of ATA-induced coagulopathy exist. We performed a single-center, retrospective analysis of renal transplant recipients (RTRs) who underwent RT followed by ATA therapy between 2007 and 2011. The protocol used for deceased donor and unrelated living donor recipient immunosuppression was Thymoglobulin (TMG), methylprednisolone, Cellcept, Prograf, and Rapamune. In related living donor recipients, Simulect (SIM) was substituted for TMG. The international normalized ratio (INR) was routinely checked on days 0 and 2, and thereafter at the discretion of the surgeon. RTRs were transfused packed red blood cells (PRBCs) or fresh frozen plasma (FFP) at the discretion of the surgeon. During the study period, 257 RTs were performed at our institution. The following 18 RTR were excluded: simultaneous kidney and pancreas transplant recipients (4), RTRs on warfarin at the time of admission (2), RTRs who received OKT3 (2), and RTRs with INR ≥ 1.2 at the time of admission (10). Of the remaining 239 RTR, 208 (87%) underwent TMG induction therapy; 31 RTR (13%) underwent SIM induction therapy. The mean INR peaked in both groups on day 4 but was higher in TMG recipients (TMG 1.35, SIM 1.20). FFP was transfused in 65 TMG (31%) and 3 SIM (10%) recipients (P = .01); PRBCs were transfused in 88 TMG (44%) and 6 SIM (19%) recipients (P = .02). No patients returned to the operating room for bleeding complications within 7 days of RT. Patient age, gender, ethnicity, and diabetes status were not statistically significant factors in the development of coagulopathy. TMG administration is associated with coagulopathy. Using an INR screening protocol and an aggressive transfusion protocol, bleeding complications associated with coagulopathy can be avoided in this higher-risk group. Copyright © 2013 Elsevier Inc. All rights reserved.

Strongyloides stercoralis infection increases the likelihood to detect Trypanosoma cruzi DNA in peripheral blood in Chagas disease patients.

PubMed

Salvador, Fernando; Sulleiro, Elena; Piron, Maria; Sánchez-Montalvá, Adrián; Sauleda, Silvia; Molina-Morant, Daniel; Moure, Zaira; Molina, Israel

2017-11-01

In a previous study performed by our group, Strongyloides stercoralis infection in patients with Chagas disease was associated with higher proportion of Trypanosoma cruzi DNA detection in peripheral blood. The aim of the study was to confirm this association in a larger cohort of patients. Cross-sectional study of all patients with Chagas disease diagnosed from 2005 to 2015 during blood donation at the Catalan Blood Bank. Demographic data and T. cruzi RT-PCR were collected. S. stercoralis infection diagnosis was based on a serological test. Two hundred and two blood donors were included. T. cruzi RT-PCR was positive in 72 (35.6%) patients, and S. stercoralis serology was positive in 22 (10.9%) patients. Patients with positive S. stercoralis serology had higher proportion of positive T. cruzi RT-PCR than those with negative serology (54.5% vs. 33.3%, P = 0.050), and the difference increased when taking a serological index cut-off of 2.5, which increases the specificity of the test to detect a confirmed strongyloidiasis (60% vs. 33%, P = 0.017). Patients with Chagas disease with positive S. stercoralis serology had higher proportion of positive T. cruzi RT-PCR in peripheral blood than those with negative serology, which reflects the potential immunomodulatory effects of S. stercoralis in T. cruzi co-infected patients. © 2017 John Wiley & Sons Ltd.

Human T-lymphotropic Virus-1/2 detected in drug abused men who have sex with men infected with HIV in Surakarta, Indonesia

NASA Astrophysics Data System (ADS)

Agung Prasetyo, Afiono; Sari, Yulia

2018-05-01

Human T-lymphotropic virus types 1 and 2 (HTLV-1/2) share similar routes of transmission with human immunodeficiency virus (HIV), and the HTLV-1/2 co-infection may affect the clinical course of HIV infection. The HIV/HTLV-1/2 co-infection risk higher if the patient performing the high-risk activities. This study evaluated the presentation of HTLV-1 and 2 in HIV-infected men who have sex with men with drug abused history in Surakarta Indonesia. Blood samples collected from HIV-infected men who have sex with men with drug abused history in Surakarta were tested using HTLV-1/2 enzyme-linked immunosorbent assays and confirmed by RT-PCR nested addressed the part of HTLV-1 LTR and HTLV-2 LTR region, respectively. The specificity of the molecular assays was confirmed by sequencing the amplicons. The anti HTLV-1/2 positive rate was 17.4% (8/46). All positive serological samples were confirmed by nested RT-PCR. Of these, three was HTLV-1 positive and five was HTLV-2 positive. Molecular analysis of positive PCR products revealed that all HTLV-1 isolates had a close relationship with HTLV-1 isolated in Japan while all HTLV-2 isolates with that of isolated in the USA. HTLV-1 and HTLV-2 were detected in drug abused men who have sex with men infected with HIV in Surakarta.

Effects of a common variant in the CD38 gene on social processing in an oxytocin challenge study: possible links to autism.

PubMed

Sauer, Carina; Montag, Christian; Wörner, Christiane; Kirsch, Peter; Reuter, Martin

2012-05-01

The intranasal application of oxytocin (OT) has been shown to influence behavioral and neural correlates of social processing. These effects are probably mediated by genetic variations within the OT system. One potential candidate could be the CD38 gene, which codes for a transmembrane protein engaged in OT secretion processes. A common variation in this gene (rs3796863) was recently found to be associated with autism spectrum disorders (ASD). Using an imaging genetics approach, we studied differential effects of an intranasal OT application on neural processing of social stimuli in 55 healthy young men depending on their CD38 gene variant in a double-blind placebo-controlled crossover design. Genotype had a significant influence on both behavioral and neuronal measures of social processing. Homozygotic risk allele carriers showed slower reaction times (RT) and higher activation of left fusiform gyrus during visual processing of social stimuli. Under OT activation differences between genotypes were more evident (though not statistically significantly increased) and RT were accelerated in homozygotic risk allele carriers. According to our data, rs3796863 mainly influences fusiform gyrus activation, an area which has been widely discussed in ASD research. OT seems to modulate this effect by enhancing activation differences between allele groups, which suggests an interaction between genetic makeup and OT availability on fusiform gyrus activation. These results support recent approaches to apply OT as a pharmacological treatment of ASD symptoms.

Assessment of microbial risk factors and impact of meteorological conditions during production of baby spinach in the Southeast of Spain.

PubMed

Castro-Ibáñez, I; Gil, M I; Tudela, J A; Ivanek, R; Allende, A

2015-08-01

There is a timely need to evaluate the effect agricultural factors and meteorological conditions on fresh produce contamination. This study evaluated those risk factors and described, for the first time, the distribution of indicator microorganisms (Escherichia coli, Enterococcus, coliforms, and Enterobacteriaceae) and the prevalence of foodborne pathogens (Enterohaemorrhagic E. coli, Listeria monocytogenes and Salmonella spp.) in baby spinach grown in the Southeast of Spain. A longitudinal study was conducted on three farms (2011-2013). Results obtained for E. coli highlighted soil and irrigation water as important factors affecting the microbial safety of baby spinach. Significant differences in the proportion of E. coli positive samples were found between treated (46.1%) and untreated (100%) irrigation water. However, the microbial quality of irrigation water didn't affect E. coli prevalence in produce. All E. coli positive spinach samples were detected at the highest observed temperature range suggesting that ambient temperature affects the probability and extent of spinach contamination. Salmonella spp. was detected by RT-PCR in manure, soil, irrigation water and baby spinach but only two of them (manure and irrigation water) were confirmed by isolation in culture media. Salmonella RT-PCR positive samples showed higher levels of E. coli than Salmonella negative samples. This preliminary finding supports recent identification of E. coli as a suitable parameter for the hygiene criterion at the primary production of leafy greens. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of sensitivity of TaqMan RT-PCR for rubella virus detection in clinical specimens.

PubMed

Okamoto, Kiyoko; Mori, Yoshio; Komagome, Rika; Nagano, Hideki; Miyoshi, Masahiro; Okano, Motohiko; Aoki, Yoko; Ogura, Atsushi; Hotta, Chiemi; Ogawa, Tomoko; Saikusa, Miwako; Kodama, Hiroe; Yasui, Yoshihiro; Minagawa, Hiroko; Kurata, Takako; Kanbayashi, Daiki; Kase, Tetsuo; Murata, Sachiko; Shirabe, Komei; Hamasaki, Mitsuhiro; Kato, Takashi; Otsuki, Noriyuki; Sakata, Masafumi; Komase, Katsuhiro; Takeda, Makoto

2016-07-01

An easy and reliable assay for detection of the rubella virus is required to strengthen rubella surveillance. Although a TaqMan RT-PCR assay for detection of the rubella virus has been established in Japan, its utility for diagnostic purposes has not been tested. To allow introduction of the TaqMan RT-PCR into the rubella surveillance system in Japan, the sensitivity of the assay was determined using representative strains for all genotypes and clinical specimens. The detection limits of the method for individual genotypes were examined using viral RNA extracted from 13 representative strains. The assay was also tested at 10 prefectural laboratories in Japan, designated as local reference laboratories for measles and rubella, to allow nationwide application of the assay. The detection limits and amplification efficiencies of the assay were similar among all the representative strains of the 13 genotypes. The TaqMan RT-PCR could detect approximately 90% of throat swab and urine samples taken up to 5days of illness. These samples were determined positive by a highly sensitive nested RT-PCR. The TaqMan RT-PCR could detect at least 10 pfu of rubella virus. Although the sensitivity was somewhat lower than that of the conventional nested RT-PCR, the TaqMan RT-PCR could be more practical to routine tests for rubella laboratory diagnosis and detection in view of the rapid response and reducing risks of contamination. Copyright © 2016 Elsevier B.V. All rights reserved.

Quantitative contrast-enhanced ultrasonography for the differential diagnosis of endometrial hyperplasia and endometrial neoplasms

PubMed Central

Liu, Ying; Xu, Yi; Cheng, Wen; Liu, Xinghan

2016-01-01

The present study aimed to investigate the feasibility of applying contrast-enhanced ultrasonography (CEUS) imaging technology for distinguishing between benign and malignant endometrial lesions, and to screen markers that could be correlated with the pathological results. In this study, endometrial diseases were diagnosed by biopsy under hysteroscopy and CEUS examinations. The intensity and time parameters of the time-intensity curve (TIC) were analyzed. The mean arrival time (AT), time-to-peak (TTP), rise time (RT), washout half-time and clearance half-time of malignant lesions were shorter than those of benign lesions (P<0.05), whereas the average peak intensity (PI) and enhancement intensity (EI) of malignant lesions were higher than those of benign lesions (P<0.05). The receiver operating characteristic curve showed the following cut-off values: PI, 29.2 dB; EI, 21.35 dB; AT, 12.75 sec; TTP, 26.75 sec; RT, 13.2 sec; clearance half-time, 89.3 sec; and washout half-time, 75.45 sec. The lesions with PI, an EI higher than that of the cut-off and lesions with an AT, TTP, RT, half clearing time and washout half-time shorter than the cut-off were considered malignant. The TTP, RT and half clearing time were negatively correlated with microvessel density (MVD), i.e., MVD was higher when the TTP, RT and half clearing time were shorter. Overall, changes in the enhancement and clearing of lesions could be quantitatively analyzed by CEUS TIC and further discriminate benign from malignant lesions. In the present study, CEUS appeared to indirectly reflect blood vessel changes inside the lesions and provided a pre-operative non-invasive fast imaging method for the diagnosis of endometrial disease. PMID:27895728

Does the Dumbbell-Carrying Position Change the Muscle Activity in Split Squats and Walking Lunges?

PubMed

Stastny, Petr; Lehnert, Michal; Zaatar, Amr M Z; Svoboda, Zdenek; Xaverova, Zuzana

2015-11-01

The forward walking lunge (WL) and split squat (SSq) are similar exercises that have differences in the eccentric phase, and both can be performed in the ipsilateral or contralateral carrying conditions. This study aimed to determine the effects of dumbbell-carrying position on the kinematics and electromyographic (EMG) amplitudes of the gluteus medius (Gmed), vastus medialis (VM), vastus lateralis (VL), and biceps femoris during WLs and SSqs. The resistance-trained (RT) and the non-resistance-trained (NT) groups (both n = 14) performed ipsilateral WLs, contralateral WLs, ipsilateral SSqs, and contralateral SSqs in a randomized order in a simulated training session. The EMG amplitude, expressed as a percentage of the maximal voluntary isometric contraction (%MVIC), and the kinematics, expressed as the range of motion (ROM) of the hip and knee, were measured during 5 repetition maximum for both legs. The repeated measure analyses of variance showed significant differences between the RT and NT groups. The NT group showed a smaller knee flexion ROM (p < 0.001, η = 0.36) during both types of WLs, whereas the RT group showed a higher eccentric Gmed amplitude (p < 0.001, η = 0.46) during all exercises and a higher eccentric VL amplitude (p < 0.001, η = 0.63) during contralateral WLs. Further differences were found between contralateral and ipsilateral WLs in both the RT (p < 0.001, η = 0.69) and NT groups (p < 0.001, η = 0.80), and contralateral WLs resulted in higher eccentric Gmed amplitudes. Contralateral WLs highly activated the Gmed (90% MVIC); therefore, this exercise can increase the Gmed maximal strength. The ipsilateral loading condition did not increase the Gmed or VM activity in the RT or NT group.

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.

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

Wong, Fuh Yong, E-mail: fuhyong@yahoo.com; Wang, Fuqiang; Chen, John Ju

Purpose: To examine the outcomes of Southeast Asian (SEA) women with low-risk ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS) and adjuvant radiation therapy. Methods and Materials: Retrospective chart reviews of patients treated with BCS for DCIS from 1995 to 2011 were performed. Patients meeting the selection criteria from Eastern Cooperative Oncology Group 5194 were included. Most patients received adjuvant radiation therapy (RT) consisting of whole-breast RT delivered to 50 Gy followed by a 10-Gy boost to the tumor bed. Results: Of 744 patients with pathologic diagnosis of pure DCIS identified, 273 met the selection criteria: low-intermediate grade (LIG),more » n=219; high grade (HG), n=54. Median follow-up for these patients was 60 months. There were 8 ipsilateral breast tumor recurrences (IBTRs) in total, 7 of which were DCIS. The estimated actuarial IBTR rates at 5 and 10 years for the entire cohort are 1.8% and 4.3%, respectively. Of the 219 patients with LIG DCIS, 210 received RT and 9 did not. There were 7 IBTRs in LIG DCIS, 2 among the 9 patients who did not receive RT. The IBTR rates in LIG DCIS at 5 and 10 years are 2.3% and 4.2%, respectively. All patients with HG DCIS received RT. There was only 1 IBTR occurring beyond 5 years, giving an estimated IBTR rate of 4.5% at 10 years. Conclusions: SEA women with screen-detected DCIS have exceedingly low rates of IBTR after BCS, comparable to that observed in reports of similar patients with low-risk DCIS treated with adjuvant radiation.« less

Postoperative Radiation Therapy after Nipple-Sparing or Skin-Sparing Mastectomy: A Survey of European, North American, and South American Practices.

PubMed

Marta, Gustavo Nader; Poortmans, Philip M; Buchholz, Thomas A; Hijal, Tarek

2017-01-01

Skin sparing mastectomy, a surgical procedure sparing a large portion of the overlying skin of the breast, and nipple-sparing mastectomy, sparing the whole nipple-areolar complex, are increasingly used, although their oncologic efficacy remains unclear. The aim of this study was to assess the radiation oncologists' opinions regarding the indications of radiation therapy (RT) after skin-sparing mastectomy and nipple-sparing mastectomy. Radiation oncology members of four national and international societies were invited to complete a questionnaire comprising of 22 questions to assess their opinions regarding RT indications in the context of skin-sparing and nipple-sparing mastectomy. A total of 298 radiation oncologists answered the questionnaire. 90.9% of respondents affirmed that breast cancer is one of their specializations. The majority declared that post-mastectomy RT is indicated for early-stage (stages I and II) breast cancer patients who present with risk factors for recurrence after skin-sparing or nipple-sparing mastectomy (87.2% and 80.2%, respectively). All suggested risk factors (tumor size, lymph node involvement, extracapsular extension, lymphovascular space invasion, positive surgical margins, triple negative tumor, multicentric tumor, and age) were considered as major elements (important or very important). There is no consensus regarding the necessity of evaluating residual breast tissue or the definition of residual breast tissue after mastectomy. All classic factors were considered as major elements, potentially influencing the decision to advice or not postoperative RT. Many uncertainties remain about the indications for RT after skin-sparing mastectomy or nipple-sparing mastectomy. © 2016 Wiley Periodicals, Inc.

Heat tolerance in Tuli-, Senepol-, and Brahman-sired F1 Angus heifers in Florida.

PubMed

Hammond, A C; Chase, C C; Bowers, E J; Olson, T A; Randel, R D

1998-06-01

We investigated heat tolerance and growth rate in two trials under ambient conditions in central Florida. Trial 1 (1994) involved 38 Brahman (B), 21 Senepol (S), 19 B x Angus (A), 20 S x A, and 20 Tuli (T) x A heifers. Trial 2 (1995) involved 13 A, 35 B, 30 S, 23 B x A, 17 S x A, and 28 T x A heifers. Measurements were made on three consecutive weeks during the hotter and cooler seasons of each year and included rectal temperature (RT, degrees C), respiration rate (RR, bpm), temperament score (TS; 1 = very docile, 5 = very aggressive), blood packed-cell volume (PCV), and plasma cortisol concentration (CORT). Data for RT were transformed (log10 [RT - 37]) before analysis. On the hottest date in Trial 1, log10 RT was not different between B (.39 +/- .011) and B x A (.37 +/- .016) or between T x A (.35 +/- .015) and B x A, but log10 RT was lower (P < .05) in S x A (.30 +/- .015) than in either S (.35 +/- .015) or T x A. On all dates in Trial 1, RR was lower (P < .05 to .001) and PCV was higher (P < .05 to .001) in B than in B x A. There were few differences in TS except on two dates when B scored higher (P < .01 to .001) than B x A, and these differences were associated with higher (P < .05) CORT in B than in B x A. Using initial BW as a covariate, adjusted ADG (kg) of T x A (.52 +/- .023) was not different from adjusted ADG of B x A (.57 +/- .024) or S x A (.54 +/- .023). On the hottest date in Trial 2, log10 RT and RR were higher (P < .001) in A (.59 +/- .017, 74 +/- 2.7) than in B (.47 +/- .010, 39 +/- 1.6), S (.42 +/- .011, 50 +/- 1.8), and crossbred heifers (.47 +/- .011, 60 +/- 1.8; .43 +/- .014, 55 +/- 2.4; and .50 +/- .012, 48 +/- 2.0 for T x A, S x A and B x A, respectively), and RR was higher (P < .001) in B x A than in B. On the coolest date in Trial 2, RR was slightly lower in B (32 +/- .5) than in A(34 +/- .7, P < .01) and B x A (36 +/- .6, P < .001) and was associated with higher PCV in B than in A. On both dates, TS and CORT were higher (P < .01) in B than in A. In Trial 2, adjusted ADG (kg) was higher (P < .01) in B (.43 +/- .017) than in A (.32 +/- .033), higher (P < .001) in S (.45 +/- .018) than in A, and higher (P < .001) in crossbreds (B x A [.53 +/- .023] + S x A [.44 +/- .025] + T x A [.46 +/- .019]) than in A. These data indicate that heat tolerance in F1 crosses of tropically adapted breeds (Tuli, Senepol, Brahman) with a temperate breed (Angus) is similar to heat tolerance displayed by purebred tropical breeds (Senepol, Brahman).

Radiotherapy boost dose-escalation for invasive breast cancer after breast-conserving surgery: 2093 patients treated with a prospective margin-directed policy.

PubMed

Livi, Lorenzo; Meattini, Icro; Franceschini, Davide; Saieva, Calogero; Meacci, Fiammetta; Marrazzo, Livia; Gerlain, Elena; Desideri, Isacco; Scotti, Vieri; Nori, Jacopo; Sanchez, Luis Jose; Orzalesi, Lorenzo; Bonomo, Pierluigi; Greto, Daniela; Bianchi, Simonetta; Biti, Giampaolo

2013-08-01

To investigate the outcome of invasive early breast cancer patients that underwent breast-conserving surgery and adjuvant radiotherapy (RT), treated with a prospective margin-directed institutional policy for RT boost dose, based on final margins status (FMS). A total of 2093 patients were treated between 2000 and 2008. 10 Gy boost was prescribed in case of FMS>5mm; 16 Gy boost with FMS between 2 and 5mm; 20 Gy boost in case of FMS<2mm or positive. After a median follow up of 5.2 years, we recorded 41 local relapse (LR, 2%). Concerning LR free survival, age at diagnosis, nuclear grade, hormonal status, T-stage, adjuvant hormonal therapy and adjuvant chemotherapy emerged as significant parameters (p-values from log rank test <0.05). FMS, that directed the RT boost dose, did not have significant impact on LRFS (p=0.46). LR rates were 2.3% for FMS<2mm, 2.6% for 2-5mm FMS and 1.8% for FMS>5mm. At multivariate analysis, higher nuclear grade (p=0.045), triple negative subtype (p=0.036) and higher T-stage (p=0.02) resulted as the independent predictors of LR occurrence. Our experience showed that a margin-directed policy of RT boost dose-escalation seems to reduce the negative impact of FMS on LR, but it is not able to overcome the unfavorable effect of higher nuclear grade, higher T stage and triple negative subtype. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Radiation therapy for duct carcinoma in situ: who needs radiation therapy, who doesn't?

PubMed

McCormick, Beryl

2013-08-01

Duct carcinoma in situ (DCIS) is a common but non-life-threatening breast cancer. Four large prospective randomized trials comparing radiation therapy (RT) with none after breast-conservation surgery have all concluded that the use of RT reduces the risk of a local recurrence (LR) in the ipsilateral breast by at least 50%. More information is needed to assess the role of antiestrogen therapy when RT is not given. When markers are validated to predict which patients will have an invasive LR versus another DCIS or no LR, it is hoped that the discussion with the patient will clarify the situation further. Copyright © 2013 Elsevier Inc. All rights reserved.

Prevention of heterotopic bone formation with early post operative irradiation in high risk patients undergoing total hip arthroplasty: comparison of 10. 00 Gy vs 20. 00 Gy schedules

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

Anthony, P.; Keys, H.; Evarts, C.M.

1987-03-01

Prior studies have demonstrated the effectiveness of postoperative radiation therapy (RT) to the hip area following total hip replacement (THR) surgery in preventing the development of heterotopic bone formation in patients considered to be at high risk for development of this complication. Previously, patients received 20.00 Gy in 10 fractions (fx) over 2 weeks, beginning as soon postop as medically feasible (usually post-op day 2). In an effort to reduce hospital stay and risk of secondary malignancy, a prospective treatment program was initiated April 1982 using a reduced dose of 10.00 Gy in 5 fx over 5-7 days. As ofmore » February 1984, 46 consecutive hips determined to be at high risk were treated with this reduced dose. Prior studies have demonstrated that heterotopic bone is always radiographically evident by 8 weeks. Of the 46 hips, 41 had been evaluated with the minimum required 8 week follow-up X ray. Twenty-five of these hips, 61%, had a mean long term follow-up of 12 months. It historical control group, consisting of 54 consecutive high risk post-THR's, was shown to have a 68.5% incidence of heterotopic bone. The 20.00 Gy group, when RT was started by post-op day 5, demonstrated a 3.2% incidence, compared to 4.9% in the 10.00 Gy group. Complication rates were also comparable in the two RT groups, 19.4% and 7.3% respectively; 10.00 Gy is apparently as effective as 20.00 Gy in preventing heterotopic bone formation in high risk post-THR patients.« less

A survey on the status of hepatitis e virus infection among slaughterhouse workers in South Korea.

PubMed

Kim, Byung-Seok; Lim, Hyun-Sul; Lee, Kwan; Min, Young-Sun; Yoon, Young-Sil; Jeong, Hye-Sook

2015-01-01

The seroprevalence of hepatitis E virus (HEV) among high-risk groups overseas is high, but studies in these groups are rare in South Korea. We conducted the present study from April to November 2012 to obtain data on the seroprevalence and associated risk factors for HEV among slaughterhouse workers in South Korea. Slaughterhouse workers from 80 workplaces nationwide were surveyed in South Korea in 2012. The subjects comprised 1848 cases: 1434 slaughter workers and 414 residual products handlers. By visiting 80 slaughterhouses, which were mixed with 75 of which also performed residual products handling, we conducted a questionnaire survey for risk factors and obtained blood samples in order to determine the seropositivity and seroprevalence of HEV. Anti-HEV IgG and IgM were measured using HEV IgG and IgM enzyme-linked immunospecific assay kits and HEV antigen was measured by reverse transcription polymerase chain reaction (RT-PCR). The seropositivity of anti-HEV IgG was 33.5% (slaughter workers 32.8% and residual products handlers 36.2%), and among the seropositive individuals the seroprevalence of anti-HEV IgM was 0.5% (slaughter workers 0.5%, residual products handlers 0.7%). The response rate of HEV-antigen as measured by RT-PCR was 0.2%. Risk factors significantly related to anti-HEV IgG seropositivity were age, sex , and working duration (slaughter workers only). There were significant risk factors (sex, age, and working duration) for HEV identified in our study. All three positive cases for HEV-antigen by RT-PCR were related to pig slaughter but without statistical significance. To prevent HEV, an educational program and working guidelines may be needed for high risk groups.

Hyperthermia enhances radiosensitivity of colorectal cancer cells through ROS inducing autophagic cell death.

PubMed

Ba, Ming-Chen; Long, Hui; Wang, Shuai; Wu, Yin-Bing; Zhang, Bo-Huo; Yan, Zhao-Fei; Yu, Fei-Hong; Cui, Shu-Zhong

2018-04-01

Hyperthermia (HT) enhances the anti-cancer effects of radiotherapy (RT), but the precise biochemical mechanisms involved are unclear. This study was aim to investigate if mild HT sensitizes colorectal cancer cells to RT through reactive oxygen species (ROS)-inducing autophagic cell death in a mice model of HCT116 human colorectal cancer. HCT116 mice model were randomly divided into five groups: mock group, hyperthermia group (HT), radiotherapy group (RT), HT + RT group, and HT + RT +N-acetyl L-cysteine (NAC) group (HT + CT + NAC). After four weeks of treatment, cancer growth inhibition, rate and mitochondrial membrane potential were measured with MTT and JC-1 assays, respectively, while ROS were estimated fluorimetrically. The relationship of these parameters to expressions of autophagy-related genes Beclin1, LC3B, and mTOR was analyzed. Gene expression was measured by Real-Time polymerase chain reaction (RT-PCR). There were significant increases in ROS levels and mitochondrial membrane potential in the HT + RT group. ROS levels in the HT + RT group increased more significantly than in any other group. In contrast, ROS levels in the HT + RT + NAC group were significantly decreased relative to the HT + RT group. The number of autophagic bodies in HT + RT group was higher than that of mock group. There were significant increases in the expression of Beclin1 and LC3B genes, while mTOR expression was significantly decreased in the HT + CT group. Treatment with NAC reversed the pattern of these changes. These results indicate that HT enhances the radiosensitivity of colorectal cancer cells to RT through ROS inducing autophagic cell death. © 2017 Wiley Periodicals, Inc.

Neoadjuvant Radiation Is Associated With Improved Survival in Patients With Resectable Pancreatic Cancer: An Analysis of Data From the Surveillance, Epidemiology, and End Results (SEER) Registry

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

Stessin, Alexander M.; Weill Medical College of Cornell University, New York, NY; Meyer, Joshua E.

2008-11-15

Purpose: Cancer of the exocrine pancreas is the fifth leading cause of cancer death in the United States. Neoadjuvant chemoradiation has been investigated in several trials as a strategy for downstaging locally advanced disease to resectability. The aim of the present study is to examine the effect of neoadjuvant radiation therapy (RT) vs. other treatments on long-term survival for patients with resectable pancreatic cancer in a large population-based sample group. Methods and Materials: The Surveillance, Epidemiology, and End Results (SEER) registry database (1994-2003) was queried for cases of surgically resected pancreatic cancer. Retrospective analysis was performed. The endpoint of themore » study was overall survival. Results: Using Kaplan-Meier analysis we found that the median overall survival of patients receiving neoadjuvant RT was 23 months vs. 12 months with no RT and 17 months with adjuvant RT. Using Cox regression and controlling for independent covariates (age, sex, stage, grade, and year of diagnosis), we found that neoadjuvant RT results in significantly higher rates of survival than other treatments (hazard ratio [HR], 0.55; 95% confidence interval, 0.38-0.79; p = 0.001). Specifically comparing adjuvant with neoadjuvant RT, we found a significantly lower HR for death in patients receiving neoadjuvant RT rather than adjuvant RT (HR, 0.63; 95% confidence interval, 0.45-0.90; p = 0.03). Conclusions: This analysis of SEER data showed a survival benefit for the use of neoadjuvant RT over surgery alone or surgery with adjuvant RT in treating pancreatic cancer. Therapeutic strategies that use neoadjuvant RT should be further explored for patients with resectable pancreatic cancer.« less

A prospective study of cerebral, frontal lobe, and temporal lobe volumes and neuropsychological performance in children with primary brain tumors treated with cranial radiation.

PubMed

Agbahiwe, Harold; Rashid, Arif; Horska, Alena; Mahone, E Mark; Lin, Doris; McNutt, Todd; Cohen, Kenneth; Redmond, Kristin; Wharam, Moody; Terezakis, Stephanie

2017-01-01

Cranial radiation therapy (RT) is an important component in the treatment of pediatric brain tumors. However, it can result in long-term effects on the developing brain. This prospective study assessed the effects of cranial RT on cerebral, frontal lobe, and temporal lobe volumes and their correlation with higher cognitive functioning. Ten pediatric patients with primary brain tumors treated with cranial RT and 14 age- and sex-matched healthy children serving as controls were evaluated. Quantitative magnetic resonance imaging and neuropsychological assessments (language, memory, auditory and visual processing, and vocabulary) were performed at the baseline and 6, 15, and 27 months after RT. The effects of age, the time since RT, and the cerebral RT dose on brain volumes and neuropsychological performance were analyzed with linear mixed effects model analyses. Cerebral volume increased significantly with age in both groups (P = .01); this increase in volume was more pronounced in younger children. Vocabulary performance was found to be significantly associated with a greater cerebral volume (P = .05) and a lower RT dose (P = .003). No relation was observed between the RT dose and the cerebral volume. There was no difference in the corresponding neuropsychological tests between the 2 groups. This prospective study found significant relations among the RT dose, cerebral volumes, and rate of vocabulary development among children receiving RT. The results of this study provide further support for clinical trials aimed at reducing cranial RT doses in the pediatric population. Cancer 2017;161-168. © 2016 American Cancer Society. © 2016 American Cancer Society.

Immune modulatory effects of radiotherapy as basis for well-reasoned radioimmunotherapies.

PubMed

Rückert, Michael; Deloch, Lisa; Fietkau, Rainer; Frey, Benjamin; Hecht, Markus; Gaipl, Udo S

2018-06-01

Radiotherapy (RT) has been known for decades as a local treatment modality for malign and benign disease. In order to efficiently exploit the therapeutic potential of RT, an understanding of the immune modulatory properties of ionizing radiation is mandatory. These should be used for improvement of radioimmunotherapies for cancer in particular. We here summarize the latest research and review articles about immune modulatory properties of RT, with focus on radiation dose and on combination of RT with selected immunotherapies. Based on the knowledge of the manifold immune mechanisms that are triggered by RT, thought-provoking impulse for multimodal radioimmunotherapies is provided. It has become obvious that ionizing radiation induces various forms of cell death and associated processes via DNA damage initiation and triggering of cellular stress responses. Immunogenic cell death (ICD) is of special interest since it activates the immune system via release of danger signals and via direct activation of immune cells. While RT with higher single doses in particular induces ICD, RT with a lower dose is mainly responsible for immune cell recruitment and for attenuation of an existing inflammation. The counteracting immunosuppression emanating from tumor cells can be overcome by combining RT with selected immunotherapies such as immune checkpoint inhibition, TGF-β inhibitors, and boosting of immunity with vaccination. In order to exploit the full power of RT and thereby develop efficient radioimmunotherapies, the dose per fraction used in RT protocols, the fractionation, the quality, and the quantity of certain immunotherapies need to be qualitatively and chronologically well-matched to the individual immune status of the patient.

Evidence for higher reaction time variability for children with ADHD on a range of cognitive tasks including reward and event rate manipulations

PubMed Central

Epstein, Jeffery N.; Langberg, Joshua M.; Rosen, Paul J.; Graham, Amanda; Narad, Megan E.; Antonini, Tanya N.; Brinkman, William B.; Froehlich, Tanya; Simon, John O.; Altaye, Mekibib

2012-01-01

Objective The purpose of the research study was to examine the manifestation of variability in reaction times (RT) in children with Attention Deficit Hyperactivity Disorder (ADHD) and to examine whether RT variability presented differently across a variety of neuropsychological tasks, was present across the two most common ADHD subtypes, and whether it was affected by reward and event rate (ER) manipulations. Method Children with ADHD-Combined Type (n=51), ADHD-Predominantly Inattentive Type (n=53) and 47 controls completed five neuropsychological tasks (Choice Discrimination Task, Child Attentional Network Task, Go/No-Go task, Stop Signal Task, and N-back task), each allowing trial-by-trial assessment of reaction times. Multiple indicators of RT variability including RT standard deviation, coefficient of variation and ex-Gaussian tau were used. Results Children with ADHD demonstrated greater RT variability than controls across all five tasks as measured by the ex-Gaussian indicator tau. There were minimal differences in RT variability across the ADHD subtypes. Children with ADHD also had poorer task accuracy than controls across all tasks except the Choice Discrimination task. Although ER and reward manipulations did affect children’s RT variability and task accuracy, these manipulations largely did not differentially affect children with ADHD compared to controls. RT variability and task accuracy were highly correlated across tasks. Removing variance attributable to RT variability from task accuracy did not appreciably affect between-group differences in task accuracy. Conclusions High RT variability is a ubiquitous and robust phenomenon in children with ADHD. PMID:21463041

Environmental Health Risk Assesement in Flood-prone Area in Tamangapa Sub-District Makassar

NASA Astrophysics Data System (ADS)

Haris, Ibrahim Abdul; Basir, Basir

2018-05-01

Environmental health in Indonesia is still caution to concern, poor sanitation in Indonesia is characterized by the high incidence of infectious diseases in society. The society in flood-prone area has a high-risk exposure on the disease based on the environment because they live in disaster-prone area. This research aimed to describe the condition of sanitary facilities and risky behavior on public health in flood-prone areas in Manggala district particularly in Tamangapa sub-district of Makassar. This reserach uses an observation method with a descriptive approach. The data is processed by using SPSS and Arc View GIS applications. Environmental risk category is determined by the approach of Environmental Health Risk Assessment (EHRA). The results showed that the flood-prone area in RT 04 RW 06 was included in very high-risk category at 229 with an index value of environmental health risks 212-229. Meanwhile, RT 04 RW 05 was in the category of low risk in the amount of 155 with an index of 155-173. Environmental health hazards identified in Tamangapa flood-prone areas sub-district includes domestic sources of clean water, domestic wastewater, and household garbage.

Use of short-term real-time continuous glucose monitoring in type 1 diabetes patients on continuous intraperitoneal insulin infusion: a feasibility study.

PubMed

Logtenberg, Susan J J; Kleefstra, Nanne; Groenier, Klaas H; Gans, Rijk O B; Bilo, Henk J G

2009-05-01

In diabetes, strict glycemic control reduces risk of complications. One mode of therapy is continuous intraperitoneal insulin infusion (CIPII). With CIPII, like all intensified treatment strategies, frequent assessment of glucose levels is mandatory. Real-time (RT)-continuous glucose monitoring (CGM) gives RT information without the need for multiple invasive measurements. In theory, CIPII combined with RT-CGM could provide near normal glucose profiles. The objective of this study is to investigate effectiveness and safety of RT-CGM in patients treated with intraperitoneal insulin through an implanted pump. In an open-label, crossover, randomized study, effects of 6-day open RT-CGM use were studied in 12 type 1 diabetes patients on CIPII, with blinded RT-CGM used as a control. Primary outcome was time in euglycemia. Secondary outcomes included time in other glucose ranges, incidence of adverse events, and patient satisfaction. Agreement of self-measurement of blood glucose (SMBG) and RT-CGM measurements was assessed. Median time spent in euglycemia was 68.2% (55.9-72.3%) with open RT-CGM and 64.9% (55.3-71.2%) with blinded RT-CGM (P = 0.25). Time spent in other glucose ranges did not differ (P > 0.05). There were no serious adverse events. Patient satisfaction was good. Median relative absolute difference of SMBG and RT-CGM values was 13.9%. Bland-Altman analysis showed a mean difference of -0.31 mg/dL with lower and upper limits of agreement of -77.0 and +76.4 mg/dL, respectively. Short-term use of RT-CGM, although safe and with good patient satisfaction, does not result in more time spent in euglycemia, nor does it change time spent in other glucose ranges in our population of type 1 diabetes patients receiving CIPII.

The effects of a 6-month resistance training and dried plum consumption intervention on strength, body composition, blood markers of bone turnover, and inflammation in breast cancer survivors.

PubMed

Simonavice, Emily; Liu, Pei-Yang; Ilich, Jasminka Z; Kim, Jeong-Su; Arjmandi, Bahram; Panton, Lynn B

2014-06-01

The purpose of this study was to examine the effects of resistance training (RT) and dried plum (DP) consumption on strength, body composition, blood markers of bone, and inflammation in breast cancer survivors (BCS). Twenty-three BCS (RT, n = 12; RT+DP, n = 11), aged 64 ± 7 years, were evaluated at baseline and after 6 months of intervention on the following: muscular strength (chest press and leg extension) via 1-repetition maximums (1RMs); body composition, specifically bone mineral density (BMD) by dual energy X-ray absorptiometry; biochemical markers of bone turnover (bone-specific alkaline phosphatase (BAP), tartrate resistant acid phosphatase (TRAP-5b)); and inflammation (C-reactive protein (CRP)). Target RT prescription was 2 days/week of 10 exercises, including 2 sets of 8-12 repetitions at ∼60%-80% of 1RM. RT+DP also consumed 90 g of DP daily. There were no baseline differences between groups or any group-by-time interactions for any of the variables. BCS increased upper (p < 0.05) (RT: 64 ± 14 to 80 ± 17 kg; RT+DP: 72 ± 23 to 91 ± 20 kg) and lower (p < 0.05) (RT: 69 ± 20 to 87 ± 28 kg; RT+DP: 78 ± 19 to 100 ± 21 kg) body strength. Body composition and BMD improvements were not observed. TRAP-5b decreased in the RT group (p < 0.05) (4.55 ± 1.57 to 4.04 ± 1.63 U/L) and the RT+DP group (p = 0.07) (5.10 ± 2.75 to 4.27 ± 2.03 U/L). Changes in BAP and CRP were not observed. RT was effective for improving biochemical markers of bone turnover and muscular strength in BCS. A longer and higher intensity intervention may be needed to reveal the true effects of RT and DP on body composition and biochemical markers of inflammation.

Concurrent Cyclophosphamide, Methotrexate, and 5-Fluorouracil Chemotherapy and Radiotherapy for Early Breast Carcinoma

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

Livi, Lorenzo; Saieva, Calogero; Borghesi, Simona

2008-07-01

Purpose: The optimal sequencing of adjuvant chemotherapy (CT) and radiation therapy (RT) in patients with early-stage breast cancer remains unclear. Patients and Methods: We retrospectively compared 485 patients treated with conservative breast surgery and postoperative whole-breast RT and six courses of CMF (cyclophosphamide 600 mg/m{sup 2}, methotrexate 40 mg/m{sup 2}, and 5-fluorouracil 600 mg/m{sup 2}) with 300 patients who received postoperative CMF only and with 509 patients treated with postoperative whole-breast RT only. The mean radiation dose delivered was 50 Gy (range, 46-52 Gy) with standard fractionation. The boost dose was 6-16 Gy according to resection margins and at themore » discretion of the radiation oncologist. Acute and late RT toxicity were scored using respectively the Radiation Therapy Oncology Group and the Late Effects in Normal Tissues Subjective, Objective, Management and Analytic scale. Results: A slightly higher Grade 2 acute skin toxicity was recorded in the concurrent group (21.2% vs. 11.2% of the RT only group, p < 0.0001). RT was interrupted more frequently in the CMF/RT group respective to the RT group (8.5% vs. 4.1%; p = 0.006). There was no difference in late toxicity between the two groups. All patients in the concurrent group successfully received the planned dose of RT and CT. Local recurrence rate was 7.6% in CT/RT group and 9.8% in RT group; this difference was not statistically significant at univariate analysis (log-rank test p = 0.98). However, at multivariate analysis adjusted also for pathological tumor, pathological nodes, and age, the CT/RT group showed a statistically lower rate of local recurrence (p = 0.04). Conclusions: Whole-breast RT and concurrent CMF are a safe adjuvant treatment in terms of toxicity.« less

Rough-and-tumble play as a window on animal communication.

PubMed

Palagi, Elisabetta; Burghardt, Gordon M; Smuts, Barbara; Cordoni, Giada; Dall'Olio, Stefania; Fouts, Hillary N; Řeháková-Petrů, Milada; Siviy, Stephen M; Pellis, Sergio M

2016-05-01

Rough-and-tumble play (RT) is a widespread phenomenon in mammals. Since it involves competition, whereby one animal attempts to gain advantage over another, RT runs the risk of escalation to serious fighting. Competition is typically curtailed by some degree of cooperation and different signals help negotiate potential mishaps during RT. This review provides a framework for such signals, showing that they range along two dimensions: one from signals borrowed from other functional contexts to those that are unique to play, and the other from purely emotional expressions to highly cognitive (intentional) constructions. Some animal taxa have exaggerated the emotional and cognitive interplay aspects of play signals, yielding admixtures of communication that have led to complex forms of RT. This complexity has been further exaggerated in some lineages by the development of specific novel gestures that can be used to negotiate playful mood and entice reluctant partners. Play-derived gestures may provide new mechanisms by which more sophisticated communication forms can evolve. Therefore, RT and playful communication provide a window into the study of social cognition, emotional regulation and the evolution of communication systems. © 2015 Cambridge Philosophical Society.

Melatonin prevents radiation-induced oxidative stress and periodontal tissue breakdown in irradiated rats with experimental periodontitis.

PubMed

Köse, O; Arabaci, T; Kizildag, A; Erdemci, B; Özkal Eminoğlu, D; Gedikli, S; Özkanlar, S; Zihni, M; Albayrak, M; Kara, A; Kermen, E

2017-06-01

The aim of this study was to analyze the biochemical and histochemical effects of radiation therapy and protective melatonin administration on periodontal tissues in rats with experimental periodontitis. Sixty male Sprague Dawley rats were divided into six groups, as follows: control; experimental periodontitis (Ped); radiotherapy administration (Rt); experimental periodontitis and exposure to irradiation (Ped-Rt); radiotherapy and protective melatonin administration (Rt-Mel); and periodontitis, radiation therapy and protective melatonin administration (Ped-Rt-Mel). The rats were killed at the end of the experimental procedure, and the oxidative stress level and periodontal destruction were compared among the groups. The oxidative stress index and the levels of 8-hydroxy-2'-deoxyguanosine, malondialdehyde and C-terminal telopeptide of type I collagen were found to be significantly higher in the Ped-Rt group compared with the Ped group (p < 0.05), and the levels were lower in the Ped-Rt-Mel group than in the Ped-Rt group (p < 0.05). Alveolar bone destruction and attachment level were also significantly lower in the Ped-Rt-Mel group than in the Ped-Rt group (p < 0.05). It was found that radiotherapy increased oxidative stress, the periodontal attachment level and alveolar bone loss, and protective melatonin administration significantly reduced the oxidative parameters and prevented periodontal damage in irradiated rats with experimental periodontitis. Further research is needed regarding the use of systemic melatonin administration before radiation therapy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A Guideline to Family-Wide Comparative State-of-the-Art Quantitative RT-PCR Analysis Exemplified with a Brassicaceae Cross-Species Seed Germination Case Study[W][OA

PubMed Central

Graeber, Kai; Linkies, Ada; Wood, Andrew T.A.; Leubner-Metzger, Gerhard

2011-01-01

Comparative biology includes the comparison of transcriptome and quantitative real-time RT-PCR (qRT-PCR) data sets in a range of species to detect evolutionarily conserved and divergent processes. Transcript abundance analysis of target genes by qRT-PCR requires a highly accurate and robust workflow. This includes reference genes with high expression stability (i.e., low intersample transcript abundance variation) for correct target gene normalization. Cross-species qRT-PCR for proper comparative transcript quantification requires reference genes suitable for different species. We addressed this issue using tissue-specific transcriptome data sets of germinating Lepidium sativum seeds to identify new candidate reference genes. We investigated their expression stability in germinating seeds of L. sativum and Arabidopsis thaliana by qRT-PCR, combined with in silico analysis of Arabidopsis and Brassica napus microarray data sets. This revealed that reference gene expression stability is higher for a given developmental process between distinct species than for distinct developmental processes within a given single species. The identified superior cross-species reference genes may be used for family-wide comparative qRT-PCR analysis of Brassicaceae seed germination. Furthermore, using germinating seeds, we exemplify optimization of the qRT-PCR workflow for challenging tissues regarding RNA quality, transcript stability, and tissue abundance. Our work therefore can serve as a guideline for moving beyond Arabidopsis by establishing high-quality cross-species qRT-PCR. PMID:21666000

Salivary gland sparing and improved target irradiation by conformal and intensity modulated irradiation of head and neck cancer.

PubMed

Eisbruch, Avraham; Ship, Jonathan A; Dawson, Laura A; Kim, Hyungjin M; Bradford, Carol R; Terrell, Jeffrey E; Chepeha, Douglas B; Teknos, Theodore N; Hogikyan, Norman D; Anzai, Yoshimi; Marsh, Lon H; Ten Haken, Randall K; Wolf, Gregory T

2003-07-01

The goals of this study were to facilitate sparing of the major salivary glands while adequately treating tumor targets in patients requiring comprehensive bilateral neck irradiation (RT), and to assess the potential for improved xerostomia. Since 1994 techniques of target irradiation and locoregional tumor control with conformal and intensity modulated radiation therapy (IMRT) have been developed. In patients treated with these modalities, the salivary flow rates before and periodically after RT have been measured selectively from each major salivary gland and the residual flows correlated with glands' dose volume histograms (DVHs). In addition, subjective xerostomia questionnaires have been developed and validated. The pattern of locoregional recurrence has been examined from computed tomography (CT) scans at the time of recurrence, transferring the recurrence volumes to the planning CT scans, and regenerating the dose distributions at the recurrence sites. Treatment plans for target coverage and dose homogeneity using static, multisegmental IMRT were found to be significantly better than standard RT plans. In addition, significant parotid gland sparing was achieved in the conformal plans. The relationships among dose, irradiated volume, and the residual saliva flow rates from the parotid glands were characterized by dose and volume thresholds. A mean radiation dose of 26 Gy was found to be the threshold for preserved stimulated saliva flow. Xerostomia questionnaire scores suggested that xerostomia was significantly reduced in patients irradiated with bilateral neck, parotid-sparing RT, compared to patients with similar tumors treated with standard RT. Examination of locoregional tumor recurrence patterns revealed that the large majority of recurrences occurred inside targets, in areas that had been judged to be at high risk and that had received RT doses according to the perceived risk. Tangible gains in salivary gland sparing and target coverage are being achieved, and an improvement in some measures of quality of life is suggested by our findings. Additional reduction of xerostomia may be achieved by further sparing of the salivary glands and the non-involved oral cavity. A mean parotid gland dose of < or = 26 Gy should be a planning objective if significant parotid function preservation is desired. The pattern of recurrence suggests that careful escalation of the dose to areas judged to be at highest risk may improve tumor control.

One-step cross-genogroup multiplex RT-qPCR with an internal control system for the detection of infectious pancreatic necrosis virus (IPNV).

PubMed

Hoferer, Marc; Braun, Anne; Skrypski, Julia; Bock, Sabine; Thalheim, Sabine; Sting, Reinhard

2017-09-01

Infectious pancreatic necrosis virus (IPNV) causes great losses in fish hatcheries world-wide. The detection of IPNV can be challenging in certain circumstances, particularly due to low viral load and the genetic variability of this RNA virus. For the first time, this project created a quantitative triplex real-time reverse transcription PCR (RT-qPCR), including an endogenous control system, for specific, sensitive and rapid detection of IPNV in routine diagnostics. Multiple sequence alignment of 46 nucleotide sequences of the segment A genome obtained from the NCBI database allowed the design of two RT-qPCR systems covering the IPNV genogroup 1 and genogroups 2-5, respectively. The completed triplex RT-qPCR including a salmonid-specific endogenous control showed high specificity and an analytical sensitivity of 20-40 oligonucleotide copies. Testing of dilution series of virus-loaded cell culture suspensions proved equality of the triplex RT-qPCR with virus detection in cell culture and a higher sensitivity than conventional RT-PCR in field samples. In comparative studies of a total of 77 field samples tested, 51 showed identical positive and 19 identical negative results in cell culture and the triplex RT-qPCR. However, seven other samples yielded positive results in the triplex RT-qPCR, but negative results in cell culture. Copyright © 2017 Elsevier B.V. All rights reserved.

Blast and Fragments from Superpressure Vessel Rupture

DTIC Science & Technology

1976-02-09

hemispheres. These plecs were accelerated to velocities of about 300 ft/second; about half the calculated fragment velocities. MCEBION Wllltl...8217 i i i i i T T i r t i t T T—T T i i i i i i i ^ T r i i i ! i-i-1 r r" rT *TT"T- rT i ’ ’FIG. 3.1 ESTIMATED DIRECTION OF ARGON JETTING...the box (line 2) are higher than along the other two lines but no higher than was predicted for a free field burst. Pressures behind the box are

The Pattern of Failure After Reirradiation of Recurrent Squamous Cell Head and Neck Cancer: Implications for Defining the Targets

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

Popovtzer, Aron; Gluck, Iris; Chepeha, Douglas B.

2009-08-01

Purpose: Reirradiation (re-RT) of recurrent head and neck cancer (HNC) may achieve long-term disease control in some patients, at the expense of high rates of late sequelae. Limiting the re-RT targets to the recurrent gross tumor volume (rGTV) would reduce the volumes of reirradiated tissues; however, its effect on tumor recurrence pattern is unknown. Methods and Materials: This is a retrospective review of 66 patients who underwent curative-intent re-RT for nonresectable recurrent or second primary mucosal squamous cell HNC. Treatment was delivered with three-dimensional conformal (3D) RT or intensity-modulated RT (IMRT). The targets in all patients consisted of the rGTVsmore » with tight (0.5-cm) margins, with no intent to treat prophylactically lymph nodes or subclinical disease in the vicinity of the rGTVs. The sites of locoregional failures (LRFs) were determined using imaging at the time of failure and were compared with the rGTVs. Results: Median re-RT dose was 68 Gy. Forty-seven patients (71%) received concomitant chemotherapy, and 31 (47%) received hyperfractionated, accelerated RT. At a median follow-up of 42 months, 16 (23%) were alive and disease-free. Fifty patients (77%) had a third recurrence or persistent disease, including 47 LRFs. All LRFs occurred within the rGTVs except for two (4%) (95% confidence interval, 0-11%). Nineteen patients (29%) had Grade {>=} 3 late complications, mostly dysphagia (12 patients). Conclusions: Almost all LRFs occurred within the reirradiated rGTVs despite avoiding prophylactic RT of tissue at risk of subclinical disease. These results support confining the re-RT targets to the rGTVs to reduce reirradiated tissue volumes.« less

Development and Validation of a qRT-PCR Classifier for Lung Cancer Prognosis

PubMed Central

Chen, Guoan; Kim, Sinae; Taylor, Jeremy MG; Wang, Zhuwen; Lee, Oliver; Ramnath, Nithya; Reddy, Rishindra M; Lin, Jules; Chang, Andrew C; Orringer, Mark B; Beer, David G

2011-01-01

Purpose This prospective study aimed to develop a robust and clinically-applicable method to identify high-risk early stage lung cancer patients and then to validate this method for use in future translational studies. Patients and Methods Three published Affymetrix microarray data sets representing 680 primary tumors were used in the survival-related gene selection procedure using clustering, Cox model and random survival forest (RSF) analysis. A final set of 91 genes was selected and tested as a predictor of survival using a qRT-PCR-based assay utilizing an independent cohort of 101 lung adenocarcinomas. Results The RSF model built from 91 genes in the training set predicted patient survival in an independent cohort of 101 lung adenocarcinomas, with a prediction error rate of 26.6%. The mortality risk index (MRI) was significantly related to survival (Cox model p < 0.00001) and separated all patients into low, medium, and high-risk groups (HR = 1.00, 2.82, 4.42). The MRI was also related to survival in stage 1 patients (Cox model p = 0.001), separating patients into low, medium, and high-risk groups (HR = 1.00, 3.29, 3.77). Conclusions The development and validation of this robust qRT-PCR platform allows prediction of patient survival with early stage lung cancer. Utilization will now allow investigators to evaluate it prospectively by incorporation into new clinical trials with the goal of personalized treatment of lung cancer patients and improving patient survival. PMID:21792073

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

Aznar, Marianne C., E-mail: marianne.camille.aznar@regionh.dk; Faculty of Sciences, Niels Bohr Institute, and Faculty of Health Sciences, University of Copenhagen, Copenhagen; Maraldo, Maja V.

Purpose: Hodgkin lymphoma (HL) survivors have an increased risk of cardiovascular disease (CD), lung cancer, and breast cancer. We investigated the risk for the development of CD and secondary lung, breast, and thyroid cancer after radiation therapy (RT) delivered with deep inspiration breath-hold (DIBH) compared with free-breathing (FB) using 3-dimensional conformal RT (3DCRT) and intensity modulated RT (IMRT). The aim of this study was to determine which treatment modality best reduced the combined risk of life-threatening late effects in patients with mediastinal HL. Methods and Materials: Twenty-two patients with early-stage mediastinal HL were eligible for the study. Treatment plans weremore » calculated with both 3DCRT and IMRT on both DIBH and FB planning computed tomographic scans. We reported the estimated dose to the heart, lung, female breasts, and thyroid and calculated the estimated life years lost attributable to CD and to lung, breast, and thyroid cancer. Results: DIBH lowered the estimated dose to heart and lung regardless of delivery technique (P<.001). There was no significant difference between IMRT-FB and 3DCRT-DIBH in mean heart dose, heart V20Gy, and lung V20Gy. The mean breast dose was increased with IMRT regardless of breathing technique. Life years lost was lowest with DIBH and highest with FB. Conclusions: In this cohort, 3DCRT-DIBH resulted in lower estimated doses and lower lifetime excess risks than did IMRT-FB. Combining IMRT and DIBH could be beneficial for a subgroup of patients.« less

Risk factors for near-miss events and safety incidents in pediatric radiation therapy.

PubMed

Baig, Nimrah; Wang, Jiangxia; Elnahal, Shereef; McNutt, Todd; Wright, Jean; DeWeese, Theodore; Terezakis, Stephanie

2018-05-01

Factors contributing to safety- or quality-related incidents (e.g. variances) in children are unknown. We identified clinical and RT treatment variables associated with risk for variances in a pediatric cohort. Using our institution's incident learning system, 81 patients age ≤21 years old who experienced variances were compared to 191 pediatric patients without variances. Clinical and RT treatment variables were evaluated as potential predictors for variances using univariate and multivariate analyses. Variances were primarily documentation errors (n = 46, 57%) and were most commonly detected during treatment planning (n = 14, 21%). Treatment planning errors constituted the majority (n = 16 out of 29, 55%) of near-misses and safety incidents (NMSI), which excludes workflow incidents. Therapists reported the majority of variances (n = 50, 62%). Physician cross-coverage (OR = 2.1, 95% CI = 1.04-4.38) and 3D conformal RT (OR = 2.3, 95% CI = 1.11-4.69) increased variance risk. Conversely, age >14 years (OR = 0.5, 95% CI = 0.28-0.88) and diagnosis of abdominal tumor (OR = 0.2, 95% CI = 0.04-0.59) decreased variance risk. Variances in children occurred in early treatment phases, but were detected at later workflow stages. Quality measures should be implemented during early treatment phases with a focus on younger children and those cared for by cross-covering physicians. Copyright © 2018 Elsevier B.V. All rights reserved.

Retroperitoneal sarcoma (RPS) high risk gross tumor volume boost (HR GTV boost) contour delineation agreement among NRG sarcoma radiation and surgical oncologists.

PubMed

Baldini, Elizabeth H; Bosch, Walter; Kane, John M; Abrams, Ross A; Salerno, Kilian E; Deville, Curtiland; Raut, Chandrajit P; Petersen, Ivy A; Chen, Yen-Lin; Mullen, John T; Millikan, Keith W; Karakousis, Giorgos; Kendrick, Michael L; DeLaney, Thomas F; Wang, Dian

2015-09-01

Curative intent management of retroperitoneal sarcoma (RPS) requires gross total resection. Preoperative radiotherapy (RT) often is used as an adjuvant to surgery, but recurrence rates remain high. To enhance RT efficacy with acceptable tolerance, there is interest in delivering "boost doses" of RT to high-risk areas of gross tumor volume (HR GTV) judged to be at risk for positive resection margins. We sought to evaluate variability in HR GTV boost target volume delineation among collaborating sarcoma radiation and surgical oncologist teams. Radiation planning CT scans for three cases of RPS were distributed to seven paired radiation and surgical oncologist teams at six institutions. Teams contoured HR GTV boost volumes for each case. Analysis of contour agreement was performed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. HRGTV boost volume contour agreement between the seven teams was "substantial" or "moderate" for all cases. Agreement was best on the torso wall posteriorly (abutting posterior chest abdominal wall) and medially (abutting ipsilateral para-vertebral space and great vessels). Contours varied more significantly abutting visceral organs due to differing surgical opinions regarding planned partial organ resection. Agreement of RPS HRGTV boost volumes between sarcoma radiation and surgical oncologist teams was substantial to moderate. Differences were most striking in regions abutting visceral organs, highlighting the importance of collaboration between the radiation and surgical oncologist for "individualized" target delineation on the basis of areas deemed at risk and planned resection.

Identification of Patients at Very Low Risk of Local Recurrence After Breast-Conserving Surgery

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

Smith, Sally L., E-mail: ssmith11@bccancer.bc.ca; Truong, Pauline T.; Lu, Linghong

2014-07-01

Purpose: To identify clinical and pathological factors that identify groups of women with stage I breast cancer with a 5-year risk of local recurrence (LR) ≤1.5% after breast-conserving therapy (BCS) plus whole-breast radiation therapy (RT). Methods and Materials: Study subjects were 5974 patients ≥50 years of age whose cancer was diagnosed between 1989 and 2006, and were referred with pT1 pN0 invasive breast cancer treated with BCS and RT. Cases of 5- and 10-year LR were examined using Kaplan-Meier methods. Recursive partitioning analysis was performed in patients treated with and without endocrine therapy to identify combinations of factors associated withmore » a 5-year LR risk ≤1.5%. Results: The median follow-up was 8.61 years. Median age was 63 years of age (range, 50 to 91). Overall 5-year LR was 1.5% (95% confidence interval [CI], 1.2%-1.9%) and 10-year LR was 3.4% (95% CI, 2.8%-4.0%). Of 2830 patients treated with endocrine therapy, patient subsets identified with 5-year LR ≤1.5% included patients with grade 1 histology (n=1038; LR, 0.2%; 95% CI, 0%-0.5%) or grade 2 histology plus ≥60 years of age (n=843; LR, 0.5%; 95% CI, 0%-1.0%). Ten-year LR for these groups were 0.8% (95% CI, 0.1%-1.6%) and 0.9% (95% CI, 0.2%-1.6%), respectively. Of 3144 patients treated without endocrine therapy, patients with grade 1 histology plus clear margins had 5-year LR ≤1.5% (n=821; LR, 0.6%; 95% CI, 0.1%-1.2%). Ten-year LR for this group was 2.2% (95% CI, 1.0%-3.4%). Conclusions: Histologic grade, age, margin status, and use of endocrine therapy identified 45% of a population-based cohort of female patients over age 50 with stage I breast cancer with a 5-year LR risk ≤1.5% after BCS plus RT. Prospective study is needed to evaluate the safety of omitting RT in patients with such a low risk of LR.« less

Necrosis predicts benefit from hypoxia-modifying therapy in patients with high risk bladder cancer enrolled in a phase III randomised trial☆

PubMed Central

Eustace, Amanda; Irlam, Joely J.; Taylor, Janet; Denley, Helen; Agrawal, Shailesh; Choudhury, Ananya; Ryder, David; Ord, Jonathan J.; Harris, Adrian L.; Rojas, Ana M.; Hoskin, Peter J.; West, Catharine M.L.

2013-01-01

Background and purpose Addition of carbogen and nicotinamide (hypoxia-modifying agents) to radiotherapy improves the survival of patients with high risk bladder cancer. The study investigated whether histopathological tumour features and putative hypoxia markers predicted benefit from hypoxia modification. Materials and methods Samples were available from 231 patients with high grade and invasive bladder carcinoma from the BCON phase III trial of radiotherapy (RT) alone or with carbogen and nicotinamide (RT + CON). Histopathological tumour features examined were: necrosis, growth pattern, growing margin, and tumour/stroma ratio. Hypoxia markers carbonic anhydrase-IX and glucose transporter-1 were examined using tissue microarrays. Results Necrosis was the only independent prognostic indicator (P = 0.04). Necrosis also predicted benefit from hypoxia modification. Five-year overall survival was 48% (RT) versus 39% (RT + CON) (P = 0.32) in patients without necrosis and 34% (RT) versus 56% (RT + CON) (P = 0.004) in patients with necrosis. There was a significant treatment by necrosis strata interaction (P = 0.001 adjusted). Necrosis was an independent predictor of benefit from RT + CON versus RT (hazard ratio [HR]: 0.43, 95% CI 0.25–0.73, P = 0.002). This trend was not observed when there was no necrosis (HR: 1.64, 95% CI 0.95–2.85, P = 0.08). Conclusions Necrosis predicts benefit from hypoxia modification in patients with high risk bladder cancer and should be used to select patients; it is simple to identify and easy to incorporate into routine histopathological examination. PMID:23773411

Prognostic factors in prostate cancer patients treated by radical external beam radiotherapy.

PubMed

Garibaldi, Elisabetta; Gabriele, Domenico; Maggio, Angelo; Delmastro, Elena; Garibaldi, Monica; Russo, Filippo; Bresciani, Sara; Stasi, Michele; Gabriele, Pietro

2017-09-01

The aim of this paper was to analyze, retrospectively, in prostate cancer patients treated in our Centre with external beam radiotherapy, the prognostic factors and their impact on the outcome in terms of cancer-specific survival (CSS), biochemical disease-free survival (BDFS) and clinical disease-free survival (CDFS). From October 1999 and March 2012, 1080 patients were treated with radiotherapy at our Institution: 87% of them were classified as ≤cT2, 83% had a Gleason Score (GS) ≤7, their mean of iPSA was 18 ng/mL, and the rate of clinical positive nodes was 1%. The mean follow-up was 81 months. The statistically significant prognostic factors for all groups of patients at both, univariate and multivariate analysis, were the GS and the iPSA. In intermediate- and high- or very-high-risk patients at multivariate analysis other prognostic factors for CSS were positive nodes on computed tomography (CT) scan and rectal preparation during the treatment; for BDFS, the prognostic factors were patient risk classification, positive lymph nodes on CT scan and rectal/bladder preparation; for CDFS, the prognostic factors were the number of positive core on biopsy (P=0.003), positive lymph nodes on CT scan, and radiotherapy (RT) dose. In high/very-high risk patient group at multivariate analysis other prognostic factors for CSS were clinical/radiological stage and RT dose, for BDFS they were adjuvant hormone therapy, clinical/radiological stage, and RT dose >77.7 Gy, and for CDFS they were clinical/radiological stage and RT dose >77.7 Gy. The results of this study confirm the prognostic factors described in the recent literature, with the addition of rectal/bladder preparation, generally known for its effect on toxicity but not yet on outcome.

Osteochondroma in long-term survivors of high-risk neuroblastoma.

PubMed

Kushner, Brian H; Roberts, Stephen S; Friedman, Danielle N; Kuk, Deborah; Ostrovnaya, Irina; Modak, Shakeel; Kramer, Kim; Basu, Ellen M; Cheung, Nai-Kong V

2015-06-15

Osteochondromas are benign bony protrusions that can be spontaneous or associated with radiotherapy (RT). Current treatment of high-risk neuroblastoma includes dose-intensive chemotherapy, local RT, an anti-GD2 monoclonal antibody (MoAb), and isotretinoin. Late effects are emerging. The authors examined osteochondromas in 362 patients who were aged <10 years when diagnosed with neuroblastoma, had received a MoAb plus isotretinoin since 2000, and had survived >24 months from the time of the first dose of the MoAb. The incidence rate of osteochondroma was determined using the competing risks approach, in which the primary event was osteochondroma calculated from the date of neuroblastoma diagnosis and the competing event was death without osteochondroma. A total of 21 osteochondroma cases were found among 14 patients who were aged 5.7 to 15.3 years (median, 10.4 years) and 3.1 to 11.2 years (median, 8.2 years) from the time of neuroblastoma diagnosis. The cumulative incidence rate was 0.6% at 5 years and 4.9% at 10 years from the neuroblastoma diagnosis. Nine osteochondromas were revealed incidentally during assessments of neuroblastoma disease status or bone age. Thirteen osteochondromas were detected outside RT portals and had characteristics of spontaneous forms. Complications were limited to pain necessitating surgical resection in 3 patients, but follow-up was short at 0.3 to 7.7 years (median, 3.5 years). Osteochondromas in long-term survivors of neuroblastoma should be expected because these benign growths can be related to RT and these patients undergo radiologic studies over years, are monitored for late toxicities through and beyond adolescence, and receive special attention (because of concerns about disease recurrence) if they develop a bony protuberance. A pathogenic role for chemotherapy, anti-GD2 MoAbs, or isotretinoin remains speculative. © 2015 American Cancer Society.

Approach to cardio-oncologic patients with special focus on patients with cardiac implantable electronic devices planned for radiotherapy: results of the European Heart Rhythm Association survey.

PubMed

Lenarczyk, Radoslaw; Potpara, Tatjana S; Haugaa, Kristina H; Deharo, Jean-Claude; Hernandez-Madrid, Antonio; Del Carmen Exposito Pineda, Maria; Kiliszek, Marek; Dagres, Nikolaos

2017-09-01

The aim of this European Heart Rhythm Association (EHRA) survey was to evaluate clinical practice regarding cardio-oncologic patients, with special focus on patients with cardiac implantable electronic devices (CIEDs) planned for anticancer radiotherapy (RT), among members of the EHRA electrophysiology research network. Of the 36 responding centres, 89% managed patients who were diagnosed or treated oncologically, and this diagnosis affected 1-5% of cardiovascular patients in majority of centres (57%). The main side effects of anticancer therapy in patients treated by cardiologists were thromboembolic complications and left ventricular dysfunction (both reported as 'frequent' by 43% of the centres). The main agents associated with complications were anthracyclines, RT, and monoclonal antibodies. Echocardiography was the most common method of screening for cardiovascular complications (93%), and 10% of the centres did not routinely screen for treatment-induced cardiotoxicity. Opinions on the safe radiation dose, methods of device shielding, and risk calculation prior to RT in CIED patients differed among centres. Precaution measures in high-risk CIED patients were very heterogeneous among centres. Our survey has shown that the awareness of cardiac consequences of anticancer therapy is high, despite relatively low proportion of patients treated oncologically among all cardiovascular patients. There is a consensus of which screening methods should be used for cardiotoxicity of anticancer treatment, but the apprehension of screening necessity is low. Methods of risk assessment and safety measures in CIED patients undergoing RT are very heterogeneous among the European centres, underscoring the need for standardization of the approach to cardio-oncologic patients. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For Permissions, please email: journals.permissions@oup.com.

Impact of obesity on outcomes after definitive dose-escalated intensity-modulated radiotherapy for localized prostate cancer.

PubMed

Wang, Lora S; Murphy, Colin T; Ruth, Karen; Zaorsky, Nicholas G; Smaldone, Marc C; Sobczak, Mark L; Kutikov, Alexander; Viterbo, Rosalia; Horwitz, Eric M

2015-09-01

Previous publications have demonstrated conflicting results regarding body mass index (BMI) and prostate cancer (CaP) outcomes after definitive radiotherapy (RT) before the dose escalation era. The goal of the current study was to determine whether increasing BMI was associated with outcomes in men with localized CaP who were treated with dose-escalated RT. The authors identified patients with localized (T1b-T4N0M0) CaP who were treated with definitive intensity-modulated RT and image-guided RT from 2001 through 2010. BMI was analyzed as a continuous variable. Adjusting for confounders, multivariable competing risk and Cox proportional hazards regression models were used to assess the association between BMI and the risk of biochemical failure (BF), distant metastases (DM), cause-specific mortality (CSM), and overall mortality. Of the 1442 patients identified, approximately 20% had a BMI <25 kg/m(2) , 48% had a BMI of 25 to 29.9 kg/m(2) , 23% had a BMI of 30 to 34.9 kg/m(2) , 6% had a BMI of 35 to 39.9 kg/m(2) , and 4% had a BMI of ≥40 kg/m(2) . The median follow-up was 47.6 months (range, 1-145 months), with a median age of 68 years (range, 36-89 years). The median dose was 78 grays (range, 76-80 grays) and 30% of patients received androgen deprivation therapy. Increasing BMI was found to be inversely associated with age (P<.001) and pretreatment prostate-specific antigen level (P = .018). On multivariable analysis, increasing BMI was associated with an increased risk of BF (hazard ratio [HR], 1.03; 95% confidence interval [95% CI], 1.00-1.07 [P = .042]), DM (HR, 1.07; 95% CI, 1.02-1.11 [P = .004]), CSM (HR, 1.15; 95% CI, 1.07-1.23 [P<.001]), and overall mortality (HR, 1.05; 95% CI, 1.02-1.08 [P = .004]). For patients with CaP receiving dose-escalated intensity-modulated RT with daily image-guidance, increasing BMI appears to be associated with an increased risk of BF, DM, CSM, and overall mortality. © 2015 American Cancer Society.

Characterization of the efficiency and uncertainty of skimmed milk flocculation for the simultaneous concentration and quantification of water-borne viruses, bacteria and protozoa.

PubMed

Gonzales-Gustavson, Eloy; Cárdenas-Youngs, Yexenia; Calvo, Miquel; da Silva, Marcelle Figueira Marques; Hundesa, Ayalkibet; Amorós, Inmaculada; Moreno, Yolanda; Moreno-Mesonero, Laura; Rosell, Rosa; Ganges, Llilianne; Araujo, Rosa; Girones, Rosina

2017-03-01

In this study, the use of skimmed milk flocculation (SMF) to simultaneously concentrate viruses, bacteria and protozoa was evaluated. We selected strains of faecal indicator bacteria and pathogens, such as Escherichia coli and Helicobacter pylori. The viruses selected were adenovirus (HAdV 35), rotavirus (RoV SA-11), the bacteriophage MS2 and bovine viral diarrhoea virus (BVDV). The protozoa tested were Acanthamoeba, Giardia and Cryptosporidium. The mean recoveries with q(RT)PCR were 66% (HAdV 35), 24% (MS2), 28% (RoV SA-11), 15% (BVDV), 60% (E. coli), 30% (H. pylori) and 21% (Acanthamoeba castellanii). When testing the infectivity, the mean recoveries were 59% (HAdV 35), 12% (MS2), 26% (RoV SA-11) and 0.7% (BVDV). The protozoa Giardia lamblia and Cryptosporidium parvum were studied by immunofluorescence with recoveries of 18% and 13%, respectively. Although q(RT)PCR consistently showed higher quantification values (as expected), q(RT)PCR and the infectivity assays showed similar recoveries for HAdV 35 and RoV SA-11. Additionally, we investigated modelling the variability and uncertainty of the recovery with this method to extrapolate the quantification obtained by q(RT)PCR and estimate the real concentration. The 95% prediction intervals of the real concentration of the microorganisms inoculated were calculated using a general non-parametric bootstrap procedure adapted in our context to estimate the technical error of the measurements. SMF shows recoveries with a low variability that permits the use of a mathematical approximation to predict the concentration of the pathogen and indicator with acceptable low intervals. The values of uncertainty may be used for a quantitative microbial risk analysis or diagnostic purposes. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Detection of Respiratory Viruses in Sputum from Adults by Use of Automated Multiplex PCR

PubMed Central

Walsh, Edward E.; Formica, Maria A.; Falsey, Ann R.

2014-01-01

Respiratory tract infections (RTI) frequently cause hospital admissions among adults. Diagnostic viral reverse transcriptase PCR (RT-PCR) of nose and throat swabs (NTS) is useful for patient care by informing antiviral use and appropriate isolation. However, automated RT-PCR systems are not amenable to utilizing sputum due to its viscosity. We evaluated a simple method of processing sputum samples in a fully automated respiratory viral panel RT-PCR assay (FilmArray). Archived sputum and NTS samples collected in 2008-2012 from hospitalized adults with RTI were evaluated. A subset of sputum samples positive for 10 common viruses by a uniplex RT-PCR was selected. A sterile cotton-tip swab was dunked in sputum, swirled in 700 μL of sterile water (dunk and swirl method) and tested by the FilmArray assay. Quantitative RT-PCR was performed on “dunked” sputum and NTS samples for influenza A (Flu A), respiratory syncytial virus (RSV), coronavirus OC43 (OC43), and human metapneumovirus (HMPV). Viruses were identified in 31% of 965 illnesses using a uniplex RT-PCR. The sputum sample was the only sample positive for 105 subjects, including 35% (22/64) of influenza cases and significantly increased the diagnostic yield of NTS alone (302/965 [31%] versus 197/965 [20%]; P = 0.0001). Of 108 sputum samples evaluated by the FilmArray assay using the dunk and swirl method, 99 (92%) were positive. Quantitative RT-PCR revealed higher mean viral loads in dunked sputum samples compared to NTS samples for Flu A, RSV, and HMPV (P = 0.0001, P = 0.006, and P = 0.011, respectively). The dunk and swirl method is a simple and practical method for reliably processing sputum samples in a fully automated PCR system. The higher viral loads in sputa may increase detection over NTS testing alone. PMID:25056335

The risk-taking and self-harm inventory for adolescents: development and psychometric evaluation.

PubMed

Vrouva, Ioanna; Fonagy, Peter; Fearon, Pasco R M; Roussow, Trudie

2010-12-01

In this study, we report on the development and psychometric evaluation of the Risk-Taking (RT) and Self-Harm (SH) Inventory for Adolescents (RTSHIA), a self-report measure designed to assess adolescent RT and SH in community and clinical settings. 651 young people from secondary schools in England ranging in age from 11.6 years to 18.7 years and 71 young people referred to mental health services for SH behavior in London between the ages of 11.9 years and 17.5 years completed the RTSHIA along with standardized measures of adolescent psychopathology. Two factors emerged from the principal axis factoring, and RT and SH were further validated by a confirmatory factor analysis as related, but different, constructs, rather than elements of a single continuum. Inter-item and test-retest reliabilities were high for both components (Cronbach's α = .85, ru = .90; Cronbach's α .93, ru = .87), and considerable evidence emerged in support of the measure's convergent, concurrent, and divergent validity. The findings are discussed with regard to potential usefulness of the RTSHIA for research and clinical purposes with adolescents.

Characteristics and Outcomes of Pediatric Patients With Ebola Virus Disease Admitted to Treatment Units in Liberia and Sierra Leone: A Retrospective Cohort Study.

PubMed

Smit, Michael A; Michelow, Ian C; Glavis-Bloom, Justin; Wolfman, Vanessa; Levine, Adam C

2017-02-01

The clinical and virologic characteristics of Ebola virus disease (EVD) in children have not been thoroughly documented. Consecutive children aged <18 years with real-time polymerase chain reaction (RT-PCR)-confirmed EVD were enrolled retrospectively in 5 Ebola treatment units in Liberia and Sierra Leone in 2014/2015. Data collection and medical management were based on standardized International Medical Corps protocols. We performed descriptive statistics, multivariate logistic regression, and Kaplan-Meier survival analyses. Of 122 children enrolled, the median age was 7 years and one-third were aged <5 years. The female-to-male ratio was 1.3. The most common clinical features at triage and during hospitalization were fever, weakness, anorexia, and diarrhea, although 21% of patients were initially afebrile and 6 patients remained afebrile. Bleeding was rare at presentation (5%) and manifested subsequently in fewer than 50%. The overall case fatality rate was 57%. Factors associated with death in bivariate analyses were age <5 years, bleeding at any time during hospitalization, and high viral load. After adjustment with logistic regression modeling, the odds of death were 14.8-fold higher if patients were aged <5 years, 5-fold higher if the patient had any evidence of bleeding, and 5.2-fold higher if EVD RT-PCR cycle threshold value was ≤20. Plasmodium parasitemia had no impact on EVD outcomes. Age <5 years, bleeding, and high viral loads were poor prognostic indicators of children with EVD. Research to understand mechanisms of these risk factors and the impact of dehydration and electrolyte imbalance will improve health outcomes. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Diurnal thermoregulatory responses in pregnant Yankasa ewes to the dry season in a tropical Savannah.

PubMed

Yaqub, Lukuman Surakat; Ayo, Joseph Olusegun; Kawu, Muhammad Umar; Rekwot, Peter Ibrahim

2017-08-01

The study investigated concomitant effect of gestation and high ambient temperature under a tropical environment on rectal temperature (RT), respiratory rate (RR) and heart rate (HR) responses in Yankasa ewes. Twenty Yankasa ewes, consisting of ten pregnant and ten non-pregnant ewes, were used for the study. Ewes were synchronised and bred, such that each gestation phase coincided with different periods of the dry-seasons, early-gestation (cold/harmattan), mid-gestation (peak hot-dry) and late-gestation (late hot-dry). The RT, RR and HR were recorded thrice, 2 days apart at middle of each gestation period at 06:00, 14:00 and 18:00 h, concurrently with dry- (DBT) and wet-bulb temperatures of the experimental pen. The DBT was positively correlated with RT, RR during the different gestation stages. The RT significantly (P < 0.001) increased with the hour of day, regardless of the physiological status of the ewes, with peak at 14:00 h. Values of RT and RR were higher (P < 0.05) in pregnant than non-pregnant ewes at mid- and late-gestation, respectively. Mean RT was lower (P < 0.001) at 06:00 h in pregnant than non-pregnant ewes at early-gestation (cold-dry). The HR was (P < 0.05) higher in pregnant than non-pregnant ewes during the different gestation phases. In conclusion, ambient temperature and gestation concomitantly modulate diurnal thermoregulatory responses of the ewes to hot-dry season. Adequate measures should be adopted to mitigate adverse impact of prolonged high RR on the dam and the foetus during the peak of ambient temperature prevailing in the tropical Savannah environment.

Changes in heart rate and heart rate variability during transportation of horses by road and air.

PubMed

Ohmura, Hajime; Hobo, Seiji; Hiraga, Atsushi; Jones, James H

2012-04-01

To determine the influence of transportation by road and air on heart rate (HR) and HR variability (HRV) in horses. Animals-6 healthy horses. ECG recordings were obtained from horses before (quarantine with stall rest [Q]; 24 hours) and during a journey that included transportation by road (RT; 4.5 hours), waiting on the ground in an air stall (W; 5.5 hours), and transportation by air (AT; 11 hours); HR was determined, and HRV indices of autonomic nervous activity (low-frequency [LF; 0.01 to 0.07 Hz] and high-frequency [HF; 0.07 to 0.6 Hz] power) were calculated. Mean ± SD HRs during Q, RT, W, and AT were 38.9 ± 1.5 beats/min, 41.7 ± 5.6 beats/min, 41.5 ± 4.3 beats/min, and 48.8 ± 5.6 beats/min, respectively; HR during AT was significantly higher than HR during Q. The LF power was significantly higher during Q (3,454 ± 1,087 milliseconds(2)) and AT (3,101 ± 567 milliseconds(2)) than it was during RT (1,824 ± 432 milliseconds(2)) and W (2,072 ± 616 milliseconds(2)). During Q, RT, W, and AT, neither HF powers (range, 509 to 927 milliseconds(2)) nor LF:HF ratios (range, 4.1 to 6.2) differed significantly. The HR during RT was highly correlated with LF power (R(2) = 0.979), and HR during AT was moderately correlated with the LF:HF ratio (R(2) = 0.477). In horses, HR and HRV indices during RT and AT differed, suggesting that exposure to different stressors results in different autonomic nervous influences on HR.

Radiation therapy dose is associated with improved survival for unresected anaplastic thyroid carcinoma: Outcomes from the National Cancer Data Base.

PubMed

Pezzi, Todd A; Mohamed, Abdallah S R; Sheu, Tommy; Blanchard, Pierre; Sandulache, Vlad C; Lai, Stephen Y; Cabanillas, Maria E; Williams, Michelle D; Pezzi, Christopher M; Lu, Charles; Garden, Adam S; Morrison, William H; Rosenthal, David I; Fuller, Clifton D; Gunn, G Brandon

2017-05-01

The outcomes of patients with unresected anaplastic thyroid carcinoma (ATC) from the National Cancer Data Base (NCDB) were assessed, and potential correlations were explored between radiation therapy (RT) dose and overall survival (OS). The study cohort was comprised of patients who underwent either no surgery or grossly incomplete resection. Correlates of OS were explored using univariate analysis and multivariable analysis (MVA). In total, 1288 patients were analyzed. The mean patient age was 70.2 years, 59.7% of patients were women, and 47.6% received neck RT. The median OS was 2.27 months, and 11% of patients remained alive at 1 year. A positive RT dose-survival correlation was observed for the entire study cohort, for those who received systemic therapy, and for those with stage IVA/IVB and IVC disease. On MVA, older age (hazard ratio [HR], 1.317; 95% confidence interval [CI], 1.137-1.526), ≥ 1 comorbidity (HR, 1.587; 95% CI, 1.379-1.827), distant metastasis (HR, 1.385; 95% CI, 1.216-1.578), receipt of systemic therapy (HR, 0.637; 95% CI, 0.547-0.742), and receipt of RT compared with no RT (<45 grays [Gy]:HR, 0.843; 95% CI, 0.718-0.988; 45-59.9 Gy: HR, 0.596; 95% CI, 0.479-0.743; 60-75 Gy: HR, 0.419; 95% CI, 0.339-0.517) correlated with OS. The RT dose-survival correlation for patients who received higher (60-75 Gy) versus lower (45-59.9 Gy) therapeutic doses was confirmed by propensity-score matching. Survival was poor in this cohort of patients with unresected ATC, and more effective therapies are needed. However, the association of RT dose with OS highlights the importance of identifying patients with unresected ATC who may still yet benefit from multimodal locoregional treatment that incorporates higher dose RT. Cancer 2017;123:1653-1661. © 2017 American Cancer Society. © 2016 American Cancer Society.

Positron Emission Tomography/Computed Tomography Assessment After Immunochemotherapy and Irradiation Using the Lugano Classification Criteria in the IELSG-26 Study of Primary Mediastinal B-Cell Lymphoma

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

Ceriani, Luca, E-mail: luca.ceriani@eoc.ch; Martelli, Maurizio; Gospodarowicz, Maria K.

Purpose: To assess the predictive value of {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) for disease recurrence after immunochemotherapy (R-CHT) and mediastinal irradiation (RT), using the recently published criteria of the Lugano classification to predict outcomes for patients with primary mediastinal large B-cell lymphoma. Methods and Materials: Among 125 patients prospectively enrolled in the IELSG-26 study, 88 were eligible for central review of PET/CT scans after completion of RT. Responses were evaluated using the 5-point Deauville scale at the end of induction R-CHT and after consolidation RT. According to the Lugano classification, a complete metabolic response (CMR) was defined bymore » a Deauville score (DS) ≤3. Results: The CMR (DS1, -2, or -3) rate increased from 74% (65 patients) after R-CHT to 89% (78 patients) after consolidation RT. Among the 10 patients (11%) with persistently positive scans, the residual uptake after RT was slightly higher than the liver uptake in 6 patients (DS4; 7%) and markedly higher in 4 patients (DS5; 4%): these patients had a significantly poorer 5-year progression-free survival and overall survival. At a median follow-up of 60 months (range, 35-107 months), no patients with a CMR after RT have relapsed. Among the 10 patients who did not reach a CMR, 3 of the 4 patients (positive predictive value, 75%) with DS5 after RT had subsequent disease progression (within the RT volume in all cases) and died. All patients with DS4 had good outcomes without recurrence. Conclusions: All the patients obtaining a CMR defined as DS ≤3 remained progression-free at 5 years, confirming the excellent negative predictive value of the Lugano classification criteria in primary mediastinal large B-cell lymphoma patients. The few patients with DS4 also had an excellent outcome, suggesting that they do not necessarily require additional therapy, because the residual {sup 18}F-fluorodeoxyglucose uptake may not reflect persistent lymphoma.« less

Predictors of post-treatment stenosis in cervical esophageal cancer undergoing high-dose radiotherapy

PubMed Central

Kim, Jun Won; Kim, Tae Hyung; Kim, Jie-Hyun; Lee, Ik Jae

2018-01-01

AIM To evaluate toxicity and treatment outcome of high-dose radiotherapy (RT) for cervical esophageal cancer (CEC). METHODS We reviewed a total of 62 consecutive patients who received definitive RT for stage I to III cervical esophageal cancer between 2001 and 2015. Patients who received < 45 Gy, treated for lesions below sternal notch, treated with palliative aim, treated with subsequent surgical resection, or diagnosed with synchronous hypopharyngeal cancer were excluded. Treatment failures were divided into local (occurring within the RT field), outfield-esophageal, and regional [occurring in regional lymph node(s)] failures. Factors predictive of esophageal stenosis requiring endoscopic dilation were analyzed. RESULTS Grade 1, 2, and 3 esophagitis occurred in 19 (30.6%), 39 (62.9%), and 4 patients (6.5%), respectively, without grade ≥ 4 toxicities. Sixteen patients (25.8%) developed post-RT stenosis, of which 7 cases (43.8%) were malignant. Four patients (6.5%) developed tracheoesophageal fistula (TEF), of which 3 (75%) cases were malignant. Factors significantly correlated with post-RT stenosis were stage T3/4 (P = 0.001), complete circumference involvement (P < 0.0001), stenosis at diagnosis (P = 0.024), and endoscopic complete response (P = 0.017) in univariate analysis, while complete circumference involvement was significant in multivariate analysis (P = 0.003). A higher dose (≥ 60 Gy) was not associated with occurrence of post-RT stenosis or TEF. With a median follow-up of 24.3 (range, 3.4-152) mo, the 2 y local control, outfield esophageal control, progression-free survival, and overall survival (OS) rates were 78.9%, 90.2%, 49.6%, and 57.3%, respectively. Factors significantly correlated with OS were complete circumference involvement (P = 0.023), stenosis at diagnosis (P < 0.0001), and occurrence of post-RT stenosis or TEF (P < 0.001) in univariate analysis, while stenosis at diagnosis (P = 0.004) and occurrence of post-RT stenosis or TEF (P = 0.023) were significant in multivariate analysis. CONCLUSION Chemoradiation for CEC was well tolerated, and a higher dose was not associated with stenosis. Patients with complete circumferential involvement require close follow-up. PMID:29467556

Predictors of post-treatment stenosis in cervical esophageal cancer undergoing high-dose radiotherapy.

PubMed

Kim, Jun Won; Kim, Tae Hyung; Kim, Jie-Hyun; Lee, Ik Jae

2018-02-21

To evaluate toxicity and treatment outcome of high-dose radiotherapy (RT) for cervical esophageal cancer (CEC). We reviewed a total of 62 consecutive patients who received definitive RT for stage I to III cervical esophageal cancer between 2001 and 2015. Patients who received < 45 Gy, treated for lesions below sternal notch, treated with palliative aim, treated with subsequent surgical resection, or diagnosed with synchronous hypopharyngeal cancer were excluded. Treatment failures were divided into local (occurring within the RT field), outfield-esophageal, and regional [occurring in regional lymph node(s)] failures. Factors predictive of esophageal stenosis requiring endoscopic dilation were analyzed. Grade 1, 2, and 3 esophagitis occurred in 19 (30.6%), 39 (62.9%), and 4 patients (6.5%), respectively, without grade ≥ 4 toxicities. Sixteen patients (25.8%) developed post-RT stenosis, of which 7 cases (43.8%) were malignant. Four patients (6.5%) developed tracheoesophageal fistula (TEF), of which 3 (75%) cases were malignant. Factors significantly correlated with post-RT stenosis were stage T3/4 ( P = 0.001), complete circumference involvement ( P < 0.0001), stenosis at diagnosis ( P = 0.024), and endoscopic complete response ( P = 0.017) in univariate analysis, while complete circumference involvement was significant in multivariate analysis ( P = 0.003). A higher dose (≥ 60 Gy) was not associated with occurrence of post-RT stenosis or TEF. With a median follow-up of 24.3 (range, 3.4-152) mo, the 2 y local control, outfield esophageal control, progression-free survival, and overall survival (OS) rates were 78.9%, 90.2%, 49.6%, and 57.3%, respectively. Factors significantly correlated with OS were complete circumference involvement ( P = 0.023), stenosis at diagnosis ( P < 0.0001), and occurrence of post-RT stenosis or TEF ( P < 0.001) in univariate analysis, while stenosis at diagnosis ( P = 0.004) and occurrence of post-RT stenosis or TEF ( P = 0.023) were significant in multivariate analysis. Chemoradiation for CEC was well tolerated, and a higher dose was not associated with stenosis. Patients with complete circumferential involvement require close follow-up.

Local and systemic oxidant/antioxidant status before and during lung cancer radiotherapy

PubMed Central

Crohns, Marika; Saarelainen, Seppo; Kankaanranta, Hannu; Moilanen, Eeva; Alho, Hannu; Kellokumpu-Lehtinen, Pirkko

2009-01-01

To examine local and systemic oxidative status of lung cancer (LC) and oxidant effects of radiotherapy (RT), this study evaluated antioxidants and markers of oxidative and nitrosative stress in bronchoalveolar lavage (BAL) fluid and in the blood of 36 LC patients and 36 non-cancer controls at baseline and during and after RT for LC. LC patients had higher baseline serum urate, plasma nitrite and lower serum oxidized proteins than controls (p = 0.016, p < 0.001 and p = 0.027, respectively), but BAL fluid oxidative stress markers were similar. RT tended to raise some antioxidants, however, significant increases were seen in serum urate, conjugated dienes and TBARS (p = 0.044, p = 0.034 and p = 0.004, respectively) 3 months after RT. High urate at baseline may compensate against the oxidative stress caused by LC. RT shifts the oxidant/antioxidant balance towards lipid peroxidation, although the antioxidant defense mechanisms of the body appear to counteract the increased oxidative stress rather effectively. PMID:19444690

Does Quality of Radiation Therapy Predict Outcomes of Multicenter Cooperative Group Trials? A Literature Review

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

Fairchild, Alysa, E-mail: alysa.fairchild@albertahealthservices.ca; Straube, William; Laurie, Fran

2013-10-01

Central review of radiation therapy (RT) delivery within multicenter clinical trials was initiated in the early 1970s in the United States. Early quality assurance publications often focused on metrics related to process, logistics, and timing. Our objective was to review the available evidence supporting correlation of RT quality with clinical outcomes within cooperative group trials. A MEDLINE search was performed to identify multicenter studies that described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicenter studies (1980-2012) were identified, plus one Patterns of Care Study. Diseasemore » sites were hematologic, head and neck, lung, breast, and pancreas. Between 0 and 97% of treatment plans received an overall grade of acceptable. In 7 trials, failure rates were significantly higher after inadequate versus adequate RT. Five of 9 and 2 of 5 trials reported significantly worse overall and progression-free survival after poor-quality RT, respectively. One reported a significant correlation, and 2 reported nonsignificant trends toward increased toxicity with noncompliant RT. Although more data are required, protocol-compliant RT may decrease failure rates and increase overall survival and likely contributes to the ability of collected data to answer the central trial question.« less

Does Quality of Radiotherapy Predict Outcomes of Multicentre Cooperative Group Trials? A Literature Review

PubMed Central

Fairchild, Alysa; Straube, William; Laurie, Fran; Followill, David

2013-01-01

Central review of radiotherapy (RT) delivery within multicentre clinical trials was initiated in the early 1970’s in the USA. Early quality assurance (QA) publications often focused on metrics related to process, logistics and timing. Our objective was to review the available evidence supporting correlation of RT quality with clinical outcomes within cooperative group trials. Medline search was performed to identify multicentre studies which described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicentre studies (1980–2012) were identified, plus one Patterns of Care Study. Disease sites were hematologic, head and neck, lung, breast and pancreas. Between 0% and 97% of treatment plans received an overall grade of acceptable. In seven trials, failure rates were significantly higher after inadequate versus adequate RT. 5/9 and 2/5 trials reported significantly worse overall and progression-free survival after poor quality RT, respectively. One reported a significant correlation and two reported non-significant trends towards increased toxicity with non-compliant RT. Although more data are required, protocol-compliant RT may decrease failure rates and increase overall survival and likely contributes to the ability of collected data to answer the central trial question. PMID:23683829

Analysis of Prognostic Factors and Patterns of Recurrence in Patients With Pathologic Stage III Endometrial Cancer

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

Patel, Samir; Portelance, Lorraine; Gilbert, Lucy

2007-08-01

Purpose: To retrospectively assess prognostic factors and patterns of recurrence in patients with pathologic Stage III endometrial cancer. Methods and Materials: Between 1989 and 2003, 107 patients with pathologic International Federation of Gynecology and Obstetrics Stage III endometrial adenocarcinoma confined to the pelvis were treated at our institution. Adjuvant radiotherapy (RT) was delivered to 68 patients (64%). The influence of multiple patient- and treatment-related factors on pelvic and distant control and overall survival (OS) was evaluated. Results: Median follow-up for patients at risk was 41 months. Five-year actuarial OS was significantly improved in patients treated with adjuvant RT (68%) comparedmore » with those with resection alone (50%; p = 0.029). Age, histology, grade, uterine serosal invasion, adnexal involvement, number of extrauterine sites, and treatment with adjuvant RT predicted for improved survival in univariate analysis. Multivariate analysis revealed that grade, uterine serosal invasion, and treatment with adjuvant RT were independent predictors of survival. Five-year actuarial pelvic control was improved significantly with the delivery of adjuvant RT (74% vs. 49%; p = 0.011). Depth of myometrial invasion and treatment with adjuvant RT were independent predictors of pelvic control in multivariate analysis. Conclusions: Multiple prognostic factors predicting for the outcome of pathologic Stage III endometrial cancer patients were identified in this analysis. In particular, delivery of adjuvant RT seems to be a significant independent predictor for improved survival and pelvic control, suggesting that pelvic RT should be routinely considered in the management of these patients.« less

The Programming Optimization of Capacitorless 1T DRAM Based on the Dual-Gate TFET

NASA Astrophysics Data System (ADS)

Li, Wei; Liu, Hongxia; Wang, Shulong; Chen, Shupeng; Wang, Qianqiong

2017-09-01

The larger volume of capacitor and higher leakage current of transistor have become the inherent disadvantages for the traditional one transistor (1T)-one capacitor (1C) dynamic random access memory (DRAM). Recently, the tunneling FET (TFET) is applied in DRAM cell due to the low off-state current and high switching ratio. The dual-gate TFET (DG-TFET) DRAM cell with the capacitorless structure has the superior performance-higher retention time (RT) and weak temperature dependence. But the performance of TFET DRAM cell is sensitive to programming condition. In this paper, the guideline of programming optimization is discussed in detail by using simulation tool—Silvaco Atlas. Both the writing and reading operations of DG-TFET DRAM depend on the band-to-band tunneling (BTBT). During the writing operation, the holes coming from BTBT governed by Gate2 are stored in potential well under Gate2. A small negative voltage is applied at Gate2 to retain holes for a long time during holding "1". The BTBT governed by Gate1 mainly influences the reading current. Using the optimized programming condition, the DG-TFET DRAM obtains the higher current ratio of reading "1" to reading "0" (107) and RT of more than 2 s. The higher RT reduces the refresh rate and dynamic power consumption of DRAM.

TGF{beta}1 polymorphisms and late clinical radiosensitivity in patients treated for gynecologic tumors

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

Ruyck, Kim de; Van Eijkeren, Marc; Claes, Kathleen

2006-07-15

Purpose: To investigate the association between six transforming growth factor {beta}1 gene (TGF{beta}1) polymorphisms (-1.552delAGG, -800G>A, -509C>T, Leu10Pro, Arg25Pro, Thr263Ile) and the occurrence of late normal tissue reactions after gynecologic radiotherapy (RT). Methods and Materials: Seventy-eight women with cervical or endometrial cancer and 140 control individuals were included in the study. According to the Common Terminology Criteria for Adverse Events version 3.0 (CTCAEv3.0) scale, 25 patients showed late adverse RT reactions (CTC2+), of whom 11 had severe complications (CTC3+). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), single base extension and genotyping assays were performed to examine the polymorphic sites inmore » TGF{beta}1. Results: Homozygous variant -1.552delAGG, -509TT, and 10Pro genotypes were associated with the risk of developing late severe RT reactions. Triple (variant) homozygous patients had a 3.6 times increased risk to develop severe RT reactions (p = 0.26). Neither the -800A allele, nor the 25Pro allele or the 263Ile allele were associated with clinical radiosensitivity. There was perfect linkage disequilibrium (LD) between the -1.552delAGG and the -509C>T polymorphisms, and tight LD between the -1.552/-509 and the Leu10Pro polymorphisms. Haplotype analysis revealed two major haplotypes but could not distinguish radiosensitive from nonradiosensitive patients. Conclusions: The present study shows that homozygous variant TGF{beta}1 -1.552delAGG, -509TT, and 10Pro genotypes may be associated with severe clinical radiosensitivity after gynecologic RT.« less

Whole Neuraxis Irradiation to Address Central Nervous System Relapse in High-Risk Neuroblastoma

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

Croog, Victoria J., E-mail: vcroog@sibley.or; Kramer, Kim; Cheung, Nai-Kong V.

Background: As systemic control of high-risk neuroblastoma (NB) has improved, relapse in the central nervous system (CNS) is an increasingly recognized entity that carries a grim prognosis. This study describes the use of craniospinal irradiation (CSI) for CNS relapse and compares outcomes to patients who received focal radiotherapy (RT). Methods: A retrospective query identified 29 children with NB treated at Memorial Sloan-Kettering Cancer Center since 1987 who received RT for CNS relapse. At CNS relapse, 16 patients received CSI (median dose, 2160cGy), and 13 received focal RT. Of those who underwent CSI, 14 (88%) received intra-Ommaya (IO) radioimmunotherapy (RIT); onemore » patient in the non-CSI cohort received IO-RIT. Results: Patient characteristics were similar between the groups. Time to CNS relapse was 20 and 17 months for the CSI and non-CSI cohorts, respectively. At a median follow-up of 28 months, 12 patients (75%) in the CSI group are alive without CNS disease, including two patients with isolated skeletal relapse. Another patient is alive without disease after a brain relapse was retreated with RT. Three patients died-one with no NB at autopsy, one of CNS disease, and one of systemic disease. The two patients who died of NB did not receive IO-RIT. All 13 patients in the non-CSI cohort died at a median of 8.8 months. Conclusions: Low-dose CSI together with IO-RIT provides durable CNS remissions and improved survival compared with focal RT and conventional therapies. Further evaluation of long-term NB survivors after CSI is warranted to determine the treatment consequences for this cohort.« less

Use of bDNA testing in the immunologically nonresponding patient who has a low or undetectable viral load by RT-PCR testing.

PubMed

Grimes, Richard M; Lewis, Stanley T; Visnegarwala, Fehmida; Goodly, Joseph; Sutton, Richard; Rodriguez-Barradas, Maria

2003-01-01

Studies have shown that reverse transcription-polymerase chain reaction (RT-PCR) technology underquantifies viral loads in patients with non-B clades of HIV-1. Testing with bDNA technology gave higher viral loads in these subtypes. A study was conducted to determine whether virologically responding patients on HAART who were not immunologically responding would have higher viral loads using bDNA technology and whether these differences were due to non-B clades. Forty-eight patients receiving HAART for more than 6 months who were having inappropriate immunologic responses in spite of undetectable or very low viral loads determined by RT-PCR (<3000 copies by Roche Amplicor 1.0) were studied. These patients had bDNA viral loads performed. All patients who had bDNA viral loads equivalent to >3000 by RT-PCR had clade and genotypic studies performed. Fifteen patients had viral loads by bDNA that were equivalent to >3000 copies by RT-PCR. Four of these were found to have non-B clades (one D clade and three AG clade). The D clade patient had multidrug resistance; none of the AG clade patients had resistance. Of the remaining 11 patients, virus could not be recovered from 2 and 9 had a B clade. Six of these nine had genotypic resistance to HAART drugs. bDNA testing may be useful in the immunologically nonresponding patient.

Temperature affects thrombolytic efficacy using rt-PA and eptifibatide, an in vitro study.

PubMed

Meunier, Jason M; Chang, Wan-Tsu W; Bluett, Brent; Wenker, Evan; Lindsell, Christopher J; Shaw, George J

2012-09-01

The potential for hypothermia as a neuroprotectant during stroke has led to its increase in clinical use. At the same time, combination pharmaceutical therapies for ischemic stroke using recombinant tissue plasminogen activator (rt-PA), and GP IIb-IIIa inhibitors, such as Eptifibatide (Epf ), are under study. However, there is little data on how the reactions triggered by these agents are impacted by temperature. Here, clot lysis during exposure to the combination of rt-PA and Epf is measured in an in vitro human clot model at hypothermic temperatures. The hypothesis is that lytic efficacy of rt-PA and Epf decreases with decreasing temperature. Whole blood clots from 31 volunteers were exposed to rt-PA (0.5 μg/mL) and Epf (0.63 μg/mL) in human fresh-frozen plasma (rt-PA+Epf ), rt-PA alone in plasma (rt-PA Alone), or to plasma alone (Control), at temperatures from 30°C to 37°C, for 30 minutes. Clot lysis was measured using a microscopic imaging technique; the mean fractional clot loss (FCL) at 30 minutes was used to determine lytic efficacy. Temperature had a significant impact on FCL in clots exposed to rt-PA+Epf, with the FCL being lower at 30°C to 36°C than at 37°C. The FCL remained significantly higher for rt-PA+Epf–treated clots than Controls regardless of temperature, with the exception of measurements made at 30°C when no significant differences in the FCL were observed between groups. The use of hypothermia as a neuroprotectant may negatively impact the therapeutic benefit of thrombolytic agents.

Temperature Affects Thrombolytic Efficacy Using rt-PA and Eptifibatide, an In Vitro Study

PubMed Central

Chang, Wan-Tsu W.; Bluett, Brent; Wenker, Evan; Lindsell, Christopher J.; Shaw, George J.

2012-01-01

The potential for hypothermia as a neuroprotectant during stroke has led to its increase in clinical use. At the same time, combination pharmaceutical therapies for ischemic stroke using recombinant tissue plasminogen activator (rt-PA), and GP IIb-IIIa inhibitors, such as Eptifibatide (Epf ), are under study. However, there is little data on how the reactions triggered by these agents are impacted by temperature. Here, clot lysis during exposure to the combination of rt-PA and Epf is measured in an in vitro human clot model at hypothermic temperatures. The hypothesis is that lytic efficacy of rt-PA and Epf decreases with decreasing temperature. Whole blood clots from 31 volunteers were exposed to rt-PA (0.5 μg/mL) and Epf (0.63 μg/mL) in human fresh-frozen plasma (rt-PA+Epf ), rt-PA alone in plasma (rt-PA Alone), or to plasma alone (Control), at temperatures from 30°C to 37°C, for 30 minutes. Clot lysis was measured using a microscopic imaging technique; the mean fractional clot loss (FCL) at 30 minutes was used to determine lytic efficacy. Temperature had a significant impact on FCL in clots exposed to rt-PA+Epf, with the FCL being lower at 30°C to 36°C than at 37°C. The FCL remained significantly higher for rt-PA+Epf–treated clots than Controls regardless of temperature, with the exception of measurements made at 30°C when no significant differences in the FCL were observed between groups. The use of hypothermia as a neuroprotectant may negatively impact the therapeutic benefit of thrombolytic agents. PMID:23667777

Radiation dose in neoadjuvant chemoradiation therapy for esophageal cancer: patterns of care and outcomes from the National Cancer Data Base.

PubMed

Haque, Waqar; Verma, Vivek; Butler, E Brian; Teh, Bin S

2018-02-01

Neoadjuvant chemoradiotherapy (CRT) for locally advanced esophageal cancer (EC) may utilize a wide variety of RT doses, without clear consensus to date. This study evaluated national practice patterns between lower dose (LD) (40-41.4 Gy) or higher dose (HD) (50-50.4 Gy) therapy, in addition to differences in survival and postoperative events. The National Cancer Data Base (NCDB) was queried [2004-2013] for patients with newly-diagnosed cT1a-T4aN0/N+M0 EC that received neoadjuvant CRT followed by esophagectomy. Multivariable logistic regression determined factors predictive of receiving LD RT. Kaplan-Meier analysis evaluated overall survival (OS), and Cox proportional hazards modeling determined variables associated with OS. Propensity score matching assessed groups in a balanced manner while reducing indication biases. Altogether, 5,025 patients met inclusion criteria; 257 (5%) received LD RT, while 4,768 (95%) received HD RT. LD RT was more likely delivered at academic centers (P=0.038), in more recent years (2009-2013, P=0.011), and to squamous cell carcinomas (P=0.001). HD RT tended to be administered with higher T stage as well as node-positive disease (P<0.05). The median OS in the LD and HD cohorts was 39.0 vs. 35.6 months (P=0.072), and 39.0 vs. 42.7 months after propensity matching (P=0.812). Dose did not independently correlate with OS on multivariate analysis (P=0.069), but treatment at academic centers correlated with improved OS (P=0.028). There were no differences between groups in the rates of 30-day readmission (P=0.182), 30-day mortality (P=0.314), or length of postoperative hospital stay (P=0.665), but the LD group experienced lower 90-day mortality (P=0.007). Although neoadjuvant LD CRT has been underutilized for EC in the United States, it is rising in more recent years. Dose did not significantly impact survival before or after propensity matching, nor did it independently predict for survival. Treatment at academic facilities independently correlated with higher survival, which has implications for patient counseling.

Disparities in the Initial Local Treatment of Older Women with Early-Stage Breast Cancer: A Population-Based Study.

PubMed

LeMasters, Traci J; Madhavan, Suresh S; Sambamoorthi, Usha; Vyas, Ami M

2017-07-01

Although breast cancer is most prevalent among older women, the majority are diagnosed at an early stage. When diagnosed at an early stage, women have the option of breast-conserving surgery (BCS) plus radiation therapy (RT) or mastectomy for the treatment of early-stage breast cancer (ESBC). Omission of RT when receiving BCS increases the risk for recurrence and poor survival. Yet, a small subset of older women may omit RT after BCS. This study examines the current patterns of local treatment for ESBC among older women. This study conducted a retrospective observational analysis using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked dataset of women age ≥66 diagnosed with stage I-II breast cancer in 2003-2009. SEER-Medicare data was additionally linked with data from the Area Resource File (ARF) to examine the association between area-level healthcare resources and treatment. Two logistic regression models were used to estimate how study factors were associated with receiving (1) BCS versus BCS+RT and (2) Mastectomy versus BCS+RT. A stratified analysis was also conducted among women aged <70 years. Among 45,924 patients, 55% received BCS+RT, 23% received mastectomy, and 22% received BCS only. Women of increasing age, comorbidity, primary care provider visits, stage II disease, and nonwhite race were more likely to have mastectomy or BCS only, than BCS+RT. Women diagnosed in 2004-2006, treated by an oncology surgeon, residing in metro areas, areas of greater education and income, were less likely to receive mastectomy or BCS only, than BCS+RT. While women aged <70 years were more likely to receive BCS+RT, socioeconomic and physician specialties were associated with receiving BCS only. Over half of older women with ESBC initially receive BCS+RT. The likelihood for mastectomy and BCS only increases with age, comorbidity, and vulnerable socio-demographic characteristics. Findings demonstrate continued treatment disparities among certain vulnerable populations.

Annual Research Review: Reaction time variability in ADHD and autism spectrum disorders: measurement and mechanisms of a proposed trans-diagnostic phenotype

PubMed Central

Karalunas, Sarah L.; Geurts, Hilde M.; Konrad, Kerstin; Bender, Stephan; Nigg, Joel T.

2014-01-01

Background Intraindividual variability in reaction time (RT) has received extensive discussion as an indicator of cognitive performance, a putative intermediate phenotype of many clinical disorders, and a possible trans-diagnostic phenotype that may elucidate shared risk factors for mechanisms of psychiatric illnesses. Scope and Methodology Using the examples of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD), we discuss RT variability. We first present a new meta-analysis of RT variability in ASD with and without comorbid ADHD. We then discuss potential mechanisms that may account for RT variability and statistical models that disentangle the cognitive processes affecting RTs. We then report a second meta-analysis comparing ADHD and non-ADHD children on diffusion model parameters. We consider how findings inform the search for neural correlates of RT variability. Findings Results suggest that RT variability is increased in ASD only when children with comorbid ADHD are included in the sample. Furthermore, RT variability in ADHD is explained by moderate to large increases (d = 0.63–0.99) in the ex-Gaussian parameter τ and the diffusion parameter drift rate, as well as by smaller differences (d = 0.32) in the diffusion parameter of nondecision time. The former may suggest problems in state regulation or arousal and difficulty detecting signal from noise, whereas the latter may reflect contributions from deficits in motor organization or output. The neuroimaging literature converges with this multicomponent interpretation and also highlights the role of top-down control circuits. Conclusion We underscore the importance of considering the interactions between top-down control, state regulation (e.g. arousal), and motor preparation when interpreting RT variability and conclude that decomposition of the RT signal provides superior interpretive power and suggests mechanisms convergent with those implicated using other cognitive paradigms. We conclude with specific recommendations for the field for next steps in the study of RT variability in neurodevelopmental disorders. PMID:24628425

Diet & Cancer: An Update for Biology Teachers.

ERIC Educational Resources Information Center

Anastasiou, Clifford J.

1988-01-01

Reports on dietary substances which act against cancer-causing agents. Indicates that adapting a lifestyle which combines reduced fat intake with increased fiber-containing foods will reduce the risk of some common cancers. Provides teaching strategies and activities to help students analyze their lifestyles for a reduction in cancer risk. (RT)

Reverse transcription loop-mediated isothermal amplification assays for rapid identification of eastern and western strains of bluetongue virus in India.

PubMed

Maan, S; Maan, N S; Batra, K; Kumar, A; Gupta, A; Rao, Panduranga P; Hemadri, Divakar; Reddy, Yella Narasimha; Guimera, M; Belaganahalli, M N; Mertens, P P C

2016-08-01

Bluetongue virus (BTV) infects all ruminants, including cattle, goats and camelids, causing bluetongue disease (BT) that is often severe in naïve deer and sheep. Reverse-transcription-loop-mediated-isothermal-amplification (RT-LAMP) assays were developed to detect eastern or western topotype of BTV strains circulating in India. Each assay uses four primers recognizing six distinct sequences of BTV genome-segment 1 (Seg-1). The eastern (e)RT-LAMP and western (w)RT-LAMP assay detected BTV RNA in all positive isolates that were tested (n=52, including Indian BTV-1, -2, -3, -5, -9, -10, -16, -21 -23, and -24 strains) with high specificity and efficiency. The analytical sensitivity of the RT-LAMP assays is comparable to real-time RT-PCR, but higher than conventional RT-PCR. The accelerated eRT-LAMP and wRT-LAMP assays generated detectable levels of amplified DNA, down to 0.216 fg of BTV RNA template or 108 fg of BTV RNA template within 60-90min respectively. The assays gave negative results with RNA from foot-and-mouth-disease virus (FMDV), peste des petits ruminants virus (PPRV), or DNA from Capripox viruses and Orf virus (n=10), all of which can cause clinical signs similar to BT. Both RT-LAMP assays did not show any cross-reaction among themselves. The assays are rapid, easy to perform, could be adapted as a 'penside' test making them suitable for 'front-line' diagnosis, helping to identify and contain field outbreaks of BTV. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of the RT-LAMP and LAMP methods for detection of Mycobacterium tuberculosis.

PubMed

Wu, Dandan; Kang, Jiwen; Li, Baosheng; Sun, Dianxing

2018-05-01

The current methods for detecting Mycobacterium tuberculosis (Mtb) are not clinically optimal. Standard culture methods (SCMs) are slow, costly, or unreliable, and loop-mediated isothermal amplification (LAMP) cannot differentiate live Mtb. This study compared reverse transcription (RT)-LAMP, LAMP, and an SCM for detecting Mtb. A first experiment tested the sensitivity and specificity of primers for 9 species of Mycobacterium (H37Rv, M. intracellulare, M. marinum, M. kansasii, M. avium, M. flavescens, M. smegmatis, M. fortuitum, and M. chelonae); and 3 non-Mycobacterium species (Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae). A second experiment tested sputum specimens for the presence of Mtb, from 100 patients with tuberculosis (clinical) and 22 from patients without tuberculosis (control), using Roche solid culture (SCM), LAMP, and RT-LAMP. In the clinical samples. The rates of positivity for Mtb of the SCM, LAMP, and RT-LAMP methods were 88%, 92%, and 100%, respectively. The difference in detection rate was significant between RT-LAMP and SCM, but RT-LAMP and LAMP were comparable. In the control group, the detection rates were nil for all three methods. The specificities of the methods were similar. The sensitivity of RT-LAMP was ~10-fold higher than that of LAMP for detecting Mtb. Unlike LAMP, RT-LAMP could identify viable bacteria, and was able to detect a single copy of Mtb. Among SCM, LAMP, and RT-LAMP, the latter is the most suitable for wide use in the lower-level hospitals and clinics of China for detecting Mtb in sputum samples. © 2017 Wiley Periodicals, Inc.

Association of childhood trauma with fatigue, depression, stress, and inflammation in breast cancer patients undergoing radiotherapy.

PubMed

Han, Tatiana J; Felger, Jennifer C; Lee, Anna; Mister, Donna; Miller, Andrew H; Torres, Mylin A

2016-02-01

This pilot study examined whether breast cancer patients with childhood trauma exhibit increased fatigue, depression, and stress in association with inflammation as a result of whole breast radiotherapy (RT). Twenty breast cancer patients were enrolled in a prospective, longitudinal study of fatigue, depression, and perceived stress prior to RT, week 6 of RT, and 6 weeks post-RT. Six weeks after RT, subjects completed the childhood trauma questionnaire (CTQ). Patients were also administered the multidimensional fatigue inventory, inventory of depressive symptomatology-self-reported, and perceived stress scale at all three time-points and underwent blood sampling prior to RT for gene expression and inflammatory markers previously associated with childhood trauma and behavioral symptoms in breast cancer patients. Eight subjects (40%) had past childhood trauma (CTQ+). Compared to CTQ- patients, CTQ+ patients had significantly higher fatigue, depression, and stress scores before, during, and after RT (p < 0.05); however, RT did not increase these symptoms in either group. CTQ+ patients also exhibited increased baseline expression of gene transcripts related to inflammatory signaling, and baseline inflammatory markers including c-reactive protein, interleukin (IL)-6, and IL-1 receptor antagonist were positively correlated with depression, fatigue, and stress scores in CTQ+ but not CTQ- patients. Childhood trauma was prevalent and was associated with increased symptoms of fatigue, depression, and stress irrespective of RT. Increased symptoms in CTQ+ patients were also associated with baseline inflammatory markers. Treatments targeting childhood trauma and related inflammation may improve symptoms in breast cancer patients. Copyright © 2015 John Wiley & Sons, Ltd.

The reverse transcriptase encoded by LINE-1 retrotransposons in the genesis, progression and therapy of cancer

NASA Astrophysics Data System (ADS)

Sciamanna, Ilaria; De Luca, Chiara; Spadafora, Corrado

2016-02-01

In higher eukaryotic genomes, Long Interspersed Nuclear Element 1 (LINE-1) retrotransposons represent a large family of repeated genomic elements. They transpose using a reverse transcriptase (RT), which they encode as part of the ORF2p product. RT inhibition in cancer cells, either via RNA interference-dependent silencing of active LINE-1 elements, or using RT inhibitory drugs, reduces cancer cell proliferation, promotes their differentiation and antagonizes tumor progression in animal models. Indeed, the nonnucleoside RT inhibitor efavirenz has recently been tested in a phase II clinical trial with metastatic prostate cancer patients. An in-depth analysis of ORF2p in a mouse model of breast cancer showed ORF2p to be precociously expressed in precancerous lesions and highly abundant in advanced cancer stages, while being barely detectable in normal breast tissue, providing a rationale for the finding that RT-expressing tumours are therapeutically sensitive to RT inhibitors. We summarise mechanistic and gene profiling studies indicating that highly abundant LINE-1-derived RT can “sequester” RNA substrates for reverse transcription in tumor cells, entailing the formation of RNA:DNA hybrid molecules and impairing the overall production of regulatory miRNAs, with a global impact on the cell transcriptome. Based on these data, LINE-1-ORF2 encoded RT has a tumor-promoting potential that is exerted at an epigenetic level. We propose a model whereby LINE1-RT drives a previously unrecognized global regulatory process, the deregulation of which drives cell transformation and tumorigenesis and possibly implicated in cancer cell heterogeneity.

A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer.

PubMed

Paik, Soonmyung; Shak, Steven; Tang, Gong; Kim, Chungyeul; Baker, Joffre; Cronin, Maureen; Baehner, Frederick L; Walker, Michael G; Watson, Drew; Park, Taesung; Hiller, William; Fisher, Edwin R; Wickerham, D Lawrence; Bryant, John; Wolmark, Norman

2004-12-30

The likelihood of distant recurrence in patients with breast cancer who have no involved lymph nodes and estrogen-receptor-positive tumors is poorly defined by clinical and histopathological measures. We tested whether the results of a reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of 21 prospectively selected genes in paraffin-embedded tumor tissue would correlate with the likelihood of distant recurrence in patients with node-negative, tamoxifen-treated breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trial B-14. The levels of expression of 16 cancer-related genes and 5 reference genes were used in a prospectively defined algorithm to calculate a recurrence score and to determine a risk group (low, intermediate, or high) for each patient. Adequate RT-PCR profiles were obtained in 668 of 675 tumor blocks. The proportions of patients categorized as having a low, intermediate, or high risk by the RT-PCR assay were 51, 22, and 27 percent, respectively. The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low-risk, intermediate-risk, and high-risk groups were 6.8 percent (95 percent confidence interval, 4.0 to 9.6), 14.3 percent (95 percent confidence interval, 8.3 to 20.3), and 30.5 percent (95 percent confidence interval, 23.6 to 37.4). The rate in the low-risk group was significantly lower than that in the high-risk group (P<0.001). In a multivariate Cox model, the recurrence score provided significant predictive power that was independent of age and tumor size (P<0.001). The recurrence score was also predictive of overall survival (P<0.001) and could be used as a continuous function to predict distant recurrence in individual patients. The recurrence score has been validated as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative, estrogen-receptor-positive breast cancer. Copyright 2004 Massachusetts Medical Society.

Monitoring Elite Soccer Players' External Loads Using Real-Time Data.

PubMed

Barrett, Steve

2017-11-01

To assess the validity of measuring locomotor activities and PlayerLoad using real-time (RT) data collection during soccer training. Twenty-nine English soccer players participated. Each player wore the same MEMS device (Micromechanical Electrical Systems; S5, Optimeye; CatapultSports, Melbourne, Australia) during 21 training sessions (N = 331 data sets) in the 2015-16 and 2016-17 seasons. An RT receiver (TRX; Catapultsports, Melbourne, Australia) was used to collect the locomotor activities and PlayerLoad data in RT and compared with the postevent downloaded (PED) data. PlayerLoad and locomotor activities (total distance covered; total high-speed running distance covered, >5.5#x00A0;m/s; total sprinting distance covered, >7 m/s; maximum velocity) were analyzed. Correlations were near perfect for all variables analyzed (r = .98-1.00), with a varied level of noise between RT and PED also (0.3-9.7% coefficient of variation). Locomotor activities and PlayerLoad can use both RT and PED concurrently to quantify a player's physical output during a training session. Caution should be taken with higher-velocity-based locomotor activities during RT compared to PED.

Chemical crosslinking of the subunits of HIV-1 reverse transcriptase.

PubMed Central

Debyser, Z.; De Clercq, E.

1996-01-01

The reverse transcriptase (RT) of the human immunodeficiency virus type 1 (HIV-1) is composed of two subunits of 66 and 51 kDa in a 1 to 1 ratio. Because dimerization is a prerequisite for enzymatic activity, interference with the dimerization process could constitute an alternative antiviral strategy for RT inhibition. Here we describe an in vitro assay for the study of the dimerization state of HIV-1 reverse transcriptase based on chemical crosslinking of the subunits with dimethylsuberimidate. Crosslinking results in the formation of covalent bonds between the subunits, so that the crosslinked species can be resolved by denaturing gel electrophoresis. Crosslinked RT species with molecular weight greater than that of the dimeric form accumulate during a 1-15-min time course. Initial evidence suggests that those high molecular weight species represent trimers and tetramers and may be the result of intramolecular crosslinking of the subunits of a higher-order RT oligomer. A peptide that corresponds to part of the tryptophan repeat motif in the connection domain of HIV-1 RT inhibits crosslink formation as well as enzymatic activity. The crosslinking assay thus allows the investigation of the effect of inhibitors on the dimerization of HIV-1 RT. PMID:8745406

Risk Analysis of Pneumonitis in Taxane Therapy After Chemoradiotherapy for Patients With Metastatic or Recurrent Esophageal Cancer.

PubMed

Kishida, Yoshihiro; Tsushima, Takahiro; Endo, Masahiro; Hamauchi, Satoshi; Todaka, Akiko; Yokota, Tomoya; Machida, Nozomu; Yamazaki, Kentaro; Fukutomi, Akira; Onozawa, Yusuke; Yasui, Hirofumi

2018-01-01

Taxane chemotherapy for esophageal cancer causes pneumonitis, not only by itself but also by radiation recall. This study aimed to clarify the risk of pneumonitis in patients with esophageal cancer who receive taxane therapy after chemoradiotherapy. The data of 129 patients with metastatic or recurrent esophageal cancer who initiated taxane therapy between September 2002 and June 2013 were retrospectively analyzed. Patient selection criteria were as follows: performance status ≤2, preserved organ functions, previous chemoradiotherapy with a radiation dose of ≥50 Gy, grade 0 or 1 pneumonitis at taxane initiation, and no concomitant malignancy. Logistic regression analysis was performed to identify risk factors for pneumonitis. Patient characteristics were as follows: males/females, 116/13; median age, 63 years (range, 44 to 80 y); performance status of 0/1/2, 61/60/8; smoking history, 112 (88%); location of the primary tumor Ce/Ut/Mt/Lt/Ae 12/30/66/20/1; median radiation dose, 60 Gy; history of radiation pneumonitis, 39 (30%); history of other pulmonary disease, 4 (3%); and median duration between the last radiation therapy (RT) exposure and taxane initiation, 6.1 months (range, 1.0 to 71 mo). During the median observation period of 7.8 months from taxane initiation, the incidence of grade 2 and 3 pneumonitis was observed in 7 (5.4%) and 3 (2.3%) patients, respectively. No patient died of pneumonitis. The only independent risk factor for pneumonitis was a ≤4-month period between the last RT exposure and taxane initiation (P=0.03). A short period between the last RT exposure and taxane initiation is an independent risk factor for pneumonitis development.

Genetic Variants in CD44 and MAT1A Confer Susceptibility to Acute Skin Reaction in Breast Cancer Patients Undergoing Radiation Therapy

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

Mumbrekar, Kamalesh Dattaram; Bola Sadashiva, Satish Rao; Kabekkodu, Shama Prasada

Purpose: Heterogeneity in radiation therapy (RT)-induced normal tissue toxicity is observed in 10% of cancer patients, limiting the therapeutic outcomes. In addition to treatment-related factors, normal tissue adverse reactions also manifest from genetic alterations in distinct pathways majorly involving DNA damage–repair genes, inflammatory cytokine genes, cell cycle regulation, and antioxidant response. Therefore, the common sequence variants in these radioresponsive genes might modify the severity of normal tissue toxicity, and the identification of the same could have clinical relevance as a predictive biomarker. Methods and Materials: The present study was conducted in a cohort of patients with breast cancer to evaluatemore » the possible associations between genetic variants in radioresponsive genes described previously and the risk of developing RT-induced acute skin adverse reactions. We tested 22 genetic variants reported in 18 genes (ie, NFE2L2, OGG1, NEIL3, RAD17, PTTG1, REV3L, ALAD, CD44, RAD9A, TGFβR3, MAD2L2, MAP3K7, MAT1A, RPS6KB2, ZNF830, SH3GL1, BAX, and XRCC1) using TaqMan assay-based real-time polymerase chain reaction. At the end of RT, the severity of skin damage was scored, and the subjects were dichotomized as nonoverresponders (Radiation Therapy Oncology Group grade <2) and overresponders (Radiation Therapy Oncology Group grade ≥2) for analysis. Results: Of the 22 single nucleotide polymorphisms studied, the rs8193 polymorphism lying in the micro-RNA binding site of 3′-UTR of CD44 was significantly (P=.0270) associated with RT-induced adverse skin reactions. Generalized multifactor dimensionality reduction analysis showed significant (P=.0107) gene–gene interactions between MAT1A and CD44. Furthermore, an increase in the total number of risk alleles was associated with increasing occurrence of overresponses (P=.0302). Conclusions: The genetic polymorphisms in radioresponsive genes act as genetic modifiers of acute normal tissue toxicity outcomes after RT by acting individually (rs8193), by gene–gene interactions (MAT1A and CD44), and/or by the additive effects of risk alleles.« less

Geographic Disparity in the Use of Hypofractionated Radiation Therapy Among Elderly Women Undergoing Breast Conservation for Invasive Breast Cancer

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

Gillespie, Erin F.; Matsuno, Rayna K.; Xu, Beibei

Purpose: To evaluate geographic heterogeneity in the delivery of hypofractionated radiation therapy (RT) for breast cancer among Medicare beneficiaries across the United States. Methods and Materials: We identified 190,193 patients from the Centers for Medicare and Medicaid Services Chronic Conditions Warehouse. The study included patients aged >65 years diagnosed with invasive breast cancer treated with breast conservation surgery followed by radiation diagnosed between 2000 and 2012. We analyzed data by hospital referral region based on patient residency ZIP code. The proportion of women who received hypofractionated RT within each region was analyzed over the study period. Multivariable logistic regression models identified predictors ofmore » hypofractionated RT. Results: Over the entire study period we found substantial geographic heterogeneity in the use of hypofractionated RT. The proportion of women receiving hypofractionated breast RT in individual hospital referral regions varied from 0% to 61%. We found no correlation between the use of hypofractionated RT and urban/rural setting or general geographic region. The proportion of hypofractionated RT increased in regions with higher density of radiation oncologists, as well as lower total Medicare reimbursements. Conclusions: This study demonstrates substantial geographic heterogeneity in the use of hypofractionated RT among elderly women with invasive breast cancer treated with lumpectomy in the United States. This heterogeneity persists despite clinical data from multiple randomized trials proving efficacy and safety compared with standard fractionation, and highlights possible inefficiency in health care delivery.« less

Evaluation of the utility of a rapid test for syphilis at a sexually transmitted disease clinic in Buenos Aires, Argentina.

PubMed

Gallo Vaulet, Lucía; Morando, Nicolás; Casco, Ricardo; Melgar, Asunta; Nacher, Silvia; Rodríguez Fermepin, Marcelo; Pando, María A

2018-05-15

Even though syphilis can be easily diagnosed by simple and low-cost laboratory methods, it continues to be an important health problem. Rapid tests (RT) for the detection of treponemal antibodies can facilitate earlier diagnosis, access to treatment and linkage to care. The aim of this study was to analyse the usefulness of the incorporation of a RT in the detection of patients infected with T. pallidum in a sexually-transmitted disease (STD) clinic. Between March and December 2015, a syphilis RT was offered to patients who spontaneously attended the clinic. Conventional serology testing was additionally indicated to every participant. The RT for syphilis was offered to 1887 patients, of whom 31.1% agreed to get tested. VDRL test was performed in 84.0% of patients that were also tested with syphilis RT, with a significantly higher frequency observed among participants with reactive RT (94.3% vs. 79.8%, p < 0.001). These results showed that 33.7% of the participants were reactive for the RT and 27.0% were reactive for the VDRL test. Both tests were reactive in 24.9% and non-reactive in 64.3%. A high prevalence of active syphilis was detected in patients attending the clinic. The use of a syphilis RT had a positive impact, which in combination with the VDRL test increased the number of patients that were effectively diagnosed.

The management of patients with esophageal cancer and coronary artery stenosis undergoing radiotherapy or concurrent chemoradiotherapy: a single-center experience.

PubMed

Luo, Hui; Chen, Xiaojian; Zhang, Qiugui; Wang, Lanhua; Qiao, Lili; Liang, Ning; Xie, Jian; Yu, Xinshuang; Song, Meijuan; Liu, Zhen; Lv, Yajuan; Liu, Fengjun; Tian, Yuan; Cheng, Jian; Deng, Guodong; Zhang, Jingxin; Li, X Allen; Zhang, Jiandong

2016-01-01

The incidence of esophageal cancer (EC) patients with coronary artery stenosis presents particular challenges. The aim of this retrospective study was to evaluate the efficiency of management on patients with both diseases treated by radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). Fifty-three patients with both EC and coronary artery stenosis from June 2009 to August 2012 were retrospectively analyzed. The patients received RT or CCRT with coronary artery stenosis management. Cardiac treatments often prescribed included aspirin, β-blockers, statins etc. The adverse effects, overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were analyzed. Most of the patients were 40-70 years old. There were 25 patients in the CCRT group and 28 patients in the RT group. The complete response (CR) rate was higher in the patients in the CCRT group than in those in the RT group (48.0 vs 21.4%; p=0.041). The median PFS was 15.9 months in the CCRT group and 11.6 months in the RT group (p=0.025). OS was 22.4 months in the CCRT group and 15.8 months in the RT group (p=0.013). Though adverse effects were less in the RT group, no significance differences in grade 3-4 toxicity were observed. With the appropriate of coronary artery stenosis management, RT and CCRT were both tolerable and effective in EC patients with coronary artery stenosis.

Advanced techniques in neoadjuvant radiotherapy allow dose escalation without increased dose to the organs at risk : Planning study in esophageal carcinoma.

PubMed

Fakhrian, K; Oechsner, M; Kampfer, S; Schuster, T; Molls, M; Geinitz, H

2013-04-01

The goal of this work was to investigate the potential of advanced radiation techniques in dose escalation in the radiotherapy (RT) for the treatment of esophageal carcinoma. A total of 15 locally advanced esophageal cancer (LAEC) patients were selected for the present study. For all 15 patients, we created a 3D conformal RT plan (3D-45) with 45 Gy in fractions of 1.8 Gy to the planning target volume (PTV1), which we usually use to employ in the neoadjuvant treatment of LAEC. Additionally, a 3D boost (as in the primary RT of LAEC) was calculated with 9 Gy in fractions of 1.8 Gy to the boost volume (PTV2) (Dmean) to a total dose of 54 Gy (3D-54 Gy), which we routinely use for the definitive treatment of LAEC. Three plans with a simultaneous integrated boost (SIB) were then calculated for each patient: sliding window intensity-modulated radiotherapy (IMRT-SIB), volumetric modulated arc therapy (VMAT-SIB), and helical tomotherapy (HT-SIB). For the SIB plans, the requirement was that 95 % of the PTV1 receive ≥ 100 % of the prescription dose (45 Gy in fractions of 1.8 Gy, D95) and the PTV2 was dose escalated to 52.5 Gy in fractions of 2.1 Gy (D95). The median PTV2 dose for 3D-45, 3D-54, HT-SIB, VMAT-SIB, and IMRT-SIB was 45, 55, 54, 56, and 55 Gy, respectively. Therefore, the dose to PTV2 in the SIB plans was comparable to the 3D-54 plan. The lung dose in the SIB plans was in the range of the standard 3D-45, which is applied for neoadjuvant radiotherapy. The mean lung dose for the same plans was 13, 15, 12, 12, and 13 Gy, respectively. The V5 lung volumes were 71, 74, 79, 75, and 73 %, respectively. The V20 lung volumes were 20, 25, 16, 18, and 19 %, respectively. New treatment planning techniques enable higher doses to be delivered for neoadjuvant radiotherapy of LAEC without a significant increase in the delivered dose to the organs at risk. Clinical investigations are warranted to study the clinical safety and feasibility of applying higher doses through advanced techniques in the neoadjuvant treatment of LAEC.

"Cor Occidere": a novel strategy of targeting the tumor core by radiosurgery in a radio- and chemo-resistant intracranial hemangiopericytoma.

PubMed

Li, You Quan; Chua, Eu Tiong; Chua, Kevin L M; Chua, Melvin L K

2018-02-01

Intracranial hemangiopericytomas (HPC) are chemotherapy- and radiotherapy (RT)-resistant. Here, we report on a novel stereotactic radiosurgery (SRS) technique-"Cor Occidere" (Latin), as a potential strategy of overcoming radioresistance of HPC. A 36-year old female presented to our clinic for consideration of a 3rd-course of RT for her recurrent cavernous sinus HPC, following previous cranial RT at 13 and 5 years prior, and a failed 9 months trial of bevacizumab/temozolomide. The tumor-adjacent brain stem and carotid artery risked substantial damage given the cumulative RT doses to these organs. We therefore designed an SRS plan targeting only the tumor core with 16 Gy single-fraction. Despite underdosing the tumor margin, we achieved stable disease over 25 months, contrasting her responses to systemic therapies. Achieving tumor control despite a suboptimal treatment that utilized high dose ablation of the tumor core suggests novel biological mechanisms to overcome radioresistance of HPC.

IFLA General Conference, 1991. Workshops' Papers: Section of Geography and Map Libraries; Section of Art Libraries; Section of Children's Libraries joint with RT of Research in Reading; Children's Literature Documentation Centres (RT); Section of Libraries for the Blind joint with Section of Interlending and Document Delivery; Section of Government Information and Official Publications; Section of Information Technology; Professional Board Working Group on Management. Booklet 9.

ERIC Educational Resources Information Center

International Federation of Library Associations and Institutions, The Hague (Netherlands).

The 29 papers in this collection were presented at 9 conference workshops: "Inset Maps and Proposals for Their Description" (V. Kusov); "The Utilization of the Old Maps in Modern Researches" (H. Melnikova); (3) "New Series of Maps for Higher Schools: Their Role in the Cartographic Provision for the Higher Education"…

Highly favorable physiological responses to concurrent resistance and high-intensity interval training during chemotherapy: the OptiTrain breast cancer trial.

PubMed

Mijwel, Sara; Backman, Malin; Bolam, Kate A; Olofsson, Emil; Norrbom, Jessica; Bergh, Jonas; Sundberg, Carl Johan; Wengström, Yvonne; Rundqvist, Helene

2018-05-01

Advanced therapeutic strategies are often accompanied by significant adverse effects, which warrant equally progressive countermeasures. Physical exercise has proven an effective intervention to improve physical function and reduce fatigue in patients undergoing chemotherapy. Effects of high-intensity interval training (HIIT) in this population are not well established although HIIT has proven effective in other clinical populations. The aim of the OptiTrain trial was to examine the effects of concurrent resistance and high-intensity interval training (RT-HIIT) or concurrent moderate-intensity aerobic and high-intensity interval training (AT-HIIT), to usual care (UC) on pain sensitivity and physiological outcomes in patients with breast cancer during chemotherapy. Two hundred and forty women were randomized to 16 weeks of RT-HIIT, AT-HIIT, or UC. cardiorespiratory fitness, muscle strength, body mass, hemoglobin levels, and pressure-pain threshold. Pre- to post-intervention, RT-HIIT (ES = 0.41) and AT-HIIT (ES = 0.42) prevented the reduced cardiorespiratory fitness found with UC. Handgrip strength (surgery side: RT-HIIT vs. UC: ES = 0.41, RT-HIIT vs. AT-HIIT: ES = 0.28; non-surgery side: RT-HIIT vs. UC: ES = 0.35, RT-HIIT vs. AT-HIIT: ES = 0.22) and lower-limb muscle strength (RT-HIIT vs. UC: ES = 0.66, RT-HIIT vs. AT-HIIT: ES = 0.23) were significantly improved in the RT-HIIT. Increases in body mass were smaller in RT-HIIT (ES = - 0.16) and AT-HIIT (ES = - 0.16) versus UC. RT-HIIT reported higher pressure-pain thresholds than UC (trapezius: ES = 0.46, gluteus: ES = 0.53) and AT-HIIT (trapezius: ES = 0.30). Sixteen weeks of RT-HIIT significantly improved muscle strength and reduced pain sensitivity. Both exercise programs were well tolerated and were equally efficient in preventing increases in body mass and in preventing declines in cardiorespiratory fitness. These results highlight the importance of implementing a combination of resistance and high-intensity interval training during chemotherapy for women with breast cancer.

Characterization of efficacy and toxicity after high-dose pelvic reirradiation with palliative intent for genitourinary second malignant neoplasms or local recurrences after full-dose radiation therapy in the pelvis: A high-volume cancer center experience.

PubMed

Kamran, Sophia C; Harshman, Lauren C; Bhagwat, Mandar S; Muralidhar, Vinayak; Nguyen, Paul L; Martin, Neil E; La Follette, Stephanie; Faso, Sarah; Viswanathan, Akila N; Efstathiou, Jason A; Beard, Clair J

2017-01-01

The use of large-field external beam reirradiation (re-RT) after pelvic radiation therapy (RT) for genitourinary (GU) cancers has not been reported. We report the results of such treatment in patients with either symptomatic GU second malignant neoplasms or locally recurrent pelvic tumors after initial RT for whom surgery or further systemic therapy was not an option. The records of 28 consecutive patients with advanced, bulky GU malignancies treated with high-dose, large-field re-RT with palliative intent between 2008 and 2014 were retrospectively reviewed. Descriptive outcome analyses focused on toxicities and symptom control, and responses were evaluated by 2 independent observers. Twenty-seven male patients (96%) were included. Median initial external beam RT dose was 64 Gy (range, 30-75.6 Gy). The median time between initial RT and re-RT was 9.5 years (range, 0.2-32 years). At the time of re-RT, there were 16 local recurrences and 12 second malignant neoplasms together comprising 16 bladder, 10 prostate, 1 ureteral, and 1 penile cancer. Indications for re-RT were pain and bleeding/hemorrhage. The median equivalent sphere diameter planning target volume for re-RT was 8.6 cm (range, 4.7-16.3 cm). Given the severity of the symptoms and the bulk of the disease at the time of re-RT, a higher dose of RT was administered. The median re-RT dose was 50 Gy (range, 27.5-66 Gy). For patients who received <60 Gy, hypofractionation of 250 cGy was used. The median cumulative dose was 113.9 Gy (range, 81.5-132.8 Gy). Re-RT was well tolerated with no Radiation Therapy Oncology Group grade 3-4 toxicities. Twenty-four patients (92%) had complete resolution of symptoms, and relief was durable in 67% of patients. The median overall survival was 5.8 months (range, 0.3-38.9 months). Of those patients who are still alive, 100% remain free of initial symptoms. This small series suggests that aggressive re-RT of inoperable and symptomatic GU malignancies that is undertaken with meticulous treatment planning is well tolerated and provides excellent, durable relief without undue short-term toxicity. Validation in a larger prospective cohort is required.

Bluetongue virus RNA detection by real-time rt-PCR in post-vaccination samples from cattle.

PubMed

De Leeuw, I; Garigliany, M; Bertels, G; Willems, T; Desmecht, D; De Clercq, K

2015-04-01

Bluetongue virus serotype 8 (BTV-8) was responsible for a large outbreak among European ruminant populations in 2006-2009. In spring 2008, a massive vaccination campaign was undertaken, leading to the progressive disappearance of the virus. During surveillance programmes in Western Europe in 2010-2011, a low but significant number of animals were found weakly positive using BTV-specific real-time RT-PCR, raising questions about a possible low level of virus circulation. An interference of the BTV-8 inactivated vaccine on the result of the real-time RT-PCR was also hypothesized. Several studies specifically addressed the potential association between a recent vaccination and BTV-8 RNA detection in the blood of sheep. Results were contradictory and cattles were not investigated. To enlighten this point, a large study was performed to determine the risks of detection of bluetongue vaccine-associated RNA in the blood and spleen of cattle using real-time RT-PCR. Overall, the results presented clearly demonstrate that vaccine viral RNA can reach the blood circulation in sufficient amounts to be detected by real-time RT-PCR in cattle. This BTV-8 vaccine RNA carriage appears as short lasting. © 2013 Blackwell Verlag GmbH.

Inflammatory biomarker C-reactive protein and radiotherapy-induced early adverse skin reactions in patients with breast cancer.

PubMed

Rodriguez-Gil, Jorge L; Takita, Cristiane; Wright, Jean; Reis, Isildinha M; Zhao, Wei; Lally, Brian E; Hu, Jennifer J

2014-09-01

Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in American women. Postsurgery adjuvant radiotherapy (RT) significantly reduced the local recurrence rate. However, many patients develop early adverse skin reactions (EASR) that impact quality of life and treatment outcomes. We evaluated an inflammatory biomarker, C-reactive protein (CRP), in predicting RT-induced EASRs in 159 patients with breast cancer undergoing RT. In each patient, we measured pre- and post-RT plasma CRP levels using a highly sensitive ELISA CRP assay. RT-induced EASRs were assessed at weeks 3 and 6 using the National Cancer Institute Common Toxicity Criteria (v3.0). Associations between EASRs and CRP levels were assessed using logistic regression models after adjusting for potential confounders. RT-induced grade 2+ EASRs were observed in 8 (5%) and 80 (50%) patients at weeks 3 and 6 (end of RT), respectively. At the end of RT, a significantly higher proportion of African Americans developed grade 3 EASRs (13.8% vs. 2.3% in others); grade 2+ EASRs were significantly associated with: change of CRP > 1 mg/L [odds ratio (OR), 2.51; 95% confidence interval (CI), 1.06-5.95; P = 0.04], obesity (OR, 2.08; 95% CI, 1.03-4.21; P = 0.04), or combined both factors (OR, 5.21; 95% CI, 1.77-15.38; P = 0.003). This is the first study to demonstrate that an inflammatory biomarker CRP is associated with RT-induced EASRs, particularly combined with obesity. Future larger studies are warranted to validate our findings and facilitate the discovery and development of anti-inflammatory agents to protect normal tissue from RT-induced adverse effects and improve quality of life in patients with breast cancer undergoing RT. ©2014 American Association for Cancer Research.

Association of Radiation Dose to the Eyes With the Risk for Cataract After Nonretinoblastoma Solid Cancers in Childhood.

PubMed

Allodji, Rodrigue S; Diallo, Ibrahima; El-Fayech, Chiraz; Kahlouche, Amar; Dumas, Agnès; Schwartz, Boris; Oberlin, Odile; Benadjaoud, Mohamed Amine; Labbé, Martine; Jackson, Angela; Bullet, Julien; Rubino, Carole; Haddy, Nadia; De Vathaire, Florent

2016-04-01

Few studies have been published on the association of the radiation dose received to the eyes during radiotherapy (RT) for childhood cancer and the risk for later cataract. To investigate the risk for cataract after treatment of nonretinoblastoma solid cancer in childhood. The study used data from the Euro2K cohort that includes 4389 5-year survivors of solid tumors treated from January 1, 1945, to December 31, 1985; of these, 3172 patients were treated in France. A self-reported questionnaire was sent to French survivors from September 1, 2005, to December 31, 2012, when follow-up was considered completed for this study. However, 619 patients died before the beginning of the study and 128 patients treated for a retinoblastoma or who underwent enucleation were excluded. Likewise, 429 patients with unknown addresses or who did not return the consent form and 163 nonresponders did not participate. The remaining 1833 patients who completed the questionnaire underwent analysis for this study from June 1, 2014, to December 7, 2015. Radiation doses in both eyes for individuals were estimated for all patients who had received RT. The role of the radiation dose in cataract risk was investigated using the Cox proportional hazard regression model and the excess relative or the absolute risk model. The role of ctytotoxic chemotherapy was also investigated. The 1833 patients (961 men [52.4%]; 872 women [47.6%]; mean [SD] age, 37.0 [8.5]) who returned the questionnaire were included in the analysis. After a mean follow-up of 32 years, 33 patients with unilateral or bilateral cataract were identified, for a total of 47 cataract events. The 47 events were validated by medical record review and by contacting the patients and the corresponding medical physician or ophthalmologist to obtain copies of diagnostic examinations or surgical reports. Overall, in a multivariable Cox proportional hazard regression analysis, patients who received RT had a 4.4-fold (95% CI, 1.5- to 13.0-fold) increased risk for cataract compared with patients who did not receive RT. Exposure to radiation doses of at least 10 Gy to the eyes increased the hazard ratio 39-fold (95% CI, 12.0- to 127.9-fold), relative to no radiation exposure. Although based on few patients, a strong increase in cataract risk (hazard ratio, 26.3; 95% CI, 7.1-96.6) was observed in patients treated with melphalan hydrochloride. This study can inform guideline-based recommendations for long-term follow-up for cataract.

Identification of Neuroprotective Factors Associated with Successful Ageing and Risk of Cognitive Impairment among Malaysia Older Adults

PubMed Central

Rajab, Nor Fadilah; Shahar, Suzana

2017-01-01

The increase of ageing population has raised public attention on the concept of successful ageing. Studies have shown that vitamin D, telomere length, and brain-derived neurotrophic factor (BDNF) have been associated with cognitive function. Therefore, this study aimed to identify neuroprotective factors for cognitive decline in different ageing groups. A total of 300 older adults aged 60 years and above were recruited in this population based cross-sectional study. Participants were categorized into three groups: mild cognitive impairment (MCI) (n = 100), usual ageing (UA) (n = 100), and successful ageing (SA) (n = 100). Dietary vitamin D intake was assessed through Diet History Questionnaire (DHQ). Out of the 300 participants, only 150 were subjected to fasting blood sample collection. These samples were used for serum vitamin D and plasma BDNF measurements. Whole blood telomere length was measured using RT-PCR method. The results show that the reduction of the risk of MCI was achieved by higher serum vitamin D level (OR: 0.96, 95% CI: 0.92–0.99, p < 0.05), higher plasma BDNF level (OR: 0.51, 95% CI: 0.30–0.88,  p < 0.05), and longer telomere (OR: 0.97, 95% CI: 0.95–0.99,  p < 0.001). In conclusion, participants with higher vitamin D level, higher BDNF level, and longer telomere length were more likely to age successfully. PMID:29109736

Bilateral lesions of nucleus subpretectalis/interstitio-pretecto-subpretectalis (SP/IPS) selectively impair figure-ground discrimination in pigeons.

PubMed

Scully, Erin N; Acerbo, Martin J; Lazareva, Olga F

2014-01-01

Earlier, we reported that nucleus rotundus (Rt) together with its inhibitory complex, nucleus subpretectalis/interstitio-pretecto-subpretectalis (SP/IPS), had significantly higher activity in pigeons performing figure-ground discrimination than in the control group that did not perform any visual discriminations. In contrast, color discrimination produced significantly higher activity than control in the Rt but not in the SP/IPS. Finally, shape discrimination produced significantly lower activity than control in both the Rt and the SP/IPS. In this study, we trained pigeons to simultaneously perform three visual discriminations (figure-ground, color, and shape) using the same stimulus displays. When birds learned to perform all three tasks concurrently at high levels of accuracy, we conducted bilateral chemical lesions of the SP/IPS. After a period of recovery, the birds were retrained on the same tasks to evaluate the effect of lesions on maintenance of these discriminations. We found that the lesions of the SP/IPS had no effect on color or shape discrimination and that they significantly impaired figure-ground discrimination. Together with our earlier data, these results suggest that the nucleus Rt and the SP/IPS are the key structures involved in figure-ground discrimination. These results also imply that thalamic processing is critical for figure-ground segregation in avian brain.

Recombinase Polymerase Amplification Assay for Rapid Diagnostics of Dengue Infection

PubMed Central

Abd El Wahed, Ahmed; Patel, Pranav; Faye, Oumar; Thaloengsok, Sasikanya; Heidenreich, Doris; Matangkasombut, Ponpan; Manopwisedjaroen, Khajohnpong; Sakuntabhai, Anavaj; Sall, Amadou A.; Hufert, Frank T.; Weidmann, Manfred

2015-01-01

Background Over 2.5 billion people are exposed to the risk of contracting dengue fever (DF). Early diagnosis of DF helps to diminish its burden on public health. Real-time reverse transcription polymerase amplification assays (RT-PCR) are the standard method for molecular detection of the dengue virus (DENV). Real-time RT-PCR analysis is not suitable for on-site screening since mobile devices are large, expensive, and complex. In this study, two RT-recombinase polymerase amplification (RT-RPA) assays were developed to detect DENV1-4. Methodology/Principal Findings Using two quantitative RNA molecular standards, the analytical sensitivity of a RT-RPA targeting the 3´non-translated region of DENV1-4 was found to range from 14 (DENV4) to 241 (DENV1-3) RNA molecules detected. The assay was specific and did not cross detect other Flaviviruses. The RT-RPA assay was tested in a mobile laboratory combining magnetic-bead based total nucleic acid extraction and a portable detection device in Kedougou (Senegal) and in Bangkok (Thailand). In Kedougou, the RT-RPA was operated at an ambient temperature of 38°C with auxiliary electricity tapped from a motor vehicle and yielded a clinical sensitivity and specificity of 98% (n=31) and 100% (n=23), respectively. While in the field trial in Bangkok, the clinical sensitivity and specificity were 72% (n=90) and 100%(n=41), respectively. Conclusions/Significance During the first 5 days of infection, the developed DENV1-4 RT-RPA assays constitute a suitable accurate and rapid assay for DENV diagnosis. Moreover, the use of a portable fluorescence-reading device broadens its application potential to the point-of-care for outbreak investigations. PMID:26075598

Quality of radiotherapy reporting in randomized controlled trials of prostate cancer.

PubMed

Soon, Yu Yang; Chen, Desiree; Tan, Teng Hwee; Tey, Jeremy

2018-06-07

Good radiotherapy reporting in clinical trials of prostate radiotherapy is important because it will allow accurate reproducibility of radiotherapy treatment and minimize treatment variations that can affect patient outcomes. The aim of our study is to assess the quality of prostate radiotherapy (RT) treatment reporting in randomized controlled trials in prostate cancer. We searched MEDLINE for randomized trials of prostate cancer, published from 1996 to 2016 and included prostate RT as one of the intervention arms. We assessed if the investigators reported the ten criteria adequately in the trial reports: RT dose prescription method; RT dose-planning procedures; organs at risk (OAR) dose constraints; target volume definition, simulation procedures; treatment verification procedures; total RT dose; fractionation schedule; conduct of quality assurance (QA) as well as presence or absence of deviations in RT treatment planning and delivery. We performed multivariate logistic regression to determine the factors that may influence the quality of reporting. We found 59 eligible trials. There was significant variability in the quality of reporting. Target volume definition, total RT dose and fractionation schedule were reported adequately in 97% of included trials. OAR constraints, simulation procedures and presence or absence of deviations in RT treatment planning and delivery were reported adequately in 30% of included trials. Twenty-four trials (40%) reported seven criteria or more adequately. Multivariable logistic analysis showed that trials that published their quality assurance results and cooperative group trials were more likely to have adequate quality in reporting in at least seven criteria. There is significant variability in the quality of reporting on prostate radiotherapy treatment in randomized trials of prostate cancer. We need to have consensus guidelines to standardize the reporting of radiotherapy treatment in randomized trials.

Patterns of Local Recurrence and Dose Fractionation of Adjuvant Radiation Therapy in 462 Patients With Soft Tissue Sarcoma of Extremity and Trunk Wall

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

Jebsen, Nina L., E-mail: nina.louise.jebsen@helse-bergen.no; Department of Oncology, Haukeland University Hospital, Bergen; Engellau, Jacob

2013-08-01

Purpose: To study the impact of dose fractionation of adjuvant radiation therapy (RT) on local recurrence (LR) and the relation of LR to radiation fields. Methods and Materials: LR rates were analyzed in 462 adult patients with soft tissue sarcoma who underwent surgical excision and adjuvant RT at five Scandinavian sarcoma centers from 1998 to 2009. Medical records were reviewed for dose fractionation parameters and to determine the location of the LR relative to the radiation portals. Results: Fifty-five of 462 patients developed a LR (11.9%). Negative prognostic factors included intralesional surgical margin (hazard ratio [HR]: 7.83, 95% confidence intervalmore » [CI]: 3.08-20.0), high malignancy grade (HR: 5.82, 95% CI: 1.31-25.8), age at diagnosis (HR per 10 years: 1.27, 95% CI: 1.03-1.56), and malignant peripheral nerve sheath tumor histological subtype (HR: 6.66, 95% CI: 2.56-17.3). RT dose was tailored to margin status. No correlation between RT dose and LR rate was found in multiple Cox regression analysis. The majority (65%) of LRs occurred within the primary RT volume. Conclusions: No significant dose–response effect of adjuvant RT was demonstrated. Interestingly, patients given 45-Gy accelerated RT (1.8 Gy twice daily/2.5 weeks) had the best local outcome. A total dose of 50 Gy in 25 fractions seemed adequate following wide margin surgery. The risk of LR was associated with histopathologic subtype, which should be included in the treatment algorithm of adjuvant RT in soft tissue sarcoma.« less

Diagnosis of bacteremia in febrile neutropenic episodes in children with cancer: microbiologic and molecular approach.

PubMed

Santolaya, María E; Farfán, Mauricio J; De La Maza, Verónica; Cociña, Manuela; Santelices, Felipe; Alvarez, Ana M; Avilés, Carmen L; Becker, Ana; O'Ryan, Miguel; Román, Paulina; Salgado, Carmen; Silva, Pamela; Topelberg, Santiago; Tordecilla, Juan; Varas, Mónica; Villarroel, Milena; Viviani, Tamara; Zubieta, Marcela; Torres, Juan P

2011-11-01

Bacterial isolation using conventional microbiologic techniques rarely surpasses 25% in children with clinical and laboratory findings indicative of an invasive bacterial infection. The aim of this study was to determine the role of real-time polymerase chain reaction (RT-PCR) from whole blood samples compared with automated blood cultures (BC) in detection of relevant microorganisms causing bacteremia in episodes of high-risk febrile neutropenia (HRFN) in children with cancer. Children presenting with HRFN at 6 hospitals in Santiago, Chile, were invited to participate. Blood samples were obtained at admission for BC, and at admission and 24 hours for RT-PCR targeting DNA of Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa causing bacteremia in children with HRFN. A total of 177 HRFN episodes were evaluated from May 2009 to August 2010, of which 29 (16.3%) had positive BC, 9 (5%) positive for 1 of the 3 selected bacterial species: 5 for E. coli, 3 for S. aureus, and 1 for P. aeruginosa. RT-PCR detected 39 bacteria in 36 episodes (20%): 14 E. coli, 20 S. aureus, and 5 P. aeruginosa. The sensitivity, specificity, and positive and negative predictive values of RT-PCR compared with BC were 56%, 80%, 13%, and 97%. The final clinical diagnosis was compatible with an invasive bacterial infection in 30/36 (83%) RT-PCR-positive episodes. In our series, RT-PCR significantly improved detection of the most relevant bacteria associated with HRFN episodes. Large number of patients and close clinical monitoring, in addition to improved RT-PCR techniques will be required to fully recommend RT-PCR-based diagnosis for the routine workup of children with cancer, fever, and neutropenia.