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Sample records for radiotherapy improved survival

  1. Does radiotherapy or lymphadenectomy improve survival in endometrial stromal sarcoma?

    PubMed

    Barney, Brandon; Tward, Jonathan D; Skidmore, Thomas; Gaffney, David K

    2009-10-01

    Endometrial stromal sarcoma (ESS) is a rare uterine malignancy characterized by cells resembling proliferative-phase endometrial stroma. Standard treatment is total hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO). The roles of radiation therapy (RT) and lymphadenectomy (LAD) remain unclear. Using a large population database, we retrospectively evaluated the addition of RT and LAD to surgery for survival impact. We identified 1010 women with ESS between 1983 and 2002 from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Kaplan-Meier method was used to estimate overall survival (OS) and cause-specific survival (CSS). Outcomes for patients treated by TAH-BSO alone and surgery plus RT were compared using Cox proportional hazards regression model. A multivariate analysis controlling for age, International Federation of Gynecology and Obstetrics (FIGO) stage, LAD, race, year of diagnosis, and tumor grade was performed. Univariate analyses were performed for individual FIGO stages, low- and high-grade tumors, and surgery with and without LAD. A literature review was performed to compile studies showing LAD data for ESS. The median follow-up was 54 months (range, 1-248 months). The 5-year OS and CSS for patients undergoing surgery plus RT were 72.2% and 80.1% and 83.2% and 90.7% for surgery alone, respectively. Worse prognoses were associated with increasing FIGO stage, tumor grade, and age. Neither did adjuvant RT correlate with improved survival within any FIGO stage nor did it alter survival for low- or high-grade tumor groups. Adding lymphadenectomy to TAH-BSO did not change survival.

  2. Radiotherapy Improves Survival in Unresected Stage I-III Bronchoalveolar Carcinoma

    SciTech Connect

    Urban, Damien; Mishra, Mark; Onn, Amir; Dicker, Adam P.; Symon, Zvi; Pfeffer, M. Raphael; Lawrence, Yaacov Richard

    2012-11-01

    Purpose: To test the hypothesis that radiotherapy (RT) improves the outcome of patients with unresected, nonmetastatic bronchoalveolar carcinoma (BAC) by performing a population-based analysis within the Surveillance, Epidemiology, and End Results (SEER) registry. Methods and Materials: Inclusion criteria were as follows: patients diagnosed with BAC, Stage I-III, between 2001 and 2007. Exclusion criteria included unknown stage, unknown primary treatment modality, Stage IV disease, and those diagnosed at autopsy. Demographic data, treatment details, and overall survival were retrieved from the SEER database. Survival was analyzed using the Kaplan-Meier method and log-rank test. Results: A total of 6933 patients with Stage I-III BAC were included in the analysis. The median age at diagnosis was 70 years (range, 10-101 years). The majority of patients were diagnosed with Stage I (74.4%); 968 patients (14%) did not undergo surgical resection. Unresected patients were more likely to be older (p < 0.0001), male (p = 0.001), black (p < 0.0001), and Stage III (p < 0.0001). Within the cohort of unresected patients, 300 (31%) were treated with RT. The estimated 2-year overall survival for patients with unresected, nonmetastatic BAC was 58%, 44%, and 27% in Stage I, II, and III, respectively. Factors associated with improved survival included female sex, earlier stage at diagnosis, and use of RT. Median survival in those not receiving RT vs. receiving RT was as follows: Stage I, 28 months vs. 33 months (n = 364, p = 0.06); Stage II, 18 months vs. not reached (n = 31, nonsignificant); Stage III, 10 months vs. 17 months (n = 517, p < 0.003). Conclusions: The use of RT is associated with improved prognosis in unresected Stage I-III BAC. Less than a third of patients who could have potentially benefited from RT received it, suggesting that the medical specialists involved in the care of these patients underappreciate the importance of RT.

  3. Improved survival in HPV/p16-positive oropharyngeal cancer patients treated with postoperative radiotherapy.

    PubMed

    Heiduschka, Gregor; Grah, Anja; Oberndorfer, Felicitas; Kadletz, Lorenz; Altorjai, Gabriela; Kornek, Gabriela; Wrba, Fritz; Thurnher, Dietmar; Selzer, Edgar

    2015-03-01

    In the literature, HPV infection and/or p16 positivity have been consistently demonstrated to correlate with improved response rates in oropharyngeal squamous cell carcinoma (OPSCC) patients treated with primary radiotherapy (RT) alone and in combination with chemotherapy. However, the exact role of HPV/p16 positivity in patients treated with postoperative RT is still unclear. We analyzed tumor samples for HPV-DNA and p16 expression and correlated these variables with treatment outcome in a series of 63 consecutively treated oropharyngeal cancer patients (95% stage III/IV). HPV and p16 analysis were performed using validated test systems. Survival was estimated by the Kaplan-Meier method. Cox proportional hazard regression models were applied to compare the risk of death among patients stratified according to risk factors. Expression of p16 or high-risk HPV-DNA was detected in 60.3% and 39.6% of the tumors, respectively. p16 expression [overall survival (OS) at 2 years: 91%] as well as HPV infection (OS at 2 years: 95%) was associated with improved OS. Mean survival in p16-positive patients was 112 months compared to 64.6 months in case of p16 negativity. All HPV-positive tumors stained positive for p16. In a multivariable analysis, p16 positivity was associated with improved OS and with disease-free survival. p16 expression and HPV infection are strongly associated with the outcome of postoperatively irradiated OPSCC patients. HPV and p16 double-negative OPSCC patients should be regarded as a distinct "very high-risk patient group" that may benefit from intensified or novel treatment combinations.

  4. High-dose nimotuzumab improves the survival rate of esophageal cancer patients who underwent radiotherapy

    PubMed Central

    Wang, Chunyu; Fu, Xiaolong; Cai, Xuwei; Wu, Xianghua; Hu, Xichun; Fan, Min; Xiang, Jiaqing; Zhang, Yawei; Chen, Haiquan; Jiang, Guoliang; Zhao, Kuaile

    2016-01-01

    Nimotuzumab (h-R3) is a humanized monoclonal antibody that is safe to use against epidermal growth factor receptor (EGFR). However, the available information is insufficient about the dose effect of monoclonal antibody against epidermal growth factor receptor for the treatment of esophageal squamous cell carcinoma (ESCC). We retrospectively recruited 66 patients with ESCC who were treated with h-R3 and chemoradiotherapy/radiotherapy. Patients who received more than 1,200 mg of h-R3 were classified as the high-dose group, and the remaining patients were classified as the low-dose group. The endpoint for efficacy was the overall survival. Differences in survival between the groups were analyzed using the log-rank test. The Cox proportional hazards model was used in multivariate analysis to identify independent prognostic factors. The low-dose and high-dose groups comprised 55 and eleven patients, respectively. The median follow-up time in the final analysis was 46 months. The high-dose group showed no increased incidence of toxicities compared to the low-dose group. The 1-, 2-, and 5-year overall survival rates in the low-dose and high-dose groups were 66.9%, 50.0%, 31.5% and 90.0%, 80.0%, 66.7%, respectively (P=0.04). Multivariate analyses showed that the high-dose group had better survival than the low-dose group (hazard ratio 0.28, 95% confidence interval 0.09–0.94, P=0.039). Taken together, high-dose h-R3 showed limited toxicity and improved survival in patients with ESCC. PMID:26766917

  5. Postoperative radiotherapy improves local control and survival in patients with uterine leiomyosarcoma

    PubMed Central

    2013-01-01

    Background To examine the role of radiotherapy (RT) in uterine leiomyosarcomas (LMS) and to determine the patient population who may benefit from RT. Methods From 1998–2008, 69 patients with primary uterine LMS underwent hysterectomy with or without pelvic radiotherapy to a median dose of 45 Gy. Univariate analysis was performed using the Kaplan-Meier method and cumulative-incidence function, and multivariate analyses using Fine and Gray or Cox proportional hazard models. Results Following surgery, 32 out of 69 patients received RT. There was no evidence of any correlation between patient, disease and treatment characteristics and the use of RT. Median follow-up was 57 months. RT was associated with reduced local recurrence (3y LR 19% vs. 39%; Gray’s p = 0.019) and improved overall survival (3y OS 69% vs. 35%; log-rank p = 0.025) on univariate analysis. Multivariate analysis demonstrated that RT reduced LR (HR: 0.28, CI: 0.11-0.69, p = 0.006) and increased OS (HR: 0.44, CI: 0.23-0.85, p = 0.014) independent of other clinical and pathologic factors. Positive surgical margins increased the odds of LR (HR: 5.6, CI: 2.3-13.4, p = 0.00012). Large tumor size and advanced stage (II-IV) were associated with the development of distant metastases and inferior OS. Conclusions Postoperative pelvic RT reduces LR and improves OS of patients with uterine LMS. PMID:23705661

  6. Prescription dose and fractionation predict improved survival after stereotactic radiotherapy for brainstem metastases.

    PubMed

    Leeman, Jonathan E; Clump, David A; Wegner, Rodney E; Heron, Dwight E; Burton, Steven A; Mintz, Arlan H

    2012-07-11

    Brainstem metastases represent an uncommon clinical presentation that is associated with a poor prognosis. Treatment options are limited given the unacceptable risks associated with surgical resection in this location. However, without local control, symptoms including progressive cranial nerve dysfunction are frequently observed. The objective of this study was to determine the outcomes associated with linear accelerator-based stereotactic radiotherapy or radiosurgery (SRT/SRS) of brainstem metastases. We retrospectively reviewed 38 tumors in 36 patients treated with SRT/SRS between February 2003 and December 2011. Treatment was delivered with the Cyberknife™ or Trilogy™ radiosurgical systems. The median age of patients was 62 (range: 28-89). Primary pathologies included 14 lung, 7 breast, 4 colon and 11 others. Sixteen patients (44%) had received whole brain radiation therapy (WBRT) prior to SRT/SRS; ten had received prior SRT/SRS at a different site (28%). The median tumor volume was 0.94 cm3 (range: 0.01-4.2) with a median prescription dose of 17 Gy (range: 12-24) delivered in 1-5 fractions. Median follow-up for the cohort was 3.2 months (range: 0.4-20.6). Nineteen patients (52%) had an MRI follow-up available for review. Of these, one patient experienced local failure corresponding to an actuarial 6-month local control of 93%. Fifteen of the patients with available follow-up imaging (79%) experienced intracranial failure outside of the treatment volume. The median time to distant intracranial failure was 2.1 months. Six of the 15 patients with distant intracranial failure (40%) had received previous WBRT. The actuarial overall survival rates at 6- and 12-months were 27% and 8%, respectively. Predictors of survival included Graded Prognostic Assessment (GPA) score, greater number of treatment fractions, and higher prescription dose. Three patients experienced acute treatment-related toxicity consisting of nausea (n = 1) and headaches (n = 2) that

  7. On the apparent failure of adjuvant pelvic radiotherapy to improve survival for women with uterine sarcomas confined to the uterus.

    PubMed

    Dusenbery, Kathryn E; Potish, Roger A; Argenta, Peter A; Judson, Patricia L

    2005-06-01

    Despite numerous studies documenting reduction of pelvic relapses after adjuvant pelvic radiotherapy stage I and II uterine sarcomas, improved survival remains unproven. This retrospective report analyzes patterns of failure, survival, and toxicity in 42 women with stage I and 7 patients with stage II uterine sarcomas treated from 1972 through 1998 to identify patients likely to benefit from pelvic or abdominal radiotherapy and chemotherapy. Four of these patients also received adjuvant chemotherapy. There were 20 leiomyosarcomas, 18 homologous mixed mullerian tumors, and 11 heterologous mixed mullerian tumors. Disease-free survivals for mixed mullerian tumors were 65% at 5 years and 61% at 15 years. Disease-free survivals for leiomyosarcomas were 40% at 5 years and 40% at 15 years. There were 14 distant only, 5 distant and abdominal, 1 abdominal, 1 distant and pelvic, and 2 unknown initial sites of failure. Acute toxicity was acceptable as measured by a median 1-kg weight loss from radiotherapy and a 2% rate of failure to complete therapy. Chronic toxicity consisted of 3 small bowel obstructions and 1 sigmoid colon obstruction. In conclusion, the efficacy of adjuvant pelvic radiation is demonstrated by the absence of any isolated pelvic failures. Although the frequent occurrence of peritoneal failures suggests a role for prophylactic abdominal radiation for mixed mullerian tumors, more effective systemic therapy is necessary to substantially increase the chance of cure for women with early-stage uterine sarcomas.

  8. Radiotherapy Is Associated With Improved Survival in Adjuvant and Palliative Treatment of Extrahepatic Cholangiocarcinomas

    SciTech Connect

    Shinohara, Eric T. Mitra, Nandita; Guo Mengye; Metz, James M.

    2009-07-15

    Purpose: Extrahepatic cholangiocarcinomas (EHC) are rare tumors of the biliary tree because of their low incidence, large randomized studies examining radiotherapy (RT) for EHC have not been performed. The purpose of this study was to examine the role of adjuvant and palliative RT in the treatment of EHC in a large patient population. Methods and Materials: This was a retrospective analysis of 4,758 patients with EHC collected from the Surveillance, Epidemiology, and End Results database. The primary endpoint was overall survival. Results: Patients underwent surgery (28.8%), RT (10.0%), surgery and RT (14.7%), or no RT or surgery (46.4%). The median age of the patient population was 73 years (range, 23-104), 52.5% were men, and 80.7% were white. The median overall survival time was 16 months (95% confidence interval [CI] 15-17), 9 months (95% CI 9-11), 9 months (95% CI 9-10), and 4 months (95% CI 3-4) for surgery and RT, surgery, RT, and no RT or surgery, respectively. The overall survival was significantly different between the surgery and surgery and RT groups (p < .0001) and RT and no RT or surgery groups (p < .0001) on the log-rank test. The propensity score-adjusted analyses of surgery and RT vs. surgery (hazard ratio, 0.94; 95% CI, 0.84-1.05) were not significantly different, but that for RT vs. no RT or surgery (hazard ratio, 0.61; 95% CI, 0.54-0.70) was significantly different. Conclusion: These results suggest that palliative RT prolongs survival in patients with EHC. The benefit associated with surgery and RT was significant on univariate analysis but not after controlling for potential confounders using the propensity score. Future studies should evaluate the addition of chemotherapy and biologic agents for the treatment of EHC.

  9. Improved overall survival with adjuvant radiotherapy for high-intermediate and high risk Stage I endometrial cancer.

    PubMed

    Harkenrider, Matthew M; Adams, William; Block, Alec M; Kliethermes, Stephanie; Small, William; Grover, Surbhi

    2017-03-01

    To perform a large analysis of Stage I endometrioid-type endometrial cancer patients to determine the impact of adjuvant radiotherapy (ART) on survival. 132,976 FIGO Stage I endometrioid-type endometrial cancer patients treated surgically were identified within the National Cancer Database (NCDB) comprising Commission on Cancer facilities in the United States. Patients were categorized as observation (OBS) or ART (vaginal brachytherapy, external beam radiotherapy, or both). Univariable generalized linear mixed effects models were used to estimate the odds of receiving ART, and a multivariable frailty survival model was used to estimate the instantaneous hazard of death for those receiving OBS versus ART. Due to the presence of a significant interaction, these estimates were stratified by PORTEC-based low, low-intermediate, high-intermediate, and high risk groups. 104,645 (79%) underwent OBS while 28,331 (21%) received ART. Of those receiving ART, 12,913 (46%) received VBT alone, 12,857 (45%) received EBRT alone, and 2561 (9%) received EBRT+VBT. On univariable analysis, increasing stage/myometrial invasion, higher grade, older age, presence of lymphovascular space invasion, and larger tumor size predicted poorer survival (all p<0.01). On multivariable analysis, patients at high-intermediate risk and high risk experienced improved survival with ART with a hazard ratio of 0.796 (95% CI: 0.731-0.867; p<0.001) and 0.783 (95% CI: 0.693-0.885; p<0.001), respectively. There was no survival benefit for ART among patients at low or low-intermediate risk. In Stage I high-intermediate and high risk endometrioid-type endometrial cancer patients, ART significantly improves overall survival. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Combination of adjuvant chemotherapy and radiotherapy is associated with improved survival at early stage type II endometrial cancer and carcinosarcoma.

    PubMed

    Sozen, Hamdullah; Çiftçi, Rumeysa; Vatansever, Dogan; Topuz, Samet; Iyibozkurt, Ahmet Cem; Bozbey, Hamza Ugur; Yaşa, Cenk; Çali, Halime; Yavuz, Ekrem; Kucucuk, Seden; Aydiner, Adnan; Salihoglu, Yavuz

    2016-04-01

    The aim of this study was to describe the impact of postoperative adjuvant treatment modalities and identify risk factors associated with recurrence and survival rates in women diagnosed with early stage type II endometrial cancer and carcinosarcoma. In this retrospective study, patients diagnosed with early stage (stages I-II) carcinosarcoma and type II endometrial cancer were reviewed. All women underwent comprehensive surgical staging. Postoperative treatment options of chemotherapy (CT), radiotherapy (RT), observation (OBS) and chemotherapy-radiotherapy (CT-RT) combination were compared in terms of recurrence and survival outcome. In CT-RT treatment arm, recurrence rate was found as 12.5% and this result is significantly lower than the other treatment approaches (P = 0.01 CT alone: 33.3%, RT alone: 26.7%, OBS: 62.5%). Three-year disease free survival(DFS) rate and overall survival (OS) rate were statistically higher for the group of women treated with combination of CT-RT (92-95%) compared to the women treated with RT alone (65-72%), treated with CT alone (67-74%) and women who received no adjuvant therapy (38-45%). The multivariate analysis revealed that carcinosarcoma histology was associated with shortened DFS and OS (P = 0.001, P = 0.002). On the other hand, being at stage Ia (P = 0.01, P = 0.04) and receiving adjuvant treatment of CT-RT combination (P = 0.005, P = 0.002) appeared to lead to increased DFS and OS rates. We identified that a combination treatment of chemotherapy and radiotherapy is superior compared to other postoperative adjuvant treatment approaches concerning PFS, OS and recurrence rates in stages I-II of type II endometrial cancers and uterine carcinosarcoma. © 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  11. Surgery Combined with Radiotherapy Improved Survival in Metastatic Esophageal Cancer in a Surveillance Epidemiology and End Results Population-based Study

    PubMed Central

    Wu, San-Gang; Xie, Wei-Hao; Zhang, Zhao-Qiang; Sun, Jia-Yuan; Li, Feng-Yan; Lin, Huan-Xin; Yong Bao; He, Zhen-Yu

    2016-01-01

    This retrospective study used a population-based national registry to determine the impact of local treatment modalities on survival in patients with metastatic esophageal cancer (EC). The Surveillance Epidemiology and End Results (SEER) database was used to identify patients with metastatic EC from 1988 to 2012. A total of 9,125 patients were identified. There were 426 patients underwent primary surgery, 4,786 patients were administered radiotherapy (RT) alone, 847 patients underwent surgery plus RT, and 3,066 patients without any local treatment. Multivariate analysis results indicated that year of diagnosis, age, race, histologic subtype, grade, and local treatment modalities were independent prognostic factors for overall survival (OS). The 5-year OS were 8.4%, 4.5%, 17.5%, and 3.4% in primary surgery, RT only, surgery plus RT, and no local treatment, respectively (P < 0.001). Subgroup analyses showed that the impact of RT was mainly reflected by preoperative radiotherapy, as patients received preoperative radiotherapy had significantly better OS than patients who underwent primary surgery alone and postoperative RT, the 5-year OS rates were 24.7%, 6.5%, and 7.8%, respectively, respectively (P < 0.001). Surgery plus RT, especially preoperative RT, may improve long-term survival of patients with metastatic EC. PMID:27323696

  12. Improved Survival in Patients With Stage III-IV Head and Neck Cancer Treated With Radiotherapy as Primary Local Treatment Modality

    SciTech Connect

    Rusthoven, Kyle E.; Raben, David; Chen Changhu

    2008-10-01

    Purpose: To evaluate the overall and cause-specific survival in patients with Stage III-IVb head and neck squamous cell carcinoma treated with radiotherapy (RT) as the primary local treatment modality. Methods and Materials: The survival of patients with American Joint Committee on Cancer Stage III-IVb head and neck squamous cell carcinoma treated with primary RT was queried using the Surveillance, Epidemiology and End Results database. The effect of the year of treatment on overall and cause-specific survival was analyzed as a categorical and continuous variable. The patterns of care for these patients were also evaluated. Results: Between 1988 and 2004, 6,759 patients were identified. Survival was significantly improved in patients treated more recently. When analyzed as a continuous variable, each year was associated with a 3% and 4.1% reduction in the relative risk of overall and cause-specific mortality, respectively (p < 0.0001). Patients treated after 1998 had a 7.6% and 6.1% absolute improvement in overall and cause-specific survival, respectively, compared with patients treated before 1998 (overall survival, hazard ratio, 0.81; cause-specific survival, hazard ratio, 0.77; p < 0.0001). This benefit in survival was limited to tumors of the oral cavity, oropharynx, and hypopharynx. The use of RT increased among patients treated more recently. This shift in patterns of care was most pronounced for tumors of the larynx and hypopharynx. Conclusions: The overall and cause-specific survival of patients with Stage III-IVb head and neck squamous cell carcinoma treated with primary RT has improved with time. The improvement is consistent with that observed in a large meta-analysis of randomized patients treated with concurrent chemoradiotherapy.

  13. Improved survival with stereotactic ablative radiotherapy (SABR) over lobectomy for early stage non-small cell lung cancer (NSCLC): addressing the fallout of disruptive randomized data

    PubMed Central

    Kavanagh, Brian D.; Karam, Sana D.

    2015-01-01

    The gold-standard therapy for early stage non-small cell lung cancer (esNSCLC) has historically been lobectomy with mediastinal lymph node dissection. However, up to one-third of patients with esNSCLC are considered medically-inoperable due to factors such as advanced age and comorbid illnesses. The past decade has witnessed a dramatic increase in the use of high-dose conformal radiotherapy delivered over 1-5 fractions, synonymously termed stereotactic ablative radiotherapy (SABR) or stereotactic body radiation therapy (SBRT). High rates of tumor control and favorable toxicity profiles have led to the adoption of SABR as the treatment of choice for medically-inoperable patients. Limited but growing data exist using SABR for medically-operable patients who are also candidates for lobectomy. A recent pooled analysis of two multicenter prospective randomized trials, the STARS (NCT00840749) and ROSEL (NCT00687986) protocols, published by Chang and colleagues (PMID 25981812) reported improved overall survival (OS) and reduced toxicity with SABR over lobectomy for medically-operable patients with esNSCLC. In this article we review the outcomes of this analysis in the context of existing radiotherapy and surgical data for NSCLC. Further, we discuss the potential causes and implications of these provocative results, including the shifting balance between oncologic control and treatment-related mortality in comparisons of SABR and surgical resection, termed the Head Start Effect. PMID:26244136

  14. A novel HSP90 inhibitor with reduced hepatotoxicity synergizes with radiotherapy to induce apoptosis, abrogate clonogenic survival, and improve tumor control in models of colorectal cancer

    PubMed Central

    Albrecht, Valerie; Hennel, Roman; Brix, Nikko; Frey, Benjamin; Gaipl, Udo S.; Zuchtriegel, Gabriele; Reichel, Christoph A.; Blutke, Andreas; Schilling, Daniela; Multhoff, Gabriele; Li, Minglun; Niyazi, Maximilian; Friedl, Anna A.; Winssinger, Nicolas; Belka, Claus; Lauber, Kirsten

    2016-01-01

    The chaperone heat shock protein 90 (HSP90) crucially supports the maturation, folding, and stability of a variety of client proteins which are of pivotal importance for the survival and proliferation of cancer cells. Consequently, targeting of HSP90 has emerged as an attractive strategy of anti-cancer therapy, and it appears to be particularly effective in the context of molecular sensitization towards radiotherapy as has been proven in preclinical models of different cancer entities. However, so far the clinical translation has largely been hampered by suboptimal pharmacological properties and serious hepatotoxicity of first- and second-generation HSP90 inhibitors. Here, we report on NW457, a novel radicicol-derived member of the pochoxime family with reduced hepatotoxicity, how it inhibits the DNA damage response and how it synergizes with ionizing irradiation to induce apoptosis, abrogate clonogenic survival, and improve tumor control in models of colorectal cancer in vitro and in vivo. PMID:27259245

  15. Adjuvant radiotherapy improves overall survival in patients with resected gastric adenocarcinoma: A National Cancer Data Base analysis.

    PubMed

    Stumpf, Priscilla K; Amini, Arya; Jones, Bernard L; Koshy, Matthew; Sher, David J; Lieu, Christopher H; Schefter, Tracey E; Goodman, Karyn A; Rusthoven, Chad G

    2017-09-01

    For patients with resectable gastric adenocarcinoma, perioperative chemotherapy and adjuvant chemoradiotherapy (CRT) are considered standard options. In the current study, the authors used the National Cancer Data Base to compare overall survival (OS) between these regimens. Patients who underwent gastrectomy for nonmetastatic gastric adenocarcinoma from 2004 through 2012 were divided into those treated with perioperative chemotherapy without RT versus those treated with adjuvant CRT. Survival was estimated and compared using univariate and multivariate models adjusted for patient and tumor characteristics, surgical margin status, and the number of lymph nodes examined. Subset analyses were performed for factors chosen a priori, and potential interactions between treatment and covariates were assessed. A total of 3656 eligible patients were identified, 52% of whom underwent perioperative chemotherapy and 48% of whom received postoperative CRT. The median follow-up was 47 months, and the median age of the patients was 62 years. Analysis of the entire cohort demonstrated improved OS with adjuvant RT on both univariate (median of 51 months vs 42 months; P = .013) and multivariate (hazard ratio, 0.874; 95% confidence interval, 0.790-0.967 [P = .009]) analyses. Propensity score-matched analysis also demonstrated improved OS with adjuvant RT (median of 49 months vs 39 months; P = .033). On subset analysis, a significant interaction was observed between the survival impact of adjuvant RT and surgical margins, with a greater benefit of RT noted among patients with surgical margin-positive disease (hazard ratio with RT: 0.650 vs 0.952; P for interaction <.001). In this National Cancer Data Base analysis, the use of adjuvant RT in addition to chemotherapy was associated with a significant OS advantage for patients with resected gastric cancer. The survival advantage observed with adjuvant CRT was most pronounced among patients with positive surgical margins. Cancer 2017

  16. The addition of high-dose tamoxifen to standard radiotherapy does not improve the survival of patients with diffuse intrinsic pontine glioma.

    PubMed

    Michalski, Antony; Bouffet, Eric; Taylor, Roger E; Hargrave, Darren; Walker, David; Picton, Susan; Robinson, Kathryn; Pizer, Barry; Bujkiewicz, Sylwia

    2010-10-01

    The study aimed to examine the tolerability of the combination of radiotherapy and tamoxifen and the effect on median and event free survival as well as collecting data on the use of steroids in this population. 31 patients with diffuse intrinsic pontine glioma, diagnosed on clinical and radiological criteria, were treated with high-dose oral tamoxifen (120 mg/m(2)/day) given concomitantly with standard dose radiotherapy (54 Gy in 1.8 Gy fractions over 6 weeks). Results Tamoxifen was well tolerated with no grade 3 or 4 CTC toxicity reported. At 1 year, the progression free and event free survival were 3.2% (95% CI: 0.2-14.1%), and at 6 months 19.4% (CI: 7.9% to 34.6%). The overall survival at 1 year was 16.1% (CI: 5.9-30.9%) with median survival 6.32 months. In this study, in which tamoxifen was used in conjunction with radiotherapy, progression free survival was shown to be less good when compared with historical data HR = 3.1 (CI: 1.7-5.7). There was no significant reduction in overall survival. The addition of high-dose tamoxifen, although well tolerated, confers no clinical benefit to patients treated with diffuse intrinsic pontine glioma treated with standard radiotherapy.

  17. Impact of intense systemic therapy and improved survival on the use of palliative radiotherapy in patients with bone metastases from prostate cancer

    PubMed Central

    Nieder, Carsten; Haukland, Ellinor; Mannsåker, Bård; Norum, Jan

    2016-01-01

    More effective drugs may reduce the requirement for palliative external beam radiotherapy for bony target volumes; however, living with metastases for prolonged periods of time may result in more frequent episodes of bone pain or serious skeletal-related events. The purpose of the present study was to evaluate how recent advances in systemic therapy impact radiotherapy utilization. A retrospective analysis of a comprehensive regional database was performed. All oncology care in this region was provided by only one center, assuring complete data. Patients that had succumbed between June 1, 2004 and June 1, 2015 were included. For all 236 patients, the median age at diagnosis of bone metastases was 75 years and median overall survival was 20 months. More intense systemic therapy was associated with a significantly longer survival time. Only 69 patients (29%) did not receive palliative radiotherapy for bony target volumes, whilst 1 course was given to 101 patients (43%), 2 courses to 34 patients (14%) and >2 courses to 32 patients (14%). Radiotherapy was used more frequently in younger patients, those with spinal cord compressions or pathological fractures, and those treated with intense and long-standing systemic therapy. Radiotherapy utilization increased with survival time. For 100 poor-prognosis patients that succumbed within 12 months, 57 courses of palliative radiotherapy were administered, whilst 100 patients that survived for 12–24 months were administered 114 courses (24–36 months, 148 courses). In conclusion, the use of palliative radiotherapy did not decrease when more effective systemic therapy was administered. However, provided that only 5% of patients received radionuclide treatment, additional studies in other populations are required. PMID:27698881

  18. Did the addition of concurrent chemotherapy to conventional radiotherapy improve survival for patients with HPV+ve and HPV-ve Oropharynx cancer? A population-based study.

    PubMed

    Hall, Stephen F; Liu, Fei-Fei; O'Sullivan, Brian; Shi, Willa; Rohland, Susan; Griffiths, Rebecca; Groome, Patti

    2017-10-10

    In the absence of clear evidence on the efficacy of concurrent chemoradiotherapy (CRT) over conventional radiotherapy (RT) for HPV+ve and for HPV-ve oropharyngeal cancer (OPC), this study compares the treatments and outcomes from pre-CRT years to post-CRT years. A population-based retrospective treatment-effectiveness study based on all patients with OPC treated in Ontario Canada in 1998, 1999, 2003 and 2004. Charts were reviewed, tissue samples were requested and tissue was tested for p16 or in situ hybridisation. Overall survival (OS) and disease-specific survival (DSS) were compared by treatment era and by treatment type for all 1028 patients, for 865 treated for cure and for 610 with HPV status. There was no improvement in OS comparing pre-CRT to post-CRT eras for the HPV+ve patients (P=0.147) or for the HPV-ve patients (P=0.362). There was no difference in OS comparing CRT to RT for the HPV+ve cohort (HR=0.948 (0.642-1.400)) or for the HPV-ve patients (HR=1.083 (0.68-1.727)). In these 'real-world' patients what appeared to be improvements in OS with CRT in clinical trials were confounded by HPV status in Ontario. CRT did not improve outcomes for HPV+ve or for HPV-ve patients.

  19. Postmastectomy Radiotherapy Improves Disease-Free Survival of High Risk of Locoregional Recurrence Breast Cancer Patients with T1-2 and 1 to 3 Positive Nodes

    PubMed Central

    Li, Fang-Yan; Lin, Qin; Lin, Huan-Xin; Sun, Jia-Yuan

    2015-01-01

    Objectives The indications for post-mastectomy radiotherapy (PMRT) with T1-2 breast cancer and 1-3 positive axillary lymph nodes is still controversial. The purpose of this study was to investigate the role of PMRT in T1-2 breast cancer with 1-3 positive axillary lymph node. Methods We retrospectively reviewed the file records of 79 patients receiving PMRT and not receiving PMRT (618 patients). Results The median follow-up was 65 months. Multivariate analysis showed that PMRT was an independent prognostic factor of locoregional recurrence-free survival (LRFS) (P = 0.010). Subgroup analysis of patients who did not undergo PMRT showed that pT stage, number of positive axillary lymph nodes, and molecular subtype were independent prognostic factors of LRFS. PMRT improved LRFS in the entire group (P = 0.005), but did not affect distant metastasis-free survival (DMFS) (P = 0.494), disease-free survival (DFS) (P = 0.215), and overall survival (OS) (P = 0.645). For patients without PMRT, the 5-year LRFS of low-risk patients (0–1 risk factor for locoregional recurrence) of 94.5% was significantly higher than that of high-risk patients (2-3 risk factors for locoregional recurrence) (80.9%, P < 0.001). PMRT improved LRFS (P = 0.001) and DFS (P = 0.027) in high-risk patients, but did not improve LRFS, DMFS, DFS, and OS in low-risk patients. Conclusions PMRT is beneficial in patients with high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes. PMID:25781605

  20. Patient Prognostic Score and Associations With Survival Improvement Offered by Radiotherapy After Breast-Conserving Surgery for Ductal Carcinoma In Situ: A Population-Based Longitudinal Cohort Study

    PubMed Central

    Freedman, Rachel A.; Vaz-Luis, Ines; Mallory, Melissa Anne; Wong, Stephanie M.; Aydogan, Fatih; DeSantis, Stephen; Barry, William T.; Golshan, Mehra

    2016-01-01

    Purpose Radiotherapy (RT) after breast-conserving surgery (BCS) is a standard treatment option for the management of ductal carcinoma in situ (DCIS). We sought to determine the survival benefit of RT after BCS on the basis of risk factors for local recurrence. Patients and Methods A retrospective longitudinal cohort study was performed to identify patients with DCIS diagnosed between 1988 and 2007 and treated with BCS by using SEER data. Patients were divided into the following two groups: BCS+RT (RT group) and BCS alone (non-RT group). We used a patient prognostic scoring model to stratify patients on the basis of risk of local recurrence. We performed a Cox proportional hazards model with propensity score weighting to evaluate breast cancer mortality between the two groups. Results We identified 32,144 eligible patients with DCIS, 20,329 (63%) in the RT group and 11,815 (37%) in the non-RT group. Overall, 304 breast cancer–specific deaths occurred over a median follow-up of 96 months, with a cumulative incidence of breast cancer mortality at 10 years in the weighted cohorts of 1.8% (RT group) and 2.1% (non-RT group; hazard ratio, 0.73; 95% CI, 0.62 to 0.88). Significant improvements in survival in the RT group compared with the non-RT group were only observed in patients with higher nuclear grade, younger age, and larger tumor size. The magnitude of the survival difference with RT was significantly correlated with prognostic score (P < .001). Conclusion In this population-based study, the patient prognostic score for DCIS is associated with the magnitude of improvement in survival offered by RT after BCS, suggesting that decisions for RT could be tailored on the basis of patient factors, tumor biology, and the prognostic score. PMID:26834064

  1. Survival and Symptom Relief after Palliative Radiotherapy for Esophageal Cancer.

    PubMed

    Welsch, Julia; Kup, Philipp Günther; Nieder, Carsten; Khosrawipour, Veria; Bühler, Helmut; Adamietz, Irenäus A; Fakhrian, Khashayar

    2016-01-01

    The aim of this study was to assess the 6-months dysphagia-free survival, improvement in swallowing function, complication rate, and overall survival in patients with incurable esophageal cancer treated with palliative radiotherapy. We retrospectively reviewed data from 139 patients (median age 72 years) with advanced/recurrent incurable esophageal cancer, who were referred to 3 German radiation oncology centers for palliative radiotherapy between 1994 and 2014. Radiotherapy consisted of external beam radiotherapy (EBRT) with 30 - 40.5 Gy/2.5 - 3 Gy per fraction, brachytherapy alone (BT) with 15 - 25 Gy/5 - 7Gy per fraction/weekly and EBRT + BT (30 - 40.5 Gy plus 10 - 14 Gy with BT) in 65, 46, and 28 patients, respectively. Dysphagia-free survival (Dy-PFS) was defined as the time to worsening of dysphagia for at least one point, a new loco-regional failure or death of any cause. Median follow-up time was 6 months (range 1-6 months). Subjective symptom relief was achieved in 72 % of patients with median response duration of 5 months. The 1-year survival rate was 30%. The 6-months Dy-PFS time for the whole group was 73 ± 4%. The 6-months Dy-PFS was 90 ± 4% after EBRT, 92 ± 5% after EBRT + BT and 37 ± 7% after BT, respectively (p<0.001). Five patients lived for more than 2 years, all of them were treated with EBRT ± BT. Ulceration, fistula and stricture developed in 3, 6 and 7 patients, respectively. Radiotherapy leads to symptom improvement in the majority of patients with advanced incurable esophageal cancer. The present results favor EBRT ± BT over BT alone. Due to the retrospective nature of this study, imbalances in baseline characteristics might have contributed to this finding, and further trials appear necessary.

  2. PTH1-34 Alleviates Radiotherapy-induced Local Bone Loss by Improving Osteoblast and Osteocyte Survival

    PubMed Central

    Chandra, Abhishek; Lin, Tiao; Tribble, Mary Beth; Zhu, Ji; Altman, Allison R.; Tseng, Weiju; Zhang, Yejia; Akintoye, Sunday O.; Cengel, Keith; Liu, X. Sherry; Qin, Ling

    2014-01-01

    Cancer radiotherapy is often complicated by a spectrum of changes in the neighboring bone from mild osteopenia to osteoradionecrosis. We previously reported that parathyroid hormone (PTH, 1–34), an anabolic agent for osteoporosis, reversed bone structural deterioration caused by multiple microcomputed tomography (microCT) scans in adolescent rats. To simulate clinical radiotherapy for cancer patients and to search for remedies, we focally irradiated the tibial metaphyseal region of adult rats with a newly available small animal radiation research platform (SARRP) and treated these rats with intermittent injections of PTH1–34. Using a unique 3D image registration method that we recently developed, we traced the local changes of the same trabecular bone before and after treatments, and observed that, while radiation caused a loss of small trabecular elements leading to significant decreases in bone mass and strength, PTH1–34 preserved all trabecular elements in irradiated bone with remarkable increases in bone mass and strength. Histomorphometry demonstrated that SARRP radiation severely reduced osteoblast number and activity, which were impressively reversed by PTH treatment. In contrast, suppressing bone resorption by alendronate failed to rescue radiation-induced bone loss and to block the rescue effect of PTH1–34. Furthermore, histological analyses revealed that PTH1–34 protected osteoblasts and osteocytes from radiation-induced apoptosis and attenuated radiation-induced bone marrow adiposity. Taken together, our data strongly support a robust radioprotective effect of PTH on trabecular bone integrity through preserving bone formation and shed light on further investigations of an anabolic therapy for radiation-induced bone damage. PMID:24998454

  3. PTH1-34 alleviates radiotherapy-induced local bone loss by improving osteoblast and osteocyte survival.

    PubMed

    Chandra, Abhishek; Lin, Tiao; Tribble, Mary Beth; Zhu, Ji; Altman, Allison R; Tseng, Wei-Ju; Zhang, Yejia; Akintoye, Sunday O; Cengel, Keith; Liu, X Sherry; Qin, Ling

    2014-10-01

    Cancer radiotherapy is often complicated by a spectrum of changes in the neighboring bone from mild osteopenia to osteoradionecrosis. We previously reported that parathyroid hormone (PTH, 1-34), an anabolic agent for osteoporosis, reversed bone structural deterioration caused by multiple microcomputed tomography (microCT) scans in adolescent rats. To simulate clinical radiotherapy for cancer patients and to search for remedies, we focally irradiated the tibial metaphyseal region of adult rats with a newly available small animal radiation research platform (SARRP) and treated these rats with intermittent injections of PTH1-34. Using a unique 3D image registration method that we recently developed, we traced the local changes of the same trabecular bone before and after treatments, and observed that, while radiation caused a loss of small trabecular elements leading to significant decreases in bone mass and strength, PTH1-34 preserved all trabecular elements in irradiated bone with remarkable increases in bone mass and strength. Histomorphometry demonstrated that SARRP radiation severely reduced osteoblast number and activity, which were impressively reversed by PTH treatment. In contrast, suppressing bone resorption by alendronate failed to rescue radiation-induced bone loss and to block the rescue effect of PTH1-34. Furthermore, histological analyses revealed that PTH1-34 protected osteoblasts and osteocytes from radiation-induced apoptosis and attenuated radiation-induced bone marrow adiposity. Taken together, our data strongly support a robust radioprotective effect of PTH on trabecular bone integrity through preserving bone formation and shed light on further investigations of an anabolic therapy for radiation-induced bone damage.

  4. Survival analysis of laryngeal carcinoma without laryngectomy, radiotherapy, or chemotherapy.

    PubMed

    Yu, Qiong; Zhang, Xueyuan; Ji, Changyou; Yang, Hua; Gao, Minghua; Hong, Suling; Hu, Guohua

    2012-09-01

    This study aimed at investigating the survival rate and prognostic factors of laryngeal carcinoma patients in the absence of the use of laryngectomy, radiotherapy, and chemotherapy. A total of 167 cases of laryngeal carcinoma without the use of laryngectomy, radiotherapy, or chemotherapy were analyzed retrospectively. Surveyed items included age, smoking history, tumor family history, tuberculosis history, primary site, pathological grade, T-stage, N-stage, clinical stage, and whether tracheotomy had been performed. Survival rates were calculated using the Kaplan-Meier method. For univariate analysis, comparison among/between groups was performed using the log-rank test. Multivariate analysis was carried out using the Cox proportional hazard model. Overall median survival time was 16 ± 1.44 months, and overall 1- and 2-year survival rates were 56.4 and 26.5%, respectively. No patient survived over 5 years in cases diagnosed for more than 5 years (except for cases that were lost). The median survival time of clinical stage 0/I/II was 28 ± 3.81 months, and 1- and 2-year survival rates were 79.3 and 59.3%, respectively; the median survival time of III/IV clinical stages was 11 ± 1.32 months, and 1- and 2-year survival rates were 45.5 and 10.6%, respectively. Univariate analysis showed that primary site, pathological grade, T-stage, N-stage, and clinical stage were significant prognostic factors for the survival of the patients (P < 0.05). Whether tracheotomy had been performed was not significant for affecting survival rates. Multivariate analysis showed survival rates were statistically correlated with T-stage and N-stage (P < 0.05). The development of laryngeal carcinoma course was faster, without treatment to the tumor itself, even if palliative surgery such as tracheostomy would not improve the survival rate. In laryngeal carcinoma patients with no surgery, radiotherapy or chemotherapy, the factors affecting the survival rates include primary site, pathological

  5. Stereotactic Body Radiotherapy for Pulmonary Metastases From Soft-Tissue Sarcomas: Excellent Local Lesion Control and Improved Patient Survival

    SciTech Connect

    Dhakal, Sughosh; Corbin, Kimberly S.; Milano, Michael T.; Philip, Abraham; Sahasrabudhe, Deepak; Jones, Carolyn

    2012-02-01

    Purpose: Patients with pulmonary metastases (PM) from soft-tissue sarcomas (STS) have historically been treated with surgery and/or chemotherapy. Since 2001, we have treated PM with stereotactic body radiation therapy (SBRT). We postulated that SBRT for PM from STS would yield excellent local control (LC) and overall survival (OS). Methods and Materials: Fifty-two patients with PM from STS, diagnosed between 1990 and 2006 at University of Rochester, were retrospectively reviewed. Most patients received multimodality treatment comprising of surgery, chemotherapy, and/or radiation. SBRT used the Novalis ExacTrac patient positioning platform, vacuum bag immobilization, and relaxed end-expiratory breath hold techniques. Results: Leiomyosarcoma (23%), malignant fibrous histiocytoma (19%), and synovial sarcoma (15%) were the most common histologies. Forty-eight percent initially presented with PM, whereas 52% developed PM at a median of 0.7 (0.3-7.3) years after initial diagnosis. Median follow-up from diagnosis of PM was 0.9 (0.3-7.3) years. Fifteen patients underwent SBRT to 74 lesions. Median number of lesions treated was 4 (1-16) per patient and 3.5 (1-6) per session. Preferred dose and fractionation was 50 Gy in 5 Gy fractions. Three-year LC was 82%. No patients experienced Grade {>=}3 toxicity. Median OS was 2.1 (0.8-11.5) years for patients treated with SBRT, and 0.6 (0.1-7.8) years for those who never received SBRT (p = 0.002). Conclusions: SBRT provides excellent LC of PM and may extend OS. SBRT should be considered for all patients with PM from STS, particularly those who are not surgical candidates. Further investigation is warranted to establish criteria for the use of SBRT for STS patients with PM.

  6. Palliative radiotherapy in addition to self-expanding metal stent for improving dysphagia and survival in advanced oesophageal cancer (ROCS: Radiotherapy after Oesophageal Cancer Stenting): study protocol for a randomized controlled trial.

    PubMed

    Adamson, Douglas; Blazeby, Jane; Nelson, Annmarie; Hurt, Chris; Nixon, Lisette; Fitzgibbon, Jim; Crosby, Tom; Staffurth, John; Evans, Mim; Kelly, Noreen Hopewell; Cohen, David; Griffiths, Gareth; Byrne, Anthony

    2014-10-22

    The single most distressing symptom for patients with advanced esophageal cancer is dysphagia. Amongst the more effective treatments for relief of dysphagia is insertion of a self-expanding metal stent (SEMS). It is possible that the addition of a palliative dose of external beam radiotherapy may prolong the relief of dysphagia and provide additional survival benefit. The ROCS trial will assess the effect of adding palliative radiotherapy after esophageal stent insertion. The study is a randomized multicenter phase III trial, with an internal pilot phase, comparing stent alone versus stent plus palliative radiotherapy in patients with incurable esophageal cancer. Eligible participants are those with advanced esophageal cancer who are in need of stent insertion for primary management of dysphagia. Radiotherapy will be administered as 20 Gray (Gy) in five fractions over one week or 30 Gy in 10 fractions over two weeks, within four weeks of stent insertion. The internal pilot will assess rates and methods of recruitment; pre-agreed criteria will determine progression to the main trial. In total, 496 patients will be randomized in a 1:1 ratio with follow up until death. The primary outcome is time to progression of patient-reported dysphagia. Secondary outcomes include survival, toxicity, health resource utilization, and quality of life. An embedded qualitative study will explore the feasibility of patient recruitment by examining patients' motivations for involvement and their experiences of consent and recruitment, including reasons for not consenting. It will also explore patients' experiences of each trial arm. The ROCS study will be a challenging trial studying palliation in patients with a poor prognosis. The internal pilot design will optimize methods for recruitment and data collection to ensure that the main trial is completed on time. As a pragmatic trial, study strengths include collection of all follow-up data in the usual place of care, and a focus on

  7. Improved outcome of nasopharyngeal carcinoma treated with conventional radiotherapy

    SciTech Connect

    Palazzi, Mauro . E-mail: mauro.palazzi@istitutotumori.mi.it; Guzzo, Marco; Tomatis, Stefano Ph.D.; Cerrotta, Annamaria; Potepan, Paolo; Quattrone, Pasquale; Cantu, Giulio

    2004-12-01

    Purpose: To describe the outcome of patients with nonmetastatic nasopharyngeal carcinoma (NPC) treated with conventional radiotherapy at a single institution. Methods and materials: From 1990 to 1999, 171 consecutive patients with NPC were treated with conventional (two-dimensional) radiotherapy. Tumor histology was undifferentiated in 82% of cases. Tumor-node-metastasis Stage (American Joint Committee on Cancer/International Union Against Cancer 1997 system) was I in 6%, II in 36%, III in 22%, and IV in 36% of patients. Mean total radiation dose was 68.4 Gy. Chemotherapy was given to 62% of the patients. The median follow-up for surviving patients was 6.3 years (range, 3.1-13.1 years). Results: The 5-year overall survival, disease-specific survival, and disease-free survival rates were 72%, 74%, and 62%, respectively. The 5-year local, regional, and distant control rates were 84%, 80%, and 83% respectively. Late effects of radiotherapy were prospectively recorded in 100 patients surviving without relapse; 44% of these patients had Grade 3 xerostomia, 33% had Grade 3 dental damage, and 11% had Grade 3 hearing loss. Conclusions: This analysis shows an improved outcome for patients treated from 1990 to 1999 compared with earlier retrospective series, despite the use of two-dimensional radiotherapy. Late toxicity, however, was substantial with conventional radiotherapy.

  8. Impact of combined modality treatment with radiotherapy and S-1 on T2N0 laryngeal cancer: Possible improvement in survival through the prevention of second primary cancer and distant metastasis.

    PubMed

    Kitani, Yosuke; Kubota, Akira; Furukawa, Madoka; Hori, Yukiko; Nakayama, Yuko; Nonaka, Tetsuo; Mizoguchi, Nobutaka; Kitani, Yuka; Hatakeyama, Hiromitsu; Oridate, Nobuhiko

    2017-08-01

    In patients with head and neck cancer, the management of second primary cancer (SPC) is particularly important for improving survival because of its high incidence and associated mortality. We evaluated the impact of combination chemotherapy on survival and SPC. We retrospectively analyzed data from 49 patients treated with definitive radiation therapy (RT) for T2N0M0 laryngeal squamous cell carcinoma between 2003 and 2011. Among them, 22 patients received combined modality treatment with radiotherapy and S-1 (RT+CT group). The median follow-up period was 71months (32-111months). A significant difference in overall survival (OS, P<0.01) was observed between the RT+CT group (n=22) and the RT alone group (n=27) though no significant differences were observed in local control and disease specific survival. Univariate analyses showed that an older age (P<0.05) and a higher grade (P<0.05) were associated with OS. Multivariate analysis identified chemotherapy as the most significant predictor of survival (OR, 0.056; 95% CI, 0.008-0.353, P<0.01). A significantly lower incidence of distant metastasis (DM)+SPC (5-year incidence: 5% vs. 19%, P<0.05) and fewer deaths from these causes (1 vs. 8: P<0.05) were observed in the RT+CT group. Multivariate analysis showed that chemotherapy was the most significant factor for the incidence of DM+SPC (OR, 0.074; 95% CI, 0.0065-0.84; P<0.05). The findings of this study suggest the possibility that combined modality treatment with radiotherapy and S-1 improve survival by preventing distant metastasis and second primary cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Hyperfractionated Accelerated Radiotherapy (HART) for Anaplastic Thyroid Carcinoma: Toxicity and Survival Analysis

    SciTech Connect

    Dandekar, Prasad; Rhys-Evans, Peter; Harrington, Kevin; Nutting, Christopher; Newbold, Kate

    2009-06-01

    Purpose: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive cancers, and the current protocol of hyperfractionated accelerated radiotherapy was initiated to improve survival while limiting toxicities. Methods and Materials: All patients with ATC from 1991 to 2002 were accrued and received megavoltage radiotherapy from the mastoid processes to the carina up to 60 Gy in twice-daily fractions of 1.8 and 2 Gy, 6 hours apart. Results: Thirty-one patients were accrued with a median age of 69 years, and 55% were women. Debulking was performed in 26%, and total thyroidectomy, in 6%, whereas 68% received radical radiotherapy alone. Local control data were available for 27 patients: 22% had a complete response, 26% had a partial response, 15% showed progressive disease, and 37% showed static disease. Median overall survival for all 31 patients was 70 days (95% confidence interval, 40-99). There was no significant difference in median survival between patients younger (70 days) and older than 70 years (42 days), between men (70 days) and women (49days), and between patients receiving postoperative radiotherapy (77 days) and radical radiotherapy alone (35 days). Grade III or higher skin erythema was seen in 56% patients; desquamation in 21%; dysphagia in 74%; and esophagitis in 79%. Conclusion: The current protocol failed to offer a significant survival benefit, was associated with severe toxicities, and thus was discontinued. There is a suggestion that younger patients with operable disease have longer survival, but this would require a larger study to confirm it.

  10. Prostate Cancer–Specific Survival Following Salvage Radiotherapy vs Observation in Men With Biochemical Recurrence After Radical Prostatectomy

    PubMed Central

    Trock, Bruce J.; Han, Misop; Freedland, Stephen J.; Humphreys, Elizabeth B.; DeWeese, Theodore L.; Partin, Alan W.; Walsh, Patrick C.

    2011-01-01

    Context Biochemical disease recurrence after radical prostatectomy often prompts salvage radiotherapy, but no studies to date have had sufficient numbers of patients or follow-up to determine whether radiotherapy improves survival, and if so, the subgroup of men most likely to benefit. Objectives To quantify the relative improvement in prostate cancer–specific survival of salvage radiotherapy vs no therapy after biochemical recurrence following prostatectomy, and to identify subgroups for whom salvage treatment is most beneficial. Design, Setting, and Patients Retrospective analysis of a cohort of 635 US men undergoing prostatectomy from 1982–2004, followed up through December 28, 2007, who experienced biochemical and/or local recurrence and received no salvage treatment (n=397), salvage radiotherapy alone (n=160), or salvage radiotherapy combined with hormonal therapy (n=78). Main Outcome Measure Prostate cancer–specific survival defined from time of recurrence until death from disease. Results With a median follow-up of 6 years after recurrence and 9 years after prostatectomy, 116 men (18%) died from prostate cancer, including 89 (22%) who received no salvage treatment, 18 (11%) who received salvage radiotherapy alone, and 9 (12%) who received salvage radiotherapy and hormonal therapy. Salvage radiotherapy alone was associated with a significant 3-fold increase in prostate cancer–specific survival relative to those who received no salvage treatment (hazard ratio [HR], 0.32 [95% confidence interval {CI}, 0.19–0.54]; P<.001). Addition of hormonal therapy to salvage radiotherapy was not associated with any additional increase in prostate cancer–specific survival (HR, 0.34 [95% CI, 0.17–0.69]; P=.003). The increase in prostate cancer–specific survival associated with salvage radiotherapy was limited to men with a prostate-specific antigen doubling time of less than 6 months and remained after adjustment for pathological stage and other established

  11. Intensity-Modulated Radiotherapy for Sinonasal Cancer: Improved Outcome Compared to Conventional Radiotherapy

    SciTech Connect

    Dirix, Piet; Vanstraelen, Bianca; Jorissen, Mark; Vander Poorten, Vincent; Nuyts, Sandra

    2010-11-15

    Purpose: To evaluate clinical outcome and toxicity of postoperative intensity-modulated radiotherapy (IMRT) for malignancies of the nasal cavity and paranasal sinuses. Methods and Materials: Between 2003 and 2008, 40 patients with cancer of the paranasal sinuses (n = 34) or nasal cavity (n = 6) received postoperative IMRT to a dose of 60 Gy (n = 21) or 66 Gy (n = 19). Treatment outcome and toxicity were retrospectively compared with that of a previous patient group (n = 41) who were also postoperatively treated to the same doses but with three-dimensional conformal radiotherapy without intensity modulation, from 1992 to 2002. Results: Median follow-up was 30 months (range, 4-74 months). Two-year local control, overall survival, and disease-free survival were 76%, 89%, and 72%, respectively. Compared to the three-dimensional conformal radiotherapy treatment, IMRT resulted in significantly improved disease-free survival (60% vs. 72%; p = 0.02). No grade 3 or 4 toxicity was reported in the IMRT group, either acute or chronic. The use of IMRT significantly reduced the incidence of acute as well as late side effects, especially regarding skin toxicity, mucositis, xerostomia, and dry-eye syndrome. Conclusions: Postoperative IMRT for sinonasal cancer significantly improves disease-free survival and reduces acute as well as late toxicity. Consequently, IMRT should be considered the standard treatment modality for malignancies of the nasal cavity and paranasal sinuses.

  12. Improving postoperative radiotherapy following radical prostatectomy.

    PubMed

    Lipman, D; Pieters, B R; De Reijke, Theo M

    2017-10-01

    Prostate cancer has one of the highest incidences in the world, with good curative treatment options like radiotherapy and radical prostatectomy. Unfortunately, about 30% of the patients initially treated with curative intent will develop a recurrence and need adjuvant treatment. Five randomized trials covered the role of postoperative radiotherapy after radical prostatectomy, but there is still a lot of debate about which patients should receive postoperative radiotherapy. Areas covered: This review will give an overview on the available literature concerning post-operative radiotherapy following radical prostatectomy with an emphasis on the five randomized trials. Also, new imaging techniques like prostate-specific membrane antigen positron emission tomography (PSMA-PET) and multiparametric magnetic resonance imaging (mp-MRI) and the development of biomarkers like genomic classifiers will be discussed in the search for an improved selection of patients who will benefit from postoperative radiotherapy following radical prostatectomy. With new treatment techniques like Intensity Modulated Radiotherapy, toxicity profiles will be kept low. Expert commentary: Patients with biochemical recurrence following radical prostatectomy with an early rise in prostate-specific antigen (PSA) will benefit most from postoperative radiotherapy. In this way, patients with only high risk pathological features can avoid unnecessary treatment and toxicity, and early intervention in progressing patients would not compromise the outcome.

  13. Long term survival of radiotherapy for esophageal cancer: analysis of 1136 patients surviving for more than 5 years

    SciTech Connect

    Yang, Z.Y.; Gu, X.; Zhao, S.

    1983-12-01

    One thousand one hundred and thirty-six patients surviving for more than five years after radiotherapy were studied. The important prognostic factors are: lesion less than 5 cm in length, lesion located in the upper-third segment and lesion that is radiosensitive. The radiation dose given to long term survivors varies greatly, i.e., 2700 to 9300 rad. Yet, for the sensitive type of lesion, doses lower than 5000 rad could also effect a cure. The delivery of an optimum dose determined by serial examinations during radiotherapy could improve the result of treatment. For local recurrent lesions, the value of a second course of radiation is extremely limited and surgery is the only means to offer a cure. For metastasis in the lymph nodes, radiation offers some hope of cure, although the long term outcome may not be satisfactory. For second primary cancer of the esophagus, aggressive radiation still gives encouraging results.

  14. Improving Survival after Cardiac Arrest.

    PubMed

    Bjørshol, Conrad Arnfinn; Søreide, Eldar

    2017-02-01

    Each year, approximately half a million people suffer out-of-hospital cardiac arrest (CA) in Europe: The majority die. Survival after CA varies greatly between regions and countries. The authors give an overview of the important elements necessary to promote improved survival after CA as a function of the chain of survival and formula for survival concepts. The chain of survival incorporates bystanders (who identify warning symptoms, call the emergency dispatch center, initiate cardiopulmonary resuscitation [CPR]), dispatchers (who identify CA, and instruct and reassure the caller), first responders (who provide high-quality CPR, early defibrillation), paramedics and other prehospital care providers (who continue high-quality CPR, and provide timely defibrillation and advanced life support, transport to CA center), and hospitals (targeted temperature management, percutaneous coronary intervention, delayed prognostication). The formula for survival concept consists of (1) medical science (international guidelines), (2) educational efficiency (e.g., low-dose, high-frequency training for lay people, first responders, and professionals; and (3) local implementation of all factors in the chain of survival and formula for survival. Survival rates after CA can be advanced through the improvement of the different factors in both the chain of survival and the formula for survival. Importantly, the neurologic outcome in the majority of CA survivors has continued to improve.

  15. Significant benefits in survival by the use of surgery combined with radiotherapy for retroperitoneal soft tissue sarcoma.

    PubMed

    Hager, Sven; Makowiec, Frank; Henne, Karl; Hopt, Ulrich T; Wittel, Uwe A

    2017-01-26

    To report the effect of intraoperative electron beam radiotherapy (IOERT) and external beam radiotherapy (EBRT) in addition to surgery as well as to evaluate the role of resectable local recurrence for long-term prognosis. In 53 patients who underwent surgery for retroperitoneal soft tissue sarcoma (RSTS) from 2001 to 2014 prognostic and epidemiologic factors were reviewed retrospectively to analyze their impact on survival and recurrence. Twenty three patients (50%) had surgery plus radiotherapy, 23 (50%) had surgery only. Histology showed 73.9% liposarcoma, 15.2% leiomyosarcoma and 6.5% pleomorphic undifferentiated sarcoma respectively. Low grade sarcoma were observed in 52.2%, high grade sarcoma in 47.8%. The latter showed a trend towards a decreased 5-year survival rate (p = 0.125). Margin status was: R0: 60.9%, R1: 23.9%, R2: 15.2%; leading to significant changes in 5-year survival rate (R0: 77.6%; R1: 70.0%; R2: 42.9%; p = 0.03). Age younger than 55 years significantly improved 5-year survival rate (p = 0.039). Patients receiving resection of multiple sarcoma recurrence showed an almost identical improved 5-year survival rate compared to patients without recurrence (no recurrence: 100.0%; single recurrence: 35.0%; multiple recurrence: 91.7%; p = 0.001). Surgery plus radiotherapy led to significantly improved survival (p = 0.04). There is a significant benefit in terms of 5-year survival after surgery plus some form of radiotherapy and a good prognosis for patients when the recurrence from RSTS was resected. Age older than 55 years and incomplete resection lowered 5-year survival rate significantly.

  16. Relations between radiotherapy resources and breast cancer patient survival rates.

    PubMed

    Mochimaru, Yuko; Ohno, Yuko; Numasaki, Hodaka; Theshima, Teruki; Shibuya, Hitoshi

    2010-01-01

    In Japan, the number of patients that have been treated with radiotherapy (RT), particularly those with breast cancer, has increased in the past decade, and is expected to double in the next decade. There is, however, a shortage of RT resources, particularly personnel, which represents a social problem. The shortage of RT resources might cause a difference in survival rate among treated patients. This study analyzed the characteristics of RT resources in RT facilities from Osaka based on the Japanese Society for Therapeutic Radiology and Oncology (JASTRO) database with principle component analysis and cluster analysis. In addition, the relation between RT resources and treatment outcome of breast cancer patients was investigated by linking together Osaka Cancer Registry (OCR) and JASTRO data via a stratified key cord. By using the linked dataset it was shown that the prognosis of breast cancer patients was highly correlated with the scale of RT resources available at the RT facilities collaterally. From cluster analysis, four groups were identified based on RT facility information. The breast cancer survival rates for localized stage patients obtained in classified hospital groups showed a similar pattern, however, large differences (up to 20%) were seen in regional stage patients. Additional findings were: RT facilities with less than 1 radiation oncologist had the poorest outcome; RT was performed primarily at University hospitals; and differences in RT resources within the RT facilities had an effect on breast cancer patient prognosis in Osaka, Japan.

  17. Independent external validation of radiotherapy and its impact on the accuracy of a nomogram for predicting survival of women with endometrial cancer.

    PubMed

    Koskas, Martin; Bendifallah, Sofiane; Luton, Dominique; Darai, Emile; Rouzier, Roman

    2011-11-01

    To externally validate and assess the impact of radiotherapy on the accuracy of a nomogram for predicting overall survival of women with endometrial cancer. Using data from the Surveillance, Epidemiology, and End Results (SEER), we assessed the concordance indexes, the discrimination and the calibration provided by a nomogram for predicting overall survival. Patients were grouped into deciles based on their survival predictions, and the three-year overall survival in each group was compared with the mean predicted probability. Between 1988 and 2006, 64,023 patients were analyzed and divided into two groups: 14,323 patients with adjuvant radiotherapy and 49,700 patients without adjuvant radiotherapy. Among the whole population, predicted and observed three-year overall survivals were 85.2% and 85.6% (+/-0.1%) respectively. In patients with adjuvant radiotherapy, overall survivals were 81.0% and 83.1% (+/-0.3%) and in patients without adjuvant radiotherapy, they were 86.5% and 86.3% (+/-0.2%) respectively. The concordance indexes for the whole population, in patients with radiotherapy and in patients without radiotherapy were 0.811 (+/-0.004), 0.751 (+/-0.009) and 0.803 (+/-0.006) respectively. The mean and maximal errors in patients with radiotherapy were 2.1% and 4.0% and in patients without radiotherapy 2.3% and 8.1%. The nomogram can accurately predict three-year overall survival, whether patients undergo adjuvant radiotherapy or not. The nomogram has an improved individual discrimination when compared with the 1988 and the 2009 staging systems for endometrial cancer. It may be useful in the information processed for patients and in building surveillance timing. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. A Population-based Model of Local Control and Survival Benefit of Radiotherapy for Lung Cancer.

    PubMed

    Shafiq, J; Hanna, T P; Vinod, S K; Delaney, G P; Barton, M B

    2016-10-01

    To estimate the population-based locoregional control and overall survival benefits of radiotherapy for lung cancer if the whole population were treated according to evidence-based guidelines. These estimates were based on a published radiotherapy utilisation (RTU) model that has been used to estimate the demand and planning of radiotherapy services nationally and internationally. The lung cancer RTU model was extended to incorporate an estimate of benefits of radiotherapy alone, and of radiotherapy in conjunction with concurrent chemotherapy (CRT). Benefits were defined as the proportional gains in locoregional control and overall survival from radiotherapy over no radiotherapy for radical indications, and from postoperative radiotherapy over surgery alone for adjuvant indications. A literature review (1990-2015) was conducted to identify benefit estimates of individual radiotherapy indications and summed to estimate the population-based gains for these outcomes. Model robustness was tested through univariate and multivariate sensitivity analyses. If evidence-based radiotherapy recommendations are followed for the whole lung cancer population, the model estimated that radiotherapy alone would result in a gain of 8.3% (95% confidence interval 7.4-9.2%) in 5 year locoregional control, 11.4% (10.8-12.0%) in 2 year overall survival and 4.0% (3.6-4.4%) in 5 year overall survival. For the use of CRT over radiotherapy alone, estimated benefits would be: locoregional control 1.7% (0.8-2.4%), 2 year overall survival 1.7% (0.5-2.8%) and 5 year overall survival 1.2% (0.7-1.9%). The model provided estimates of radiotherapy benefit that could be achieved if treatment guidelines are followed for all cancer patients. These can be used as a benchmark so that the effects of a shortfall in the utilisation of radiotherapy can be better understood and addressed. The model can be adapted to other populations with known epidemiological parameters to ensure the planning of equitable

  19. Changing incidence and improved survival of gliomas.

    PubMed

    Ho, Vincent K Y; Reijneveld, Jaap C; Enting, Roelien H; Bienfait, Henri P; Robe, Pierre; Baumert, Brigitta G; Visser, Otto

    2014-09-01

    Tumours of the central nervous system (CNS) represent a relatively rare but serious health burden. This study provides insight into the incidence and survival patterns of gliomas in the Netherlands diagnosed in adult patients during the time period 1989-2010, with a focus on glioblastoma and low-grade gliomas. Data on 21,085 gliomas (excluding grade I tumours) were obtained from the Netherlands Cancer Registry, including tumours of the CNS without pathological confirmation. We calculated the age-standardised incidence rates and the estimated annual percentage change (EAPC) for all glioma subtypes. Crude and relative survival rates were estimated using information on the vital status obtained from the Dutch Municipal Personal Records Database. Incidence of gliomas in adults increased over time, from 4.9 per 100,000 in 1989 to 5.9 in 2010 (EAPC 0.7%, p<0.001). Two thirds were astrocytoma, 10% oligodendroglioma/oligoastrocytoma, 3% ependymoma and 21% were unspecified. Within the group of astrocytic tumours, the proportion of glioblastoma rose, while the proportion of anaplastic and unspecified astrocytoma decreased. Unspecified neoplasms also decreased, but this was significant only after 2005. Over the course of the study period, glioblastoma patients more often received multimodality treatment with chemotherapy concomitant and adjuvant to radiotherapy. The crude two-year survival rate of glioblastoma patients improved significantly, from 5% in the time period 1989-1994 to 15% in 2006-2010, with median survival increasing from 5.5 to 9 months. The incidence of low-grade gliomas did not change over time. Survival rates for low-grade oligodendroglial and mixed tumours show a modest improvement. The incidence rate for the total group of gliomas slightly increased, with a decrease of anaplastic and unspecified tumours and an increase of glioblastoma. Following the introduction of combined chemoradiation, two-year survival rates for glioblastoma significantly improved

  20. Children Undergoing Radiotherapy: Swedish Parents' Experiences and Suggestions for Improvement.

    PubMed

    Ångström-Brännström, Charlotte; Engvall, Gunn; Mullaney, Tara; Nilsson, Kristina; Wickart-Johansson, Gun; Svärd, Anna-Maja; Nyholm, Tufve; Lindh, Jack; Lindh, Viveca

    2015-01-01

    Approximately 300 children, from 0 to 18 years old, are diagnosed with cancer in Sweden every year. Of these children, 80-90 of them undergo radiotherapy treatment for their cancer. Although radiotherapy is an encounter with advanced technology, few studies have investigated the child's and the parent's view of the procedure. As part of an ongoing multicenter study aimed to improve patient preparation and the care environment in pediatric radiotherapy, this article reports the findings from interviews with parents at baseline. The aim of the present study was twofold: to describe parents' experience when their child undergoes radiotherapy treatment, and to report parents' suggestions for improvements during radiotherapy for their children. Sixteen mothers and sixteen fathers of children between 2-16 years old with various cancer diagnoses were interviewed. Data were analyzed using content analysis. The findings showed that cancer and treatment turns people's lives upside down, affecting the entire family. Further, the parents experience the child's suffering and must cope with intense feelings. Radiotherapy treatment includes preparation by skilled and empathetic staff. The parents gradually find that they can deal with the process; and lastly, parents have suggestions for improvements during the radiotherapy treatment. An overarching theme emerged: that despair gradually turns to a sense of security, with a sustained focus on and close interaction with the child. In conclusion, an extreme burden was experienced around the start of radiotherapy, though parents gradually coped with the process.

  1. Children Undergoing Radiotherapy: Swedish Parents’ Experiences and Suggestions for Improvement

    PubMed Central

    Mullaney, Tara; Nilsson, Kristina; Wickart-Johansson, Gun; Svärd, Anna-Maja; Nyholm, Tufve; Lindh, Jack; Lindh, Viveca

    2015-01-01

    Approximately 300 children, from 0 to 18 years old, are diagnosed with cancer in Sweden every year. Of these children, 80–90 of them undergo radiotherapy treatment for their cancer. Although radiotherapy is an encounter with advanced technology, few studies have investigated the child’s and the parent’s view of the procedure. As part of an ongoing multicenter study aimed to improve patient preparation and the care environment in pediatric radiotherapy, this article reports the findings from interviews with parents at baseline. The aim of the present study was twofold: to describe parents’ experience when their child undergoes radiotherapy treatment, and to report parents’ suggestions for improvements during radiotherapy for their children. Sixteen mothers and sixteen fathers of children between 2–16 years old with various cancer diagnoses were interviewed. Data were analyzed using content analysis. The findings showed that cancer and treatment turns people’s lives upside down, affecting the entire family. Further, the parents experience the child’s suffering and must cope with intense feelings. Radiotherapy treatment includes preparation by skilled and empathetic staff. The parents gradually find that they can deal with the process; and lastly, parents have suggestions for improvements during the radiotherapy treatment. An overarching theme emerged: that despair gradually turns to a sense of security, with a sustained focus on and close interaction with the child. In conclusion, an extreme burden was experienced around the start of radiotherapy, though parents gradually coped with the process. PMID:26509449

  2. Effect of Radiotherapy Planning Complexity on Survival of Elderly Patients With Unresected Localized Lung Cancer

    SciTech Connect

    Park, Chang H.; Bonomi, Marcelo; Cesaretti, Jamie; Neugut, Alfred I.; Wisnivesky, Juan P.

    2011-11-01

    Purpose: To evaluate whether complex radiotherapy (RT) planning was associated with improved outcomes in a cohort of elderly patients with unresected Stage I-II non-small-cell lung cancer (NSCLC). Methods and Materials: Using the Surveillance, Epidemiology, and End Results registry linked to Medicare claims, we identified 1998 patients aged >65 years with histologically confirmed, unresected stage I-II NSCLC. Patients were classified into an intermediate or complex RT planning group using Medicare physician codes. To address potential selection bias, we used propensity score modeling. Survival of patients who received intermediate and complex simulation was compared using Cox regression models adjusting for propensity scores and in a stratified and matched analysis according to propensity scores. Results: Overall, 25% of patients received complex RT planning. Complex RT planning was associated with better overall (hazard ratio 0.84; 95% confidence interval, 0.75-0.95) and lung cancer-specific (hazard ratio 0.81; 95% confidence interval, 0.71-0.93) survival after controlling for propensity scores. Similarly, stratified and matched analyses showed better overall and lung cancer-specific survival of patients treated with complex RT planning. Conclusions: The use of complex RT planning is associated with improved survival among elderly patients with unresected Stage I-II NSCLC. These findings should be validated in prospective randomized controlled trials.

  3. The effect of radiotherapy on survival of dental implants in head and neck cancer patients.

    PubMed

    Shugaa-Addin, Bassam; Al-Shamiri, Hashem-Motahir; Al-Maweri, Sadeq; Tarakji, Bassel

    2016-04-01

    To explore the current literature of the survival of dental implants in irradiated head and neck cancer patients considering the role of implant location, bone augmentation, dose of radiation and timing of implant placement. Pubmed search was conducted to identify articles published between January 2000 and December 2014 and presenting data of dental implant survival with radiotherapy in head and neck cancer patients. Studies on animal subjects and craniofacial implants were excluded. 18 articles out of 27 were eligible for inclusion in this systematic review. 12 out of 18 studies reported favorable outcome of dental implants and radiotherapy with survival rates between 74.4% and 97%. Seven out of ten studies comparing the survival rates according to site of implant placement reported that implants were found to osseointegrate with greater success in the irradiated mandible than irradiated maxilla. 5 studies which compared implant survival in irradiated native bone versus irradiated grafted bone reported that irradiated grafted bone showed a significantly reduced dental implant survival rate in comparison to irradiated native bone. 6 out of 18studies in which radiation doses exceeded 70 Gy reported lower survival rates of dental implants in comparison to the studies in which radiation doses were ≤70Gy. Higher survival rates were reported in 2 studies in which implants placement was before radiotherapy in comparison to the remaining 16 studies in which implants placement was after radiotherapy. Dental implants may be affected by radiotherapy especially when they are placed in maxilla, in grafted bone, or after radiation, however, they remain a functional option for rehabilitation of head and cancer patients. More Prospective cohort studies and randomized controlled trails are still needed to draw more evidence based conclusions. Dental implants, implant survival, radiotherapy, head and neck cancer.

  4. Improving radiotherapy in cancer treatment: Promises and challenges

    PubMed Central

    Chen, Helen H.W.; Kuo, Macus Tien

    2017-01-01

    Effective radiotherapy for cancer has relied on the promise of maximally eradicating tumor cells while minimally killing normal cells. Technological advancement has provided state-of-the-art instrumentation that enables delivery of radiotherapy with great precision to tumor lesions with substantial reduced injury to normal tissues. Moreover, better understanding of radiobiology, particularly the mechanisms of radiation sensitivity and resistance in tumor lesions and toxicity in normal tissues, has improved the treatment efficacy of radiotherapy. Previous mechanism-based studies have identified many cellular targets that can affect radiation sensitivity, notably reactive oxygen species, DNA-damaging response signals, and tumor microenvironments. Several radiation sensitizers and protectors have been developed and clinically evaluated; however, many of these results are inconclusive, indicating that improvement remains needed. In this era of personalized medicine in which patients’ genetic variations, transcriptome and proteomics, tumor metabolism and microenvironment, and tumor immunity are available. These new developments have provided opportunity for new target discovery. Several radiotherapy sensitivity-associated “gene signatures” have been reported although clinical validations are needed. Recently, several immune modifiers have been shown to associate with improved radiotherapy in preclinical models and in early clinical trials. Combination of radiotherapy and immunocheckpoint blockade has shown promising results especially in targeting metastatic tumors through abscopal response. In this article, we succinctly review recent advancements in the areas of mechanism-driven targets and exploitation of new targets from current radio-oncogenomic and radiation-immunotherapeutic approaches that bear clinical implications for improving the treatment efficacy of radiotherapy.

  5. Effect of Concurrent High-Dose Cisplatin Chemotherapy and Conformal Radiotherapy on Cervical Esophageal Cancer Survival

    SciTech Connect

    Huang Shaohui; Lockwood, Gina; Brierley, James; Cummings, Bernard; Kim, John; Wong, Rebecca; Bayley, Andrew; Ringash, Jolie

    2008-07-01

    Purpose: To determine whether a change in treatment policy to conformal, elective nodal radiotherapy and concurrent high-dose cisplatin improved survival for cervical esophageal cancer patients. Methods and Materials: All cervical esophageal cancer patients treated between 1997 and 2005 were restaged (1983 American Joint Committee on Cancer criteria). Patients treated before 2001 (previous cohort [PC]) were compared with those treated from 2001 onward (recent cohort [RC]). The PC institutional chemoradiotherapy protocol was 54 Gy in 20 fractions within 4 weeks, with 5-fluorouracil (1,000 mg/m{sup 2}) on Days 1-4 and either mitomycin C (10 mg/m{sup 2}) or cisplatin (75 mg/m{sup 2}) on Day 1. The RC institutional chemoradiotherapy protocol was conformal radiotherapy, 70 Gy in 35 fractions within 7 weeks, to the primary tumor and elective nodes, with high-dose cisplatin (100 mg/m{sup 2}) on Days 1, 22, and 43. Results: The median follow-up was 3.1 years (PC, 8.1 and RC, 2.3). Of 71 patients (25 women and 46 men), 21 of 29 in the PC and 29 of 42 in the RC were treated curatively (curative subgroup, n = 50). Between the two groups, no differences in overall survival or locoregional relapse-free survival were seen. The overall survival rate at 2 and 5 years was 35% (range, 24-47%) and 21% (range, 12-32%) in the whole group and 46% (range 32-60%) and 28% (range, 15-42%) in the curative group, respectively. In the curative group, no statistically significant prognostic factors were found. Trends toward better locoregional relapse-free survival were seen in women (2-year rate, 73% vs. for men, 36%; p = 0.08) and in patients aged >64 years (2-year rate, 68% vs. age {<=}64 years, 34%; p = 0.10). Conclusion: No survival improvement could be demonstrated after changing the treatment policy to high-dose cisplatin-based, conventionally fractionated conformal chemoradiotherapy. Female gender and older age might predict for better outcomes.

  6. Induction Chemotherapy Improved Long-term Outcomes of Patients with Locoregionally Advanced Nasopharyngeal Carcinoma: A Propensity Matched Analysis of 5-year Survival Outcomes in the Era of Intensity-modulated Radiotherapy

    PubMed Central

    Peng, Hao; Chen, Lei; Zhang, Jian; Li, Wen-Fei; Mao, Yan-Ping; Zhang, Yuan; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2017-01-01

    Background: The aim of this study is to evaluate the long-term therapeutic gain of induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiotherapy (IMRT). Methods: Data on 957 patients with stage T1-2N2-3 or T3-4N1-3 NPC treated with IMRT were retrospectively reviewed. Propensity score matching (PSM) method was adopted to balance influence of various covariates. Patient survival between IC and non-IC groups were compared. Results: For the 318 pairs selected from the original 957 patients by PSM, the median follow-up duration was 57.13 months (range, 1.27-78.1 months). The 5-year overall survival (OS), distant metastasis-free survival (DMFS), disease-free survival (DFS) and locoregional relapse-free survival (LRRFS) rates for IC group vs. non-IC group were 87.2% vs. 80.8% (P = 0.023), 88.1% vs. 83.2% (P = 0.071), 80.7% vs. 71.4% (P = 0.011) and 92.1% vs. 86.7% (P = 0.081), respectively. Multivariate analysis identify IC as an independent prognostic factor for OS (HR, 0.595; 95% CI, 0.397-0.891; P = 0.012) and DFS (HR, 0.627; 95% CI, 0.451-0.872; P = 0.006). After excluding the patients not receiving concurrent chemotherapy, IC was found to be an independent prognostic factor for OS (HR, 0.566; 95% CI, 0.368-0.872; P = 0.01), DMFS (HR, 0.580; 95% CI, 0.367-0.916; P = 0.02) and DFS (HR, 0.633; 95% CI, 0.444-0.903; P = 0.012). Conclusions: IC is an effective treatment modality for patients with stage T1-2N2-3 and T3-4N1-3 NPC, and the incorporation of IC with standard CCRT could achieve the best therapeutic gain. PMID:28261337

  7. Survival of women with clear cell and papillary serous endometrial cancer after adjuvant radiotherapy.

    PubMed

    Foerster, Robert; Kluck, Robert; Rief, Harald; Rieken, Stefan; Debus, Juergen; Lindel, Katja

    2014-06-18

    Type II (papillary serous and clear cell) endometrial carcinoma (EC) is a rare subgroup and is considered to have an unfavorable prognosis. The purpose of this retrospective analysis was to elucidate the meaning of adjuvant radiotherapy (RT) for clinical outcome and to define prognostic factors in these patients (pts). From 2004-2012 forty-two pts with type II EC underwent surgery followed by adjuvant RT at our department. Median age was 72 years. The majority were early stage carcinomas (FIGO I n = 27 [64.3%], FIGO II n = 4 [9.5%], FIGO III n = 11 [26.2%]. Seven pts (16.7%) received adjuvant chemotherapy (ChT). Pts were treated with external beam radiotherapy (EBRT) and brachytherapy (IVB) boost. Five-year local recurrence free survival (LRFS), distant metastases free survival (DMFS) and overall survival (OS) were 85.4%, 78%, and 64.5% respectively. LRFS was better with lower pT stage, without lymphangiosis (L0), without haemangiosis (V0) and negative resection margins (R0). DMFS was prolonged in lymph node negatives (N0), L0, V0 and R0. OS was improved in younger pts, N0, L0, V0 and after lymphadenectomy (LNE). Multivariate analysis revealed haemangiosis (V1) as the only independent prognostic factor for OS (p = .014) and DMFS (p = .008). For LRFS pT stage remained as an independent prognostic factor (p = .028). Adjuvant RT with EBRT/IVB ensures adequate local control in type II EC, but control rates remain lower than in type I EC. A benefit of additional adjuvant ChT could not be demonstrated and a general omission of EBRT cannot be recommended at this point. Lymphovascular infiltration and pT stage might be the best predictive factors for a benefit from combined local and systemic treatment.

  8. Radiotherapy Alone is Associated with Improved Outcomes Over Surgery in the Management of Solitary Plasmacytoma.

    PubMed

    Li, Qi-Wen; Niu, Shao-Qing; Wang, Han-Yu; Wen, Ge; Li, Yi-Yang; Xia, Yun-Fei; Zhang, Yu-Jing

    2015-01-01

    A moderate dose of radiation is the recommended treatment for solitary plasmacytoma (SP), but there is controversy over the role of surgery. Our study aimed at comparing different treatment modalities in the management of SP. Data from 38 consecutive patients with solitary plasmacytoma, including 16 with bone plasmacytoma and 22 with extramedullary plasmacytoma, were retrospectively reviewed. 15 patients received radiotherapy alone; 11 received surgery alone, and 12 received both. The median radiation dose was 50Gy. All operations were performed as radical resections. Local progression-free survival (LPFS), multiple myeloma-free survival (MMFS), progression-free survival (PFS) and overall survival (OS) were calculated and outcomes of different therapies were compared. The median follow-up time was 55 months. 5-year LPFS, MMFS, PFS and OS were 87.0%, 80.9%, 69.8% and 87.4%, respectively. Univariate analysis revealed, compared with surgery alone, radiotherapy alone was associated with significantly higher 5-year LPFS (100% vs 69.3%, p=0.016), MMFS (100% vs 51.4%, p=0.006), PFS (100% vs 33.7%, p=0.0004) and OS (100% vs 70%, p=0.041). Radiotherapy alone can be considered as a more effective treatment for SP over surgery. Whether a combination of radiotherapy and surgery improves outcomes requires further study.

  9. Integer programming for improving radiotherapy treatment efficiency.

    PubMed

    Lv, Ming; Li, Yi; Kou, Bo; Zhou, Zhili

    2017-01-01

    Patients received by radiotherapy departments are diverse and may be diagnosed with different cancers. Therefore, they need different radiotherapy treatment plans and thus have different needs for medical resources. This research aims to explore the best method of scheduling the admission of patients receiving radiotherapy so as to reduce patient loss and maximize the usage efficiency of service resources. A mix integer programming (MIP) model integrated with special features of radiotherapy is constructed. The data used here is based on the historical data collected and we propose an exact method to solve the MIP model. Compared with the traditional First Come First Served (FCFS) method, the new method has boosted patient admission as well as the usage of linear accelerators (LINAC) and beds. The integer programming model can be used to describe the complex problem of scheduling radio-receiving patients, to identify the bottleneck resources that hinder patient admission, and to obtain the optimal LINAC-bed radio under the current data conditions. Different management strategies can be implemented by adjusting the settings of the MIP model. The computational results can serve as a reference for the policy-makers in decision making.

  10. Improving fish survival through turbines

    SciTech Connect

    Ferguson, J.W. )

    1993-04-01

    Much of what is known about fish passage through hydroturbines has been developed by studying migratory species of fish passing through large Kaplan turbine units. A review of the literature on previous fish passage research presented in the accompanying story illustrates that studies have focused on determining mortality levels, rather than identifying the causal mechanism involved. There is a need for understanding how turbine designs could be altered to improve fish passage conditions, how to retrofit existing units, and how proposed hydro plant operational changes may affect fish survival. The US Army Corps of Engineers has developed a research program to define biologically based engineering criteria for improving fish passage conditions. Turbine designs incorporating these criteria can be evaluated for their effects on fish survival, engineering issues, costs, and power production. The research program has the following objectives: To gain a thorough knowledge of the mechanisms of fish mortality; To define the biological sensitivities of key fish species to these mechanisms of mortality; To develop new turbine design criteria to reduce fish mortality; To construct prototype turbine designs, and to test these designs for fish passage, hydro-mechanical operation, and power production; and To identify construction and power costs associated with new turbine designs.

  11. Patient compliance for postoperative radiotherapy and survival outcome of women with stage I endometrioid endometrial cancer.

    PubMed

    Matsuo, Koji; Machida, Hiroko; Ragab, Omar M; Garcia-Sayre, Jocelyn; Yessaian, Annie A; Roman, Lynda D

    2017-09-01

    To examine characteristics and survival outcome of women with endometrial cancer who declined postoperative radiotherapy. A retrospective study was conducted to examine surgically-treated grade 1-2 stage IB and grade 3 stage IA-IB endometrioid endometrial cancer in the Surveillance, Epidemiology, and End Results Program between 1983 and 2013 (n = 10 613). Associations of patient declination for guideline-based postoperative radiotherapy and clinico-pathological demographics or survival outcome were examined on multivariable analysis. There were 323 (3.0%) women who declined adjuvant radiotherapy. Women who declined postoperative radiotherapy were more likely to be older, White, Western U.S. residents, and register in recent years (all, adjusted-P < 0.05). On multivariable analysis, patient declination for guideline-based postoperative radiotherapy remained an independent prognostic factor for decreased endometrial cancer-specific survival in unstaged grade 1-2 stage IB or staged/unstated grade 3 stage IA-IB diseases (adjusted-hazard ratio 1.84, 95% confidence interval 1.34-2.51, P = 0.001). Association of patient declination for guideline-based postoperative radiotherapy and decreased overall survival remained independent in the entire cohort on multivariable analysis (adjuvant-hazard ratio 1.71, 95% confidence interval 1.44-2.02, P < 0.001). Our study suggested that patient compliance to guideline-based postoperative radiotherapy is a prognostic factor for women with stage I endometrioid endometrial cancer. © 2017 Wiley Periodicals, Inc.

  12. Concurrent Chemoradiotherapy Improves Survival in Patients With Hypopharyngeal Cancer

    SciTech Connect

    Paximadis, Peter; Yoo, George; Lin, Ho-Sheng; Jacobs, John; Sukari, Ammar; Dyson, Greg; Christensen, Michael; Kim, Harold

    2012-03-15

    Purpose: To retrospectively review our institutional experience with hypopharyngeal carcinoma with respect to treatment modality. Methods and Materials: A total of 70 patients with hypopharyngeal cancer treated between 1999 and 2009 were analyzed for functional and survival outcomes. The treatments included surgery alone (n = 5), surgery followed by radiotherapy (RT) (n = 3), surgery followed by chemoradiotherapy (CRT) (n = 13), RT alone (n = 2), CRT alone (n = 22), induction chemotherapy followed by RT (n = 3), and induction chemotherapy followed by CRT (n = 22). Results: The median follow-up was 18 months. The median overall survival and disease-free survival for all patients was 28.3 and 17.6 months, respectively. The 1- and 2-year local control rate for all patients was 87.1% and 80%. CRT, given either as primary therapy or in the adjuvant setting, improved overall survival and disease-free survival compared with patients not receiving CRT. The median overall survival and disease-free survival for patients treated with CRT was 36.7 and 17.6 months vs. 14.0 and 8.0 months, respectively (p < .01). Of the patients initially treated with an organ-preserving approach, 4 (8.2%) required salvage laryngectomy for local recurrence or persistent disease; 8 (16.3%) and 12 (24.5%) patients were dependent on a percutaneous gastrostomy and tracheostomy tube, respectively. The 2-year laryngoesophageal dysfunction-free survival rate for patients treated with an organ-preserving approach was estimated at 31.7%. Conclusions: Concurrent CRT improves survival in patients with hypopharyngeal cancer. CRT given with conventional radiation techniques yields poor functional outcomes, and future efforts should be directed at determining the feasibility of pharyngeal-sparing intensity-modulated radiotherapy in patients with hypopharyngeal tumors.

  13. Radiotherapy and Survival in Prostate Cancer Patients: A Population-Based Study

    SciTech Connect

    Zhou, Esther H. Ellis, Rodney J.; Cherullo, Edward; Colussi, Valdir; Xu Fang; Chen Weidong; Gupta, Sanjay; Whalen, Christopher C.; Bodner, Donald; Resnick, Martin I.; Rimm, Alfred A.

    2009-01-01

    Purpose: To investigate the association of overall and disease-specific survival with the five standard treatment modalities for prostate cancer (CaP): radical prostatectomy (RP), brachytherapy (BT), external beam radiotherapy, androgen deprivation therapy, and no treatment (NT) within 6 months after CaP diagnosis. Methods and Materials: The study population included 10,179 men aged 65 years and older with incident CaP diagnosed between 1999 and 2001. Using the linked Ohio Cancer Incidence Surveillance System, Medicare, and death certificate files, overall and disease-specific survival through 2005 among the five clinically accepted therapies were analyzed. Results: Disease-specific survival rates were 92.3% and 23.9% for patients with localized vs. distant disease at 7 years, respectively. Controlling for age, race, comorbidities, stage, and Gleason score, results from the Cox multiple regression models indicated that the risk of CaP-specific death was significantly reduced in patients receiving RP or BT, compared with NT. For localized disease, compared with NT, in the monotherapy cohort, RP and BT were associated with reduced hazard ratios (HR) of 0.25 and 0.45 (95% confidence intervals 0.13-0.48 and 0.23-0.87, respectively), whereas in the combination therapy cohort, HR were 0.40 (0.17-0.94) and 0.46 (0.27-0.80), respectively. Conclusions: The present population-based study indicates that RP and BT are associated with improved survival outcomes. Further studies are warranted to improve clinical determinates in the selection of appropriate management of CaP and to improve predictive modeling for which patient subsets may benefit most from definitive therapy vs. conservative management and/or observation.

  14. Apoptosis in cervical squamous carcinoma: predictive value for survival following radiotherapy

    PubMed Central

    Paxton, J; Bolger, B; Armour, A; Symonds, R; Mao, J; Burnett, R

    2000-01-01

    Background—Apoptosis, or programmed cell death, can be induced by radiotherapy. The extent of apoptosis in a tumour before treatment may have important implications for response to radiotherapy and long term survival. Aim—To examine the extent of apoptosis in tumour tissue from patients with squamous carcinoma of the cervix before radiotherapy, and to correlate this with response to treatment and prognosis. Methods—The percentage of apoptotic cells was assessed in 146 carcinomas of the cervix from patients scheduled to receive radiotherapy. The CAS 200 static image analysis system was used to count the number of tumour nuclei per high power field, while the numbers of apoptotic cells in the same field were visualised simultaneously on the image analyser and recorded manually. Results—The median apoptotic level was 0.73%. Patients were divided into two groups around the median. There was no statistically significant difference in outcome between the two groups as determined by long term survival following radiotherapy. Conclusions—The CAS 200 static image analyser system can be used to assist in the rapid semiautomated assessment of apoptosis in conventionally prepared tissue. The results suggest that the apoptotic state of a tumour before treatment is of no value in predicting response to radiotherapy and subsequent prognosis. Tumour stage, size, and BrdU labelling index, as a measure of proliferation rate, remain the most important prognostic factors in terms of predicting local tumour control. Key Words: apoptosis • uterine cervix • squamous cell carcinoma PMID:10823138

  15. Motor function and survival following radiotherapy alone for metastatic epidural spinal cord compression in melanoma patients.

    PubMed

    Huttenlocher, Stefan; Sehmisch, Lena; Rudat, Volker; Rades, Dirk

    2014-12-01

    The major goal of this study was the identification of predictors for motor function and survival after irradiation alone for metastatic epidural spinal cord compression (MESCC) from melanoma. Ten variables (age, gender, performance status, number of involved vertebrae, pre-radiotherapy ambulatory status, further bone metastases, visceral metastases, interval from melanoma diagnosis to MESCC, time developing motor deficits before radiotherapy, fractionation regimen) were investigated for post-radiotherapy motor function, ambulatory status and survival in 27 patients. On multivariate analysis, motor function was significantly associated with time developing motor deficits (P = 0.006). On univariate analysis, post-radiotherapy ambulatory rates were associated with pre-radiotherapy ambulatory status (P < 0.001) and performance status (P = 0.046). Variables having a significant impact on survival in the univariate analysis were performance status (P < 0.001), number of involved vertebrae (P = 0.007), pre-radiotherapy ambulatory status (P = 0.020), further bone metastases (P = 0.023), visceral metastases (P < 0.001), and time developing motor deficits (P = 0.038). On multivariate analysis of survival, the Eastern Cooperative Oncology Group (ECOG) performance status (risk ratio [RR] = 4.35; 95% confidence interval [CI] = 1.04-16.67; P = 0.044) and visceral metastases (RR = 3.70; 95% CI = 1.10-12.50; P = 0.034) remained significant and were included in a survival score. Scoring points were obtained from 6-month survival rates divided by 10. Total scores represented the sum scores of both variables and were 3, 9 or 15 points. Six-month survival rates were 7%, 29% and 100% (P = 0.004). Thus, three predictors for functional outcomes were identified. The newly developed survival score included three prognostic groups. Patients with 3 points may receive 1 × 8 Gy, patients with 9 points 5 × 4 Gy and patients achieving 15 points longer

  16. Adverse effect of excess body weight on survival in cervical cancer patients after surgery and radiotherapy.

    PubMed

    Choi, Yunseon; Ahn, Ki Jung; Park, Sung Kwang; Cho, Heunglae; Lee, Ji Young

    2017-03-01

    This study aimed to assess the effects of body mass index (BMI) on survival in cervical cancer patients who had undergone surgery and radiotherapy (RT). We retrospectively reviewed the medical records of 70 cervical cancer patients who underwent surgery and RT from 2007 to 2012. Among them, 40 patients (57.1%) had pelvic lymph node metastases at the time of diagnosis. Sixty-seven patients (95.7%) had received chemotherapy. All patients had undergone surgery and postoperative RT. Median BMI of patients was 22.8 kg/m(2) (range, 17.7 to 35.9 kg/m(2)). The median duration of follow-up was 52.3 months (range, 16 to 107 months). Twenty-four patients (34.3%) showed recurrence. Local failure, regional lymph nodal failure, and distant failure occurred in 4 (5.7%), 6 (8.6%), and 17 (24.3%) patients, respectively. The 5-year actuarial pelvic control rate was 83.4%. The 5-year cancer-specific survival (CSS) and disease-free survival (DFS) rates were 85.1% and 65.0%, respectively. The presence of pelvic lymph node metastases (n = 30) and being overweight or obese (n = 34, BMI ≥ 23 kg/m(2)) were poor prognostic factors for CSS (p = 0.003 and p = 0.045, respectively). Of these, pelvic lymph node metastasis was an independent prognostic factor (p = 0.030) for CSS. Overweight or obese cervical cancer patients showed poorer survival outcomes than normal weight or underweight patients. Weight control seems to be important in cervical cancer patients to improve clinical outcomes.

  17. The Geriatric Nutritional Risk Index Predicts Survival in Elderly Esophageal Squamous Cell Carcinoma Patients with Radiotherapy

    PubMed Central

    Wang, Kunlun; Liu, Yang; You, Jie; Cui, Han; Zhu, Yiwei; Yuan, Ling

    2016-01-01

    The impact of nutritional status on survival among elderly esophageal squamous cell carcinoma (ESCC) patients undergoing radiotherapy is unclear. In this study, we aimed at validating the performance of the geriatric nutritional risk index (GNRI) in predicting overall survival time in elderly ESCC patients with radiotherapy. A retrospective cohort study was conducted on 239 ESCC patients aged 60 and over admitted consecutively from January 2008 to November 2014 in the Department of Radiotherapy, Henan Tumor Hospital (Affiliated Tumor Hospital of Zhengzhou University), Zhengzhou, Henan, China. All patients were subjected to nutritional screening using GNRI, and were followed for the occurrence of lymphatic node metastasis, radiation complication and mortality. The Kaplan–Meier method with Log-rank test was used to estimate survival curves. Univariable Cox regression analysis was used to identify variables associated with overall survival time. Among the 239 patients, 184 patients (76.9%) took no nutritional risk, 32 patients (13.4%) took moderate risk of malnutrition, and 23 patients (9.7%) took a high risk of malnutrition. Univariable Cox regression showed that both high nutritional risk group and moderate nutritional risk group were significantly less likely to survive than no nutritional risk patients (hazard ratio (HR) = 1.688, 95% confidence interval (CI) = 1.019–2.798 for moderate risk group, and HR = 2.699, 95% CI = 1.512–4.819 for high risk group, respectively). The GNRI is an independent prognostic factor for overall survival time in elderly ESCC patients with radiotherapy. A GNRI ≤98 can be suggested as an indicator of surviving less. PMID:27196126

  18. Pre-radiotherapy plasma carotenoids and markers of oxidative stress are associated with survival in head and neck squamous cell carcinoma patients: a prospective study

    PubMed Central

    2009-01-01

    patients compared to healthy controls, and radiotherapy affects many of these biomarkers. Increasing levels of antioxidant biomarkers before radiotherapy and increasing oxidative stress during radiotherapy may improve survival indicating that different factors/mechanisms may be important for survival before and during radiotherapy in HNSCC patients. Thus, the therapeutic potential of optimizing antioxidant status and oxidative stress should be explored further in these patients. PMID:20025747

  19. Morbidity and survival patterns in patients after radical hysterectomy and postoperative adjuvant pelvic radiotherapy

    SciTech Connect

    Fiorica, J.V.; Roberts, W.S.; Greenberg, H.; Hoffman, M.S.; LaPolla, J.P.; Cavanagh, D. )

    1990-03-01

    Morbidity and survival patterns were reviewed in 50 patients who underwent radical hysterectomy, pelvic lymphadenectomy, and adjuvant postoperative pelvic radiotherapy for invasive cervical cancer. Ninety percent of the patients were FIGO stage IB, and 10% were clinical stage IIA or IIB. Indications for adjuvant radiotherapy included pelvic lymph node metastasis, large volume, deep stromal penetration, lower uterine segment involvement, or capillary space involvement. Seventy-two percent of the patients had multiple high-risk factors. An average of 4700 cGy of whole-pelvis radiotherapy was administered. Ten percent of the patients suffered major gastrointestinal complications, 14% minor gastrointestinal morbidity, 12% minor genitourinary complications, one patient a lymphocyst, and one patient lymphedema. Of the five patients with major gastrointestinal morbidity, all occurred within 12 months of treatment. Three patients required intestinal bypass surgery for distal ileal obstructions and all are currently doing well and free of disease. All of the patients who developed recurrent disease had multiple, high-risk factors. The median time of recurrence was 12 months. All patients recurred within the radiated field. Actuarial survival was 90% and disease-free survival 87% at 70 months. It is our opinion that the morbidity of postoperative pelvic radiotherapy is acceptable, and benefit may be gained in such a high-risk patient population.

  20. Number of Negative Lymph Nodes Can Predict Survival after Postmastectomy Radiotherapy According to Different Breast Cancer Subtypes

    PubMed Central

    Wu, San-Gang; Peng, Fang; Zhou, Juan; Sun, Jia-Yuan; Li, Feng-Yan; Lin, Qin; Lin, Huan-Xin; Bao, Yong; He, Zhen-Yu

    2015-01-01

    Purpose: To assess the prognostic value of the number of negative lymph nodes (NLNs) in breast cancer patients with positive axillary lymph nodes after mastectomy and its predictive value for radiotherapy efficacy of different breast cancer subtypes (BCS). Methods: The records of 1,260 breast cancer patients with positive axillary lymph nodes who received mastectomy between January 1998 and December 2007 were reviewed. The prognostic impact and predictive value of the number of NLNs with respect to locoregional recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS) were analyzed. Results: The median follow-up time was 58 months, and 444 patients (35.2%) received postmastectomy radiotherapy (PMRT). Univariate and multivariate Cox survival analysis indicated the number of NLNs was an independent prognostic factor of LRFS, DFS, and OS. Patients with a higher number of NLNs had better survival. PMRT improved the LRFS of patients with ≤ 8 NLNs ( p < 0.001), while failing to improve the LRFS of patients with > 8 NLNs (p = 0.075). In patients with luminal A subtype, PMRT improved the LRFS, DFS, and OS of patients with ≤ 8 NLNs, but in patients with > 8 NLNs only the LRFS was improved. For patients with luminal B subtype, PMRT only improved the LRFS of patients with ≤ 8 NLNs. The number of NLNs had no predictive value for the efficacy with PMRT in Her2+ and triple-negative subtypes. Conclusions: The number of NLNs is a prognostic indicator in patients with node-positive breast cancer, and it can predict the efficacy of PMRT according to different BCS. PMID:25663944

  1. Survival improvements with adjuvant therapy in patients with glioblastoma.

    PubMed

    Jayamanne, Dasantha; Wheeler, Helen; Cook, Raymond; Teo, Charles; Brazier, David; Schembri, Geoff; Kastelan, Marina; Guo, Linxin; Back, Michael F

    2017-09-18

    Evaluate survival of patients diagnosed with glioblastoma multiforme (GBM) managed with adjuvant intensity modulated radiation therapy and temozolomide since the introduction of the European Organisation for Research and Treatment of Cancer and National Cancer Institute of Canada Clinical Trials Group (EORTC-NCIC) protocol. All patients with GBM managed between May 2007 and December 2014 with EORTC-NCIC protocol were entered into a prospective database. The primary endpoint was the median survival. Univariate predictors of survival were evaluated with respect to tumour resection, age and Eastern Cooperative Oncology Group (ECOG) performance status using log-rank comparisons. Two hundred and thirty-three patients were managed under the protocol and analysed for outcome. The median age was 57 years; the rate of gross total resection, subtotal resection and biopsy were 47.2%, 35.2% and 17.6%, respectively. At progression, 49 patients had re-resection, and in addition to second-line chemotherapy, 86 patients had Bevacizumab including 26 with re-irradiation. Median survival was 17.0 months (95% CI: 15.4-18.6). On univariate evaluation, extent of resection (P = 0.001), age, ECOG performance status and recursive partitioning analysis class III were shown to significantly improve survival (P < 0.0001). The median survival for gross total resection, age <50 years, ECOG 0-1 and recursive partitioning analysis class III were 21, 27, 20 and 47 months, respectively. This study confirms the significant improvement in median survival in GBM that has occurred in recent years since introduction of the EORTC-NCIC protocol. Further improvements have occurred presumably related to subspecialized care, improved resection rates, sophisticated radiotherapy targeting and early systemic salvage therapies. However, the burden of the disease within the community remains high and the median survival improvements over time have plateaued. © 2017 Royal Australasian College of

  2. MRE11 and ATM Expression Levels Predict Rectal Cancer Survival and Their Association with Radiotherapy Response

    PubMed Central

    Revoltar, Maxine; Lim, Stephanie H.; Tut, Thein-Ga; Abubakar, Askar; Henderson, Chris J.; Chua, Wei; Ng, Weng; Lee, Mark; De Souza, Paul; Morgan, Matthew; Lee, C. Soon; Shin, Joo-Shik

    2016-01-01

    Background Aberrant expression of DNA repair proteins is associated with poor survival in cancer patients. We investigated the combined expression of MRE11 and ATM as a predictive marker of response to radiotherapy in rectal cancer. Methods MRE11 and ATM expression were examined in tumor samples from 262 rectal cancer patients who underwent surgery for rectal cancer, including a sub-cohort of 54 patients who were treated with neoadjuvant radiotherapy. The relationship between expression of the two-protein panel and tumor regression grade (TRG) was assessed by Mann–Whitney U test and receiver operating characteristics area under curve (ROC-AUC) analysis. The association between expression of the two-protein panel and clinicopathologic variables and survival was examined by Kaplan-Meier methods and Cox regression analysis. Results A high score for two-protein combined expression in the tumor center (TC) was significantly associated with worse disease-free survival (DFS) (P = 0.035) and overall survival (OS) (P = 0.003) in the whole cohort, and with DFS (P = 0.028) and OS (P = 0.024) in the neoadjuvant subgroup (n = 54). In multivariate analysis, the two-protein combination panel (HR = 2.178, 95% CI 1.115–4.256, P = 0.023) and perineural invasion (HR = 2.183, 95% CI 1.222–3.899, P = 0.008) were significantly associated with DFS. Using ROC-AUC analysis of good versus poor histological tumor response among patients treated preoperatively with radiotherapy, the average ROC-AUC was 0.745 for the combined panel, 0.618 for ATM alone, and 0.711 for MRE11 alone. Conclusions The MRE11/ATM two-protein panel developed in this study may have clinical value as a predictive marker of tumor response to neoadjuvant radiotherapy, and a prognostic marker for disease-free and overall survival. PMID:27930716

  3. MRE11 and ATM Expression Levels Predict Rectal Cancer Survival and Their Association with Radiotherapy Response.

    PubMed

    Ho, Vincent; Chung, Liping; Revoltar, Maxine; Lim, Stephanie H; Tut, Thein-Ga; Abubakar, Askar; Henderson, Chris J; Chua, Wei; Ng, Weng; Lee, Mark; De Souza, Paul; Morgan, Matthew; Lee, C Soon; Shin, Joo-Shik

    2016-01-01

    Aberrant expression of DNA repair proteins is associated with poor survival in cancer patients. We investigated the combined expression of MRE11 and ATM as a predictive marker of response to radiotherapy in rectal cancer. MRE11 and ATM expression were examined in tumor samples from 262 rectal cancer patients who underwent surgery for rectal cancer, including a sub-cohort of 54 patients who were treated with neoadjuvant radiotherapy. The relationship between expression of the two-protein panel and tumor regression grade (TRG) was assessed by Mann-Whitney U test and receiver operating characteristics area under curve (ROC-AUC) analysis. The association between expression of the two-protein panel and clinicopathologic variables and survival was examined by Kaplan-Meier methods and Cox regression analysis. A high score for two-protein combined expression in the tumor center (TC) was significantly associated with worse disease-free survival (DFS) (P = 0.035) and overall survival (OS) (P = 0.003) in the whole cohort, and with DFS (P = 0.028) and OS (P = 0.024) in the neoadjuvant subgroup (n = 54). In multivariate analysis, the two-protein combination panel (HR = 2.178, 95% CI 1.115-4.256, P = 0.023) and perineural invasion (HR = 2.183, 95% CI 1.222-3.899, P = 0.008) were significantly associated with DFS. Using ROC-AUC analysis of good versus poor histological tumor response among patients treated preoperatively with radiotherapy, the average ROC-AUC was 0.745 for the combined panel, 0.618 for ATM alone, and 0.711 for MRE11 alone. The MRE11/ATM two-protein panel developed in this study may have clinical value as a predictive marker of tumor response to neoadjuvant radiotherapy, and a prognostic marker for disease-free and overall survival.

  4. Impact of the number of resected lymph nodes on survival after preoperative radiotherapy for esophageal cancer

    PubMed Central

    He, Zhen-Yu; Li, Feng-Yan; Lin, Huan-Xin; Sun, Jia-Yuan; Lin, Hui; Li, Qun

    2016-01-01

    To assess the impact of the number of resected lymph nodes (RLNs) for survival in esophageal cancer (EC) patients treated with preoperative radiotherapy and cancer-directed surgery. The Surveillance Epidemiology and End Results (SEER) database was queried to identify EC patients treated from 1988 to 2012 who had complete data on the number of positive lymph nodes and number of RLNs. Kaplan–Meier survival analysis and Cox regression proportional hazard methods were used to determine factors that significantly impact cause-specific survival (CSS) and overall survival (OS). There were a total of 3,159 patients who received preoperative radiotherapy and cancer-directed surgery. The median number of RLNs was 10 in both patients who received and did not receive preoperative radiotherapy (P = 0.332). Cox regression univariate and multivariate analysis showed that RLN count was a significant prognostic factor for CSS and OS. Patients with 11–71 RLNs had better CSS (hazard ratio [HR] = 0.694, 95% confidence interval [CI]: 0.603–0.799, P < 0.001) and OS (HR = 0.724, 95% CI: 0.636–0.824, P < 0.001) than patients with 1–10 RLNs. The 5-year CSS rates were 39.1% and 44.8% in patients with 1–10 RLNs and 11–71 RLNs, respectively (P < 0.001). The 5-year OS rates were 33.7% and 39.9% in patients with 1–10 RLNs and 11–71 RLNs, respectively (P < 0.001). A higher number of RLNs was associated with better survival by tumor stage and nodal stage (all P < 0.05). RLN count is an independent prognostic factor in EC patients who undergo preoperative radiotherapy and cancer-directed surgery. PMID:26992210

  5. Does postoperative radiotherapy provide any survival advantage over observation in stage IC endometrial cancer after comprehensive surgical staging?

    PubMed

    Taşkın, Salih; Güngör, Mete; Ortaç, Fırat; Öztuna, Derya

    2011-02-01

    To compare postoperative radiotherapy and observation for survival and recurrence rates in stage IC endometrial carcinoma patients who underwent comprehensive surgical staging. Fifty-seven stage IC endometrial cancer patients who underwent surgical staging were included in this study. Twenty cases (35%) received postoperative radiotherapy and 37 (65%) were observed without additional therapy. The two groups were compared for survival and recurrence rates. Mean follow-up times for the radiotherapy and observation groups were 52.05 and 38.71 months, respectively. Five-year disease-free survival rates for the radiotherapy and observation groups were 91% and 63%, respectively, and 5-year overall survival rates for the radiotherapy and observation groups were 90.0% and 80.8%, respectively. Both the disease-free and overall survival rates were similar between the two groups (p > 0.05). One (5%) of the 20 patients in the radiotherapy group, and four (10.8%) of the 37 patients in the observation group had recurrences and there was no statistical difference for the recurrence rates (p > 0.05). Disease grade had no prognostic significance in terms of survival after surgical staging. Comprehensive surgical staging might minimize the unfavorable role of deep myometrial invasion and grade. After surgical staging, postoperative observation without radiotherapy may be an appropriate approach in stage IC, all grades, endometrial carcinoma. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  6. Childhood craniopharyngioma: survival, local control, endocrine and neurologic function following radiotherapy

    SciTech Connect

    Danoff, B.F.; Cowchock, F.S.; Kramer, S.

    1983-02-01

    Between 1961 and 1978, 19 patients with a diagnosis of childhood or teenage craniopharyngioma received supervoltage radiotherapy. All patients had previously undergone either partial surgical resection (10 patients), total gross resection (3 patients), or aspiration and biopsy (6 patients). Fourteen patients were treated primarily and five were treated for recurrence. The five-year survival was 73% with a 10-year survival of 64%. Sixteen percent developed a recurrence following radiotherapy. Long term effects were assesed in terms of neurologic, intellectual, psychological and endocrine function. Seventy-nine percent had none or minimal neurologic disability. The mean full scale IQ for the group was 90. There were no additional endocrine deficiencies that could be directly attributed to radiation. Behavioral disorders occurred in 50%. These results are at least comparable, if not superior, to those of surgery.

  7. Quality of Life and Survival Outcome for Patients With Nasopharyngeal Carcinoma Receiving Three-Dimensional Conformal Radiotherapy vs. Intensity-Modulated Radiotherapy-A Longitudinal Study

    SciTech Connect

    Fang, F.-M. Chien, C.-Y.; Tsai, W.-L.; Chen, H.-C.; Hsu, H.-C.; Lui, C.-C.; Huang, T.-L.

    2008-10-01

    Purpose: To investigate the changes of quality of life (QoL) and survival outcomes for patients with nasopharyngeal carcinoma (NPC) treated by three-dimensional conformal radiotherapy (3D-CRT) vs. intensity-modulated radiotherapy (IMRT). Methods and Materials: Two hundred and three newly diagnosed NPC patients, who were curatively treated by 3D-CRT (n = 93) or IMRT (n = 110) between March 2002 and July 2004, were analyzed. The distributions of clinical stage according to American Joint Committee on Cancer 1997 were I: 15 (7.4%), II: 78 (38.4%), III: 74 (36.5%), and IV: 36 (17.7%). QoL was longitudinally assessed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the EORTC QLQ-H and N35 questionnaires at the five time points: before RT, during RT (36 Gy), and 3 months, 12 months, and 24 months after RT. Results: The 3-year locoregional control, metastasis-free survival, and overall survival rates were 84.8%, 76.7%, and 81.7% for the 3D-CRT group, respectively, compared with 84.2%, 82.6%, and 85.4% for the IMRT group (p value > 0.05). A general trend of maximal deterioration in most QoL scales was observed during RT, followed by a gradual recovery thereafter. There was no significant difference in most scales between the two groups at each time point. The exception was that patients treated by IMRT had a both statistically and clinically significant improvement in global QoL, fatigue, taste/smell, dry mouth, and feeling ill at the time point of 3 months after RT. Conclusions: The potential advantage of IMRT over 3D-CRT in treating NPC patients might occur in QoL outcome during the recovery phase of acute toxicity.

  8. Survival Outcomes in Resected Extrahepatic Cholangiocarcinoma: Effect of Adjuvant Radiotherapy in a Surveillance, Epidemiology, and End Results Analysis

    SciTech Connect

    Vern-Gross, Tamara Z.; Shivnani, Anand T.; Chen, Ke; Lee, Christopher M.; Tward, Jonathan D.; MacDonald, O. Kenneth; Crane, Christopher H.; Talamonti, Mark S.; Munoz, Louis L.; Small, William

    2011-09-01

    Purpose: The benefit of adjuvant radiotherapy (RT) after surgical resection for extrahepatic cholangiocarcinoma has not been clearly established. We analyzed survival outcomes of patients with resected extrahepatic cholangiocarcinoma and examined the effect of adjuvant RT. Methods and Materials: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) program between 1973 and 2003. The primary endpoint was the overall survival time. Cox regression analysis was used to perform univariate and multivariate analyses of the following clinical variables: age, year of diagnosis, histologic grade, localized (Stage T1-T2) vs. regional (Stage T3 or greater and/or node positive) stage, gender, race, and the use of adjuvant RT after surgical resection. Results: The records for 2,332 patients were obtained. Patients with previous malignancy, distant disease, incomplete or conflicting records, atypical histologic features, and those treated with preoperative/intraoperative RT were excluded. Of the remaining 1,491 patients eligible for analysis, 473 (32%) had undergone adjuvant RT. After a median follow-up of 27 months (among surviving patients), the median overall survival time for the entire cohort was 20 months. Patients with localized and regional disease had a median survival time of 33 and 18 months, respectively (p < .001). The addition of adjuvant RT was not associated with an improvement in overall or cause-specific survival for patients with local or regional disease. Conclusion: Patients with localized disease had significantly better overall survival than those with regional disease. Adjuvant RT was not associated with an improvement in long-term overall survival in patients with resected extrahepatic bile duct cancer. Key data, including margin status and the use of combined chemotherapy, was not available through the SEER database.

  9. Overall survival and the response to radiotherapy among molecular subtypes of breast cancer brain metastases treated with targeted therapies.

    PubMed

    Miller, Jacob A; Kotecha, Rupesh; Ahluwalia, Manmeet S; Mohammadi, Alireza M; Chao, Samuel T; Barnett, Gene H; Murphy, Erin S; Vogelbaum, Michael A; Angelov, Lilyana; Peereboom, David M; Suh, John H

    2017-06-15

    The current study was conducted to investigate survival and the response to radiotherapy among patients with molecular subtypes of breast cancer brain metastases treated with or without targeted therapies. Patients diagnosed with breast cancer brain metastases at a single tertiary care institution were included. The primary outcome was overall survival, whereas secondary outcomes included the cumulative incidences of distant intracranial failure, local failure, and radiation necrosis. Competing risks regression was used to model secondary outcomes. Within the study period, 547 patients presented with 3224 brain metastases and met inclusion criteria. Among patients with human epidermal growth factor receptor 2 (HER2)-amplified disease, 80% received HER2 antibodies and 38% received HER2/epidermal growth factor receptor tyrosine kinase inhibitors (TKIs). The median survival was significantly shorter in the basal cohort (8.4 months), and progressively increased in the luminal A (12.3 months), HER2-positive (15.4 months), and luminal B (18.8 months) cohorts (P<.001). Among patients with HER2-amplified disease, the median survival was extended with the use of both HER2 antibodies (17.9 months vs 15.1 months; P = .04) and TKIs (21.1 months vs 15.4 months; P = .03). The 12-month cumulative incidences of local failure among molecular subtypes were 6.0% in the luminal A cohort, 10.3% in the luminal B cohort, 15.4% in the HER2-positive cohort, and 9.9% in the basal cohort (P = .01). Concurrent HER2/epidermal growth factor receptor TKIs with stereotactic radiosurgery significantly decreased the 12-month cumulative incidence of local failure from 15.1% to 5.7% (P<.001). Molecular subtypes appear to be prognostic for survival and predictive of the response to radiotherapy. TKIs were found to improve survival and local control, and may decrease the rate of distant failure. To preserve neurocognition, these results support a paradigm of upfront radiosurgery and HER2

  10. Universal Survival Curve and Single Fraction Equivalent Dose: Useful Tools in Understanding Potency of Ablative Radiotherapy

    SciTech Connect

    Park, Clint; Papiez, Lech; Zhang Shichuan; Story, Michael; Timmerman, Robert D.

    2008-03-01

    Purpose: Overprediction of the potency and toxicity of high-dose ablative radiotherapy such as stereotactic body radiotherapy (SBRT) by the linear quadratic (LQ) model led to many clinicians' hesitating to adopt this efficacious and well-tolerated therapeutic option. The aim of this study was to offer an alternative method of analyzing the effect of SBRT by constructing a universal survival curve (USC) that provides superior approximation of the experimentally measured survival curves in the ablative, high-dose range without losing the strengths of the LQ model around the shoulder. Methods and Materials: The USC was constructed by hybridizing two classic radiobiologic models: the LQ model and the multitarget model. We have assumed that the LQ model gives a good description for conventionally fractionated radiotherapy (CFRT) for the dose to the shoulder. For ablative doses beyond the shoulder, the survival curve is better described as a straight line as predicted by the multitarget model. The USC smoothly interpolates from a parabola predicted by the LQ model to the terminal asymptote of the multitarget model in the high-dose region. From the USC, we derived two equivalence functions, the biologically effective dose and the single fraction equivalent dose for both CFRT and SBRT. Results: The validity of the USC was tested by using previously published parameters of the LQ and multitarget models for non-small-cell lung cancer cell lines. A comparison of the goodness-of-fit of the LQ and USC models was made to a high-dose survival curve of the H460 non-small-cell lung cancer cell line. Conclusion: The USC can be used to compare the dose fractionation schemes of both CFRT and SBRT. The USC provides an empirically and a clinically well-justified rationale for SBRT while preserving the strengths of the LQ model for CFRT.

  11. Long-Term Survival and Risk of Second Cancers After Radiotherapy for Cervical Cancer

    SciTech Connect

    Ohno, Tatsuya; Kato, Shingo; Sato, Shinichiro; Fukuhisa, Kenjiro; Nakano, Takashi; Tsujii, Hirohiko; Arai, Tatsuo

    2007-11-01

    Purpose: To evaluate the risk of second cancers after cervical cancer treated with radiotherapy for Asian populations. Methods and Materials: We reviewed 2,167 patients with cervical cancer undergoing radiotherapy between 1961 and 1986. Intracavitary brachytherapy was performed with high-dose rate source (82%) or low-dose rate source (12%). Relative risk (RR), absolute excess risk (AR), and cumulative risk of second cancer were calculated using the Japanese disease expectancy table. For 1,031 patients, the impact of smoking habit on the increasing risk of second cancer was also evaluated. Results: The total number of person-years of follow-up was 25,771, with 60 patients being lost to follow-up. Among the 2,167 patients, 1,063 (49%) survived more than 10 years. Second cancers were observed in 210 patients, representing a significant 1.2-fold risk (95% confidence interval [CI], 1.1-1.4) of developing second cancer compared with the general population, 1.6% excess risk per person per decade of follow-up, and elevating cumulative risk up to 23.8% (95% CI, 20.3-27.3) at 30 years after radiotherapy. The RR of second cancer was 1.6-fold for patients with the smoking habit and 1.4-fold for those without. Conclusions: Small but significant increased risk of second cancer was observed among Japanese women with cervical cancer mainly treated with high-dose rate brachytherapy. Considering the fact that about half of the patients survived more than 10 years, the benefit of radiotherapy outweighs the risk of developing second cancer.

  12. A stochastic model of cell survival for high-Z nanoparticle radiotherapy

    SciTech Connect

    Zygmanski, Piotr; Tsiamas, Panagiotis; Ngwa, Wil; Berbeco, Ross; Makrigiorgos, Mike; Hoegele, Wolfgang; Cifter, Fulya; Sajo, Erno

    2013-02-15

    Purpose: The authors present a stochastic framework for the assessment of cell survival in gold nanoparticle radiotherapy. Methods: The authors derive the equations for the effective macroscopic dose enhancement for a population of cells with nonideal distribution of gold nanoparticles (GNP), allowing different number of GNP per cell and different distances with respect to the cellular target. They use the mixed Poisson distribution formalism to model the impact of the aforementioned physical factors on the effective dose enhancement. Results: The authors show relatively large differences in the estimation of cell survival arising from using approximated formulae. They predict degeneration of the cell killing capacity due to different number of GNP per cell and different distances with respect to the cellular target. Conclusions: The presented stochastic framework can be used in interpretation of experimental cell survival or tumor control probability studies.

  13. Survival benefit associated with adjuvant androgen deprivation therapy combined with radiotherapy for high- and low-risk patients with nonmetastatic prostate cancer

    SciTech Connect

    Zeliadt, Steven B. . E-mail: szeliadt@fhcrc.org; Potosky, Arnold L.; Penson, David F.

    2006-10-01

    Background: The use of adjuvant androgen deprivation therapy (ADT) combined with radiotherapy has become common in low-risk patients, although clinical trials have focused primarily on high-risk patients. This study examines the effectiveness of adjuvant ADT combined with radiotherapy for a wide range of patients treated in the 1990s. Methods and Materials: Prostate cancer survival was examined in a population based cohort of 31,643 patients aged 65 to 85 years who were diagnosed with nonmetastatic prostate cancer and treated with external beam radiotherapy and/or brachytherapy. Instrumental variable analysis methods were used to control for selection bias. Results: Patients with stage T3/T4 disease who received adjuvant ADT experienced improved 5-year and 8-year survival. No survival advantage was observed for men with T1/T2 disease during this interval. Conclusion: High-risk patients who receive primary radiotherapy have benefited from adjuvant ADT, whereas low-risk patients with disease confined to the prostate have not yet benefited from adjuvant therapy within the first 8 years after treatment. These findings are consistent with practice guidelines, which recommend adjuvant ADT for patients with high-risk disease.

  14. Microsimulation Model Predicts Survival Benefit of Radiofrequency Ablation and Stereotactic Body Radiotherapy Versus Radiotherapy for Treating Inoperable Stage I Non–Small Cell Lung Cancer

    PubMed Central

    Tramontano, Angela C.; Cipriano, Lauren E.; Kong, Chung Yin; Shepard, Jo-Anne O.; Lanuti, Michael; Gazelle, G. Scott; McMahon, Pamela M.

    2013-01-01

    OBJECTIVE A subset of patients with stage IA and IB non–small cell lung cancer (NSCLC) is ineligible for surgical resection and undergoes radiation therapy. Radiofrequency ablation (RFA) and stereotactic body radiotherapy are newer potentially attractive alternative therapies. MATERIALS AND METHODS We added RFA and stereotactic body radiotherapy treatment modules to a microsimulation model that simulates lung cancer’s natural history, detection, and treatment. Natural history parameters were previously estimated via calibration against tumor registry data and cohort studies; the model was validated with screening study and cohort data. RFA model parameters were calibrated against 2-year survival from the Radiofrequency Ablation of Pulmonary Tumor Response Evaluation (RAPTURE) study, and stereotactic body radiotherapy model parameters were calibrated against 3-year survival from a phase 2 prospective trial. We simulated lifetime histories of identical patients with early-stage NSCLC who were ineligible for resection, who were treated with radiation therapy, RFA, or stereotactic body radiotherapy under a range of scenarios. From 5,000,000 simulated individuals, we selected a cohort of patients with stage I medically inoperable cancer for analysis (n = 2056 per treatment scenario). Main outcomes were life expectancy gains. RESULTS RFA or stereotactic body radiotherapy treatment in patients with peripheral stage IA or IB NSCLC who were nonoperative candidates resulted in life expectancy gains of 1.71 and 1.46 life-years, respectively, compared with universal radiation therapy. A strategy where patients with central tumors underwent stereotactic body radiotherapy and those with peripheral tumors underwent RFA resulted in a gain of 2.02 life-years compared with universal radiation therapy. Findings were robust with respect to changes in model parameters. CONCLUSION Microsimulation modeling results suggest that RFA and stereotactic body radiotherapy could provide life

  15. Bladder Preservation for Localized Muscle-Invasive Bladder Cancer: The Survival Impact of Local Utilization Rates of Definitive Radiotherapy

    SciTech Connect

    Kozak, Kevin R.; Hamidi, Maryam; Manning, Matthew; Moody, John S.

    2012-06-01

    Purpose: This study examines the management and outcomes of muscle-invasive bladder cancer in the United States. Methods and Materials: Patients with muscle-invasive bladder cancer diagnosed between 1988 and 2006 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Patients were classified according to three mutually exclusive treatment categories based on the primary initial treatment: no local management, radiotherapy, or surgery. Overall survival was assessed with Kaplan-Meier analysis and Cox models based on multiple factors including treatment utilization patterns. Results: The study population consisted of 26,851 patients. Age, sex, race, tumor grade, histology, and geographic location were associated with differences in treatment (all p < 0.01). Patients receiving definitive radiotherapy tended to be older and have less differentiated tumors than patients undergoing surgery (RT, median age 78 years old and 90.6% grade 3/4 tumors; surgery, median age 71 years old and 77.1% grade 3/4 tumors). No large shifts in treatment were seen over time, with most patients managed with surgical resection (86.3% for overall study population). Significant survival differences were observed according to initial treatment: median survival, 14 months with no definitive local treatment; 17 months with radiotherapy; and 43 months for surgery. On multivariate analysis, differences in local utilization rates of definitive radiotherapy did not demonstrate a significant effect on overall survival (hazard ratio, 1.002; 95% confidence interval, 0.999-1.005). Conclusions: Multiple factors influence the initial treatment strategy for muscle-invasive bladder cancer, but definitive radiotherapy continues to be used infrequently. Although patients who undergo surgery fare better, a multivariable model that accounted for patient and tumor characteristics found no survival detriment to the utilization of definitive radiotherapy. These results support continued

  16. Adjuvant sequential chemo and radiotherapy improves the oncological outcome in high risk endometrial cancer

    PubMed Central

    Signorelli, Mauro; Lissoni, Andrea Alberto; De Ponti, Elena; Grassi, Tommaso; Ponti, Serena

    2015-01-01

    Objective Evaluation of the impact of sequential chemoradiotherapy in high risk endometrial cancer (EC). Methods Two hundred fifty-four women with stage IB grade 3, II and III EC (2009 FIGO staging), were included in this retrospective study. Results Stage I, II, and III was 24%, 28.7%, and 47.3%, respectively. Grade 3 tumor was 53.2% and 71.3% had deep myometrial invasion. One hundred sixty-five women (65%) underwent pelvic (+/- aortic) lymphadenectomy and 58 (22.8%) had nodal metastases. Ninety-eight women (38.6%) underwent radiotherapy, 59 (23.2%) chemotherapy, 42 (16.5%) sequential chemoradiotherapy, and 55 (21.7%) were only observed. After a median follow-up of 101 months, 78 women (30.7%) relapsed and 91 women (35.8%) died. Sequential chemoradiotherapy improved survival rates in women who did not undergo nodal evaluation (disease-free survival [DFS], p=0.040; overall survival [OS], p=0.024) or pelvic (+/- aortic) lymphadenectomy (DFS, p=0.008; OS, p=0.021). Sequential chemoradiotherapy improved both DFS (p=0.015) and OS (p=0.014) in stage III, while only a trend was found for DFS (p=0.210) and OS (p=0.102) in stage I-II EC. In the multivariate analysis, only age (≤65 years) and sequential chemoradiotherapy were statistically related to the prognosis. Conclusion Sequential chemoradiotherapy improves survival rates in high risk EC compared with chemotherapy or radiotherapy alone, in particular in stage III. PMID:26197768

  17. Adjuvant sequential chemo and radiotherapy improves the oncological outcome in high risk endometrial cancer.

    PubMed

    Signorelli, Mauro; Lissoni, Andrea Alberto; De Ponti, Elena; Grassi, Tommaso; Ponti, Serena; Fruscio, Robert

    2015-10-01

    Evaluation of the impact of sequential chemoradiotherapy in high risk endometrial cancer (EC). Two hundred fifty-four women with stage IB grade 3, II and III EC (2009 FIGO staging), were included in this retrospective study. Stage I, II, and III was 24%, 28.7%, and 47.3%, respectively. Grade 3 tumor was 53.2% and 71.3% had deep myometrial invasion. One hundred sixty-five women (65%) underwent pelvic (+/- aortic) lymphadenectomy and 58 (22.8%) had nodal metastases. Ninety-eight women (38.6%) underwent radiotherapy, 59 (23.2%) chemotherapy, 42 (16.5%) sequential chemoradiotherapy, and 55 (21.7%) were only observed. After a median follow-up of 101 months, 78 women (30.7%) relapsed and 91 women (35.8%) died. Sequential chemoradiotherapy improved survival rates in women who did not undergo nodal evaluation (disease-free survival [DFS], p=0.040; overall survival [OS], p=0.024) or pelvic (+/- aortic) lymphadenectomy (DFS, p=0.008; OS, p=0.021). Sequential chemoradiotherapy improved both DFS (p=0.015) and OS (p=0.014) in stage III, while only a trend was found for DFS (p=0.210) and OS (p=0.102) in stage I-II EC. In the multivariate analysis, only age (≤ 65 years) and sequential chemoradiotherapy were statistically related to the prognosis. Sequential chemoradiotherapy improves survival rates in high risk EC compared with chemotherapy or radiotherapy alone, in particular in stage III.

  18. Adjuvant radiotherapy in stage 1 seminoma: Evaluation of prognostic factors and results of survival.

    PubMed

    Serdar, Lasif; Canyilmaz, Emine; Topcu, Turkan Ozturk; Sahbaz, Asli; Memis, Yahyahan; Soydemir, Gulsen; Aynaci, Ozlem; Kandaz, Mustafa; Bahat, Zümrüt; Yoney, Adnan

    2015-01-01

    The purpose of this study was to evaluate the prognostic factors affecting overall survival (OS), cause-specific survival (CSS), progression-free survival (PFS), and survival among patients undergoing adjuvant radiotherapy (RT) for stage-1 seminoma. Between August 1997 and May 2013, 68 patients diagnosed with stage-1 seminoma were retrospectively evaluated. The median age was 39 (24-74) years. All patients received adjuvant RT after inguinal orchiectomy. Fifty-eight (85.3%) patients received paraaortic RT; 10 (14.7%) received dog-leg field RT. The median RT dose was 23.4 (23.4-30.6) Gy. The median follow-up period was 77.5 (6.7-198.5) months. During the follow-up period, two patients developed distant metastasis, and none developed local recurrence. Two patients died from seminoma, and three died for other reasons. The 5, 10, and 15-year OS rates were 94.7%, 89.6%, and 89.6%, respectively. The 5, 10, and 15-year CSS rates were 98.5%, 96%, and 96%, respectively. The 5, 10, and 15-year PFS rate was 96.1%. The univariate analysis showed that only histological subtype was significant for OS. The 10-year survival rate was 100% among patients with seminoma histology, 90.8% among patients with a classic seminoma histology, and 50% among patients with an anaplastic seminoma histology (P < 0.001). A multivariate analysis showed that the anaplastic seminoma was a negative prognostic indicator for OS (P = 0.042). Adjuvant RT resulted in excellent long-term survival and local control in patients with stage-1 seminoma after orchiectomy. During a short follow-up, secondary malignancy (SM) and late cardiovascular morbidity were not observed. Despite those results, concern of SM and late cardiovascular morbidity remains.

  19. Functional outcome and survival after radiotherapy of metastatic spinal cord compression in patients with cancer of unknown primary

    SciTech Connect

    Rades, Dirk . E-mail: Rades.Dirk@gmx.net; Fehlauer, Fabian; Veninga, Theo; Stalpers, Lukas J.A.; Basic, Hiba; Hoskin, Peter J.; Rudat, Volker; Karstens, Johann H.; Schild, Steven E.; Dunst, Juergen

    2007-02-01

    Purpose: Patients with cancer of unknown primary (CUP) account for about 10% of patients with metastatic spinal cord compression (MSCC). This study aims to define the appropriate radiation regimen for these patients. Methods and Materials: Data of 143 CUP patients irradiated for MSCC were retrospectively evaluated. Short-course radiotherapy (RT) (1x8 Gy, 5x4 Gy, n = 68) and long-course RT (10x3 Gy, 15x2.5 Gy, 20x2 Gy, n = 75) plus 8 further potential prognostic factors (age, gender, performance status, visceral metastases, other bone metastases, number of involved vertebrae, ambulatory status, time of developing motor deficits before RT) were compared for functional outcome and survival. Results: Improvement of motor function occurred in 10% of patients, no further progression of motor deficits in 57%, and deterioration in 33%. On multivariate analysis, functional outcome was positively associated with slower development of motor deficits (p < 0.001), absence of visceral metastases (p = 0.008) and other bone metastases (p = 0.027), and ambulatory status (p = 0.054), not with the radiation regimen (p = 0.74). Recurrence of MSCC in the irradiated region occurred in 7 patients after median 6 months. Median survival was 4 months. On multivariate analysis, better survival was significantly associated with absence of visceral metastases (p < 0.001), absence of other bone metastases (p = 0.005), ambulatory status (p = 0.001), and slower development of motor deficits (p = 0.030). Conclusions: For MSCC treatment in patients with CUP, no significant difference was observed between short-course and long-course RT regarding functional outcome and survival. Short-course RT appears preferable, at least for patients with a poor predicted survival, as it is more patient convenient and more cost-effective.

  20. Intensity modulated radiotherapy induces pro-inflammatory and pro-survival responses in prostate cancer patients

    PubMed Central

    EL-SAGHIRE, HOUSSEIN; VANDEVOORDE, CHARLOT; OST, PIET; MONSIEURS, PIETER; MICHAUX, ARLETTE; DE MEERLEER, GERT; BAATOUT, SARAH; THIERENS, HUBERT

    2014-01-01

    Intensity modulated radiotherapy (IMRT) is one of the modern conformal radiotherapies that is widely used within the context of cancer patient treatment. It uses multiple radiation beams targeted to the tumor, however, large volumes of the body receive low doses of irradiation. Using γ-H2AX and global genome expression analysis, we studied the biological responses induced by low doses of ionizing radiation in prostate cancer patients following IMRT. By means of different bioinformatics analyses, we report that IMRT induced an inflammatory response via the induction of viral, adaptive, and innate immune signaling. In response to growth factors and immune-stimulatory signaling, positive regulation in the progression of cell cycle and DNA replication were induced. This denotes pro-inflammatory and pro-survival responses. Furthermore, double strand DNA breaks were induced in every patient 30 min after the treatment and remaining DNA repair and damage signaling continued after 18–24 h. Nine genes belonging to inflammatory responses (TLR3, SH2D1A and IL18), cell cycle progression (ORC4, SMC2 and CCDC99) and DNA damage and repair (RAD17, SMC6 and MRE11A) were confirmed by quantitative RT-PCR. This study emphasizes that the risk assessment of health effects from the out-of-field low doses during IMRT should be of concern, as these may increase the risk of secondary cancers and/or systemic inflammation. PMID:24435511

  1. Centromere and kinetochore gene misexpression predicts cancer patient survival and response to radiotherapy and chemotherapy

    PubMed Central

    Zhang, Weiguo; Mao, Jian-Hua; Zhu, Wei; Jain, Anshu K.; Liu, Ke; Brown, James B.; Karpen, Gary H.

    2016-01-01

    Chromosomal instability (CIN) is a hallmark of cancer that contributes to tumour heterogeneity and other malignant properties. Aberrant centromere and kinetochore function causes CIN through chromosome missegregation, leading to aneuploidy, rearrangements and micronucleus formation. Here we develop a Centromere and kinetochore gene Expression Score (CES) signature that quantifies the centromere and kinetochore gene misexpression in cancers. High CES values correlate with increased levels of genomic instability and several specific adverse tumour properties, and prognosticate poor patient survival for breast and lung cancers, especially early-stage tumours. They also signify high levels of genomic instability that sensitize cancer cells to additional genotoxicity. Thus, the CES signature forecasts patient response to adjuvant chemotherapy or radiotherapy. Our results demonstrate the prognostic and predictive power of the CES, suggest a role for centromere misregulation in cancer progression, and support the idea that tumours with extremely high CIN are less tolerant to specific genotoxic therapies. PMID:27577169

  2. TERT promoter mutations and long telomere length predict poor survival and radiotherapy resistance in gliomas

    PubMed Central

    Qu, Yiping; Wang, Maode; Cui, Bo; Ji, Meiju; Shi, Bingyin; Hou, Peng

    2016-01-01

    Increasing evidences have implicated somatic gain-of-function mutations at the telomerase reverse transcriptase (TERT) promoter as one of the major mechanisms that promote transcriptional activation of TERT and subsequently maintain telomere length in human cancers including glioma. To investigate the prognostic value of these mutations and telomere length, individually and their coexistence, in gliomas, we analyzed two somatic mutations C228T and C250T in the TERT promoter, relative telomere length (RTL), IDH1 mutation and MGMT methylation in 389 glioma patients, and explored their associations with patient characteristics and clinical outcomes. Our data showed that C228T and C250T mutations were found in 17.0% (66 of 389) and 11.8% (46 of 389) of gliomas, respectively, and these two mutations were mutually exclusive in this cancer. Moreover, they were significantly associated with WHO grade. We also found that the RTL was significant longer in gliomas than in meningiomas and normal brain tissues (Median, 0.89 vs. 0.44 and 0.50; P < 0.001), and demonstrated that the RTL was strongly correlated with tumor recurrence. Importantly, TERT promoter mutations or long RTL caused a significantly poorer survival than TERT wild-type or short RTL. Coexisting TERT promoter mutations and long RTL were more commonly associated with poor patient survival than they were individually. Notably, the patients with TERT promoter mutations particularly C228T or long RTL were resistant to radiotherapy. Collectively, TERT promoter mutations and long RTL are not only prognostic factors for poor clinical outcomes, but also the predictors of radiotherapy resistance in gliomas. PMID:26556853

  3. TERT promoter mutations and long telomere length predict poor survival and radiotherapy resistance in gliomas.

    PubMed

    Gao, Ke; Li, Gang; Qu, Yiping; Wang, Maode; Cui, Bo; Ji, Meiju; Shi, Bingyin; Hou, Peng

    2016-02-23

    Increasing evidences have implicated somatic gain-of-function mutations at the telomerase reverse transcriptase (TERT) promoter as one of the major mechanisms that promote transcriptional activation of TERT and subsequently maintain telomere length in human cancers including glioma. To investigate the prognostic value of these mutations and telomere length, individually and their coexistence, in gliomas, we analyzed two somatic mutations C228T and C250T in the TERT promoter, relative telomere length (RTL), IDH1 mutation and MGMT methylation in 389 glioma patients, and explored their associations with patient characteristics and clinical outcomes. Our data showed that C228T and C250T mutations were found in 17.0% (66 of 389) and 11.8% (46 of 389) of gliomas, respectively, and these two mutations were mutually exclusive in this cancer. Moreover, they were significantly associated with WHO grade. We also found that the RTL was significant longer in gliomas than in meningiomas and normal brain tissues (Median, 0.89 vs. 0.44 and 0.50; P < 0.001), and demonstrated that the RTL was strongly correlated with tumor recurrence. Importantly, TERT promoter mutations or long RTL caused a significantly poorer survival than TERT wild-type or short RTL. Coexisting TERT promoter mutations and long RTL were more commonly associated with poor patient survival than they were individually. Notably, the patients with TERT promoter mutations particularly C228T or long RTL were resistant to radiotherapy. Collectively, TERT promoter mutations and long RTL are not only prognostic factors for poor clinical outcomes, but also the predictors of radiotherapy resistance in gliomas.

  4. Prognostic Factors and Survival in Patients with Radiation-Related Second Malignant Neoplasms Following Radiotherapy for Nasopharyngeal Carcinoma

    PubMed Central

    Zhao, Lei; Shen, Jing-Xian; Zhang, Li; Zhang, Peng; Liu, Meng-Zhong

    2013-01-01

    Purpose To analyze the clinicopathological characteristics, treatment modalities, and potential prognostic factors of radiation-related second malignant neoplasms (SMNs) in a large group of nasopharyngeal carcinoma (NPC) cases. Methods and Materials Institutional electronic medical records of 39,118 patients with NPC treated by definitive radiotherapy between February 1964 and December 2003 were reviewed. A total of 247 patients with confirmed SMN attributable to radiotherapy were included. Results Median latency between radiotherapy for NPC and the diagnosis of SMN was 9.5 years (range, 3.1–36.8 years). Squamous cell carcinoma was the most common histologic type, followed by fibrosarcoma and adenocarcinoma. Median progression-free survival and overall survival (OS) of the 235 patients who underwent treatment were 17.3 months and 28.5 months, respectively. The 5-year OS rates were 42.9%, 23.7%, and 0% for the surgery, radiotherapy, and chemotherapy groups, respectively. The independent prognostic factors associated with survival were sex, histologic type, and treatment modality in both the early stage subgroup and the advanced stage subgroup of SMN. Conclusions Sex, histologic type, and treatment modality were the significant prognostic factors for SMN. Complete resection offers the best chance for long-term survival. In select patients with locally advanced and unresectable SMN, reirradiation should be strongly considered as a curative option. PMID:24367679

  5. Effect of Radiotherapy Interruptions on Survival in Medicare Enrollees With Local and Regional Head-and-Neck Cancer

    SciTech Connect

    Fesinmeyer, Megan Dann; Mehta, Vivek; Blough, David; Tock, Lauri; Ramsey, Scott D.

    2010-11-01

    Purpose: To investigate whether interruptions in radiotherapy are associated with decreased survival in a population-based sample of head-and-neck cancer patients. Methods and Materials: Using the Surveillance, Epidemiology, and End Results-Medicare linked database we identified Medicare beneficiaries aged 66 years and older diagnosed with local-regional head-and-neck cancer during the period 1997-2003. We examined claims records of 3864 patients completing radiotherapy for the presence of one or more 5-30-day interruption(s) in therapy. We then performed Cox regression analyses to estimate the association between therapy interruptions and survival. Results: Patients with laryngeal tumors who experienced an interruption in radiotherapy had a 68% (95% confidence interval, 41-200%) increased risk of death, compared with patients with no interruptions. Patients with nasal cavity, nasopharynx, oral, salivary gland, and sinus tumors had similar associations between interruptions and increased risk of death, but these did not reach statistical significance because of small sample sizes. Conclusions: Treatment interruptions seem to influence survival time among patients with laryngeal tumors completing a full course of radiotherapy. At all head-and-neck sites, the association between interruptions and survival is sensitive to confounding by stage and other treatments. Further research is needed to develop methods to identify patients most susceptible to interruption-induced mortality.

  6. Translational Research to Improve the Efficacy of Carbon Ion Radiotherapy: Experience of Gunma University

    PubMed Central

    Oike, Takahiro; Sato, Hiro; Noda, Shin-ei; Nakano, Takashi

    2016-01-01

    Carbon ion radiotherapy holds great promise for cancer therapy. Clinical data show that carbon ion radiotherapy is an effective treatment for tumors that are resistant to X-ray radiotherapy. Since 1994 in Japan, the National Institute of Radiological Sciences has been heading the development of carbon ion radiotherapy using the Heavy Ion Medical Accelerator in Chiba. The Gunma University Heavy Ion Medical Center (GHMC) was established in the year 2006 as a proof-of-principle institute for carbon ion radiotherapy with a view to facilitating the worldwide spread of compact accelerator systems. Along with the management of more than 1900 cancer patients to date, GHMC engages in translational research to improve the treatment efficacy of carbon ion radiotherapy. Research aimed at guiding patient selection is of utmost importance for making the most of carbon ion radiotherapy, which is an extremely limited medical resource. Intratumoral oxygen levels, radiation-induced cellular apoptosis, the capacity to repair DNA double-strand breaks, and the mutational status of tumor protein p53 and epidermal growth factor receptor genes are all associated with X-ray sensitivity. Assays for these factors are useful in the identification of X-ray-resistant tumors for which carbon ion radiotherapy would be beneficial. Research aimed at optimizing treatments based on carbon ion radiotherapy is also important. This includes assessment of dose fractionation, normal tissue toxicity, tumor cell motility, and bystander effects. Furthermore, the efficacy of carbon ion radiotherapy will likely be enhanced by research into combined treatment with other modalities such as chemotherapy. Several clinically available chemotherapeutic drugs (carboplatin, paclitaxel, and etoposide) and drugs at the developmental stage (Wee-1 and heat shock protein 90 inhibitors) show a sensitizing effect on tumor cells treated with carbon ions. Additionally, the efficacy of carbon ion radiotherapy can be improved by

  7. Translational Research to Improve the Efficacy of Carbon Ion Radiotherapy: Experience of Gunma University.

    PubMed

    Oike, Takahiro; Sato, Hiro; Noda, Shin-Ei; Nakano, Takashi

    2016-01-01

    Carbon ion radiotherapy holds great promise for cancer therapy. Clinical data show that carbon ion radiotherapy is an effective treatment for tumors that are resistant to X-ray radiotherapy. Since 1994 in Japan, the National Institute of Radiological Sciences has been heading the development of carbon ion radiotherapy using the Heavy Ion Medical Accelerator in Chiba. The Gunma University Heavy Ion Medical Center (GHMC) was established in the year 2006 as a proof-of-principle institute for carbon ion radiotherapy with a view to facilitating the worldwide spread of compact accelerator systems. Along with the management of more than 1900 cancer patients to date, GHMC engages in translational research to improve the treatment efficacy of carbon ion radiotherapy. Research aimed at guiding patient selection is of utmost importance for making the most of carbon ion radiotherapy, which is an extremely limited medical resource. Intratumoral oxygen levels, radiation-induced cellular apoptosis, the capacity to repair DNA double-strand breaks, and the mutational status of tumor protein p53 and epidermal growth factor receptor genes are all associated with X-ray sensitivity. Assays for these factors are useful in the identification of X-ray-resistant tumors for which carbon ion radiotherapy would be beneficial. Research aimed at optimizing treatments based on carbon ion radiotherapy is also important. This includes assessment of dose fractionation, normal tissue toxicity, tumor cell motility, and bystander effects. Furthermore, the efficacy of carbon ion radiotherapy will likely be enhanced by research into combined treatment with other modalities such as chemotherapy. Several clinically available chemotherapeutic drugs (carboplatin, paclitaxel, and etoposide) and drugs at the developmental stage (Wee-1 and heat shock protein 90 inhibitors) show a sensitizing effect on tumor cells treated with carbon ions. Additionally, the efficacy of carbon ion radiotherapy can be improved by

  8. Tissue expander placement and adjuvant radiotherapy after surgical resection of retroperitoneal liposarcoma offers improved local control

    PubMed Central

    Park, Hyojun; Lee, Sanghoon; Kim, BoKyong; Lim, Do Hoon; Choi, Yoon-La; Choi, Gyu Seong; Kim, Jong Man; Park, Jae Berm; Kwon, Choon Hyuck David; Joh, Jae-Won; Kim, Sung Joo

    2016-01-01

    Abstract Given that retroperitoneal liposarcoma (LPS) is extremely difficult to completely resect, and has a relatively high rate of recurrence, radiotherapy (RT) is the treatment of choice after surgical resection. However, it is difficult to obtain a sufficient radiation field because of the close proximity of surrounding organs. We introduce the use of tissue expanders (TEs) after LPS resection in an attempt to secure a sufficient radiation field and to improve recurrence-free survival. This study is a retrospective review of 53 patients who underwent surgical resection of LPS at Samsung Medical Center between January 1, 2005, and December 31, 2012, and had no residual tumor detected 2 months postoperatively. The median follow-up period was 38.9 months. Patients were divided into 3 groups. Those in group 1 (n = 17) had TE inserted and received postoperative RT. The patients in group 2 (n = 9) did not have TE inserted and received postoperative RT. Finally, those in group 3 (n = 27) did not receive postoperative RT. Multivariate analysis was performed to identify the risk factors associated with recurrence-free survival within 3 years. Younger age, history of LPS treatment, and RT after TE insertion (group 1 vs group 2 or 3) were significantly favorable factors influencing 3-year recurrence-free survival. TE insertion after LPS resection is associated with increased 3-year recurrence-free survival, most likely because it allows effective delivery of postoperative RT. PMID:27512857

  9. Tissue expander placement and adjuvant radiotherapy after surgical resection of retroperitoneal liposarcoma offers improved local control.

    PubMed

    Park, Hyojun; Lee, Sanghoon; Kim, BoKyong; Lim, Do Hoon; Choi, Yoon-La; Choi, Gyu Seong; Kim, Jong Man; Park, Jae Berm; Kwon, Choon Hyuck David; Joh, Jae-Won; Kim, Sung Joo

    2016-08-01

    Given that retroperitoneal liposarcoma (LPS) is extremely difficult to completely resect, and has a relatively high rate of recurrence, radiotherapy (RT) is the treatment of choice after surgical resection. However, it is difficult to obtain a sufficient radiation field because of the close proximity of surrounding organs. We introduce the use of tissue expanders (TEs) after LPS resection in an attempt to secure a sufficient radiation field and to improve recurrence-free survival.This study is a retrospective review of 53 patients who underwent surgical resection of LPS at Samsung Medical Center between January 1, 2005, and December 31, 2012, and had no residual tumor detected 2 months postoperatively. The median follow-up period was 38.9 months.Patients were divided into 3 groups. Those in group 1 (n = 17) had TE inserted and received postoperative RT. The patients in group 2 (n = 9) did not have TE inserted and received postoperative RT. Finally, those in group 3 (n = 27) did not receive postoperative RT. Multivariate analysis was performed to identify the risk factors associated with recurrence-free survival within 3 years. Younger age, history of LPS treatment, and RT after TE insertion (group 1 vs group 2 or 3) were significantly favorable factors influencing 3-year recurrence-free survival.TE insertion after LPS resection is associated with increased 3-year recurrence-free survival, most likely because it allows effective delivery of postoperative RT.

  10. Failure-Free Survival and Radiotherapy in Patients With Newly Diagnosed Nonmetastatic Prostate Cancer

    PubMed Central

    James, Nicholas D.; Spears, Melissa R.; Clarke, Noel W.; Dearnaley, David P.; Mason, Malcolm D.; Parker, Christopher C.; Ritchie, Alastair W. S.; Russell, J. Martin; Schiavone, Francesca; Attard, Gerhardt; de Bono, Johann S.; Birtle, Alison; Engeler, Daniel S.; Elliott, Tony; Matheson, David; O’Sullivan, Joe; Pudney, Delia; Srihari, Narayanan; Wallace, Jan; Barber, Jim; Syndikus, Isabel; Parmar, Mahesh K. B.; Sydes, Matthew R.

    2016-01-01

    IMPORTANCE The natural history of patients with newly diagnosed high-risk nonmetastatic (M0) prostate cancer receiving hormone therapy (HT) either alone or with standard-of-care radiotherapy (RT) is not well documented. Furthermore, no clinical trial has assessed the role of RT in patients with node-positive (N+) M0 disease. The STAMPEDE Trial includes such individuals, allowing an exploratory multivariate analysis of the impact of radical RT. OBJECTIVE To describe survival and the impact on failure-free survival of RT by nodal involvement in these patients. DESIGN, SETTING, AND PARTICIPANTS Cohort study using data collected for patients allocated to the control arm (standard-of-care only) of the STAMPEDE Trial between October 5, 2005, and May 1, 2014. Outcomes are presented as hazard ratios (HRs) with 95% CIs derived from adjusted Cox models; survival estimates are reported at 2 and 5 years. Participants were high-risk, hormone-naive patients with newly diagnosed M0 prostate cancer starting long-term HT for the first time. Radiotherapy is encouraged in this group, but mandated for patients with node-negative (N0) M0 disease only since November 2011. EXPOSURES Long-term HT either alone or with RT, as per local standard. Planned RT use was recorded at entry. MAIN OUTCOMES AND MEASURES Failure-free survival (FFS) and overall survival. RESULTS A total of 721 men with newly diagnosed M0 disease were included: median age at entry, 66 (interquartile range [IQR], 61-72) years, median (IQR) prostate-specific antigen level of 43 (18-88) ng/mL. There were 40 deaths (31 owing to prostate cancer) with 17 months’ median follow-up. Two-year survival was 96% (95% CI, 93%-97%) and 2-year FFS, 77% (95% CI, 73%-81%). Median (IQR) FFS was 63 (26 to not reached) months. Time to FFS was worse in patients with N+ disease (HR, 2.02 [95% CI, 1.46-2.81]) than in those with N0 disease. Failure-free survival outcomes favored planned use of RT for patients with both N0M0 (HR, 0.33 [95% CI

  11. Validation of a Predictive Model for Survival in Metastatic Cancer Patients Attending an Outpatient Palliative Radiotherapy Clinic

    SciTech Connect

    Chow, Edward Abdolell, Mohamed; Panzarella, Tony; Harris, Kristin; Bezjak, Andrea; Warde, Padraig; Tannock, Ian

    2009-01-01

    Purpose: To validate a predictive model for survival of patients attending a palliative radiotherapy clinic. Methods and Materials: We described previously a model that had good predictive value for survival of patients referred during 1999 (1). The six prognostic factors (primary cancer site, site of metastases, Karnofsky performance score, and the fatigue, appetite and shortness-of-breath items from the Edmonton Symptom Assessment Scale) identified in this training set were extracted from the prospective database for the year 2000. We generated a partial score whereby each prognostic factor was assigned a value proportional to its prognostic weight. The sum of the partial scores for each patient was used to construct a survival prediction score (SPS). Patients were also grouped according to the number of these risk factors (NRF) that they possessed. The probability of survival at 3, 6, and 12 months was generated. The models were evaluated for their ability to predict survival in this validation set with appropriate statistical tests. Results: The median survival and survival probabilities of the training and validation sets were similar when separated into three groups using both SPS and NRF methods. There was no statistical difference in the performance of the SPS and NRF methods in survival prediction. Conclusion: Both the SPS and NRF models for predicting survival in patients referred for palliative radiotherapy have been validated. The NRF model is preferred because it is simpler and avoids the need to remember the weightings among the prognostic factors.

  12. Association of Body Composition With Survival and Locoregional Control of Radiotherapy-Treated Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Grossberg, Aaron J.; Chamchod, Sasikarn; Fuller, Clifton D.; Mohamed, Abdallah SR; Heukelom, Jolien; Eichelberger, Hillary; Kantor, Michael E.; Hutcheson, Katherine A.; Gunn, G. Brandon; Garden, Adam S.; Frank, Steven; Phan, Jack; Beadle, Beth; Skinner, Heath D; Morrison, William H.; Rosenthal, David I.

    2016-01-01

    IMPORTANCE Major weight loss is common in patients with head and neck squamous cell carcinoma (HNSCC) who undergo radiotherapy (RT). How baseline and posttreatment body composition affects outcome is unknown. OBJECTIVE To determine whether lean body mass before and after RT for HNSCC predicts survival and locoregional control. DESIGN, SETTING, AND PARTICIPANT Retrospective study of 2840 patients with pathologically proven HNSCC undergoing curative RT at a single academic cancer referral center from October 1, 2003, to August 31, 2013. One hundred ninety patients had computed tomographic (CT) scans available for analysis of skeletal muscle (SM). The effect of pre-RT and post-RT SM depletion (defined as a CT-measured L3 SM index of less than 52.4 cm2 /m2 for men and less than 38.5 cm2 /m2 for women) on survival and disease control was evaluated. Final follow-up was completed on September 27, 2014, and data were analyzed from October 1, 2014, to November 29, 2015. MAIN OUTCOMES AND MEASURES Primary outcomes were overall and disease-specific survival and locoregional control. Secondary analyses included the influence of pre-RT body mass index (BMI) and interscan weight loss on survival and recurrence. RESULTS Among the 2840 consecutive patients who underwent screening, 190 had whole-body positron emission tomography–CT or abdominal CT scans before and after RT and were included for analysis. Of these, 160 (84.2%) were men and 30 (15.8%) were women; their mean (SD) age was 57.7 (9.4) years. Median follow up was 68.6 months. Skeletal muscle depletion was detected in 67 patients (35.3%) before RT and an additional 58 patients (30.5%) after RT. Decreased overall survival was predicted by SM depletion before RT (hazard ratio [HR], 1.92; 95% CI, 1.19–3.11; P = .007) and after RT (HR, 2.03; 95% CI, 1.02–4.24; P = .04). Increased BMI was associated with significantly improved survival (HR per 1-U increase in BMI, 0.91; 95% CI, 0.87–0.96; P < .001). Weight loss without

  13. Concurrent Radiotherapy and Gemcitabine for Unresectable Pancreatic Adenocarcinoma: Impact of Adjuvant Chemotherapy on Survival

    SciTech Connect

    Ogawa, Kazuhiko; Ito, Yoshinori; Hirokawa, Naoki; Shibuya, Keiko; Kokubo, Masaki; Ogo, Etsuyo; Shibuya, Hitoshi; Saito, Tsutomu; Onishi, Hiroshi; Karasawa, Katsuyuki; Nemoto, Kenji; Nishimura, Yasumasa

    2012-06-01

    Purpose: To retrospectively analyze results of concurrent chemoradiotherapy (CCRT) using gemcitabine (GEM) for unresectable pancreatic adenocarcinoma. Methods and Materials: Records of 108 patients treated with concurrent external beam radiotherapy (EBRT) and GEM were reviewed. The median dose of EBRT in all 108 patients was 50.4 Gy (range, 3.6-60.8 Gy), usually administered in conventional fractionations (1.8-2 Gy/day). During radiotherapy, most patients received GEM at a dosage of 250 to 350 mg/m{sup 2} intravenously weekly for approximately 6 weeks. After CCRT, 59 patients (54.6%) were treated with adjuvant chemotherapy (AC), mainly with GEM. The median follow-up for all 108 patients was 11.0 months (range, 0.4-37.9 months). Results: Initial responses after CCRT for 85 patients were partial response: 26 patients, no change: 51 patients and progressive disease: 8 patients. Local progression was observed in 35 patients (32.4%), and the 2-year local control (LC) rate in all patients was 41.9%. Patients treated with total doses of 50 Gy or more had significantly more favorable LC rates (2-year LC rate, 42.9%) than patients treated with total doses of less than 50 Gy (2-year LC rate, 29.6%). Regional lymph node recurrence was found in only 1 patient, and none of the 57 patients with clinical N0 disease had regional lymph node recurrence. The 2-year overall survival (OS) rate and the median survival time in all patients were 23.5% and 11.6 months, respectively. Patients treated with AC had significantly more favorable OS rates (2-year OS, 31.8%) than those treated without AC (2-year OS, 12.4%; p < 0.0001). On multivariate analysis, AC use and clinical T stage were significant prognostic factors for OS. Conclusions: CCRT using GEM yields a relatively favorable LC rate for unresectable pancreatic adenocarcinoma, and CCRT with AC conferred a survival benefit compared to CCRT without AC.

  14. Revisiting the impact of age and molecular subtype on overall survival after radiotherapy in breast cancer patients.

    PubMed

    Mao, Jian-Hua; Diest, Paul J van; Perez-Losada, Jesus; Snijders, Antoine M

    2017-10-03

    Adjuvant radiotherapy (RT) in breast cancer (BC) is often used to eradicate remaining tumor cells following surgery with the goal of maximizing local control and increasing overall survival. The current study investigated the impact of age and BC molecular subtype on overall survival after RT using a meta-analysis of the METABRIC and TCGA BC patient cohorts. We found that RT significantly prolonged survival across the whole BC patient population. The survival benefit of RT was predominantly observed in stage II BC patients treated with breast conserving surgery. Patients were then stratified by age and molecular subtype to investigate survival rate associated with RT. An increase in survival for the luminal-A and basal BC molecular subtypes was observed after RT. Stratifying patients based on age revealed that increased survival was restricted to younger patients (≤60 years of age at diagnosis). There was a significant survival benefit of radiotherapy for younger patients with tumors of the luminal A and basal molecular subtypes. Patients with other breast tumor subtypes or older breast cancer patients did not seem to benefit effects of RT. Therefore, alternate local treatment strategies should be considered for older, luminal B, and HER2 driven BC patients.

  15. Radiotherapy in conjunction with superficial and intracavitary hyperthermia for the treatment of solid tumors: survival and thermal parameters.

    PubMed

    Triantopoulou, S; Efstathopoulos, E; Platoni, K; Uzunoglou, N; Kelekis, N; Kouloulias, V

    2013-02-01

    Hyperthermia is an effective modality for the treatment of cancer, which is mainly used in conjunction with radiotherapy as this combined treatment offers a better clinical outcome. There are many ways that hyperthermia can be applied and depends on the kind of tumor of the patients. The great advantage of this method is that it is tolerable for the majority of patients without severe toxicity. Many clinical trials have been realized in order to prove that hyperthermia in addition to radiotherapy offers an advantage in the survival and local control of patients in comparison to radiotherapy alone. Many studies have also investigated if exists any correlation between the thermal parameters of hyperthermia and the clinical outcome. This is a review of these studies and it concerns superficial hyperthermia for superficial tumors-melanoma, head and neck, breast cancer-and intracavitary hyperthermia for rectal cancer, esophageal cancer and prostate carcinoma.

  16. Investigation of long-term survival outcomes and failure patterns of patients with nasopharyngeal carcinoma receiving intensity-modulated radiotherapy: a retrospective analysis

    PubMed Central

    Zhao, Wei; Lei, Hao; Zhu, Xiaodong; Li, Ling; Qu, Song; Liang, Xia

    2016-01-01

    Intensity-modulated radiotherapy (IMRT) has replaced the conventional radiotherapy (2D-RT) and improved clinical efficacy in Nasopharyngeal Carcinoma (NPC) patients. In the present study, we retrospectively analyzed the clinical characteristics of patients with NPC treated with IMRT to assess the long-term survival outcomes and failure patterns. Of the 527 patients, One hundred and twenty-one patients experienced treatment failure, 86 patients developed distant metastases, and 12 patients developed a second primary tumor. The local and regional recurrence rates were 31.4% and 14.0%, respectively. The 5-year overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), regional relapse-free survival (RRFS), and distant metastatic relapse-free survival (DMFS) rates were 80.9%, 75.6%, 91.7%, 96.2%, and 83.0%, respectively. The 5-year LRFS rates of Stage T1-4 patients were 100.0%, 93.1%, 92.0%, and 85.8%, respectively. The 5-year DMFS rates of Stage N0-3 patients were 95.0%, 86.1%, 79.5%, and 67.2%, respectively. Multivariate analysis showed age and T-stage were independent predictors of OS, T-stage was an independent predictor of LRFS, and age and N-stage were independent predictors of PFS and DMFS. In summary, the improved treatment results with IMRT are primarily due to the achievement of a higher local tumor control rate and OS in NPC patients. However, distant metastasis was the most commonly observed failure pattern after treatment. These results provide deep insights about the value of IMRT in the treatment and prognosis of NPC patients. PMID:27894100

  17. Image guided dose escalated prostate radiotherapy: still room to improve

    PubMed Central

    Martin, Jarad M; Bayley, Andrew; Bristow, Robert; Chung, Peter; Gospodarowicz, Mary; Menard, Cynthia; Milosevic, Michael; Rosewall, Tara; Warde, Padraig R; Catton, Charles N

    2009-01-01

    Background Prostate radiotherapy (RT) dose escalation has been reported to result in improved biochemical control at the cost of greater late toxicity. We report on the application of 79.8 Gy in 42 fractions of prostate image guided RT (IGRT). The primary objective was to assess 5-year biochemical control and potential prognostic factors by the Phoenix definition. Secondary endpoints included acute and late toxicity by the Radiotherapy Oncology Group (RTOG) scoring scales. Methods From October/2001 and June/2003, 259 men were treated with at least 2-years follow-up. 59 patients had low, 163 intermediate and 37 high risk disease. 43 had adjuvant hormonal therapy (HT), mostly for high- or multiple risk factor intermediate-risk disease (n = 25). They received either 3-dimensional conformal RT (3DCRT, n = 226) or intensity modulated RT (IMRT) including daily on-line IGRT with intraprostatic fiducial markers. Results Median follow-up was 67.8 months (range 24.4-84.7). There was no severe (grade 3-4) acute toxicity, and grade 2 acute gastrointestinal (GI) toxicity was unusual (10.1%). The 5-year incidence of grade 2-3 late GI and genitourinary (GU) toxicity was 13.7% and 12.1%, with corresponding grade 3 figures of 3.5% and 2.0% respectively. HT had an association with an increased risk of grade 2-3 late GI toxicity (11% v 21%, p = 0.018). Using the Phoenix definition for biochemical failure, the 5 year-bNED is 88.4%, 76.5% and 77.9% for low, intermediate and high risk patients respectively. On univariate analysis, T-category and Gleason grade correlated with Phoenix bNED (p = 0.006 and 0.039 respectively). Hormonal therapy was not a significant prognostic factor on uni- or multi-variate analysis. Men with positive prostate biopsies following RT had a lower chance of bNED at 5 years (34.4% v 64.3%; p = 0.147). Conclusion IGRT to 79.8 Gy results in favourable rates of late toxicity compared with published non-IGRT treated cohorts. Future avenues of investigation for

  18. Normal tissue protection for improving radiotherapy: Where are the Gaps?

    PubMed Central

    Prasanna, Pataje G.S.; Stone, Helen B.; Wong, Rosemary S.; Capala, Jacek; Bernhard, Eric J.; Vikram, Bhadrasain; Coleman, C. N.

    2012-01-01

    Any tumor could be controlled by radiation therapy if sufficient dose were delivered to all tumor cells. Although technological advances in physical treatment delivery have been developed to allow more radiation dose conformity, normal tissues are invariably included in any radiation field within the tumor volume and also as part of the exit and entrance doses relevant for particle therapy. Mechanisms of normal tissue injury and related biomarkers are now being investigated, facilitating the discovery and development of a next generation of radiation protectors and mitigators. Bringing recent research advances stimulated by development of radiation countermeasures for mass casualties, to clinical cancer care requires understanding the impact of protectors and mitigators on tumor response. These may include treatments that modify cellular damage and death processes, inflammation, alteration of normal flora, wound healing, tissue regeneration and others, specifically to counter cancer site-specific adverse effects to improve outcome of radiation therapy. Such advances in knowledge of tissue and organ biology, mechanisms of injury, development of predictive biomarkers and mechanisms of radioprotection have re-energized the field of normal tissue protection and mitigation. Since various factors, including organ sensitivity to radiation, cellular turnover rate, and differences in mechanisms of injury manifestation and damage response vary among tissues, successful development of radioprotectors/mitigators/treatments may require multiple approaches to address cancer site specific needs. In this review, we discuss examples of important adverse effects of radiotherapy (acute and intermediate to late occurring, when it is delivered either alone or in conjunction with chemotherapy, and important limitations in the current approaches of using radioprotectors and/or mitigators for improving radiation therapy. Also, we are providing general concepts for drug development for

  19. Incidental receipt of cardiac medications and survival outcomes among patients with stage III non-small-cell lung cancer after definitive radiotherapy.

    PubMed

    Wang, Hongmei; Liao, Zhongxing; Zhuang, Yan; Liu, Ying; Levy, Lawrence B; Xu, Ting; Yusuf, Syed Wamique; Gomez, Daniel R

    2015-03-01

    Preclinical and epidemiologic studies suggest that receipt of some cardiac medications such as angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, or aspirin may have antiproliferative effects in several types of cancer. The aim of this study was to estimate survival outcomes in patients receiving incidental cardiac medications during treatment for lung cancer, and to compare outcomes with those patients not receiving these medications. We retrospectively reviewed 673 patients who had received definitive radiotherapy for stage III non-small-cell lung cancer (NSCLC). Cox proportional hazard models were used to assess associations between receipt of ACEIs, ARBs, β-blockers, or aspirin and locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). Multivariate analyses showed that ACEI receipt was associated with poorer LRPFS but had no effect on DMFS, DFS, or OS. Aspirin receipt was associated only with improved DMFS, and β-blocker receipt was associated with improved DMFS, DFS, and OS. Incidental receipt of ACEIs was associated with a higher prevalence of local failure, whereas receipt of either β-blockers or aspirin had protective effects on survival outcomes in this large group of patients with lung cancer. This finding warrants further clinical and preclinical exploration, as it may have important implications for treating patients with lung cancer who are also receiving cardiac medications. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Prognostic factors affecting survival after whole brain radiotherapy in patients with brain metastasized lung cancer.

    PubMed

    Tsakonas, Georgios; Hellman, Fatou; Gubanski, Michael; Friesland, Signe; Tendler, Salomon; Lewensohn, Rolf; Ekman, Simon; de Petris, Luigi

    2017-10-06

    Whole-brain radiotherapy (WBRT) has been the standard of care for multiple NSCLC brain metastases but due to its toxicity and lack of survival benefit, its use in the palliative setting is being questioned. This was a single institution cohort study including brain metastasized lung cancer patients who received WBRT at Karolinska University Hospital. Information about Recursive Partitioning Analysis (RPA) and Graded Prognostic Assessment (GPA) scores, demographics, histopathological results and received oncological therapy were collected. Predictors of overall survival (OS) from the time of received WBRT were identified by Cox regression analyses. OS between GPA and RPA classes were compared by pairwise log rank test. A subgroup OS analysis was performed stratified by RPA class. The cohort consisted of 280 patients. RPA 1 and 2 classes had better OS compared to class 3, patients with GPA <1.5 points had better OS compared to GPA≥ 1.5 points and age >70 years was associated with worse OS (p< .0001 for all comparisons). In RPA class 2 subgroup analysis GPA ≥1.5 points, age ≤70 years and CNS surgery before salvage WBRT were independent positive prognostic factors. RPA class 3 patients should not receive WBRT, whereas RPA class 1 patients should receive WBRT if clinically indicated. RPA class 2 patients with age ≤70 years and GPA ≥1.5 points should be treated as RPA 1. WBRT should be omitted in RPA 2 patients with age >70. In RPA 2 patients with age ≤70 years and GPA <1.5 points WBRT could be a reasonable option.

  1. Improved survival time trends in Hodgkin's lymphoma.

    PubMed

    Koshy, Matthew; Fairchild, Andrew; Son, Christina H; Mahmood, Usama

    2016-06-01

    There have been dramatic changes in the staging and treatment of Hodgkin's lymphoma (HL) over the past 30 years. We undertook this study to determine if a stage migration had occurred and also examined if treatment associated with later years has improved survival. Patients with stage I-IV HL between 1983 and 2011 were selected from the Surveillance, Epidemiology, and End Results database. Multivariable analysis (MVA) was performed using Cox proportional hazards modeling. The study cohort included 35,680 patients. The stage breakdown in 1983 according to A and B symptoms was follows: 18%, 21%, 12%, and 5% for stage IA, IIA, IIIA, and IVA disease, respectively, and 6%, 11%, 12%, and 15% for stage IB, IIB, IIIB, and IVB disease. The stage breakdown in 2011 according to A and B symptoms was follows: 9%, 29%, 10%, and 6% for stage IA, IIA, IIIA, and IVA disease, respectively, and 4%, 16%, 12%, and 13% for stage IB, IIB, IIIB, and IVB disease. The median follow-up for the entire cohort is 6.1 years. On MVA, the HR for mortality of patients diagnosed in 2006 was 0.60 (95% Confidence Interval (CI): 0.52-0.70) compared to 1983. For stage I and II patients diagnosed in 2006 the HR was 0.62 (95% CI: 0.44-0.87) and 0.40 (95% CI: 0.30-0.55), respectively, compared to patients diagnosed in 1983. For stage III and IV patients diagnosed in 2006 the HR was 0.72 (95% CI: 0.53-0.98) and 0.74 (95% CI: 0.56-0.99), respectively, compared to patients diagnosed in 1983. This is the first study to demonstrate a significant stage migration in early stage Hodgkin's lymphoma. Furthermore, these results demonstrate an improvement in survival over time for patients with Hodgkin's lymphoma which was particularly notable for those with early stage disease.

  2. Adjuvant Radiation Improves Survival in Older Women Following Breast-Conserving Surgery for Estrogen Receptor-Negative Breast Cancer.

    PubMed

    Daugherty, Emily C; Daugherty, Michael R; Bogart, Jeffrey A; Shapiro, Anna

    2016-12-01

    Published prospective trials have questioned the role of post-lumpectomy radiotherapy in older women with early-stage, estrogen receptor-positive (ER(+)) breast cancer. As the population with ER(-) tumors may be at greater risk for relapse, particularly given that endocrine therapy is not effective, we hypothesize the addition of radiation would be of benefit in patients age ≥ 70. The Surveillance, Epidemiology, and End Results database was queried from 1998 to 2011 for patients age ≥ 70 years receiving breast-conserving surgery for T1, ER(-) invasive ductal carcinoma. Patients were separated into 2 cohorts: those treated with and without adjuvant radiotherapy. Chi-square analysis, unpaired t test and Kaplan-Meier log-rank were used to compare patient and tumor characteristics as well as overall and cancer-specific survival between the cohorts. Overall, 3685 patients received radiation and 1493 patients received lumpectomy alone. Patients treated with adjuvant radiation were younger (median age 76 vs. 78 years, P < .0001). Patients who received radiation had improved overall survival, with 5-year survival rates of 81.0% versus 61.7% without radiation (P < .0001). Cancer-specific survival was also improved with radiotherapy, with 5-year cancer-specific survival rates of 93.1% versus 85.0% (P < .0001). This analysis of the SEER database demonstrates that women ages 70 and older treated with lumpectomy and radiotherapy for ER(-), early-stage breast cancer have improved overall survival and breast cancer-specific survival compared with patients treated with lumpectomy alone. This information may help in the decision-making process for this patient population. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Comparative survival in patients with postresection recurrent versus newly diagnosed non-small-cell lung cancer treated with radiotherapy.

    PubMed

    Cai, Xu-Wei; Xu, Lu-Ying; Wang, Li; Hayman, James A; Chang, Andrew C; Pickens, Allan; Cease, Kemp B; Orringer, Mark B; Kong, Feng-Ming

    2010-03-15

    To compare the survival of postresection recurrent vs. newly diagnosed non-small-cell lung cancer (NSCLC) patients treated with radiotherapy or chemoradiotherapy. The study population consisted of 661 consecutive patients with NSCLC registered in the radiation oncology databases at two medical centers in the United States between 1992 and 2004. Of the 661 patients, 54 had postresection recurrent NSCLC and 607 had newly diagnosed NSCLC. Kaplan-Meier and Cox regression models were used for the survival analyses. The distribution of relevant clinical factors between these two groups was similar. The median survival time and 5-year overall survival rates were 19.8 months (95% confidence interval [CI], 13.9-25.7) and 14.8% (95% confidence interval, 5.4-24.2%) vs. 12.2 months (95% CI, 10.8-13.6) and 11.0% (95% CI, 8.5-13.5%) for recurrent vs. newly diagnosed patients, respectively (p = .037). For Stage I-III patients, no significant difference was observed in the 5-year overall survival (p = .297) or progression-free survival (p = .935) between recurrent and newly diagnosed patients. For the 46 patients with Stage I-III recurrent disease, multivariate analysis showed that chemotherapy was a significant prognostic factor for 5-year progression-free survival (hazard ratio, 0.45; 95% CI, 0.224-0.914; p = .027). Our institutional data have shown that patients with postresection recurrent NSCLC achieved survival comparable to that of newly diagnosed NSCLC patients when they were both treated with radiotherapy or chemoradiotherapy. These findings suggest that patients with postresection recurrent NSCLC should be treated as aggressively as those with newly diagnosed disease. Copyright 2010 Elsevier Inc. All rights reserved.

  4. Comparative Survival in Patients With Postresection Recurrent Versus Newly Diagnosed Non-Small-Cell Lung Cancer Treated With Radiotherapy

    SciTech Connect

    Cai Xuwei; Xu Luying; Wang Li; Hayman, James A.; Chang, Andrew C.; Pickens, Allan; Cease, Kemp B.; Orringer, Mark B.; Kong, F.-M.

    2010-03-15

    Purpose: To compare the survival of postresection recurrent vs. newly diagnosed non-small-cell lung cancer (NSCLC) patients treated with radiotherapy or chemoradiotherapy. Methods and Materials: The study population consisted of 661 consecutive patients with NSCLC registered in the radiation oncology databases at two medical centers in the United States between 1992 and 2004. Of the 661 patients, 54 had postresection recurrent NSCLC and 607 had newly diagnosed NSCLC. Kaplan-Meier and Cox regression models were used for the survival analyses. Results: The distribution of relevant clinical factors between these two groups was similar. The median survival time and 5-year overall survival rates were 19.8 months (95% confidence interval [CI], 13.9-25.7) and 14.8% (95% confidence interval, 5.4-24.2%) vs. 12.2 months (95% CI, 10.8-13.6) and 11.0% (95% CI, 8.5-13.5%) for recurrent vs. newly diagnosed patients, respectively (p = .037). For Stage I-III patients, no significant difference was observed in the 5-year overall survival (p = .297) or progression-free survival (p = .935) between recurrent and newly diagnosed patients. For the 46 patients with Stage I-III recurrent disease, multivariate analysis showed that chemotherapy was a significant prognostic factor for 5-year progression-free survival (hazard ratio, 0.45; 95% CI, 0.224-0.914; p = .027). Conclusion: Our institutional data have shown that patients with postresection recurrent NSCLC achieved survival comparable to that of newly diagnosed NSCLC patients when they were both treated with radiotherapy or chemoradiotherapy. These findings suggest that patients with postresection recurrent NSCLC should be treated as aggressively as those with newly diagnosed disease.

  5. Opposite association of serum prolactin and survival in patients with colon and rectal carcinomas: influence of preoperative radiotherapy.

    PubMed

    Barrera, Marcos Gutiéerrez De La; Trejo, Belem; Luna-Péerez, Pedro; López-Barrera, Fernándo; Escalera, Gonzalo Martínez De La; Clapp, Carmen

    2006-01-01

    Prolactin (PRL) is a pleiotropic hormone associated with the progression of various cancers, including colorectal cancer (CRC). Here we investigate whether the association of serum PRL concentration and survival is affected by tumor location and preoperative radiotherapy (PRERT) in patients with CRC cancer. Serum PRL was determined in 82 CRC patients without previous treatment. Patients with PRL concentrations at and above the 75th percentile (high PRL) or below this level (low PRL), had a significant correlation with overall survival determined using the Kaplan-Meier method. In colon cancer, there was an increased risk of mortality when PRL values were at and above the highest quartile (22% vs. 73%; P = 0.01). In contrast, in rectal cancer, high PRL values were associated with a significant overall survival advantage (88% vs. 44%; P = 0.05), which became more significant (100% vs. 34%; P = 0.005) when only rectal cancer patients receiving PRERT were compared. These findings suggest that tumor location and adjuvant radiotherapy influence the association between circulating PRL and survival in CRC.

  6. Survival Continues to Improve for Most Cancers

    MedlinePlus

    ... and breast cancers. However, death rates rose for cancers of the liver, pancreas and brain in men and for the liver ... myeloma and leukemia. The lowest survival rates for cancers diagnosed between 2006 and 2012 were: pancreas (8.5 percent survival five years after diagnosis); ...

  7. Methods and computer readable medium for improved radiotherapy dosimetry planning

    DOEpatents

    Wessol, Daniel E.; Frandsen, Michael W.; Wheeler, Floyd J.; Nigg, David W.

    2005-11-15

    Methods and computer readable media are disclosed for ultimately developing a dosimetry plan for a treatment volume irradiated during radiation therapy with a radiation source concentrated internally within a patient or incident from an external beam. The dosimetry plan is available in near "real-time" because of the novel geometric model construction of the treatment volume which in turn allows for rapid calculations to be performed for simulated movements of particles along particle tracks therethrough. The particles are exemplary representations of alpha, beta or gamma emissions emanating from an internal radiation source during various radiotherapies, such as brachytherapy or targeted radionuclide therapy, or they are exemplary representations of high-energy photons, electrons, protons or other ionizing particles incident on the treatment volume from an external source. In a preferred embodiment, a medical image of a treatment volume irradiated during radiotherapy having a plurality of pixels of information is obtained.

  8. Improving external beam radiotherapy by combination with internal irradiation.

    PubMed

    Dietrich, A; Koi, L; Zöphel, K; Sihver, W; Kotzerke, J; Baumann, M; Krause, M

    2015-07-01

    The efficacy of external beam radiotherapy (EBRT) is dose dependent, but the dose that can be applied to solid tumour lesions is limited by the sensitivity of the surrounding tissue. The combination of EBRT with systemically applied radioimmunotherapy (RIT) is a promising approach to increase efficacy of radiotherapy. Toxicities of both treatment modalities of this combination of internal and external radiotherapy (CIERT) are not additive, as different organs at risk are in target. However, advantages of both single treatments are combined, for example, precise high dose delivery to the bulk tumour via standard EBRT, which can be increased by addition of RIT, and potential targeting of micrometastases by RIT. Eventually, theragnostic radionuclide pairs can be used to predict uptake of the radiotherapeutic drug prior to and during therapy and find individual patients who may benefit from this treatment. This review aims to highlight the outcome of pre-clinical studies on CIERT and resultant questions for translation into the clinic. Few clinical data are available until now and reasons as well as challenges for clinical implementation are discussed.

  9. Improving external beam radiotherapy by combination with internal irradiation

    PubMed Central

    Koi, L; Zöphel, K; Sihver, W; Kotzerke, J; Baumann, M; Krause, M

    2015-01-01

    The efficacy of external beam radiotherapy (EBRT) is dose dependent, but the dose that can be applied to solid tumour lesions is limited by the sensitivity of the surrounding tissue. The combination of EBRT with systemically applied radioimmunotherapy (RIT) is a promising approach to increase efficacy of radiotherapy. Toxicities of both treatment modalities of this combination of internal and external radiotherapy (CIERT) are not additive, as different organs at risk are in target. However, advantages of both single treatments are combined, for example, precise high dose delivery to the bulk tumour via standard EBRT, which can be increased by addition of RIT, and potential targeting of micrometastases by RIT. Eventually, theragnostic radionuclide pairs can be used to predict uptake of the radiotherapeutic drug prior to and during therapy and find individual patients who may benefit from this treatment. This review aims to highlight the outcome of pre-clinical studies on CIERT and resultant questions for translation into the clinic. Few clinical data are available until now and reasons as well as challenges for clinical implementation are discussed. PMID:25782328

  10. Altered and Conventional Fractionated Radiotherapy in Locoregional Control and Survival of Patients with Squamous Cell Carcinoma of the Larynx, Oropharynx, and Hypopharynx

    PubMed Central

    Krstevska, Valentina; Crvenkova, Simonida

    2006-01-01

    Aim To compare the efficacy of two altered fractionation radiotherapy treatment protocols (hyperfractionation and accelerated fractionation with concomitant boost) with conventional fractionation in improvement of locoregional disease control and survival of patients with squamous cell carcinoma of the larynx, oropharynx, or hypopharynx. Methods From March 1999 to December 2000, 51 patients with previously untreated squamous cell carcinoma of the larynx, oropharynx or hypopharynx underwent conventionally fractionated radiotherapy and received 66-70 Gy in 6˝-7 weeks (2 Gy per fraction a day, 5 fractions a week). From January 2001 to June 2004, 101 patients with the same diagnoses underwent either hyperfractionated radiotherapy, with 74.4-79.2 Gy delivered in 6.2-7 weeks (1.2 Gy per fraction twice a day), or accelerated fractionation with concomitant boost, which delivered 68.7-72 Gy in 6 weeks (1.8 Gy per fraction a day and 1.5 Gy per fraction a day to a boost filed as a second daily treatment for the last 11-12 treatment days). Locoregional relapse and overall survival were recorded. Results Complete response to treatment was obtained in 31 of 51 patients treated with conventional fractionation, 33 of 50 patients treated with hyperfractionation, and 36 of 51 patients treated with accelerated fractionation. No significant differences were observed among the patients treated with conventional, hyperfractionated, or accelerated radiotherapy modalities either in locoregional control rate (41% vs 35% vs 49%, respectively; P = 0.690) or overall survival rate (50% vs 40% vs 51%, respectively; P = 0.760). The grade of acute reactions of the larynx significantly differed among the treatment groups (Fisher exact test; P = 0.039). The difference in the grade of acute side effects in the skin among the treatment groups was of borderline significance (χ22 test; P = 0.054). There was also a borderline difference among the groups in the grade of late side

  11. Abiraterone Improves Survival in Metastatic Prostate Cancer

    Cancer.gov

    A multinational phase III trial found that the drug abiraterone acetate prolonged the median survival of patients with metastatic castration-resistant prostate cancer by 4 months compared with patients who received a placebo.

  12. National trends in the recommendation of radiotherapy after prostatectomy for prostate cancer before and after the reporting of a survival benefit in March 2009.

    PubMed

    Mahal, Brandon A; Hoffman, Karen E; Efstathiou, Jason A; Nguyen, Paul L

    2015-06-01

    Three randomized trials demonstrated that postprostatectomy adjuvant radiotherapy improves biochemical disease-free survival for patients with adverse pathologic features, and 1 trial found adjuvant radiotherapy improves overall survival. We sought to determine whether postprostatectomy radiotherapy (PPRT) utilization changed after publication of the survival benefit in March 2009. The Surveillance, Epidemiology, and End Results database was used to identify men diagnosed with prostate cancer from 2004 to 2011 who met criteria for enrollment in the randomized trials (positive margins and/or pT3-4 disease at radical prostatectomy). Joinpoint regression identified inflection points in PPRT utilization. Logistic regression was used to evaluate factors associated with PPRT recommendation. Of 35,361 men, 5104 (14.4%) received a recommendation for PPRT. In joinpoint regression, 2009 was the inflection point in PPRT utilization. In multivariable analysis, PPRT recommendations were more likely after March 2009 than before 15.8% vs. 13.5%, adjusted odds ratio (AOR; 1.09; 95% confidence interval [CI], 1.02-1.16; P = .008), in men with pT3 (vs. pT2, AOR, 2.81; 95% CI, 2.53-3.11; P < .001), pT4 (vs. pT2 AOR, 4.62; 95% CI, 3.85-5.54; P < .001), or margin positive (AOR, 1.46; 95% CI, 1.34-1.58; P < .001) disease and in men who were younger (per year decrease, AOR, 1.02; 95% CI, 1.02-1.03; P < .001), married (AOR, 1.10; 95% CI, 1.02-1.19; P = .01), or lived in metropolitan areas (AOR, 1.30; 95% CI, 1.16-1.47; P < .001). PPRT recommendations increased after the reporting of a survival benefit in March 2009, but absolute utilization rates remain low, suggesting that the oncologic community remains unconvinced that PPRT is needed for most patients with adverse features. Further work is needed to identify patients who might benefit most from PPRT. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Chemotherapy in head and neck osteosarcoma: Adjuvant chemotherapy improves overall survival.

    PubMed

    Chen, YiMing; Gokavarapu, Sandhya; Shen, QingCheng; Liu, Feng; Cao, Wei; Ling, YueHua; Ji, Tong

    2017-10-01

    Osteosarcoma is an aggressive bone malignancy presenting uncommonly in head and neck sites. Surgery is mainstay in treatment. However; trials show an improved survival with addition of chemotherapy in the treatment of extremity osteosarcoma. The head and neck osteosarcomas(HNOs) were excluded in these trials because of atypical presentation and disease course. Further; sufficient numbers were not possible for a trial. We present the largest retrospective study from single institute investigating the role of chemotherapy in the management of HNOs. The retrospective cohort of HNOs treated from 2007 to 2015 of a tertiary hospital were charted. The therapeutic and prognostic factors were analyzed for overall survival(OS), disease free survival(DFS), local control(LC) and metastasis(MT) in univariate and multivariate analysis. The minimum and median period of follow up was 12months and 56.04months respectively. There was a total of 157 patients definitively treated with surgery in the time period. 7 patients had positive margins and all were maxillary or skull base tumors. The multivariate cox regression showed significance of tumor site(p=0.034), margin status (p=0.006), chemotherapy(p=0.025), histological subtype(p=0.012) as predictors of overall survival. The margin status(p=0.002), Radiotherapy(p=0.005) were significant predictors for local recurrence. The age and histology subtype(p=0.058) were borderline significant predictors of metastasis(p=0.065). The KM method for OS of different chemotherapy groups(p=0.013), and survival with and without chemotherapy(p=0.007) was significant. The OS was significantly better with adjuvant chemotherapy among various treatment plans(p=0.034). Adjuvant chemotherapy improved OS while adjuvant radiotherapy improved local control of HNOs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Video-assisted thoracoscopic lobectomy is associated with greater recurrence-free survival than stereotactic body radiotherapy for clinical stage I lung cancer.

    PubMed

    Cornwell, Lorraine D; Echeverria, Alfredo E; Samuelian, Jason; Mayor, Jessica; Casal, Roberto F; Bakaeen, Faisal G; Omer, Shuab; Preventza, Ourania; Mai, Weiyuan; Chen, George; Simpson, Katherine H; Moghanaki, Drew; Zhu, Angela W

    2017-08-16

    Stereotactic body radiotherapy is the standard treatment for medically inoperable early-stage non-small cell lung cancer. Recent data suggest that in operable patients, stereotactic body radiotherapy produces outcomes comparable to those of surgical resection. In veterans with early non-small cell lung cancer, we compared the outcomes of stereotactic body radiotherapy and video-assisted thoracoscopic lobectomy. We retrospectively reviewed data from 183 patients (94.0% male) with clinical stage I non-small cell lung cancer who underwent stereotactic body radiotherapy (n = 56) or video-assisted thoracoscopic lobectomy (n = 127) from 2009 to 2014. Propensity matching was used to produce more comparable groups. Primary end points were tumor control and overall, recurrence-free, and lung-cancer-specific survival, as estimated by Kaplan-Meier actuarial analysis. Multivariable analysis was used to identify independent predictors. In the overall cohort, the patients who received stereotactic body radiotherapy were older than the patients who received video-assisted thoracoscopic lobectomy (median age, 79.5 vs 64 years) and had more comorbidities. In the 37 propensity-matched pairs, the 3-year actuarial tumor control rate was 54.3% after stereotactic body radiotherapy and 90.6% after video-assisted thoracoscopic lobectomy (P = .0038). Actuarial lung cancer-specific 3-year survival was 78.1% (stereotactic body radiotherapy) versus 93.6% (video-assisted thoracoscopic lobectomy) (P = .055). One-year overall, 3-year overall, and 3-year recurrence-free survivals were 89.2%, 52.9%, and 38.5% after stereotactic body radiotherapy and 94.6%, 85.7%, and 82.8% after video-assisted thoracoscopic lobectomy (P < .005 for all), respectively. In multivariable analysis, stereotactic body radiotherapy independently predicted recurrence and poorer survival. In veteran patients with early-stage non-small cell lung cancer, video-assisted thoracoscopic lobectomy resulted in better

  15. Radiation Oncology In Vitro: Trends to Improve Radiotherapy through Molecular Targets

    PubMed Central

    Feofanova, Natália; Geraldo, Jony Marques; de Andrade, Lídia Maria

    2014-01-01

    Much has been investigated to improve the beneficial effects of radiotherapy especially in that case where radioresistant behavior is observed. Beyond simple identification of resistant phenotype the discovery and development of specific molecular targets have demonstrated therapeutic potential in cancer treatment including radiotherapy. Alterations on transduction signaling pathway related with MAPK cascade are the main axis in cancer cellular proliferation even as cell migration and invasiveness in irradiated tumor cell lines; then, for that reason, more studies are in course focusing on, among others, DNA damage enhancement, apoptosis stimulation, and growth factors receptor blockages, showing promising in vitro results highlighting molecular targets associated with ionizing radiation as a new radiotherapy strategy to improve clinical outcome. In this review we discuss some of the main molecular targets related with tumor cell proliferation and migration as well as their potential contributions to radiation oncology improvements. PMID:25302298

  16. Radiation oncology in vitro: trends to improve radiotherapy through molecular targets.

    PubMed

    Feofanova, Natália; Geraldo, Jony Marques; de Andrade, Lídia Maria

    2014-01-01

    Much has been investigated to improve the beneficial effects of radiotherapy especially in that case where radioresistant behavior is observed. Beyond simple identification of resistant phenotype the discovery and development of specific molecular targets have demonstrated therapeutic potential in cancer treatment including radiotherapy. Alterations on transduction signaling pathway related with MAPK cascade are the main axis in cancer cellular proliferation even as cell migration and invasiveness in irradiated tumor cell lines; then, for that reason, more studies are in course focusing on, among others, DNA damage enhancement, apoptosis stimulation, and growth factors receptor blockages, showing promising in vitro results highlighting molecular targets associated with ionizing radiation as a new radiotherapy strategy to improve clinical outcome. In this review we discuss some of the main molecular targets related with tumor cell proliferation and migration as well as their potential contributions to radiation oncology improvements.

  17. Improvement in High-Grade Osteosarcoma Survival

    PubMed Central

    Hung, Giun-Yi; Yen, Hsiu-Ju; Yen, Chueh-Chuan; Wu, Po-Kuei; Chen, Cheng-Fong; Chen, Paul C-H; Wu, Hung-Ta H.; Chiou, Hong-Jen; Chen, Wei-Ming

    2016-01-01

    Abstract The aim of this study was to compare survival before and after 2004 and define the prognostic factors for high-grade osteosarcomas beyond those of typical young patients with localized extremity disease. Few studies have reported the long-term treatment outcomes of high-grade osteosarcoma in Taiwan. A total of 202 patients with primary high-grade osteosarcoma who received primary chemotherapy at Taipei Veterans General Hospital between January 1995 and December 2011 were retrospectively evaluated and compared by period (1995–2003 vs 2004–2011). Patients of all ages and tumor sites and those following or not following controlled protocols were included in analysis of demographic, tumor-related, and treatment-related variables and survival. Overall survival and progression-free survival at 5 years were, respectively, 67.7% and 48% for all patients (n = 202), 77.3% and 57.1% for patients without metastasis (n = 157), and 33.9% and 14.8% for patients with metastasis (n = 45). The survival rates of patients treated after 2004 were significantly higher (by 13%–16%) compared with those of patients treated before 2004, with an accompanying 30% increase in histological good response rate (P = .002). Factors significantly contributing to inferior survival in univariate and multivariate analyses were diagnosis before 2004, metastasis at diagnosis, and being a noncandidate for a controlled treatment protocol. By comparison with the regimens used at our institution before 2004, the current results support the effectiveness of the post-2004 regimens, which consisted of substantially reduced cycles of high-dose methotrexate and a higher dosage of ifosfamide per cycle, cisplatin, and doxorubicin, for treating high-grade osteosarcoma in Asian patients. PMID:27082623

  18. How to Improve Therapeutic Ratio in Radiotherapy of HCC

    PubMed Central

    Tsai, Chiao-Ling; Hsu, Feng-Ming; Cheng, Jason Chia-Hsien

    2016-01-01

    Background During the past two decades, external-beam radiation technology has substantially changed from traditional two-dimensional to conformal three-dimensional to intensity-modulated planning and stereotactic body radiotherapy (SBRT). Summary Modern techniques of radiotherapy (RT) are highly focused and capable of delivering an ablative dose to targeted hepatocellular carcinoma (HCC) tumors. SBRT is an option for selected patients with limited tumor volume and non-eligibility for other invasive treatments. Moreover, RT combined with a radiation sensitizer (RS) to increase the therapeutic ratio has shown promising results in select studies, prompting further investigation of this combination. With the undetermined role of RT in treatment guidelines and variation in patterns of treatment failure after RT in patient with HCC, useful biomarkers to guide RT decision-making and selection of patients are needed and emerging. Key Message The objective of this review is to summarize the current RS with SBRT schemes and biomarkers for patient selection used to maximize the effect of RT on HCC. PMID:27493896

  19. Discovery and Validation of Predictive Biomarkers of Survival for Non-small Cell Lung Cancer Patients Undergoing Radical Radiotherapy: Two Proteins With Predictive Value.

    PubMed

    Walker, Michael J; Zhou, Cong; Backen, Alison; Pernemalm, Maria; Williamson, Andrew J K; Priest, Lynsey J C; Koh, Pek; Faivre-Finn, Corinne; Blackhall, Fiona H; Dive, Caroline; Whetton, Anthony D

    2015-08-01

    Lung cancer is the most frequent cause of cancer-related death world-wide. Radiotherapy alone or in conjunction with chemotherapy is the standard treatment for locally advanced non-small cell lung cancer (NSCLC). Currently there is no predictive marker with clinical utility to guide treatment decisions in NSCLC patients undergoing radiotherapy. Identification of such markers would allow treatment options to be considered for more effective therapy. To enable the identification of appropriate protein biomarkers, plasma samples were collected from patients with non-small cell lung cancer before and during radiotherapy for longitudinal comparison following a protocol that carries sufficient power for effective discovery proteomics. Plasma samples from patients pre- and during radiotherapy who had survived > 18 mo were compared to the same time points from patients who survived < 14 mo using an 8 channel isobaric tagging tandem mass spectrometry discovery proteomics platform. Over 650 proteins were detected and relatively quantified. Proteins which showed a change during radiotherapy were selected for validation using an orthogonal antibody-based approach. Two of these proteins were verified in a separate patient cohort: values of CRP and LRG1 combined gave a highly significant indication of extended survival post one week of radiotherapy treatment.

  20. Did the addition of concomitant chemotherapy to radiotherapy improve outcomes in hypopharyngeal cancer? A population-based study

    PubMed Central

    Hall, S.F.; Griffiths, R.

    2016-01-01

    Background For oncologists and for patients, no site-specific clinical trial evidence has emerged for the use of concurrent chemotherapy with radiotherapy (ccrt) over radiotherapy (rt) alone for cancer of the hypopharynx (hpc) or for other human papilloma virus–negative head-and-neck cancers. Methods This retrospective population-based cohort study using administrative data compared treatments over time (1990–2000 vs. 2000–2010), treatment outcomes, and outcomes over time in 1333 cases of hpc diagnosed in Ontario between January 1990 and December 2010. Results The incidence of hpc is declining; the use of ccrt that began in 2001 is increasing; and the 3-year overall survival for all patients remains poor at 34.6%. No difference in overall survival was observed in a comparison of patients treated in the decade before ccrt and of patients treated in the decade during the uptake of ccrt. Conclusions The addition of ccrt to the armamentarium of treatment options for oncologists treating head-and-neck patients did not improve outcomes for hpc at the population level. PMID:27536177

  1. Effectiveness of Radiotherapy for Elderly Patients With Glioblastoma

    SciTech Connect

    Scott, Jacob; Tsai, Ya-Yu; Chinnaiyan, Prakash; Yu, Hsiang-Hsuan Michael

    2011-09-01

    Purpose: Radiotherapy plays a central role in the definitive treatment of glioblastoma. However, the optimal management of elderly patients with glioblastoma remains controversial, as the relative benefit in this patient population is unclear. To better understand the role that radiation plays in the treatment of glioblastoma in the elderly, we analyzed factors influencing patient survival using a large population-based registry. Methods and Materials: A total of 2,836 patients more than 70 years of age diagnosed with glioblastoma between 1993 and 2005 were identified from the Surveillance, Epidemiology, and End Results (SEER) registry. Demographic and clinical variables used in the analysis included gender, ethnicity, tumor size, age at diagnosis, surgery, and radiotherapy. Cancer-specific survival and overall survival were evaluated using the Kaplan-Meier method. Univariate and multivariate analysis were performed using Cox regression. Results: Radiotherapy was administered in 64% of these patients, and surgery was performed in 68%. Among 2,836 patients, 46% received surgery and radiotherapy, 22% underwent surgery only, 18% underwent radiotherapy only, and 14% did not undergo either treatment. The median survival for patients who underwent surgery and radiotherapy was 8 months. The median survival for patients who underwent radiotherapy only was 4 months, and for patients who underwent surgery only was 3 months. Those who received neither surgery nor radiotherapy had a median survival of 2 months (p < 0.001). Multivariate analysis showed that radiotherapy significantly improved cancer-specific survival (hazard ratio [HR], 0.43, 95% confidence interval [CI] 0.38-0.49) after adjusting for surgery, tumor size, gender, ethnicity, and age at diagnosis. Other factors associated with Cancer-specific survival included surgery, tumor size, age at diagnosis, and ethnicity. Analysis using overall survival as the endpoint yielded very similar results. Conclusions: Elderly

  2. Effect of Thoracic Radiotherapy Timing and Fractionation on Survival in Nonmetastatic Small Cell Lung Carcinoma.

    PubMed

    Wong, Andrew T; Rineer, Justin; Schwartz, David; Becker, Daniel; Safdieh, Joseph; Osborn, Virginia; Schreiber, David

    2017-03-01

    The optimal timing of thoracic radiation therapy (RT) in relation to chemotherapy is unknown in the treatment of nonmetastatic small cell lung cancer (SCLC). We analyzed the National Cancer Data Base (NCDB) to assess the effect on overall survival (OS) of RT timing with chemotherapy for patients with SCLC. The NCDB was queried for patients diagnosed with nonmetastatic SCLC from 1998 to 2011 who had undergone definitive chemoradiation. The patients were stratified into quartiles according to the interval between the start of chemotherapy and the start of RT. The first and second quartiles (RT started 0-20 days after chemotherapy) were classified as "early" RT and the third and fourth quartiles (RT started 21-126 days after chemotherapy) as "late" RT. Patients were included if they had received hyperfractionated 45 Gy in 30 fractions or standard fractionation of ≥ 60 Gy in 1.8- to 2-Gy fractions. Kaplan-Meier analyses of OS were performed, and multivariable Cox regression analysis was conducted to assess the effect of the covariates on OS. A total of 8391 patients were included (50.5% had received early RT). Early RT was associated with significant improvement in survival (5-year OS, 21.9% vs. 19.1%; P = .01). On subgroup analysis, the survival advantage for early RT was significant for patients receiving hyperfractionated RT (5-year OS, 28.2% vs. 21.2%; P = .004) but not for those receiving standard fractionation (19.8% vs. 18.4%; P = .29). On multivariable Cox regression analysis, hyperfractionated RT was associated with reduced mortality (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.85-0.96; P = .001), but early RT was not (HR, 0.98; 95% CI, 0.94-1.04; P = .53). These data support the early initiation of hyperfractionated thoracic RT for nonmetastatic SCLC. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Valproic acid reduces hair loss and improves survival in patients receiving temozolomide-based radiation therapy for high-grade glioma.

    PubMed

    Watanabe, Shinichi; Kuwabara, Yui; Suehiro, Satoshi; Yamashita, Daisuke; Tanaka, Mamoru; Tanaka, Akihiro; Ohue, Shiro; Araki, Hiroaki

    2017-03-01

    Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, is also used to manage seizures in glioblastoma patients. HDAC inhibitors can protect normal cells and tissues from the deleterious effects of radiotherapy, and VPA is reported to improve the survival of glioblastoma patients receiving chemoradiation therapy. VPA also promotes hair growth, and thus has the potential to reduce the radiotherapy side effect of hair loss while improving the survival of patients with glioblastoma. The purpose of this study was to determine whether VPA use during radiotherapy for high-grade glioma is associated with decreased side effects of radiotherapy and an improvement in overall survival (OS) and progression-free survival (PFS). Medical records of 112 patients with high-grade glioma were retrospectively reviewed. We grouped patients by VPA use or non-use during radiotherapy, and evaluated hair loss, OS, and PFS. The radiation dose and fractionation at the onset of hair loss were 4 Gy and two fractions higher, respectively, in the VPA group compared with the VPA non-use group (P < 0.01). Median OS was 42.2 and 20.3 months in the VPA use and non-use groups, respectively (P < 0.01; hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.18-0.74). Median PFS was 22.7 and 11.0 months in the VPA use and non-use groups, respectively (P = 0.099; HR, 0.62; 95% CI, 0.36-1.09). VPA use during radiotherapy for glioma is associated with delayed hair loss and improvement in survival. Hair loss prevention benefits patients suffering from the deleterious effects of radiation.

  4. Preoperative radiotherapy for inoperable stage II endometrial cancer: insights into improving treatment and outcomes.

    PubMed

    Lee, Marette H; Aquino-Parsons, Christina; Hoskins, Paul J; Lim, Peter; Kwon, Janice S

    2013-07-01

    To review recurrence patterns and survival outcomes of women receiving preoperative radiotherapy for clinical stage II endometrial cancer in British Columbia. We performed a retrospective population-based cohort study of all patients with clinical stage II endometrial cancer who were referred to the British Columbia Cancer Agency from 2000 to 2008, deemed ineligible for primary surgery, and therefore offered preoperative radiotherapy followed by surgery. Patient demographics, uterine risk factors, timing and details of treatments, and timing and sites of recurrence were obtained from patient records. Primary outcome measures were the sites and rates of recurrence and recurrence-free survival. We identified 29 patients with a mean age of 61 years (range 41 to 83) and median follow-up of 3.1 years (range 0.3 to 5.3). Three-year overall survival was 79%, and median recurrence-free survival was 2.5 years. Eight patients had recurrence of disease (27.6%), with a median time to recurrence of 1.3 years, (range 0.4 to 2.7). Six of these eight women had two or more high-risk uterine factors (deep myometrial invasion, grade 3 tumour), ovarian involvement, or adverse histological type (carcinosarcoma), compared with only one of 21 patients without recurrence. Seven of eight women had recurrence outside the radiated volume of tissue. Median survival after recurrence was 1.0 years (range 0.4 to 2.2). Women with clinical stage II endometrial cancer had a significant risk of recurrence when treated with preoperative radiotherapy followed by surgery. They were more likely to have distant recurrences, implying the need for an alternate treatment paradigm.

  5. XRCC3 is a promising target to improve the radiotherapy effect of esophageal squamous cell carcinoma.

    PubMed

    Cheng, Jingjing; Liu, Weiran; Zeng, Xianliang; Zhang, Bin; Guo, Yihang; Qiu, Minghan; Jiang, Chao; Wang, Huanhuan; Wu, Zhiqiang; Meng, Maobin; Zhuang, Hongqing; Zhao, Lujun; Hao, Jihui; Cai, Qingqing; Xie, Dan; Pang, Qingsong; Wang, Ping; Yuan, Zhiyong; Qian, Dong

    2015-12-01

    Radiotherapy is widely applied for treatment of esophageal squamous cell carcinoma (ESCC). The Rad51-related protein XRCC3 plays roles in the recombinational repair of DNA double-strand breaks to maintain chromosome stability and repair DNA damage. The present study aimed to investigate the effect of XRCC3 on the radiotherapy response of ESCC and the underlying mechanisms of the roles of XRCC3 in ESCC radiosensitivity. XRCC3 expression in ESCC cells and tissues was higher than that in normal esophageal epithelial cells and corresponding adjacent noncancerous esophageal tissue. High XRCC3 expression was positively correlated with resistance to chemoradiotherapy in ESCC and an independent predictor for short disease-specific survival of ESCC patients. Furthermore, the therapeutic efficacy of radiotherapy in vitro and in vivo was substantially increased by knockdown of XRCC3 in ESCC cells. Ectopic overexpression of XRCC3 in both XRCC3-silenced ESCC cells dramatically enhanced ESCC cells' resistance to radiotherapy. Moreover, radiation resistance conferred by XRCC3 was attributed to enhancement of homologous recombination, maintenance of telomere stability, and a reduction of ESCC cell death by radiation-induced apoptosis and mitotic catastrophe. Our data suggest that XRCC3 protects ESCC cells from ionizing radiation-induced death by promoting DNA damage repair and/or enhancing telomere stability. XRCC3 may be a novel radiosensitivity predictor and promising therapeutic target for ESCC.

  6. Survival and level of care among breast cancer patients with brain metastases treated with whole brain radiotherapy.

    PubMed

    Frisk, Gabriella; Tinge, Beatrice; Ekberg, Sara; Eloranta, Sandra; Bäcklund, L Magnus; Lidbrink, Elisabet; Smedby, Karin E

    2017-08-22

    The benefit of whole brain radiotherapy (WBRT) for late stage breast cancer patients with brain metastases has been questioned. In this study we evaluated survival and level of care (hospital or home) following WBRT in a population-based cohort by personal and tumor characteristics. We identified 241 consecutive patients with breast cancer and brain metastases receiving WBRT in Stockholm, Sweden, 1999-2012. Through review of medical records, we collected data on prognostic determinants including level of care before and after WBRT. Survival was estimated using Cox regression, and odds ratios (OR) of not coming home using logistic regression. Median age at WBRT was 58 years (range 30---88 years). Most patients (n = 212, 88%) were treated with 4 Gray × 5. Median survival following WBRT was 2.9 months (interquartile range 1.1-6.6 months), and 57 patients (24%) were never discharged from hospital. Poor performance status and triple-negative tumors were associated with short survival (WHO 3-4 median survival 0.9 months, HR = 5.96 (3.88-9.17) versus WHO 0-1; triple-negative tumors median survival 2.0 months, HR = 1.87 (1.23-2.84) versus Luminal A). Poor performance status and being hospitalized before WBRT were associated with increased ORs of not coming home whereas cohabitation with children at home was protective. Survival was short following WBRT, and one in four breast cancer patients with brain metastases could never be discharged from hospital. When deciding about WBRT, WHO score, level of care before WBRT, and the patient's choice of level of care in the end-of-life period should be considered.

  7. Have Changes in Systemic Treatment Improved Survival in Patients with Breast Cancer Metastatic to the Brain?

    PubMed Central

    Nieder, Carsten; Marienhagen, Kirsten; Dalhaug, Astrid; Norum, Jan

    2008-01-01

    Newly developed systemic treatment regimens might lead to improved survival also in the subgroup of breast cancer patients that harbour brain metastases. In order to examine this hypothesis, a matched pairs analysis was performed that involved one group of patients, which were treated after these new drugs were introduced, and one group of patients, which were treated approximately 10 years earlier. The two groups were well balanced for the known prognostic factors age, KPS, extracranial disease status, and recursive partitioning analysis class, as well as for the extent of brain treatment. The results show that the use of systemic chemotherapy has increased over time, both before and after the diagnosis of brain metastases. However, such treatment was performed nearly exclusively in those patients with brain metastases that belonged to the prognostically more favourable groups. Survival after whole-brain radiotherapy has remained unchanged in patients without further active treatment. It has improved in prognostically better patients and especially patients that received active treatment, where the 1-year survival rates have almost doubled. As these patient groups were small, confirmation of the results in other series should be attempted. Nevertheless, the present results are compatible with the hypothesis that improved systemic therapy might contribute to prolonged survival in patients with brain metastases from breast cancer. PMID:19259331

  8. Radiotherapy dosimetry audit: three decades of improving standards and accuracy in UK clinical practice and trials

    PubMed Central

    Aird, Edwin GA; Bolton, Steve; Miles, Elizabeth A; Nisbet, Andrew; Snaith, Julia AD; Thomas, Russell AS; Venables, Karen; Thwaites, David I

    2015-01-01

    Dosimetry audit plays an important role in the development and safety of radiotherapy. National and large scale audits are able to set, maintain and improve standards, as well as having the potential to identify issues which may cause harm to patients. They can support implementation of complex techniques and can facilitate awareness and understanding of any issues which may exist by benchmarking centres with similar equipment. This review examines the development of dosimetry audit in the UK over the past 30 years, including the involvement of the UK in international audits. A summary of audit results is given, with an overview of methodologies employed and lessons learnt. Recent and forthcoming more complex audits are considered, with a focus on future needs including the arrival of proton therapy in the UK and other advanced techniques such as four-dimensional radiotherapy delivery and verification, stereotactic radiotherapy and MR linear accelerators. The work of the main quality assurance and auditing bodies is discussed, including how they are working together to streamline audit and to ensure that all radiotherapy centres are involved. Undertaking regular external audit motivates centres to modernize and develop techniques and provides assurance, not only that radiotherapy is planned and delivered accurately but also that the patient dose delivered is as prescribed. PMID:26329469

  9. Radiotherapy dosimetry audit: three decades of improving standards and accuracy in UK clinical practice and trials.

    PubMed

    Clark, Catharine H; Aird, Edwin G A; Bolton, Steve; Miles, Elizabeth A; Nisbet, Andrew; Snaith, Julia A D; Thomas, Russell A S; Venables, Karen; Thwaites, David I

    2015-01-01

    Dosimetry audit plays an important role in the development and safety of radiotherapy. National and large scale audits are able to set, maintain and improve standards, as well as having the potential to identify issues which may cause harm to patients. They can support implementation of complex techniques and can facilitate awareness and understanding of any issues which may exist by benchmarking centres with similar equipment. This review examines the development of dosimetry audit in the UK over the past 30 years, including the involvement of the UK in international audits. A summary of audit results is given, with an overview of methodologies employed and lessons learnt. Recent and forthcoming more complex audits are considered, with a focus on future needs including the arrival of proton therapy in the UK and other advanced techniques such as four-dimensional radiotherapy delivery and verification, stereotactic radiotherapy and MR linear accelerators. The work of the main quality assurance and auditing bodies is discussed, including how they are working together to streamline audit and to ensure that all radiotherapy centres are involved. Undertaking regular external audit motivates centres to modernize and develop techniques and provides assurance, not only that radiotherapy is planned and delivered accurately but also that the patient dose delivered is as prescribed.

  10. Comparison of survival outcomes among standard radiotherapy regimens in limited-stage small cell lung cancer patients receiving concurrent chemoradiation.

    PubMed

    Rutter, Charles E; Park, Henry S; Corso, Christopher D; Yeboa, Debra N; Mancini, Brandon R; Lester-Coll, Nataniel H; Kim, Anthony W; Decker, Roy H

    2015-11-01

    The optimal radiotherapy dose in concurrent chemoradiation (CRT) for limited-stage small cell lung cancer (SCLC) is controversial. We compared the effectiveness of several high-dose chemoradiation regimens using a large national dataset. Patients with non-metastatic SCLC treated with concurrent CRT were identified in the National Cancer Database base. Overall survival (OS) of patients receiving dose-fractionation regimens, matching those in the ongoing CALGB 30610 trial [45 Gy in 30 fractions (Fx) (45 Gy/30Fx), 70 Gy in 35 fractions (70 Gy/35Fx), and 61.2 Gy in 34 fractions (61.2 Gy/34Fx)], were compared using Kaplan-Meier analysis and multivariable Cox proportional hazards modeling. We included 1228 patients treated between 1998 and 2006 with CRT. Mean age was 62 years and 50% of patients were women. Radiotherapy dose-fractionation was 45 Gy/30Fx in 707 (57.6%), 70 Gy/35Fx in 53 (4.3%), and 61.2 Gy/34Fx in 468 (38.1%). Overall survival was similar among patients treated with 45 Gy/30Fx, 70 Gy/35Fx, and 61.2 Gy/34Fx, with median survival times of 21.5, 21.5, and 20.2 months, respectively (p=0.438). Older age, male sex, larger tumor size, and more advanced stage were associated with inferior OS on Kaplan-Meier (all p<0.001). Cox proportional hazards modeling adjusting for these factors demonstrated similar OS among patients receiving these three dose-fractionation regimens (p=0.815). We observed equivalent OS among patients with limited-stage SCLC being treated with three dose-fractionation regimens of concurrent CRT. This supports the use of any one of these regimens while awaiting the results of ongoing randomized trials. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Additional androgen deprivation makes the difference: Biochemical recurrence-free survival in prostate cancer patients after HDR brachytherapy and external beam radiotherapy.

    PubMed

    Schiffmann, Jonas; Lesmana, Hans; Tennstedt, Pierre; Beyer, Burkhard; Boehm, Katharina; Platz, Volker; Tilki, Derya; Salomon, Georg; Petersen, Cordula; Krüll, Andreas; Graefen, Markus; Schwarz, Rudolf

    2015-04-01

    The role of additional androgen deprivation therapy (ADT) in prostate cancer (PCa) patients treated with combined HDR brachytherapy (HDR-BT) and external beam radiotherapy (EBRT) is still unknown. Consecutive PCa patients classified as D'Amico intermediate and high-risk who underwent HDR-BT and EBRT treatment ± ADT at our institution between January 1999 and February 2009 were assessed. Multivariable Cox regression models predicting biochemical recurrence (BCR) were performed. BCR-free survival was assessed with Kaplan-Meier analyses. Overall, 392 patients were assessable. Of these, 221 (56.4 %) underwent trimodality (HDR-BT and EBRT and ADT) and 171 (43.6 %) bimodality (HDR-BT and EBRT) treatment. Additional ADT administration reduced the risk of BCR (HR: 0.4, 95 % CI: 0.3-0.7, p < 0.001). D'Amico high-risk patients had superior BCR-free survival when additional ADT was administered (log-rank p < 0.001). No significant difference for BCR-free survival was recorded when additional ADT was administered to D'Amico intermediate-risk patients (log-rank p = 0.2). Additional ADT administration improves biochemical control in D'Amico high-risk patients when HDR-BT and EBRT are combined. Physicians should consider the oncological benefit of ADT administration for these patients during the decision-making process.

  12. [Respiratory synchronization and breast radiotherapy].

    PubMed

    Mège, A; Ziouèche-Mottet, A; Bodez, V; Garcia, R; Arnaud, A; de Rauglaudre, G; Pourel, N; Chauvet, B

    2016-10-01

    Adjuvant radiation therapy following breast cancer surgery continues to improve locoregional control and overall survival. But the success of highly targeted-conformal radiotherapy such as intensity-modulated techniques, can be compromised by respiratory motion. The intrafraction motion can potentially result in significant under- or overdose, and also expose organs at risk. This article summarizes the respiratory motion and its effects on imaging, dose calculation and dose delivery by radiotherapy for breast cancer. We will review the methods of respiratory synchronization available for breast radiotherapy to minimize the respiratory impact and to spare organs such as heart and lung.

  13. Platonin improves survival of skin allografts.

    PubMed

    Cheng, Shih-Ping; Lee, Jie-Jen; Chi, Chin-Wen; Chang, Kuo-Ming; Chen, Yu-Jen

    2010-11-01

    Platonin is an immunomodulator with NF-κB inhibitory activity. It not only inhibits interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α production in sepsis, but also attenuates heatstroke reactions. In addition, platonin redirects differentiation of dendritic cells toward an intermediate stage of maturation. The study was designed to examine whether platonin can reduce acute graft rejection. A C57BL/6 to BALB/c mice skin transplantation model was used. Platonin was given intraperitoneally to transplant recipients at various doses. Skin grafts were submitted to histologic analysis. NF-κB DNA binding activity and inducible nitric oxide synthase (iNOS) expression were determined in harvested draining lymph nodes. Leukocyte count, hepatic and renal functions were serially assessed. An array of serum cytokines was evaluated on d 1, 3, 5, and 7 after skin transplantation. Platonin resulted in significantly prolonged skin allograft survival in a dose- and time-dependent manner. Histologic changes in the skin allografts paralleled the gross appearance of rejection. Serum cytokine analysis shows that platonin significantly suppressed the production of the proinflammatory cytokines IL-6 and TNF-α. However, no significant changes occurred in the serum levels of Th1-type and Th2-type cytokines. NF-κB activity and iNOS expression were remarkably suppressed in draining lymph nodes. In terms of toxicity, there were no significant differences in body weight, leukocyte count, plasma alanine aminotransferase, or creatinine between the platonin-treated and control groups. Platonin effectively prolongs skin allograft survival without major toxicity. Copyright © 2010 Elsevier Inc. All rights reserved.

  14. Optimisation of chemotherapy and radiotherapy for untreated Hodgkin lymphoma patients with respect to second malignant neoplasms, overall and progression-free survival: individual participant data analysis.

    PubMed

    Franklin, Jeremy; Eichenauer, Dennis A; Becker, Ingrid; Monsef, Ina; Engert, Andreas

    2017-09-13

    radiotherapy; early stages). Fewer chemotherapy courses probably has little or no effect on SMN risk (Peto OR 1.10, 95% CI 0.74 to 1.62), OS (HR 0.99, 95% CI 0.73 to1.34) or PFS (HR 1.15, 95% CI 0.91 to 1.45).Outcomes had a moderate (SMN) or high (OS, PFS) quality of evidence. Dose-intensified versus ABVD-like chemotherapy (with or without radiotherapy in each case). In the mainly advanced-stage patients who were treated with intensified chemotherapy, the rate of secondary malignancies was low. There was insufficient evidence to determine the effect of chemotherapy intensification (Peto OR 1.37, CI 0.89 to 2.10, low quality of evidence). The rate of secondary acute leukemias (and for younger patients, all secondary malignancies) was probably higher than among those who had treatment with standard-dose ABVD-like protocols. In contrast, the intensified chemotherapy protocols probably improved PFS (eight-year PFS 75% versus 69% for ABVD-like treatment, HR 0.82, 95% CI 0.7 to 0.95, moderate quality of evidence). Evidence suggesting improved survival with intensified chemotherapy was not conclusive (HR: 0.85, CI 0.70 to 1.04), although escalated-dose BEACOPP appeared to lengthen survival compared to ABVD-like chemotherapy (HR 0.58, 95% CI 0.43 to 0.79, moderate quality of evidence).Generally, we could draw valid conclusions only in terms of secondary haematological malignancies, which usually occur less than 10 years after initial treatment, while follow-up within the present analysis was too short to record all solid tumours. The risk of secondary acute myeloid leukaemia and myelodysplastic syndrome (AML/MDS) is increased but efficacy is improved among patients treated with intensified chemotherapy protocols. Treatment decisions must be tailored for individual patients. Consolidating radiotherapy is associated with an increased rate of secondary malignancies; therefore it appears important to define which patients can safely be treated without radiotherapy after chemotherapy, both

  15. Number and Location of Positive Nodes, Postoperative Radiotherapy, and Survival After Esophagectomy With Three-Field Lymph Node Dissection for Thoracic Esophageal Squamous Cell Carcinoma

    SciTech Connect

    Chen Junqiang; Pan Jianji; Zheng Xiongwei; Zhu Kunshou; Li Jiancheng; Chen Mingqiang; Wang Jiezhong; Liao Zhongxing

    2012-01-01

    Purpose: To analyze influences of the number and location of positive lymph nodes and postoperative radiotherapy on survival for patients with thoracic esophageal squamous cell carcinoma (TE-SCC) treated with radical esophagectomy with three-field lymphadenectomy. Methods and Materials: A total of 945 patients underwent radical esophagectomy plus three-field lymph node dissection for node-positive TE-SCC at Fujian Provincial Tumor Hospital between January 1993 and March 2007. Five hundred ninety patients received surgery only (S group), and 355 patients received surgery, followed 3 to 4 weeks later by postoperative radiotherapy (S+R group) to a median total dose of 50 Gy in 25 fractions. We assessed potential associations among patient-, tumor-, and treatment-related factors and overall survival. Results: Five-year overall survival rates were 32.8% for the entire group, 29.6% for the S group, and 38.0% for the S+R group (p = 0.001 for S vs. S+R). Treatment with postoperative radiotherapy was particularly beneficial for patients with {>=}3 positive nodes and for those with metastasis in the upper (supraclavicular and upper mediastinal) region or both the upper and lower (mediastinal and abdominal) regions (p < 0.05). Postoperative radiotherapy was also associated with lower recurrence rates in the supraclavicular and upper and middle mediastinal regions (p < 0.05). Sex, primary tumor length, number of positive nodes, pathological T category, and postoperative radiotherapy were all independent predictors of survival. Conclusions: Postoperative radiotherapy was associated with better survival for patients with node-positive TE-SCC, particularly those with three or more positive nodes and positive nodes in the supraclavicular and superior mediastinal regions.

  16. Number and location of positive nodes, postoperative radiotherapy, and survival after esophagectomy with three-field lymph node dissection for thoracic esophageal squamous cell carcinoma.

    PubMed

    Chen, Junqiang; Pan, Jianji; Zheng, Xiongwei; Zhu, Kunshou; Li, Jiancheng; Chen, Mingqiang; Wang, Jiezhong; Liao, Zhongxing

    2012-01-01

    To analyze influences of the number and location of positive lymph nodes and postoperative radiotherapy on survival for patients with thoracic esophageal squamous cell carcinoma (TE-SCC) treated with radical esophagectomy with three-field lymphadenectomy. A total of 945 patients underwent radical esophagectomy plus three-field lymph node dissection for node-positive TE-SCC at Fujian Provincial Tumor Hospital between January 1993 and March 2007. Five hundred ninety patients received surgery only (S group), and 355 patients received surgery, followed 3 to 4 weeks later by postoperative radiotherapy (S+R group) to a median total dose of 50 Gy in 25 fractions. We assessed potential associations among patient-, tumor-, and treatment-related factors and overall survival. Five-year overall survival rates were 32.8% for the entire group, 29.6% for the S group, and 38.0% for the S+R group (p = 0.001 for S vs. S+R). Treatment with postoperative radiotherapy was particularly beneficial for patients with ≥3 positive nodes and for those with metastasis in the upper (supraclavicular and upper mediastinal) region or both the upper and lower (mediastinal and abdominal) regions (p < 0.05). Postoperative radiotherapy was also associated with lower recurrence rates in the supraclavicular and upper and middle mediastinal regions (p < 0.05). Sex, primary tumor length, number of positive nodes, pathological T category, and postoperative radiotherapy were all independent predictors of survival. Postoperative radiotherapy was associated with better survival for patients with node-positive TE-SCC, particularly those with three or more positive nodes and positive nodes in the supraclavicular and superior mediastinal regions. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. WE-E-17A-03: FDG-PET-Based Radiomics to Predict Local Control and Survival Following Radiotherapy

    SciTech Connect

    Oh, J; Apte, A; Folkerts, M; Kohutek, Z; Wu, A; Rimmer, A; Lee, N; Deasy, J

    2014-06-15

    Purpose: An exploding field in cancer research is “radiomics,” based on the hypothesis that there is statistical (hidden) information in medical images that is prognostic or predictive of outcomes. Our group has developed an efficient pipeline to extract and analyze quantitative image features from medical images as related to outcomes or diagnosis. In this work, we summarize our previous studies with positron emission tomography (PET) images and show the potential of the use of radiomics for outcomes research. Methods: We analyzed two cancer datasets, each consisting of pre-radiotherapy-treatment PET scans: 163 T1-2N0M0 non-small cell lung cancer (NSCLC) patients and 174 head and neck (H and N) cancer patients with stage III–IV. The PET scans were converted to Computational Environment for Radiological Research (CERR) format, and CERR was used to generate 24 shape, texture, and intensity-histogram based image features. Data-mining and logistic regression methods were then used to model local failure (LF) and overall survival (OS). Unbiased estimates of performance were generated using leave-one-out cross-validation (LOOCV). Results: For predicting LF, the models with biologically equivalent dose (BED) and TLG (metabolic tumor volume (MTV) x SUVmean) in NSCLC, and skewness and MTV in H and N, achieved the best performance with AUC=0.818 (p<0.0001) and AUC=0.826 (p=0.0002), respectively. For predicting OS, the models with kurtosis and volume in NSCLC and SUVmax and homogeneity in H and N achieved the best performance with AUC=0.706 (p<0.0001) and AUC=0.656 (p=0.0003), respectively. On LOOCV, all these models retained significant predictive power. Interestingly, MTV was highly correlated with LF in both sites. Conclusion: PET-based imaged features are promising tools for improving treatment management decision making. Much more research is needed to identify optimal radiomics metrics and to correlate imaging phenotype with other clinical or genomic information.

  18. Can Aidi injection alleviate the toxicity and improve the clinical efficacy of radiotherapy in lung cancer?

    PubMed Central

    Xiao, Zheng; Liang, Rui; Wang, Cheng-qiong; Xu, Shaofeng; Li, Nana; He, Yuejuan; Tang, Fushan; Chen, Ling; Ma, Hu

    2016-01-01

    Abstract Background/Introduction: Aidi injection plus radiotherapy is widely used for lung cancer in China. Can Aidi injection alleviate the toxicity and improve the clinical efficacy of radiotherapy in lung cancer? Has Aidi injection the attenuation and synergistic efficacy to radiotherapy? There is lack of strong evidence to prove it. Objectives: To reveal its real attenuation and synergistic efficacy to radiotherapy and provide sufficient evidence for adjuvant chemotherapy strategies to lung cancer, we systematically evaluated all related studies. Data Sources: We collected all studies about Aidi injection plus radiotherapy for lung cancer in Medline, Embase, Web of Science, China national knowledge infrastructure database (CNKI), Chinese scientific journals full-text database (VIP), Wanfang database, China biological medicine database (CBM) (established to June 2015), and Cochrane Central Register of Controlled Trials (June 2015), evaluated their quality according to the Cochrane evaluation handbook of randomized controlled trials (5.1.0), extracted data following the PICO principles and synthesized the data by Meta analysis. Results: Sixteen randomized controlled trials (RCTs) with 1192 lung cancer patients were included, with general methodological quality in most trials. The merged relative risk (RR) values and their 95% CI of meta-analysis for objective response rate (ORR), disease control rate (DCR), and quality of life (QOL) were as follows: 1.54, (1.39,1.70), 1.10 (1.02, 1.19), and 2.13 (1.68, 2.68). The merged RR values and their 95% CI of meta-analysis for myelosuppression and neutropenia, radiation pneumonitis, and radiation esophagitis were as follows: 0.51 (0.38, 0.69), 0.53 (0.42, 0.65), 0.52 (0.41, 0.67), and 0.52 (0.40, 0.68). All were statistically significant. The possibility of publication bias was small which objectively reported the results. Conclusions: The evidence available indicates that Aidi injection plus radiotherapy can significantly

  19. Adjuvant Radiotherapy and Survival for Patients With Node-Positive Head and Neck Cancer: An Analysis by Primary Site and Nodal Stage

    SciTech Connect

    Kao, Johnny Lavaf, Amir; Teng, Marita S.; Huang, Delphine; Genden, Eric M.

    2008-06-01

    Purpose: Adjuvant radiotherapy (RT) is frequently recommended for node-positive head and neck squamous cell carcinoma (HNSCC) treated with primary surgery. The impact of RT on survival for various subgroups of node-positive HNSCC has not been clearly demonstrated. Methods and Materials: Within the Surveillance, Epidemiology, and End Results (SEER) Database, we identified 5297 patients with node-positive (N1 to N3) HNSCC treated with definitive surgery with or without adjuvant RT between 1988 and 2001. The median follow-up was 4.4 years. Results: Adjuvant RT significantly improved 5-year overall survival (46.3%: 95% confidence interval [CI], 44.7-48.0% for surgery + RT, vs. 35.2%: 95% CI, 32.0-38.5% for surgery alone, p < 0.001) and cancer-specific survival (54.8%: 95% CI, 53.2-56.4% for surgery + RT, vs. 46.2% for surgery alone 95% CI, 42.4-50.0%, p < 0.05). Use of adjuvant RT remained a significant predictor of survival on multivariable analysis (hazard ratio [HR], 0.75; 95% CI, 0.68-0.83; p < 0.001). Subset analyses demonstrated that adjuvant RT was associated with significantly improved survival for N1 (HR, 0.78; 95% CI; 0.67-0.90; p = 0.001), N2a (HR, 0.82; 95% CI, 0.67-0.99, p = 0.048) and N2b to N3 nodal disease (HR, 0.62; 95% CI, 0.51-0.75; p < 0.001). Adjuvant RT increased overall survival for node-positive patients with oropharynx (HR, 0.72; 95% CI, 0.57-0.90; p 0.004), hypopharynx (HR, 0.66; 95% CI, 0.49 to 0.88; p = 0.004), larynx (HR, 0.66; 95% CI, 0.52-0.84; p = 0.001), and oral cavity (HR, 0.84; 95% CI, 0.73-0.98; p = 0.025) primary tumors. Conclusions: In a large population-based analysis, adjuvant RT significantly improves overall survival for patients with node-positive HNSCC. All nodal stages, including N1, appear to benefit from the addition of RT to definitive surgery.

  20. Eribulin Improves Survival of Women with Metastatic Breast Cancer

    Cancer.gov

    Treatment with eribulin (Halaven™) improved overall survival in women with metastatic breast cancer whose disease progressed despite multiple rounds of prior chemotherapy, according to the results of a phase III clinical trial called EMBRACE.

  1. Hibernation Based Therapy to Improve Survival of Severe Blood Loss

    DTIC Science & Technology

    2016-06-01

    AWARD NUMBER: W81XWH-10-2-0121 TITLE: Hibernation-Based Therapy to Improve Survival of Severe Blood Loss PRINCIPAL INVESTIGATOR: Greg Beilman...Hibernation-Based Therapy to Improve Survival of Severe Blood 5a. CONTRACT NUMBER Loss 5b. GRANT NUMBER W81XWH-10-2-0121 5c. PROGRAM ELEMENT NUMBER...political conflict. The injuries sustained are often accompanied by severe blood loss , and shock from this blood loss is the most common cause of

  2. Targeting angiogenesis as a therapeutic means to reinforce osteocyte survival and prevent nonunions in the aftermath of radiotherapy

    PubMed Central

    Donneys, Alexis; Nelson, Noah S.; Page, Erin E.; Deshpande, Sagar S.; Felice, Peter A.; Tchanque–Fossuo, Catherine N.; Spiegel, Joshua P.; Buchman, Steven R.

    2016-01-01

    Background Radiotherapy (XRT) exerts detrimental collateral effects on bone tissue through mechanisms of vascular damage and impediments to osteocytes, ultimately predisposing patients to the debilitating problems of late pathologic fractures and nonunions. We posit that angiogenic therapy will reverse these pathologic effects in a rat model of radiated fracture healing. Methods Three groups of rats underwent mandibular osteotomy. Radiated groups received a fractionated 35 Gy dose before surgery. The deferoxamine (DFO) group received local injections postoperatively. A 40-day healing period was allowed before histology. Analysis of variance (ANOVA; p < .05) was used for group comparisons. Results Radiated fractures revealed a significantly decreased osteocyte count and corresponding increase in empty lacunae when compared to nonradiated fractures (p = .001). With the addition of DFO, these differences were not appreciated. Further, a 42% increase in bony unions was observed after DFO therapy. Conclusion Targeting angiogenesis is a useful means for promoting osteocyte survival and preventing bone pathology after XRT. PMID:24801669

  3. Potentially Curative Radiotherapy for Non-Small-Cell Lung Cancer in Norway: A Population-Based Study of Survival

    SciTech Connect

    Strand, Trond-Eirik; Brunsvig, Paal Fredrik; Johannessen, Dag Clement; Sundstrom, Stein; Wang, Mari; Hornslien, Kjersti; Bremnes, Roy Martin; Stensvold, Andreas; Garpestad, Oddveig; Norstein, Jarle

    2011-05-01

    Purpose: The efficacy of curative irradiation in the treatment of non-small-cell lung cancer patients is considered limited. The purpose of this study was to evaluate long-term survival in a population-based approach. Methods and Materials: Cases of non-small-cell lung cancer diagnosed from 1993 to 2001 were identified in the Cancer Registry of Norway. Electronic linkage with national data from the hospitals' radiotherapy verification systems identified those who received potentially curative doses ({>=}50 Gy). Hospital records were reviewed for all patients. Results: A total of 497 patients (336 men) were identified with a radiation dose of {>=}50 Gy delivered to the lung region. Of these, 41% received 60 Gy or more. The majority (70%) of patients included had advanced stage disease: 24% Stage IIIA and 46% Stage IIIB. The overall 1-, 3-, and 5-year observed survival rates were 53%, 16%, and 9%, respectively. Multivariable analyses identified stage and chemotherapy, but not radiation dose, as significant independent prognostic variables for survival. However, 68% of patients treated with chemotherapy participated in prospective studies with inclusion criteria that excluded patients with less favorable prognostic factors, leading to a selection bias. The number of fractions and the radiation doses varied widely among different hospitals. Conclusion: The long-term prognosis after radiation therapy is poor. More sophisticated, targeted, and uniform delivery of radiation therapy is needed. The apparent benefit of chemotherapy may in part be due to selection of patients with more favorable prognostic factors for this therapy.

  4. Prognostic factors for survival in patients treated with stereotactic radiosurgery for recurrent brain metastases after prior whole brain radiotherapy.

    PubMed

    Caballero, Jorge A; Sneed, Penny K; Lamborn, Kathleen R; Ma, Lijun; Denduluri, Sandeep; Nakamura, Jean L; Barani, Igor J; McDermott, Michael W

    2012-05-01

    To evaluate prognostic factors for survival after stereotactic radiosurgery (SRS) for new, progressive, or recurrent brain metastases (BM) after prior whole brain radiotherapy (WBRT). Patients treated between 1991 and 2007 with Gamma Knife SRS for BM after prior WBRT were retrospectively reviewed. Potential prognostic factors were analyzed overall and by primary site using univariate and stepwise multivariate analyses and recursive partitioning analysis, including age, Karnofsky performance status (KPS), primary tumor control, extracranial metastases, number of BM treated, total SRS target volume, and interval from WBRT to SRS. A total of 310 patients were analyzed, including 90 breast, 113 non-small-cell lung, 31 small-cell lung, 42 melanoma, and 34 miscellaneous patients. The median age was 56, KPS 80, number of BM treated 3, and interval from WBRT to SRS 8.1 months; 76% had controlled primary tumor and 60% had extracranial metastases. The median survival was 8.4 months overall and 12.0 vs. 7.9 months for single vs. multiple BM treated (p = 0.001). There was no relationship between number of BM and survival after excluding single-BM patients. On multivariate analysis, favorable prognostic factors included age <50, smaller total target volume, and longer interval from WBRT to SRS in breast cancer patients; smaller number of BM, KPS >60, and controlled primary in non-small-cell lung cancer patients; and smaller total target volume in melanoma patients. Among patients treated with salvage SRS for BM after prior WBRT, prognostic factors appeared to vary by primary site. Although survival time was significantly longer for patients with a single BM, the median survival time of 7.9 months for patients with multiple BM seems sufficiently long for salvage SRS to appear to be worthwhile, and no evidence was found to support the use of a cutoff for number of BM appropriate for salvage SRS. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Prognostic Factors for Survival in Patients Treated With Stereotactic Radiosurgery for Recurrent Brain Metastases After Prior Whole Brain Radiotherapy

    SciTech Connect

    Caballero, Jorge A.; Sneed, Penny K.; Lamborn, Kathleen R.; Ma, Lijun; Denduluri, Sandeep; Nakamura, Jean L.; Barani, Igor J.; McDermott, Michael W.

    2012-05-01

    Purpose: To evaluate prognostic factors for survival after stereotactic radiosurgery (SRS) for new, progressive, or recurrent brain metastases (BM) after prior whole brain radiotherapy (WBRT). Methods and Materials: Patients treated between 1991 and 2007 with Gamma Knife SRS for BM after prior WBRT were retrospectively reviewed. Potential prognostic factors were analyzed overall and by primary site using univariate and stepwise multivariate analyses and recursive partitioning analysis, including age, Karnofsky performance status (KPS), primary tumor control, extracranial metastases, number of BM treated, total SRS target volume, and interval from WBRT to SRS. Results: A total of 310 patients were analyzed, including 90 breast, 113 non-small-cell lung, 31 small-cell lung, 42 melanoma, and 34 miscellaneous patients. The median age was 56, KPS 80, number of BM treated 3, and interval from WBRT to SRS 8.1 months; 76% had controlled primary tumor and 60% had extracranial metastases. The median survival was 8.4 months overall and 12.0 vs. 7.9 months for single vs. multiple BM treated (p = 0.001). There was no relationship between number of BM and survival after excluding single-BM patients. On multivariate analysis, favorable prognostic factors included age <50, smaller total target volume, and longer interval from WBRT to SRS in breast cancer patients; smaller number of BM, KPS >60, and controlled primary in non-small-cell lung cancer patients; and smaller total target volume in melanoma patients. Conclusions: Among patients treated with salvage SRS for BM after prior WBRT, prognostic factors appeared to vary by primary site. Although survival time was significantly longer for patients with a single BM, the median survival time of 7.9 months for patients with multiple BM seems sufficiently long for salvage SRS to appear to be worthwhile, and no evidence was found to support the use of a cutoff for number of BM appropriate for salvage SRS.

  6. Postoperative adjuvant radiotherapy improves loco-regional recurrence of head and neck mucosal melanoma.

    PubMed

    Wushou, Alimujiang; Hou, Jing; Zhao, Ya-Jun; Miao, Xin-chao

    2015-05-01

    Primary head and neck mucosal melanoma (HNMM) is a rare tumor with a poor prognosis. Controversy remains as to whether postoperative adjuvant radiotherapy (PORT) achieves a significant benefit in HNMM treatment. Because of the lack of available conclusive prospective data, we performed a systematic review and meta-analysis of all relevant available studies to clarify the benefits of PORT. A comprehensive literature search of PubMed and Google Scholar electronic databases was conducted to collect relevant studies until April 30, 2014. Studies published in the English language comparing surgery alone and surgery plus PORT for HNMM were included, with more than 15 study populations. All statistical analyses were performed using STATA version 12.0. A total of 423 patients were available from eight studies and the median sample size was 53 cases. The median follow-up time was 38.2 months (range 18.3-65.2 months). There was a positive association between PORT and loco-regional recurrence of HNMM (odds ratio [OR] = 0.36, 95% confidence interval [CI] = 0.22-0.60, P = 0.000). No associations were found between the PORT and 3-year and 5-year overall survival (OS) (OR = 1.41, 95% CI = 0.94-2.09, P = 0.093 and OR = 1.06, 95% CI = 0.70-1.61, P = 0.161, respectively). PORT had no impact on 3-year and 5-year OS (hazard ratio [HR] = 1.14, 95% CI = 0.80-1.61, P = 0.472 and HR = 1.34, 95% CI = 0.97-1.85, P = 0.227, respectively). PORT improved loco-regional recurrence of HNMM independent of OS.

  7. Improving radiotherapy planning, delivery accuracy, and normal tissue sparing using cutting edge technologies

    PubMed Central

    Glide-Hurst, Carri K.

    2014-01-01

    In the United States, more than half of all new invasive cancers diagnosed are non-small cell lung cancer, with a significant number of these cases presenting at locally advanced stages, resulting in about one-third of all cancer deaths. While the advent of stereotactic ablative radiation therapy (SABR, also known as stereotactic body radiotherapy, or SBRT) for early-staged patients has improved local tumor control to >90%, survival results for locally advanced stage lung cancer remain grim. Significant challenges exist in lung cancer radiation therapy including tumor motion, accurate dose calculation in low density media, limiting dose to nearby organs at risk, and changing anatomy over the treatment course. However, many recent technological advancements have been introduced that can meet these challenges, including four-dimensional computed tomography (4DCT) and volumetric cone-beam computed tomography (CBCT) to enable more accurate target definition and precise tumor localization during radiation, respectively. In addition, advances in dose calculation algorithms have allowed for more accurate dosimetry in heterogeneous media, and intensity modulated and arc delivery techniques can help spare organs at risk. New delivery approaches, such as tumor tracking and gating, offer additional potential for further reducing target margins. Image-guided adaptive radiation therapy (IGART) introduces the potential for individualized plan adaptation based on imaging feedback, including bulky residual disease, tumor progression, and physiological changes that occur during the treatment course. This review provides an overview of the current state of the art technology for lung cancer volume definition, treatment planning, localization, and treatment plan adaptation. PMID:24688775

  8. The MET/AXL/FGFR Inhibitor S49076 Impairs Aurora B Activity and Improves the Antitumor Efficacy of Radiotherapy.

    PubMed

    Clémenson, Céline; Chargari, Cyrus; Liu, Winchygn; Mondini, Michele; Ferté, Charles; Burbridge, Mike F; Cattan, Valérie; Jacquet-Bescond, Anne; Deutsch, Eric

    2017-10-01

    Several therapeutic agents targeting HGF/MET signaling are under clinical development as single agents or in combination, notably with anti-EGFR therapies in non-small cell lung cancer (NSCLC). However, despite increasing data supporting a link between MET, irradiation, and cancer progression, no data regarding the combination of MET-targeting agents and radiotherapy are available from the clinic. S49076 is an oral ATP-competitive inhibitor of MET, AXL, and FGFR1-3 receptors that is currently in phase I/II clinical trials in combination with gefitinib in NSCLC patients whose tumors show resistance to EGFR inhibitors. Here, we studied the impact of S49076 on MET signaling, cell proliferation, and clonogenic survival in MET-dependent (GTL16 and U87-MG) and MET-independent (H441, H460, and A549) cells. Our data show that S49076 exerts its cytotoxic activity at low doses on MET-dependent cells through MET inhibition, whereas it inhibits growth of MET-independent cells at higher but clinically relevant doses by targeting Aurora B. Furthermore, we found that S49076 improves the antitumor efficacy of radiotherapy in both MET-dependent and MET-independent cell lines in vitro and in subcutaneous and orthotopic tumor models in vivo In conclusion, our study demonstrates that S49076 has dual antitumor activity and can be used in combination with radiotherapy for the treatment of both MET-dependent and MET-independent tumors. These results support the evaluation of combined treatment of S49076 with radiation in clinical trials without patient selection based on the tumor MET dependency status. Mol Cancer Ther; 16(10); 2107-19. ©2017 AACR. ©2017 American Association for Cancer Research.

  9. Apparent improvement in survival for carcinoma of the cervix following the introduction of chemoradiation--a Will Rogers phenomenon.

    PubMed

    Foley, M E; Ryan, H; Kearney, E; Herlihy, A; Craig, H; Kelehan, P; Mooney, E; Lenehan, P; Flannelly, G

    2013-03-01

    The improved survival for bulky cervical cancers (> 4cm) reported with combination platinum based chemoradiation (1999) prompted a move away from surgery as these cases frequently received adjuvant radiotherapy and were exposed to the morbidity of multimodality treatment. The period pre-1999 (Group 1) was compared with post-1999 (Group 2) when chemoradiation was the preferred treatment for bulky operable cervical cancer. Significantly more cases were treated surgically among Group 1 compared with Group 2 (79% vs. 62%; P < 0.001). Switching from surgery to radiotherapy improved survival in both treatment categories (73% vs. 78% and 37% vs. 44%, respectively) but with no improvement in overall survival (70%/ov.s 70%). Survival (86%) was similar in both groups among surgically treated women with tumors < 4 cm, but significantly more in Group 2 with negative nodes received postoperative adjuvant chemoradiotherapy (Groups 1 vs. 2; 16% vs.37.5%: P < 0.001) and overall the surgically treated patients received more not less multimodality treatment (46.5% vs. 59%; P = 0.7).

  10. Improved Dosimetric and Clinical Outcomes With Intensity-Modulated Radiotherapy for Head-and-Neck Cancer of Unknown Primary Origin

    SciTech Connect

    Chen, Allen M.; Li Baoqing; Farwell, D. Gregory; Marsano, Joseph; Vijayakumar, Srinivasan; Purdy, James A.

    2011-03-01

    Purpose: To compare differences in dosimetric, clinical, and quality-of-life endpoints among a cohort of patients treated by intensity-modulated radiotherapy (IMRT) and conventional radiotherapy (CRT) for head-and-neck cancer of unknown primary origin. Methods and Materials: The medical records of 51 patients treated by radiation therapy for squamous cell carcinoma of the head and neck presenting as cervical lymph node metastasis of occult primary origin were reviewed. Twenty-four patients (47%) were treated using CRT, and 27 (53%) were treated using IMRT. The proportions of patients receiving concurrent chemotherapy were 54% and 63%, respectively. Results: The 2-year estimates of overall survival, local-regional control, and disease-specific survival for the entire patient population were 86%, 89%, and84%, respectively. There were no significant differences in any of these endpoints with respect to radiation therapy technique (p > 0.05 for all). Dosimetric analysis revealed that the use of IMRT resulted in significant improvements with respect to mean dose and V30 to the contralateral (spared) parotid gland. In addition, mean doses to the ipsilateral inner and middle ear structures were significantly reduced with IMRT (p < 0.05 for all). The incidence of severe xerostomia in the late setting was 58% and 11% among patients treated by CRT and IMRT, respectively (p < 0.001). The percentages of patients who were G-tube dependent at 6 months after treatment were 42% and 11%, respectively (p < 0.001). Conclusions: IMRT results in significant improvements in the therapeutic ratio among patients treated by radiation therapy for head-and-neck cancer of unknown primary origin.

  11. Dependence of Cell Survival on Iododeoxyuridine Concentration in 35-keV Photon-Activated Auger Electron Radiotherapy

    SciTech Connect

    Dugas, Joseph P.; Varnes, Marie E.; Sajo, Erno; Welch, Christopher E.; Ham, Kyungmin; Hogstrom, Kenneth R.

    2011-01-01

    Purpose: To measure and compare Chinese hamster ovary cell survival curves using monochromatic 35-keV photons and 4-MV x-rays as a function of concentration of the radiosensitizer iododeoxyuridine (IUdR). Methods and Materials: IUdR was incorporated into Chinese hamster ovary cell DNA at 16.6 {+-} 1.9%, 12.0 {+-} 1.4%, and 9.2 {+-} 1.3% thymidine replacement. Cells were irradiated from 1 to 8 Gy with 35-keV synchrotron-generated photons and conventional radiotherapy 4-MV x-rays. The effects of the radiation were measured via clonogenic survival assays. Surviving fraction was plotted vs. dose and fit to a linear quadratic model. Sensitization enhancement ratios (SER{sub 10}) were calculated as the ratio of doses required to achieve 10% surviving fraction for cells without and with DNA-incorporated IUdR. Results: At 4 MV, SER{sub 10} values were 2.6 {+-} 0.1, 2.2 {+-} 0.1, and 1.5 {+-} 0.1 for 16.6%, 12.0%, and 9.2% thymidine replacement, respectively. At 35 keV, SER{sub 10} values were 4.1 {+-} 0.2, 3.0 {+-} 0.1, and 2.0 {+-} 0.1, respectively, which yielded SER{sub 10} ratios (35 keV:4 MV) of 1.6 {+-} 0.1, 1.4 {+-} 0.1, and 1.3 {+-} 0.1, respectively. Conclusions: SER{sub 10} increases monotonically with percent thymidine replacement by IUdR for both modalities. As compared to 4-MV x-rays, 35-keV photons produce enhanced SER{sub 10} values whose ratios are linear with percent thymidine replacement and assumed to be due to Auger electrons contributing to enhanced dose to DNA. Although this Auger effectiveness factor is less than the radiosensitization factor of IUdR, both could be important for the clinical efficacy of IUdR radiotherapy.

  12. High dose and compartmental target volume may improve patient outcome after radiotherapy for pelvic bone metastases from hepatocellular carcinoma

    PubMed Central

    Kim, Taehyung; Cha, Hye Jung; Kim, Jun Won; Seong, Jinsil; Lee, Ik Jae

    2016-01-01

    Purpose Pelvic bone metastases are difficult to treat because of complex pelvic bone anatomy and the proximity of normal organs. The adequacy of radiation dose and field coverage was evaluated. Patients and methods We analyzed 146 cases of pelvic bone metastases from HCC treated with radiotherapy (RT). Bone metastases were confirmed using CT/MRI. Subjective pain response was assessed using the visual analogue scale, and treatment-related toxicity with the Common Terminology Criteria for Adverse Events v3.0. Local failure free survival (LFFS) and overall survival were estimated using the Kaplan-Meier method. Results The local control rate was 80.1% and the pain control rate was 68.5%. Compartmental target volume (CTV), encompassing the whole compartment of the involved bone, was found to be a significant factor (1-year LFFS, 78% vs. 50%; p=0.001). Sites of metastasis were categorized as either upper or lower pelvic bone; both categories showed improved local control with CTV. Metastatic lesions that received more than 50 Gy of EQD2 showed more partial response in pain after RT (58% vs. 79%; p=0.007). No patient showed toxicity higher than Grade IV. Conclusion Compartmental RT targeted to the involved bone was associated with improved local control and LFFS. High-dose radiation was associated with an improved treatment response. PMID:27259272

  13. Survival benefit of anti-HER2 therapy after whole-brain radiotherapy in HER2-positive breast cancer patients with brain metastasis.

    PubMed

    Zhang, Qian; Chen, Jian; Yu, Xiaoli; Cai, Gang; Yang, Zhaozhi; Cao, Lu; Hu, Chaosu; Guo, Xiaomao; Sun, Jing; Chen, Jiayi

    2016-09-01

    We aimed to assess the survival benefit of epidermal growth factor receptor 2 (HER2)-positive breast cancer patients with brain metastasis (BM) after whole-brain radiotherapy (WBRT) in combination with systemic treatments, especially anti-HER2 therapy. This retrospective study analyzed the overall survival (OS) of 60 HER2-positive breast cancer patients with BM after WBRT in combination with systemic treatments. Among them, 42 patients received chemotherapy while 18 patients did not receive after WBRT. With regard to anti-HER2 therapy, after WBRT, 17 patients received anti-HER2 treatment without prior adjuvant trastuzumab-based therapy, 7 patients received anti-HER2 treatment with prior adjuvant trastuzumab-based therapy, and 36 patients did not receive further anti-HER2 treatment. All patients were followed up regularly until January 23, 2013. The median OS of patients with BM was 12 months. Patients who received anti-HER2 therapy and chemotherapy after WBRT had significantly better survival compared with patients who did not receive further treatment. Patients who received anti-HER2 treatment after WBRT but did not receive adjuvant trastuzumab-based therapy for early breast cancer had better OS, followed by patients who received anti-HER2 agent both in adjuvant treatment and after WBRT and patients who did not receive anti-HER2 treatment. Multivariate analysis showed that Karnofsky Performance Status, control of extracranial metastases, chemotherapy after WBRT, and anti-HER2 therapy combined with WBRT were all independent predictors for OS. Both chemotherapy and anti-HER2 therapy after WBRT could improve OS. Moreover, patients without prior exposure to adjuvant anti-HER2 treatment may have survival benefit superior to those of patients with prior exposure.

  14. Survival of Danish patients with endometrial cancer in the intermediate-risk group not given postoperative radiotherapy: the Danish Endometrial Cancer Study (DEMCA).

    PubMed

    Bertelsen, Kamma; Ortoft, Gitte; Hansen, Estrid Stæhr

    2011-10-01

    In a prospective study during the years 1986 to 1988, the Danish Endometrial Cancer Group (DEMCA) demonstrated that postoperative radiotherapy was unnecessary for low-risk patients with stage I disease. In the present study, we evaluated in a population-based study if radiotherapy could also be omitted for intermediate-risk patients with stage I disease without loss of survival. From 1998 to 1999, 1166 patients newly diagnosed with carcinoma of the uterus were included in this prospective nationwide study. Of these, 232 were intermediate-risk patients with stage I disease. All intermediate-risk patients received standard primary surgery (hysterectomy, bilateral salpingo-oophorectomy, and peritoneal washings), and no postoperative radiotherapy was given. Survival analyses were performed using Kaplan-Meier survival estimates. The results were compared to the 1986-1988 DEMCA data. The 5-year overall survival (OS) rate for the entire population was 77% (stages I-IV). The patients with stage I disease were divided into low-, intermediate-, and high-risk; the OS rates were 91%, 78%, and 62%, and the endometrial cancer-specific survival rates were 97%, 87%, and 72%, respectively. Using patients' age, tumor grade, myometrial invasion, we divided the intermediate-risk group into "high risk" intermediate and "low-risk" intermediate with OS rates of 70% and 90% and cancer-specific survival of 81% and 96%, respectively. The OS rate (78%) of the intermediate-risk group after radiation had been omitted was comparable to the OS rate (79%) of the intermediate-risk group in the earlier DEMCA (1986-1988) study where postoperative radiation was still the standard of care. We conclude that in a population-based study, radiotherapy can be omitted for intermediate-risk patients with stage I endometrial cancer without loss of survival.

  15. CAFFEINE IMPROVES HEART RATE WITHOUT IMPROVING SEPSIS SURVIVAL

    PubMed Central

    Bauzá, Gustavo; Remick, Daniel

    2015-01-01

    Introduction Caffeine is consumed on a daily basis for its nervous system stimulant properties and is a global adenosine receptor antagonist. Since adenosine receptors have been found to play a major role in regulating the immune response to a septic insult, we investigated if caffeine consumption prior to a septic insult would alter immunological and physiological responses, as well as survival. Methods Two separate experimental designs were employed, both using outbred female ICR mice. In the first experiment mice were administered 20mg/kg of caffeine (equal to 2–3 cups of coffee for a human) or normal saline intraperitoneally at the time of cecal ligation and puncture (CLP). Immunological parameters including cytokines and local cell recruitment measured. In the second experiment caffeine (10mg/kg/hr) was delivered continuously for 24 hours via a subcutaneous infusion pump placed the day prior to CLP and hemodynamic parameters were examined. In both experiments survival was followed for five days. Results A single dose of caffeine at the initiation of sepsis did not alter survival. This single dose of caffeine did significantly increase in plasma levels of the chemokine KC six hours after the onset of sepsis compared to septic mice given normal saline. There were no changes in IL-6 or IL-10 levels in the caffeine groups. Peritoneal lavages performed 24 hours post-CLP showed no difference in the levels of IL-6, TNF, KC, MIP-1, IL-10 or the IL-1 receptor antagonist between caffeine and normal saline treated mice. Additionally, the lavages yielded similar numbers of cells (4.1×106 vehicle vs. 6.9×106 caffeine) and bacterial colony forming units (CFU, 4.1 million CFU vehicle vs. 2.8 million CFU caffeine). In the infusion group, caffeine also did not alter survival. However, caffeine infusion did increase heart rate prior to CLP, and prevented the decline in heart rate after CLP. Conclusion Caffeine increased heart rate in mice but does not impact cytokine

  16. Improvement in survival for patients with synchronous metastatic esophageal cancer in the south of the Netherlands from 1994 to 2013.

    PubMed

    Bernards, N; Haj Mohammad, N; Creemers, G J; Rozema, T; Roukema, J A; Nieuwenhuijzen, G A P; van Laarhoven, H W M; van der Sangen, M; Lemmens, V E P P

    We assessed the use of external beam radiotherapy, brachytherapy chemoradiotherapy and chemotherapy in patients with metastatic esophageal cancer and evaluated the effect on overall survival. We included all patients diagnosed with synchronous metastatic esophageal cancer in the south of the Netherlands between 1 January 1994 and 31 December 2013. Proportions of patients treated with external beam radiotherapy, brachytherapy, chemoradiotherapy and chemotherapy were described with respect to the period of diagnosis, patient and tumor characteristics. Independent risk factors for death were discriminated. A total of 1020 patients were included, 61.5% of these patients received palliative treatment with external beam radiotherapy, chemoradiotherapy, brachytherapy and/or chemotherapy. The use of external beam radiotherapy decreased from 44.5% in 1994 to 22.2% in 2013 (p = 0.0001), whereas the use of chemoradiotherapy increased from 2.9% in 1994 to 19.1% in 2013 (p < 0.0001). The prescription of systemic chemotherapy as single modality increased from 13.9% to 30.5% (p < 0.0001). The use of brachytherapy decreased from 20.9% in 1994 to 7.4% in 2013 (p = 0.0013). The odds of receiving external beam radiotherapy, brachytherapy, chemoradiotherapy and chemotherapy were influenced by different tumor and patient characteristics, such as age, gender, histologic subtype and number of metastatic sites. The median overall survival in patients with metastatic esophageal cancer significantly improved over time from 18 weeks (one-year survival rate 14.4%) in 1994-1998 to 25 weeks (one-year survival rate 22.4%) in 2009-2013. Patients treated with chemoradiotherapy had the most favorable prognosis, followed by patients treated with chemotherapy as a single modality. The median overall survival of patients diagnosed with metastatic esophageal cancer improved from 18 weeks in 1994-1998 to 25 weeks in 2009-2013. Although this increase could be attributed to stage migration

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

    SciTech Connect

    Kollmeier, Marisa A.; Katz, Matthew S.; Mak, Kimberley; Yamada, Yoshiya; Feder, David J.; Zhang Zhigang; Jia Xiaoyu; Shi Weiji; Zelefsky, Michael J.

    2011-03-01

    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- 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.

  18. Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery

    SciTech Connect

    Walker, M.D.; Green, S.B.; Byar, D.P.

    1980-12-04

    Within three weeks of definitive surgical intervention, 467 patients with histologically proved malignant glioma were randomized to receive one of four treatment regimens: semustine (MeCCNU), radiotherapy, carmustine (BCNU) plus radiotherapy, or semustine plus radiotherapy. We analyzed the data for the total randomized population and for the 358 patients in whom the initial protocol specifications were met (the valid study group). Observed toxicity included acceptable skin reactions secondary to radiotherapy and reversible leukopenia and thrombocytopenia due to chemotherapy. Radiotherapy used alone or in combination with a nitrosourea significantly improved survival in comparison with semustine alone. The group receiving carmustine plus radiotherapy had the best survival, but the difference in survival between the groups receiving carmustine plus radiotherapy and semustine plus radiotherapy was not statistically significant. The combination of carmustine plus radiotherapy produced a modest benefit in long-term (18-month) survival as compared with radiotherapy alone, although the difference between survival curves was not significant at the 0.05 level. This study suggests that it is best to use radiotherapy in the post-surgical treatment of malignant glioma and to continue the search for an effective chemotherapeutic regimen to use in addition to radiotherapy.

  19. Postoperative Proton Radiotherapy for Localized and Locoregional Breast Cancer: Potential for Clinically Relevant Improvements?

    SciTech Connect

    Ares, Carmen; Khan, Shaka; MacArtain, Anne M.; Heuberger, Juerg; Goitein, Gudrun; Gruber, Guenther; Lutters, Gerd; Hug, Eugen B.; Bodis, Stephan; Lomax, Antony J.

    2010-03-01

    Purpose: To study the potential reduction of dose to organs at risk (OARs) with intensity-modulated proton radiotherapy (IMPT) compared with intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) photon radiotherapy for left-sided breast cancer patients. Methods and Materials: Comparative treatment-planning was performed using planning computed tomography scans of 20 left-sided breast cancer patients. For each patient, three increasingly complex locoregional volumes (planning target volumes [PTVs]) were defined: whole breast (WB) or chest wall (CW) = (PTV1), WB/CW plus medial-supraclavicular (MSC), lateral-supraclavicular (LSC), and level III axillary (AxIII) nodes = (PTV2) and WB/CW+MSC+LSC+AxIII plus internal mammary chain = (PTV3). For each patient, 3D-CRT, IMRT, and IMPT plans were optimized for PTV coverage. Dose to OARs was compared while maintaining target coverage. Results: All the techniques met the required PTV coverage except the 3D-CRT plans for PTV3-scenario. All 3D-CRT plans for PTV3 exceeded left-lung V20. IMPT vs. 3D-CRT: significant dose reductions were observed for all OARs using IMPT for all PTVs. IMPT vs. IMRT: For PTV2 and PTV3, low (V5) left lung and cardiac doses were reduced by a factor >2.5, and cardiac doses (V22.5) were by a factor of >20 lower with IMPT compared with IMRT. Conclusions: When complex-target irradiation is needed, 3D-CRT often compromises the target coverage and increases the dose to OARs; IMRT can provide better results but will increase the integral dose. The benefit of IMPT is based on improved target coverage and reduction of low doses to OARs, potentially reducing the risk of late-toxicity. These results indicate a potential role of proton-radiotherapy for extended locoregional irradiation in left breast cancer.

  20. Challenges to Improving Combat Casualty Survivability on the Battlefield

    DTIC Science & Technology

    2015-01-01

    closing the gap in prehospital survival. Improving pre - hospital combat casualty care, however, may be significantly more challenging than improving...facts must be collected on each case; however, as we discuss shortly, pre - hospital data are often difficult to collect. The potentially preventable

  1. Survival and Quality of Life After Stereotactic or 3D-Conformal Radiotherapy for Inoperable Early-Stage Lung Cancer

    SciTech Connect

    Widder, Joachim; Postmus, Douwe; Ubbels, Jan F.; Wiegman, Erwin M.; Langendijk, Johannes A.

    2011-11-15

    Purpose: To investigate survival and local recurrence after stereotactic ablative radiotherapy (SABR) or three-dimensional conformal radiotherapy (3D-CRT) administered for early-stage primary lung cancer and to investigate longitudinal changes of health-related quality of life (HRQOL) parameters after either treatment. Methods and Materials: Two prospective cohorts of inoperable patients with T1-2N0M0 primary lung tumors were analyzed. Patients received 70 Gy in 35 fractions with 3D-CRT or 60 Gy in three to eight fractions with SABR. Global quality of life (GQOL), physical functioning (PF), and patient-rated dyspnea were assessed using the respective dimensions of European Organization for Research and Treatment of Cancer Core Questionnaire-C30 and LC13. HRQOL was analyzed using multivariate linear mixed-effects modeling, survival and local control (LC) using the Kaplan-Meier method, Cox proportional hazards analysis, and Fine and Gray multivariate competing risk analysis as appropriate. Results: Overall survival (OS) was better after SABR compared with 3D-CRT with a HR of 2.6 (95% confidence interval [CI]: 1.5-4.8; p < 0.01). 3D-CRT conferred a subhazard ratio for LC of 5.0 (95% CI: 1.7-14.7; p < 0.01) compared with SABR. GQOL and PF were stable after SABR (p = 0.21 and p = 0.62, respectively). Dyspnea increased after SABR by 3.2 out of 100 points (95% CI: 1.0-5.3; p < 0.01), which is clinically insignificant. At 1 year, PF decreased by an excess of 8.7 out of 100 points (95% CI: 2.8-14.7; p < 0.01) after 3D-CRT compared with SABR. Conclusion: In this nonrandomized comparison of two prospective cohorts of medically inoperable patients with Stage I lung cancer, OS and LC were better after SABR. GQOL, PF, and patient-rated dyspnea were stable after SABR, whereas PF decreased after 3D-CRT approaching clinical significance already at 1 year.

  2. Addition of Androgens Improves Survival in Elderly Patients With Acute Myeloid Leukemia: A GOELAMS Study.

    PubMed

    Pigneux, Arnaud; Béné, Marie C; Guardiola, Philippe; Recher, Christian; Hamel, Jean-Francois; Sauvezie, Mathieu; Harousseau, Jean-Luc; Tournilhac, Olivier; Witz, Francis; Berthou, Christian; Escoffre-Barbe, Martine; Guyotat, Denis; Fegueux, Nathalie; Himberlin, Chantal; Hunault, Mathilde; Delain, Martine; Lioure, Bruno; Jourdan, Eric; Bauduer, Frederic; Dreyfus, Francois; Cahn, Jean-Yves; Sotto, Jean-Jacques; Ifrah, Norbert

    2017-02-01

    Purpose Elderly patients with acute myeloid leukemia (AML) have a poor prognosis, and innovative maintenance therapy could improve their outcomes. Androgens, used in the treatment of aplastic anemia, have been reported to block proliferation of and initiate differentiation in AML cells. We report the results of a multicenter, phase III, randomized open-label trial exploring the benefit of adding androgens to maintenance therapy in patients 60 years of age or older. Patients and Methods A total of 330 patients with AML de novo or secondary to chemotherapy or radiotherapy were enrolled in the study. Induction therapy included idarubicin 8 mg/m(2) on days 1 to 5, cytarabine 100 mg/m(2) on days 1 to 7, and lomustine 200 mg/m(2) on day 1. Patients in complete remission or partial remission received six reinduction courses, alternating idarubicin 8 mg/m(2) on day 1, cytarabine 100 mg/m(2) on days 1 to 5, and a regimen of methotrexate and mercaptopurine. Patients were randomly assigned to receive norethandrolone 10 or 20 mg/day, according to body weight, or no norethandrolone for a 2-year maintenance therapy regimen. The primary end point was disease-free survival by intention to treat. Secondary end points were event-free survival, overall survival, and safety. This trial was registered at www.ClinicalTrials.gov identifier NCT00700544. Results Random assignment allotted 165 patients to each arm; arm A received norethandrolone, and arm B did not receive norethandrolone. Complete remission or partial remission was achieved in 247 patients (76%). The Schoenfeld time-dependent model showed that norethandrolone significantly improved survival for patients still in remission at 1 year after induction. In arms A and B, respectively, 5-year disease-free survival was 31.2% and 16.2%, event-free survival was 21.5% and 12.9%, and overall survival was 26.3% and 17.2%. Norethandrolone improved outcomes irrelevant to all prognosis factors. Only patients with baseline leukocytes > 30

  3. Delay in initiating adjuvant radiotherapy following breast conservation surgery and its impact on survival

    SciTech Connect

    Hershman, Dawn L. . E-mail: dlh23@columbia.edu; Wang Xiaoyan; McBride, Russell

    2006-08-01

    Purpose: Delays in the diagnosis of breast cancer are associated with advanced stage and poor survival, but the importance of the time interval between lumpectomy and initiation of radiation therapy (RT) has not been well studied. We investigated factors that influence the time interval between lumpectomy and RT, and the association between that interval and survival. Patients and Methods: We used data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database on women aged 65 years and older, diagnosed with Stages I-II breast cancer, between 1991 and 1999. Among patients who did not receive chemotherapy, we studied factors associated with the time interval between lumpectomy and the initiation of RT, and the association of delay with survival, using linear regression and Cox proportional hazards modeling. Results: Among 24,833 women with who underwent lumpectomy, 13,907 (56%) underwent RT. Among those receiving RT, 97% started treatment within 3 months; older age, black race, advanced stage, more comorbidities, and being unmarried were associated with longer time intervals between surgery and RT. There was no benefit to earlier initiation of RT; however, delays >3 months were associated with higher overall mortality (hazard ratio, 1.92; 95% confidence interval, 1.64-2.24) and cancer-specific mortality (hazard ratio, 3.84; 95% confidence interval 3.01-4.91). Conclusions: Reassuringly, early initiation of RT was not associated with survival. Although delays of >3 months are uncommon, they are associated with poor survival. Whether this association is causal or due to confounding factors, such as poor health behaviors, is unknown; until it is better understood, efforts should be made to initiate RT in a timely fashion.

  4. Breast Cancer in Developing Countries: Opportunities for Improved Survival

    PubMed Central

    Shulman, Lawrence N.; Willett, Walter; Sievers, Amy; Knaul, Felicia M.

    2010-01-01

    Breast cancer survival in the USA has continually improved over the last six decades and has largely been accredited to the use of mammography, advanced surgical procedures, and adjuvant therapies. Data indicate, however, that there were substantial improvements in survival in the USA even prior to these technological and diagnostic advances, suggesting important opportunities for early detection and treatment in low- and middle-income countries where these options are often unavailable and/or unaffordable. Thus, while continuing to strive for increased access to more advanced technology, improving survival in these settings should be more immediately achievable through increased awareness of breast cancer and of the potential for successful treatment, a high-quality primary care system without economic or cultural barriers to access, and a well-functioning referral system for basic surgical and hormonal treatment. PMID:21253541

  5. The remarkable improvements in survival at older ages.

    PubMed

    Vaupel, J W

    1997-12-29

    The belief that old-age mortality is intractable remains deeply held by many people. Remarkable progress, however, has been made since 1950, and especially since 1970, in substantially improving survival at older ages, even the most advanced ages. The pace of mortality improvement at older ages continues to be particularly rapid in Japan, even though mortality levels in Japan are lower than elsewhere. The progress in improving survival has accelerated the growth of the population of older people and has advanced the frontier of human survival substantially beyond the extremes of longevity attained in pre-industrial times. Little, however, is known about why mortality among the oldest-old has been so plastic since 1950. The little that is known has largely been learned within the past few years. New findings, especially concerning genetic factors that influence longevity, are emerging at accelerating rate.

  6. Evidence of improving survival of patients with rectal cancer in France: a population based study

    PubMed Central

    Finn-Faivre, C; Maurel, J; Benhamiche, A; Herbert, C; Mitry, E; Launoy, G; Faivre, J

    1999-01-01

    BACKGROUND—Over the past 20 years there have been many changes in the management of rectal cancer. Their impact on the overall population is not well known. 
AIMS—To determine trends in management and prognosis of rectal cancer in two French regions. 
SUBJECTS—1978 patients with a rectal carcinoma diagnosed between 1978 and 1993. 
METHODS—Time trends in treatment, stage at diagnosis, operative mortality, and survival were studied on a four year basis. A non-conditional logistic regression was performed to obtain an odds ratio for each period adjusted for the other variables. To estimate the independent effect of the period a multivariate relative survival analysis was performed. 
RESULTS—Over the 16 year period resection rates increased from 66.0% to 80.1%; the increase was particularly noticeable for sphincter saving procedures (+30.6% per four years, p=0.03). The percentage of patients receiving adjuvant radiotherapy increased from 24.0% to 40.0% (p=0.02). The proportion of patients with Dukes' type A cancer increased from 17.7% to 30.6% with a corresponding decrease in those with more advanced disease. Operative mortality decreased by 31.1% per four years (p=0.03). All these improvements have resulted in a dramatic increase in relative survival (from 35.4% for the 1978-1981 period to 57.0% for the 1985-1989 period). 
CONCLUSIONS—Substantial advances in the management of rectal cancer have been achieved, but there is evidence that further improvements can be made in order to increase survival. 

 Keywords: rectal cancer; treatment; stage at diagnosis; survival; time trends; cancer registries PMID:10026324

  7. Improvements in CVD diamond properties for radiotherapy dosimetry.

    PubMed

    De Angelis, C; Bucciolini, M; Casati, M; Løvik, I; Bruzzi, M; Lagomarsino, S; Sciortino, S; Onori, S

    2006-01-01

    The goal of this work was to compare the behaviour of a chemical vapour deposited (CVD) diamond sample, grown at the University of Florence using a local procedure, with that of a commercial CVD diamond. The comparison was performed exposing both systems to 25 MV photons and measuring the current response during irradiation. Properties of dosimetric interest such as stability of response, dose rate dependence and rise time were investigated. After a preliminary study, which evidenced better performances of the commercial device with respect to the local CVD diamond, the latter was irradiated with a high fluence of fast neutrons. As a result of the neutron treatment, the quality of the CVD home-made diamond has been improved to match with that of the commercial dosemeter.

  8. Comparison of Bayesian network and support vector machine models for two-year survival prediction in lung cancer patients treated with radiotherapy

    SciTech Connect

    Jayasurya, K.; Fung, G.; Yu, S.; Dehing-Oberije, C.; De Ruysscher, D.; Hope, A.; De Neve, W.; Lievens, Y.; Lambin, P.; Dekker, A. L. A. J.

    2010-04-15

    Purpose: Classic statistical and machine learning models such as support vector machines (SVMs) can be used to predict cancer outcome, but often only perform well if all the input variables are known, which is unlikely in the medical domain. Bayesian network (BN) models have a natural ability to reason under uncertainty and might handle missing data better. In this study, the authors hypothesize that a BN model can predict two-year survival in non-small cell lung cancer (NSCLC) patients as accurately as SVM, but will predict survival more accurately when data are missing. Methods: A BN and SVM model were trained on 322 inoperable NSCLC patients treated with radiotherapy from Maastricht and validated in three independent data sets of 35, 47, and 33 patients from Ghent, Leuven, and Toronto. Missing variables occurred in the data set with only 37, 28, and 24 patients having a complete data set. Results: The BN model structure and parameter learning identified gross tumor volume size, performance status, and number of positive lymph nodes on a PET as prognostic factors for two-year survival. When validated in the full validation set of Ghent, Leuven, and Toronto, the BN model had an AUC of 0.77, 0.72, and 0.70, respectively. A SVM model based on the same variables had an overall worse performance (AUC 0.71, 0.68, and 0.69) especially in the Ghent set, which had the highest percentage of missing the important GTV size data. When only patients with complete data sets were considered, the BN and SVM model performed more alike. Conclusions: Within the limitations of this study, the hypothesis is supported that BN models are better at handling missing data than SVM models and are therefore more suitable for the medical domain. Future works have to focus on improving the BN performance by including more patients, more variables, and more diversity.

  9. Declining Use of Radiotherapy in Stage I and II Hodgkin's Disease and Its Effect on Survival and Secondary Malignancies

    SciTech Connect

    Koshy, Matthew; Rich, Shayna E.; Mahmood, Usama; Kwok, Young

    2012-02-01

    Purpose: Concerns regarding long-term toxicities have led some to withhold radiotherapy (RT) for the treatment of Stage I and II Hodgkin's disease (HD). The present study was undertaken to assess the use of RT for HD and its effect on overall survival and the development of secondary malignancies. Methods and Materials: The present study included data from the Surveillance, Epidemiology, and End Results database from patients aged {>=}20 years who had been diagnosed with Stage I or II HD between 1988 and 2006. Overall survival was estimated using the Kaplan-Meier method, and the Cox multivariate regression model was used to analyze trends. Results: A total of 12,247 patients were selected, and 51.5% had received RT. The median follow-up for the present cohort was 4.9 years, with 21% of the cohort having >10 years of follow-up. Between 1988 and 1991, 62.9% had undergone RT, but between 2004 and 2006, only 43.7% had undergone RT (p < .001). The 5-year overall survival rate was 76% for patients who had not received RT and 87% for those who had (p < .001). The hazard ratio adjusted for other variables in the regression model showed that patients who had not undergone RT (hazard ratio, 1.72; 95% confidence interval, 1.72-2.02) was associated with significantly worse survival compared with patients who had received RT. The actuarial rate of developing a second malignancy was 14.6% vs. 15.0% at 15 years for those who had and had not undergone RT, respectively (p = .089). Conclusions: The present study is one of the largest studies to examine the role of RT for Stage I and II HD. Our results revealed a survival benefit with the addition of RT with no increase in the development of secondary malignancies compared with patients who had not received RT. Furthermore, the present nationwide study revealed a >20% absolute decrease in the use of RT from 1988 to 2006.

  10. Long-term survival after surgical resection for recurrent nasopharyngeal cancer after radiotherapy failure.

    PubMed

    Fee, W E; Roberson, J B; Goffinet, D R

    1991-11-01

    Results are reported of transpalatal, transcervical, and transmaxillary resection in 15 patients with recurrent nasopharyngeal cancer after failure of primary radiotherapy. Seven patients treated for cure have been followed up for more than 3 years (mean, 55 months; range, 40 to 82 months), with three (43%) remaining free of disease. Two patients are living with local disease (59 and 40 months postoperatively), while two have died of their local and regional recurrence (40 and 17 months postoperatively). Two additional patients underwent nasopharyngectomy for palliation. One of these patients died of uncontrolled disease 12 months postoperatively; the other remains alive with disease 70 months after resection. Six patients have been followed up for less than 3 years (mean, 22.3 months; range, 16 to 32 months). Of this group, one (17%) is without evidence of disease, four are living with local disease (13, 16, 17, and 27 months postoperatively), and one has died of disease (13 months postoperatively). Recurrence (10 of 13 patients) has occurred an average of 8 months after surgery (range, 4 to 17 months). Complications include transient marginal mandibular nerve weakness (one), permanent cranial nerve paralysis (two), nasopharyngitis and/or osteomyelitis of the cervical vertebrae or base of skull requiring intravenous antibiotics (two), aspiration pneumonia (two), prolonged nasogastric tube feeding (two), and intraoperative thyroid storm (one). No cerbrospinal fluid leaks or perioperative deaths occurred. The long-term cure rate and disease-free interval of transpalatal nasopharyngectomy lead us to believe that this technique is probably only slightly better than reirradiation in the appropriately selected patient.

  11. Reducing synuclein accumulation improves neuronal survival after spinal cord injury

    PubMed Central

    Fogerson, Stephanie M.; van Brummen, Alexandra J.; Busch, David J.; Allen, Scott R.; Roychaudhuri, Robin; Banks, Susan M. L.; Klärner, Frank-Gerrit; Schrader, Thomas; Bitan, Gal; Morgan, Jennifer R.

    2016-01-01

    Spinal cord injury causes neuronal death, limiting subsequent regeneration and recovery. Thus, there is a need to develop strategies for improving neuronal survival after injury. Relative to our understanding of axon regeneration, comparatively little is known about the mechanisms that promote the survival of damaged neurons. To address this, we took advantage of lamprey giant reticulospinal neurons whose large size permits detailed examination of post-injury molecular responses at the level of individual, identified cells. We report here that spinal cord injury caused a select subset of giant reticulospinal neurons to accumulate synuclein, a synaptic vesicle-associated protein best known for its atypical aggregation and causal role in neurodegeneration in Parkinson’s and other diseases. Post-injury synuclein accumulation took the form of punctate aggregates throughout the somata and occurred selectively in dying neurons, but not in those that survived. In contrast, another synaptic vesicle protein, synaptotagmin, did not accumulate in response to injury. We further show that the post-injury synuclein accumulation was greatly attenuated after single dose application of either the “molecular tweezer” inhibitor, CLR01, or a translation-blocking synuclein morpholino. Consequently, reduction of synuclein accumulation not only improved neuronal survival, but also increased the number of axons in the spinal cord proximal and distal to the lesion. This study is the first to reveal that reducing synuclein accumulation is a novel strategy for improving neuronal survival after spinal cord injury. PMID:26854933

  12. Dose escalation for prostate cancer radiotherapy: predictors of long-term biochemical tumor control and distant metastases-free survival outcomes.

    PubMed

    Zelefsky, Michael J; Pei, Xin; Chou, Joanne F; Schechter, Michael; Kollmeier, Marisa; Cox, Brett; Yamada, Yoshiya; Fidaleo, Anthony; Sperling, Dahlia; Happersett, Laura; Zhang, Zhigang

    2011-12-01

    Higher radiation dose levels have been shown to be associated with improved tumor-control outcomes in localized prostate cancer (PCa) patients. Identify predictors of biochemical tumor control and distant metastases-free survival (DMFS) outcomes for patients with clinically localized PCa treated with conformal external-beam radiotherapy (RT) as well as present an updated nomogram predicting long-term biochemical tumor control after RT. This retrospective analysis comprised 2551 patients with clinical stages T1-T3 PCa. Median follow-up was 8 yr, extending >20 yr. Prescription doses ranged from 64.8 to 86.4 Gy. A total of 1249 patients (49%) were treated with neoadjuvant and concurrent androgen-deprivation therapy (ADT); median duration of ADT was 6 mo. A proportional hazards regression model predicting the probability of biochemical relapse and distant metastases after RT included pretreatment prostate-specific antigen (PSA) level, clinical stage, biopsy Gleason sum, ADT use, and radiation dose. A nomogram predicting the probability of biochemical relapse after RT was developed. Radiation dose was one of the important predictors of long-term biochemical tumor control. Dose levels < 70.2 Gy and 70.2-79.2 Gy were associated with 2.3- and 1.3-fold increased risks of PSA relapse compared with higher doses. Improved PSA relapse-free survival (PSA-RFS) outcomes with higher doses were observed for all risk groups. Use of ADT, especially for intermediate- and high-risk patients, was associated with significantly improved biochemical tumor-control outcomes. A nomogram predicting PSA-RFS was generated and was associated with a concordance index of 0.67. T stage, Gleason score, pretreatment PSA, ADT use, and higher radiation doses were also noted to be significant predictors of improved DMFS outcomes. Higher radiation dose levels were consistently associated with improved biochemical control outcomes and reduction in distant metastases. The use of short-course ADT in

  13. Impact of histological subtype on survival in patients with locally advanced cervical cancer that were treated with definitive radiotherapy: adenocarcinoma/adenosquamous carcinoma versus squamous cell carcinoma

    PubMed Central

    Kuroda, Hiromasa; Kimura, Tadashi

    2017-01-01

    Objective To compare the survival outcomes of patients with cervical squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC) among patients with locally advanced cervical cancer that were treated with definitive radiotherapy. Methods The baseline characteristics and outcome data of patients with locally advanced cervical cancer who were treated with definitive radiotherapy between November 1993 and February 2014 were collected and retrospectively reviewed. A Cox proportional hazards regression model was used to investigate the prognostic significance of AC/ASC histology. Results The patients with AC/ASC of the cervix exhibited significantly shorter overall survival (OS) (p=0.004) and progression-free survival (PFS) (p=0.002) than the patients with SCC of the cervix. Multivariate analysis showed that AC/ASC histology was an independent negative prognostic factor for PFS. Among the patients who displayed AC/ASC histology, larger tumor size, older age, and incomplete response to radiotherapy were found to be independent prognostic factors. PFS was inversely associated with the number of poor prognostic factors the patients exhibited (the estimated 1-year PFS rates; 100.0%, 77.8%, 42.8%, 0.0% for 0, 1, 2, 3 factors, respectively). Conclusion Locally advanced cervical cancer patients with AC/ASC histology experience significantly worse survival outcomes than those with SCC. Further clinical studies are warranted to develop a concurrent chemoradiotherapy (CCRT) protocol that is specifically tailored to locally advanced cervical AC/ASC. PMID:28028992

  14. Surviving Performance Improvement "Solutions": Aligning Performance Improvement Interventions

    ERIC Educational Resources Information Center

    Bernardez, Mariano L.

    2009-01-01

    How can organizations avoid the negative, sometimes chaotic, effects of multiple, poorly coordinated performance improvement interventions? How can we avoid punishing our external clients or staff with the side effects of solutions that might benefit our bottom line or internal efficiency at the expense of the value received or perceived by…

  15. Surviving Performance Improvement "Solutions": Aligning Performance Improvement Interventions

    ERIC Educational Resources Information Center

    Bernardez, Mariano L.

    2009-01-01

    How can organizations avoid the negative, sometimes chaotic, effects of multiple, poorly coordinated performance improvement interventions? How can we avoid punishing our external clients or staff with the side effects of solutions that might benefit our bottom line or internal efficiency at the expense of the value received or perceived by…

  16. Improving survival after endometrial cancer: the big picture.

    PubMed

    Kwon, Janice S

    2015-07-01

    To improve survival in women with endometrial cancer, we need to look at the "big picture" beyond initial treatment. Although the majority of women will be diagnosed with early stage disease and are cured with surgery alone, there is a subgroup of women with advanced and high-risk early stage disease whose life expectancy may be prolonged with the addition of chemotherapy. Immunohistochemistry will help to identify those women with Lynch syndrome who will benefit from more frequent colorectal cancer surveillance and genetic counseling. If they happen to be diagnosed with colorectal cancer, this information has an important therapeutic implication. And finally, because the majority of women will survive their diagnosis of endometrial cancer, they remain at risk for breast and colorectal cancer, so these women should be counselled about screening for these cancers. These three interventions will contribute to improving the overall survival of women with endometrial cancer.

  17. Does chronomodulated radiotherapy improve pathological response in locally advanced rectal cancer?

    PubMed

    Squire, Tim; Buchanan, Grant; Rangiah, David; Davis, Ian; Yip, Desmond; Chua, Yu Jo; Rich, Tyvin; Elsaleh, Hany

    2017-01-01

    The predominant mode of radiation-induced cell death for solid tumours is mitotic catastrophe, which is in part dependent on sublethal damage repair being complete at around 6 h. Circadian variation appears to play a role in normal cellular division, and this could influence tumour response of radiation treatment depending on the time of treatment delivery. We tested the hypothesis that radiation treatment later in the day may improve tumour response and nodal downstaging in rectal cancer patients treated neoadjuvantly with radiation therapy. Recruitment was by retrospective review of 267 rectal cancer patients treated neoadjuvantly in the Department of Radiation Oncology at the Canberra Hospital between January 2010 and November 2015. One hundred and fifty-five patients met the inclusion criteria for which demographic, pathological and imaging data were collected, as well as the time of day patients received treatment with each fraction of radiotherapy. Data analysis was performed using the Statistical Package R with nonparametric methods of significance for all tests set at p < 0.05. Of the 45 female and 110 male patients, the median age was 64. Seventy-three percent had cT3 disease and there was a mean tumour distance from the anal verge of 7 cm. Time to surgical resection following radiotherapy ranged from 4 to 162 days with a median of 50 days, with a complete pathological response seen in 21% of patients. Patients exhibiting a favourable pathological response had smaller median pre- and postradiotherapy tumour size and had a greater change in tumour size following treatment (p < 0.01). Patients who received the majority of their radiotherapy fractions after 12:00 pm were more likely to show a complete or moderate pathological response (p = 0.035) and improved nodal downstaging. There were also more favourable responses amongst patients with longer time to surgical resection postradiotherapy (p < 0.004), although no relationship was seen between response and

  18. VEGF improves survival of mesenchymal stem cells in infarcted hearts

    SciTech Connect

    Pons, Jennifer; Huang Yu; Arakawa-Hoyt, Janice; Washko, Daniel; Takagawa, Junya; Ye, Jianqin; Grossman, William; Su Hua

    2008-11-14

    Bone marrow-derived mesenchymal stem cells (MSC) are a promising source for cell-based treatment of myocardial infarction (MI), but existing strategies are restricted by low cell survival and engraftment. We examined whether vascular endothelial growth factor (VEGF) improve MSC viability in infracted hearts. We found long-term culture increased MSC-cellular stress: expressing more cell cycle inhibitors, p16{sup INK}, p21 and p19{sup ARF}. VEGF treatment reduced cellular stress, increased pro-survival factors, phosphorylated-Akt and Bcl-xL expression and cell proliferation. Co-injection of MSCs with VEGF to MI hearts increased cell engraftment and resulted in better improvement of cardiac function than that injected with MSCs or VEGF alone. In conclusion, VEGF protects MSCs from culture-induce cellular stress and improves their viability in ischemic myocardium, which results in improvements of their therapeutic effect for the treatment of MI.

  19. A retrospective analysis of survival outcomes for two different radiotherapy fractionation schedules given in the same overall time for limited stage small cell lung cancer.

    PubMed

    Bettington, Catherine S; Tripcony, Lee; Bryant, Guy; Hickey, Brigid; Pratt, Gary; Fay, Michael

    2013-02-01

    To compare survival outcomes for two fractionation schedules of thoracic radiotherapy, both given over 3 weeks, in patients with limited stage small cell lung cancer (LS-SCLC). At Radiation Oncology Mater Centre (ROMC) and the Royal Brisbane & Women's Hospital (RBWH), patients with LS-SCLC treated with curative intent are given radiotherapy (with concurrent chemotherapy) to a dose of either 40 Gy in 15 fractions ('the 40 Gy/15# group') or 45 Gy in 30 fractions ('the 45 Gy/30# group'). The choice largely depends on institutional preference. Both these schedules are given over 3 weeks, using daily and twice-daily fractionation respectively. The records of all such patients treated from January 2000 to July 2009 were retrospectively reviewed and survival outcomes between the two groups compared. Of 118 eligible patients, there were 38 patients in the 40 Gy/15# group and 41 patients in the 45 Gy/30# group. The median relapse-free survival time was 12 months in both groups. Median overall survival was 21 months (95% CI 2-37 months) in the 40 Gy/15# group and 26 months (95% CI 1-48 months) in the 45 Gy/30# group. The 5-year overall survival rates were 20% and 25%, respectively (P = 0.24). On multivariate analysis, factors influencing overall survival were: whether prophylactic cranial irradiation (PCI) was given (P = 0.01) and whether salvage chemotherapy was given at the time of relapse (P = 0.057). Given the small sample size, the potential for selection bias and the retrospective nature of our study it is not possible to draw firm conclusions regarding the efficacy of hypofractionated thoracic radiotherapy compared with hyperfractionated accelerated thoracic radiotherapy however hypofractionated radiotherapy may result in equivalent relapse-free survival. © 2013 The Authors. Journal of Medical Imaging and Radiation Oncology © 2013 The Royal Australian and New Zealand College of Radiologists.

  20. Ablative Radiotherapy Doses Lead to a Substantial Prolongation of Survival in Patients With Inoperable Intrahepatic Cholangiocarcinoma: A Retrospective Dose Response Analysis

    PubMed Central

    Tao, Randa; Krishnan, Sunil; Bhosale, Priya R.; Javle, Milind M.; Aloia, Thomas A.; Shroff, Rachna T.; Kaseb, Ahmed O.; Bishop, Andrew J.; Swanick, Cameron W.; Koay, Eugene J.; Thames, Howard D.; Hong, Theodore S.; Das, Prajnan

    2016-01-01

    Purpose Standard therapies for localized inoperable intrahepatic cholangiocarcinoma (IHCC) are ineffective. Advances in radiotherapy (RT) techniques and image guidance have enabled ablative doses to be delivered to large liver tumors. This study evaluated the effects of RT dose escalation in the treatment of IHCC. Patients and Methods Seventy-nine consecutive patients with inoperable IHCC were identified and treated with definitive RT from 2002 to 2014. At diagnosis, the median tumor size was 7.9 cm (range, 2.2 to 17 cm). Seventy patients (89%) received systemic chemotherapy before RT. RT doses were 35 to 100 Gy (median, 58.05 Gy) in three to 30 fractions for a median biologic equivalent dose (BED) of 80.5 Gy (range, 43.75 to 180 Gy). Results Median follow-up time for patients alive at time of analysis was 33 months (range, 11 to 93 months). Median overall survival (OS) time after diagnosis was 30 months; 3-year OS rate was 44%. Radiation dose was the single most important prognostic factor; higher doses correlated with an improved local control (LC) rate and OS. The 3-year OS rate for patients receiving BED greater than 80.5 Gy was 73% versus 38% for those receiving lower doses (P = .017); 3-year LC rate was significantly higher (78%) after a BED greater than 80.5 Gy than after lower doses (45%, P = .04). BED as a continuous variable significantly affected LC (P = .009) and OS (P = .004). There were no significant treatment-related toxicities. Conclusion Delivery of higher doses of RT improves LC and OS in inoperable IHCC. A BED greater than 80.5 Gy seems to be an ablative dose of RT for large IHCCs, with long-term survival rates that compare favorably with resection. PMID:26503201

  1. Targeting the AKT/GSK3{beta}/Cyclin D1/Cdk4 Survival Signaling Pathway for Eradication of Tumor Radioresistance Acquired by Fractionated Radiotherapy

    SciTech Connect

    Shimura, Tsutomu; Kakuda, Satoshi; Ochiai, Yasushi; Kuwahara, Yoshikazu; Takai, Yoshihiro; Fukumoto, Manabu

    2011-06-01

    Purpose: Radioresistance is a major cause of treatment failure of radiotherapy (RT) in human cancer. We have recently revealed that acquired radioresistance of tumor cells induced by fractionated radiation is attributable to cyclin D1 overexpression as a consequence of the downregulation of GSK3{beta}-dependent cyclin D1 proteolysis mediated by a constitutively activated serine-threonine kinase, AKT. This prompted us to hypothesize that targeting the AKT/GSK3{beta}/cyclin D1 pathway may improve fractionated RT by suppressing acquired radioresistance of tumor cells. Methods and Materials: Two human tumor cell lines with acquired radioresistance were exposed to X-rays after incubation with either an AKT inhibitor, AKT/PKB signaling inhibitor-2 (API-2), or a Cdk4 inhibitor (Cdk4-I). Cells were then subjected to immunoblotting, clonogenic survival assay, cell growth analysis, and cell death analysis with TUNEL and annexin V staining. In vivo radiosensitivity was assessed by growth of human tumors xenografted into nude mice. Results: Treatment with API-2 resulted in downregulation of cyclin D1 expression in cells with acquired radioresistance. Cellular radioresistance disappeared completely both in vitro and in vivo with accompanying apoptosis when treated with API-2. Furthermore, inhibition of cyclin D1/Cdk4 by Cdk4-I was sufficient for abolishing radioresistance. Treatment with either API-2 or Cdk4-I was also effective in suppressing resistance to cis-platinum (II)-diamine-dichloride in the cells with acquired radioresistance. Interestingly, the radiosensitizing effect of API-2 was canceled by overexpression of cyclin D1 whereas Cdk4-I was still able to sensitize cells with cyclin D1 overexpression. Conclusion: Cyclin D1/Cdk4 is a critical target of the AKT survival signaling pathway responsible for tumor radioresistance. Targeting the AKT/GSK3{beta}/cyclin D1/Cdk4 pathway would provide a novel approach to improve fractionated RT and would have an impact on tumor

  2. Nitrite therapy improves survival postexposure to chlorine gas

    PubMed Central

    Honavar, Jaideep; Doran, Stephen; Oh, Joo-Yeun; Steele, Chad; Matalon, Sadis

    2014-01-01

    Exposure to relatively high levels of chlorine (Cl2) gas can occur in mass-casualty scenarios associated with accidental or intentional release. Recent studies have shown a significant postexposure injury phase to the airways, pulmonary, and systemic vasculatures mediated in part by oxidative stress, inflammation, and dysfunction in endogenous nitric oxide homeostasis pathways. However, there is a need for therapeutics that are amenable to rapid and easy administration in the field and that display efficacy toward toxicity after chlorine exposure. In this study, we tested whether nitric oxide repletion using nitrite, by intramuscular injection after Cl2 exposure, could prevent Cl2 gas toxicity. C57bl/6 male mice were exposed to 600 parts per million Cl2 gas for 45 min, and 24-h survival was determined with or without postexposure intramuscular nitrite injection. A single injection of nitrite (10 mg/kg) administered either 30 or 60 min postexposure significantly improved 24-h survival (from ∼20% to 50%). Survival was associated with decreased neutrophil accumulation in the airways. Rendering mice neutropenic before Cl2 exposure improved survival and resulted in loss of nitrite-dependent survival protection. Interestingly, female mice were more sensitive to Cl2-induced toxicity compared with males and were also less responsive to postexposure nitrite therapy. These data provide evidence for efficacy and define therapeutic parameters for a single intramuscular injection of nitrite as a therapeutic after Cl2 gas exposure that is amenable to administration in mass-casualty scenarios. PMID:25326579

  3. PSA nadir as a predictive factor for biochemical disease-free survival and overall survival following whole-gland salvage HIFU following radiotherapy failure

    PubMed Central

    Shah, T T; Peters, M; Kanthabalan, A; McCartan, N; Fatola, Y; van der Voort van Zyp, J; van Vulpen, M; Freeman, A; Moore, C M; Arya, M; Emberton, M; Ahmed, H U

    2016-01-01

    Background: Treatment options for radio-recurrent prostate cancer are either androgen-deprivation therapy or salvage prostatectomy. Whole-gland high-intensity focussed ultrasound (HIFU) might have a role in this setting. Methods: An independent HIFU registry collated consecutive cases of HIFU. Between 2005 and 2012, we identified 50 men who underwent whole-gland HIFU following histological confirmation of localised disease following prior external beam radiotherapy (2005–2012). No upper threshold was applied for risk category, PSA or Gleason grade either at presentation or at the time of failure. Progression was defined as a composite with biochemical failure (Phoenix criteria (PSA>nadir+2 ng ml−1)), start of systemic therapies or metastases. Results: Median age (interquartile range (IQR)), pretreatment PSA (IQR) and Gleason score (range) were 68 years (64–72), 5.9 ng ml−1 (2.2–11.3) and 7 (6–9), respectively. Median follow-up was 64 months (49–84). In all, 24/50 (48%) avoided androgen-deprivation therapies. Also, a total of 28/50 (56%) achieved a PSA nadir <0.5 ng ml−1, 15/50 (30%) had a nadir ⩾0.5 ng ml−1 and 7/50 (14%) did not nadir (PSA non-responders). Actuarial 1, 3 and 5-year progression-free survival (PFS) was 72, 40 and 31%, respectively. Actuarial 1, 3 and 5-year overall survival (OS) was 100, 94 and 87%, respectively. When comparing patients with PSA nadir <0.5 ng ml−1, nadir ⩾0.5 and non-responders, a statistically significant difference in PFS was seen (P<0.0001). Three-year PFS in each group was 57, 20 and 0%, respectively. Five-year OS was 96, 100 and 38%, respectively. Early in the learning curve, between 2005 and 2007, 3/50 (6%) developed a fistula. Intervention for bladder outlet obstruction was needed in 27/50 (54%). Patient-reported outcome measure questionnaires showed incontinence (any pad-use) as 8/26 (31%). Conclusions: In our series of high-risk patients, in whom 30–50% may have micro

  4. PSA nadir as a predictive factor for biochemical disease-free survival and overall survival following whole-gland salvage HIFU following radiotherapy failure.

    PubMed

    Shah, T T; Peters, M; Kanthabalan, A; McCartan, N; Fatola, Y; van der Voort van Zyp, J; van Vulpen, M; Freeman, A; Moore, C M; Arya, M; Emberton, M; Ahmed, H U

    2016-09-01

    Treatment options for radio-recurrent prostate cancer are either androgen-deprivation therapy or salvage prostatectomy. Whole-gland high-intensity focussed ultrasound (HIFU) might have a role in this setting. An independent HIFU registry collated consecutive cases of HIFU. Between 2005 and 2012, we identified 50 men who underwent whole-gland HIFU following histological confirmation of localised disease following prior external beam radiotherapy (2005-2012). No upper threshold was applied for risk category, PSA or Gleason grade either at presentation or at the time of failure. Progression was defined as a composite with biochemical failure (Phoenix criteria (PSA>nadir+2 ng ml(-1))), start of systemic therapies or metastases. Median age (interquartile range (IQR)), pretreatment PSA (IQR) and Gleason score (range) were 68 years (64-72), 5.9 ng ml(-1) (2.2-11.3) and 7 (6-9), respectively. Median follow-up was 64 months (49-84). In all, 24/50 (48%) avoided androgen-deprivation therapies. Also, a total of 28/50 (56%) achieved a PSA nadir <0.5 ng ml(-1), 15/50 (30%) had a nadir ⩾0.5 ng ml(-1) and 7/50 (14%) did not nadir (PSA non-responders). Actuarial 1, 3 and 5-year progression-free survival (PFS) was 72, 40 and 31%, respectively. Actuarial 1, 3 and 5-year overall survival (OS) was 100, 94 and 87%, respectively. When comparing patients with PSA nadir <0.5 ng ml(-1), nadir ⩾0.5 and non-responders, a statistically significant difference in PFS was seen (P<0.0001). Three-year PFS in each group was 57, 20 and 0%, respectively. Five-year OS was 96, 100 and 38%, respectively. Early in the learning curve, between 2005 and 2007, 3/50 (6%) developed a fistula. Intervention for bladder outlet obstruction was needed in 27/50 (54%). Patient-reported outcome measure questionnaires showed incontinence (any pad-use) as 8/26 (31%). In our series of high-risk patients, in whom 30-50% may have micro-metastases, disease control rates were promising in PSA

  5. Exhaled pentane as a possible marker for survival and lipid peroxidation during radiotherapy for lung cancer--a pilot study.

    PubMed

    Crohns, Marika; Saarelainen, Seppo; Laitinen, Jukka; Peltonen, Kimmo; Alho, Hannu; Kellokumpu-Lehtinen, Pirkko

    2009-10-01

    To examine lipid peroxidation during radiotherapy (RT), exhaled pentane samples were collected from 11 lung cancer patients before RT and 30 and 120 min after the start of RT on days 1, 4 and 5 and at 30 and 40 Grays, if possible. Exhaled pentane samples were collected once from 30 healthy controls. Serum thiobarbituric-acid-reactive substances (TBARS) and conjugated dienes (CD) were obtained from patients on each exhaled air collection day. Lung cancer patients had higher exhaled pentane levels than controls (1.73 ng/L vs 0.83 ng/L, p=0.017). Exhaled pentane levels tended to decrease during the first RT day (p=0.075) and levels of CD decreased during the first week of RT (p=0.014). Higher pre-treatment pentane levels predicted better survival (p=0.003). Elevated exhaled pentane levels before RT may be due to the lipid peroxidation burden associated with cancer. The decrease of lipid peroxidation markers during RT may be attributable to enhanced antioxidant defense mechanisms.

  6. Quality of life as predictor of survival: a prospective study on patients treated with combined surgery and radiotherapy for advanced oral and oropharyngeal cancer.

    PubMed

    Oskam, Inge M; Verdonck-de Leeuw, Irma M; Aaronson, Neil K; Kuik, Dirk J; de Bree, Remco; Doornaert, Patricia; Langendijk, Johannes A; Leemans, C René

    2010-11-01

    The relation between health-related quality of life (HRQOL) and survival was investigated at baseline and 6 months in 80 patients with advanced oral or oropharyngeal cancer after microvascular reconstructive surgery and (almost all) adjuvant radiotherapy. Multivariate Cox regression analyses of overall and disease-specific survival were performed including sociodemographic (age, gender, marital status, comorbidity), and clinical (tumor stage and site, radical surgical, metastasis, radiotherapy) parameters, and HRQOL (EORTC QLQ-C30 global quality of life scale). Before treatment, younger age and having a partner were predictors of disease-specific survival; younger age predicted overall survival. At 6 months post-treatment, disease-specific and overall survival was predicted by (deterioration of) global quality of life solely. Global health-related quality of life after treatment was mainly influenced by emotional functioning. Deterioration of global quality of life after treatment is an independent predictor of survival in patients with advanced oral or oropharyngeal cancer. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  7. Improved survival of children and adolescents with sickle cell disease.

    PubMed

    Quinn, Charles T; Rogers, Zora R; McCavit, Timothy L; Buchanan, George R

    2010-04-29

    The survival of young children with sickle cell disease (SCD) has improved, but less is known about older children and adolescents. We studied the Dallas Newborn Cohort (DNC) to estimate contemporary 18-year survival for newborns with SCD and document changes in the causes and ages of death over time. We also explored whether improvements in the quality of medical care were temporally associated with survival. The DNC now includes 940 subjects with 8857 patient-years of follow-up. Most children with sickle cell anemia (93.9%) and nearly all children with milder forms of SCD (98.4%) now live to become adults. The incidence of death and the pattern of mortality changed over the duration of the cohort. Sepsis is no longer the leading cause of death. All the recent deaths in the cohort occurred in patients 18 years or older, most shortly after the transition to adult care. Quality of care in the DNC has improved over time, with significantly more timely initial visits and preventive interventions for young children. In summary, most children with SCD now survive the childhood years, but young adults who transition to adult medical care are at high risk for early death.

  8. [Recurrent breast cancer obtained long-term survival with local treatment(surgery and stereotactic body radiotherapy)and systemic therapy].

    PubMed

    Morioka, Emi; Ohno, Yukako; Noguchi, Miki; Nakano, Yasuharu; Noguchi, Masakuni; Kosaka, Takeo; Takanaka, Tsuyoshi

    2012-11-01

    A 52-year-old woman developed right breast cancer and underwent modified radical mastectomy in 1994. Histologically, the tumor was invasive ductal carcinoma. She was positive for estrogen receptor (ER) but negative for progesterone receptor(PgR), while her human epidermal growth factor receptor type 2(HER2) status was not examined. Although she received adjuvant hormone therapy and chemotherapy[cyclophosphamide+doxorubicin+5-fluorouraci(l CAF), 6 courses ], she underwent partial pulmonary resection on both sides with right oophorectomy in 1997. Subsequently, she was treated with weekly doses paclitaxel(12 courses). However, she developed a pulmonary metastasis in the left breast. In 2002, she underwent a partial left pulmonary resection (ER-positive and HER2 3+) and treatment with an aromatase inhibitor. Subsequently, she was treated with trastuzumab because of repeated lung metastasis. A complete response was obtained after the administration of trastuzumab. In 2008, she developed bone metastasis in the sternum and the left seventh rib, and subsequently underwent stereotactic body radiotherapy (SBRT). She was treated with trastuzumab and aromatase inhibitor. At present, she is free of pain and is still living 15 years after breast cancer recurrence. This case suggests that the interaction of local treatment(surgery and SBRT) and systemic therapy(chemotherapy, hormonal therapy, and monoclonal therapy) may improve the survival of patients with recurrent breast cancer.

  9. Improvement in toxicity in high risk prostate cancer patients treated with image-guided intensity-modulated radiotherapy compared to 3D conformal radiotherapy without daily image guidance

    PubMed Central

    2014-01-01

    Background Image-guided radiotherapy (IGRT) facilitates the delivery of a very precise radiation dose. In this study we compare the toxicity and biochemical progression-free survival between patients treated with daily image-guided intensity-modulated radiotherapy (IG-IMRT) and 3D conformal radiotherapy (3DCRT) without daily image guidance for high risk prostate cancer (PCa). Methods A total of 503 high risk PCa patients treated with radiotherapy (RT) and endocrine treatment between 2000 and 2010 were retrospectively reviewed. 115 patients were treated with 3DCRT, and 388 patients were treated with IG-IMRT. 3DCRT patients were treated to 76 Gy and without daily image guidance and with 1–2 cm PTV margins. IG-IMRT patients were treated to 78 Gy based on daily image guidance of fiducial markers, and the PTV margins were 5–7 mm. Furthermore, the dose-volume constraints to both the rectum and bladder were changed with the introduction of IG-IMRT. Results The 2-year actuarial likelihood of developing grade > = 2 GI toxicity following RT was 57.3% in 3DCRT patients and 5.8% in IG-IMRT patients (p < 0.001). For GU toxicity the numbers were 41.8% and 29.7%, respectively (p = 0.011). On multivariate analysis, 3DCRT was associated with a significantly increased risk of developing grade > = 2 GI toxicity compared to IG-IMRT (p < 0.001, HR = 11.59 [CI: 6.67-20.14]). 3DCRT was also associated with an increased risk of developing GU toxicity compared to IG-IMRT. The 3-year actuarial biochemical progression-free survival probability was 86.0% for 3DCRT and 90.3% for IG-IMRT (p = 0.386). On multivariate analysis there was no difference in biochemical progression-free survival between 3DCRT and IG-IMRT. Conclusion The difference in toxicity can be attributed to the combination of the IMRT technique with reduced dose to organs-at-risk, daily image guidance and margin reduction. PMID:24495815

  10. Effect of radiotherapy delay in overall treatment time on local control and survival in head and neck cancer: Review of the literature

    PubMed Central

    González Ferreira, José A.; Jaén Olasolo, Javier; Azinovic, Ignacio; Jeremic, Branislav

    2015-01-01

    Treatment delays in completing radiotherapy (RT) for many neoplasms are a major problem affecting treatment outcome, as increasingly shown in the literature. Overall treatment time (OTT) could be a critical predictor of local tumor control and/or survival. In an attempt to establish a protocol for managing delays during RT, especially for heavily overloaded units, we have extensively reviewed the available literature on head and neck cancer. We confirmed a large deleterious effect of prolonged OTT on both local control and survival of these patients. PMID:26549990

  11. Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia

    PubMed Central

    Rockman-Greenberg, Cheryl; Ozono, Keiichi; Riese, Richard; Moseley, Scott; Melian, Agustin; Thompson, David D.; Bishop, Nicholas; Hofmann, Christine

    2016-01-01

    Context: Hypophosphatasia (HPP) is an inborn error of metabolism that, in its most severe perinatal and infantile forms, results in 50–100% mortality, typically from respiratory complications. Objectives: Our objective was to better understand the effect of treatment with asfotase alfa, a first-in-class enzyme replacement therapy, on mortality in neonates and infants with severe HPP. Design/Setting: Data from patients with the perinatal and infantile forms of HPP in two ongoing, multicenter, multinational, open-label, phase 2 interventional studies of asfotase alfa treatment were compared with data from similar patients from a retrospective natural history study. Patients: Thirty-seven treated patients (median treatment duration, 2.7 years) and 48 historical controls of similar chronological age and HPP characteristics. Interventions: Treated patients received asfotase alfa as sc injections either 1 mg/kg six times per week or 2 mg/kg thrice weekly. Main Outcome Measures: Survival, skeletal health quantified radiographically on treatment, and ventilatory status were the main outcome measures for this study. Results: Asfotase alfa was associated with improved survival in treated patients vs historical controls: 95% vs 42% at age 1 year and 84% vs 27% at age 5 years, respectively (P < .0001, Kaplan-Meier log-rank test). Whereas 5% (1/20) of the historical controls who required ventilatory assistance survived, 76% (16/21) of the ventilated and treated patients survived, among whom 75% (12/16) were weaned from ventilatory support. This better respiratory outcome accompanied radiographic improvements in skeletal mineralization and health. Conclusions: Asfotase alfa mineralizes the HPP skeleton, including the ribs, and improves respiratory function and survival in life-threatening perinatal and infantile HPP. PMID:26529632

  12. Radiotherapy and local control in rectal cancer.

    PubMed

    Valentini, V; Rosetto, M E; Fares, C; Mantini, G; Salvi, G; Turriziani, A

    1998-01-01

    Recurrence is a stage in the natural history of rectal cancer. Preoperative radiotherapy or postoperative radiochemotherapy lower the rate of recurrence, improving local control. From 1980 to 1997, at the "Divisione di Radioterapia" of the "Università Cattolica del S. Cuore" of Rome 380 patients with rectal cancer of early clinical stage T2-3, candidates for surgery for cure, underwent radiation therapy. 119 patients underwent postoperative radiotherapy (45-50 Gy); 45 patients underwent "sandwich" radiotherapy (45 Gy:27 Gy before and 28 Gy after surgery), of whom 7 were treated with preoperative radiotherapy alone; 145 patients underwent preoperative concomitant radiochemotherapy according to 3 different protocols, radiotherapy (38 Gy) combined with mitomycin C and 5-FU; radiotherapy (50.4 Gy) combined with cisplatin and 5-FU; radiotherapy (45 Gy) combined with 5-FU and folinic acid. 71 patients were treated with preoperative radiotherapy (38 Gy) combined with IORT (10 Gy). Median follow-up was 6 years. Overall local control was 85% at 3 years, 83% at 5 years, 81% at 10 years. The rate of local control at 5 years was: 76% for postoperative radiotherapy, 83% for "sandwich" radiotherapy, 84% for preoperative radiochemotherapy and 93% for preoperative radiotherapy combined with IORT. Local control was shown to be significantly better with preoperative treatment as compared to postoperative treatment (p = 0.02). The incidence of metastases was 35% in the patients with local recurrence and 16% in those with local control. The difference in survival was highly significant in patients with local control as compared to those with local recurrence: at 5 years 87% and 32% respectively. Patients with local control showed a lower incidence of metastasis and a better survival.

  13. [Preliminary application of an improved Demons deformable registration algorithm in tumor radiotherapy].

    PubMed

    Zhou, Lu; Zhen, Xin; Lu, Wenting; Dou, Jianhong; Zhou, Linghong

    2012-01-01

    To validate the efficiency of an improved Demons deformable registration algorithm and evaluate its application in registration of the treatment image and the planning image in image-guided radiotherapy (IGRT). Based on Brox's gradient constancy assumption and Malis's efficient second-order minimization algorithm, a grey value gradient similarity term was added into the original energy function, and a formula was derived to calculate the update of transformation field. The limited Broyden-Fletcher-Goldfarb-Shanno (L-BFGS) algorithm was used to optimize the energy function for automatic determination of the iteration number. The proposed algorithm was validated using mathematically deformed images, physically deformed phantom images and clinical tumor images. Compared with the original Additive Demons algorithm, the improved Demons algorithm achieved a higher precision and a faster convergence speed. Due to the influence of different scanning conditions in fractionated radiation, the density range of the treatment image and the planning image may be different. The improved Demons algorithm can achieve faster and more accurate radiotherapy.

  14. The survival outcome and patterns of failure in node positive endometrial cancer patients treated with surgery and adjuvant radiotherapy with curative intent.

    PubMed

    Rajasooriyar, Chrishanthi; Bernshaw, David; Kondalsamy-Chennakesavan, Srinivas; Mileshkin, Linda; Narayan, Kailash

    2014-10-01

    The purpose of this study was to evaluate the patterns of failure, overall survival (OS), disease-free survival (DFS) and factors influencing outcome in endometrial cancer patients who presented with metastatic lymph nodes and were treated with curative intent. One hundred and twenty-six patients treated between January 1996 to December 2008 with surgery and adjuvant radiotherapy were identified from our service's prospective database. Radiotherapy consisted of 45 Gy in 1.8 Gy fractions to the whole pelvis. The involved nodal sites were boosted to a total dose of 50.4 to 54 Gy. The 5-year OS rate was 61% and the 5-year DFS rate was 59%. Grade 3 endometrioid, serous, and clear cell histologies and involvement of upper para-aortic nodes had lower OS and DFS. The number of positive nodes did not influence survival. Among the histological groups, serous histology had the worst survival. Among the 54 patients relapsed, only three (6%) failed exclusively in the pelvis and the rest of the 94% failed in extrapelvic nodal or distant sites. Patients with grade 3 endometrioid, serous and clear cell histologies did not influence pelvic failure but had significant extrapelvic failures (p<0.001). Majority of node positive endometrial cancer patients fail at extrapelvic sites. The most important factors influencing survival and extrapelvic failure are grade 3 endometrioid, clear cell and serous histologies and involvement of upper para-aortic nodes.

  15. The survival outcome and patterns of failure in node positive endometrial cancer patients treated with surgery and adjuvant radiotherapy with curative intent

    PubMed Central

    Bernshaw, David; Kondalsamy-Chennakesavan, Srinivas; Mileshkin, Linda; Narayan, Kailash

    2014-01-01

    Objective The purpose of this study was to evaluate the patterns of failure, overall survival (OS), disease-free survival (DFS) and factors influencing outcome in endometrial cancer patients who presented with metastatic lymph nodes and were treated with curative intent. Methods One hundred and twenty-six patients treated between January 1996 to December 2008 with surgery and adjuvant radiotherapy were identified from our service's prospective database. Radiotherapy consisted of 45 Gy in 1.8 Gy fractions to the whole pelvis. The involved nodal sites were boosted to a total dose of 50.4 to 54 Gy. Results The 5-year OS rate was 61% and the 5-year DFS rate was 59%. Grade 3 endometrioid, serous, and clear cell histologies and involvement of upper para-aortic nodes had lower OS and DFS. The number of positive nodes did not influence survival. Among the histological groups, serous histology had the worst survival. Among the 54 patients relapsed, only three (6%) failed exclusively in the pelvis and the rest of the 94% failed in extrapelvic nodal or distant sites. Patients with grade 3 endometrioid, serous and clear cell histologies did not influence pelvic failure but had significant extrapelvic failures (p<0.001). Conclusion Majority of node positive endometrial cancer patients fail at extrapelvic sites. The most important factors influencing survival and extrapelvic failure are grade 3 endometrioid, clear cell and serous histologies and involvement of upper para-aortic nodes. PMID:25142629

  16. The kallikrein-kinin-system in head and neck squamous cell carcinoma (HNSCC) and its role in tumour survival, invasion, migration and response to radiotherapy.

    PubMed

    Beck, Carolin; Piontek, Guido; Haug, Anna; Bas, Murat; Knopf, Andreas; Stark, Thomas; Mißlbeck, Martin; Rudelius, Martina; Reiter, Rudolf; Brandstetter, Markus; Pickhard, Anja

    2012-12-01

    In this study, we investigated the role of the kallikrein-kinin-system in head and neck squamous cell carcinoma (HNSCC) and its implication on tumour survival, invasion, migration and response to radiotherapy. The expression of BKB2R was studied in a series of 180 tumour samples to determine the functional significance of BKB2R in HNSCC. Additionally, four different HNSCC cell lines were treated with an irradiation dose of 8Gy following bradykinin receptor stimulation or blockage. Tumour cell survival was tested using a colony formation assay. The invasive potential of tumour cells was assessed using Matrigel invasion chambers, the cells' ability to migrate was determined with a wound-healing assay. To examine the biochemical activation of BKB2R, the epidermal growth factor receptor (EGFR) and its downstream pathways, western blot analyses were conducted. Immunohistochemistry revealed an over-expression of BKB2R in HNSCC tumour cells in comparison to normal peritumoural tissue. Blocking the BKB2R at irradiated tumour cells led to a reduced response to radiotherapy of tumour cells and led to an activation of the EGFR and its downstream pathways, known mediators of tumour cell survival, migration and invasion. Bradykinin stimulation also resulted in a better tumour cell survival, but these effects were achieved via an EGFR-independent signalling. Our results demonstrate that the kallikrein-kinin-system is involved in survival, invasion and migration of HNSCC cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Concomitant treatment of brain metastasis with Whole Brain Radiotherapy [WBRT] and Temozolomide [TMZ] is active and improves Quality of Life

    PubMed Central

    Addeo, Raffaele; Caraglia, Michele; Faiola, Vincenzo; Capasso, Elena; Vincenzi, Bruno; Montella, Liliana; Guarrasi, Rosario; Caserta, Luigi; Del Prete, Salvatore

    2007-01-01

    Background Brain metastases (BM) represent one of the most frequent complications related to cancer, and their treatment continues to evolve. We have evaluated the activity, toxicity and the impact on Quality of Life (QoL) of a concomitant treatment with whole brain radiotherapy (WBRT) and Temozolomide (TMZ) in patients with brain metastases from solid tumors in a prospective Simon two stage study. Methods Fifty-nine patients were enrolled and received 30 Gy WBRT with concomitant TMZ (75 mg/m2/day) for ten days, and subsequently TMZ (150 mg/m2/day) for up to six cycles. The primary end points were clinical symptoms and radiologic response. Results Five patients had a complete response, 21 patients had a partial response, while 18 patients had stable disease. The overall response rate (45%) exceeded the target activity per study design. The median time to progression was 9 months. Median overall survival was 13 months. The most frequent toxicities included grade 3 neutropenia (15%) and anemia (13%), and only one patient developed a grade 4 thrombocytopenia. Age, Karnofsky performance status, presence of extracranial metastases and the recursive partitioning analysis (RPA) were found to be predictive factors for response in patients. Overall survival (OS) and progression-free survival (PFS) were dependent on age and on the RPA class. Conclusion We conclude that this treatment is well tolerated, with an encouraging objective response rate, and a significant improvement in quality of life (p < 0.0001) demonstrated by FACT-G analysis. All patients answered the questionnaires and described themselves as 'independent' and able to act on their own initiatives. Our study found a high level of satisfaction for QoL, this provides useful information to share with patients in discussions regarding chemotherapy treatment of these lesions. PMID:17254350

  18. Temozolomide treatment can improve overall survival in aggressive pituitary tumors and pituitary carcinomas.

    PubMed

    Lasolle, Hélène; Cortet, Christine; Castinetti, Fréderic; Cloix, Lucie; Caron, Philippe; Delemer, Brigitte; Desailloud, Rachel; Jublanc, Christel; Lebrun-Frenay, Christine; Sadoul, Jean-Louis; Taillandier, Luc; Batisse-Lignier, Marie; Bonnet, Fabrice; Bourcigaux, Nathalie; Bresson, Damien; Chabre, Olivier; Chanson, Philippe; Garcia, Cyril; Haissaguerre, Magalie; Reznik, Yves; Borot, Sophie; Villa, Chiara; Vasiljevic, Alexandre; Gaillard, Stephan; Jouanneau, Emmanuel; Assié, Guillaume; Raverot, Gérald

    2017-06-01

    Only few retrospective studies have reported an efficacy rate of temozolomide (TMZ) in pituitary tumors (PT), all around 50%. However, the long-term survival of treated patients is rarely evaluated. We therefore aimed to describe the use of TMZ on PT in clinical practice and evaluate the long-term survival. Multicenter retrospective study by members of the French Society of Endocrinology. Forty-three patients (14 women) treated with TMZ between 2006 and 2016 were included. Most tumors were corticotroph (n = 23) or lactotroph (n = 13), and 14 were carcinomas. Clinical/pathological characteristics of PT, as well as data from treatment evaluation and from the last follow-up were recorded. A partial response was considered as a decrease in the maximal tumor diameter by more than 30% and/or in the hormonal rate by more than 50% at the end of treatment. The median treatment duration was 6.5 cycles (range 2-24), using a standard regimen for most and combined radiotherapy for six. Twenty-two patients (51.2%) were considered as responders. Silent tumor at diagnosis was associated with a poor response. The median follow-up after the end of treatment was 16 months (0-72). Overall survival was significantly higher among responders (P = 0.002); however, ten patients relapsed 5 months (0-57) after the end of TMZ treatment, five in whom TMZ was reinitiated without success. Patients in our series showed a 51.2% response rate to TMZ, with an improved survival among responders despite frequent relapses. Our study highlights the high variability and lack of standardization of treatment protocols. © 2017 European Society of Endocrinology.

  19. STI571 (Gleevec) improves tumor growth delay and survival in irradiated mouse models of glioblastoma

    SciTech Connect

    Geng Ling; Shinohara, Eric T.; Kim, Dong; Tan Jiahuai; Osusky, Kate; Shyr, Yu; Hallahan, Dennis E. . E-mail: Dennis.Hallahan@mcmail.vanderbilt.edu

    2006-01-01

    Purpose: Glioblastoma multiforme (GBM) is a devastating brain neoplasm that is essentially incurable. Although radiation therapy prolongs survival, GBMs progress within areas of irradiation. Recent studies in invertebrates have shown that STI571 (Gleevec; Novartis, East Hanover, NJ) enhances the cytotoxicity of ionizing radiation. In the present study, the effectiveness of STI571 in combination with radiation was studied in mouse models of GBM. Methods and Materials: Murine GL261 and human D54 GBM cell lines formed tumors in brains and hind limbs of C57BL6 and nude mice, respectively. GL261 and D54 cells were treated with 5 {mu}mol/L of STI571 for 1 h and/or irradiated with 3 Gy. Protein was analyzed by Western immunoblots probed with antibodies to caspase 3, cleaved caspase 3, phospho-Akt, Akt, and platelet-derived growth factor receptor (PDGFR) {alpha} and {beta}. Tumor volumes were assessed in mice bearing GL261 or D54 tumors treated with 21 Gy administered in seven fractionated doses. Histologic sections from STI571-treated mice were stained with phospho-Akt and phospho-PDGFR {beta} antibodies. Kaplan-Meier survival curves were used to study the response of mice bearing intracranial implants of GL261. Results: STI571 penetrated the blood-brain barrier, which resulted in a reduction in phospho-PDGFR in GBM. STI571-induced apoptosis in GBM was significantly enhanced by irradiation. STI571 combined with irradiation induced caspase 3 cleavage in GBM cells. Glioblastoma multiforme response to therapy correlated with an increase in tumor growth delay and survival when STI571 was administered in conjunction with daily irradiation. Conclusion: These findings suggest that STI571 has the potential to augment radiotherapy and thereby improve median survival.

  20. Benefit of Adjuvant Radiotherapy for Local Control, Distant Metastasis, and Survival Outcomes in Patients with Localized Soft Tissue Sarcoma: Comparative Effectiveness Analysis of an Observational Cohort Study.

    PubMed

    Posch, Florian; Partl, Richard; Döller, Carmen; Riedl, Jakob M; Smolle, Maria; Leitner, Lukas; Bergovec, Marko; Liegl-Atzwanger, Bernadette; Stotz, Michael; Bezan, Angelika; Gerger, Armin; Pichler, Martin; Kapp, Karin S; Stöger, Herbert; Leithner, Andreas; Szkandera, Joanna

    2017-09-11

    This study aimed to quantify the benefit of adjuvant radiotherapy (AXRT) for local control, distant metastasis, and long-term survival outcomes in patients with localized soft tissue sarcoma (STS). This single-center retrospective observational study enrolled 433 STS patients who underwent surgery with curative intent. An inverse probability of treatment-weighted (IPTW) analysis was implemented to account rigorously for imbalances in prognostic variables between the adjuvant treatment groups. During a median follow-up period of 5.5 years, the study observed 38 local recurrences (9%), 73 occurrences of distant metastasis (17%), 63 STS-related deaths (15%), and 57 deaths from other causes (13%). As expected, patients receiving AXRT (n = 258, 60%) were more likely to have high-grade G3 tumors (p < 0.0001) than patients not receiving AXRT. A crude analysis showed that AXRT was not associated with improved recurrence-free survival [hazard ratio (HR) 1.00; 95% confidence interval (CI) 0.72-1.38; p = 0.98]. However, after IPTW, AXRT was associated with a 38% relative reduction in the risk of recurrence or death (HR 0.62; 95% CI 0.39-1.00; p = 0.05). This benefit was driven by a strong reduction in the risk of local recurrence (HR 0.42; 95% CI 0.19-0.91; p = 0.03), whereas the relative risk of distant metastasis (HR 0.69; 95% CI 0.39-1.25; p = 0.22) and overall survival (HR 0.76; 95% CI 0.44-1.30; p = 0.32) were only nonsignificantly in favor of AXRT. An exploratory analysis showed an overall survival benefit of AXRT for patients with high-grade G3 tumors (HR 0.51; 95% CI 0.33-0.78; p = 0.002). However, this finding may have been attributable to residual confounding. In this observational cohort, AXRT was associated with a 58% reduction in the relative risk of local recurrence. No consistent association between AXRT and lower risks of distant metastasis or death was observed.

  1. Improving rotorcraft survivability to RPG attack using inverse methods

    NASA Astrophysics Data System (ADS)

    Anderson, D.; Thomson, D. G.

    2009-09-01

    This paper presents the results of a preliminary investigation of optimal threat evasion strategies for improving the survivability of rotorcraft under attack by rocket propelled grenades (RPGs). The basis of this approach is the application of inverse simulation techniques pioneered for simulation of aggressive helicopter manoeuvres to the RPG engagement problem. In this research, improvements in survivability are achieved by computing effective evasive manoeuvres. The first step in this process uses the missile approach warning system camera (MAWS) on the aircraft to provide angular information of the threat. Estimates of the RPG trajectory and impact point are then estimated. For the current flight state an appropriate evasion response is selected then realised via inverse simulation of the platform dynamics. Results are presented for several representative engagements showing the efficacy of the approach.

  2. Peripherally administered orexin improves survival of mice with endotoxin shock

    PubMed Central

    Ogawa, Yasuhiro; Irukayama-Tomobe, Yoko; Murakoshi, Nobuyuki; Kiyama, Maiko; Ishikawa, Yui; Hosokawa, Naoto; Tominaga, Hiromu; Uchida, Shuntaro; Kimura, Saki; Kanuka, Mika; Morita, Miho; Hamada, Michito; Takahashi, Satoru; Hayashi, Yu; Yanagisawa, Masashi

    2016-01-01

    Sepsis is a systemic inflammatory response to infection, accounting for the most common cause of death in intensive care units. Here, we report that peripheral administration of the hypothalamic neuropeptide orexin improves the survival of mice with lipopolysaccharide (LPS) induced endotoxin shock, a well-studied septic shock model. The effect is accompanied by a suppression of excessive cytokine production and an increase of catecholamines and corticosterone. We found that peripherally administered orexin penetrates the blood-brain barrier under endotoxin shock, and that central administration of orexin also suppresses the cytokine production and improves the survival, indicating orexin’s direct action in the central nervous system (CNS). Orexin helps restore body temperature and potentiates cardiovascular function in LPS-injected mice. Pleiotropic modulation of inflammatory response by orexin through the CNS may constitute a novel therapeutic approach for septic shock. DOI: http://dx.doi.org/10.7554/eLife.21055.001 PMID:28035899

  3. Stereotactic body radiotherapy versus lobectomy for operable clinical stage IA lung adenocarcinoma: comparison of survival outcomes in two clinical trials with propensity score analysis (JCOG1313-A).

    PubMed

    Eba, Junko; Nakamura, Kenichi; Mizusawa, Junki; Suzuki, Kenji; Nagata, Yasushi; Koike, Teruaki; Hiraoka, Masahiro; Watanabe, Shun-Ichi; Ishikura, Satoshi; Asamura, Hisao; Fukuda, Haruhiko

    2016-08-01

    No randomized controlled trials comparing stereotactic body radiotherapy and lobectomy for operable early-stage non-small-cell lung cancer have been successfully conducted. This study compared survival outcomes in two multi-institutional clinical trials for stereotactic body radiotherapy (Japan Clinical Oncology Group JCOG0403) and lobectomy (Japan Clinical Oncology Group JCOG0201) with propensity score analysis. Inclusion criteria were operable, cT1N0M0 and adenocarcinoma diagnosed prior to registration of each trial. Forty of 169 patients from JCOG0403 and 219 of 811 patients from JCOG0201 were included. The primary endpoint was overall survival adjusted with propensity score analysis. The patient selection factors included in the logistic model to estimate the propensity score were age, sex, tumor diameter and consolidation/tumor ratio. Among patient selection factors, age distribution was quite different with little overlap: the median was 79 (interquartile range: 74.5-83.5) in stereotactic body radiotherapy and 62 (interquartile range: 55-68) in lobectomy. In propensity score analysis, 21 patients from each group were matched and the hazard ratio for stereotactic body radiotherapy over lobectomy was 9.00 (95% confidence interval: 1.14-71.04). In the post hoc subgroup analysis with propensity score analysis of inverse probability of treatment weighting, patients were limited to be aged 75 or younger because JCOG0201 only included them when aged 75 or younger. Thirteen patients for stereotactic body radiotherapy and 219 for lobectomy were compared, and the hazard ratio for stereotactic body radiotherapy over lobectomy was 1.19 (95% confidence interval: 0.38-3.73). The point estimates of hazard ratio favored lobectomy over stereotactic body radiotherapy in the limited number of patients. A randomized controlled study is needed for valid comparison. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please

  4. Improving Oral Cancer Survival: The Role of Dental Providers

    PubMed Central

    MESSADI, DIANA V.; WILDER-SMITH, PETRA; WOLINSKY, LAWRENCE

    2010-01-01

    Oral cancer accounts for 2 percent to 4 percent of all cancers diagnosed each year in the United States. In contrast to other cancers, the overall U.S. survival rate from oral cancer has not improved during the past 50 years, mostly due to late-stage diagnosis. Several noninvasive oral cancer detection techniques that emerged in the past decade will be discussed, with a brief overview of most common oral cancer chemopreventive agents. PMID:19998655

  5. Improving survival rates after civilian gunshot wounds to the brain.

    PubMed

    Joseph, Bellal; Aziz, Hassan; Pandit, Viraj; Kulvatunyou, Narong; O'Keeffe, Terence; Wynne, Julie; Tang, Andrew; Friese, Randall S; Rhee, Peter

    2014-01-01

    Gunshot wounds to the brain are the most lethal of all firearm injuries, with reported survival rates of 10% to 15%. The aim of this study was to determine outcomes in patients with gunshot wounds to the brain, presenting to our institution over time. We hypothesized that aggressive management can increase survival and the rate of organ donation in patients with gunshot wounds to the brain. We analyzed all patients with gunshot wounds to the brain presenting to our level 1 trauma center over a 5-year period. Aggressive management was defined as resuscitation with blood products, hyperosmolar therapy, and/or prothrombin complex concentrate (PCC). The primary outcome was survival and the secondary outcome was organ donation. There were 132 patients with gunshot wounds to the brain, and the survival rates increased incrementally every year, from 10% in 2008 to 46% in 2011, with the adoption of aggressive management. Among survivors, 40% (16 of 40) of the patients had bi-hemispheric injuries. Aggressive management with blood products (p = 0.02) and hyperosmolar therapy (p = 0.01) was independently associated with survival. Of the survivors, 20% had a Glasgow Coma Scale score ≥ 13 at hospital discharge. In patients who died (n = 92), 56% patients were eligible for organ donation, and they donated 60 organs. Aggressive management is associated with significant improvement in survival and organ procurement in patients with gunshot wounds to the brain. The bias of resource use can no longer be used to preclude trauma surgeons from abandoning aggressive attempts to save patients with gunshot wound to the brain. Published by Elsevier Inc.

  6. Long term survival with stereotactic ablative radiotherapy (SABR) versus thoracoscopic sublobar lung resection in elderly people: national population based study with propensity matched comparative analysis

    PubMed Central

    Paul, Subroto; Lee, Paul C; Mao, Jialin; Isaacs, Abby J

    2016-01-01

    Objectives To compare cancer specific survival after thoracoscopic sublobar lung resection and stereotactic ablative radiotherapy (SABR) for tumors ≤2 cm in size and thoracoscopic resection (sublobar resection or lobectomy) and SABR for tumors ≤5 cm in size. Design National population based retrospective cohort study with propensity matched comparative analysis. Setting Surveillance, Epidemiology, and End Results (SEER) registry linked with Medicare database in the United States. Participants Patients aged ≥66 with lung cancer undergoing SABR or thoracoscopic lobectomy or sublobar resection from 1 Oct 2007 to 31 June 2012 and followed up to 31 December 2013. Main outcome measures Cancer specific survival after SABR or thoracoscopic surgery for lung cancer. Results 690 (275 (39.9%) SABR and 415 (60.1%) thoracoscopic sublobar lung resection) and 2967 (714 (24.1%) SABR and 2253 (75.9%) thoracoscopic resection) patients were included in primary and secondary analyses. The average age of the entire cohort was 76. Follow-up of the entire cohort ranged from 0 to 6.25 years, with an average of three years. In the primary analysis of patients with tumors sized ≤2 cm, 37 (13.5%) undergoing SABR and 44 (10.6%) undergoing thoracoscopic sublobar resection died from lung cancer, respectively. The cancer specific survival diverged after one year, but in the matched analysis (201 matched patients in each group) there was no significant difference between the groups (SABR v sublobar lung resection mortality: hazard ratio 1.32, 95% confidence interval 0.77 to 2.26; P=0.32). Estimated cancer specific survival at three years after SABR and thoracoscopic sublobar lung resection was 82.6% and 86.4%, respectively. The secondary analysis (643 matched patients in each group) showed that thoracoscopic resection was associated with improved cancer specific survival over SABR in patients with tumors sized ≤5 cm (SABR v resection mortality: hazard ratio 2.10, 1.52 to 2.89; P<0

  7. Resveratrol Improves Survival and Prolongs Life Following Hemorrhagic Shock

    PubMed Central

    Ayub, Ahmar; Poulose, Ninu; Raju, Raghavan

    2015-01-01

    Resveratrol has been shown to potentiate mitochondrial function and extend longevity; however, there is no evidence to support whether resveratrol can improve survival or prolong life following hemorrhagic shock. We sought to determine whether (a) resveratrol can improve survival following hemorrhage and resuscitation and (b) prolong life in the absence of resuscitation. Using a hemorrhagic injury (HI) model in the rat, we describe for the first time that the naturally occurring small molecule, resveratrol, may be an effective adjunct to resuscitation fluid. In a series of three sets of experiments we show that resveratrol administration during resuscitation improves survival following HI (p < 0.05), resveratrol and its synthetic mimic SRT1720 can significantly prolong life in the absence of resuscitation fluid (<30 min versus up to 4 h; p < 0.05), and resveratrol as well as SRT1720 restores left ventricular function following HI. We also found significant changes in the expression level of mitochondria-related transcription factors Ppar-α and Tfam, as well as Pgc-1α in the left ventricular tissues of rats subjected to HI and treated with resveratrol. The results indicate that resveratrol is a strong candidate adjunct to resuscitation following severe hemorrhage. PMID:25879628

  8. Preoperative or postoperative radiotherapy versus surgery alone for retroperitoneal sarcoma: a case-control, propensity score-matched analysis of a nationwide clinical oncology database.

    PubMed

    Nussbaum, Daniel P; Rushing, Christel N; Lane, Whitney O; Cardona, Diana M; Kirsch, David G; Peterson, Bercedis L; Blazer, Dan G

    2016-07-01

    -matched datasets. 9068 patients were included in this analysis: 563 in the preoperative radiotherapy group, 2215 in the postoperative radiotherapy group, and 6290 in the no radiotherapy group. Matching resulted in two comparison groups (preoperative radiotherapy vs no radiotherapy, and postoperative radiotherapy vs no radiotherapy) with negligible differences in all demographic, clinicopathological, and treatment-level variables. In the matched case-control analysis for preoperative radiotherapy median follow-up time was 42 months (IQR 27-70) for the preoperative radiotherapy group versus 43 months (25-64) for the no radiotherapy group; median overall survival was 110 months (95% CI 75-not estimable) versus 66 months (61-76), respectively. In the matched case-control analysis for postoperative radiotherapy median follow-up time was 54 months (IQR 32-79) for patients in the postoperative radiotherapy group and 47 months (26-72) for patients in the no radiotherapy group; median overall survival was 89 months (95% CI 79-100) versus 64 months (59-69), respectively. Both preoperative radiotherapy (HR 0·70, 95% CI 0·59-0·82; p<0·0001) and postoperative radiotherapy (HR 0·78, 0·71-0·85; p<0·0001) were significantly associated with improved overall survival compared with surgery alone. To the best of our knowledge, this is the largest study to date of the effect of radiotherapy on overall survival in patients with retroperitoneal sarcoma. Radiotherapy was associated with improved overall survival compared with surgery alone when delivered as either preoperative radiotherapy or postoperative radiotherapy. Together with the results from the ongoing randomised EORTC trial (62092-22092; NCT01344018) investigating preoperative radiotherapy for retroperitoneal sarcoma pending, these data might provide additional support for the increasing use of radiotherapy for patients with retroperitoneal sarcoma undergoing surgical resection. Department of Surgery, Duke University School of Medicine

  9. Assessment of improved organ at risk sparing for advanced cervix carcinoma utilizing precision radiotherapy techniques.

    PubMed

    Georg, Dietmar; Georg, Petra; Hillbrand, Martin; Pötter, Richard; Mock, Ulrike

    2008-11-01

    To evaluate the potential benefit of proton therapy and photon based intensity-modulated radiotherapy in comparison to 3-D conformal photon radiotherapy (3D-CRT) in locally advanced cervix cancer. In five patients with advanced cervix cancer 3D-CRT (four-field box) was compared with intensity modulated photon (IMXT) and proton therapy (IMPT) as well as proton beam therapy (PT) based on passive scattering. Planning target volumes (PTVs) included primary tumor and pelvic and para-aortic lymph nodes. Dose-volume histograms (DVHs) were analyzed for the PTV and various organs at risk (OARs) (rectal wall, bladder, small bowel, colon, femoral heads, and kidneys). In addition dose conformity, dose inhomogeneity and overall volumes of 50% isodoses were assessed. All plans were comparable concerning PTV parameters. Large differences between photon and proton techniques were seen in volumes of the 50% isodoses and conformity indices. DVH for colon and small bowel were significantly improved with PT and IMPT compared to IMXT, with D(mean) reductions of 50-80%. Doses to kidneys and femoral heads could also be substantially reduced with PT and IMPT. Sparing of rectum and bladder was superior with protons as well but less pronounced. Proton beam RT has significant potential to improve treatment related side effects in the bowel compared to photon beam RT in patients with advanced cervix carcinoma.

  10. Exposure to sperm competition risk improves survival of virgin males.

    PubMed

    Moatt, Joshua P; Dytham, Calvin; Thom, Michael D F

    2013-04-23

    Sperm competition between the ejaculates of multiple males for the fertilization of a given set of ova is taxonomically widespread. Males have evolved remarkable adaptations to increase their reproductive success under postcopulatory sexual selection, which in many species includes the ability to modify behaviour and ejaculate characteristics plastically to match the perceived level of sperm competition. Males of the model species Drosophila melanogaster increase mating duration and modify seminal fluid composition in response to short-term changes in sperm competition risk. If these responses increase a male's total investment in reproduction, he must either trade-off this cost against other life-history traits or suffer reduced survival. We tested whether mounting a plastic sperm competition response bears an instantaneous survival cost, and instead found that male D. melanogaster exposed to a high risk of sperm competition survive 12 per cent longer than those at low risk, equating to a 49 per cent reduction in the hourly hazard of death. This striking effect was found only among virgins: the high cost of mating in this species eliminates any such benefit among non-virgin males. Our results suggest that the improvement in survival found among virgins may be a product of males' tactical responses to sperm competition.

  11. Postoperative radiotherapy for lung cancer: improvement in locoregional control using three-dimensional compared with two-dimensional technique.

    PubMed

    Masson-Côté, Laurence; Couture, Christian; Fortin, André; Dagnault, Anne

    2011-07-01

    To determine whether lung cancer patients treated with three-dimensional (3D) postoperative radiotherapy (PORT) have more favorable outcomes than those treated with two-dimensional (2D) PORT. We retrospectively analyzed the charts of 153 lung cancer patients who underwent PORT with curative intent at our center between 1995 and 2007. The patients were grouped according to the RT technique; 66 patients were in the 2D group and 87 in the 3D group. The outcomes included locoregional control, survival, and secondary effects. All patients were treated using a linear accelerator at a total dose of approximately 50 Gy and 2 Gy/fraction. A few patients (21%) also received chemotherapy. Most tumors were in the advanced stage, either Stage II (30%) or Stage III (65%). The main clinical indications for PORT were positive resection margins (23%) and Stage pN2 (52%) and pN1 (22%). The patient characteristics were comparable in both groups. Kaplan-Meier analysis showed that the 3D technique significantly improved the locoregional control rate at 5 years compared with the 2D technique (81% vs. 56%, p = .007 [Cox]). The 2D technique was associated with a more than twofold increased risk of locoregional recurrence (hazard ratio, 2.7; 95% confidence interval, 1.3-5.5; p = .006). The overall survival rate did not differ at 5 years (38% vs. 20%, p = .3 [Cox]). The toxicities were also similar and acceptable in both groups. The 3D technique for conformal PORT for lung cancer improved the locoregional control rates of patients compared with the 2D technique. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Postoperative Radiotherapy for Lung Cancer: Improvement in Locoregional Control Using Three-Dimensional Compared With Two-Dimensional Technique

    SciTech Connect

    Masson-Cote, Laurence; Couture, Christian; Fortin, Andre; Dagnault, Anne

    2011-07-01

    Purpose: To determine whether lung cancer patients treated with three-dimensional (3D) postoperative radiotherapy (PORT) have more favorable outcomes than those treated with two-dimensional (2D) PORT. Patients and Methods: We retrospectively analyzed the charts of 153 lung cancer patients who underwent PORT with curative intent at our center between 1995 and 2007. The patients were grouped according to the RT technique; 66 patients were in the 2D group and 87 in the 3D group. The outcomes included locoregional control, survival, and secondary effects. All patients were treated using a linear accelerator at a total dose of approximately 50 Gy and 2 Gy/fraction. A few patients (21%) also received chemotherapy. Most tumors were in the advanced stage, either Stage II (30%) or Stage III (65%). The main clinical indications for PORT were positive resection margins (23%) and Stage pN2 (52%) and pN1 (22%). The patient characteristics were comparable in both groups. Results: Kaplan-Meier analysis showed that the 3D technique significantly improved the locoregional control rate at 5 years compared with the 2D technique (81% vs. 56%, p = .007 [Cox]). The 2D technique was associated with a more than twofold increased risk of locoregional recurrence (hazard ratio, 2.7; 95% confidence interval, 1.3-5.5; p = .006). The overall survival rate did not differ at 5 years (38% vs. 20%, p = .3 [Cox]). The toxicities were also similar and acceptable in both groups. Conclusion: The 3D technique for conformal PORT for lung cancer improved the locoregional control rates of patients compared with the 2D technique.

  13. Microvascular Fragment Transplantation Improves Rat Dorsal Skin Flap Survival

    PubMed Central

    Rathbone, Christopher R.

    2016-01-01

    Background: The development of flap necrosis distally remains a concern during microsurgical flap transfers because, at least in part, of decreased perfusion. Microvascular fragments (MVFs) are microvessels isolated from adipose tissue that are capable of improving tissue perfusion in a variety of tissue defects. The aim of this study was to determine whether the transplantation of MVFs in a dorsal rat skin flap model can improve flap survival. Methods: A 10 × 3 cm flap was raised in a cranial to caudal fashion on the dorsal side of 16 Lewis rats, with the caudal side remaining intact. The rats were equally divided into a treatment group (MVFs) and a control group (sterile saline). At the time of surgery, sterile saline with or without MVFs was injected directly into the flap. Microvessel density was determined after harvesting flap tissue by counting vessels that positively stained for Griffonia simplicifolia lectin I-isolectin B4. Laser Doppler was used to measure blood flow before and after surgery and 7 and 14 days later. Flap survival was evaluated 7 and 14 days after surgery by evaluating the percentage of viable tissue of the flap with photodigital planimetry. Results: Despite the lack of a significant difference in microvessel density and tissue perfusion, flap survival increased 6.4% (P < 0.05) in MVF-treated animals compared with controls. Conclusions: The use of MVFs may be a means to improve flap survival. Future studies are required to delineate mechanisms whereby this occurs and to further optimize their application. PMID:28293502

  14. Postoperative Irradiation of Gynecologic Malignancies: Improving Treatment Delivery Using Aperture-Based Intensity-Modulated Radiotherapy

    SciTech Connect

    Nadeau, Sylvain . E-mail: sylvainn@rrsb.nb.ca; Bouchard, Myriam; Germain, Isabelle; Raymond, Paul-Emile; Beaulieu, Frederic; Beaulieu, Luc; Roy, Rene; Gingras, Luc

    2007-06-01

    Purpose: To evaluate dosimetric and treatment delivery advantages of aperture-based intensity-modulated radiotherapy (AB-IMRT) for the treatment of patients receiving whole pelvic radiotherapy for gynecologic malignancies. Methods and Materials: Nineteen patients undergoing pelvic radiotherapy after resection of endometrial cancers were selected. A 45-Gy dose was prescribed to the target volume delineated on a planning CT scan. An in-house inverse planning system, Ballista, was used to develop a treatment plan using aperture-based multileaf collimator segments. This approach was compared with conventional four-field, enlarged four-field, and static beamlet-based IMRT (BB-IMRT) techniques in terms of target coverage, dose-volume histogram statistics for surrounding normal tissues, and numbers of segments and monitor units (MU). Results: Three quarters (76.4%) of the planning target volume received the prescription dose with conventional four-field plans. With adequate target coverage, the Ballista plans significantly reduced the volume of bowel and bladder irradiated at the prescribed dose (p < 0.001), whereas the two approaches provided equivalent results for the rectum (p 0.5). On the other hand, AB-IMRT and BB-IMRT plans showed only small differences in dose-volume histogram statistics of unknown clinical impact, whereas Ballista plan delivery required on average 73% and 59% fewer segments and MU, respectively. Conclusion: With respect to conventional techniques, AB-IMRT for the treatment of gynecologic malignancies provides dosimetric advantages similar to those with BB-IMRT but with clear treatment delivery improvements.

  15. High-dose stereotactic body radiotherapy correlates increased local control and overall survival in patients with inoperable hepatocellular carcinoma

    PubMed Central

    2013-01-01

    Background Recent studies using stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) have reported high tumor response and local control. However, the optimal SBRT dose remains unknown, and it is still not clear whether a dose response relationship for local control (LC) and overall survival (OS) exist or not. We performed this study to determine whether a dose response relationship for LC and OS is observed in SBRT for inoperable HCC. Methods Between 2003 and 2011, 108 patients with HCC were treated with SBRT. All patients were unsuitable for surgery or local ablation and had incomplete response to transarterial chemoembolization. Eighty-two patients with a longest tumor diameter (LD) less than or equal to 7.0 cm who were treated with 3-fraction SBRT and were analyzed. This cohort comprised 74 Child-Turcotte-Pugh (CTP) class A patients and 8 CTP class B7 patients. The median LD was 3.0 cm (range, 1.0–7.0 cm), and the median dose was 51 Gy (range, 33–60 Gy). Results LC and OS rates at 2 years after SBRT were 87% and 63%, respectively, with a median follow-up duration of 30 months for all patients. The 2-year LC/OS rates for patients treated with doses of > 54, 45–54, and < 45 Gy were 100/71, 78/64, and 64%/30%, respectively (p = .009/p < .001). Multivariate analysis revealed that the SBRT dose (p = .005) and Barcelona Clinic Liver Cancer stage (p = .015) were significant prognostic factors for OS. Correlation analysis revealed a positive linear relationship between the SBRT dose and LC (p = .006, R = .899)/OS (p = .002, R = .940) at 2 years. Based on the tumor-control probability model, a dose of 54.8 Gy provides 2-year LC with a 90% probability. Five patients experienced grade 3 or higher gastrointestinal toxicity, and 6 had deteriorating of CTP score by greater than or equal to 2 within 3 months of SBRT. Conclusions This study demonstrated a dose response relationship for LC and OS with SBRT for HCC. Higher LC rates resulting from an

  16. Improved Correlation of the Neuropathologic Classification According to Adapted World Health Organization Classification and Outcome After Radiotherapy in Patients With Atypical and Anaplastic Meningiomas

    SciTech Connect

    Combs, Stephanie E.; Schulz-Ertner, Daniela; Debus, Juergen; Deimling, Andreas von; Hartmann, Christian

    2011-12-01

    Purpose: To evaluate the correlation between the 1993 and 2000/2007 World Health Organization (WHO) classification with the outcome in patients with high-grade meningiomas. Patients and Methods: Between 1985 and 2004, 73 patients diagnosed with atypical or anaplastic meningiomas were treated with radiotherapy. Sections from the paraffin-embedded tumor material from 66 patients (90%) from 13 different pathology departments were re-evaluated according to the first revised WHO classification from 1993 and the revised classifications from 2000/2007. In 4 cases, the initial diagnosis meningioma was not reproducible (5%). Therefore, 62 patients with meningiomas were analyzed. Results: All 62 tumors were reclassified according to the 1993 and 2000/2007 WHO classification systems. Using the 1993 system, 7 patients were diagnosed with WHO grade I meningioma (11%), 23 with WHO grade II (37%), and 32 with WHO grade III meningioma (52%). After scoring using the 2000/2007 system, we found 17 WHO grade I meningiomas (27%), 32 WHO grade II meningiomas (52%), and 13 WHO grade III meningiomas (21%). According to the 1993 classification, the difference in overall survival was not statistically significant among the histologic subgroups (p = .96). Using the 2000/2007 WHO classifications, the difference in overall survival became significant (p = .02). Of the 62 reclassified patients 29 developed tumor progression (47%). No difference in progression-free survival was observed among the histologic subgroups (p = .44). After grading according to the 2000/2007 WHO classifications, significant differences in progression-free survival were observed among the three histologic groups (p = .005). Conclusion: The new 2000/2007 WHO classification for meningiomas showed an improved correlation between the histologic grade and outcome. This classification therefore provides a useful basis to determine the postoperative indication for radiotherapy. According to our results, a comparison of the

  17. Kaempferol and Chrysin Synergies to Improve Septic Mice Survival.

    PubMed

    Harasstani, Omar A; Tham, Chau Ling; Israf, Daud A

    2017-01-06

    Previously, we reported the role of synergy between two flavonoids-namely, chrysin and kaempferol-in inhibiting the secretion of a few major proinflammatory mediators such as tumor necrosis factor-alpha (TNF-α), prostaglandin E₂ (PGE₂), and nitric oxide (NO) from lipopolysaccharide (LPS)-induced RAW 264.7 cells. The present study aims to evaluate the effects of this combination on a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Severe sepsis was induced in male ICR mice (n = 7) via the CLP procedure. The effects of chrysin and kaempferol combination treatment on septic mice were investigated using a 7-day survival study. The levels of key proinflammatory mediators and markers-such as aspartate aminotransferase (AST), TNF-α, and NO-in the sera samples of the septic mice were determined via ELISA and fluorescence determination at different time point intervals post-CLP challenge. Liver tissue samples from septic mice were harvested to measure myeloperoxidase (MPO) levels using a spectrophotometer. Moreover, intraperitoneal fluid (IPF) bacterial clearance and total leukocyte count were also assessed to detect any antibacterial effects exerted by chrysin and kaempferol, individually and in combination. Kaempferol treatment improved the survival rate of CLP-challenged mice by up to 16%. During this treatment, kaempferol expressed antibacterial, antiapoptotic and antioxidant activities through the attenuation of bacterial forming units, AST and NO levels, and increased polymorphonuclear leukocyte (PMN) count in the IPF. On the other hand, the chrysin treatment significantly reduced serum TNF-α levels. However, it failed to significantly improve the survival rate of the CLP-challenged mice. Subsequently, the kaempferol/chrysin combination treatment significantly improved the overall 7-day survival rate by 2-fold-up to 29%. Kaempferol and chrysin revealed some synergistic effects by acting individually upon multiple

  18. Centrilobular emphysema combined with pulmonary fibrosis results in improved survival

    PubMed Central

    2011-01-01

    Background We hypothesized that, in patients with pulmonary fibrosis combined with emphysema, clinical characteristics and outcomes may differ from patients with pulmonary fibrosis without emphysema. We identified 102 patients who met established criteria for pulmonary fibrosis. The amount of emphysema (numerical score) and type of emphysema (centrilobular, paraseptal, or mixed) were characterized in each patient. Clinical characteristics, pulmonary function tests and patient survival were analysed. Results Based on the numerical emphysema score, patients were classified into those having no emphysema (n = 48), trivial emphysema (n = 26) or advanced emphysema (n = 28). Patients with advanced emphysema had a significantly higher amount of smoking in pack/years than patients with no emphysema or trivial emphysema (P < 0.0001). Median survival [1st, 3rd quartiles] of patients with advanced emphysema was 63 [36, 82] months compared to 29 [18, 49] months in patients without emphysema and 32 [19, 48] months in patients with trivial emphysema (P < 0.001). Median forced vital capacity (FVC) and total lung capacity (TLC) were higher in the advanced emphysema group compared to patients with no emphysema (P < 0.01 and P < 0.001, respectively), whereas median DLCO did not differ among groups and was overall low. Within the advanced emphysema group (n = 28), further characterization of the type of emphysema was performed and, within these subgroups of patients, survival was 75 [58, 85] months for patients with centrilobular emphysema, 75 [48, 85] months for patients with mixed centrilobular/paraseptal emphysema, and 24 [22, 35] months for patients with paraseptal emphysema (P < 0.01). Patients with advanced paraseptal emphysema had similar survival times to patients without emphysema. Conclusions Patients with pulmonary fibrosis combined with advanced centrilobular or mixed emphysema have an improved survival compared with patients with pulmonary fibrosis without emphysema

  19. Combining Gene Signatures Improves Prediction of Breast Cancer Survival

    PubMed Central

    Zhao, Xi; Naume, Bjørn; Langerød, Anita; Frigessi, Arnoldo; Kristensen, Vessela N.; Børresen-Dale, Anne-Lise; Lingjærde, Ole Christian

    2011-01-01

    Background Several gene sets for prediction of breast cancer survival have been derived from whole-genome mRNA expression profiles. Here, we develop a statistical framework to explore whether combination of the information from such sets may improve prediction of recurrence and breast cancer specific death in early-stage breast cancers. Microarray data from two clinically similar cohorts of breast cancer patients are used as training (n = 123) and test set (n = 81), respectively. Gene sets from eleven previously published gene signatures are included in the study. Principal Findings To investigate the relationship between breast cancer survival and gene expression on a particular gene set, a Cox proportional hazards model is applied using partial likelihood regression with an L2 penalty to avoid overfitting and using cross-validation to determine the penalty weight. The fitted models are applied to an independent test set to obtain a predicted risk for each individual and each gene set. Hierarchical clustering of the test individuals on the basis of the vector of predicted risks results in two clusters with distinct clinical characteristics in terms of the distribution of molecular subtypes, ER, PR status, TP53 mutation status and histological grade category, and associated with significantly different survival probabilities (recurrence: p = 0.005; breast cancer death: p = 0.014). Finally, principal components analysis of the gene signatures is used to derive combined predictors used to fit a new Cox model. This model classifies test individuals into two risk groups with distinct survival characteristics (recurrence: p = 0.003; breast cancer death: p = 0.001). The latter classifier outperforms all the individual gene signatures, as well as Cox models based on traditional clinical parameters and the Adjuvant! Online for survival prediction. Conclusion Combining the predictive strength of multiple gene signatures improves prediction of breast

  20. Intensive Hemodialysis Associates with Improved Survival Compared with Conventional Hemodialysis

    PubMed Central

    Lindsay, Robert M.; Cuerden, Meaghan S.; Garg, Amit X.; Port, Friedrich; Austin, Peter C.; Moist, Louise M.; Pierratos, Andreas; Chan, Christopher T.; Zimmerman, Deborah; Lockridge, Robert S.; Couchoud, Cécile; Chazot, Charles; Ofsthun, Norma; Levin, Adeera; Copland, Michael; Courtney, Mark; Steele, Andrew; McFarlane, Philip A.; Geary, Denis F.; Pauly, Robert P.; Komenda, Paul; Suri, Rita S.

    2012-01-01

    Patients undergoing conventional maintenance hemodialysis typically receive three sessions per week, each lasting 2.5–5.5 hours. Recently, the use of more intensive hemodialysis (>5.5 hours, three to seven times per week) has increased, but the effects of these regimens on survival are uncertain. We conducted a retrospective cohort study to examine whether intensive hemodialysis associates with better survival than conventional hemodialysis. We identified 420 patients in the International Quotidian Dialysis Registry who received intensive home hemodialysis in France, the United States, and Canada between January 2000 and August 2010. We matched 338 of these patients to 1388 patients in the Dialysis Outcomes and Practice Patterns Study who received in-center conventional hemodialysis during the same time period by country, ESRD duration, and propensity score. The intensive hemodialysis group received a mean (SD) 4.8 (1.1) sessions per week with a mean treatment time of 7.4 (0.87) hours per session; the conventional group received three sessions per week with a mean treatment time of 3.9 (0.32) hours per session. During 3008 patient-years of follow-up, 45 (13%) of 338 patients receiving intensive hemodialysis died compared with 293 (21%) of 1388 patients receiving conventional hemodialysis (6.1 versus 10.5 deaths per 100 person-years; hazard ratio, 0.55 [95% confidence interval, 0.34–0.87]). The strength and direction of the observed association between intensive hemodialysis and improved survival were consistent across all prespecified subgroups and sensitivity analyses. In conclusion, there is a strong association between intensive home hemodialysis and improved survival, but whether this relationship is causal remains unknown. PMID:22362910

  1. Automatic block-matching registration to improve lung tumor localization during image-guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Robertson, Scott Patrick

    To improve relatively poor outcomes for locally-advanced lung cancer patients, many current efforts are dedicated to minimizing uncertainties in radiotherapy. This enables the isotoxic delivery of escalated tumor doses, leading to better local tumor control. The current dissertation specifically addresses inter-fractional uncertainties resulting from patient setup variability. An automatic block-matching registration (BMR) algorithm is implemented and evaluated for the purpose of directly localizing advanced-stage lung tumors during image-guided radiation therapy. In this algorithm, small image sub-volumes, termed "blocks", are automatically identified on the tumor surface in an initial planning computed tomography (CT) image. Each block is independently and automatically registered to daily images acquired immediately prior to each treatment fraction. To improve the accuracy and robustness of BMR, this algorithm incorporates multi-resolution pyramid registration, regularization with a median filter, and a new multiple-candidate-registrations technique. The result of block-matching is a sparse displacement vector field that models local tissue deformations near the tumor surface. The distribution of displacement vectors is aggregated to obtain the final tumor registration, corresponding to the treatment couch shift for patient setup correction. Compared to existing rigid and deformable registration algorithms, the final BMR algorithm significantly improves the overlap between target volumes from the planning CT and registered daily images. Furthermore, BMR results in the smallest treatment margins for the given study population. However, despite these improvements, large residual target localization errors were noted, indicating that purely rigid couch shifts cannot correct for all sources of inter-fractional variability. Further reductions in treatment uncertainties may require the combination of high-quality target localization and adaptive radiotherapy.

  2. Has survival following pancreaticoduodenectomy for pancreas adenocarcinoma improved over time?

    PubMed

    Salem, Ahmed I; Alfi, Mina; Winslow, Emily; Cho, Clifford S; Weber, Sharon M

    2015-11-01

    Survival following resection of pancreas cancer is poor. It is uncertain whether outcome improved overtime. Due to the recent advances in surgical techniques, diagnostic evaluation, and systemic treatment, we sought to evaluate pancreas cancer outcome over time. Prospectively collected data on patients who underwent pancreaticoduodenectomy for pathologically confirmed pancreatic adenocarcinoma from 1999 to 2012 were analyzed. Perioperative and long-term outcomes were analyzed, comparing patients from era 1 (1999-2005) to patients from era 2 (2006-2012). Two-hundred sixteen patients were evaluated, including 76 in era 1 and 140 in era 2. There was no difference in 30-day mortality (1.3%, era 1 vs. 1.4%, era 2; P = 0.95) or rates of overall 30-day morbidity (49%, era 1 vs. 62%, era 2; P = 0.06). On multivariable analysis after adjusting for perineural invasion, lymphovascular invasion, margin status, EBL, and venous resection, there was no difference in survival between eras (HR = 0.81, P = 0.27, CI = 0.57-1.16). After adjusting for clinicopathological features, there was no association of improved outcome over time. However, despite an increasing prevalence of anatomically advanced and histologically aggressive tumors, perioperative outcomes such as blood loss and margin negativity improved over time, with no increase in 30-day mortality. © 2015 Wiley Periodicals, Inc.

  3. Conformal Therapy Improves the Therapeutic Index of Patients with Anal Canal Cancer Treated with Combined Chemotherapy and External Beam Radiotherapy

    SciTech Connect

    Vuong, Te . E-mail: te.vuong@muhc.mcgill.ca; Kopek, Neil; Ducruet, Thierry; Portelance, Lorraine; Faria, Sergio; Bahoric, Boris; Devic, Slobodan

    2007-04-01

    Purpose: To evaluate the clinical outcomes of three-dimensional conformal radiotherapy (3D-CRT) in patients with anal canal cancer, in terms of local control (LC), freedom from relapse (FFR), and overall survival (OS) rates, and to estimate long-term toxicity data. Methods and Materials: Sixty historical patients, treated with conventional radiation techniques (C-RT), were used as controls, and 62 consecutive patients were treated with 3D-CRT. Patients treated with 3D-CRT received 54 Gy in 30 fractions delivered continuously, compared with 45-58.9 Gy (median dose, 54 Gy) in a split course in patients treated with C-RT. Chemotherapy consisted of 5-fluorouracil with either mitomycin-C or cis-platinum given concurrently with radiation. Survival curves were performed using the Kaplan-Meier model, and the Cox proportional hazards model was used for multivariate analysis of risk factors. Results: No differences in stage and age distribution were observed between the two groups. Patients treated with 3D-CRT and C-RT had an actuarial 5-year LC rate of 85.1% and 61.1%, respectively (p = 0.0056); the FFR rate was 70.2% and 46.1% (p = 0.0166), and the OS rate was 80.7% and 53.9% (p = 0.0171). In multivariate analysis, factors of significance for LC were nodal (N) status (p < 0.001); for OS, 3D-CRT (p = 0.038), N status (p 0.011), and T status (p = 0.012); and for FFR, 3D-CRT (p = 0.024) and N status (p < 0.001). Conclusion: The use of 3D-CRT allows patients with anal canal cancer to complete radiation and chemotherapy without interruption for toxicity, with significant improvements in LC, FFR, and OS.

  4. SU-E-T-427: Cell Surviving Fractions Derived From Tumor-Volume Variation During Radiotherapy for Non-Small Cell Lung Cancer: Comparison with Predictive Assays

    SciTech Connect

    Chvetsov, A; Schwartz, J; Mayr, N; Yartsev, S

    2014-06-01

    Purpose: To show that a distribution of cell surviving fractions S{sub 2} in a heterogeneous group of patients can be derived from tumor-volume variation curves during radiotherapy for non-small cell lung cancer. Methods: Our analysis was based on two data sets of tumor-volume variation curves for heterogeneous groups of 17 patients treated for nonsmall cell lung cancer with conventional dose fractionation. The data sets were obtained previously at two independent institutions by using megavoltage (MV) computed tomography (CT). Statistical distributions of cell surviving fractions S{sup 2} and cell clearance half-lives of lethally damaged cells T1/2 have been reconstructed in each patient group by using a version of the two-level cell population tumor response model and a simulated annealing algorithm. The reconstructed statistical distributions of the cell surviving fractions have been compared to the distributions measured using predictive assays in vitro. Results: Non-small cell lung cancer presents certain difficulties for modeling surviving fractions using tumor-volume variation curves because of relatively large fractional hypoxic volume, low gradient of tumor-volume response, and possible uncertainties due to breathing motion. Despite these difficulties, cell surviving fractions S{sub 2} for non-small cell lung cancer derived from tumor-volume variation measured at different institutions have similar probability density functions (PDFs) with mean values of 0.30 and 0.43 and standard deviations of 0.13 and 0.18, respectively. The PDFs for cell surviving fractions S{sup 2} reconstructed from tumor volume variation agree with the PDF measured in vitro. Comparison of the reconstructed cell surviving fractions with patient survival data shows that the patient survival time decreases as the cell surviving fraction increases. Conclusion: The data obtained in this work suggests that the cell surviving fractions S{sub 2} can be reconstructed from the tumor volume

  5. Investigating the Temporal Effects of Respiratory-Gated and Intensity-Modulated Radiotherapy Treatment Delivery on In Vitro Survival: An Experimental and Theoretical Study

    SciTech Connect

    Keall, Paul J. Chang, Michael; Benedict, Stanley; Thames, Howard; Vedam, S. Sastry; Lin, Peck-Sun

    2008-08-01

    Purpose: To experimentally and theoretically investigate the temporal effects of respiratory-gated and intensity-modulated radiotherapy (IMRT) treatment delivery on in vitro survival. Methods and Materials: Experiments were designed to isolate the effects of periodic irradiation (gating), partial tumor irradiation (IMRT), and extended treatment time (gating and IMRT). V79 Chinese hamster lung fibroblast cells were irradiated to 2 Gy with four delivery methods and a clonogenic assay performed. Theoretical incomplete repair model calculations were performed using the incomplete repair model. Results: Treatment times ranged from 1.67 min (conformal radiotherapy, CRT) to 15 min (gated IMRT). Survival fraction calculations ranged from 68.2% for CRT to 68.7% for gated IMRT. For the same treatment time (5 min), gated delivery alone and IMRT delivery alone both had a calculated survival fraction of 68.3%. The experimental values ranged from 65.7% {+-} 1.0% to 67.3% {+-} 1.3%, indicating no significant difference between the experimental observations and theoretical calculations. Conclusion: The theoretical results predicted that of the three temporal effects of radiation delivery caused by gating and IMRT, extended treatment time was the dominant effect. Care should be taken clinically to ensure that the use of gated IMRT does not significantly increase treatment times, by evaluating appropriate respiratory gating duty cycles and IMRT delivery complexity.

  6. Exclusive intraoperative radiotherapy for invasive breast cancer in elderly patients (>70 years): proportion of eligible patients and local recurrence-free survival.

    PubMed

    Lambaudie, Eric; Houvenaeghel, Gilles; Ziouèche, Amira; Knight, Sophie; Dravet, François; Garbay, Jean Remy; Giard, Sylvie; Charitansky, Hélène; Cohen, Monique; Faure, Christelle; Hudry, Delphine; Azuar, Paul; Villet, Richard; Gimbergues, Pierre; de Lara, Christine Tunon; Tallet, Agnès; Bannier, Marie; Minsat, Mathieu; Resbeut, Michel

    2016-11-15

    To estimate the proportion of elderly patients (>70 years) with breast cancer eligible for an Exclusive IntraOperative RadioTherapy (E-IORT) and to evaluate their local recurrence-free survival rate. This retrospective study examining two cohorts focuses on patients over 70 years old: a multi-centric cohort of 1411 elderly patients and a mono-centric cohort of 592 elderly patients. All patients underwent conservative surgery followed by external radiotherapy for T0-T3 N0-N1 invasive breast cancer, between 1980 and 2008. Within each cohort two groups were identified according to the inclusion criteria of the RIOP trial (R group) and TARGIT E study (T group). Each group was divided into two sub-groups, patients eligible (E) or non-eligible (nE) for IORT. The population of patients that were eligible in the TARGIT E study but not in the RIOP trial were also studied in both cohorts. The proportion of patients eligible for IORT was calculated, according to the eligibility criteria of each study. A comparison of the 5-year local or locoregional recurrence-free survival rate between eligible vs non-eligible patients was made. In both cohorts, the proportion of patients eligible according to the RIOP trial's eligibility criteria was 35.4 and 19.3%, and according to the TARGIT E study criteria was 60.9 and 45.3%. The 5-year locoregional recurrence-free survival rate was not significantly different between RE and RnE groups, TE and TnE groups. In both cohorts RE and (TE-RE) groups were not significantly different. Our results encourage further necessary studies to define and to extend the eligibility criteria for per operative exclusive radiotherapy.

  7. Salvage Treatment Improved Survival of Patients With Relapsed Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type

    SciTech Connect

    Zhang Xinxing; Xie Conghua; Xu Yong; Deng Di; Zhao Yanhai; Zou Bingwen; Zhou Lin; Li Mei; Wang Jin; Liu Weiping; Huang Meijuan

    2009-07-01

    Purpose: To evaluate the clinical outcome of salvage treatment for patients with relapsed natural killer (NK)/T-cell lymphoma, nasal type. Methods and Materials: Forty-four patients who had achieved complete response during initial treatment and experienced histologically proven relapse were reviewed. Twenty-nine of them received salvage treatment with radiotherapy (RT) alone (n = 7), chemotherapy (CT) alone (n = 10), or both RT and CT (n = 12); the other 15 patients received best supportive care alone. Results: The estimated 5-year overall survival (OS) rate for patients with or without salvage treatment was 37.8% vs. 0 (p < 0.0001), respectively. Salvage CT did not improve survival of relapsed Stage IE and IIE patients. Among relapsed Stage IIIE and IVE patients who received salvage treatment, RT developed significantly better survival when compared with that of non-RT (1-year OS, 62.5% vs. 0, p = 0.006). Relapsed Ann Arbor stage and receiving salvage treatment were found to be significant factors influencing OS at both univariate and multivariate levels. Conclusions: Salvage treatment improved survival in patients with relapsed NK/T-cell lymphoma, nasal type. Salvage RT may play an important role in salvage treatment of relapsed extranodal NK/T-cell lymphoma.

  8. Improved human observer performance in digital reconstructed radiograph verification in head and neck cancer radiotherapy.

    PubMed

    Sturgeon, Jared D; Cox, John A; Mayo, Lauren L; Gunn, G Brandon; Zhang, Lifei; Balter, Peter A; Dong, Lei; Awan, Musaddiq; Kocak-Uzel, Esengul; Mohamed, Abdallah Sherif Radwan; Rosenthal, David I; Fuller, Clifton David

    2015-10-01

    Digitally reconstructed radiographs (DRRs) are routinely used as an a priori reference for setup correction in radiotherapy. The spatial resolution of DRRs may be improved to reduce setup error in fractionated radiotherapy treatment protocols. The influence of finer CT slice thickness reconstruction (STR) and resultant increased resolution DRRs on physician setup accuracy was prospectively evaluated. Four head and neck patient CT-simulation images were acquired and used to create DRR cohorts by varying STRs at 0.5, 1, 2, 2.5, and 3 mm. DRRs were displaced relative to a fixed isocenter using 0-5 mm random shifts in the three cardinal axes. Physician observers reviewed DRRs of varying STRs and displacements and then aligned reference and test DRRs replicating daily KV imaging workflow. A total of 1,064 images were reviewed by four blinded physicians. Observer errors were analyzed using nonparametric statistics (Friedman's test) to determine whether STR cohorts had detectably different displacement profiles. Post hoc bootstrap resampling was applied to evaluate potential generalizability. The observer-based trial revealed a statistically significant difference between cohort means for observer displacement vector error ([Formula: see text]) and for [Formula: see text]-axis [Formula: see text]. Bootstrap analysis suggests a 15% gain in isocenter translational setup error with reduction of STR from 3 mm to [Formula: see text]2 mm, though interobserver variance was a larger feature than STR-associated measurement variance. Higher resolution DRRs generated using finer CT scan STR resulted in improved observer performance at shift detection and could decrease operator-dependent geometric error. Ideally, CT STRs [Formula: see text]2 mm should be utilized for DRR generation in the head and neck.

  9. Improved human observer performance in digital reconstructed radiograph verification in head and neck cancer radiotherapy

    PubMed Central

    Sturgeon, Jared D.; Cox, John A.; Mayo, Lauren L.; Gunn, G. Brandon; Zhang, Lifei; Balter, Peter A.; Dong, Lei; Awan, Musaddiq; Kocak-Uzel, Esengul; Mohamed, Abdallah Sherif Radwan; Rosenthal, David I.

    2016-01-01

    Purpose Digitally reconstructed radiographs (DRRs) are routinely used as an a priori reference for setup correction in radiotherapy. The spatial resolution of DRRs may be improved to reduce setup error in fractionated radiotherapy treatment protocols. The influence of finer CT slice thickness reconstruction (STR) and resultant increased resolution DRRs on physician setup accuracy was prospectively evaluated. Methods Four head and neck patient CT-simulation images were acquired and used to create DRR cohorts by varying STRs at 0.5, 1, 2, 2.5, and 3 mm. DRRs were displaced relative to a fixed isocenter using 0–5 mm random shifts in the three cardinal axes. Physician observers reviewed DRRs of varying STRs and displacements and then aligned reference and test DRRs replicating daily KV imaging workflow. A total of 1,064 images were reviewed by four blinded physicians. Observer errors were analyzed using nonparametric statistics (Friedman’s test) to determine whether STR cohorts had detectably different displacement profiles. Post hoc bootstrap resampling was applied to evaluate potential generalizability. Results The observer-based trial revealed a statistically significant difference between cohort means for observer displacement vector error (p = 0.02) and for Z-axis (p < 0.01). Bootstrap analysis suggests a 15% gain in isocenter translational setup error with reduction of STR from 3 mm to ≤2 mm, though interobserver variance was a larger feature than STR-associated measurement variance. Conclusions Higher resolution DRRs generated using finer CT scan STR resulted in improved observer performance at shift detection and could decrease operator-dependent geometric error. Ideally, CT STRs ≤2 mm should be utilized for DRR generation in the head and break neck. PMID:25477277

  10. Surgery of the primary tumor improves survival in women with stage IV breast cancer in Southwest China: A retrospective analysis.

    PubMed

    Xie, Yuxin; Lv, Xingxing; Luo, Chuanxu; Hu, Kejia; Gou, Qiheng; Xie, Keqi; Zheng, Hong

    2017-06-01

    The International Consensus Guidelines for advanced breast cancer (ABC) considers that the surgery of the primary tumor for stage IV breast cancer patients does not usually improve the survival. However, studies have showed that resection of the primary tumor may benefit these patients. The correlation between surgery and survival remains unclear.The impact of surgery and other clinical factors on overall survival (OS) of stage IV patients is investigated in West China Hospital. Female patients diagnosed with stage IV breast cancer between 1999 and 2014 were included (N = 223). Univariate and multivariate analysis assessed the association between surgery and OS.One hundred seventy-seven (79.4%) underwent surgery for the primary tumor, and 46 (20.6%) had no surgery. No significant differences were observed in age at diagnosis, T-stage, N-stage, histological grade, molecular subtype, hormone receptor (HR), and number of metastatic sites between 2 groups. Patients in the surgery group had dramatically longer OS (45.6 vs 21.3 months, log-rank P < .001). In univariate analysis, survival was associated with surgical treatment, residence, tumor size, lymph node, HR status, hormonal therapy, and radiotherapy. In multivariate analysis, surgery was an independent prognostic factor for OS [hazard ratio (HR), 0.569; 95% confidence interval (CI) 0.329-0.984, P = .044]. Additional independent prognostic factors were hormonal therapy (HR, 0.490; 95% CI 0.300-0.800) and radiotherapy (HR, 0.490; 95% CI 0.293-0.819). In addition, a favorable impact of surgery was observed by subgroup analysis.Our study showed that surgery of the primary breast tumor has a positive impact on OS in with stage IV breast cancer patients.

  11. Radiotherapy improves serum fatty acids and lipid profile in breast cancer.

    PubMed

    Shaikh, Sana; Channa, Naseem Aslam; Talpur, Farha Naz; Younis, Muhammad; Tabassum, Naila

    2017-05-18

    Breast cancer is a disease with diverse clinical symptoms, molecular profiles, and its nature to response its therapeutic treatments. Radiotherapy (RT), along with surgery and chemotherapy is a part of treatment in breast cancer. The aim of present study was to investigate pre and post treatment effects of radiotherapy in serum fatty acids and its lipids profile in patients with breast cancer. In this comparative as well as follow up study, Serum fatty acids were performed by gas chromatography to investigate fatty acids and Microlab for analysis of lipid profile. Among serum free and total fatty acids the major saturated fatty acids (SFAs) in serum lipids of breast cancer patients (pre and post treated) were stearic acid (18:0) and palmitic acid (16:0). These fatty acids contributed about 35-50% of total fatty acids. The decreased concentrations of linoleic acid (C18:2) and arachidonic acid (C20:4) with a lower ratio of C18:2/C18:1 was found in pretreated breast cancer patients as compared to controls. The n-3/n-6 ratio of breast cancer patients was decreased before treatment but it was 35% increased after treatment. In addition, plasma activity of D6 desaturase was increased in the breast cancer patients, while the activity of D5 desaturase was decreased. Increased levels of SFAs, monounsaturated fatty acids (MUFAs) and decreased polyunsaturated fatty acids (PUFAs) levels in breast cancer patients (pre and post treated) as compared to controls. Serum total cholesterol (TC) (224.4 mg/dL) and low density lipoprotein cholesterol (LDL-C) (142.9 mg/dL) were significantly increased in pretreated breast cancer patients but after the radiotherapy treatment, the TC (150.2 mg/dL) and LDL-C (89.8 mg/dL) were decreased. It seems that RT would have played a potential role in the treatment of BC. After RT the serum levels of PUFAs, TC, and LDL-C are improved. Our study reinforces the important role of RT in the management of BC. The level of PUFAs, TC, and LDL-C can be

  12. Survival outcomes of combined external beam radiotherapy and brachytherapy vs. brachytherapy alone for intermediate-risk prostate cancer patients using the National Cancer Data Base.

    PubMed

    Amini, Arya; Jones, Bernard L; Jackson, Matthew W; Rusthoven, Chad G; Maroni, Paul; Kavanagh, Brian D; Raben, David

    2016-01-01

    The purpose was to evaluate survival outcomes between external beam radiotherapy (EBRT) plus brachytherapy and brachytherapy alone for intermediate-risk prostate cancer, using the National Cancer Data Base. The National Cancer Data Base was queried for cN0M0 intermediate-risk patients treated from 2004 to 2006, with available data for Gleason score (GS), prostate-specific antigen (PSA), tumor stage, and receipt of radiation therapy (RT) and androgen deprivation therapy. RT comparison groups were the following: EBRT (40-50.4 Gy) plus brachytherapy and brachytherapy alone. A total of 10,571 patients were included: 3,148 received EBRT plus brachytherapy and 7,423 received brachytherapy alone. Median followup was 84 months (2-122 months); median age was 68 years (40-90 years). Unadjusted 5- and 7-year overall survival (OS) rates between EBRT plus brachytherapy vs. brachytherapy alone were 91.4% vs. 90.2% and 85.7% vs. 82.9%, respectively (p < 0.001). EBRT plus brachytherapy was associated with longer OS compared with brachytherapy alone under multivariate (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.75-0.93; p = 0.001) and propensity score-matched analyses (HR, 0.85; 95% CI, 0.75-0.97; p = 0.006). Further subset analysis performed based on the Radiation Therapy Oncology Group 0232 inclusion criteria (GS 7 if PSA < 10 or GS < 7 if PSA 10-20) also demonstrated longer OS with EBRT plus brachytherapy (HR, 0.87; 95% CI, 0.77-0.98; p = 0.026). EBRT plus brachytherapy is associated with a modest OS improvement compared with brachytherapy alone in this population-based analysis. Although this benefit appears statistically significant, the relatively small difference in OS raises the question of overall clinical benefit with combined modality RT for intermediate-risk prostate cancer, given the potential increased risk for toxicities. Future results from Radiation Therapy Oncology Group 0232 should provide further insight on this topic. Copyright © 2016 American

  13. MRI to CT prostate registration for improved targeting in cancer external beam radiotherapy.

    PubMed

    Commandeur, Frederic; Simon, Antoine; Mathieu, Romain; Nassef, Mohamed; Ospina, Juan David; Rolland, Yan; Haigron, Pascal; De Crevoisier, Renaud; Acosta, Oscar

    2016-06-16

    External radiotherapy is a major clinical treatment for localized prostate cancer. Currently, computed tomography (CT) is used to delineate the prostate and to plan the radiotherapy treatment. However, CT images suffer from a poor soft tissue contrast and do not allow an accurate organ delineation. On the contrary, Magnetic resonance imaging (MRI) provides rich details and high soft tissue contrast, allowing tumor detection. Thus, the intra-individual propagation of MRI delineations towards the planning CT may improve tumor targeting. In this paper we introduce a new method to propagate MRI prostate delineations to the planning CT. In a first step, a random forest (RF) classification is performed to coarsely detect the prostate in the CT images, yielding a prostate probability membership for each voxel and a prostate hard segmentation. Then the registration is performed using a new similarity metric which maximizes the probability and the collinearity between the normals of the MR existing contour and the contour resulting from the CT classification. A first study on synthetic data was performed to analyze the influence of the metric parameters with different levels of noise. Then, the method was also evaluated on real MR-CT data using manual alignments and intraprostatic fiducial markers and compared to a classically used mutual information (MI) approach. The proposed metric outperformed MI by 7% in terms of Dice score coefficient (DSC), by 3.14 mm the Hausdorff Distance (HD) and 2.13 mm the markers position errors (MPE). Finally, the impact of registration uncertainties on the treatment planning was evaluated, demonstrating the potential advantage of the proposed approach in a clinical setup to define a precise target.

  14. Improving DNA double-strand repair inhibitor KU55933 therapeutic index in cancer radiotherapy using nanoparticle drug delivery.

    PubMed

    Tian, Xi; Lara, Haydee; Wagner, Kyle T; Saripalli, Srinivas; Hyder, Syed Nabeel; Foote, Michael; Sethi, Manish; Wang, Edina; Caster, Joseph M; Zhang, Longzhen; Wang, Andrew Z

    2015-12-21

    Radiotherapy is a key component of cancer treatment. Because of its importance, there has been high interest in developing agents and strategies to further improve the therapeutic index of radiotherapy. DNA double-strand repair inhibitors (DSBRIs) are among the most promising agents to improve radiotherapy. However, their clinical translation has been limited by their potential toxicity to normal tissue. Recent advances in nanomedicine offer an opportunity to overcome this limitation. In this study, we aim to demonstrate the proof of principle by developing and evaluating nanoparticle (NP) formulations of KU55933, a DSBRI. We engineered a NP formulation of KU55933 using nanoprecipitation method with different lipid polymer nanoparticle formulation. NP KU55933 using PLGA formulation has the best loading efficacy as well as prolonged drug release profile. We demonstrated that NP KU55933 is a potent radiosensitizer in vitro using clonogenic assay and is more effective as a radiosensitizer than free KU55933 in vivo using mouse xenograft models of non-small cell lung cancer (NSCLC). Western blots and immunofluorescence showed NP KU55933 exhibited more prolonged inhibition of DNA repair pathway. In addition, NP KU55933 leads to lower skin toxicity than KU55933. Our study supports further investigations using NP to deliver DSBRIs to improve cancer radiotherapy treatment.

  15. Improving DNA double-strand repair inhibitor KU55933 therapeutic index in cancer radiotherapy using nanoparticle drug delivery

    NASA Astrophysics Data System (ADS)

    Tian, Xi; Lara, Haydee; Wagner, Kyle T.; Saripalli, Srinivas; Hyder, Syed Nabeel; Foote, Michael; Sethi, Manish; Wang, Edina; Caster, Joseph M.; Zhang, Longzhen; Wang, Andrew Z.

    2015-11-01

    Radiotherapy is a key component of cancer treatment. Because of its importance, there has been high interest in developing agents and strategies to further improve the therapeutic index of radiotherapy. DNA double-strand repair inhibitors (DSBRIs) are among the most promising agents to improve radiotherapy. However, their clinical translation has been limited by their potential toxicity to normal tissue. Recent advances in nanomedicine offer an opportunity to overcome this limitation. In this study, we aim to demonstrate the proof of principle by developing and evaluating nanoparticle (NP) formulations of KU55933, a DSBRI. We engineered a NP formulation of KU55933 using nanoprecipitation method with different lipid polymer nanoparticle formulation. NP KU55933 using PLGA formulation has the best loading efficacy as well as prolonged drug release profile. We demonstrated that NP KU55933 is a potent radiosensitizer in vitro using clonogenic assay and is more effective as a radiosensitizer than free KU55933 in vivo using mouse xenograft models of non-small cell lung cancer (NSCLC). Western blots and immunofluorescence showed NP KU55933 exhibited more prolonged inhibition of DNA repair pathway. In addition, NP KU55933 leads to lower skin toxicity than KU55933. Our study supports further investigations using NP to deliver DSBRIs to improve cancer radiotherapy treatment.

  16. Starvation Improves Survival of Bacteria Introduced into Activated Sludge

    PubMed Central

    Watanabe, Kazuya; Miyashita, Mariko; Harayama, Shigeaki

    2000-01-01

    A phenol-degrading bacterium, Ralstonia eutropha E2, was grown in Luria-Bertani (LB) medium or in an inorganic medium (called MP) supplemented with phenol and harvested at the late-exponential-growth phase. Phenol-acclimated activated sludge was inoculated with the E2 cells immediately after harvest or after starvation in MP for 2 or 7 days. The densities of the E2 populations in the activated sludge were then monitored by quantitative PCR. The E2 cells grown on phenol and starved for 2 days (P-2 cells) survived in the activated sludge better than those treated differently: the population density of the P-2 cells 7 days after their inoculation was 50 to 100 times higher than the population density of E2 cells without starvation or that with 7-day starvation. LB medium-grown cells either starved or nonstarved were rapidly eliminated from the sludge. The P-2 cells showed a high cell surface hydrophobicity and retained metabolic activities. Cells otherwise prepared did not have one of these two features. From these observations, it is assumed that hydrophobic cell surface and metabolic activities higher than certain levels were required for the inoculated bacteria to survive in the activated sludge. Reverse transcriptase PCR analyses showed that the P-2 cells initiated the expression of phenol hydroxylase within 1 day of their inoculation into the sludge. These results suggest the utility of a short starvation treatment for improving the efficacy of bioaugumentation. PMID:10966407

  17. Adult Rhabdomyosarcoma Survival Improved With Treatment on Multimodality Protocols

    SciTech Connect

    Gerber, Naamit Kurshan; Wexler, Leonard H.; Singer, Samuel; Alektiar, Kaled M.; Keohan, Mary Louise; Shi, Weiji; Zhang, Zhigang; Wolden, Suzanne

    2013-05-01

    Purpose: Rhabdomyosarcoma (RMS) is a pediatric sarcoma rarely occurring in adults. For unknown reasons, adults with RMS have worse outcomes than do children. Methods and Materials: We analyzed data from all patients who presented to Memorial Sloan-Kettering Cancer Center between 1990 and 2011 with RMS diagnosed at age 16 or older. One hundred forty-eight patients met the study criteria. Ten were excluded for lack of adequate data. Results: The median age was 28 years. The histologic diagnoses were as follows: embryonal 54%, alveolar 33%, pleomorphic 12%, and not otherwise specified 2%. The tumor site was unfavorable in 67% of patients. Thirty-three patients (24%) were at low risk, 61 (44%) at intermediate risk, and 44 (32%) at high risk. Forty-six percent were treated on or according to a prospective RMS protocol. The 5-year rate of overall survival (OS) was 45% for patients with nonmetastatic disease. The failure rates at 5 years for patients with nonmetastatic disease were 34% for local failure and 42% for distant failure. Among patients with nonmetastatic disease (n=94), significant factors associated with OS were histologic diagnosis, site, risk group, age, and protocol treatment. On multivariate analysis, risk group and protocol treatment were significant after adjustment for age. The 5-year OS was 54% for protocol patients versus 36% for nonprotocol patients. Conclusions: Survival in adult patients with nonmetastatic disease was significantly improved for those treated on RMS protocols, most of which are now open to adults.

  18. Improved oil-off survivability of tapered roller bearings

    NASA Technical Reports Server (NTRS)

    Kreider, Gary E.; Lee, Peter W.

    1987-01-01

    The aim of this program is to improve the oil-off survivability of a tapered roller bearing when applied to a helicopter transmission, since the tapered bearing has shown a performance advantage in this application. However, the critical roller end-rib conjunction is vulnerable to damage in an oil-off condition. Three powdered metal materials were selected to use as the rib material for oil-off evaluation. These were: M2 steel to a 65% density, CBS 1000M 65% density, and CBS 1000M 75% density. The bearing styles tested were ribbed cone (inner race) and ribbed cup (outer race). Carburized solid CBS 600 was also used as a ribbed material for comparison of oil-off results. The tests were conducted at six speeds from 4000 rpm (0.26 million DN) through 37000 rpm (2.4 million DN).The ribbed cup style bearing achieved longer lives than the ribbed cone style. A standard bearing lasted only 10 minutes at 4000 rpm; however, the 30-min oil-off goal was achieved through 11000 rpm using the survivable ribbed cup bearing. The oil-off lives at 37000 rpm were less than 10 seconds. The grinding of the powder metal materials and surface preparation to achieve an open porosity is extremely critical to the oil-off performance of the powder metal component.

  19. Primary Tumor Standardized Uptake Value Measured on F18-Fluorodeoxyglucose Positron Emission Tomography Is of Prediction Value for Survival and Local Control in Non–Small-Cell Lung Cancer Receiving Radiotherapy

    PubMed Central

    Na, Feifei; Wang, Jingwen; Li, Cong; Deng, Lei; Xue, Jianxin

    2014-01-01

    Introduction: The 2-[18F]-Fluorodeoxyglucose (FDG) positron emission tomography (PET/CT) has become an imaging tool for clinical assessment of tumor, node, metastasis in non–small-cell lung cancer (NSCLC). Primary tumor maximum standardized uptake value (SUVmax) on 18F-FDG PET/CT before and after radiation therapy (RT) has been studied as a potential prognostic factor for NSCLC patients receiving radiotherapy. However, the sample sizes of most studies were small, and the results of the prediction value of SUVmax remained undetermined, which lead us to perform a meta-analysis to improve the precision in estimating its effect. Methods: We performed a meta-analysis of published literature for primary tumor SUVmax-based biomarkers of the outcome of NSCLC receiving radiotherapy. The required data for estimation of individual hazard ratios (HRs) to compare patients with a low and a high SUVmax were extracted from each publication. A combined HR was calculated by Stata statistical software (Version 11). All of the results were verified by two persons to ensure its accuracy. Results: Thirteen studies were finally included into this meta-analysis; data are available in 13 studies for pre-RT primary tumor SUVmax and in five studies for post-RT. For overall survival, the combined HR estimate was 1.05 (95% confidence interval [CI], 1.02–1.08) and 1.32 (95% CI, 1.15–1.51) for pre-RT SUVmax and post-RT SUVmax, respectively; 1.26 (95% CI, 1.05–1.52) and 2.01 (95% CI, 1.16–3.46) for local control (LC). In stereotactic body radiotherapy (SBRT) group, HR for LC was 1.11 (95% CI, 1.06–1.18) and 2.19 (95% CI, 1.34–3.60) for pre-SBRT SUVmax and post-SBRT SUVmax, respectively. Conclusion: Both pre-RT and post-RT primary tumor SUVmax can predict the outcome of patients with NSCLC treated with radiotherapy. Patients with high levels of pre-RT SUVmax seemed to have poorer overall survival and LC. PMID:24787963

  20. Development and Validation of a Prognostic Model Using Blood Biomarker Information for Prediction of Survival of Non-Small-Cell Lung Cancer Patients Treated With Combined Chemotherapy and Radiation or Radiotherapy Alone (NCT00181519, NCT00573040, and NCT00572325)

    SciTech Connect

    Dehing-Oberije, Cary; Aerts, Hugo; Yu Shipeng; De Ruysscher, Dirk; Menheere, Paul; Hilvo, Mika; Weide, Hiska van der; Rao, Bharat; Lambin, Philippe

    2011-10-01

    Purpose: Currently, prediction of survival for non-small-cell lung cancer patients treated with (chemo)radiotherapy is mainly based on clinical factors. The hypothesis of this prospective study was that blood biomarkers related to hypoxia, inflammation, and tumor load would have an added prognostic value for predicting survival. Methods and Materials: Clinical data and blood samples were collected prospectively (NCT00181519, NCT00573040, and NCT00572325) from 106 inoperable non-small-cell lung cancer patients (Stages I-IIIB), treated with curative intent with radiotherapy alone or combined with chemotherapy. Blood biomarkers, including lactate dehydrogenase, C-reactive protein, osteopontin, carbonic anhydrase IX, interleukin (IL) 6, IL-8, carcinoembryonic antigen (CEA), and cytokeratin fragment 21-1, were measured. A multivariate model, built on a large patient population (N = 322) and externally validated, was used as a baseline model. An extended model was created by selecting additional biomarkers. The model's performance was expressed as the area under the curve (AUC) of the receiver operating characteristic and assessed by use of leave-one-out cross validation as well as a validation cohort (n = 52). Results: The baseline model consisted of gender, World Health Organization performance status, forced expiratory volume, number of positive lymph node stations, and gross tumor volume and yielded an AUC of 0.72. The extended model included two additional blood biomarkers (CEA and IL-6) and resulted in a leave-one-out AUC of 0.81. The performance of the extended model was significantly better than the clinical model (p = 0.004). The AUC on the validation cohort was 0.66 and 0.76, respectively. Conclusions: The performance of the prognostic model for survival improved markedly by adding two blood biomarkers: CEA and IL-6.

  1. Evaluation of adjuvant postoperative radiotherapy for lung cancer

    SciTech Connect

    Chung, C.K.; Stryker, J.H.; O'Neill, M. Jr.; DeMuth, W.E. Jr.

    1982-11-01

    One hundred eighteen patients with lung cancer were retrospectively analyzed to determine whether postoperative radiotherapy (RT) improves survival. Patterns of treatment failure and three year NED (no evidence of disease) survival rates were assessed according to extent of tumor spread, histology, and treatment method. Patients with hilar or mediastinal node metastases were at higher risk of local failure compared to those with negative nodes. Postoperative RT reduced local recurrence and improved 3 year survival among patients with positive nodes. However, postoperative RT did not improve survival among those with negative nodes. Our data indicated that patients with positive hilar or mediastinal nodes may require postoperative RT to improve survival.

  2. Radiotherapy for non-small cell lung cancer in patients aged 75 and over: safety, effectiveness and possible impact on survival.

    PubMed

    Lonardi, F; Coeli, M; Pavanato, G; Adami, F; Gioga, G; Campostrini, F

    2000-04-01

    For patients with advanced, inoperable non-small cell lung cancer (NSCLC), increasing age seems to be the primary reason of receiving no treatment. The elderly aged 75 years and over are more likely to be given only supportive care (irrespective of symptoms) or no therapy at all. We evaluated the outcome of 48 patients, aged 75 years and over, treated with radiation therapy for advanced (stage IIIA-B), inoperable, symptomatic NSCLC. A median dose of 50 Gy was delivered to the primary site and mediastinum with standard fractionation. Based on WHO criteria, of 47 assessable patients, 21 had partial remission, 17 stable disease, and nine had progressive disease. Most symptoms were successfully palliated. Toxicity was negligible and mainly consisted of WHO grade I-II esophagitis. Despite the overall median survival being short (5 months), dose-related survival was much better in patients given at least 50 Gy than in those treated with lower doses: 52% versus 35% at 6 months, and 28% versus 4% at 13 months. These results confirm that radiation therapy may be safely delivered to very aged patients with advanced NSCLC at not merely palliative doses, both to achieve better local control and to give likely survival benefits. Adequate pretreatment evaluation should be always performed to exclude any comorbidity unfit to chest radiation and to individualize treatment to the single patient requirements. Because a large amount of literature data now concurs with the feasibility and safety of high-dose radiotherapy in the elderly, specifically designed, age-oriented trials are needed to settle definitively the issue of survival advantage from curative radiotherapy in these patients.

  3. Stereotactic ablative body radiotherapy (SABR) for primary and secondary lung tumours

    PubMed Central

    Gaya, Andrew

    2012-01-01

    Abstract Stereotactic ablative body radiotherapy (SABR) represents a technological breakthrough in radiotherapy technique, with proven benefits to patients in terms of improved tumour control and overall survival. The key components of SABR are described. The current evidence base for SABR for the treatment of primary and secondary lung tumours is appraised, and key ongoing trials are identified. PMID:23023165

  4. A longitudinal evaluation of improvements in radiotherapy treatment plan quality for head and neck cancer patients.

    PubMed

    Tol, Jim P; Doornaert, Patricia; Witte, Birgit I; Dahele, Max; Slotman, Ben J; Verbakel, Wilko F A R

    2016-05-01

    To investigate changes in head-and-neck cancer (HNC) plan quality following the introduction of new technologies and planning techniques in the last decade. Thirty plans were selected from each of four successive periods (P). P1: 7-field static intensity-modulated radiotherapy (IMRT) with parotid gland sparing; P2: dual-arc volumetric-modulated arc therapy (VMAT, similar to P3-P4), including submandibular gland sparing; P3: inclusion of individual swallowing muscles and attempts to further reduce parotid and oral cavity doses through manual interactive optimization; P4: containing the same organs-at-risk (OARs) as P3, but automatically interactively optimized. Plan benchmarking included mean salivary gland/swallowing muscle/oral cavity (Dsal/Dswal/Doc) doses. Differences in mean doses between the periods were analyzed by an ANCOVA, taking geometric differences across periods into account. Compared to P1, P2 plans improved Dsal by 3.4Gy on average. P3 improved Dsal/Dswal/Doc by 6.9/11.5/7.2Gy over P2, showing that Dswal and Dsal could be improved simultaneously. In P4, Doc/Dswal slightly improved over P3 by 1.7/3.8Gy. Improved OAR sparing in P3/P4 did not come at the cost of increased dose deposition elsewhere and planning target volume (PTV) dose homogeneity was similar. New technologies and planning techniques were successfully implemented into routine clinical care and resulting in improved HNC plan quality. Copyright © 2016. Published by Elsevier Ireland Ltd.

  5. TH-E-BRF-05: Comparison of Survival-Time Prediction Models After Radiotherapy for High-Grade Glioma Patients Based On Clinical and DVH Features

    SciTech Connect

    Magome, T; Haga, A; Igaki, H; Sekiya, N; Masutani, Y; Sakumi, A; Mukasa, A; Nakagawa, K

    2014-06-15

    Purpose: Although many outcome prediction models based on dose-volume information have been proposed, it is well known that the prognosis may be affected also by multiple clinical factors. The purpose of this study is to predict the survival time after radiotherapy for high-grade glioma patients based on features including clinical and dose-volume histogram (DVH) information. Methods: A total of 35 patients with high-grade glioma (oligodendroglioma: 2, anaplastic astrocytoma: 3, glioblastoma: 30) were selected in this study. All patients were treated with prescribed dose of 30–80 Gy after surgical resection or biopsy from 2006 to 2013 at The University of Tokyo Hospital. All cases were randomly separated into training dataset (30 cases) and test dataset (5 cases). The survival time after radiotherapy was predicted based on a multiple linear regression analysis and artificial neural network (ANN) by using 204 candidate features. The candidate features included the 12 clinical features (tumor location, extent of surgical resection, treatment duration of radiotherapy, etc.), and the 192 DVH features (maximum dose, minimum dose, D95, V60, etc.). The effective features for the prediction were selected according to a step-wise method by using 30 training cases. The prediction accuracy was evaluated by a coefficient of determination (R{sup 2}) between the predicted and actual survival time for the training and test dataset. Results: In the multiple regression analysis, the value of R{sup 2} between the predicted and actual survival time was 0.460 for the training dataset and 0.375 for the test dataset. On the other hand, in the ANN analysis, the value of R{sup 2} was 0.806 for the training dataset and 0.811 for the test dataset. Conclusion: Although a large number of patients would be needed for more accurate and robust prediction, our preliminary Result showed the potential to predict the outcome in the patients with high-grade glioma. This work was partly supported by

  6. Image-Guided Radiotherapy and -Brachytherapy for Cervical Cancer

    PubMed Central

    Dutta, Suresh; Nguyen, Nam Phong; Vock, Jacqueline; Kerr, Christine; Godinez, Juan; Bose, Satya; Jang, Siyoung; Chi, Alexander; Almeida, Fabio; Woods, William; Desai, Anand; David, Rick; Karlsson, Ulf Lennart; Altdorfer, Gabor

    2015-01-01

    Conventional radiotherapy for cervical cancer relies on clinical examination, 3-dimensional conformal radiotherapy (3D-CRT), and 2-dimensional intracavitary brachytherapy. Excellent local control and survival have been obtained for small early stage cervical cancer with definitive radiotherapy. For bulky and locally advanced disease, the addition of chemotherapy has improved the prognosis but toxicity remains significant. New imaging technology such as positron-emission tomography and magnetic resonance imaging has improved tumor delineation for radiotherapy planning. Image-guided radiotherapy (IGRT) may decrease treatment toxicity of whole pelvic radiation because of its potential for bone marrow, bowel, and bladder sparring. Tumor shrinkage during whole pelvic IGRT may optimize image-guided brachytherapy (IGBT), allowing for better local control and reduced toxicity for patients with cervical cancer. IGRT and IGBT should be integrated in future prospective studies for cervical cancer. PMID:25853092

  7. Image-guided radiotherapy and -brachytherapy for cervical cancer.

    PubMed

    Dutta, Suresh; Nguyen, Nam Phong; Vock, Jacqueline; Kerr, Christine; Godinez, Juan; Bose, Satya; Jang, Siyoung; Chi, Alexander; Almeida, Fabio; Woods, William; Desai, Anand; David, Rick; Karlsson, Ulf Lennart; Altdorfer, Gabor

    2015-01-01

    Conventional radiotherapy for cervical cancer relies on clinical examination, 3-dimensional conformal radiotherapy (3D-CRT), and 2-dimensional intracavitary brachytherapy. Excellent local control and survival have been obtained for small early stage cervical cancer with definitive radiotherapy. For bulky and locally advanced disease, the addition of chemotherapy has improved the prognosis but toxicity remains significant. New imaging technology such as positron-emission tomography and magnetic resonance imaging has improved tumor delineation for radiotherapy planning. Image-guided radiotherapy (IGRT) may decrease treatment toxicity of whole pelvic radiation because of its potential for bone marrow, bowel, and bladder sparring. Tumor shrinkage during whole pelvic IGRT may optimize image-guided brachytherapy (IGBT), allowing for better local control and reduced toxicity for patients with cervical cancer. IGRT and IGBT should be integrated in future prospective studies for cervical cancer.

  8. Trastuzumab improves locoregional control in HER2-positive breast cancer patients following adjuvant radiotherapy

    PubMed Central

    Cao, Lu; Cai, Gang; Xu, Fei; Yang, Zhao-Zhi; Yu, Xiao-Li; Ma, Jin-Li; Zhang, Qian; Wu, Jiong; Guo, Xiao-Mao; Chen, Jia-Yi

    2016-01-01

    Abstract The benefit of adjuvant trastuzumab in disease-free and overall survival for human epidermal receptor 2–positive (HER2+) breast cancer patients is well established. However, the effect of trastuzumab on locoregional control remains unclear, particularly in patients treated with adjuvant radiotherapy (RT). In this study, we investigated the locoregional benefit of trastuzumab in patients with HER2+ breast cancer after adjuvant RT. Using a single institutional database, we identified 278 patients with stage II/III invasive HER2+ breast tumors receiving adjuvant RT between January 2008 and July 2011. We compared the locoregional outcomes of 134 patients who received trastuzumab to 144 patients without trastuzumab within the same period. Clinical and biological factors that might impact on the locoregional benefit of trastuzumab were also assessed. At the median follow-up of 45 months, trastuzumab significantly lowered the risk of locoregional recurrence (LRR) with a 3-year LRR rate of 2.4% versus 7.5% for the cohort with and without trastuzumab (P = 0.019). Trastuzumab was associated with a more significant locoregional benefit in the hormone receptor–positive (HR+)/HER2+ subgroup, with a 3-year LRR of 0% versus 6.7% in the cohort with and without trastuzumab (P = 0.027). For HR−/HER2+ breast tumor patients, the 3-year LRR rate was still lower for the cohort with trastuzumab (4.7% vs 8.6%). However, statistical significance was not found (P = 0.179). Both univariate and multivariate analyses confirmed that trastuzumab treatment was the only significant predictive factor for LRR (hazard ratio, 4.05; 95% confidence interval, 1.07–15.35; P = 0.039). Adjuvant trastuzumab in addition to RT is associated with significant reduced LRR risk in HER2+ breast cancer. PMID:27512838

  9. {sup 18}Fluorodeoxyglucose PET Is Prognostic of Progression-Free and Overall Survival in Locally Advanced Pancreas Cancer Treated With Stereotactic Radiotherapy

    SciTech Connect

    Schellenberg, Devin; Quon, Andy; Minn, A. Yuriko; Graves, Edward E.; Kunz, Pamela; Ford, James M.; Fisher, George A.; Goodman, Karyn A.; Koong, Albert C.; Chang, Daniel T.

    2010-08-01

    Purpose: This study analyzed the prognostic value of positron emission tomography (PET) for locally advanced pancreas cancer patients undergoing stereotactic body radiotherapy (SBRT). Patients and Methods: Fifty-five previously untreated, unresectable pancreas cancer patients received a single fraction of 25-Gy SBRT sequentially with gemcitabine-based chemotherapy. On the preradiation PET-CT, the tumor was contoured and the maximum standardized uptake value (SUVmax) and metabolic tumor burden (MTB) were calculated using an in-house software application. High-SUVmax and low-SUVmax subgroups were created by categorizing patients above or below the median SUVmax. The analysis was repeated to form high-MTB and low-MTB subgroups as well as clinically relevant subgroups with SUVmax values of <5, 5-10, or >10. Multivariate analysis analyzing SUVmax, MTB, age, chemotherapy cycles, and pretreatment carbohydrate antigen (CA)19-9 was performed. Results: For the entire population, median survival was 12.7 months. Median survival was 9.8 vs.15.3 months for the high- and low- SUVmax subgroups (p <0.01). Similarly, median survival was 10.1 vs. 18.0 months for the high MTB and low MTB subgroups (p <0.01). When clinical SUVmax cutoffs were used, median survival was 6.4 months in those with SUVmax >10, 9.5 months with SUVmax 5.0-10.0, and 17.7 months in those with SUVmax <5 (p <0.01). On multivariate analysis, clinical SUVmax was an independent predictor for overall survival (p = 0.03) and progression-free survival (p = 0.03). Conclusion: PET scan parameters can predict for length of survival in locally advanced pancreas cancer patients.

  10. Pegfilgrastim Improves Survival of Lethally Irradiated Nonhuman Primates.

    PubMed

    Hankey, Kim G; Farese, Ann M; Blaauw, Erica C; Gibbs, Allison M; Smith, Cassandra P; Katz, Barry P; Tong, Yan; Prado, Karl L; MacVittie, Thomas J

    2015-06-01

    Leukocyte growth factors (LGF), such as filgrastim, pegfilgrastim and sargramostim, have been used to mitigate the hematologic symptoms of acute radiation syndrome (ARS) after radiation accidents. Although these pharmaceuticals are currently approved for treatment of chemotherapy-induced myelosuppression, such approval has not been granted for myelosuppression resulting from acute radiation exposure. Regulatory approval of drugs used to treat radiological or nuclear exposure injuries requires their development and testing in accordance with the Animal Efficacy Rule, set forth by the U.S. Food and Drug Administration. To date, filgrastim is the only LGF that has undergone efficacy assessment conducted under the Animal Efficacy Rule. To confirm the efficacy of another LGF with a shorter dosing regimen compared to filgrastim, we evaluated the use of pegfilgrastim (Neulasta(®)) in a lethal nonhuman primate (NHP) model of hematopoietic acute radiation syndrome (H-ARS). Rhesus macaques were exposed to 7.50 Gy total-body irradiation (the LD(50/60)), delivered at 0.80 Gy/min using linear accelerator 6 MV photons. Pegfilgrastim (300 μg/kg, n = 23) or 5% dextrose in water (n = 23) was administered on day 1 and 8 postirradiation and all animals received medical management. Hematologic and physiologic parameters were evaluated for 60 days postirradiation. The primary, clinically relevant end point was survival to day 60; secondary end points included hematologic-related parameters. Pegfilgrastim significantly (P = 0.0014) increased 60 day survival to 91.3% (21/23) from 47.8% (11/23) in the control. Relative to the controls, pegfilgrastim also significantly: 1. decreased the median duration of neutropenia and thrombocytopenia; 2. improved the median time to recovery of absolute neutrophil count (ANC) ≥500/μL, ANC ≥1,000/μL and platelet (PLT) count ≥20,000/μL; 3. increased the mean ANC at nadir; and 4. decreased the incidence of Gram-negative bacteremia. These data

  11. Whole-brain radiotherapy with or without efaproxiral for the treatment of brain metastases: Determinants of response and its prognostic value for subsequent survival

    SciTech Connect

    Stea, Baldassarre . E-mail: bstea@azcc.arizona.edu; Suh, John H.; Boyd, Adam P. M.S.; Cagnoni, Pablo J.; Shaw, Edward

    2006-03-15

    Purpose: To determine the prognostic factors for radiographic response and its prognostic value for subsequent survival in patients undergoing whole-brain radiotherapy (WBRT) for brain metastases. Methods and Materials: Five hundred fifteen eligible patients were randomized in a phase III trial evaluating WBRT and supplemental oxygen with or without efaproxiral, an allosteric modifier of hemoglobin that reduces hemoglobin oxygen-binding affinity and enhances tumor oxygenation, potentially increasing tumor radiosensitivity. Brain images were obtained at baseline and at scheduled follow-up visits after WBRT. Landmark analysis was used to assess the ability of response at selected time points to predict subsequent survival. Logistic regression was used to assess determinants of response at 3 months. Results: Treatment arm, Karnofsky Performance Status, presence or absence of liver metastases, and primary site were all determinants of response at the 3-month follow-up visit, with patients in the efaproxiral arm experiencing a 67% greater odds of response at this visit (p = 0.02). Response at 3 and 6 months was a significant prognostic factor for longer subsequent survival. Conclusions: The 3-month scan is a valuable prognostic factor for subsequent survival in patients with brain metastases treated with WBRT. Patients in the efaproxiral arm had a higher response rate at 3 and 6 months than those in the control arm.

  12. Clinical Outcomes among Children with Standard Risk Medulloblastoma Treated with Proton and Photon Radiotherapy: A Comparison of Disease Control and Overall Survival

    PubMed Central

    Eaton, Bree R; Esiashvili, Natia; Kim, Sungjin; Weyman, Elizabeth A.; Thornton, Lauren T.; Mazewski, Claire; MacDonald, Tobey; Ebb, David; MacDonald, Shannon M.; Tarbell, Nancy J.; Yock, Torunn

    2015-01-01

    Purpose/Objective(s) To compare long-term disease control and overall survival between children treated with proton and photon radiotherapy (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 among the two cohorts. Results Median (range) age at diagnosis was 6 yrs (3 - 21) for proton pts vs. 8 yrs (3 -19) for photon pts (p=0.011). Cohorts were similar with respect to gender, histology, extent of surgical resection, craniospinal (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) and a boost of 30.6 Gy (27 - 37.8). Median (95% CI) f/up time is 6.2 yrs (5.1 – 6.6) for proton pts vs. 7.0 yrs (5.8 – 8.9) for photon pts. There was no significant difference in RFS or OS between pts treated with proton vs. photon RT: 6 yr RFS 78.8% vs. 76.5% (p=0.948) and 6 yr OS 82.0 vs. 87.6% (p=0.285). On multivariable analysis, there was a trend for longer RFS with female gender (p=0.058) and higher CSI dose (p=0.096), and for longer OS with female gender (p=0.093). Patterns of failure were similar among the two cohorts (p=0.908). Conclusions Disease control with proton and photon radiotherapy appears equivalent for standard risk medulloblastoma. PMID:26700707

  13. Surgical spacer placement prior carbon ion radiotherapy (CIRT): an effective feasible strategy to improve the treatment for sacral chordoma.

    PubMed

    Lorenzo, Cobianchi; Andrea, Peloso; Barbara, Vischioni; Denis, Panizza; Rosaria, Fiore Maria; Piero, Fossati; Viviana, Vitolo; Alberto, Iannalfi; Mario, Ciocca; Brugnatelli, Silvia; Tommaso, Dominioni; Bugada, Dario; Marcello, Maestri; Mario, Alessiani; Francesca, Valvo; Roberto, Orecchia; Paolo, Dionigi

    2016-08-09

    Sacral chordoma (SC) is a neoplasm arising from residual notochordal cells degeneration. SC is difficult to manage mainly because of anatomic location and tendency to extensive spread. Carbon ion radiotherapy (CIRT) is highly precise to selectively deliver high biological effective dose to the tumor target sparing the anatomical structure on its path even if when SC is contiguous to the intestine, and a surgical spacer might be an advantageous tool to create a distance around the target volume allowing radical curative dose delivery with a safe dose gradient to the surrounding organs. This paper describes a double approach-open and hand-assisted laparoscopic-for a silicon spacer placement in patients affected by sacral chordoma undergoing carbon ion radiotherapy. Six consecutive patients have been enrolled for surgical spacer placement-open (three) or hand-assisted (three)-prior carbon ion radiotherapy treatment in order to increase efficacy of carbon ion radiotherapy minimizing its side effects. Results showed that silicon spacer placement for SC treatment is feasible both via laparoscopic and laparotomic approach. Its use might improve CIRT safety and thus efficacy for SC treatment.

  14. Effect of postoperative radiotherapy on survival for surgically managed pT3N0 and pT4aN0 laryngeal cancer: Analysis of the National Cancer Data Base.

    PubMed

    Graboyes, Evan M; Zhan, Kevin Y; Garrett-Mayer, Elizabeth; Lentsch, Eric J; Sharma, Anand K; Day, Terry A

    2017-06-15

    The current study was conducted to determine the effect of postoperative radiotherapy (PORT) on overall survival in patients with surgically managed pT3-T4aN0 laryngeal squamous cell carcinoma (SCC). A review of the National Cancer Data Base from 2004 through 2013 was performed. Patients with surgically managed pT3-4aN0 laryngeal SCC with negative surgical margins were included. Univariable and multivariable Cox regression analyses were used to determine factors associated with survival. A total of 1460 patients were included, 46.2% of whom had pT3N0 disease (674 patients) and 53.8% of whom had pT4aN0 disease (786 patients). Approximately 72.0% of the patients with pT3N0 disease (485 patients) and 50.1% of the patients with pT4aN0 disease (394 patients) received PORT. PORT was not found to be associated with improved overall survival on univariable analysis for patients with pT3N0 disease (hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62-1.14), but was for patients with pT4aN0 disease (HR, 0.57; 95% CI, 0.45-0.71). For patients with pT3N0 SCC of the larynx, in a multivariable Cox regression analysis adjusting for age >65 years, severity of comorbidities, larynx subsite, extent of laryngectomy, and number of lymph nodes removed, PORT was not found to be associated with improved survival (adjusted HR, 0.88; 95% CI, 0.64-1.21). For patients with pT4aN0 disease, the administration of PORT was associated with improved survival on multivariable analysis adjusting for age >65 years, severity of comorbidities, larynx subsite, number of lymph nodes removed, and type of hospital (adjusted HR, 0.58; 95% CI, 0.46-0.73). For patients with surgically managed pT3N0 laryngeal SCC with negative margins, PORT does not appear to be associated with improved survival. Despite a survival benefit, nearly 50% of patients with pT4aN0 laryngeal SCC and negative surgical margins do not receive standard-of-care PORT. Cancer 2017;123:2248-2257. © 2017 American Cancer Society.

  15. MRI micturating urethrography for improved urethral delineation in prostate radiotherapy planning: a case study

    NASA Astrophysics Data System (ADS)

    Rai, Robba; Sidhom, Mark; Lim, Karen; Ohanessian, Lucy; Liney, Gary P.

    2017-04-01

    Stereotactic ablative body radiotherapy is used in prostate cancer to deliver a high dose of radiation to the tumour over a small number of treatments. This involves the simulation of the patient using both CT and MRI. Current practice is to insert an indwelling catheter (IDC) during CT to assist with visualisation of the urethra and subsequently minimise dose to this highly critical structure. However, this procedure is invasive and has an associated risk of infection. This is a case study, which demonstrates our initial experience of using a real-time non-invasive MRI technique to replace the use of IDC for prostate cancer patients. The patient was scanned on a dedicated 3T MRI and was instructed to micturate in their own time whereupon a sagittal T2 weighted HASTE sequence was acquired every 5 s. This was subsequently followed by T2 weighted axial imaging at the level of mid prostate to provide improved urethral definition. Acquired images showed bladder voidance in real-time and an increase in signal intensity in the proximal urethra post voiding allowing for delineation of the urethra. The dimension and shape of the proximal urethra was well visualised and accumulation time of urine in the urethra was sufficient to enable optimum timing of the scanning technique. We have presented for the first time a micturating urethography technique using MRI, which has allowed us to visualise the urethra without contrast and with minimal invasiveness to the patient.

  16. Quality assurance of radiotherapy in cancer treatment: toward improvement of patient safety and quality of care.

    PubMed

    Ishikura, Satoshi

    2008-11-01

    The process of radiotherapy (RT) is complex and involves understanding of the principles of medical physics, radiobiology, radiation safety, dosimetry, radiation treatment planning, simulation and interaction of radiation with other treatment modalities. Each step in the integrated process of RT needs quality control and quality assurance (QA) to prevent errors and to give high confidence that patients will receive the prescribed treatment correctly. Recent advances in RT, including intensity-modulated and image-guided RT, focus on the need for a systematic RTQA program that balances patient safety and quality with available resources. It is necessary to develop more formal error mitigation and process analysis methods, such as failure mode and effect analysis, to focus available QA resources optimally on process components. External audit programs are also effective. The International Atomic Energy Agency has operated both an on-site and off-site postal dosimetry audit to improve practice and to assure the dose from RT equipment. Several countries have adopted a similar approach for national clinical auditing. In addition, clinical trial QA has a significant role in enhancing the quality of care. The Advanced Technology Consortium has pioneered the development of an infrastructure and QA method for advanced technology clinical trials, including credentialing and individual case review. These activities have an impact not only on the treatment received by patients enrolled in clinical trials, but also on the quality of treatment administered to all patients treated in each institution, and have been adopted globally; by the USA, Europe and Japan also.

  17. Improved planning time and plan quality through multicriteria optimization for intensity-modulated radiotherapy.

    PubMed

    Craft, David L; Hong, Theodore S; Shih, Helen A; Bortfeld, Thomas R

    2012-01-01

    To test whether multicriteria optimization (MCO) can reduce treatment planning time and improve plan quality in intensity-modulated radiotherapy (IMRT). Ten IMRT patients (5 with glioblastoma and 5 with locally advanced pancreatic cancers) were logged during the standard treatment planning procedure currently in use at Massachusetts General Hospital (MGH). Planning durations and other relevant planning information were recorded. In parallel, the patients were planned using an MCO planning system, and similar planning time data were collected. The patients were treated with the standard plan, but each MCO plan was also approved by the physicians. Plans were then blindly reviewed 3 weeks after planning by the treating physician. In all cases, the treatment planning time was vastly shorter for the MCO planning (average MCO treatment planning time was 12 min; average standard planning time was 135 min). The physician involvement time in the planning process increased from an average of 4.8 min for the standard process to 8.6 min for the MCO process. In all cases, the MCO plan was blindly identified as the superior plan. This provides the first concrete evidence that MCO-based planning is superior in terms of both planning efficiency and dose distribution quality compared with the current trial and error-based IMRT planning approach. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. IMPROVED PLANNING TIME AND PLAN QUALITY THROUGH MULTICRITERIA OPTIMIZATION FOR INTENSITY-MODULATED RADIOTHERAPY

    PubMed Central

    Craft, David L.; Hong, Theodore S.; Shih, Helen A.; Bortfeld, Thomas R.

    2011-01-01

    Purpose To test whether multicriteria optimization (MCO) can reduce treatment planning time and improve plan quality in intensity-modulated radiotherapy (IMRT). Methods and Materials Ten IMRT patients (5 with glioblastoma and 5 with locally advanced pancreatic cancers) were logged during the standard treatment planning procedure currently in use at Massachusetts General Hospital (MGH). Planning durations and other relevant planning information were recorded. In parallel, the patients were planned using an MCO planning system, and similar planning time data were collected. The patients were treated with the standard plan, but each MCO plan was also approved by the physicians. Plans were then blindly reviewed 3 weeks after planning by the treating physician. Results In all cases, the treatment planning time was vastly shorter for the MCO planning (average MCO treatment planning time was 12 min; average standard planning time was 135 min). The physician involvement time in the planning process increased from an average of 4.8 min for the standard process to 8.6 min for the MCO process. In all cases, the MCO plan was blindly identified as the superior plan. Conclusions This provides the first concrete evidence that MCO-based planning is superior in terms of both planning efficiency and dose distribution quality compared with the current trial and error–based IMRT planning approach. PMID:21300448

  19. Improved Planning Time and Plan Quality Through Multicriteria Optimization for Intensity-Modulated Radiotherapy

    SciTech Connect

    Craft, David L.; Hong, Theodore S.; Shih, Helen A.; Bortfeld, Thomas R.

    2012-01-01

    Purpose: To test whether multicriteria optimization (MCO) can reduce treatment planning time and improve plan quality in intensity-modulated radiotherapy (IMRT). Methods and Materials: Ten IMRT patients (5 with glioblastoma and 5 with locally advanced pancreatic cancers) were logged during the standard treatment planning procedure currently in use at Massachusetts General Hospital (MGH). Planning durations and other relevant planning information were recorded. In parallel, the patients were planned using an MCO planning system, and similar planning time data were collected. The patients were treated with the standard plan, but each MCO plan was also approved by the physicians. Plans were then blindly reviewed 3 weeks after planning by the treating physician. Results: In all cases, the treatment planning time was vastly shorter for the MCO planning (average MCO treatment planning time was 12 min; average standard planning time was 135 min). The physician involvement time in the planning process increased from an average of 4.8 min for the standard process to 8.6 min for the MCO process. In all cases, the MCO plan was blindly identified as the superior plan. Conclusions: This provides the first concrete evidence that MCO-based planning is superior in terms of both planning efficiency and dose distribution quality compared with the current trial and error-based IMRT planning approach.

  20. Survival and secondary tumors in children with medulloblastoma receiving radiotherapy and adjuvant chemotherapy: results of Children's Oncology Group trial A9961.

    PubMed

    Packer, Roger J; Zhou, Tianni; Holmes, Emi; Vezina, Gilbert; Gajjar, Amar

    2013-01-01

    The purpose of the trial was to determine the survival and incidence of secondary tumors in children with medulloblastoma receiving radiotherapy plus chemotherapy. Three hundred seventy-nine eligible patients with nondisseminated medulloblastoma between the ages of 3 and 21 years were treated with 2340 cGy of craniospinal and 5580 cGy of posterior fossa irradiation. Patients were randomized between postradiation cisplatin and vincristine plus either CCNU or cyclophosphamide. Survival, pattern of relapse, and occurrence of secondary tumors were assessed. Five- and 10-year event-free survivals were 81 ± 2% and 75.8 ± 2.3%; overall survivals were 87 ± 1.8% and 81.3 ± 2.1%. Event-free survival was not impacted by chemotherapeutic regimen, sex, race, age at diagnosis, or gender. Seven patients had disease relapse beyond 5 years after diagnosis; relapse was local in 4 patients, local plus supratentorial in 2, and supratentorial alone in 1. Fifteen patients experienced secondary tumors as a first event at a median time of 5.8 years after diagnosis (11 >5 y postdiagnosis). All non-CNS solid secondary tumors (4) occurred in regions that had received radiation. Of the 6 high-grade gliomas, 5 occurred >5 years postdiagnosis. The estimated cumulative 10-year incidence rate of secondary malignancies was 4.2% (1.9%-6.5%). Few patients with medulloblastoma will relapse ≥ 5 years postdiagnosis; relapse will occur predominantly at the primary tumor site. Patients are at risk for development of secondary tumors, many of which are malignant gliomas. This may become an increasing issue as more children survive.

  1. HLA-E expression in cervical adenocarcinomas: association with improved long-term survival

    PubMed Central

    2012-01-01

    Background Cervical cancer is the third most common cancer in women worldwide. The most common histopathological subtype is cervical squamous cell carcinoma (SCC, 75-80%), followed by adenocarcinoma (AC) and adenosquamous carcinoma (ASC; together 15-20%). Rising incidence rates of AC have been observed relative and absolute to SCC and evidence is accumulating that cervical AC is a distinct clinical entity. Cervical SCC, ASC, and AC are caused by a persistent infection with high-risk human papillomavirus (HPV) and failed control of the immune system plays a pivotal role in the carcinogenesis of all three histopathological subtypes. Human leukocyte antigen E (HLA-E), a non-classical HLA class Ib molecule, plays an important role in immune surveillance and immune escape of virally infected cells. In this study we investigated HLA-E expression in three well-defined cohorts of cervical AC, ASC, and SCC patients, and determined whether HLA-E expression was associated with histopathological parameters and patient survival. Methods and results HLA-E expression was assessed by immunohistochemistry on formalin-fixed, paraffin-embedded tissue sections of 79 SCC, 38 ASC, and 75 AC patients. All patients included were International Federation of Gynaecology and Obstetrics stage I-II and underwent radical hysterectomy with lymphadenectomy as primary treatment. Significant differences between the histopathological subgroups were detected for age distribution, HPV positivity, HPV type distribution, tumour size, tumour infiltration depth, lymph-vascular space invasion, and adjuvant radiotherapy. High expression of HLA-E was found in 107/192 (56%) cervical carcinomas, with significantly more overexpression in cervical AC compared to SCC and ASC (37/79 SCC, 18/38 ASC, and 52/75 AC; P = 0.010). High HLA-E expression in cervical AC was associated with favourable long term disease-specific and recurrence-free survival (P = 0.005 and P = 0.001, respectively). Conclusion

  2. Developing a rat model of dilated cardiomyopathy with improved survival* #

    PubMed Central

    Shen, Li-juan; Lu, Shu; Zhou, Yong-hua; Li, Lan; Xing, Qing-min; Xu, Yong-liang

    2016-01-01

    To compare the continuous infusion and intermittent bolus injection administration protocols of doxorubicin (Dox) under the same cumulative dose (12 mg/kg), and establish a rat dilated cardiomyopathy model with improved survival, a total of 150 Sprague-Dawley (SD) rats were divided into three groups: a control group, administered with normal saline; a Dox 1 group, administration twice a week at 1 mg/kg; a Dox 2, administration once a week at 2 mg/kg. Mortality rates in the Dox 1 and Dox 2 groups were 22% and 48%, respectively (P<0.05). As shown by echocardiography, both Dox groups exhibited significant chamber dilatation and reduced cardiac function (all P<0.05 vs. control). Plasma brain natriuretic peptide and C-reactive protein concentrations were significantly increased (P<0.05) with both Dox regimens. The concentrations of Caspase-3 in myocardial tissues of rats significantly increased in both doxorubicin regimens. Myocardial metabolism imaging by histology and 18F-fluoro-deoxyglucose-positron emission tomography (18FDG-PET) both revealed decreased myocardial viability and necrosis, and even interstitial fibrosis, in left ventricles (LVs) in both Dox groups. Serum creatinine and aspartate aminotransferase concentrations were significantly higher in the Dox 2 model than in the Dox 1 model. Doxorubicin given at both regimens induced dilated cardiomyopathy, while its administration at lower doses with more frequent infusions reduced the mortality rate. PMID:27921402

  3. CSF1R signaling blockade stanches tumor-infiltrating myeloid cells and improves the efficacy of radiotherapy

    PubMed Central

    Xu, Jingying; Escamilla, Jemima; Mok, Stephen; David, John; Priceman, Saul; West, Brian; Bollag, Gideon; McBride, William; Wu, Lily

    2014-01-01

    Radiotherapy is used to treat many types of cancer, but many treated patients relapse with local tumor recurrence. Tumor-infiltrating myeloid cells (TIMs), including CD11b (ITGAM)+F4/80 (EMR1)+ tumor-associated macrophages (TAMs) and CD11b+Gr-1 (LY6G)+ myeloid-derived suppressor cells (MDSCs), respond to cancer-related stresses and play critical roles in promoting tumor angiogenesis, tissue remodeling and immunosuppression. In this report, we employed a prostate cancer model to investigate the effects of irradiation on TAMs and MDSCs in tumor-bearing animals. Unexpectedly, when primary tumor sites were irradiated we observed a systemic increase of MDSCs in spleen, lung, lymph nodes and peripheral blood. Cytokine analysis showed that the macrophage colony-stimulating factor CSF1 increased by 2-fold in irradiated tumors. Enhanced macrophage migration induced by conditioned media from irradiated tumor cells was completely blocked by a selective inhibitor of CSF1R. These findings were confirmed in prostate cancer patients, where serum levels of CSF1 increased after radiotherapy. Mechanistic investigations revealed the recruitment of the DNA damage-induced kinase ABL1 into cell nuclei where it bound the CSF1 gene promoter and enhanced CSF1 gene transcription. When added to radiotherapy, a selective inhibitor of CSF1R suppressed tumor growth more effectively than radiation alone. Our results highlight the importance of CSF1/CSF1R signaling in the recruitment of TIMs which can limit the efficacy of radiotherapy. Further, they suggest that CSF1 inhibitors should be evaluated in clinical trials in combination with radiotherapy as a strategy to improve outcomes. PMID:23418320

  4. CSF1R signaling blockade stanches tumor-infiltrating myeloid cells and improves the efficacy of radiotherapy in prostate cancer.

    PubMed

    Xu, Jingying; Escamilla, Jemima; Mok, Stephen; David, John; Priceman, Saul; West, Brian; Bollag, Gideon; McBride, William; Wu, Lily

    2013-05-01

    Radiotherapy is used to treat many types of cancer, but many treated patients relapse with local tumor recurrence. Tumor-infiltrating myeloid cells (TIM), including CD11b (ITGAM)(+)F4/80 (EMR1)+ tumor-associated macrophages (TAM), and CD11b(+)Gr-1 (LY6G)+ myeloid-derived suppressor cells (MDSC), respond to cancer-related stresses and play critical roles in promoting tumor angiogenesis, tissue remodeling, and immunosuppression. In this report, we used a prostate cancer model to investigate the effects of irradiation on TAMs and MDSCs in tumor-bearing animals. Unexpectedly, when primary tumor sites were irradiated, we observed a systemic increase of MDSCs in spleen, lung, lymph nodes, and peripheral blood. Cytokine analysis showed that the macrophage colony-stimulating factor CSF1 increased by two-fold in irradiated tumors. Enhanced macrophage migration induced by conditioned media from irradiated tumor cells was completely blocked by a selective inhibitor of CSF1R. These findings were confirmed in patients with prostate cancer, where serum levels of CSF1 increased after radiotherapy. Mechanistic investigations revealed the recruitment of the DNA damage-induced kinase ABL1 into cell nuclei where it bound the CSF1 gene promoter and enhanced CSF1 gene transcription. When added to radiotherapy, a selective inhibitor of CSF1R suppressed tumor growth more effectively than irradiation alone. Our results highlight the importance of CSF1/CSF1R signaling in the recruitment of TIMs that can limit the efficacy of radiotherapy. Furthermore, they suggest that CSF1 inhibitors should be evaluated in clinical trials in combination with radiotherapy as a strategy to improve outcomes.

  5. Methods for improving limited field-of-view radiotherapy reconstructions using imperfect a priori images.

    PubMed

    Ruchala, Kenneth J; Olivera, Gustavo H; Kapatoes, Jeffrey M; Reckwerdt, Paul J; Mackie, Thomas R

    2002-11-01

    There are many benefits to having an online CT imaging system for radiotherapy, as it helps identify changes in the patient's position and anatomy between the time of planning and treatment. However, many current online CT systems suffer from a limited field-of-view (LFOV) in that collected data do not encompass the patient's complete cross section. Reconstruction of these data sets can quantitatively distort the image values and introduce artifacts. This work explores the use of planning CT data as a priori information for improving these reconstructions. Methods are presented to incorporate this data by aligning the LFOV with the planning images and then merging the data sets in sinogram space. One alignment option is explicit fusion, producing fusion-aligned reprojection (FAR) images. For cases where explicit fusion is not viable, FAR can be implemented using the implicit fusion of normal setup error, referred to as normal-error-aligned reprojection (NEAR). These methods are evaluated for multiday patient images showing both internal and skin-surface anatomical variation. The iterative use of NEAR and FAR is also investigated, as are applications of NEAR and FAR to dose calculations and the compensation of LFOV online MVCT images with kVCT planning images. Results indicate that NEAR and FAR can utilize planning CT data as imperfect a priori information to reduce artifacts and quantitatively improve images. These benefits can also increase the accuracy of dose calculations and be used for augmenting CT images (e.g., MVCT) acquired at different energies than the planning CT.

  6. Improving target definition for head and neck radiotherapy: a place for magnetic resonance imaging and 18-fluoride fluorodeoxyglucose positron emission tomography?

    PubMed

    Prestwich, R J D; Sykes, J; Carey, B; Sen, M; Dyker, K E; Scarsbrook, A F

    2012-10-01

    Defining the target for head and neck radiotherapy is a critical issue with the introduction of steep dose gradients associated with intensity-modulated radiotherapy. Tumour delineation inaccuracies are a major source of error in radiotherapy planning. The integration of 18-fluoride fluorodeoxyglucose positron emission tomography ((18)FDG-PET) and magnetic resonance imaging directly into the radiotherapy planning process has the potential to greatly improve target identification/selection and delineation. This raises a range of new issues surrounding image co-registration, delineation methodology and the use of functional data and treatment adaptation. This overview will discuss the practical aspects of integrating (18)FDG-PET and magnetic resonance imaging into head and neck radiotherapy planning.

  7. Long-Term Improvement in Treatment Outcome After Radiotherapy and Hyperthermia in Locoregionally Advanced Cervix Cancer: An Update of the Dutch Deep Hyperthermia Trial

    SciTech Connect

    Franckena, Martine Stalpers, Lukas J.A.; Koper, Peter C.M.; Wiggenraad, Ruud G.J.; Hoogenraad, Wim J.; Dijk, Jan D.P. van; Warlam-Rodenhuis, Carla C.; Jobsen, Jan J.; Rhoon, Gerard C. van; Zee, Jacoba van der

    2008-03-15

    Purpose: The local failure rate in patients with locoregionally advanced cervical cancer is 41-72% after radiotherapy (RT) alone, whereas local control is a prerequisite for cure. The Dutch Deep Hyperthermia Trial showed that combining RT with hyperthermia (HT) improved 3-year local control rates of 41-61%, as we reported earlier. In this study, we evaluate long-term results of the Dutch Deep Hyperthermia Trial after 12 years of follow-up. Methods and Materials: From 1990 to 1996, a total of 114 women with locoregionally advanced cervical carcinoma were randomly assigned to RT or RT + HT. The RT was applied to a median total dose of 68 Gy. The HT was given once weekly. The primary end point was local control. Secondary end points were overall survival and late toxicity. Results: At the 12-year follow-up, local control remained better in the RT + HT group (37% vs. 56%; p = 0.01). Survival was persistently better after 12 years: 20% (RT) and 37% (RT + HT; p = 0.03). World Health Organization (WHO) performance status was a significant prognostic factor for local control. The WHO performance status, International Federation of Gynaecology and Obstetrics (FIGO) stage, and tumor diameter were significant for survival. The benefit of HT remained significant after correction for these factors. European Organization for Research and Treatment of Cancer Grade 3 or higher radiation-induced late toxicities were similar in both groups. Conclusions: For locoregionally advanced cervical cancer, the addition of HT to RT resulted in long-term major improvement in local control and survival without increasing late toxicity. This combined treatment should be considered for patients who are unfit to receive chemotherapy. For other patients, the optimal treatment strategy is the subject of ongoing research.

  8. Private Payer's Status Improves Male Breast Cancer Survival.

    PubMed

    Shi, Runhua; Taylor, Hannah; Liu, Lihong; Mills, Glenn; Burton, Gary

    2016-01-01

    Survival from male breast cancer is influenced by many factors. This study assessed payer's status effect on survival of male breast cancer patients. This study included 8,828 male breast cancer patients diagnosed between 1998-2006 and followed to 2011 in the National Cancer Data Base. Cox regression was used to investigate the effect of payer's status and other factors on overall survival. Patients had 36.2%, 42.7%, 14.7%, and 6.5% of stage I to IV cancer, respectively. Payer status was private 47.7%, Medicare 42.6%, Medicaid 3.24%, unknown 3.59%, and uninsured 2.95%. Median overall survival (MOS) for all patients was 10.6 years. In multivariate analysis, Direct adjusted MOS was 12.46, 11.89, 9.99, 9.02, and 8.29 years for private, "unknown," Medicare, uninsured, and Medicaid payer's status, respectively. Patients with private and "unknown" payer's status showed a significant difference in survival compared to uninsured patients, while Medicaid and Medicare patients did not. Age, race, stage, grade, income, comorbidity, distance travelled, and diagnosing/treating facility were also significant predictors of survival. Treatment delay and cancer program did not have a significant influence on survival. © 2015 Wiley Periodicals, Inc.

  9. Local Tumor Control, Visual Acuity, and Survival After Hypofractionated Stereotactic Photon Radiotherapy of Choroidal Melanoma in 212 Patients Treated Between 1997 and 2007

    SciTech Connect

    Dunavoelgyi, Roman; Dieckmann, Karin; Gleiss, Andreas; Sacu, Stefan; Kircher, Karl; Georgopoulos, Michael; Georg, Dietmar; Zehetmayer, Martin; Poetter, Richard

    2011-09-01

    Purpose: To evaluate long-term local tumor control, visual acuity, and survival after hypofractionated linear accelerator-based stereotactic photon radiotherapy in patients with choroidal melanoma. Methods and Materials: Between 1997 and 2007, 212 patients with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated stereotactically at a linear accelerator with 6-MV photon beams at the Medical University of Vienna in five fractions over 7 days. Twenty-four patients received a total dose of 70 Gy (five fractions of 14 Gy), 158 a total dose of 60 Gy (five fractions of 12 Gy) and 30 patients a total dose of 50 Gy (five fractions of 10 Gy) applied on the 80% isodose. Ophthalmologic examinations were performed at baseline and every 3 months in the first 2 years, every 6 months until 5 years, and once a year thereafter until 10 years after radiotherapy. Assessment of visual acuity, routine ophthalmologic examinations, and measurement of tumor base dimension and height using standardized A-scan and B-scan echography were done at each visit. Funduscopy and fluorescein angiography were done when necessary to document tumor response. Results: Median tumor height and volume decreased from 4.8 mm and 270.7 mm{sup 3} at baseline to 2.6 mm and 86.6 mm{sup 3} at the last individual follow-up, respectively (p < 0.001, p < 0.001). Median visual acuity decreased from 0.55 at baseline to hand motion at the last individual follow-up (p < 0.001). Local tumor control was 95.9% after 5 years and 92.6% after 10 years. Thirty-two patients developed metastatic disease, and 22 of these patients died during the follow-up period. Conclusion: Hypofractionated stereotactic photon radiotherapy with 70 to 50 Gy delivered in five fractions in 7 days is sufficient to achieve excellent local tumor control in patients with malignant melanoma of the choroid. Disease outcome and vision are comparable to those achieved with proton beam radiotherapy. Decreasing the

  10. Disparities in receipt of radiotherapy and survival by age, sex, and race among patients with non-metastatic squamous cell carcinoma of the anus.

    PubMed

    Baughman, Doug M; Shah, Binay K

    2016-12-01

    Combination chemoradiotherapy is the standard of care for treatment of non-metastatic squamous cell carcinoma of the anus (SCCA). This population based study evaluated disparities in receipt of radiotherapy (RT) as well as comparative survival rates for SCCA patients in the United States. The Surveillance, Epidemiology, and End Results (SEER) 18 database was used to identify patients with non-metastatic SCCA diagnosed between 1998 and 2008. Multivariate logistic regression was used to model the relationships between age, sex, and race and the receipt of RT, adjusting for marital status and stage of disease. Relative survival (RS) rates were compared by each factor, with added adjustment for RT status, using Cox proportional hazards model. A total of 3,885 patients with localized or regional SCCA as the only primary malignancy were included in the study, of which, 3,192 (82%) received RT. In our multivariate analysis, lower rates of RT were found for those 65+ years old [adjusted odds ratio (OR) 0.71; P<0.001], males (adjusted OR 0.65; P<0.001), and blacks (adjusted OR 0.78; P=0.049). Multivariate survival analysis showed worse survival among those 65+ years old (adjusted HR 1.65; P<0.001), males (adjusted HR 1.53; P<0.001), and blacks (adjusted HR 1.35; P=0.001). This population based study identified older patients, males, and blacks as less likely to receive RT. Worse survival was also found in these groups.

  11. Disparities in receipt of radiotherapy and survival by age, sex, and race among patients with non-metastatic squamous cell carcinoma of the anus

    PubMed Central

    Baughman, Doug M.

    2016-01-01

    Background Combination chemoradiotherapy is the standard of care for treatment of non-metastatic squamous cell carcinoma of the anus (SCCA). This population based study evaluated disparities in receipt of radiotherapy (RT) as well as comparative survival rates for SCCA patients in the United States. Methods The Surveillance, Epidemiology, and End Results (SEER) 18 database was used to identify patients with non-metastatic SCCA diagnosed between 1998 and 2008. Multivariate logistic regression was used to model the relationships between age, sex, and race and the receipt of RT, adjusting for marital status and stage of disease. Relative survival (RS) rates were compared by each factor, with added adjustment for RT status, using Cox proportional hazards model. Results A total of 3,885 patients with localized or regional SCCA as the only primary malignancy were included in the study, of which, 3,192 (82%) received RT. In our multivariate analysis, lower rates of RT were found for those 65+ years old [adjusted odds ratio (OR) 0.71; P<0.001], males (adjusted OR 0.65; P<0.001), and blacks (adjusted OR 0.78; P=0.049). Multivariate survival analysis showed worse survival among those 65+ years old (adjusted HR 1.65; P<0.001), males (adjusted HR 1.53; P<0.001), and blacks (adjusted HR 1.35; P=0.001). Conclusions This population based study identified older patients, males, and blacks as less likely to receive RT. Worse survival was also found in these groups. PMID:28078120

  12. Omitting adjuvant radiotherapy in endometrial cancer increases the rate of locoregional recurrences but has no effect on long-term survival: the Danish Endometrial Cancer Study.

    PubMed

    Ørtoft, Gitte; Hansen, Estrid Stæhr; Bertelsen, Kamma

    2013-10-01

    In 2 prospective nationwide studies, the Danish Endometrial Cancer Study demonstrated that postoperative radiotherapy (RT) could be omitted in low- and intermediate-risk stage I patients without loss of survival when evaluated after 5 years. In the present study, we evaluated the consequence of this decision on the long-term risk of recurrence and death. From 1998 to 1999, 1166 patients newly diagnosed with uterine carcinoma were included. Of these, 586 were low-risk, 231 intermediate-risk, and 78 high-risk stage I. Low- and intermediate-risk patients received standard primary surgery (hysterectomy and bilateral salpingo-oophorectomy), and no postoperative RT was given. Long-term recurrence and survival rates were estimated. After 14 years, 6.3% of low-risk and 22% of intermediate-risk patients had relapsed compared with 32% of high-risk patients. Recurrences were dominated by locoregional relapse in the low and intermediate risk, whereas non-locoregional relapses were prominent in high risk. After locoregional relapse, 1.5% of low and 4.3% of intermediate risk experienced a second relapse dominated by non-locoregional relapses. After curative-intended treatment of vaginal recurrence in the low- and intermediate-risk patients, 100% had complete remission after the first vaginal recurrence, whereas only 74% was cured after the first or the second recurrence. The increased recurrence rate, however, does not seem to affect survival because the survival rate did not change compared to earlier Danish population-based data. We conclude that omitting RT in early stage endometrial cancer increase local recurrences, but without affecting long-term survival.

  13. Overexpression of Phosphorylated 4E-BP1 Predicts for Tumor Recurrence and Reduced Survival in Cervical Carcinoma Treated With Postoperative Radiotherapy

    SciTech Connect

    Benavente, Sergio; Verges, Ramona; Hermosilla, Eduardo; Fumanal, Victor; Casanova, Nathalie; Garcia, Angel; Ramon y Cajal, Santiago; Giralt, Jordi

    2009-12-01

    Purpose: To examine the prognostic value of the 4E-BP1 activation state and related upstream/downstream signaling proteins on the clinical outcome of patients with intermediate- or high-risk early-stage cervical carcinoma treated with postoperative radiotherapy and to determine the optimal treatment of early-stage cervical carcinoma. Methods and Materials: Immunohistochemical staining was performed on 64 formalin-fixed, paraffin-embedded cervical carcinoma surgical specimens for each protein of the panel (p4E-BP1, phosphorylated mitogen-activated protein kinase, pAkt, vascular endothelial growth factor, KDR, Bcl-2, TP53, receptor for activated C-kinase 1). The expression patterns were related to the clinical data. All patients received postoperative radiotherapy. Concurrent chemotherapy was added if high-risk features were present. The median follow-up was 40 months. Results: Of the 64 patients, 13 received concomitant chemotherapy. p4E-BP1 overexpression in moderate/high-risk early-stage cervical carcinoma correlated significantly with disease-free survival (hazard ratio, 4.39; p = .009) and overall survival (hazard ratio, 4.88; p = .005). Vascular endothelial growth factor, and its receptor KDR, had positive immunoreactivity in all tumor samples. No correlation with clinical outcome was found for the remaining proteins evaluated. Conclusion: In this study, moderate/high-risk early-stage cervical carcinoma with low p4E-BP1 expression was highly curable with the current postoperative treatments. For tumors with p4E-BP1 overexpression, new investigational strategies are needed.

  14. Preoperative Chemotherapy, Radiation Improve Survival in Esophageal Cancer (Updated)

    Cancer.gov

    Patients with esophageal cancer who received chemotherapy and radiation before surgery survived, on average, nearly twice as long as patients treated with surgery alone, according to results of a randomized clinical trial published May 31, 2012, in NEJM.

  15. Prognostic Factors of Survival in the Trastuzumab Era Among Women With Breast Cancer and Brain Metastases Who Receive Whole Brain Radiotherapy

    PubMed Central

    Dawood, Shaheenah; Gonzalez-Angulo, Ana M.; Albarracin, Constance; Yu, Tse Kuan; Hortobagyi, Gabriel N.; Buchholz, Thomas A.; Woodward, Wendy A.

    2011-01-01

    BACKGROUND The objective of this study was to review the outcome of women with breast cancer with known receptor status who were treated with whole brain radiotherapy for brain metastases and to determine factors that impact survival. METHODS A total of 223 women with breast cancer and brain metastases, who received whole brain radiotherapy, were identified. All women with HER-2–positive disease had received trastuzumab. Kaplan-Meier prodct limit method was used to determine overall survival (OS) estimates. Cox proportional hazards models were then fitted to explore the association of OS with various patient and tumor characteristics. RESULTS Median age at brain metastases diagnosis was 50 years. Sixty-seven (30.2%) patients had hormone receptor-positive/HER-2–negative disease, 101 (45.50%) had HER-2–positive disease, and 54 (24.3%) had triple receptor-negative disease. Median OS from brain metastases was 6 months, with 1-year survival of 30% (95% confidence interval [CI], 23%-36%). Women with hormone receptor-positive/HER-2–negative, HER-2–positive, and triple-negative tumors had median survivals of 5, 9, and 5 months, respectively (P =.0069). In the multivariate model, women with HER-2–positive disease had a significantly decreased risk of death compared with women with hormone receptor-positive/HER-2–negative disease (hazard ratio, 0.63; 95%CI, 0.42-0.94; P =.02). The risk of death among women with triple-negative disease compared with hormone receptor-positive/HER-2–negative disease was not significantly different (P =.54). Lower recursive partitioning analysis class and ≥30-gray brain radiation dose were also significantly associated with a decreased risk of death. CONCLUSIONS Breast tumor subtype has a significant prognostic role among women with breast cancer and brain metastases. In addition, in the trastuzumab era factors such as recursive partitioning analysis and adequate radiation dose continue to be important prognostic factors. PMID

  16. Method of freezing living cells and tissues with improved subsequent survival

    DOEpatents

    Senkan, Selim M.; Hirsch, Gerald P.

    1980-01-01

    This invention relates to an improved method for freezing red blood cells, ther living cells, or tissues with improved subsequent survival, wherein constant-volume freezing is utilized that results in significantly improved survival compared with constant-pressure freezing; optimization is attainable through the use of different vessel geometries, cooling baths and warming baths, and sample concentrations.

  17. 38 CFR 3.24 - Improved pension rates-Surviving children.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-Surviving children. 3.24 Section 3.24 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... rates—Surviving children. (a) General. The provisions of this section apply to children of a deceased.... Children in custody of a surviving spouse who has basic eligibility to receive improved pension do not...

  18. 38 CFR 3.24 - Improved pension rates-Surviving children.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-Surviving children. 3.24 Section 3.24 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... rates—Surviving children. (a) General. The provisions of this section apply to children of a deceased.... Children in custody of a surviving spouse who has basic eligibility to receive improved pension do not...

  19. 38 CFR 3.24 - Improved pension rates-Surviving children.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-Surviving children. 3.24 Section 3.24 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... rates—Surviving children. (a) General. The provisions of this section apply to children of a deceased.... Children in custody of a surviving spouse who has basic eligibility to receive improved pension do not...

  20. Radiotherapy Can Decrease Locoregional Recurrence and Increase Survival in Mastectomy Patients With T1 to T2 Breast Cancer and One to Three Positive Nodes With Negative Estrogen Receptor and Positive Lymphovascular Invasion Status

    SciTech Connect

    Yang, P.S.; Chen, C.M.; Liu, M.C.; Jian, J.M.; Horng, C.F.; Liu, M.J.; Yu, B.L.; Lee, M.Y.; Chi, C.W.

    2010-06-01

    Purpose: To define a subgroup of patients at high risk of locoregional recurrence (LRR) who might be benefit from postmastectomy radiotherapy in invasive breast cancer and tumor size <5 cm with one to three involved axillary lymph nodes (T1-2 N1). Methods and Materials: Between April 1991 and December 2005, 544 patients with T1-2 N1 invasive breast cancer were treated with modified radical mastectomy. Of the 544 patients, 383 patients (70.4%) had no radiotherapy, and 161 patients (29.6%) received radiotherapy. We retrospectively compared these two patient groups. Results: With a median follow-up of 40.3 months, LRR occurred in 40 (7.4%) of 544 patients. On univariate analysis, high nuclear grade (p = 0.04), negative estrogen receptor (ER) status (p = 0.001), presence of lymphovascular invasion (LVI) (p = 0.003), and no radiotherapy (p = 0.0015) were associated with a significantly higher rate of LRR. Negative ER status (hazard ratio = 5.1) and presence of LVI (hazard ratio = 2.5) were the risk factors for LRR with statistical significance in the multivariate analysis. Radiotherapy reduced the LRR in patients with the following characteristics: age <40 years, T2 stage, high nuclear grade, negative ER status, and presence of LVI. For 41 patients with negative ER and positive LVI status, radiotherapy can reduce LRR from 10 of 25 (40%) to 2 of 16 (12.5%) and increase the 5-year overall survival from 43.7% to 87.1%. Conclusion: Radiotherapy can reduce LRR and increase survival in T1-2 N1 breast cancer patients with negative ER status and presence of LVI.

  1. Antimicrobial Treatment Improves Mycobacterial Survival in Nonpermissive Growth Conditions

    PubMed Central

    Turapov, Obolbek; Waddell, Simon J.; Burke, Bernard; Glenn, Sarah; Sarybaeva, Asel A.; Tudo, Griselda; Labesse, Gilles; Young, Danielle I.; Young, Michael; Andrew, Peter W.; Butcher, Philip D.; Cohen-Gonsaud, Martin

    2014-01-01

    Antimicrobials targeting cell wall biosynthesis are generally considered inactive against nonreplicating bacteria. Paradoxically, we found that under nonpermissive growth conditions, exposure of Mycobacterium bovis BCG bacilli to such antimicrobials enhanced their survival. We identified a transcriptional regulator, RaaS (for regulator of antimicrobial-assisted survival), encoded by bcg1279 (rv1219c) as being responsible for the observed phenomenon. Induction of this transcriptional regulator resulted in reduced expression of specific ATP-dependent efflux pumps and promoted long-term survival of mycobacteria, while its deletion accelerated bacterial death under nonpermissive growth conditions in vitro and during macrophage or mouse infection. These findings have implications for the design of antimicrobial drug combination therapies for persistent infectious diseases, such as tuberculosis. PMID:24590482

  2. Caloric restriction improves health and survival of rhesus monkeys.

    PubMed

    Mattison, Julie A; Colman, Ricki J; Beasley, T Mark; Allison, David B; Kemnitz, Joseph W; Roth, George S; Ingram, Donald K; Weindruch, Richard; de Cabo, Rafael; Anderson, Rozalyn M

    2017-01-17

    Caloric restriction (CR) without malnutrition extends lifespan and delays the onset of age-related disorders in most species but its impact in nonhuman primates has been controversial. In the late 1980s two parallel studies were initiated to determine the effect of CR in rhesus monkeys. The University of Wisconsin study reported a significant positive impact of CR on survival, but the National Institute on Aging study detected no significant survival effect. Here we present a direct comparison of longitudinal data from both studies including survival, bodyweight, food intake, fasting glucose levels and age-related morbidity. We describe differences in study design that could contribute to differences in outcomes, and we report species specificity in the impact of CR in terms of optimal onset and diet. Taken together these data confirm that health benefits of CR are conserved in monkeys and suggest that CR mechanisms are likely translatable to human health.

  3. Caloric restriction improves health and survival of rhesus monkeys

    PubMed Central

    Mattison, Julie A.; Colman, Ricki J.; Beasley, T. Mark; Allison, David B.; Kemnitz, Joseph W.; Roth, George S.; Ingram, Donald K.; Weindruch, Richard; de Cabo, Rafael; Anderson, Rozalyn M.

    2017-01-01

    Caloric restriction (CR) without malnutrition extends lifespan and delays the onset of age-related disorders in most species but its impact in nonhuman primates has been controversial. In the late 1980s two parallel studies were initiated to determine the effect of CR in rhesus monkeys. The University of Wisconsin study reported a significant positive impact of CR on survival, but the National Institute on Aging study detected no significant survival effect. Here we present a direct comparison of longitudinal data from both studies including survival, bodyweight, food intake, fasting glucose levels and age-related morbidity. We describe differences in study design that could contribute to differences in outcomes, and we report species specificity in the impact of CR in terms of optimal onset and diet. Taken together these data confirm that health benefits of CR are conserved in monkeys and suggest that CR mechanisms are likely translatable to human health. PMID:28094793

  4. The impact of regional nodal radiotherapy (dose/volume) on regional progression and survival in unresectable non-small cell lung cancer: an analysis of RTOG data.

    PubMed

    Emami, Bahman; Mirkovic, Nena; Scott, Charles; Byhardt, Roger; Graham, Mary V; James Andras, E; John, Madhu; Herskovic, Arnold; Urtasun, Raul; Asbell, Sucha O; Perez, Carlos A; Cox, James

    2003-08-01

    To evaluate in-field progression and survival of patients with unresectable non-small cell lung cancer (NSCLC) in relation to adequacy of coverage of thoracic regional nodal areas in the radiotherapy volume. A total of 1705 patients from four large RTOG trials (78-11, 79-17, 83-11 and 84-07) were analyzed for this purpose. For each of these trials, the dose delivered to nodal regions was recorded and an assessment of adequacy of field borders was made. Each nodal site was assessed for progression, defined as in-field or out-of-field. In patients who had adequate borders on nodal regions, the results were analyzed according to the dose delivered. The majority (74%) of patients were between the age of 55-75. Forty-six percent of the patients had KPS of 60-80 and 52% had KPS of 90-100. Sixty percent of patients had a weight loss of less than 5% in the 6 months prior to diagnosis. Deviations from the protocol in field borders (borders not per protocol) were most frequent for the contralateral hilum (25.2%) and least frequent in the ipsilateral hilum (6.3%). The adequacy of ipsilateral hilar coverage was important for preventing the in-field progression (11.6 vs. 22% for adequately vs. inadequately covered ipsilateral hilum, respectively, P=0.01), however, did not influence the 2-year-survival (35 vs. 37%) or median survival (1.3 vs. 1.1 year). Neither the in-field progression nor the 2-year-survival were affected by adequacy of nodal coverage in the mediastinum, ipsilateral supraclavicular area and contralateral hilum, even when different doses were analyzed. These data suggest that elective irradiation of mediastinal, contralateral hilar and supraclavicular lymph nodes may not be necessary in the treatment of unresectable NSCLC.

  5. 10-Year Survival and Quality of Life in Patients With High-Risk {sub P}N{sub 0} Prostate Cancer Following Definitive Radiotherapy

    SciTech Connect

    Berg, Arne Lilleby, Wolfgang; Bruland, Oyvind Sverre; Fossa, Sophie Dorothea

    2007-11-15

    Purpose: To evaluate long-term overall survival (OS), cancer-specific survival (CSS), clinical progression-free survival (cPFS), and health-related quality of life (HRQoL) following definitive radiotherapy (RT) given to T{sub 1-4p}N{sub 0}M{sub 0} prostate cancer patients provided by a single institution between 1989 and 1996. Methods and Materials: We assessed outcome among 203 patients who had completed three-dimensional conformal RT (66 Gy) without hormone treatment and in whom staging by lymphadenectomy had been performed. OS was compared with an age-matched control group from the general population. A cross-sectional, self-report survey of HRQoL was performed among surviving patients. Results: Median observation time was 10 years (range, 1-16 years). Eighty-one percent had high-risk tumors defined as T{sub 3-4} or Gleason score (GS) {>=}7B (4+3). Among these, 10-year OS, CSS, and cPFS rates were 52%, 66%, and 39%, respectively. The corresponding fractions in low-risk patients (T{sub 1-2} and GS {<=}7A [3+4]) were 79%, 95%, and 73%, respectively. Both CSS and cPFS were predicted by GS and T-classification; OS was associated with GS only. High-risk, but not low-risk, patients had reduced OS compared with the general population (p < 0.0005). When pelvis-related side effects were included in multivariate analyzes together with physical function and pain, sexual, urinary, and bowel function were not independently associated with self-reported global quality of life. Conclusions: Despite surgically proven {sub p}N{sub 0}, RT with dosage <70 Gy as monotherapy does not give satisfactory CSS rates after 10 years in patients with T{sub 3-4} or GS {>=}7B.

  6. [Can the prophylactic treatment of mycotic mucositis improve the time of performing radiotherapy in head and neck tumors?].

    PubMed

    Gava, A; Ferrarese, F; Tonetto, V; Coghetto, F; Marazzato, G; Zorat, P L

    1996-04-01

    Radiotherapy-related mucositis is the most frequent complication in the patients submitted to irradiation for head and neck cancers. Many such patients may develop mycotic infections which may lead to treatment discontinuation, with possible consequences on the local control of these cancers. In this study, we investigated the efficacy of fluconazole in preventing mycotic mucositis in 80 patients undergoing radiation therapy for head and neck cancers. The patients were randomized to two groups: 41 patients in group A received the supporting treatment we usually administer, plus fluconazole (50 mg/day) starting from the 6th irradiation session throughout the treatment; 39 patients in group B received the same baseline treatment, but were given the drug only when mycotic infections appeared. The clinical characteristics, treated sites, treatment doses and volumes were similar in the two groups of patients. Fluconazole was well tolerated and no early or late toxicity was observed. We had 1 mycotic mucositis and 14 non-scheduled treatment discontinuations in group A, vs. 19 and 30, respectively, in group B. Radiation therapy lasted 52.3 days (mean) in group A and 55.6 days (mean) in group B; the differences were statistically significant. In our experience, fluconazole, used prophylactically from the 6th radiotherapy session on, reduced the number of mycotic infections and improved radiotherapy schedule in our head and neck cancer patients.

  7. Posttreatment TNM staging is a prognostic indicator of survival and recurrence in tethered or fixed rectal carcinoma after preoperative chemotherapy and radiotherapy

    SciTech Connect

    Chan, Alexander K.P. . E-mail: alexc@cancerboard.ab.ca; Wong, Alfred; Jenken, Daryl; Heine, John; Buie, Donald; Johnson, Douglas

    2005-03-01

    Purpose: To evaluate the prognostic value of the posttreatment TNM stage as a predictor of outcome in locally advanced rectal cancers treated with preoperative chemotherapy and radiotherapy. Methods and materials: Between 1993 and 2000, 128 patients with tethered (103) or fixed (25) rectal cancers were treated with 50 Gy preoperative pelvic radiotherapy and two cycles of concurrent 5-fluorouracil infusion (20 mg/kg/d) and leucovorin (200 mg/m{sup 2}/d) chemotherapy on Days 1-4 and 22-25 and a single bolus mitomycin C injection (8 mg/m{sup 2}) on Day 1. Of the 128 patients, 111 had Stage T3 and 17 Stage T4 according to the rectal ultrasound or CT findings and clinical evaluation. All 128 patients underwent surgery 8 weeks after chemoradiotherapy. Postoperatively, the disease stage was determined according to the surgical and pathologic findings using the American Joint Committee on Cancer TNM staging system. Results: Of the 128 patients, 32 had postchemoradiotherapy (pCR) Stage 0 (T0N0M0), 37 pCR Stage I, 26 pCR Stage II, 28 pCR Stage III, and 5 pCR Stage IV disease. Of the 128 patients, 79 had pCR Stage T0-T2, 35 pCR Stage T3, and 14 pCR Stage T4. The rate of T stage downstaging was 66% (84 of 128). Of the 128 patients, 25% achieved a pathologic complete response, and 31 (24%) had positive nodal disease. Lymphovascular or perineural invasion was found in 13 patients (10%). The 5-year disease-specific survival rate was 97% for pCR Stage 0, 88% for pCR Stage I, 74% for pCR Stage II, 44% for pCR Stage III, and 0% for pCR Stage IV (p = 0.0000059). The 5-year relapse-free survival rate was 97% for pCR Stage 0, 80% for pCR Stage I, 72% for pCR Stage II, 42% for pCR Stage III, and 0% for pCR Stage IV (p < 0.000001). In univariate analysis, the pretreatment tumor status (fixed vs. tethered tumors), the pCR TNM stage, T stage downstaging, pathologic T4 tumors, node-positive disease after chemoradiotherapy, and lymphovascular or perineural invasion were statistically

  8. High-dose Neural Stem Cell Radiation May Not Improve Survival in Glioblastoma.

    PubMed

    Achari, R; Arunsingh, M; Badgami, R K; Saha, A; Chatterjee, S; Shrimali, R K; Mallick, I; Arun, B

    2017-06-01

    To evaluate the effect of radiotherapy dose-volume parameters of neural stem cell (NSC) compartment on progression-free survival (PFS) and overall survival after post-resection chemoradiation in newly diagnosed glioblastoma. Sixty-one patients with unifocal glioblastoma were included. Ipsilateral (NSC_Ipsi), contralateral (NSC_Contra) and combined NSC (NSC_Combined) were contoured on radiotherapy planning computerised tomography datasets. NSC dose-volume parameters were correlated with PFS and overall survival. Serial magnetic resonance imaging scans were assessed to understand the frequency of pre- and post-treatment involvement of the NSC by contrast enhancing lesions (CELs). Baseline involvement of NSC with CELs was seen in 67.2% and 95.9% had CELs and FLAIR abnormalities at progression. With a median follow-up of 14.1 months (interquartile range 9.4-20.6 months), median PFS and overall survival were 14.5 (95% confidence interval 11.6-17.5) and 16.2 (95% confidence interval 13.3-19.2) months, respectively. Poor Eastern Cooperative Oncology Group performance score, advanced recursive partitioning analysis class, unmethylated O6-methylguanine methyltransferase (MGMT) status, higher than median of mean NSC_Ipsi dose were associated with significantly inferior PFS and overall survival on univariate analysis. On multivariate analysis, unmethylated MGMT status, higher than median of mean doses to NSC_Ipsi and poor compliance to adjuvant temozolomide were independent predictors of inferior survival. In this cohort, 67.2% of newly diagnosed glioblastoma patients had NSC involved with CELs at presentation and 95.9% at progression. This might be an imaging surrogate of the current notion of gliomagenesis and progression from NSC rests. A high radiation dose to NSC_Ipsi was significantly associated with inferior survival. This could be a function of larger tumours and planning target volumes in those with pre-treatment NSC involvement. Methylated MGMT and good compliance

  9. Stereotactic body radiotherapy for Stage I lung cancer with chronic obstructive pulmonary disease: special reference to survival and radiation-induced pneumonitis

    PubMed Central

    Inoue, Toshihiko; Shiomi, Hiroya; Oh, Ryoong-Jin

    2015-01-01

    This retrospective study aimed to evaluate radiation-induced pneumonitis (RIP) and a related condition that we define in this report—prolonged minimal RIP (pmRIP)—after stereotactic body radiotherapy (SBRT) for Stage I primary lung cancer in patients with chronic obstructive pulmonary disease (COPD). We assessed 136 Stage I lung cancer patients with COPD who underwent SBRT. Airflow limitation on spirometry was classified into four Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades, with minor modifications: GOLD 1 (mild), GOLD 2 (moderate), GOLD 3 (severe) and GOLD 4 (very severe). On this basis, we defined two subgroups: COPD-free (COPD −) and COPD-positive (COPD +). There was no significant difference in overall survival or cause-specific–survival between these groups. Of the 136 patients, 44 (32%) had pmRIP. Multivariate analysis showed that COPD and the Brinkman index were statistically significant risk factors for the development of pmRIP. COPD and the Brinkman index were predictive factors for pmRIP, although our findings also indicate that SBRT can be tolerated in early lung cancer patients with COPD. PMID:25887042

  10. Stereotactic body radiotherapy for Stage I lung cancer with chronic obstructive pulmonary disease: special reference to survival and radiation-induced pneumonitis.

    PubMed

    Inoue, Toshihiko; Shiomi, Hiroya; Oh, Ryoong-Jin

    2015-07-01

    This retrospective study aimed to evaluate radiation-induced pneumonitis (RIP) and a related condition that we define in this report--prolonged minimal RIP (pmRIP)--after stereotactic body radiotherapy (SBRT) for Stage I primary lung cancer in patients with chronic obstructive pulmonary disease (COPD). We assessed 136 Stage I lung cancer patients with COPD who underwent SBRT. Airflow limitation on spirometry was classified into four Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades, with minor modifications: GOLD 1 (mild), GOLD 2 (moderate), GOLD 3 (severe) and GOLD 4 (very severe). On this basis, we defined two subgroups: COPD-free (COPD -) and COPD-positive (COPD +). There was no significant difference in overall survival or cause-specific-survival between these groups. Of the 136 patients, 44 (32%) had pmRIP. Multivariate analysis showed that COPD and the Brinkman index were statistically significant risk factors for the development of pmRIP. COPD and the Brinkman index were predictive factors for pmRIP, although our findings also indicate that SBRT can be tolerated in early lung cancer patients with COPD.

  11. Chemotherapy response as a prognosticator for survival in patients with limited squamous cell lung cancer treated with combined chemotherapy and radiotherapy

    SciTech Connect

    Eagan, R.T.; Fleming, T.R.; Lee, R.E.; Ingle, J.N.; Frytak, S.; Creagan, E.T.

    1980-07-01

    Twenty-two patients with limited unresectable squamous cell lung cancer were treated with 6 courses of combination chemotherapy consisting of cyclophosphamide, adriamycin, cisplatin, and bleomycin (CAP-Bleo) and short-course thoracic irradiation started after the first 4 weeks of chemotherapy. Of 20 patients with visible tumor who were treated with 4 weeks of chemotherapy alone, 10 (50%) had a tumor regression in that 4 week period and 10 did not. Those patients with tumor regression had significantly better progression free and overall survivals than did patients with no chemotherapy regressions (medians of 258 days vs. 136 days and 356 days vs. 150 days respectively). The original bleomycin dose had to be reduced by 50% primarily because of excessive radiation esophagitis that has not been reported with use of either the CAP regimen or bleomycin along in conjunction with thoracic irradiation. An initial chemotherapy regression seems to be a good prognosticator for progression-free and overall survival in patients with limited squamous cell lung cancer treated with combined chemotherapy and radiotherapy.

  12. Prognostic factors predicting functional outcomes, recurrence-free survival, and overall survival after radiotherapy for metastatic spinal cord compression in breast cancer patients.

    PubMed

    Rades, Dirk; Veninga, Theo; Stalpers, Lukas J A; Schulte, Rainer; Hoskin, Peter J; Poortmans, Philip; Schild, Steven E; Rudat, Volker

    2006-01-01

    To identify significant prognostic factors after irradiation of metastatic spinal cord compression (MSCC) in 335 breast cancer patients. The potential prognostic factors investigated included involved vertebra, other bone metastases, visceral metastases, performance status, pretreatment ambulatory status, time until motor deficits developed before RT, radiation schedule (shorter-course RT [one fraction of 8 Gy/five fractions of 4 Gy] vs. longer-course RT [10 fractions of 3 Gy/15 fractions of 2.5 Gy/20 fractions of 2 Gy), and the response to RT. On multivariate analysis, better functional outcome was associated with slower development of motor deficits (p <0.001) and being ambulatory before RT (p <0.001). The overall recurrence rate of MSCC was greater if other bone metastases were present (p <0.001) and if shorter-course RT was used (p <0.001). In-field recurrences alone were more frequent after shorter-course RT (p = 0.008). Survival was negatively affected by the presence of visceral metastases (p <0.001), deterioration of motor function after RT (p <0.001), reduced performance status (p <0.001), and the rapid development of motor deficits (p = 0.044). Outcomes and survival after RT for MSCC in breast cancer patients are associated with several prognostic factors. Patients with poor expected survival may be treated with shorter-course RT to keep the overall treatment time short. If survival is expected to be relatively favorable, longer-course RT appears preferable, because it is associated with fewer MSCC recurrences.

  13. Prognostic factors predicting functional outcomes, recurrence-free survival, and overall survival after radiotherapy for metastatic spinal cord compression in breast cancer patients

    SciTech Connect

    Rades, Dirk . E-mail: Rades.Dirk@gmx.net; Veninga, Theo; Stalpers, Lukas J.A.; Schulte, Rainer; Hoskin, Peter J.; Poortmans, Philip; Schild, Steven E.; Rudat, Volker

    2006-01-01

    Purpose: To identify significant prognostic factors after irradiation of metastatic spinal cord compression (MSCC) in 335 breast cancer patients. Methods and Materials: The potential prognostic factors investigated included involved vertebra, other bone metastases, visceral metastases, performance status, pretreatment ambulatory status, time until motor deficits developed before RT, radiation schedule (shorter-course RT [one fraction of 8 Gy/five fractions of 4 Gy] vs. longer-course RT [10 fractions of 3 Gy/15 fractions of 2.5 Gy/20 fractions of 2 Gy), and the response to RT. Results: On multivariate analysis, better functional outcome was associated with slower development of motor deficits (p <0.001) and being ambulatory before RT (p <0.001). The overall recurrence rate of MSCC was greater if other bone metastases were present (p <0.001) and if shorter-course RT was used (p <0.001). In-field recurrences alone were more frequent after shorter-course RT (p = 0.008). Survival was negatively affected by the presence of visceral metastases (p <0.001), deterioration of motor function after RT (p <0.001), reduced performance status (p <0.001), and the rapid development of motor deficits (p = 0.044). Conclusion: Outcomes and survival after RT for MSCC in breast cancer patients are associated with several prognostic factors. Patients with poor expected survival may be treated with shorter-course RT to keep the overall treatment time short. If survival is expected to be relatively favorable, longer-course RT appears preferable, because it is associated with fewer MSCC recurrences.

  14. Higher Biologically Effective Dose of Radiotherapy Is Associated With Improved Outcomes for Locally Advanced Non-Small Cell Lung Carcinoma Treated With Chemoradiation: An Analysis of the Radiation Therapy Oncology Group

    SciTech Connect

    Machtay, Mitchell; Movsas, Benjamin; Paulus, Rebecca; Gore, Elizabeth M.; Komaki, Ritsuko; Albain, Kathy; Sause, William T.; Curran, Walter J.

    2012-01-01

    Purpose: Patients treated with chemoradiotherapy for locally advanced non-small-cell lung carcinoma (LA-NSCLC) were analyzed for local-regional failure (LRF) and overall survival (OS) with respect to radiotherapy dose intensity. Methods and Materials: This study combined data from seven Radiation Therapy Oncology Group (RTOG) trials in which chemoradiotherapy was used for LA-NSCLC: RTOG 88-08 (chemoradiation arm only), 90-15, 91-06, 92-04, 93-09 (nonoperative arm only), 94-10, and 98-01. The radiotherapeutic biologically effective dose (BED) received by each individual patient was calculated, as was the overall treatment time-adjusted BED (tBED) using standard formulae. Heterogeneity testing was done with chi-squared statistics, and weighted pooled hazard ratio estimates were used. Cox and Fine and Gray's proportional hazard models were used for OS and LRF, respectively, to test the associations between BED and tBED adjusted for other covariates. Results: A total of 1,356 patients were analyzed for BED (1,348 for tBED). The 2-year and 5-year OS rates were 38% and 15%, respectively. The 2-year and 5-year LRF rates were 46% and 52%, respectively. The BED (and tBED) were highly significantly associated with both OS and LRF, with or without adjustment for other covariates on multivariate analysis (p < 0.0001). A 1-Gy BED increase in radiotherapy dose intensity was statistically significantly associated with approximately 4% relative improvement in survival; this is another way of expressing the finding that the pool-adjusted hazard ratio for survival as a function of BED was 0.96. Similarly, a 1-Gy tBED increase in radiotherapy dose intensity was statistically significantly associated with approximately 3% relative improvement in local-regional control; this is another way of expressing the finding that the pool-adjusted hazard ratio as a function of tBED was 0.97. Conclusions: Higher radiotherapy dose intensity is associated with improved local-regional control and

  15. Hibernation-Based Therapy to Improve Survival of Severe Blood Loss

    DTIC Science & Technology

    2011-10-01

    Award Number: W81XWH-10-2-0121 TITLE: Hibernation -Based Therapy to Improve Survival of Severe Blood Loss PRINCIPAL INVESTIGATOR: Gregory...SUBTITLE 5a. CONTRACT NUMBER Hibernation -Based Therapy to Improve Survival of Severe Blood Loss 5b. GRANT NUMBER W81XWH-10-2-0121 5c. PROGRAM...death. The overall strategy is to use strategies learned from study of hibernating mammals to survive a potentially life-threatening blood loss and allow

  16. Improving Survival and Promoting Respiratory Motor Function after Cervical Spinal Cord Injury

    DTIC Science & Technology

    2016-09-01

    AWARD NUMBER: W81XWH-15-1-0378 TITLE: Improving Survival and Promoting Respiratory Motor Function after Cervical Spinal Cord Injury PRINCIPAL...Aug 2015 - 14 Aug 2016 4. TITLE AND SUBTITLE CordCorInjury 5a. CONTRACT NUMBER Improvi g Survival and Promoting Respiratory Motor Function After... respiratory complications. This application proposes to help improve survival, decrease early dependence on mechanical ventilation, and restore breathing

  17. Long-term Effect of Radiotherapy in Rectal Cancer Patients with Mucinous Tumor: A Large Population Based Study

    PubMed Central

    Guan, Xu; Jia, Senhao; Chen, Wei; Jiang, Zheng; Liu, Zheng; Chen, Yinggang; Wang, Guiyu; Wang, Xishan

    2017-01-01

    Due to distinct biological behavior of mucinous adenocarcinoma (MAC) and signet ring cell cancer (SRC), the efficacy of radiotherapy on long-term outcome for rectal cancer (RC) patients with mucinous tumors is still unclear. Here, we identified 1808 RC patients with MAC/SRC from Surveillance, Epidemiology, and End-Results (SEER) database from 2004 to 2013. Patients were divided into two subgroups according to different therapeutic strategies, including surgery alone and surgery combined with radiotherapy. Kaplan–Meier methods and Cox regression models were used to access the influence of therapeutic strategy on long-term survival outcomes. The 5-year and 10-year cancer specific survival (CSS) were improved in stage II and III patients who underwent surgery and radiotherapy compared with patients who underwent surgery alone. These results were further confirmed following propensity score matching. In addition, radiotherapy was deemed as independent good prognostic factor in patient with MAC/SRC. In subgroup analysis, the result also demonstrated that long-term survival was improved following radiotherapy. However, there was no prognostic difference between preoperative and postoperative radiotherapy. In conclusion, radiotherapy could improve survival for RC patients with MAC and SRC, but only for patients in stage II and III. This finding supported the application of radiotherapy in clinical practice. PMID:28272410

  18. Implications of improved treatment of malignant salivary gland tumors by fast neutron radiotherapy

    SciTech Connect

    Catterall, M.; Errington, R.D.

    1987-09-01

    The conventional treatment for cancer of the salivary glands is surgery, with or without X ray therapy. In advanced tumors (Stage III and IV), local control and 5-year survival rates are less than 35%. Radical surgery severs the facial nerve in the majority of operations on parotid gland tumors. Local control of unresectable salivary gland tumors was achieved, in 74% of cases, by fast neutron therapy. From the MRC cyclotron at Hammersmith Hospital neutrons were given to 65 patients, with locally advanced or recurrent tumors, 89% of which were Stage IV. Local control and 5-year survival rates were 72% and 50%, respectively. The facial nerve was not damaged by neutron therapy. In patients with parotid gland tumors, 77% regained or maintained function. Function was lost in 14% through recurrence and 9% remained paralyzed. The results were achieved using beams from primitive machines with serious disadvantages. The results from neutrons implicate improvements for locally advanced tumors of non-epidermal origin in other sites of the body, especially with the high energy neutrons now available from modern cyclotrons.

  19. Use of Aspirin postdiagnosis improves survival for colon cancer patients

    PubMed Central

    Bastiaannet, E; Sampieri, K; Dekkers, O M; de Craen, A J M; van Herk-Sukel, M P P; Lemmens, V; van den Broek, C B M; Coebergh, J W; Herings, R M C; van de Velde, C J H; Fodde, R; Liefers, G J

    2012-01-01

    Background: The preventive role of non-steroid anti-inflammatory drugs (NSAIDs) and aspirin, in particular, on colorectal cancer is well established. More recently, it has been suggested that aspirin may also have a therapeutic role. Aim of the present observational population-based study was to assess the therapeutic effect on overall survival of aspirin/NSAIDs as adjuvant treatment used after the diagnosis of colorectal cancer patients. Methods: Data concerning prescriptions were obtained from PHARMO record linkage systems and all patients diagnosed with colorectal cancer (1998–2007) were selected from the Eindhoven Cancer Registry (population-based cancer registry). Aspirin/NSAID use was classified as none, prediagnosis and postdiagnosis and only postdiagnosis. Patients were defined as non-user of aspirin/NSAIDs from the date of diagnosis of the colorectal cancer to the date of first use of aspirin or NSAIDs and user from first use to the end of follow-up. Poisson regression was performed with user status as time-varying exposure. Results: In total, 1176 (26%) patients were non-users, 2086 (47%) were prediagnosis and postdiagnosis users and 1219 (27%) were only postdiagnosis users (total n=4481). Compared with non-users, a survival gain was observed for aspirin users; the adjusted rate ratio (RR) was 0.77 (95% confidence interval (CI) 0.63–0.95; P=0.015). Stratified for colon and rectal, the survival gain was only present in colon cancer (adjusted RR 0.65 (95%CI 0.50–0.84; P=0.001)). For frequent users survival gain was larger (adjusted RR 0.61 (95%CI 0.46–0.81; P=0.001). In rectal cancer, aspirin use was not associated with survival (adjusted RR 1.10 (95%CI 0.79–1.54; P=0.6). The NSAIDs use was associated with decreased survival (adjusted RR 1.93 (95%CI 1.70–2.20; P<0.001). Conclusion: Aspirin use initiated or continued after diagnosis of colon cancer is associated with a lower risk of overall mortality. These findings strongly support initiation of

  20. Summer Fallowinng Improves Survival and Growth of Cottonwood on Old Fields

    Treesearch

    James B. Baker; B. G. Blackmon

    1973-01-01

    Fallowing an old-field site during the summer prior to planting and applying a herbicide in September improved survival and growth of eastern cottonwood cuttings. Summer fallowing without applying herbicide also improved height growth of cottonwood through age 2. Deep plowing and cover cropping, alone or in combination, did not influence growth or survival during the...

  1. Radiotherapy planning for glioblastoma based on a tumor growth model: improving target volume delineation

    NASA Astrophysics Data System (ADS)

    Unkelbach, Jan; Menze, Bjoern H.; Konukoglu, Ender; Dittmann, Florian; Le, Matthieu; Ayache, Nicholas; Shih, Helen A.

    2014-02-01

    Glioblastoma differ from many other tumors in the sense that they grow infiltratively into the brain tissue instead of forming a solid tumor mass with a defined boundary. Only the part of the tumor with high tumor cell density can be localized through imaging directly. In contrast, brain tissue infiltrated by tumor cells at low density appears normal on current imaging modalities. In current clinical practice, a uniform margin, typically two centimeters, is applied to account for microscopic spread of disease that is not directly assessable through imaging. The current treatment planning procedure can potentially be improved by accounting for the anisotropy of tumor growth, which arises from different factors: anatomical barriers such as the falx cerebri represent boundaries for migrating tumor cells. In addition, tumor cells primarily spread in white matter and infiltrate gray matter at lower rate. We investigate the use of a phenomenological tumor growth model for treatment planning. The model is based on the Fisher-Kolmogorov equation, which formalizes these growth characteristics and estimates the spatial distribution of tumor cells in normal appearing regions of the brain. The target volume for radiotherapy planning can be defined as an isoline of the simulated tumor cell density. This paper analyzes the model with respect to implications for target volume definition and identifies its most critical components. A retrospective study involving ten glioblastoma patients treated at our institution has been performed. To illustrate the main findings of the study, a detailed case study is presented for a glioblastoma located close to the falx. In this situation, the falx represents a boundary for migrating tumor cells, whereas the corpus callosum provides a route for the tumor to spread to the contralateral hemisphere. We further discuss the sensitivity of the model with respect to the input parameters. Correct segmentation of the brain appears to be the most

  2. Stereotactic Body Radiotherapy for Hepatocellular Carcinoma Resulting in a Durable Relapse-Free Survival: A Case Report

    PubMed Central

    Francis, Samual; Williams, Ned; Anker, Christopher J; Shaaban, Akram; Kim, Robin; Shrieve, Dennis

    2016-01-01

    The standard of care for localized hepatocellular carcinoma (HCC) is surgical resection. For patients who decline or who are unfit for surgery, stereotactic body radiotherapy (SBRT) is emerging as a viable treatment approach. We present a case of a 77-year-old female in whom an early stage HCC was incidentally discovered. Given her religious edicts as a devout Jehovah’s Witness and her subsequent desire to avoid a blood transfusion, she declined surgical resection or transplant due to the risk of hemorrhage. Ablative therapy was deemed inappropriate given the mass’s size and location adjacent to the inferior vena cava and diaphragm. She was treated with definitive SBRT to a total dose of 60 Gy administered in three 20 Gy fractions every other day. She had a complete response to the treatment and remains without evidence of disease after 39 months of follow-up. Her only treatment-related side effect is a persistent CTCAE Grade 1 myositis on her back overlying the treatment area. We report this case to add to the growing body of literature suggesting SBRT as an effective and safe alternative treatment modality for HCC. PMID:27909629

  3. Radiotherapy in Glioblastoma: the Past, the Present and the Future.

    PubMed

    Gzell, C; Back, M; Wheeler, H; Bailey, D; Foote, M

    2017-01-01

    The aim of this review is to explore the changing utility of radiotherapy in the treatment of patients with glioblastoma over the past 60 years. Together with surgery, radiotherapy has always been the cornerstone of treatment of glioblastoma, but techniques have significantly advanced over this time. The exploration of early two-dimensional techniques, investigation of dose escalation, concomitant chemotherapy and modern techniques, including intensity-modulated radiotherapy, image-guided radiotherapy, and volumetric-modulated arc therapy will be covered. In addition, current controversies including decreasing margin size, re-irradiation, treatment of elderly patients, and novel imaging tracers will be discussed. Future directions including immunotherapy and tumour treating fields are examined. Radiotherapy-based treatments cannot rely solely on advances in chemotherapy or immunotherapy to improve the overall survival of patients with glioblastoma. Radiation oncology needs to continue to develop and improve the delivery, target definition, and dose of radiotherapy to these patients to improve their survival and the toxicity associated with treatment.

  4. Filgrastim Improves Survival in Lethally Irradiated Nonhuman Primates

    PubMed Central

    Farese, Ann M.; Cohen, Melanie V.; Katz, Barry P.; Smith, Cassandra P.; Gibbs, Allison; Cohen, Daniel M.; MacVittie, Thomas J.

    2015-01-01

    Treatment of individuals exposed to potentially lethal doses of radiation is of paramount concern to health professionals and government agencies. We evaluated the efficacy of filgrastim to increase survival of nonhuman primates (NHP) exposed to an approximate mid-lethal dose (LD50/60) (7.50 Gy) of LINAC-derived photon radiation. Prior to total-body irradiation (TBI), nonhuman primates were randomized to either a control (n =22) or filgrastim-treated (n =24) cohorts. Filgrastim (10 μg/kg/d) was administered beginning 1 day after TBI and continued daily until the absolute neutrophil count (ANC) was >1,000/μL for 3 consecutive days. All nonhuman primates received medical management as per protocol. The primary end point was all cause overall mortality over the 60 day in-life study. Secondary end points included mean survival time of decedents and all hematologic-related parameters. Filgrastim significantly (P < 0.004) reduced 60 day overall mortality [20.8% (5/24)] compared to the controls [59.1% (13/22)]. Filgrastim significantly decreased the duration of neutropenia, but did not affect the absolute neutrophil count nadir. Febrile neutropenia (ANC <500/μL and body temperature ≥103°F) was experienced by 90.9% (20/22) of controls compared to 79.2% (19/24) of filgrastim-treated animals (P = 0.418). Survival was significantly increased by 38.3% over controls. Filgrastim, administered at this dose and schedule, effectively mitigated the lethality of the hematopoietic subsyndrome of the acute radiation syndrome. PMID:23210705

  5. [Radiotherapy of skin cancers].

    PubMed

    Hennequin, C; Rio, E; Mahé, M-A

    2016-09-01

    The indications of radiotherapy for skin cancers are not clearly defined because of the lack of randomised trials or prospective studies. For basal cell carcinomas, radiotherapy frequently offers a good local control, but a randomized trial showed that surgery is more efficient and less toxic. Indications of radiotherapy are contra-indications of surgery for patients older than 60, non-sclerodermiform histology and occurring in non-sensitive areas. Adjuvant radiotherapy could be proposed to squamous cell carcinomas, in case of poor prognostic factors. Dose of 60 to 70Gy are usually required, and must be modulated to the size of the lesions. Adjuvant radiotherapy seems beneficial for desmoplastic melanomas but not for the other histological types. Prophylactic nodal irradiation (45 to 50Gy), for locally advanced tumours (massive nodal involvement), decreases the locoregional failure rate but do not increase survival. Adjuvant radiotherapy (50 to 56Gy) for Merckel cell carcinomas increases also the local control rate, as demonstrated by meta-analysis and a large epidemiological study. Nodal areas must be included, if there is no surgical exploration (sentinel lymph node dissection). Kaposi sarcomas are radiosensitive and could be treated with relatively low doses (24 to 30Gy). Also, cutaneous lymphomas are good indications for radiotherapy: B lymphomas are electively treated with limited fields. The role of total skin electron therapy for T-lymphomas is still discussed; but palliative radiotherapy is very efficient in case of cutaneous nodules.

  6. Failure to Achieve a PSA Level {<=}1 ng/mL After Neoadjuvant LHRHA Therapy Predicts for Lower Biochemical Control Rate and Overall Survival in Localized Prostate Cancer Treated With Radiotherapy

    SciTech Connect

    Mitchell, Darren M. McAleese, Jonathan; Park, Richard M.; Stewart, David P.; Stranex, Stephen; Eakin, Ruth L.; Houston, Russell F.; O'Sullivan, Joe M.

    2007-12-01

    Purpose: To investigate whether failure to suppress the prostate-specific antigen (PSA) level to {<=}1 ng/mL after {>=}2 months of neoadjuvant luteinizing hormone-releasing hormone agonist therapy in patients scheduled to undergo external beam radiotherapy for localized prostate carcinoma is associated with reduced biochemical failure-free survival. Methods and Materials: A retrospective case note review of consecutive patients with intermediate- or high-risk localized prostate cancer treated between January 2001 and December 2002 with neoadjuvant hormonal deprivation therapy, followed by concurrent hormonal therapy and radiotherapy was performed. Patient data were divided for analysis according to whether the PSA level in Week 1 of radiotherapy was {<=}1.0 ng/mL. Biochemical failure was determined using the American Society for Therapeutic Radiology and Oncology (Phoenix) definition. Results: A total of 119 patients were identified. The PSA level after neoadjuvant hormonal deprivation therapy was {<=}1 ng/mL in 67 patients and >1 ng/mL in 52. At a median follow-up of 49 months, the 4-year actuarial biochemical failure-free survival rate was 84% vs. 60% (p = 0.0016) in favor of the patients with a PSA level after neoadjuvant hormonal deprivation therapy of {<=}1 ng/mL. The overall survival rate was 94% vs. 77.5% (p = 0.0045), and the disease-specific survival rate at 4 years was 98.5% vs. 82.5%. Conclusions: The results of our study have shown that patients with a PSA level >1 ng/mL at the beginning of external beam radiotherapy after {>=}2 months of neoadjuvant luteinizing hormone-releasing hormone agonist therapy have a significantly greater rate of biochemical failure and lower survival rate compared with those with a PSA level of {<=}1 ng/mL. Patients without adequate PSA suppression should be considered a higher risk group and considered for dose escalation or the use of novel treatments.

  7. Sublobar resection is associated with improved outcomes over radiotherapy in the management of high-risk elderly patients with Stage I non-small cell lung cancer: a systematic review and meta-analysis

    PubMed Central

    Zhang, Bai-Lin; Chen, Jie; Zeng, Xian-Liang; Deng, Lei; Meng, Mao-Bin

    2017-01-01

    Background and Aim A matched-pair comparison was performed to compare the efficacy and safety of sublobar resection versus radiotherapy for high-risk elderly patients with Stage I non-small cell lung cancer (NSCLC). Patients and Methods We searched the Cochrane Library, MEDLINE, CENTRAL, EMBASE and manual searches. The meta-analysis was performed to compare overall survival, pattern of failure, and toxicity among the homogeneous studies. Subdivided analyses were also performed. Results Sixteen studies containing 11540 patients were included in the meta-analysis. Among these studies, 9 were propensity-score matched (PSM) cohort studies, and 7 were cohort studies. Sublobar resection, compared with radiotherapy (either conventional fraction radiation therapy or stereotactic body radiation therapy), significantly improved the overall survival regardless in both PSM and non-PSM analyses (all p < 0.05). However, the difference in the pattern of failure and toxicity were not significant (all p > 0.05). Conclusions Sublobar resection was associated with improved outcomes in high-risk elderly patients with Stage I NSCLC, which supports the need to compare both treatments in large prospective, randomized, controlled clinical trials. PMID:28002808

  8. Stereotactic body radiotherapy for oligometastases.

    PubMed

    Tree, Alison C; Khoo, Vincent S; Eeles, Rosalind A; Ahmed, Merina; Dearnaley, David P; Hawkins, Maria A; Huddart, Robert A; Nutting, Christopher M; Ostler, Peter J; van As, Nicholas J

    2013-01-01

    The management of metastatic solid tumours has historically focused on systemic treatment given with palliative intent. However, radical surgical treatment of oligometastases is now common practice in some settings. The development of stereotactic body radiotherapy (SBRT), building on improvements in delivery achieved by intensity-modulated and image-guided radiotherapy, now allows delivery of ablative doses of radiation to extracranial sites. Many non-randomised studies have shown that SBRT for oligometastases is safe and effective, with local control rates of about 80%. Importantly, these studies also suggest that the natural history of the disease is changing, with 2-5 year progression-free survival of about 20%. Although complete cure might be possible in a few patients with oligometastases, the aim of SBRT in this setting is to achieve local control and delay progression, and thereby also postpone the need for further treatment. We review published work showing that SBRT offers durable local control and the potential for progression-free survival in non-liver, non-lung oligometastatic disease at a range of sites. However, to test whether SBRT really does improve progression-free survival, randomised trials will be essential. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Impact of radiotherapy on implant-based prosthetic rehabilitation in patients with head and neck cancer: A prospective observational study on implant survival and quality of life-Preliminary results.

    PubMed

    Ettl, Tobias; Weindler, Janet; Gosau, Martin; Müller, Steffen; Hautmann, Matthias; Zeman, Florian; Koller, Michael; Papavasileiou, Dimitrios; Bürgers, Ralf; Driemel, Oliver; Schneider, Isabel; Klingelhöffer, Christoph; Meier, Johannes; Wahlmann, Ulrich; Reichert, Torsten E

    2016-09-01

    To study implant-based prosthetic rehabilitation of head and neck cancer patients with focus on implant survival and quality of life. The prospective observational study presents preliminary results of 29 edentulous head neck cancer patients (20 patients after radiotherapy) with 165 OsseoSpeed implants. Implant success after 1-year follow-up was evaluated by means of the Albrektsson criteria. Quality of life was analysed with the EORTC QLQ-C30, QLQ-H&N35, and OHIP 14 questionnaires. The overall implant survival rate after 1 year was 95.2% (157/165). Implant success measured by the Albrektsson criteria showed a lower success rate of 86.7% (143/165), mainly because of peri-implant marginal bone loss with a mean of 0.8 mm after 1 year. Xerostomia (p = 0.008), implant insertion within the radiation target volume (p = 0.09), implantation in transplanted bone (p = 0.05), and smoking (p = 0.041) were the main reasons for implant failure, followed by D4 bone quality, maxillary implant site, and insufficient primary stability. Speaking, swallowing, eating, as well as social integration and individual self-confidence had considerably improved 1 year after denture placement compared to before treatment. Implant-based prosthetic rehabilitation of head and neck cancer patients is possible at a calculable risk and significantly improves patients' quality of life. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  10. Does a central review platform improve the quality of radiotherapy for rectal cancer? Results of a national quality assurance project.

    PubMed

    Joye, Ines; Lambrecht, Maarten; Jegou, David; Hortobágyi, Eszter; Scalliet, Pierre; Haustermans, Karin

    2014-06-01

    Quality assurance (QA) for radiation treatment has become a priority since poorly delivered radiotherapy can negatively influence patient outcome. Within a national project we evaluated the feasibility of a central review platform and its role in improving uniformity of clinical target volume (CTV) delineation in daily practice. All Belgian radiotherapy departments were invited to participate and were asked to upload CTVs for rectal cancer treatment onto a secured server. These were centrally reviewed and feedback was given per e-mail. For each five consecutive patients per centre, the overlap parameter dice coefficient (DC) and the volumetric parameters volumetric ratio (RV) and commonly contoured volume (VCC) were calculated. Twenty departments submitted 1224 eligible cases of which 909 were modified (74.3%). There was a significant increase in RV and VCC between the first ten patients per centre and the others. This was not seen for DC. Statistical analysis did not show a further significant improvement in delineation over the entire review period. Central review was feasible and increased the uniformity in CTV delineation in the first ten rectal cancer patients per centre. The observations in this study can be used to optimize future QA initiatives. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Central versus Peripheral Tumor Location: Influence on Survival, Local Control, and Toxicity Following Stereotactic Body Radiotherapy for Primary Non-Small-Cell Lung Cancer.

    PubMed

    Park, Henry S; Harder, Eileen M; Mancini, Brandon R; Decker, Roy H

    2015-05-01

    Stereotactic body radiotherapy (SBRT) has been increasingly utilized for medically inoperable early stage non-small-cell lung cancer. However, a lower biological equivalent dose (BED) is often used for central tumors given toxicity concerns, potentially leading to decreased local control (LC). We compared survival, LC, and toxicity outcomes for SBRT patients with centrally versus peripherally located tumors. We included patients with primary cT1-2N0M0 non-small-cell lung cancer treated with SBRT at our institution from September 2007 to August 2013 with follow-up through August 2014. Central tumor location was defined as within 2 cm of the proximal bronchial tree, heart, great vessels, trachea, or other mediastinal structures. Kaplan-Meier analysis and multivariable Cox regression modeling were used for overall survival (OS) and LC, and the χ test and multivariable logistic regression modeling were used for toxicity. We included 251 patients (111 central, 140 peripheral) with median follow-up of 31.2 months. Patients with central tumors were more likely to be older (mean 75.8 versus 73.5 years; p = 0.04), have larger tumors (mean 2.5 cm versus 1.9 cm; p < 0.001), and be treated with a lower BED (mean 120.2 Gy versus 143.5 Gy; p < 0.001). Multivariable analysis revealed that tumor location was not associated with worse OS, LC, or toxicity. Patients with central tumors were less likely to have acute grade greater than or equal to three toxicity than those with peripheral tumors (odds ratio: 0.24; p = 0.02). Central tumor location did not predict for inferior OS, LC, or toxicity following SBRT when a lower mean BED was utilized.

  12. Effect on long-term survival of psychiatric disorder, inflammation, malnutrition, and radiotherapy-related toxicity in patients with locally advanced head and neck cancer.

    PubMed

    Unal, Dilek; Eroglu, Celalettin; Ozsoy, Saliha Demirel; Besirli, Asli; Orhan, Okan; Kaplan, Bunyamin

    2015-01-01

    To evaluate the effects on the long-term survival of psychiatric disorders, inflammation, malnutrition, and radiotherapy (RT)-related toxicity in patients with locally advanced head and neck cancer. Included were 47 patients who received RT for non-metastatic locally advanced head and neck cancer. The diagnosis of psychiatric disorder was made by the Diagnostic and Statistical Manual of Mental disorders (4th edn) (DSM-IV) criteria. Malnutrition was defined as weight loss >5% of baseline during RT. Interleukin 1β (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) were analyzed by enzyme-linked immunosorbent assay (ELISA). RT-related acute toxicity was evaluated once a week using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 2.0. The mean patient age was 57.3±11.4 years (range 33-80); 42 (89.4%) patients were male. Mean disease-free (DFS) and overall survival (OS) were 53 and 55 months, respectively. Mean DFS was significantly lower in patients with psychiatric disorder compared with those without (35 vs 59 months, p=0.013) and the same applied for mean OS (41 vs 61 months, p=0.008). There was no significant difference between patients with and without malnutrition in terms of OS. Similarly, no significant difference was seen between patients with and without RT-related toxicities in terms of OS. Age, psychiatric disorder, T status, and stage differed significantly between these groups (p<0.10) in univariate analysis. The multivariate Cox regression analysis identified that the OS was significantly associated only with psychiatric disorder (odds ratio/OR: 3.22, 95% confidence interval/CI: 1.29-8.41, p=0.013). Psychiatric disorders had unfavorable effects on OS in patients with locally advanced head and neck cancer. Inflammation, malnutrition and RT-related toxicity had no significant impact on OS.

  13. Patients With Proneural Glioblastoma May Derive Overall Survival Benefit From the Addition of Bevacizumab to First-Line Radiotherapy and Temozolomide: Retrospective Analysis of the AVAglio Trial

    PubMed Central

    Sandmann, Thomas; Bourgon, Richard; Garcia, Josep; Li, Congfen; Cloughesy, Timothy; Chinot, Olivier L.; Wick, Wolfgang; Nishikawa, Ryo; Mason, Warren; Henriksson, Roger; Saran, Frank; Lai, Albert; Moore, Nicola; Kharbanda, Samir; Peale, Franklin; Hegde, Priti; Abrey, Lauren E.; Phillips, Heidi S.; Bais, Carlos

    2015-01-01

    Purpose The AVAglio (Avastin in Glioblastoma) and RTOG-0825 randomized, placebo-controlled phase III trials in newly diagnosed glioblastoma reported prolonged progression-free survival (PFS), but not overall survival (OS), with the addition of bevacizumab to radiotherapy plus temozolomide. To establish whether certain patient subgroups derived an OS benefit from the addition of bevacizumab to first-line standard-of-care therapy, AVAglio patients were retrospectively evaluated for molecular subtype, and bevacizumab efficacy was assessed for each patient subgroup. Patients and Methods A total of 349 pretreatment specimens (bevacizumab arm, n = 171; placebo arm, n = 178) from AVAglio patients (total, N = 921) were available for biomarker analysis. Samples were profiled for gene expression and isocitrate dehydrogenase 1 (IDH1) mutation status and classified into previously identified molecular subtypes. PFS and OS were assessed within each subtype. Results A multivariable analysis accounting for prognostic covariates revealed that bevacizumab conferred a significant OS advantage versus placebo for patients with proneural IDH1 wild-type tumors (17.1 v 12.8 months, respectively; hazard ratio, 0.43; 95% CI, 0.26 to 0.73; P = .002). This analysis also revealed an interaction between the proneural subtype biomarker and treatment arm (P = .023). The group of patients with mesenchymal and proneural tumors derived a PFS benefit from bevacizumab compared with placebo; however, this translated to an OS benefit in the proneural subset only. Conclusion Retrospective analysis of AVAglio data suggests that patients with IDH1 wild-type proneural glioblastoma may derive an OS benefit from first-line bevacizumab treatment. The predictive value of the proneural subtype observed in AVAglio should be validated in an independent data set. PMID:26124478

  14. SU-F-R-27: Use Local Shape Descriptor Based On Geodesic Distance to Predict Survival in Non-Small Cell Lung Cancer After Radiotherapy

    SciTech Connect

    Zhang, H; Yan, L; Huang, K; Kong, F; Jin, J

    2016-06-15

    Purpose: The shape of the Positron Emission Tomography (PET) image represents the heterogeneity of tumor growth in various directions, and thus could be associated with tumor malignancy. We have proposed a median geodesic distance (MGD) to represent the local complexity of the shape and use a normalized MGD (NMGD) to quantify the shape, and found a potential correlation of NMGD to survival in a 20-patient pilot study. This study was to verify the finding in a larger patient cohort. Methods: Geodesic distance of two vertices on a surface is defined as the shortest path on the surface connecting the two vertices. The MGD was calculated for each vertex on the surface to display the local complexity of the shape. The NMGD was determined as: NMGD = 100*standard deviation(MGDs)/mean(MGDs). We applied the NMGD to 40 NSCLC patients who were enrolled in prospective PET image protocols and received radiotherapy. Each patient had a pre-treatment PET scan with the resolution of 4mm*4mm*5mm. Tumors were contoured by a professional radiation oncologist and triangulation meshes were built up based on the contours. Results: The mean and standard deviation of NMGD was 6.4±3.0. The OS was 33.1±16.9 months for low NMGD group, and 15.4±15.6 months for the high NMGD group. The low NMGD group had significant better OS than the high NMGD group (p=0.0013). Conclusion: NMGD could be used as a shape biomarker to predict survival and the MGD could be combined with image texture in future to increase prediction accuracy. This study was supported by Award Number 1R01CA166948 from the NIH and National Cancer Institute.

  15. Definitive radiotherapy for head and neck squamous cell carcinoma: update and perspectives on the basis of EBM.

    PubMed

    Kodaira, Takeshi; Nishimura, Yasumasa; Kagami, Yoshikazu; Ito, Yoshinori; Shikama, Naoto; Ishikura, Satoshi; Hiraoka, Masahiro

    2015-03-01

    Radiotherapy plays an essential role in the management of head and neck squamous cell carcinoma. Radiotherapy has a distinct advantage over surgical procedures in that it could achieve organ and function preservation with an efficacy similar to that of surgical series. To improve the clinical outcomes achievable by radiotherapy, altered fractionated radiotherapy has been prospectively tested for early and intermediate risk diseases, and was previously shown to be beneficial for local control and survival. Radiotherapy alone is insufficient for locally advanced disease; therefore, concurrent chemoradiotherapy is typically performed and plays an important role. A meta-analysis (Level Ia) revealed that the concurrent use of platinum agents appeared to improve tumor control and survival; however, this was accompanied by increases in the rates of both acute and late toxicities. Regarding radiation techniques, intensity modulated radiotherapy evolved in the 1990s, and has been globally used to treat head and neck squamous cell carcinoma patients. Intensity modulated radiotherapy reduces the exposure of normal tissue to radiation while preserving excellent dose coverage to the target volume; therefore, the rate of late toxicities especially xerostomia is minimized. Small size randomized studies and a meta-analysis have provided evidence to support the benefits of intensity modulated radiotherapy over two-dimensional or three-dimensional radiation therapy. Intensity modulated radiotherapy can also preserve quality of life following definitive chemoradiotherapy. Further improvements using intensity modulated proton therapy are warranted. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Further improvement in outcomes of nasopharyngeal carcinoma with optimized radiotherapy and induction plus concomitant chemotherapy: an update of the Milan experience.

    PubMed

    Palazzi, Mauro; Orlandi, Ester; Bossi, Paolo; Pignoli, Emanuele; Potepan, Paolo; Guzzo, Marco; Franceschini, Marzia; Scaramellini, Gabriele; Cantù, Giulio; Licitra, Lisa; Olmi, Patrizia; Tomatis, Stefano

    2009-07-01

    To report the outcome of a consecutive series of patients with nonmetastatic nasopharyngeal carcinoma (NPC), focusing on the impact of treatment-related factors. Between 2000 and 2006, 87 patients with NPC were treated with either conventional (two- or three-dimensional) radiotherapy (RT) or with intensity-modulated RT (IMRT). Of these patients, 81 (93%) received either concomitant CHT (24%) or both induction and concomitant chemotherapy (CHT) (69%). Stage was III in 36% and IV in 39% of patients. Outcomes in this study population were compared with those in the previous series of 171 patients treated during 1990 to 1999. With a median follow-up of 46 months, actuarial rates at 3 years were the following: local control, 96%; local-regional control, 93%; distant control (DC), 90%; disease-free survival (DFS), 82%; overall survival, 90%. In Stage III to IV patients, distant control at 3 years was 56% in patients treated with concomitant CHT only and 92% in patients treated with both induction and concomitant CHT (p = 0.014). At multivariate analysis, histology, N-stage, RT technique, and total RT dose had the strongest independent impact on DFS (p < 0.05). Induction CHT had a borderline effect on DC (p = 0.07). Most dosimetric statistics were improved in the group of patients treated with IMRT compared with conventional 3D technique. All outcome endpoints were substantially better in the study population compared with those in the previous series. Outcome of NPC has further improved in the study period compared with the previous decade, with a significant effect of RT technique optimization. The impact of induction CHT remains to be demonstrated in controlled trials.

  17. Further Improvement in Outcomes of Nasopharyngeal Carcinoma With Optimized Radiotherapy and Induction Plus Concomitant Chemotherapy: An Update of the Milan Experience

    SciTech Connect

    Palazzi, Mauro Orlandi, Ester; Bossi, Paolo; Pignoli, Emanuele; Potepan, Paolo; Guzzo, Marco; Franceschini, Marzia; Scaramellini, Gabriele; Cantu, Giulio; Licitra, Lisa; Olmi, Patrizia; Tomatis, Stefano

    2009-07-01

    Purpose: To report the outcome of a consecutive series of patients with nonmetastatic nasopharyngeal carcinoma (NPC), focusing on the impact of treatment-related factors. Methods and Materials: Between 2000 and 2006, 87 patients with NPC were treated with either conventional (two- or three-dimensional) radiotherapy (RT) or with intensity-modulated RT (IMRT). Of these patients, 81 (93%) received either concomitant CHT (24%) or both induction and concomitant chemotherapy (CHT) (69%). Stage was III in 36% and IV in 39% of patients. Outcomes in this study population were compared with those in the previous series of 171 patients treated during 1990 to 1999. Results: With a median follow-up of 46 months, actuarial rates at 3 years were the following: local control, 96%; local-regional control, 93%; distant control (DC), 90%; disease-free survival (DFS), 82%; overall survival, 90%. In Stage III to IV patients, distant control at 3 years was 56% in patients treated with concomitant CHT only and 92% in patients treated with both induction and concomitant CHT (p = 0.014). At multivariate analysis, histology, N-stage, RT technique, and total RT dose had the strongest independent impact on DFS (p < 0.05). Induction CHT had a borderline effect on DC (p = 0.07). Most dosimetric statistics were improved in the group of patients treated with IMRT compared with conventional 3D technique. All outcome endpoints were substantially better in the study population compared with those in the previous series. Conclusions: Outcome of NPC has further improved in the study period compared with the previous decade, with a significant effect of RT technique optimization. The impact of induction CHT remains to be demonstrated in controlled trials.

  18. Evaluation of adjuvant postoperative radiotherapy for lung cancer. [/sup 60/Co; X-ray

    SciTech Connect

    Chung, C.K.; Stryker, J.A.; O'Neill, M. Jr.; DeMuth, W.E. Jr.

    1982-11-01

    One hundred eighteen patients with lung cancer were retrospectively analyzed to determine whether postoperative radiotherapy (RT) improves survival. Patterns of treatment failure and three year NED (no evidence of disease) survival rates were assessed according to extent of tumor spread, histology, and treatment method. Patients with hilar or mediastinal node metastases were at higher risk of local failure compared to those with negative nodes. Postoperative RT reduced local recurrence and improved 3 year survival among patients with positive nodes. However, postoperative RT did not improve survival among those with negative nodes. Our data indicated that patients with positive hilar or mediastinal nodes may require postoperative RT to improve survival.

  19. Improving the efficiency of breast radiotherapy treatment planning using a semi-automated approach.

    PubMed

    Mitchell, Robert A; Wai, Philip; Colgan, Ruth; Kirby, Anna M; Donovan, Ellen M

    2017-01-01

    To reduce treatment planning times while maintaining plan quality through the introduction of semi-automated planning techniques for breast radiotherapy. Automatic critical structure delineation was examined using the Smart Probabilistic Image Contouring Engine (SPICE) commercial autosegmentation software (Philips Radiation Oncology Systems, Fitchburg, WI) for a cohort of ten patients. Semiautomated planning was investigated by employing scripting in the treatment planning system to automate segment creation for breast step-and-shoot planning and create objectives for segment weight optimization; considerations were made for three different multileaf collimator (MLC) configurations. Forty patients were retrospectively planned using the script and a planning time comparison performed. The SPICE heart and lung outlines agreed closely with clinician-defined outlines (median Dice Similarity Coefficient > 0.9); median difference in mean heart dose was 0.0 cGy (range -10.8 to 5.4 cGy). Scripted treatment plans demonstrated equivalence with their clinical counterparts. No statistically significant differences were found for target parameters. Minimal ipsilateral lung dose increases were also observed. Statistically significant (P < 0.01) time reductions were achievable for MLCi and Agility MLC (Elekta Ltd, Crawley, UK) plans (median 4.9 and 5.9 min, respectively). The use of commercial autosegmentation software enables breast plan adjustment based on doses to organs at risk. Semi-automated techniques for breast radiotherapy planning offer modest reductions in planning times. However, in the context of a typical department's breast radiotherapy workload, minor savings per plan translate into greater efficiencies overall. © 2016 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

  20. Survival improvements in adolescents and young adults after myeloablative allogeneic transplantation for acute lymphoblastic leukemia.

    PubMed

    Wood, William A; Lee, Stephanie J; Brazauskas, Ruta; Wang, Zhiwei; Aljurf, Mahmoud D; Ballen, Karen K; Buchbinder, David K; Dehn, Jason; Freytes, Cesar O; Lazarus, Hillard M; Lemaistre, Charles F; Mehta, Paulette; Szwajcer, David; Joffe, Steven; Majhail, Navneet S

    2014-06-01

    Adolescents and young adults (AYAs, ages 15 to 40 years) with cancer have not experienced survival improvements to the same extent as younger and older patients. We compared changes in survival after myeloablative allogeneic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia (ALL) among children (n = 981), AYAs (n = 1218), and older adults (n = 469) who underwent transplantation over 3 time periods: 1990 to 1995, 1996 to 2001, and 2002 to 2007. Five-year survival varied inversely with age group. Survival improved over time in AYAs and paralleled that seen in children; however, overall survival did not change over time for older adults. Survival improvements were primarily related to lower rates of early treatment-related mortality in the most recent era. For all cohorts, relapse rates did not change over time. A subset of 222 AYAs between the ages of 15 and 25 at 46 pediatric or 49 adult centers were also analyzed to describe differences by center type. In this subgroup, there were differences in transplantation practices among pediatric and adult centers, although HCT outcomes did not differ by center type. Survival for AYAs undergoing myeloablative allogeneic HCT for ALL improved at a similar rate as survival for children.

  1. Centrilobular emphysema combined with pulmonary fibrosis results in improved survival: a response.

    PubMed

    Cottin, Vincent; Cordier, Jean-François; Wells, Athol U

    2011-07-25

    Better survival in combined pulmonary fibrosis and emphysema than in lone pulmonary fibrosis: bias or reality? A response to Centrilobular emphysema combined with pulmonary fibrosis results in improved survival by Todd et al., Fibrogenesis & Tissue Repair 2011, 4:6.Please see related letter http://fibrogenesis.com/content/4/1/17.

  2. Improving village poultry's survival rate through community-based poultry health management: evidence from Benin.

    PubMed

    Sodjinou, Epiphane; Henningsen, Arne; Koudande, Olorounto Delphin

    2013-01-01

    Community-based poultry health management (CBM) is a strategy for village poultry improvement based on the installment of "poultry interest groups" in experimental villages. These groups serve as a channel for the dissemination of village poultry improvement technologies. The use of CBM is due to the fact that village poultry farming is practiced in a total or partial scavenging system which gives the impression that all the birds in the village belong to the same flock. Accordingly, actions that target all farmers of the same village may have a larger impact on the village poultry's survival rate than actions that target individual producers. The objective of this study is to assess the impact of CBM on the survival rate of village poultry. Based on data collected on 353 poultry keepers, the study shows that CBM significantly improves the survival rate of village poultry. The adoption of technologies--poultry vaccination, construction of henhouses, and improved feed--disseminated through the CBM also significantly improves the survival rate. The access to markets for inputs and veterinary services is also important in improving the survival rate of poultry. Finally, the study suggests that governments and development agencies can improve village poultry survival rates by investing in the dissemination of information regarding best husbandry management practices through approaches that rely on the community such as CBM because CBM groups serve as channels for the dissemination of village poultry improvement technologies.

  3. Genetic improvement of laying hens viability using survival analysis

    PubMed Central

    Ducrocq, Vincent; Besbes, Badi; Protais, Michel

    2000-01-01

    The survival of about eight generations of a large strain of laying hens was analysed separating the rearing period (RP) from the production period (PP), after hens were housed. For RP (respectively PP), 97.8% (resp., 94.1% ) of the 109 160 (resp., 100 665) female records were censored after 106 days (resp., 313 days) on the average. A Cox proportional hazards model stratified by flock (= season) and including a hatch-within-flock (HWF) fixed effect seemed to reasonably fit the RP data. For PP, this model could be further simplified to a non-stratified Weibull model. The extension of these models to sire-dam frailty (mixed) models permitted the estimation of the sire genetic variances at 0.261 ± 0.026 and 0.088 ± 0.010 for RP and PP, respectively. Heritabilities on the log scale were equal to 0.48 and 0.19. Non-additive genetic effects could not be detected. Selection was simulated by evaluating all sires and dams, after excluding all records from the last generation. Then, actual parents of this last generation were distributed into four groups according to their own pedigree index. Raw survivor curves of the progeny of extreme parental groups substantially differed (e.g., by 1.7% at 300 days for PP), suggesting that selection based on solutions from the frailty models could be efficient, despite the very large proportion of censored records. PMID:14736405

  4. Improved survival of newborns receiving leukocyte transfusions for sepsis

    SciTech Connect

    Cairo, M.S.; Rucker, R.; Bennetts, G.A.; Hicks, D.; Worcester, C.; Amlie, R.; Johnson, S.; Katz, J.

    1984-11-01

    To determine the role of polymorphonuclear (PMN) leukocyte transfusions in neonates with sepsis, 23 consecutive newborns were prospectively randomly selected during an 18-month period in a treatment plan to receive polymorphonuclear leukocyte transfusions with supportive care or supportive care alone. Thirteen neonates received transfusions every 12 hours for a total of five transfusions. Each transfusion consisting of 15 mL/kg of polymorphonuclear leukocytes was subjected to 1,500 rads of radiation. The polymorphonuclear leukocytes were obtained by continuous-flow centrifugation leukapheresis and contained 0.5 to 1.0 X 10(9) granulocytes per 15 mL with less than 10% lymphocytes. Positive findings on blood cultures were obtained in 14/23 patients and seven were randomly selected for each treatment group. Absolute granulocyte counts were less than 1,500/microL in 13 patients but tibial bone marrow examinations revealed that the neutrophil supply pool was depleted in only three patients. The survival was significantly greater in the treatment group compared with the group that did not receive transfusions.

  5. Filial cannibalism improves survival and development of beaugregory damselfish embryos.

    PubMed Central

    Payne, Adam G; Smith, Carl; Campbell, Andrew C

    2002-01-01

    Cannibalism of small numbers of offspring by a parent has been proposed as an adaptive parental strategy, by providing energy to support parental care. However, there are few empirical studies to support this hypothesis. We conducted field and laboratory experiments to investigate partial filial cannibalism in Stegastes leucostictus, a coral reef fish with paternal care. Partial cannibalism was shown to be common, and males were found to remove developing embryos from throughout a clutch in a random pattern, rather than in the more aggregated pattern seen during embryo predation. Males that received a diet supplement grew faster than control males, but did not engage in less cannibalism. Also, males did not concentrate cannibalism on early embryonic stages with the highest energetic value. Experimental reduction of embryo densities was found to significantly increase embryo development rate and survival from egg deposition to hatching, and experimental reduction of oxygen levels significantly increased rates of partial filial cannibalism by males. Artificial spawning sites with low oxygen levels were avoided by spawning females, and cannibalism rates by males were higher. We propose that partial filial cannibalism serves as an adaptive parental strategy to low oxygen levels in S. leucostictus by increasing the hatching success of embryos. PMID:12396483

  6. Low protein diets improve survival from peritonitis in guinea pigs.

    PubMed Central

    Peck, M D; Alexander, J W; Gonce, S J; Miskell, P W

    1989-01-01

    Enteral diets with different protein content were tested to determine their effect on outcome in a model of protracted bacterial peritonitis. Hartley guinea pigs were provided with gastrostomies, and 1 week later, osmotic pumps were implanted into the peritoneal cavity to allow for continuous release of live bacteria over the course of 1 week. Three days after pump implantation, the animals began receiving isocaloric enteral diets that contained 5%, 10%, 15%, or 20% of total calories as protein. After 2 weeks of observation, the survivors were killed. All animals lost weight during the 2-weeks period, but there was no difference in weight lost. Nitrogen balance correlated with dietary protein. The mortality rate was significantly higher in the groups that received 15% and 20% of total calories compared with the group that received 5% (p less than 0.05). Although dietary protein in the 5% group was insufficient for meeting the nutritional needs of the animal, survival was best in this group. Possible explanations are that protein restriction in this model may either augment host defence or impair bacterial virulence. PMID:2494959

  7. Technically accurate intracavitary insertions improve pelvic control and survival among patients with locally advanced carcinoma of the uterine cervix.

    PubMed

    Corn, B W; Hanlon, A L; Pajak, T F; Owen, J; Hanks, G E

    1994-06-01

    The purpose of this study was to document whether the technical qualities of a brachytherapy application impacts on the outcome of patients with locally advanced cervix cancer treated by definitive irradiation. A previous report from the patterns of care study demonstrated the importance of brachytherapy in the treatment of locally advanced cervix cancer. Locally advanced disease was defined as FIGO stages Ib (if tumor diameter was < or = 4 cm), IIb (if disease was bilateral or involved the lateral aspect of either parametrium), and III. Localization films from 128 patients with locally advanced squamous cell carcinoma of the cervix were reviewed by a radiation physicist and a radiation oncologist with expertise in gynecologic radiotherapy. All patients received external beam irradiation followed by one brachytherapy application (median point A dose = 8040 cGy; range, 4083-10,020 cGy). Brachytherapy parameters assessed were (a) the distance between the right colpostat source and the distal tandem source, (b) the distance between the left colpostat source and the distal tandem source, and (c) the symmetry of colpostat placement. Implants were scored as "ideal" (n = 8) when all three parameters were deemed satisfactory, "unacceptable" (n = 17) when none of the parameters was deemed satisfactory, and "adequate" (n = 41) in all other cases. Significantly improved 5-year local control was seen when comparing ideal and adequate placements to unacceptable placements (68% vs 34%, P = 0.02). A strong trend toward improved 5-year survival was also noted among the group with ideal and adequate implants as opposed to unacceptable implants (60% vs 40%). Multivariate analysis showed that the technical adequacy of the brachytherapy implant was the most important prognostic discriminant of local control. In conclusion, these analyses demonstrate the direct influence of competent technical implant performance on tumor control and even survival. While only a small fraction of

  8. The Radiobiological Basis for Improvements in Radiotherapy and Low Dose Risk Assessment

    SciTech Connect

    Hei, Tom K

    2009-12-09

    Overall Goal: This conference grant was proposed to organize and host an international conference at Columbia University in New York to critically assess the cellular and molecular signaling events and tissue response following radiation damage. The conference would also serve as a venue to play tribute to the more than forty years contributions made by Professor Eric J. Hall to the radiation biology field. The goals of the meeting were to examine tumor hypoxia and sensitizer development; recent advances made in clinical radiotherapy; addressed several low dose phenomena, including genomic instability and bystander effects that are important in radiation risk assessment. Study and Results: The symposium was held on October 13th and 14th, 2008 at the Alfred Lerner Hall in the Morningside campus of Columbia University. The symposium, entitled “From Beans to Genes: A Forty Year Odyssey in Radiation Biology” was attended by more than 120 faculty, scientists, clinicians, fellows and students. The symposium, spanned over a day and a half, covered four scientific themes. These included tumor hypoxia and radiosensitizers; low dose radiation response; radiation biology in the practice of radiotherapy, and radiation hazard in space and genetic predisposition to cancer. The program of the symposium is as follow:

  9. The Impact of Improved Population Life Expectancy in Survival Trend Analyses of Specific Diseases.

    PubMed

    van Walraven, Carl

    2016-08-01

    Survival trend analyses examine mortality outcomes over time. The impact of conducting survival trend analyses without accounting for improved population survival has not been systematically studied. The 1-year risk of death in the 100 most common hospital admissions for Ontario adults in 1994, 1999, 2004, and 2009 was determined. Generalized linear models were used to determine if adjusted death risk changed significantly over time with and without accounting for population survival. The statistical significance of temporal trends in survival changed after accounting for population life expectancy in 16 diagnoses (16 percent) (in 13 of 55 diagnoses, statistically significant decreasing mortality trends became insignificant; in 3 of 15 diagnoses, insignificant trends changed to a significant increase in mortality risk over time). These results highlight the importance of accounting for population life-expectancy changes in survival trend analyses. © Health Research and Educational Trust.

  10. Photochemical Internalization of Bleomycin Before External-Beam Radiotherapy Improves Locoregional Control in a Human Sarcoma Model

    SciTech Connect

    Norum, Ole-Jacob; Bruland, Oyvind Sverre; Gorunova, Ludmila; Berg, Kristian

    2009-11-01

    Purpose: The aim of this study was to explore the tumor growth response of the combination photochemical internalization and external-beam radiotherapy. Photochemical internalization is a technology to improve the utilization of therapeutic macromolecules in cancer therapy by photochemical release of endocytosed macromolecules into the cytosol. Methods and Materials: A human sarcoma xenograft TAX-1 was inoculated subcutaneously into nude mice. The photosensitizer AlPcS{sub 2a} and bleomycin were intraperitoneally administrated 48 h and 30 min, respectively, before diode laser light exposure at 670 nm (20 J/cm{sup 2}). Thirty minutes or 7 days after photochemical treatment, the animals were subjected to 4 Gy of ionizing radiation. Results: Using photochemical internalization of bleomycin as an adjunct to ionizing radiation increased the time to progression for the tumors from 17 to 33 days as compared with that observed with photodynamic therapy combined with ionizing radiation as well as for radiochemotherapy with bleomycin. The side effects observed when photochemical internalization of bleomycin was given shortly before ionizing radiation were eliminated by separating the treatment modalities in time. Conclusion: Photochemical internalization of bleomycin combined with ionizing radiation increased the time to progression and showed minimal toxicity and may therefore reduce the total radiation dose necessary to obtain local tumor control while avoiding long-term sequelae from radiotherapy.

  11. Improving the Survivability of a Stochastic Communication Network

    DTIC Science & Technology

    1988-12-01

    algorithm is called a labelling algorithm, and it has been the basis for other researchers, such as Edmonds and Karp [15], for developing a more...15. Edmonds, J. and R. M. Karp . "Theoretical Improvements in Logorithmic Effi- ciency for Network Flow Problems," Jour. A CM, 19: 248-264 (April, 1972...Conference Proceedings, 41: 49-54 (1972). 19. Hillier, Frederick S. and Gerald J. Lievernan. Introduction to Opt rafio., R(- search (Fourth Edition). Oakland

  12. Application of Artificial Intelligence to Improve Aircraft Survivability.

    DTIC Science & Technology

    1985-12-01

    AD-A164 172 APPLICATION OF ARTIFICIAL INTELLIGENCE TO IMPROVE 1/1 AIRCRAFT SURVASRILITY(U) NAVAL POSTGRADUATE SCHOOL UNCR7SIFEDMONTEREY CA N L DECKER...4 5- * . . . . . . 5~5~ * . . - -- &:~~-::-~&~ S.- ~ ~ S. . ~ ~.’ ~ VV ~ NAVAL POSTGRADUATE SCHOOL Monterey, California DTIC FEB 1406 D4 THESIS... School 6 7 Naval Postgraduate School 6C ADDRESS (City, State. and ZIP Code) 7b. ADDRESS (City, State, and ZIP Code) Monterey, California 93943-5100

  13. Hibernation-Based Therapy to Improve Survival of Severe Blood Loss

    DTIC Science & Technology

    2016-06-01

    AWARD NUMBER: W81XWH-10-2-0121 TITLE: Hibernation-Based Therapy to Improve Survival of Severe Blood Loss PRINCIPAL INVESTIGATOR: Greg Beilman...Hibernation-Based Therapy to Improve Survival of Severe Blood 5a. CONTRACT NUMBER Loss 5b. GRANT NUMBER W81XWH-10-2-0121 5c. PROGRAM ELEMENT NUMBER...political conflict. The injuries sustained are often accompanied by severe blood loss , and shock from this blood loss is the most common cause of

  14. Association of Adjuvant Chemoradiotherapy vs Radiotherapy Alone With Survival in Patients With Resected Major Salivary Gland Carcinoma: Data From the National Cancer Data Base.

    PubMed

    Amini, Arya; Waxweiler, Timothy V; Brower, Jeffrey V; Jones, Bernard L; McDermott, Jessica D; Raben, David; Ghosh, Debashis; Bowles, Daniel W; Karam, Sana D

    2016-11-01

    Data on adjuvant concurrent chemoradiotherapy (CRT) after resection of salivary gland carcinomas (SGCs) are limited. To examine overall survival (OS) outcomes of patients who receive CRT vs radiotherapy (RT) alone after resection of SGCs. The National Cancer Data Base (NCDB), a hospital-based registry that represents 70% of all cancer cases in the United States, was queried for patients who underwent resection of major SGCs with at least 1 high-risk feature (T3-T4 stage, N1-N3 stage, or positive margins). Included patients had histologic findings for malignant SGC with grades 2 to 3 disease and at least 1 high-risk feature. All patients underwent resection with postoperative CRT or RT alone. Patients were treated from 1998 to 2011. Data were analyzed from January to March 2016. Patients received CRT, defined as chemotherapy start within 14 days of RT initiation, or RT alone. Univariate, multivariate, and propensity score-matched analyses were performed to compare OS for patients undergoing CRT vs RT alone. Analyses included 2210 eligible patients (1372 men [62.1%] and 838 women [37.9%]; median age [range], 63 [18-90] years); of these, 1842 (83.3%) received RT alone and 368 (16.7%) received CRT. Median follow-up was 39 (range, 2-188) months. Most of the resected major SGCs occurred at the parotid gland (1852 [83.8%]), followed by the submandibular gland (276 [12.5%]), major gland not otherwise specified (66 [3.0%]), and sublingual gland (16 [0.7%]). Unadjusted 2-year OS was worse with adjuvant CRT vs RT alone (71.3% vs 80.2%), as was 5-year OS (38.5% vs 54.2%) (hazard ratio [HR], 1.51; 95% CI, 1.29-1.76; P < .001). Overall survival was inferior with adjuvant CRT on multivariate analysis (HR, 1.22; 95% CI, 1.03-1.44; P = .02) and propensity score-matched analysis (HR, 1.20; 95% CI, 0.98-1.47; P = .08) compared with RT alone. Subgroup analyses by age, comorbidity score, primary site, histologic type, grade, T stage, N stage, margin status, and chemotherapy

  15. Comorbidity as a predictor of overall survival in prostate cancer patients treated with external beam radiotherapy combined with HDR brachytherapy boosts.

    PubMed

    Hjälm-Eriksson, Marie; Ullén, Anders; Johansson, Hemming; Levitt, Seymoure; Nilsson, Sten; Kälkner, Karl-Mikael

    2017-01-01

    The risk stratification currently applied prior to curative treatment for localized prostate cancer (PC) does not take into account comorbidity or age. Therefore, we investigated the impact of comorbidity on overall survival (OS) in PC patients treated with external beam radiotherapy (EBRT) and high-dose rate (HDR) brachytherapy boost. At a single center, 611 consecutive patients diagnosed with localized PC from 1998 to 2004 underwent definitive EBRT (50 Gy) and HDR brachytherapy boosts (2 × 10 Gy) combined with neoadjuvant total androgen blockade. Comorbidity was assessed with the Charlson comorbidity score. The impact of risk factors on OS and disease-free survival (DFS) was calculated using Cox proportional hazard ratios. Risk groups were defined as follows: low-risk PC: PSA <10, WHO grade 1 and T stage 1; high-risk PC: PSA >20 and/or WHO grade 3 and/or T stage 3a; intermediate-risk PC representing patients who did not fit either the low- or high-risk PC group. Mean age in the study cohort was 66.4 years, and 51% of the patients reported some degree of comorbidity. Divided into risk groups 8.2% were categorized as low-risk, 64% as intermediate-risk and 27.8% as high-risk PC. Overall 10-year survival was 72.2%, and 89% of the patients were relapse-free. In the univariate and multivariate analyses using Cox proportional hazard ratios, age, comorbidity and T stage were statistically significant predictors of OS: hazard ratios 1.56, 1.44 and 1.2 (p-values .002, .04 and .05), respectively. WHO grade, PSA at diagnosis, T stage and comorbidity were also significant predictors of DFS (p-values .0001, .0001, .009 and .003, respectively). Comorbidity assessed with the Charlson score predicts OS in patients with localized PC treated with curative intent using combined EBRT and HDR brachytherapy boost, and should be considered when making decisions before radical treatment.

  16. Accelerated partial breast irradiation using intensity-modulated radiotherapy versus whole breast irradiation: 5-year survival analysis of a phase 3 randomised controlled trial.

    PubMed

    Livi, Lorenzo; Meattini, Icro; Marrazzo, Livia; Simontacchi, Gabriele; Pallotta, Stefania; Saieva, Calogero; Paiar, Fabiola; Scotti, Vieri; De Luca Cardillo, Carla; Bastiani, Paolo; Orzalesi, Lorenzo; Casella, Donato; Sanchez, Luis; Nori, Jacopo; Fambrini, Massimiliano; Bianchi, Simonetta

    2015-03-01

    Accelerated partial breast irradiation (APBI) has been introduced as an alternative treatment method for selected patients with early stage breast cancer (BC). Intensity-modulated radiotherapy (IMRT) has the theoretical advantage of a further increase in dose conformity compared with three-dimensional techniques, with more normal tissue sparing. The aim of this randomised trial is to compare the local recurrence and survival of APBI using the IMRT technique after breast-conserving surgery to conventional whole-breast irradiation (WBI) in early stage BC. This study was performed at the University of Florence (Florence, Italy). Women aged more than 40years affected by early BC, with a maximum pathological tumour size of 25mm, were randomly assigned in a 1:1 ratio to receive either WBI or APBI using IMRT. Patients in the APBI arm received a total dose of 30 Gy to the tumour bed in five daily fractions. The WBI arm received 50Gy in 25 fractions, followed by a boost on the tumour bed of 10Gy in five fractions. The primary end-point was occurrence of ipsilateral breast tumour recurrences (IBTRs); the main analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT02104895. A total of 520 patients were randomised (260 to external WBI and 260 to APBI with IMRT) between March 2005 and June 2013. At a median follow-up of 5.0 years (Interquartile Range (IQR) 3.4-7.0), the IBTR rate was 1.5% (three cases) in the APBI group (95% confidence interval (CI) 0.1-3.0) and in the WBI group (three cases; 95% CI 0.0-2.8). No significant difference emerged between the two groups (log rank test p=0.86). We identified seven deaths in the WBI group and only one in the APBI group (p=0.057). The 5-year overall survival was 96.6% for the WBI group and 99.4% for the APBI group. The APBI group presented significantly better results considering acute (p=0.0001), late (p=0.004), and cosmetic outcome (p=0.045). To our knowledge, this is the first randomised

  17. Improved Survival in Male Melanoma Patients in the Era of Sentinel Node Biopsy.

    PubMed

    Koskivuo, I; Vihinen, P; Mäki, M; Talve, L; Vahlberg, T; Suominen, E

    2017-03-01

    Sentinel node biopsy is a standard method for nodal staging in patients with clinically localized cutaneous melanoma, but the survival advantage of sentinel node biopsy remains unsolved. The aim of this case-control study was to investigate the survival benefit of sentinel node biopsy. A total of 305 prospective melanoma patients undergoing sentinel node biopsy were compared with 616 retrospective control patients with clinically localized melanoma whom have not undergone sentinel node biopsy. Survival differences were calculated with the median follow-up time of 71 months in sentinel node biopsy patients and 74 months in control patients. Analyses were calculated overall and separately in males and females. Overall, there were no differences in relapse-free survival or cancer-specific survival between sentinel node biopsy patients and control patients. Male sentinel node biopsy patients had significantly higher relapse-free survival ( P = 0.021) and cancer-specific survival ( P = 0.024) than control patients. In females, no differences were found. Cancer-specific survival rates at 5 years were 87.8% in sentinel node biopsy patients and 85.2% in controls overall with 88.3% in male sentinel node biopsy patients and 80.6% in male controls and 87.3% in female sentinel node biopsy patients and 89.8% in female controls. Sentinel node biopsy did not improve survival in melanoma patients overall. While females had no differences in survival, males had significantly improved relapse-free survival and cancer-specific survival following sentinel node biopsy.

  18. Improved biochemical outcome with adjuvant radiotherapy after radical prostatectomy for prostate cancer with poor pathologic features

    SciTech Connect

    Vargas, Carlos; Kestin, Larry L. . E-mail: lkestin@beaumont.edu; Weed, Dan W.; Krauss, Daniel; Vicini, Frank A.; Martinez, Alvaro A.

    2005-03-01

    Purpose: The indications for adjuvant external beam radiotherapy (EBRT) after radical prostatectomy (RP) are poorly defined. We performed a retrospective comparison of our institution's experience treating prostate cancer with RP vs. RP followed by adjuvant EBRT. Methods and materials: Between 1987 and 1998, 617 patients with clinical Stage T1-T2N0M0 prostate cancer underwent RP. Patients who underwent preoperative androgen deprivation and those with positive lymph nodes were excluded. Of the 617 patients, 34 (5.5%) with an undetectable postoperative prostate-specific antigen (PSA) level underwent adjuvant prostatic fossa RT at a median of 0.25 year (range, 0.1-0.6) postoperatively because of poor pathologic features. The median total dose was 59.4 Gy (range, 50.4-66.6 Gy) in 1.8-2.0-Gy fractions. These 34 RP+RT patients were compared with the remaining 583 RP patients. Biochemical failure was defined as any postoperative PSA level {>=}0.1 ng/mL and any postoperative PSA level {>=}0.3 ng/mL (at least 30 days after surgery). Administration of androgen deprivation was also scored as biochemical failure when applying either definition. The median clinical follow-up was 8.2 years (range, 0.1-11.2 years) for RP and 8.4 years (range, 0.3-13.8 years) for RP+RT. Results: Radical prostatectomy + radiation therapy patients had a greater pathologic Gleason score (mean, 7.3 vs. 6.5; p < 0.01) and pathologic T stage (median, T3a vs. T2c; p < 0.01). Age (median, 65.7 years) and pretreatment PSA level (median, 7.9 ng/mL) were similar between the treatment groups. Extracapsular extension was present in 72% of RP+RT patients vs. 27% of RP patients (p < 0.01). The RP+RT patients were more likely to have seminal vesicle invasion (29% vs. 9%, p < 0.01) and positive margins (73% vs. 36%, p < 0.01). Despite these poor pathologic features, the 5-year biochemical control (BC) rate (PSA < 0.1 ng/mL) was 57% for RP+RT and 47% for RP (p = 0.28). For patients with extracapsular extension, the

  19. Evolving Clinical Cancer Radiotherapy: Concerns Regarding Normal Tissue Protection and Quality Assurance

    PubMed Central

    Choi, Won Hoon

    2016-01-01

    Radiotherapy, which is one of three major cancer treatment methods in modern medicine, has continued to develop for a long period, more than a century. The development of radiotherapy means allowing the administration of higher doses to tumors to improve tumor control rates while minimizing the radiation doses absorbed by surrounding normal tissues through which radiation passes for administration to tumors, thereby reducing or removing the incidence of side effects. Such development of radiotherapy was accomplished by the development of clinical radiation oncology, the development of computers and machine engineering, the introduction of cutting-edge imaging technology, a deepened understanding of biological studies on the effects of radiation on human bodies, and the development of quality assurance (QA) programs in medical physics. The development of radiotherapy over the last two decades has been quite dazzling. Due to continuous improvements in cancer treatment, the average five-year survival rate of cancer patients has been close to 70%. The increases in cancer patients’ complete cure rates and survival periods are making patients’ quality of life during or after treatment a vitally important issue. Radiotherapy is implemented in approximately 1/3 to 2/3s of all cancer patients; and has improved the quality of life of cancer patients in the present age. Over the last century, as a noninvasive treatment, radiotherapy has unceasingly enhanced complete tumor cure rates and the side effects of radiotherapy have been gradually decreasing, resulting in a tremendous improvement in the quality of life of cancer patients. PMID:26908993

  20. Evolving Clinical Cancer Radiotherapy: Concerns Regarding Normal Tissue Protection and Quality Assurance.

    PubMed

    Choi, Won Hoon; Cho, Jaeho

    2016-02-01

    Radiotherapy, which is one of three major cancer treatment methods in modern medicine, has continued to develop for a long period, more than a century. The development of radiotherapy means allowing the administration of higher doses to tumors to improve tumor control rates while minimizing the radiation doses absorbed by surrounding normal tissues through which radiation passes for administration to tumors, thereby reducing or removing the incidence of side effects. Such development of radiotherapy was accomplished by the development of clinical radiation oncology, the development of computers and machine engineering, the introduction of cutting-edge imaging technology, a deepened understanding of biological studies on the effects of radiation on human bodies, and the development of quality assurance (QA) programs in medical physics. The development of radiotherapy over the last two decades has been quite dazzling. Due to continuous improvements in cancer treatment, the average five-year survival rate of cancer patients has been close to 70%. The increases in cancer patients' complete cure rates and survival periods are making patients' quality of life during or after treatment a vitally important issue. Radiotherapy is implemented in approximately 1/3 to 2/3s of all cancer patients; and has improved the quality of life of cancer patients in the present age. Over the last century, as a noninvasive treatment, radiotherapy has unceasingly enhanced complete tumor cure rates and the side effects of radiotherapy have been gradually decreasing, resulting in a tremendous improvement in the quality of life of cancer patients.

  1. Improved Survival with the Patients with Variceal Bleed

    PubMed Central

    Sharma, Praveen; Sarin, Shiv K.

    2011-01-01

    Variceal hemorrhage is a major cause of death in patients with cirrhosis. Over the past two decades new treatment modalities have been introduced in the management of acute variceal bleeding (AVB) and several recent studies have suggested that the outcome of patients with cirrhosis and AVB has improved. Improved supportive measures, combination therapy which include early use of portal pressure reducing drugs with low rates of adverse effects (somatostatin, octerotide or terlipressin) and endoscopic variceal ligation has become the first line treatment in the management of AVB. Short-term antibiotic prophylaxis, early use of lactulose for prevention of hepatic encephalopathy, application of early transjugular intrahepatic portasystemic shunts (TIPS), fully covered self-expandable metallic stent in patients for AVB may be useful in those cases where balloon tamponade is considered. Early and wide availability of liver transplantation has changed the armamentarium of the clinician for patients with AVB. High hepatic venous pressure gradient (HVPG) >20 mmHg in AVB has become a useful predictor of outcomes and more aggressive therapies with early TIPS based on HVPG measurement may be the treatment of choice to reduce mortality further. PMID:21994853

  2. Improved survival with the patients with variceal bleed.

    PubMed

    Sharma, Praveen; Sarin, Shiv K

    2011-01-01

    Variceal hemorrhage is a major cause of death in patients with cirrhosis. Over the past two decades new treatment modalities have been introduced in the management of acute variceal bleeding (AVB) and several recent studies have suggested that the outcome of patients with cirrhosis and AVB has improved. Improved supportive measures, combination therapy which include early use of portal pressure reducing drugs with low rates of adverse effects (somatostatin, octerotide or terlipressin) and endoscopic variceal ligation has become the first line treatment in the management of AVB. Short-term antibiotic prophylaxis, early use of lactulose for prevention of hepatic encephalopathy, application of early transjugular intrahepatic portasystemic shunts (TIPS), fully covered self-expandable metallic stent in patients for AVB may be useful in those cases where balloon tamponade is considered. Early and wide availability of liver transplantation has changed the armamentarium of the clinician for patients with AVB. High hepatic venous pressure gradient (HVPG) >20 mmHg in AVB has become a useful predictor of outcomes and more aggressive therapies with early TIPS based on HVPG measurement may be the treatment of choice to reduce mortality further.

  3. Radiotherapy enhances laser palliation of malignant dysphagia: a randomised study.

    PubMed Central

    Sargeant, I R; Tobias, J S; Blackman, G; Thorpe, S; Glover, J R; Bown, S G

    1997-01-01

    BACKGROUND/AIMS: A major drawback of laser endoscopy in the palliation of malignant dysphagia is the need for repeated treatments. This study was designed to test whether external beam radiotherapy would reduce the necessity for repeated laser therapy. PATIENTS/METHODS: Sixty seven patients with inoperable oesophageal or gastric cardia cancers and satisfactory swallowing after initial laser recanalisation were randomised to palliative external beam radiotherapy (30 Gy in 10 fractions) or no radiotherapy. All patients underwent a 'check' endoscopy five weeks after initial recanalisation and were subsequently reendoscoped only for recurrent dysphagia, which occurred in 59 patients. RESULTS: Dysphagia was relieved equally well in both groups and the improvement was maintained with further endoscopic treatment. The initial dysphagia controlled interval and the duration between procedures required to maintain lifelong palliation (treatment interval) increased from five to nine weeks (median) in the radiotherapy group (p < 0.01 both parameters). Radiotherapy was well tolerated in all but three patients. One perforation occurred and two fistulae opened after dilatation in patients who received radiotherapy. CONCLUSION: Additional radiotherapy reduces the necessity for therapeutic endoscopy for a patient's remaining life. It has an important role in relatively well patients who are likely to survive long enough to benefit. PMID:9135526

  4. Virtual 3D tumor marking-exact intraoperative coordinate mapping improve post-operative radiotherapy

    PubMed Central

    2011-01-01

    The quality of the interdisciplinary interface in oncological treatment between surgery, pathology and radiotherapy is mainly dependent on reliable anatomical three-dimensional (3D) allocation of specimen and their context sensitive interpretation which defines further treatment protocols. Computer-assisted preoperative planning (CAPP) allows for outlining macroscopical tumor size and margins. A new technique facilitates the 3D virtual marking and mapping of frozen sections and resection margins or important surgical intraoperative information. These data could be stored in DICOM format (Digital Imaging and Communication in Medicine) in terms of augmented reality and transferred to communicate patient's specific tumor information (invasion to vessels and nerves, non-resectable tumor) to oncologists, radiotherapists and pathologists. PMID:22087558

  5. Adipocyte Secretome Increases Radioresistance of Malignant Melanocytes by Improving Cell Survival and Decreasing Oxidative Status.

    PubMed

    Coelho, Pedro; Silva, Liliana; Faria, Isabel; Vieria, Mónica; Monteiro, Armanda; Pinto, Gabriela; Prudêncio, Cristina; Fernandes, Rúben; Soares, Raquel

    2017-05-01

    Radiotherapy is a treatment option for the majority of malignancies. However, because melanoma is known to be radioresistant, the use of ionizing radiation as an adjuvant therapy in cutaneous melanoma patients is ineffective. Obesity has now been recognized as a risk factor for melanoma. High adiposity is generally associated with a more pro-oxidative status. Oxidative stress is a major player in radiation therapy and also a common link between obesity and cancer. Several adipocyte-released proteins are known to have a role in controlling cellular growth and pro-survival signaling. For that reason, we investigated the influence of 3T3-L1 mature adipocyte secretome in B16-F10 malignant melanocyte radiosensitivity. We evaluated B16-F10 cell survival and redox homeostasis when exposed to four daily doses of ionizing radiation (2 Gy per day) up to a total of 8 Gy in a medical linear accelerator. B16-F10 melanocytes exhibited slight alterations in survival, catalase activity, nitrative stress and total oxidant concentration after the first 2 Gy irradiation. The motility of the melanocytes was also delayed by ionizing radiation. Subsequent irradiations of the malignant melanocytes led to more prominent reductions in overall survival. Remarkably, 3T3-L1 adipocyte-secreted molecules were able to increase the viability and migration of melanocytes, as well as lessen the pro-oxidant burden induced by both the single and cumulative X-ray doses. In vitro adipocyte-released factors protected B16-F10 malignant melanocytes from both oxidative stress and loss of viability triggered by radiation, enhancing the radioresistant phenotype of these cells with a concomitant activation of the AKT signaling pathway. These results both help to elucidate how obesity influences melanoma radioresistance and support the usage of conventional medical linear accelerators as a valid model for the in vitro radiobiological study of tumor cell lines.

  6. Improved Survival Among Children with Spina Bifida in the United States

    PubMed Central

    Shin, Mikyong; Kucik, James E.; Siffel, Csaba; Lu, Chengxing; Shaw, Gary M.; Canfield, Mark A.; Correa, Adolfo

    2015-01-01

    Objective To evaluate trends in survival among children with spina bifida by race/ethnicity and possible prognostic factors in 10 regions of the United States. Study design A retrospective cohort study was conducted of 5165 infants with spina bifida born during 1979-2003, identified by 10 birth defects registries in the United States. Survival probabilities and adjusted hazard ratios were estimated for race/ethnicity and other characteristics using the Cox proportional hazard model. Results During the study period, the 1-year survival probability among infants with spina bifida showed improvements for whites (from 88% to 96%), blacks (from 79% to 88%), and Hispanics (from 88% to 93%). The impact of race/ethnicity on survival varied by birth weight, which was the strongest predictor of survival through age 8. There was little racial/ethnic variation in survival among children born of very low birth weight. Among children born of low birth weight, the increased risk of mortality to Hispanics was approximately 4-6 times that of whites. The black-white disparity was greatest among children born of normal birth weight. Congenital heart defects did not affect the risk of mortality among very low birth weight children but increased the risk of mortality 4-fold among children born of normal birth weight. Conclusions The survival of infants born with spina bifida has improved; however, improvements in survival varied by race/ethnicity, and blacks and Hispanics continued to have poorer survival than whites in the most recent birth cohort from 1998-2002. Further studies are warranted to elucidate possible reasons for the observed differences in survival. PMID:22727874

  7. Lack of improvement in survival rates for women under 50 with endometrial cancer, 2000-2011.

    PubMed

    Rodriguez, Ana M; Schmeler, Kathleen M; Kuo, Yong-Fang

    2016-04-01

    To assess how first course of treatment affects cancer-specific survival in women diagnosed with endometrial cancer younger than 50 years old. Public-use data from the Surveillance, Epidemiology, and End Results program were used. The study included 82,721 women diagnosed with primary, invasive endometrial cancer between 2000 and 2011. We assessed type of treatment using Cox's proportional hazards models to determine survival disparity by age and stage. Cancer-specific survival significantly improved for those aged ≥50 years with late stage, but did not improve for those <50. First course of treatment significantly affected cancer-specific survival for endometrial cancer patients. Regardless of age, survival was greatly improved for late-stage patients who received a combination of surgery and radiation [hazard ratio (HR) 0.62 [95 % confidence interval (CI) 0.47-0.78] and 0.64 (95 % CI 0.59-0.68)] compared to those who received total hysterectomy with removal of ovaries and tubes. However, the proportion of patients who received combination therapy decreased over time. The magnitude of decrease was larger in patients <50 than in those aged ≥50. Overall, about 24-57 % of the difference in cancer-specific survival over time in patients aged <50 was explained by their initial treatment. Improvement in cancer-specific survival was only seen in older women with late-stage diagnosis. Despite improvements in diagnoses and treatments, the difference in age-specific survival indicates that more should be done to understand why these rates are not improving for those younger than 50 years old.

  8. Probabilistic mortality forecasting with varying age-specific survival improvements.

    PubMed

    Bohk-Ewald, Christina; Rau, Roland

    2017-01-01

    Many mortality forecasting approaches extrapolate past trends. Their predictions of the future development can be quite precise as long as turning points and/or age-shifts of mortality decline are not present. To account even for such mortality dynamics, we propose a model that combines recently developed ideas in a single framework. It (1) uses rates of mortality improvement to model the aging of mortality decline, and it (2) optionally combines the mortality trends of multiple countries to catch anticipated turning points. We use simulation-based Bayesian inference to estimate and run this model that also provides prediction intervals to quantify forecast uncertainty. Validating mortality forecasts for British and Danish women from 1991 to 2011 suggest that our model can forecast regular and irregular mortality developments and that it can perform at least as well as other widely accepted approaches like, for instance, the Lee-Carter model or the UN Bayesian approach. Moreover, prospective mortality forecasts from 2012 to 2050 suggest gradual increases for British and Danish life expectancy at birth.

  9. SRT1720 improves survival and healthspan of obese mice

    PubMed Central

    Minor, Robin K.; Baur, Joseph A.; Gomes, Ana P.; Ward, Theresa M.; Csiszar, Anna; Mercken, Evi M.; Abdelmohsen, Kotb; Shin, Yu-Kyong; Canto, Carles; Scheibye-Knudsen, Morten; Krawczyk, Melissa; Irusta, Pablo M.; Martín-Montalvo, Alejandro; Hubbard, Basil P.; Zhang, Yongqing; Lehrmann, Elin; White, Alexa A.; Price, Nathan L.; Swindell, William R.; Pearson, Kevin J.; Becker, Kevin G.; Bohr, Vilhelm A.; Gorospe, Myriam; Egan, Josephine M.; Talan, Mark I.; Auwerx, Johan; Westphal, Christoph H.; Ellis, James L.; Ungvari, Zoltan; Vlasuk, George P.; Elliott, Peter J.; Sinclair, David A.; de Cabo, Rafael

    2011-01-01

    Sirt1 is an NAD+-dependent deacetylase that extends lifespan in lower organisms and improves metabolism and delays the onset of age-related diseases in mammals. Here we show that SRT1720, a synthetic compound that was identified for its ability to activate Sirt1 in vitro, extends both mean and maximum lifespan of adult mice fed a high-fat diet. This lifespan extension is accompanied by health benefits including reduced liver steatosis, increased insulin sensitivity, enhanced locomotor activity and normalization of gene expression profiles and markers of inflammation and apoptosis, all in the absence of any observable toxicity. Using a conditional SIRT1 knockout mouse and specific gene knockdowns we show SRT1720 affects mitochondrial respiration in a Sirt1- and PGC-1α-dependent manner. These findings indicate that SRT1720 has long-term benefits and demonstrate for the first time the feasibility of designing novel molecules that are safe and effective in promoting longevity and preventing multiple age-related diseases in mammals. PMID:22355589

  10. Improvement of child survival in Mexico: the diagonal approach.

    PubMed

    Sepúlveda, Jaime; Bustreo, Flavia; Tapia, Roberto; Rivera, Juan; Lozano, Rafael; Oláiz, Gustavo; Partida, Virgilio; García-García, Lourdes; Valdespino, José Luis

    2006-12-02

    Public health interventions aimed at children in Mexico have placed the country among the seven countries on track to achieve the goal of child mortality reduction by 2015. We analysed census data, mortality registries, the nominal registry of children, national nutrition surveys, and explored temporal association and biological plausibility to explain the reduction of child, infant, and neonatal mortality rates. During the past 25 years, child mortality rates declined from 64 to 23 per 1000 livebirths. A dramatic decline in diarrhoea mortality rates was recorded. Polio, diphtheria, and measles were eliminated. Nutritional status of children improved significantly for wasting, stunting, and underweight. A selection of highly cost-effective interventions bridging clinics and homes, what we called the diagonal approach, were central to this progress. Although a causal link to the reduction of child mortality was not possible to establish, we saw evidence of temporal association and biological plausibility to the high level of coverage of public health interventions, as well as significant association to the investments in women education, social protection, water, and sanitation. Leadership and continuity of public health policies, along with investments on institutions and human resources strengthening, were also among the reasons for these achievements.

  11. Improved survival using oxygen free radical scavengers in the presence of ischemic bowel anastomosis.

    PubMed

    Bergren, C T; Bodzin, J H; Cortez, J A

    1988-06-01

    A rat model was developed to determine the efficacy of oxygen free radical scavenger compounds in improving small bowel anastomotic healing in ischemia. 50 Sprague-Dawley rats underwent laparotomy and were divided into groups: I. sham operation; II. ischemia produced by ligation of mesenteric vessels along 3-5 cm of bowel; III. bowel transection and anastomosis; IV. ligation of vessels with bowel transection and anastomosis; V. ligation of vessels, bowel transection and IV administration of superoxide dismutase (SOD) (5000 U/kg) prior to anastomosis. All surviving animals were sacrificed after 2 weeks. Anastomotic tensile strength and histology were evaluated. Percent survival and the average length of survival for all groups is seen in the table below. (table: see text) A significant decrease in survival was present with the anastomotic group and the ischemic anastomotic group when compared with controls. An improved survival similar to ischemia alone was present in SOD group. No significant difference was noted between SOD and control groups. The results of this study indicate an improved survival rate and length of survival similar to controls in animals undergoing ischemic and penetrating injury to the bowel with the use of oxygen free radical scavenger compounds prior to anastomosis.

  12. Epoetin alfa improves survival after chemoradiation for Stage III esophageal cancer: Final results of a prospective observational study

    SciTech Connect

    Rades, Dirk . E-mail: Rades.Dirk@gmx.net; Tribius, Silke; Yekebas, Emre F.; Bahrehmand, Roia; Wildfang, Ingeborg; Kilic, Ergin; Muellerleile, Ulrich; Gross, Eberhard; Schild, Steven E.; Alberti, Winfried

    2006-06-01

    Purpose: This prospective, nonrandomized study evaluates the effectiveness of epoetin alfa to maintain the hemoglobin levels at 12 to14 g/dL (optimal range for tumor oxygenation) during chemoradiation for Stage III esophageal cancer and its impact on overall survival (OS), metastatic-free survival (MFS), and locoregional control (LC). Methods and Materials: Ninety-six patients were included. Forty-two patients received epoetin alfa (150 IU/kg, 3 times a week) during radiotherapy, which was started at hemoglobin less than 13 g/dL and stopped at 14 g/dL or higher. Hemoglobin levels were measured weekly during RT. Results: Both groups were balanced for age, sex, performance status, tumor length/location, histology, grading, T-stage/N-stage, chemotherapy, treatment schedule, and hemoglobin before RT. Median change of hemoglobin was +0.3 g/dL/wk with epoetin alfa and -0.5 g/dL/wk without epoetin alfa. At least 60% of hemoglobin levels were 12 to 14 g/dL in 64% and 17% of the patients, respectively (p < 0.001). Patients who received epoetin alfa had better OS (32% vs. 8% at 2 years, p = 0.009) and LC (67% vs. 15% at 2 years, p = 0.001). MFS was not significantly different (42% vs. 18% at 2 years, p = 0.09). Conclusions: The findings suggest that epoetin alfa when used to maintain the hemoglobin levels at 12 to 14 g/dL can improve OS and LC of Stage III esophageal cancer patients.

  13. Dietary Curcumin Increases Antioxidant Defenses in Lung, Ameliorates Radiation-Induced Pulmonary Fibrosis, and Improves Survival in Mice

    PubMed Central

    Lee, James C.; Kinniry, Paul A.; Arguiri, Evguenia; Serota, Matthew; Kanterakis, Stathis; Chatterjee, Shampa; Solomides, Charalambos C.; Javvadi, Prashanthi; Koumenis, Constantinos; Cengel, Keith A.; Christofidou-Solomidou, Melpo

    2010-01-01

    The effectiveness of lung radiotherapy is limited by radiation tolerance of normal tissues and by the intrinsic radiosensitivity of lung cancer cells. The chemopreventive agent curcumin has known antioxidant and tumor cell radiosensitizing properties. Its usefulness in preventing radiation-induced pneumonopathy has not been tested previously. We evaluated dietary curcumin in radiation-induced pneumonopathy and lung tumor regression in a murine model. Mice were given 1%or 5%(w/w) dietary curcumin or control diet prior to irradiation and for the duration of the experiment. Lungs were evaluated at 3 weeks after irradiation for acute lung injury and inflammation by evaluating bronchoalveolar lavage (BAL) fluid content for proteins, neutrophils and at 4 months for pulmonary fibrosis. In a separate series of experiments, an orthotopic model of lung cancer using intravenously injected Lewis lung carcinoma (LLC) cells was used to exclude possible tumor radioprotection by dietary curcumin. In vitro, curcumin boosted antioxidant defenses by increasing heme oxygenase 1 (HO-1) levels in primary lung endothelial and fibroblast cells and blocked radiation-induced generation of reactive oxygen species (ROS). Dietary curcumin significantly increased HO-1 in lungs as early as after 1 week of feeding, coinciding with a steady-state level of curcumin in plasma. Although both 1% and 5% w/w dietary curcumin exerted physiological changes in lung tissues by significantly decreasing LPS-induced TNF-α production in lungs, only 5%dietary curcumin significantly improved survival of mice after irradiation and decreased radiation-induced lung fibrosis. Importantly, dietary curcumin did not protect LLC pulmonary metastases from radiation killing. Thus dietary curcumin ameliorates radiation-induced pulmonary fibrosis and increases mouse survival while not impairing tumor cell killing by radiation. PMID:20426658

  14. Pulmonary function changes after radiotherapy in non-small-cell lung cancer patients with long-term disease-free survival

    SciTech Connect

    Borst, Gerben R.; Jaeger, Katrien de; Belderbos, Jose; Burgers, Sjaak A.; Lebesque, Joos V. . E-mail: j.lebesque@nki.nl

    2005-07-01

    Purpose: To evaluate the changes in pulmonary function after high-dose radiotherapy (RT) for non-small-cell lung cancer in patients with a long-term disease-free survival. Methods and Materials: Pulmonary function was measured in 34 patients with inoperable non-small-cell lung cancer before RT and at 3 and 18 months of follow-up. Thirteen of these patients had a pulmonary function test (PFT) 36 months after RT. The pulmonary function parameters (forced expiratory volume in 1 s [FEV{sub 1}], diffusion capacity [T{sub lcoc}], forced vital capacity, and alveolar volume) were expressed as a percentage of normal values. Changes were expressed as relative to the pre-RT value. We evaluated the impact of chronic obstructive pulmonary disease, radiation pneumonitis, mean lung dose, and PFT results before RT on the changes in pulmonary function. Results: At 3, 18, and 36 months, a significant decrease was observed for the T{sub lcoc} (9.5%, 14.6%, and 22.0%, respectively) and the alveolar volume (5.8%, 6.6%, and 15.8%, respectively). The decrease in FEV{sub 1} was significant at 18 and 36 months (8.8% and 13.4%, respectively). No recovery of any of the parameters was observed. Chronic obstructive pulmonary disease was an important risk factor for larger PFT decreases. FEV{sub 1} and T{sub lcoc} decreases were dependent on the mean lung dose. Conclusion: A significant decrease in pulmonary function was observed 3 months after RT. No recovery in pulmonary function was seen at 18 and 36 months after RT. The decrease in pulmonary function was dependent on the mean lung dose, and patients with chronic obstructive pulmonary disease had larger reductions in the PFTs.

  15. The C-reactive Protein/Albumin Ratio Is an independent Prognostic Factor for Overall Survival in Patients with Nasopharyngeal Carcinoma Receiving Intensity-Modulated Radiotherapy

    PubMed Central

    Tao, Chang-Juan; Chen, Yuan-Yuan; Jiang, Feng; Feng, Xing-Lai; Jin, Qi-Feng; Jin, Ting; Piao, Yong-Feng; Chen, Xiao-Zhong

    2016-01-01

    This study aims to investigate the prognostic value of the C-reactive protein/albumin (CRP/ALB) ratio in nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era. A total of 719 patients with NPC treated between January 2007 and December 2012 were retrospectively reviewed. Serum albumin and CRP levels were measured before treatment. The associations between the CRP/ALB ratio and clinicopathological parameters were analyzed. Multivariate analyses using the Cox proportional hazards model were performed to identify significant prognostic factors associated with overall survival (OS). The prognostic value of the CRP/ALB ratio was determined using receiver operating characteristic (ROC) curve analysis. The optimal CRP/ALB ratio cutoff value was 0.141. High CRP/ALB ratio was significantly associated with older age (P < 0.001), more advanced T category (P < 0.001) and advanced TNM stage (P = 0.024). Patients with an elevated CRP/ALB ratio (≥ 0.141) had poorer OS than those with a CRP/ALB ratio < 0.141 (5-year OS rates: 91.9% vs. 78.1%; P < 0.001). Multivariate analysis suggested clinical T category [hazard ratio (HR) 2.284; 95% confidence interval (CI), 1.429-3.652; P = 0.001]; clinical N category (HR 1.575; 95% CI, 1.007-2.464; P = 0.047) and CRP/ALB ratio (HR 2.173; 95% CI, 1.128-3.059; P = 0.015) were independently associated with OS. In conclusion, pretreatment CRP/ALB ratio is an objective biomarker with significant prognostic value for OS in NPC. The CRP/ALB ratio can enhance conventional TNM staging to stratify patients and may help facilitate individualized treatment of high-risk cases. PMID:27877215

  16. Plasma levels of soluble programmed death ligand-1 may be associated with overall survival in nonsmall cell lung cancer patients receiving thoracic radiotherapy

    PubMed Central

    Zhao, Jing; Zhang, Peng; Wang, Jianhua; Xi, Qingsong; Zhao, Xueqi; Ji, Minghua; Hu, Guangyuan

    2017-01-01

    Abstract Immune-checkpoint signaling plays an important role in immunosuppression of tumors. We aimed to investigate the association of soluble programmed death-ligand 1 (sPD-L1) level in plasma with overall survival (OS) in locally advanced or inoperable nonsmall-cell lung cancer (NSCLC) patients treated with thoracic radiotherapy (TRT). We used ELISA to evaluate the sPD-L1 levels at diagnosis and during TRT in 126 clinically inoperable NSCLC patients. OS rates were followed up and recorded. SPSS software and GraphPad Prism 5 were used for statistics. In this study, the average sPD-L1 levels at baseline, week 2, and week 4 during TRT and post-TRT were 107.2, 51.3, 65.4, and 111.1 pg/mL, respectively. Levels of sPD-L1 at week 2 and week 4 were significantly less than at baseline, with both P values < 0.001. Using 96.5 pg/mL as the cutoff, patients with lower baseline sPD-L1 level had longer OS than those with higher sPD-L1 level (27.8 months vs 15.5 months, P = 0.005). Using multivariate analysis, the following factors were significantly associated with longer OS: female, adenocarcinoma, higher TRT dose, and lower baseline sPD-L1 level. Patients with both characteristics of lower baseline sPD-L1 level and higher TRT dose (BED10 ≥84 Gy) had the longest OS. To conclude, the lower baseline sPD-L1 level was significantly associated with longer OS in NSCLC patients treated with TRT, which may serve as an independent biomarker and needs further clinical study. PMID:28207525

  17. The C-reactive Protein/Albumin Ratio Is an independent Prognostic Factor for Overall Survival in Patients with Nasopharyngeal Carcinoma Receiving Intensity-Modulated Radiotherapy.

    PubMed

    Tao, Chang-Juan; Chen, Yuan-Yuan; Jiang, Feng; Feng, Xing-Lai; Jin, Qi-Feng; Jin, Ting; Piao, Yong-Feng; Chen, Xiao-Zhong

    2016-01-01

    This study aims to investigate the prognostic value of the C-reactive protein/albumin (CRP/ALB) ratio in nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era. A total of 719 patients with NPC treated between January 2007 and December 2012 were retrospectively reviewed. Serum albumin and CRP levels were measured before treatment. The associations between the CRP/ALB ratio and clinicopathological parameters were analyzed. Multivariate analyses using the Cox proportional hazards model were performed to identify significant prognostic factors associated with overall survival (OS). The prognostic value of the CRP/ALB ratio was determined using receiver operating characteristic (ROC) curve analysis. The optimal CRP/ALB ratio cutoff value was 0.141. High CRP/ALB ratio was significantly associated with older age (P < 0.001), more advanced T category (P < 0.001) and advanced TNM stage (P = 0.024). Patients with an elevated CRP/ALB ratio (≥ 0.141) had poorer OS than those with a CRP/ALB ratio < 0.141 (5-year OS rates: 91.9% vs. 78.1%; P < 0.001). Multivariate analysis suggested clinical T category [hazard ratio (HR) 2.284; 95% confidence interval (CI), 1.429-3.652; P = 0.001]; clinical N category (HR 1.575; 95% CI, 1.007-2.464; P = 0.047) and CRP/ALB ratio (HR 2.173; 95% CI, 1.128-3.059; P = 0.015) were independently associated with OS. In conclusion, pretreatment CRP/ALB ratio is an objective biomarker with significant prognostic value for OS in NPC. The CRP/ALB ratio can enhance conventional TNM staging to stratify patients and may help facilitate individualized treatment of high-risk cases.

  18. Halofuginone improves muscle-cell survival in muscular dystrophies.

    PubMed

    Bodanovsky, Anna; Guttman, Noga; Barzilai-Tutsch, Hila; Genin, Ola; Levy, Oshrat; Pines, Mark; Halevy, Orna

    2014-07-01

    Halofuginone has been shown to prevent fibrosis via the transforming growth factor-β/Smad3 pathway in muscular dystrophies. We hypothesized that halofuginone would reduce apoptosis--the presumed cause of satellite-cell depletion during muscle degradation-in the mdx mouse model of Duchenne muscular dystrophy. Six-week-old mdx mouse diaphragm exhibited fourfold higher numbers of apoptotic nuclei compared with wild-type mice as determined by a TUNEL assay. Apoptotic nuclei were found in macrophages and in Pax7-expressing cells; some were located in centrally-nucleated regenerating myofibers. Halofuginone treatment of mdx mice reduced the apoptotic nuclei number in the diaphragm, together with reduction in Bax and induction in Bcl2 levels in myofibers isolated from these mice. A similar effect was observed when halofuginone was added to cultured myofibers. No apparent effect of halofuginone was observed in wild-type mice. Inhibition of apoptosis or staurosporine-induced apoptosis by halofuginone in mdx primary myoblasts and C2 myogenic cell line, respectively, was reflected by less pyknotic/apoptotic cells and reduced Bax expression. This reduction was reversed by a phosphinositide-3-kinase and mitogen-activated protein kinase/extracellular signal-regulated protein kinase inhibitors, suggesting involvement of these pathways in mediating halofuginone's effects on apoptosis. Halofuginone increased apoptosis in α smooth muscle actin- and prolyl 4-hydroxylase β-expressing cells in mdx diaphragm and in myofibroblasts, the major source of extracellular matrix. The data suggest an additional mechanism by which halofuginone improves muscle pathology and function in muscular dystrophies.

  19. Adjuvant radiotherapy for locally advanced upper tract urothelial carcinoma

    PubMed Central

    Huang, Yun-Ching; Chang, Ying-Hsu; Chiu, Kuo-Hsiung; Shindel, Alan W.; Lai, Chia-Hsuan

    2016-01-01

    There is relatively little literature on adjuvant radiotherapy after radical nephroureterectomy with bladder cuff excision (RNU) for patients with upper tract urothelial carcinoma (UTUC). This study was designed to determine the efficacy of adjuvant radiotherapy for patients with pT3N0M0 UTUC. We retrospectively reviewed 198 patients treated with RNU between December 2001 and January 2015. Postoperative radiotherapy was administered in 40 (20.2%) of patients. Patients who received radiotherapy were younger than those that did not (65.2 vs. 70.5 years, p = 0.023). With median follow up of 29.1 months, Kaplan-Meier analysis with the log-rank test demonstrated no significant differences between those omitting vs receiving adjuvant radiotherapy in regards to 2-year rates of overall survival (72.0% vs. 73.4%, p = 0.979), cancer-specific survival (73.2% vs. 75.3%, p = 0.844), and recurrence-free survival (61.2% vs. 66.3%, p = 0.742). However, in multivariable analysis with Cox regression, young age, absence of chronic kidney disease, negative lymphovascular invasion, negative surgical margin, and adjuvant chemotherapy were also associated with better cancer-specific survival. In conclusion, adjuvant radiotherapy did not offer any significant benefit in terms of overall, cancer-specific, and recurrence-free survivals in patients with pT3N0M0 UTUC after RNU. More effective systemic adjuvant chemotherapy is necessary to improve the outcome of these patients. PMID:27910890

  20. Cone beam CT with zonal filters for simultaneous dose reduction, improved target contrast and automated set-up in radiotherapy.

    PubMed

    Moore, C J; Marchant, T E; Amer, A M

    2006-05-07

    Cone beam CT (CBCT) using a zonal filter is introduced. The aims are reduced concomitant imaging dose to the patient, simultaneous control of body scatter for improved image quality in the tumour target zone and preserved set-up detail for radiotherapy. Aluminium transmission diaphragms added to the CBCT x-ray tube of the Elekta Synergytrade mark linear accelerator produced an unattenuated beam for a central "target zone" and a partially attenuated beam for an outer "set-up zone". Imaging doses and contrast noise ratios (CNR) were measured in a test phantom for transmission diaphragms 12 and 24 mm thick, for 5 and 10 cm long target zones. The effect on automatic registration of zonal CBCT to conventional CT was assessed relative to full-field and lead-collimated images of an anthropomorphic phantom. Doses along the axis of rotation were reduced by up to 50% in both target and set-up zones, and weighted dose (two thirds surface dose plus one third central dose) was reduced by 10-20% for a 10 cm long target zone. CNR increased by up to 15% in zonally filtered CBCT images compared to full-field images. Automatic image registration remained as robust as that with full-field images and was superior to CBCT coned down using lead-collimation. Zonal CBCT significantly reduces imaging dose and is expected to benefit radiotherapy through improved target contrast, required to assess target coverage, and wide-field edge detail, needed for robust automatic measurement of patient set-up error.

  1. Combined total body X-ray irradiation and total skin electron beam radiotherapy with an improved technique for mycosis fungoides

    SciTech Connect

    Halberg, F.E.; Fu, K.K.; Weaver, K.A.; Zackheim, H.S.; Epstein, E.H. Jr.; Wintroub, B.U.

    1989-08-01

    Twelve consecutive patients with advanced stage mycosis fungoides (MF) were treated with combined total body X ray irradiation (TBI) and total skin electron beam radiotherapy (EBRT). Six had generalized plaque disease and dermatopathic nodes, three had tumor stage disease and node biopsy positive for mycosis fungoides, and three had erythroderma/Sezary syndrome. The treatment regimen consisted of split course total body X ray irradiation, given in twice weekly 15 cGy fractions to 75 cGy, then total skin electron beam radiation therapy given in once weekly 400 cGy fractions to a total dose of 2400 cGy. Underdosed areas and areas of greatest initial involvement were boosted 400 cGy twice weekly for an additional 1200 cGy. This was followed by a second course of total body X ray irradiation, to a total dose of 150 cGy. The total skin electron beam radiotherapy technique is a modification of an established six position EBRT technique for mycosis fungoides. Measurements to characterize the beam with and without a lexan scattering plate, demonstrated that the combination of no-plate beams produced better dose uniformity with a much higher dose rate. This improved technique is particularly advantageous for elderly and/or frail patients. Nine (75%) of the 12 patients achieved complete response (CR). The other three had significant improvement with greater than 80% clearing of their disease and resolution of symptoms. All six patients with generalized plaque disease achieved complete response and remained free of disease from 2 to 16 months. Two of three node positive patients also achieved complete response; one, with massive biopsy-documented mycosis fungoides nodal disease and deep open tumors, remained relapse-free over 2 years. Only one of the three patients with erythroderma/Sezary syndrome achieved a complete response, which was short lived.

  2. Steroidal and nonsteroidal antiinflammatory medications can improve photoreceptor survival after laser retinal photocoagulation.

    PubMed

    Brown, Jeremiah; Hacker, Henry; Schuschereba, Steven T; Zwick, Harry; Lund, David J; Stuck, Bruce E

    2007-10-01

    To determine whether methylprednisolone or indomethacin can enhance photoreceptor survival after laser retinal injury in an animal model. Experimental study. Twenty rhesus monkeys. Twenty rhesus monkeys (Macaca mulatta) received a grid of argon green (514.5 nm, 10 ms) laser lesions in the macula of the right eye and a grid of neodymium:yttrium-aluminum-garnet (Nd:YAG; 1064 nm, 10 ns) lesions in the macula of the left eye, followed by randomization to 2 weeks of treatment in 1 of 4 treatment groups: high-dose methylprednisolone, moderate-dose methylprednisolone, indomethacin, or control. The lesions were assessed at day 1, day 14, 2 months, and 4 months. The authors were masked to the treatment group. This report discusses the histologic results of ocular tissue harvested at 4 months. The number of surviving photoreceptor cell nuclei within each lesion was compared with the number of photoreceptor nuclei in surrounding unaffected retina. The proportion of surviving photoreceptor nuclei was compared between each treatment group. Argon retinal lesions in the high-dose steroid treatment group and the indomethacin treatment group demonstrated improved photoreceptor survival compared with the control group (P = 0.004). Hemorrhagic Nd:YAG lesions demonstrated improved survivability with indomethacin treatment compared with controls (P = 0.003). In nonhemorrhagic Nd:YAG laser retinal lesions, the lesions treated with moderate-dose steroids demonstrated improved photoreceptor survival compared with the control group (P = 0.004). Based on histologic samples of retinal laser lesions 4 months after injury, treatment with indomethacin resulted in improved photoreceptor survival in argon laser lesions and hemorrhagic Nd:YAG laser lesions. Treatment with systemic methylprednisolone demonstrated improved photoreceptor survival in argon retinal lesions and in nonhemorrhagic Nd:YAG lesions.

  3. [Radiotherapy of bladder cancer].

    PubMed

    Riou, O; Chauvet, B; Lagrange, J-L; Martin, P; Llacer Moscardo, C; Charissoux, M; Lauche, O; Aillères, N; Fenoglietto, P; Azria, D

    2016-09-01

    Surgery (radical cystectomy) is the standard treatment of muscle-invasive bladder cancer. Radiochemotherapy has risen as an alternative treatment option to surgery as part as organ-sparing combined modality treatment or for patients unfit for surgery. Radiochemotherapy achieves 5-year bladder intact survival of 40 to 65% and 5-year overall survival of 40 to 50% with excellent quality of life. This article introduces the French recommendations for radiotherapy of bladder cancer: indications, exams, technique, dosimetry, delivery and image guidance.

  4. Intermediate-fraction neoadjuvant radiotherapy for rectal cancer.

    PubMed

    Zhan, Tiancheng; Gu, Jin; Li, Ming; Du, Changzheng

    2013-04-01

    have introduced bias, particularly because patients with greater financial means were more likely to choose to undergo the preoperative radiotherapy regimen. Compared with surgery alone, this modified preoperative radiotherapy regimen is associated with significantly reduced local recurrence and complication rates, with improved survival in patients who show downstaging. The modified protocol offers a clinical outcome equivalent to standard preoperative radiotherapy regimens while offering an alternative for increasing the flexibility of preoperative radiation regimens in China.

  5. The fall in mortality from ischemic heart disease in Australia: has survival after myocardial infarction improved?

    PubMed

    Martin, C A; Hobbs, M S; Armstrong, B K

    1984-08-01

    Trends in mortality and survival after myocardial infarction (MI) were studied by use of computerised death and hospital discharge records for 25 to 64 year old residents of the Perth Statistical Division between 1971 and 1979. Highly significant falls in ischemic heart disease (IHD) mortality rates were found for men (18%) and women (29%) but 4, 26 and 52 week survival after hospital admission for MI remained constant at around 88%, 84% and 81% respectively. Further, as 75% of all IHD deaths between 1971 and 1979 occurred before the victim was admitted to hospital, the survival of those receiving treatment would have had to be greatly improved to influence total mortality from IHD appreciably. As the age and sex composition of persons hospitalised for MI and the proportion of MI victims hospitalised did not change during the study period it would seem that improved survival after hospital admission for MI did not contribute to the fall in IHD deaths between 1971 and 1979.

  6. Does lean management improve patient safety culture? An extensive evaluation of safety culture in a radiotherapy institute.

    PubMed

    Simons, Pascale A M; Houben, Ruud; Vlayen, Annemie; Hellings, Johan; Pijls-Johannesma, Madelon; Marneffe, Wim; Vandijck, Dominique

    2015-02-01

    The importance of a safety culture to maximize safety is no longer questioned. However, achieving sustainable culture improvements are less evident. Evidence is growing for a multifaceted approach, where multiple safety interventions are combined. Lean management is such an integral approach to improve safety, quality and efficiency and therefore, could be expected to improve the safety culture. This paper presents the effects of lean management activities on the patient safety culture in a radiotherapy institute. Patient safety culture was evaluated over a three year period using triangulation of methodologies. Two surveys were distributed three times, workshops were performed twice, data from an incident reporting system (IRS) was monitored and results were explored using structured interviews with professionals. Averages, chi-square, logistical and multi-level regression were used for analysis. The workshops showed no changes in safety culture, whereas the surveys showed improvements on six out of twelve dimensions of safety climate. The intention to report incidents not reaching patient-level decreased in accordance with the decreasing number of reports in the IRS. However, the intention to take action in order to prevent future incidents improved (factorial survey presented β: 1.19 with p: 0.01). Due to increased problem solving and improvements in equipment, the number of incidents decreased. Although the intention to report incidents not reaching patient-level decreased, employees experienced sustained safety awareness and an increased intention to structurally improve. The patient safety culture improved due to the lean activities combined with an organizational restructure, and actual patient safety outcomes might have improved as well. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Metastatic lung cancer in the age of targeted therapy: improving long-term survival

    PubMed Central

    Del Rivero, Jaydira; Thomas, Anish

    2016-01-01

    Epidermal growth factor receptor (EGFR) mutations are the most frequent targetable genetic abnormality observed in non-small cell lung cancer (NSCLC). More than a decade after EGFR mutations were shown to predict sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKI), retrospective cohort studies are now identifying and characterizing 5-year survivors. While these studies indicate subsets of patients achieving long-term survival, there is paucity of data pertaining to the long-term survival benefits of these targeted therapies at a population level. Improving access to molecular testing and treatment are key to maximizing the survival benefits at a population level. PMID:28149768

  8. [Improvment of survival in cystic fibrosis patients from 1962 to 1971].

    PubMed

    Högger, G P

    1975-07-01

    The survival rate of 42 patients with cystic fibrosis diagnosed during the five year period before institution of full prophylactic aerosol, mist tent and postural drainage therapy in 1967 was compared with that of 32 cases diagnosed in the five following years. The mean survival rate of the latter group was 81%, 81% and 73% at 1, 2 and 3 years respectivly, compared with 64%, 59% and 57% in the former group. The main difference was due to the significantly improved survival rate of cases diagnosed during the first year of life.

  9. Hibernation-Based Therapy to Improve Survival of Severe Blood Loss

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-10-2-0121 TITLE: Hibernation -Based Therapy to Improve Survival of Severe Blood Loss PRINCIPAL INVESTIGATOR: Gregory...PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE 2. REPORT TYPE 3. DATES COVERED 4. TITLE AND SUBTITLE Hibernation -Based Therapy to... hibernating mammals to aid in salvage of a patient with a potentially life-threatening blood loss, permitting survival to reach effective medical

  10. Fontan Patient Survival After Pediatric Heart Transplantation Has Improved in the Current Era.

    PubMed

    Simpson, Kathleen E; Pruitt, Elizabeth; Kirklin, James K; Naftel, David C; Singh, Rakesh K; Edens, R Erik; Barnes, Aliessa P; Canter, Charles E

    2017-04-01

    Historically, patients with a prior Fontan procedure for complex congenital heart disease (CHD) have been considered at higher risk for death after heart transplant (HT) compared with other HT transplant candidates. With the overall trend of improved survival of pediatric HT recipients, it is unclear of Fontan patient post-HT survival has also improved in the current era. Data from the Pediatric Heart Transplant Study database for Fontan patients who underwent HT was compared between the early era (1993 to 2006, n = 150) and late era (2007 to 2014, n = 252). Post-HT survival and pre-HT characteristics were compared among eras and also with non-Fontan CHD patients. At time of HT, Fontan patients in the late era were more likely to require inotropic support, have protein-losing enteropathy, have failure to thrive, and be further from time of Fontan, although less likely to be on ventilator support. Only ventilator support and earlier year of HT were significant risk factors for death in the multivariate analysis. Post-HT Fontan patient survival significantly improved from the early to late era (p = 0.02), particularly in the early phase, with 1-year survival of 77% in the early era and 89% in the late era. Late era non-Fontan CHD patient 1-year post-HT survival was similar to Fontan patients at 92%. Survival of Fontan patients after HT has significantly improved in the current era. Currently, expected post-HT survival for Fontan patients is on par with other CHD patients. Fontan patients should not be excluded from consideration for HT solely on a history of Fontan. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  11. Improvement of dose distribution with irregular surface compensator in whole breast radiotherapy

    PubMed Central

    Hideki, Fujita; Nao, Kuwahata; Hiroyuki, Hattori; Hiroshi, Kinoshita; Haruyuki, Fukuda

    2013-01-01

    Aim of this study was to compare the dosimetric aspects of whole breast radiotherapy (WBRT) between an irregular surface compensator (ISC) and a conventional tangential field technique using physical wedges. Treatment plans were produced for 20 patients. The Eclipse treatment planning system (Varian Medical Systems) was used for the dose calculation: For the physical wedge technique, the wedge angle was selected to provide the best dose homogeneity; for the ISC technique, the fluence editor application was used to extend the optimal fluence. These two treatment plans were compared in terms of doses in the planning target volume, the dose homogeneity index, the maximum dose, ipsilateral lung and heart doses for left breast irradiation, and the monitor unit counts required for treatment. Compared with the physical wedge technique, the ISC technique significantly reduced the dose homogeneity index, the maximum dose, the volumes received at 105% of the prescription dose, as well as reducing both the ipsilateral lung and heart doses (P < 0.01 for all comparisons). However, the monitor unit counts were not significantly different between the techniques (P > 0.05). Thus, the ISC technique for WBRT enables significantly better dose distribution in the planning target volume. PMID:24049317

  12. In situ vaccination by radiotherapy to improve responses to anti-CTLA-4 treatment.

    PubMed

    Vanpouille-Box, Claire; Pilones, Karsten A; Wennerberg, Erik; Formenti, Silvia C; Demaria, Sandra

    2015-12-16

    Targeting immune checkpoint receptors has emerged as an effective strategy to induce immune-mediated cancer regression in the subset of patients who have significant pre-existing anti-tumor immunity. For the remainder, effective anti tumor responses may require vaccination. Radiotherapy, traditionally used to achieve local tumor control, has acquired a new role, that of a partner for immunotherapy. Ionizing radiation has pro-inflammatory effects that facilitate tumor rejection. Radiation alters the tumor to enhance the concentration of effector T cells via induction of chemokines, cytokines and adhesion molecules. In parallel, radiation can induce an immunogenic death of cancer cells, promoting cross-presentation of tumor-derived antigens by dendritic cells to T cells. Newly generated anti-tumor immune responses have been demonstrated post-radiation in both murine models and occasional patients, supporting the hypothesis that the irradiated tumor can become an in situ vaccine. It is in this role, that radiation can be applied to induce anti-tumor T cells in lymphocyte-poor tumors, and possibly benefit patients who would otherwise fail to respond to immune checkpoint inhibitors. This review summarizes preclinical and clinical data demonstrating that radiation acts in concert with antibodies targeting the immune checkpoint cytotoxic T-lymphocyte antigen-4 (CTLA-4), to induce therapeutically effective anti-tumor T cell responses in tumors otherwise non responsive to anti-CTLA-4 therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Improving patient safety in radiotherapy by learning from near misses, incidents and errors.

    PubMed

    Williams, M V

    2007-05-01

    Radiotherapy incidents involving a major overdose such as that which affected a patient in Glasgow in 2006 are rare. The publicity surrounding this patient's treatment and the subsequent publication of the enquiry by the Scottish Executive have led to a re-evaluation of procedures in many departments. However, other incidents and near misses that might also generate learning are often surrounded by obsessive secrecy. With the passage of time, even those incidents that have been subject to a public enquiry are lost from view. Indeed, the report on the incident in Glasgow draws attention to strong parallels with that in North Staffordshire, the report of which is not freely available despite being in the public domain. A web-based system to archive and make available previously published reports should be relatively simple to establish. A greater challenge is to achieve open reporting of near misses, incidents and errors. The key elements would be the effective use of keywords, a system of classification and a searchable anonymized database with free access. There should be a well designed system for analysis, response and feedback. This would ensure the dissemination of learning. The development of a more open culture for reports under the Ionising Radiation (Medical Exposure) Regulations (IR(ME)R) is essential: at the very least, their main findings and recommendations should be routinely published. These changes should help us to achieve greater safety for our patients.

  14. An active lifestyle prior to coronary surgery is associated with improved survival in elderly patients.

    PubMed

    Rengo, Giuseppe; Galasso, Gennaro; Vitale, Dino F; Furgi, Giuseppe; Zincarelli, Carmela; Golino, Luca; Femminella, Grazia D; Piscione, Federico; Rengo, Franco; Leosco, Dario

    2010-07-01

    An active lifestyle is associated with a reduced cardiovascular risk in middle-aged as well as in elderly patients. In the present study, we investigated the association between physical activity habits of elderly participants prior to coronary artery bypass grafting (CABG) and survival free from both all-cause and cardiac death. Study population consisted of 587 elderly patients (>or=70 years) CABG patients stratified, according to the Physical Activity Scale for the Elderly (PASE), into less active (low PASE) and exercised (high PASE) groups. At follow-up (mean: 44.3 +/- 21.0 months), 33 (37.1%) of 89 total deaths occurred for cardiac causes. Sixty-month survival rate was 65% and 96% for low-PASE and high-PASE groups, respectively (log rank = 49.460, p < .0001). Cox survival analysis indicated a significant (p < .0001) nonlinear association between PASE score increments and improved survival with the most evident differences in the lowest score categories. A robust association was also found between low PASE score and increased cardiac-related mortality (p < .0001). Our data indicate that a more active lifestyle is significantly associated with improved survival in elderly CABG patients. The nonlinearity of the relation suggests that more sedentary patients could have the most benefit on survival by increasing their exercise lifestyle habits. The improved outcome is explained by both cardiac and overall mortality reduction.

  15. Limiting Radiotherapy to the Contralateral Retropharyngeal and High Level II Lymph Nodes in Head and Neck Squamous Cell Carcinoma is Safe and Improves Quality of Life

    PubMed Central

    Spencer, Christopher R.; Gay, Hiram A.; Haughey, Bruce H.; Nussenbaum, Brian; Adkins, Douglas R.; Wildes, Tanya M.; DeWees, Todd A.; Lewis, James S.; Thorstad, Wade L.

    2014-01-01

    Background Radiation treatment volumes in head and neck squamous cell carcinoma (HNSCC) are controversial. Here we report the outcomes, failures, and quality of life (QOL) of patients treated using intensity modulated radiation therapy (IMRT) that eliminated treatment of contralateral retropharyngeal lymph nodes (RPLN) in the clinically uninvolved neck. Methods A prospective institutional database identified patients with primary oral cavity, oropharynx, hypopharynx, larynx and unknown primary HNSCC treated using IMRT. There were three temporal groups (G1-3). G1 received comprehensive neck IMRT with parotid sparing, G2 eliminated the contralateral high level II (HLII) lymph nodes, and G3 further eliminated the contralateral RPLN in the clinically uninvolved neck. Patterns of failure and survival analyses were completed and QOL data measured by the MD Anderson Dysphagia Inventory (MDADI) was compared in a subset of patients from G1 and G3. Results There were 748 patients identified. Of the 488 patients treated in G2 or G3, 406 had a clinically uninvolved contralateral neck. There were no failures in the spared RPLNs (95% CI; 0-1.3%) or high contralateral neck (95% CI; 0-0.7%). QOL data was compared between 44 patients in G1 and 51 patients in G3. QOL improved both globally and in all domains assessed for G3 in which reduced radiotherapy volumes were used (p < 0.007). Conclusions For patients with locally advanced HNSCC, eliminating coverage to the contralateral HLII and contralateral RPLN in the clinically uninvolved side of the neck is associated with minimal risk of failure in these regions and significantly improved patient-reported QOL. PMID:25143048

  16. Lysophosphatidic acid (LPA) as a pro-fibrotic and pro-oncogenic factor: a pivotal target to improve the radiotherapy therapeutic index.

    PubMed

    Rancoule, Chloé; Espenel, Sophie; Trone, Jane-Chloé; Langrand-Escure, Julien; Vallard, Alexis; Rehailia-Blanchard, Amel; El Meddeb Hamrouni, Anis; Xia, Yaxiong; Guy, Jean-Baptiste; Ben-Mrad, Majed; Magné, Nicolas

    2017-06-27

    Radiation-induced fibrosis is widely considered as a common but forsaken phenomenon that can lead to clinical sequela and possibly vital impairments. Lysophosphatidic acid is a bioactive lipid involved in fibrosis and probably in radiation-induced fibrosis as suggested in recent studies. Lysophosphatidic acid is also a well-described pro-oncogenic factor, involved in carcinogenesis processes (proliferation, survival, angiogenesis, invasion, migration). The present review highlights and summarizes the links between lysophosphatidic acid and radiation-induced fibrosis, lysophosphatidic acid and radioresistance, and proposes lysophosphatidic acid as a potential central actor of the radiotherapy therapeutic index. Besides, we hypothesize that following radiotherapy, the newly formed tumour micro-environment, with increased extracellular matrix and increased lysophosphatidic acid levels, is a favourable ground to metastasis development. Lysophosphatidic acid could therefore be an exciting therapeutic target, minimizing radio-toxicities and radio-resistance effects.

  17. Lysophosphatidic acid (LPA) as a pro-fibrotic and pro-oncogenic factor: a pivotal target to improve the radiotherapy therapeutic index

    PubMed Central

    Rancoule, Chloé; Espenel, Sophie; Trone, Jane-Chloé; Langrand-Escure, Julien; Vallard, Alexis; Rehailia-Blanchard, Amel; Hamrouni, Anis El Meddeb; Xia, Yaxiong; Guy, Jean-Baptiste; Ben-Mrad, Majed; Magné, Nicolas

    2017-01-01

    Radiation-induced fibrosis is widely considered as a common but forsaken phenomenon that can lead to clinical sequela and possibly vital impairments. Lysophosphatidic acid is a bioactive lipid involved in fibrosis and probably in radiation-induced fibrosis as suggested in recent studies. Lysophosphatidic acid is also a well-described pro-oncogenic factor, involved in carcinogenesis processes (proliferation, survival, angiogenesis, invasion, migration). The present review highlights and summarizes the links between lysophosphatidic acid and radiation-induced fibrosis, lysophosphatidic acid and radioresistance, and proposes lysophosphatidic acid as a potential central actor of the radiotherapy therapeutic index. Besides, we hypothesize that following radiotherapy, the newly formed tumour micro-environment, with increased extracellular matrix and increased lysophosphatidic acid levels, is a favourable ground to metastasis development. Lysophosphatidic acid could therefore be an exciting therapeutic target, minimizing radio-toxicities and radio-resistance effects. PMID:28402936

  18. Improvement of dose distribution in breast radiotherapy using a reversible transverse magnetic field Linac-MR unit

    SciTech Connect

    Esmaeeli, A. D.; Mahdavi, S. R.; Pouladian, M.; Bagheri, S.; Monfared, A. S.

    2014-01-15

    Purpose: To investigate the improvement in dose distribution in tangential breast radiotherapy using a reversible transverse magnetic field that maintains the same direction of Lorentz force between two fields. The investigation has a potential application in future Linac-MR units. Methods: Computed tomography images of four patients and magnetic fields of 0.25–1.5 Tesla (T) were used for Monte Carlo simulation. Two patients had intact breast while the other two had mastectomy. Simulations of planning and chest wall irradiation were similar to the actual clinical process. The direction of superior-inferior magnetic field for the medial treatment beam was reversed for the lateral beam. Results: For the ipsilateral lung and heart mean doses were reduced by a mean (range) of 45.8% (27.6%–58.6%) and 26.0% (20.2%–38.9%), respectively, depending on various treatment plan setups. The mean V{sub 20} for ipsilateral lung was reduced by 55.0% (43.6%–77.3%). In addition acceptable results were shown after simulation of 0.25 T magnetic field demonstrated in dose-volume reductions of the heart, ipsilateral lung, and noninvolved skin. Conclusions: Applying a reversible magnetic field during breast radiotherapy, not only reduces the dose to the lung and heart but also produces a sharp drop dose volume histogram for planning target volume, because of bending of the path of secondary charged particles toward the chest wall by the Lorentz force. The simulations have shown that use of the magnetic field at 1.5 T is not feasible for clinical applications due to the increase of ipsilateral chest wall skin dose in comparison to the conventional planning while 0.25 T is suitable for all patients due to dose reduction to the chest wall skin.

  19. Locally Advanced Stage IV Squamous Cell Carcinoma of the Head and Neck: Impact of Pre-Radiotherapy Hemoglobin Level and Interruptions During Radiotherapy

    SciTech Connect

    Rades, Dirk Stoehr, Monika; Kazic, Nadja; Hakim, Samer G.; Walz, Annette; Schild, Steven E.; Dunst, Juergen

    2008-03-15

    Purpose: Stage IV head and neck cancer patients carry a poor prognosis. Clear understanding of prognostic factors can help to optimize care for the individual patient. This study investigated 11 potential prognostic factors including pre-radiotherapy hemoglobin level and interruptions during radiotherapy for overall survival (OS), metastases-free survival (MFS), and locoregional control (LC) after radiochemotherapy. Methods and Materials: Eleven factors were investigated in 153 patients receiving radiochemotherapy for Stage IV squamous cell head and neck cancer: age, gender, Karnofsky performance score (KPS), tumor site, grading, T stage, N stage, pre-radiotherapy hemoglobin level, surgery, chemotherapy type, and interruptions during radiotherapy >1 week. Results: On multivariate analysis, improved OS was associated with KPS 90-100 (relative risk [RR], 2.36; 95% confidence interval [CI], 1.20-4.93; p = .012), hemoglobin {>=}12 g/dL (RR, 1.88; 95% CI, 1.01-3.53; p = .048), and no radiotherapy interruptions (RR, 2.59; 95% CI, 1.15-5.78; p = .021). Improved LC was significantly associated with lower T stage (RR, 2.17; 95% CI, 1.16-4.63; p = .013), hemoglobin {>=}12 g/dL (RR, 4.12; 95% CI, 1.92-9.09; p < .001), surgery (RR, 2.67; 95% CI, 1.28-5.88; p = .008), and no radiotherapy interruptions (RR, 3.32; 95% CI, 1.26-8.79; p = .015). Improved MFS was associated with KPS 90-100 (RR, 3.41; 95% CI, 1.46-8.85; p = .012). Conclusions: Significant predictors for outcome in Stage IV head and neck cancer were performance status, stage, surgery, pre-radiotherapy hemoglobin level, and interruptions during radiotherapy >1 week. It appears important to avoid anemia and radiotherapy interruptions to achieve the best treatment results.

  20. Post-radiotherapy neck dissection improves control at non-regional disease sites after definitive chemoradiation for squamous cell carcinoma of the head and neck

    PubMed Central

    Ranck, Mark C.; Abundo, Rainier; Jefferson, Gina; Kolokythas, Antonia; Wenig, Barry L.; Weichselbaum, Ralph R.; Spiotto, Michael T.

    2015-01-01

    Importance After chemoradiation for head and neck cancer, over ninety percent of patients who achieved a complete response by imaging were regionally controlled without post-radiotherapy neck dissections (PRND). Since several groups have reported that lymph node involvement also predicted failure at both primary and distant sites, it remains unclear the extent to which PRND impacts non-regional sites of disease. Objective Here, we evaluated how PRND impacted local and distant control in patients who achieved a clinical complete response. Design We retrospectively reviewed patients treated for stage III/IV disease with definitive chemoradiation between 1990 to 2012. Setting University of Illinois at Chicago. Participants 287 patients were treated with definitive CRT, of whom seventy-four underwent PRND. Median follow up was 25.4 months. Interventions Chemoradiation followed by lymph node dissection or observation. Main Outcomes and Measures Endpoints evaluated included local control (LC), regional control (RC), freedom from distant metastasis (FFDM), progression free survival (PFS) and overall survival (OS) using first-failure analysis. Results Patients with advanced nodal disease (≥N2b; n=176) had improved PFS (74.6% vs. 39.1%; P<.001) while patients with lesser nodal disease had similar PFS. For patients with advanced nodal disease, PRND improved 2-year LC (85.5 vs. 53.5%; p<.001), locoregional control with PRND (78.9% vs. 45.7%; P<.001), FFDM (79.5% vs. 67.5%%; P=.03) and OS (84.5% vs. 61.7%; P=.004) but not RC (96.9% vs. 90.1%; P=.21) The benefit in LC (87.4% vs. 66.2%; P=.02) and PFS (80.7% vs. 53.4%; P=.01) persisted for those with negative post-treatment imaging who underwent PRND. On univariate analysis, PRND, alcohol use, nodal stage and chemoradiation significantly impacted 2 year LC and/or PFS. On multivariate analysis, PRND remained strongly prognostic for 2 year LC (HR 0.22; P=.0007) and PFS (HR 0.42; P=.002). Conclusions and Relevance PRND improved

  1. TGFβ1 overexpression is associated with improved survival and low tumor cell proliferation in patients with early-stage pancreatic ductal adenocarcinoma

    PubMed Central

    Glazer, Evan S.; Welsh, Eric; Pimiento, Jose M.; Teer, Jamie K.; Malafa, Mokenge P.

    2017-01-01

    The role of transforming growth factor beta-type-1 (TGFβ1) in pancreatic ductal adenocarcinoma (PDAC) progression is stage-dependent. We hypothesized that TGFβ1 expression is associated with survival and proliferation markers in patients with early-stage PDAC. We acquired clinicopathologic, treatment, and mRNA expression data from The Cancer Genome Atlas data set for 106 patients identified with stage I/II PDAC who underwent pancreaticoduodenectomy. Patients were categorized as high expression when mRNA expression was ≥75th percentile for each gene. Average log2 mRNA expression of TGFβ1 in patients with high expression was 11.6 ± 0.2 and 10.5 ± 0.6 in patients with low expression (P<0.001). Low TGFβ1 expression is associated with shorter median survival compared with high TGFβ1 expression (17 versus at least 60 months; P=0.005). Patients with tumors demonstrating high MKI67 (the gene encoding Ki-67) expression have shorter median survival versus those with lowerMKI67 expression (16 versus 20 months; P=0.026). TGFβ1 and MKI67 are inversely associated (P=0.009). On multivariate analysis, improved survival is associated with TGFβ1 overexpression (P=0.017), adjuvant chemotherapy (P=0.001), and adjuvant radiotherapy (P=0.017), whereas positive surgical margins are associated with worse survival (P=0.002). In patients who undergo pancreaticoduodenectomy for PDAC, high TGFβ1 expression may counteract the worse survival associated with high proliferation. PMID:27895310

  2. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer.

    PubMed

    James, Nicholas D; Hussain, Syed A; Hall, Emma; Jenkins, Peter; Tremlett, Jean; Rawlings, Christine; Crundwell, Malcolm; Sizer, Bruce; Sreenivasan, Thiagarajan; Hendron, Carey; Lewis, Rebecca; Waters, Rachel; Huddart, Robert A

    2012-04-19

    Radiotherapy is an alternative to cystectomy in patients with muscle-invasive bladder cancer. In other disease sites, synchronous chemoradiotherapy has been associated with increased local control and improved survival, as compared with radiotherapy alone. In this multicenter, phase 3 trial, we randomly assigned 360 patients with muscle-invasive bladder cancer to undergo radiotherapy with or without synchronous chemotherapy. The regimen consisted of fluorouracil (500 mg per square meter of body-surface area per day) during fractions 1 to 5 and 16 to 20 of radiotherapy and mitomycin C (12 mg per square meter) on day 1. Patients were also randomly assigned to undergo either whole-bladder radiotherapy or modified-volume radiotherapy (in which the volume of bladder receiving full-dose radiotherapy was reduced) in a partial 2-by-2 factorial design (results not reported here). The primary end point was survival free of locoregional disease. Secondary end points included overall survival and toxic effects. At 2 years, rates of locoregional disease-free survival were 67% (95% confidence interval [CI], 59 to 74) in the chemoradiotherapy group and 54% (95% CI, 46 to 62) in the radiotherapy group. With a median follow-up of 69.9 months, the hazard ratio in the chemoradiotherapy group was 0.68 (95% CI, 0.48 to 0.96; P=0.03). Five-year rates of overall survival were 48% (95% CI, 40 to 55) in the chemoradiotherapy group and 35% (95% CI, 28 to 43) in the radiotherapy group (hazard ratio, 0.82; 95% CI, 0.63 to 1.09; P=0.16). Grade 3 or 4 adverse events were slightly more common in the chemoradiotherapy group than in the radiotherapy group during treatment (36.0% vs. 27.5%, P=0.07) but not during follow-up (8.3% vs. 15.7%, P=0.07). Synchronous chemotherapy with fluorouracil and mitomycin C combined with radiotherapy significantly improved locoregional control of bladder cancer, as compared with radiotherapy alone, with no significant increase in adverse events. (Funded by Cancer

  3. Increasing Winter Maximal Metabolic Rate Improves Intrawinter Survival in Small Birds.

    PubMed

    Petit, Magali; Clavijo-Baquet, Sabrina; Vézina, François

    Small resident bird species living at northern latitudes increase their metabolism in winter, and this is widely assumed to improve their chances of survival. However, the relationship between winter metabolic performance and survival has yet to be demonstrated. Using capture-mark-recapture, we followed a population of free-living black-capped chickadees (Poecile atricapillus) over 3 yr and evaluated their survival probability within and among winters. We also measured the size-independent body mass (Ms), hematocrit (Hct), basal metabolic rate (BMR), and maximal thermogenic capacity (Msum) and investigated how these parameters influenced survival within and among winters. Results showed that survival probability was high and constant both within (0.92) and among (0.96) winters. They also showed that while Ms, Hct, and BMR had no significant influence, survival was positively related to Msum-following a sigmoid relationship-within but not among winter. Birds expressing an Msum below 1.26 W (i.e., similar to summer levels) had a <50% chance of survival, while birds with an Msum above 1.35 W had at least a 90% chance of surviving through the winter. Our data therefore suggest that black-capped chickadees that are either too slow or unable to adjust their phenotype from summer to winter have little chances of survival and thus that seasonal upregulation of metabolic performance is highly beneficial. This study is the first to document in an avian system the relationship between thermogenic capacity and winter survival, a proxy of fitness.

  4. Brachytherapy Improves Survival in Stage III Endometrial Cancer With Cervical Involvement.

    PubMed

    Bingham, Brian; Orton, Andrew; Boothe, Dustin; Stoddard, Greg; Huang, Y Jessica; Gaffney, David K; Poppe, Matthew M

    2017-04-01

    To evaluate the survival benefit of adding vaginal brachytherapy (BT) to pelvic external beam radiation therapy (EBRT) in women with stage III endometrial cancer. The National Cancer Data Base was used to identify patients with stage III endometrial cancer from 2004 to 2013. Only women who received adjuvant EBRT were analyzed. Women were grouped according to receipt of BT. Logistic regression modeling was used to identify predictors of receiving BT. Log-rank statistics were used to compare survival outcomes. Cox proportional hazards modeling was used to evaluate the effect of BT on survival. A propensity score-matched analysis was also conducted among women with cervical involvement. We evaluated 12,988 patients with stage III endometrial carcinoma, 39% of whom received EBRT plus BT. Women who received BT were more likely to have endocervical or cervical stromal involvement (odds ratios 2.03 and 1.77; P<.01, respectively). For patients receiving EBRT alone, the 5-year survival was 66% versus 69% with the addition of BT at 5 years (P<.01). Brachytherapy remained significantly predictive of decreased risk of death (hazard ratio 0.86; P<.01) on multivariate Cox regression. The addition of BT to EBRT did not affect survival among women without cervical involvement (P=.84). For women with endocervical or cervical stromal invasion, the addition of BT significantly improved survival (log-rank P<.01). Receipt of EBRT plus BT was associated with improved survival in women with positive and negative surgical margins, and receiving chemotherapy did not alter the benefit of BT. Propensity score-matched analysis results confirmed the benefit of BT among women with cervical involvement (hazard ratio 0.80; P=.01). In this population of women with stage III endometrial cancer the addition of BT to EBRT was associated with an improvement in survival for women with endocervical or cervical stromal invasion. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Zinc supplementation leads to immune modulation and improved survival in a juvenile model of murine sepsis.

    PubMed

    Ganatra, Hammad A; Varisco, Brian M; Harmon, Kelli; Lahni, Patrick; Opoka, Amy; Wong, Hector R

    2017-01-01

    Children with severe sepsis are known to have altered zinc homeostasis and decreased circulating zinc levels, suggesting a role for zinc supplementation to improve outcomes. We tested the hypothesis that zinc supplementation would improve survival in a juvenile model of polymicrobial sepsis. Juvenile (13-14-d-old) C57BL/6 mice were treated with 10 mg/kg of zinc via i.p. injections (or vehicle) for 3 d prior to induction of polymicrobial sepsis via i.p. cecal slurry injections. Survival after sepsis was followed for 3 d, and bacterial clearance, ex vivo phagocytosis, systemic inflammatory markers and neutrophil extracellular trap (NET) formation were quantified. We found a significant survival benefit and decreased bacterial burden among zinc supplemented mice when compared with the control group. Zinc supplementation also resulted in enhanced phagocytic activity, greater neutrophil recruitment in the peritoneal cavity and NET formation, suggesting a possible mechanism for improved bacterial clearance and survival. We also noted decreased serum cytokine levels and decreased myeloperoxidase activity in lung tissue following zinc supplementation, suggesting attenuation of the systemic inflammatory response. In conclusion, zinc supplementation improves bacterial clearance, and hence survival, in juvenile mice with polymicrobial sepsis.

  6. The use of theranostic gadolinium-based nanoprobes to improve radiotherapy efficacy

    PubMed Central

    Sancey, L; Kotb, S; Roux, S; Dufort, S; Bianchi, A; Crémillieux, Y; Fries, P; Coll, J-L; Rodriguez-Lafrasse, C; Janier, M; Dutreix, M; Barberi-Heyob, M; Boschetti, F; Denat, F; Louis, C; Porcel, E; Lacombe, S; Le Duc, G; Deutsch, E; Perfettini, J-L; Detappe, A; Verry, C; Berbeco, R; Butterworth, K T; McMahon, S J; Prise, K M; Perriat, P; Tillement, O

    2014-01-01

    A new efficient type of gadolinium-based theranostic agent (AGuIX®) has recently been developed for MRI-guided radiotherapy (RT). These new particles consist of a polysiloxane network surrounded by a number of gadolinium chelates, usually 10. Owing to their small size (<5 nm), AGuIX typically exhibit biodistributions that are almost ideal for diagnostic and therapeutic purposes. For example, although a significant proportion of these particles accumulate in tumours, the remainder is rapidly eliminated by the renal route. In addition, in the absence of irradiation, the nanoparticles are well tolerated even at very high dose (10 times more than the dose used for mouse treatment). AGuIX particles have been proven to act as efficient radiosensitizers in a large variety of experimental in vitro scenarios, including different radioresistant cell lines, irradiation energies and radiation sources (sensitizing enhancement ratio ranging from 1.1 to 2.5). Pre-clinical studies have also demonstrated the impact of these particles on different heterotopic and orthotopic tumours, with both intratumoural or intravenous injection routes. A significant therapeutical effect has been observed in all contexts. Furthermore, MRI monitoring was proven to efficiently aid in determining a RT protocol and assessing tumour evolution following treatment. The usual theoretical models, based on energy attenuation and macroscopic dose enhancement, cannot account for all the results that have been obtained. Only theoretical models, which take into account the Auger electron cascades that occur between the different atoms constituting the particle and the related high radical concentrations in the vicinity of the particle, provide an explanation for the complex cell damage and death observed. PMID:24990037

  7. Metabolic control improves long-term renal allograft and patient survival in type 1 diabetes.

    PubMed

    Morath, Christian; Zeier, Martin; Döhler, Bernd; Schmidt, Jan; Nawroth, Peter P; Opelz, Gerhard

    2008-08-01

    It is a matter of debate whether pancreas allografts independently contribute to renal allograft and patient survival in individuals who have type 1 diabetes and receive a simultaneous pancreas and kidney transplant (SPK). Using data from the Collaborative Transplant Study, we studied patients who had type 1 diabetes and were recipients of deceased-donor kidneys (DDK), living-donor kidneys (LDK), or SPK. We analyzed graft and patient survival rates with a maximum of 18 yr of follow-up. DDK recipients had inferior graft and patient survival compared with LDK and SPK recipients. LDK recipients had superior graft and patient survival rates initially, but SPK recipients demonstrated equal survival rates toward the end of follow-up. Multivariate analysis, adjusting for pretransplantation cardiovascular risk, showed that patient survival of SPK recipients was superior to that of LDK recipients beyond the 10th year after transplantation (hazard ratio 0.55; P = 0.005). In summary, the early survival advantage of LDK over SPK is lost during long-term follow-up, probably as a result of improved glycemic control in SPK recipients.

  8. Effect of radiotherapy on expression of hyaluronan and EGFR and presence of mast cells in squamous cell carcinoma of the head and neck

    PubMed Central

    JONSSON, EVA LINDELL; NYLANDER, KARIN; HALLÉN, LARS; LAURELL, GÖRAN

    2012-01-01

    Head and neck squamous cell carcinoma is a common form of cancer, and despite improvements in treatment during the last decades, survival rates have not significantly increased. There is therefore a need to better understand how these tumours and the adjacent tissues react to radiotherapy, the most common type of treatment for this group of tumours. In order to improve this understanding, the expression of hyaluronan (HA) and epidermal growth factor receptor (EGFR) and the presence of mast cells were mapped before and after radiotherapy using immunohistochemistry. The results showed HA and EGFR to have similar expression patterns in tumour tissue and histologically normal squamous epithelium prior to radiotherapy. Following radiotherapy, EGFR increased in histologically normal epithelium. An increased number of mast cells were also observed as a result of radiotherapy. No expression of EGFR was observed in the connective tissue either prior to or following radiotherapy. PMID:23205115

  9. Parasitic Infection Improves Survival from Septic Peritonitis by Enhancing Mast Cell Responses to Bacteria in Mice

    PubMed Central

    Sutherland, Rachel E.; Xu, Xiang; Kim, Sophia S.; Seeley, Eric J.; Caughey, George H.; Wolters, Paul J.

    2011-01-01

    Mammals are serially infected with a variety of microorganisms, including bacteria and parasites. Each infection reprograms the immune system's responses to re-exposure and potentially alters responses to first-time infection by different microorganisms. To examine whether infection with a metazoan parasite modulates host responses to subsequent bacterial infection, mice were infected with the hookworm-like intestinal nematode Nippostrongylus brasiliensis, followed in 2–4 weeks by peritoneal injection of the pathogenic bacterium Klebsiella pneumoniae. Survival from Klebsiella peritonitis two weeks after parasite infection was better in Nippostrongylus-infected animals than in unparasitized mice, with Nippostrongylus-infected mice having fewer peritoneal bacteria, more neutrophils, and higher levels of protective interleukin 6. The improved survival of Nippostrongylus-infected mice depends on IL-4 because the survival benefit is lost in mice lacking IL-4. Because mast cells protect mice from Klebsiella peritonitis, we examined responses in mast cell-deficient KitW-sh/KitW-sh mice, in which parasitosis failed to improve survival from Klebsiella peritonitis. However, adoptive transfer of cultured mast cells to KitW-sh/KitW-sh mice restored survival benefits of parasitosis. These results show that recent infection with Nippostrongylus brasiliensis protects mice from Klebsiella peritonitis by modulating mast cell contributions to host defense, and suggest more generally that parasitosis can yield survival advantages to a bacterially infected host. PMID:22110673

  10. Surgery Followed by Radiotherapy Versus Radiotherapy Alone for Metastatic Spinal Cord Compression From Unfavorable Tumors

    SciTech Connect

    Rades, Dirk; Huttenlocher, Stefan; Bajrovic, Amira; Karstens, Johann H.; Adamietz, Irenaeus A.; Kazic, Nadja; Rudat, Volker; Schild, Steven E.

    2011-12-01

    Purpose: Despite a previously published randomized trial, controversy exists regarding the benefit of adding surgery to radiotherapy for metastatic spinal cord compression (MSCC). It is thought that patients with MSCC from relatively radioresistant tumors or tumors associated with poor functional outcome after radiotherapy alone may benefit from surgery. This study focuses on these tumors. Methods and Materials: Data from 67 patients receiving surgery plus radiotherapy (S+RT) were matched to 134 patients (1:2) receiving radiotherapy alone (RT). Groups were matched for 10 factors and compared for motor function, ambulatory status, local control, and survival. Additional separate matched-pair analyses were performed for patients receiving direct decompressive surgery plus stabilization of involved vertebrae (DDSS) and patients receiving laminectomy (LE). Results: Improvement of motor function occurred in 22% of patients after S+RT and 16% after RT (p = 0.25). Posttreatment ambulatory rates were 67% and 61%, respectively (p = 0.68). Of nonambulatory patients, 29% and 19% (p = 0.53) regained ambulatory status. One-year local control rates were 85% and 89% (p = 0.87). One-year survival rates were 38% and 24% (p = 0.20). The matched-pair analysis of patients receiving LE showed no significant differences between both therapies. In the matched-pair analysis of patients receiving DDSS, improvement of motor function occurred more often after DDSS+RT than RT (28% vs. 19%, p = 0.024). Posttreatment ambulatory rates were 86% and 67% (p = 0.30); 45% and 18% of patients regained ambulatory status (p = 0.29). Conclusions: Patients with MSCC from an unfavorable primary tumor appeared to benefit from DDSS but not LE when added to radiotherapy in terms of improved functional outcome.

  11. Improving survival of probiotic bacteria using bacterial poly-γ-glutamic acid.

    PubMed

    Bhat, A R; Irorere, V U; Bartlett, T; Hill, D; Kedia, G; Charalampopoulos, D; Nualkaekul, S; Radecka, I

    2015-03-02

    A major hurdle in producing a useful probiotic food product is bacterial survival during storage and ingestion. The aim of this study was to test the effect of γ-PGA immobilisation on the survival of probiotic bacteria when stored in acidic fruit juice. Fruit juices provide an alternative means of probiotic delivery, especially to lactose intolerant individuals. In addition, the survival of γ-PGA-immobilised cells in simulated gastric juice was also assessed. Bifidobacteria strains (Bifidobacteria longum, Bifidobacteria breve), immobilised on 2.5% γ-PGA, survived significantly better (P<0.05) in orange and pomegranate juice for 39 and 11 days respectively, compared to free cells. However, cells survived significantly better (P<0.05) when stored in orange juice compared to pomegranate juice. Moreover, both strains, when protected with 2.5% γ-PGA, survived in simulated gastric juice (pH2.0) with a marginal reduction (<0.47 log CFU/ml) or no significant reduction in viable cells after 4h, whereas free cells died within 2h. In conclusion, this research indicates that γ-PGA can be used to protect Bifidobacteria cells in fruit juice, and could also help improve the survival of cells as they pass through the harsh conditions of the gastrointestinal tract (GIT). Following our previous report on the use of γ-PGA as a cryoprotectant for probiotic bacteria, this research further suggests that γ-PGA could be used to improve probiotic survival during the various stages of preparation, storage and ingestion of probiotic cells. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Prefabricated Flaps: Identification of Microcirculation Structure and Supercharging Technique Improving Survival Area.

    PubMed

    Xu, Heng; Feng, Shaoqing; Xia, Yimeng; Steinberger, Zvi; Xi, Wenjing; Fang, Hongwei; Li, Zhiwei; Xie, Yixin; Zhang, Yixin

    2017-02-01

    Background Microcirculation is an important factor frequently overlooked when studying the survival of prefabricated flaps. In the current study, we use different prefabrication techniques for characterizing microcirculation within the flap, with the goal of finding an effective way to improve its survival area. Methods An abdominal prefabricated flap rodent model was created using a two-stage operation. All rats were randomly divided into six groups (n = 10/group): group A, prefabricated femoral vessels; group B, prefabricated femoral artery with a connected superficial inferior epigastric vein (SIEV); group C, connected superficial inferior epigastric artery (SIEA) with a prefabricated femoral vein; group D was similar to group A along with a prefabricated SIEA, and group E was similar to group A along with a prefabricated SIEV; and group F acted as a control group and consisted of an axial flap nourished by superficial inferior epigastric vessels. Flaps were assessed for survival area, blood perfusion area, and capillary density using macroscopic analysis, near-infrared fluorescence imaging (NIFI), and histology. Results The survival area was not significantly different when comparing groups B to C, and D to E. The survival area of groups D and E was larger than that of groups B and C. Groups B through E had a smaller survival area in comparison to group F and a larger survival area than group A. NIFI were consistent with the macroscopic outcomes. The capillary density was not significantly different between groups A to C and groups D to F. Conclusion Both arterial and venous supercharging could potentially improve the survival area of prefabricated flaps. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  13. Role of radiotherapy fractionation in head and neck cancers (MARCH): an updated meta-analysis.

    PubMed

    Lacas, Benjamin; Bourhis, Jean; Overgaard, Jens; Zhang, Qiang; Grégoire, Vincent; Nankivell, Matthew; Zackrisson, Björn; Szutkowski, Zbigniew; Suwiński, Rafał; Poulsen, Michael; O'Sullivan, Brian; Corvò, Renzo; Laskar, Sarbani Ghosh; Fallai, Carlo; Yamazaki, Hideya; Dobrowsky, Werner; Cho, Kwan Ho; Garden, Adam S; Langendijk, Johannes A; Viegas, Celia Maria Pais; Hay, John; Lotayef, Mohamed; Parmar, Mahesh K B; Aupérin, Anne; van Herpen, Carla; Maingon, Philippe; Trotti, Andy M; Grau, Cai; Pignon, Jean-Pierre; Blanchard, Pierre

    2017-09-01

    The Meta-Analysis of Radiotherapy in squamous cell Carcinomas of Head and neck (MARCH) showed that altered fractionation radiotherapy is associated with improved overall and progression-free survival compared with conventional radiotherapy, with hyperfractionated radiotherapy showing the greatest benefit. This update aims to confirm and explain the superiority of hyperfractionated radiotherapy over other altered fractionation radiotherapy regimens and to assess the benefit of altered fractionation within the context of concomitant chemotherapy with the inclusion of new trials. For this updated meta-analysis, we searched bibliography databases, trials registries, and meeting proceedings for published or unpublished randomised trials done between Jan 1, 2009, and July 15, 2015, comparing primary or postoperative conventional fractionation radiotherapy versus altered fractionation radiotherapy (comparison 1) or conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone (comparison 2). Eligible trials had to start randomisation on or after Jan 1, 1970, and completed accrual before Dec 31, 2010; had to have been randomised in a way that precluded prior knowledge of treatment assignment; and had to include patients with non-metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx undergoing first-line curative treatment. Trials including a non-conventional radiotherapy control group, investigating hypofractionated radiotherapy, or including mostly nasopharyngeal carcinomas were excluded. Trials were grouped in three types of altered fractionation: hyperfractionated, moderately accelerated, and very accelerated. Individual patient data were collected and combined with a fixed-effects model based on the intention-to-treat principle. The primary endpoint was overall survival. Comparison 1 (conventional fractionation radiotherapy vs altered fractionation radiotherapy) included 33

  14. Oral glutamine enhances heat shock protein expression and improves survival following hyperthermia.

    PubMed

    Singleton, Kristen D; Wischmeyer, Paul E

    2006-03-01

    No pharmacologic agent has shown benefit in treating heatstroke. Previous data indicate that enhanced heat shock protein 70 (HSP-70) expression can improve survival postexperimental heatstroke. Glutamine (GLN) can enhance HSP-70 expression in other injury models. This study assessed if orally administered GLN could enhance tissue HSP expression and could improve survival following whole body hyperthermia. Intestinal permeability and plasma endotoxin were assayed to determine if enhanced HSP expression correlated with improved organ function. GLN (0.65 g/kg) or an iso-nitrogenous control (Travasol; T) was given to rats via gavage twice daily for 5 days pre-heatstroke. Hyperthermia was performed in anesthetized rats by heating animals to 42 degrees C (rectal temperature) for 30 min. HSP-70 analyzed via Western blot. Gut permeability was measured 6 and 24 h post-hyperthermia. Plasma endotoxin was measured 24 h post-hyperthermia. Survival was analyzed for 5 days post-hyperthermia. GLN administration enhanced gut and lung HSP-70 post-hyperthermia. GLN administration led to significantly enhanced gut heat shock factor 1 (HSF-1) activation before heatstroke and at 1 h postheat stress. GLN decreased gut permeability at 6 and 24 h post-hyperthermia versus T. Plasma endotoxin also decreased in GLN-treated rats 24 h post-hyperthermia. Oral GLN therapy significantly improved survival (P < 0.05). Our results indicate that oral GLN can enhance tissue HSP-70 and HSF-1 activation post-hyperthermia. These results also indicate that enhanced HSP-70 may have functional significance as GLN-treated animals had decreased gut permeability, plasma endotoxin, and improve survival following lethal hyperthermia. Enhanced expression of HSP-70 may be an important mechanism leading to enhanced survival via GLN. These data indicate that oral GLN may useful in prevention of mortality from heatstroke in at risk populations.

  15. Does complete resection of melanoma metastatic to solid intra-abdominal organs improve survival?

    PubMed

    Wood, T F; DiFronzo, L A; Rose, D M; Haigh, P I; Stern, S L; Wanek, L; Essner, R; Morton, D L

    2001-09-01

    Patients with distant melanoma metastases have median survivals of 4 to 8 months. Previous studies have demonstrated improved survival after complete resection of pulmonary and hollow viscus gastrointestinal metastases. We hypothesized that patients with metastatic disease to intra-abdominal solid organs might also benefit from complete surgical resection. A prospectively acquired database identified patients treated for melanoma metastatic to the liver, pancreas, spleen, adrenal glands, or a combination of these from 1971 to 2000. The primary intervention was complete or incomplete surgical resection of intra-abdominal solid-organ metastases, and the main outcome measure was postoperative overall survival (OS). Disease-free survival (DFS) was a secondary outcome measure. Sixty patients underwent adrenalectomy, hepatectomy, splenectomy, or pancreatectomy. Median OS was significantly improved after complete versus incomplete resections, but median OS after complete resection was not significantly different for single-site versus synchronous multisite metastases. The 5-year survival in the group after complete resection was 24%, whereas in the incomplete resection group, there were no 5-year survivors. Median DFS after complete resection was 15 months. Of note, the 2-year DFS after complete resection was 53% for synchronous multi-site metastases versus 26% for single-site metastases. In highly selected patients with melanoma metastatic to intra-abdominal solid organs, aggressive attempts at complete surgical resection may improve OS. It is important that the number of metastatic sites does not seem to affect the OS after complete resection.

  16. Combined treatment with atorvastatin and imipenem improves survival and vascular functions in mouse model of sepsis.

    PubMed

    Choudhury, Soumen; Kannan, Kandasamy; Pule Addison, M; Darzi, Sazad A; Singh, Vishakha; Singh, Thakur Uttam; Thangamalai, Ramasamy; Dash, Jeevan Ranjan; Parida, Subhashree; Debroy, Biplab; Paul, Avishek; Mishra, Santosh Kumar

    2015-08-01

    We have recently reported that pre-treatment, but not the post-treatment with atorvastatin showed survival benefit and improved hemodynamic functions in cecal ligation and puncture (CLP) model of sepsis in mice. Here we examined whether combined treatment with atorvastatin and imipenem after onset of sepsis can prolong survival and improve vascular functions. At 6 and 18h after sepsis induction, treatment with atorvastatin plus imipenem, atorvastatin or imipenem alone or placebo was initiated. Ex vivo experiments were done on mouse aorta to examine the vascular reactivity to nor-adrenaline and acetylcholine and mRNA expressions of α1D AR, GRK2 and eNOS. Atorvastatin plus imipenem extended the survival time to 56.00±4.62h from 20.00±1.66h observed in CLP mice. The survival time with atorvastatin or imipenem alone was 20.50±1.89h and 27.00±4.09h, respectively. The combined treatment reversed the hyporeactivity to nor-adrenaline through preservation of α1D AR mRNA/protein expression and reversal of α1D AR desensitization mediated by GRK2/Gβγ pathway. The treatment also restored endothelium-dependent relaxation to ACh through restoration of aortic eNOS mRNA expression and NO availability. In conclusion, combined treatment with atorvastatin and imipenem exhibited survival benefit and improved vascular functions in septic mice. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. SynCAM 1 improves survival of adult-born neurons by accelerating synapse maturation.

    PubMed

    Doengi, Michael; Krupp, Alexander J; Körber, Nils; Stein, Valentin

    2016-03-01

    The survival of adult-born dentate gyrus granule cells critically depends on their synaptic integration into the existing neuronal network. Excitatory inputs are thought to increase the survival rate of adult born neurons. Therefore, whether enhancing the stability of newly formed excitatory synapses by overexpressing the synaptic cell adhesion molecule SynCAM 1 improves the survival of adult-born neurons was tested. Here it is shown that overexpression of SynCAM 1 improves survival of adult-born neurons, but has no effect on the proliferation rate of precursor cells. As expected, overexpression of SynCAM 1 increased the synapse density in adult-born granule neurons. While adult-born granule neurons have very few functional synapses 15 days after birth, it was found that at this age adult-born neurons in SynCAM 1 overexpressing mice exhibited around three times more excitatory synapses, which were stronger than synapses of adult-born neurons of control littermates. In summary, the data indicated that additional SynCAM 1 accelerated synapse maturation, which improved the stability of newly formed synapses and in turn increased the likelihood of survival of adult-born neurons.

  18. Evaluation of risk factors associated with clinical improvement and survival of horses with equine protozoal myeloencephalitis.

    PubMed

    Saville, W J; Morley, P S; Reed, S M; Granstrom, D E; Kohn, C W; Hinchcliff, K W; Wittum, T E

    2000-10-15

    To investigate risk factors for use in predicting clinical improvement and survival of horses with equine protozoal myeloencephalitis (EPM). Longitudinal epidemiologic study. 251 horses with EPM. Between 1992 and 1995, 251 horses with EPM were admitted to our facility. A diagnosis of EPM was made on the basis of neurologic abnormalities and detection of antibody to Sarcocystis neurona or S neurona DNA in CSF. Data were obtained from hospital records and through telephone follow-up interviews. Factors associated with clinical improvement and survival were analyzed, using multivariable logistic regression. The likelihood of clinical improvement after diagnosis of EPM was lower in horses used for breeding and pleasure activities. Treatment for EPM increased the probability that a horse would have clinical improvement. The likelihood of survival among horses with EPM was lower among horses with more severe clinical signs and higher among horses that improved after EPM was diagnosed. Treatment of horses with EPM is indicated in most situations; however, severity of clinical signs should be taken into consideration when making treatment decisions. Response to treatment is an important indicator of survival.

  19. Clinical analysis of cholangiocarcinoma patients receiving adjuvant radiotherapy

    PubMed Central

    Nantajit, Danupon; Trirussapanich, Pornwaree; Rojwatkarnjana, Sunanta; Soonklang, Kamonwan; Pattaranutraporn, Poompis; Laebua, Kanyanee; Chamchod, Sasikarn

    2016-01-01

    Cholangiocarcinoma (CCA) or bile duct cancer is a rare cancer type in developed countries, while its prevalence is increased in southeast Asia, affecting ~33.4 men and ~12.3 women per 100,000 individuals. CCA is one of the most lethal types of cancer. Neo-adjuvant and adjuvant therapies have been shown to have limited efficacy in improving the overall prognosis of patients. Radiotherapy has been reported to prolong the survival times of patients with certain characteristics. The present study retrospectively evaluated the medical records and follow-up data from 27 CCA patients who received radiotherapy at Chulabhorn Hospital (Bangkok, Thailand) between 2008 and 2014. A total of 14 patients underwent surgery followed by adjuvant chemoradiotherapy. Of the 27 CCA patients, 14 had intrahepatic CCA, 2 had extrahepatic CCA and 11 had hilar CCA. The 2-year survival rate was 40.7%. Tumor resectability, clinical symptoms and the Eastern Cooperative Oncology Group performance status score were found to be indicative of patient prognosis. In addition, the planning target volume and biologically effective radiotherapy dose were of prognostic value; however, initial treatment response was ambiguous in predicting survival time. The findings of the present study suggested that the currently used radiotherapy protocols for CCA may require modification to improve their efficacy. PMID:28105359

  20. SU-C-BRD-07: The Radiological Physics Center (RPC): 45 Years of Improving Radiotherapy Dosimetry

    SciTech Connect

    Followill, D; Lowenstein, J; Molineu, A; Alvarez, P; Summers, P; Kry, S

    2014-06-15

    Purpose: The RPC, established in 1968 has contributed to the development, conduct, and QA of NCI funded multi-institutional cooperative group clinical trials and institutions, primarily in the USA/Canada and 242 other countries, participating in trials. Methods: The RPC QA program components were designed to audit the radiation dose calculation chain from the NIST traceable reference beam calibration, to inclusion of dosimetry parameters used to calculate tumor doses, to the delivery of the radiation dose. The QA program included: 1) remote TLD/OSLD audit of machine output, 2) on-site dosimetry review visits, 3) credentialing for advanced technologies, and 4) review of patient treatment records. The RPC presented and published their findings to the radiation oncology community. Results: The number of institutions monitored by the RPC increased from around 1200 in the late 90s, to ∼2000 in 2013. There were over 4000 megavoltage therapy machines and ∼28,000 therapy beams in the 1991 institutions monitored by the RPC by the end of 2013. Within the 14,000 photon, electron and proton beam outputs remotely monitored with TLD/OSLD annually, between 10-20% of the institutions have one or more beams outside the RPC 5% criterion. Dosimetry site visits to photon and proton centers continue to result in 2-4 recommendations affecting key dosimetry parameters that impact patient treatment times. One in four patient treatment records reviewed by the RPC have their dose data corrected by >5% before trial groups use them for outcomes analysis. Twelve of fourteen clinically active proton centers are approved to participate in NCI funded clinical trials. The RPC published 222 peer reviewed articles since 1972. Conclusion: Findings from the RPC suggest that human errors continue to play a role in radiotherapy discrepancies and without the RPC independent QA program, the number of undetected errors and time elapsed before their discovery would have been greater. Work supported by

  1. Improved patient survival using a modified resuscitation protocol for out-of-hospital cardiac arrest.

    PubMed

    Garza, Alex G; Gratton, Matthew C; Salomone, Joseph A; Lindholm, Daniel; McElroy, James; Archer, Rex

    2009-05-19

    Cardiac arrest continues to have poor survival in the United States. Recent studies have questioned current practice in resuscitation. Our emergency medical services system made significant changes to the adult cardiac arrest resuscitation protocol, including minimizing chest compression interruptions, increasing the ratio of compressions to ventilation, deemphasizing or delaying intubation, and advocating chest compressions before initial countershock. This retrospective observational cohort study reviewed all adult primary ventricular fibrillation and pulseless ventricular tachycardia cardiac arrests 36 months before and 12 months after the protocol change. Primary outcome was survival to discharge; secondary outcomes were return of spontaneous circulation and cerebral performance category. Survival of out-of-hospital arrest of presumed primary cardiac origin improved from 7.5% (82 of 1097) in the historical cohort to 13.9% (47 of 339) in the revised protocol cohort (odds ratio, 1.80; 95% confidence interval, 1.19 to 2.70). Similar increases in return of spontaneous circulation were achieved for the subset of witnessed cardiac arrest patients with initial rhythm of ventricular fibrillation from 37.8% (54 of 143) to 59.6% (34 of 57) (odds ratio, 2.44; 95% confidence interval, 1.24 to 4.80). Survival to hospital discharge also improved from an unadjusted survival rate of 22.4% (32 of 143) to 43.9% (25 of 57) (odds ratio, 2.71; 95% confidence interval, 1.34 to 1.59) with the protocol. Of the 25 survivors, 88% (n=22) had favorable cerebral performance categories on discharge. The changes to our prehospital protocol for adult cardiac arrest that optimized chest compressions and reduced disruptions increased the return of spontaneous circulation and survival to discharge in our patient population. These changes should be further evaluated for improving survival of out-of-hospital cardiac arrest patients.

  2. Improved renal survival in Japanese children with IgA nephropathy.

    PubMed

    Yata, Nahoko; Nakanishi, Koichi; Shima, Yuko; Togawa, Hiroko; Obana, Mina; Sako, Mayumi; Nozu, Kandai; Tanaka, Ryojiro; Iijima, Kazumoto; Yoshikawa, Norishige

    2008-06-01

    Since the beginning of the 1990s, Japanese medical practitioners have extensively prescribed angiotensin-converting enzyme (ACE) inhibitors for children with mild IgA nephropathy (IgA-N) and steriods for those with severe IgA-N. We have performed a retrospective cohort study to clarify whether the long-term outcome has improved in Japanese children with IgA-N. Renal survival was defined as the time from onset to end-stage renal disease (ESRD). We divided the study period into two time periods based on the occurrence of the initial renal biopsy:1976-1989 and 1990-2004. Actuarial survivals were calculated by Kaplan-Meier method, and comparisons were made with the logrank test. The Cox proportional hazard model was used for multivariate analysis. Between 1976 and 2004, 500 children were diagnosed as having IgA-N in our hospitals. The actuarial renal survival from the time of apparent disease onset was 96.4% at 10 years, 84.5% at 15 years and 73.9% at 20 years. Renal survival in the 1990-2004 period was significantly better than that in 1976-1989 (p=0.008), and a marked improvement in renal survival in patients with severe IgA-N was also observed (p=0.0003). Multivariate analysis indicated that diagnosis year was a significant factor for ESRD-free survival independently of baseline characteristics. The results of this study show that there has been an improvement in terms of renal survival in Japanese children with IgA-N.

  3. Improved renal survival in Japanese children with IgA nephropathy

    PubMed Central

    Yata, Nahoko; Nakanishi, Koichi; Shima, Yuko; Togawa, Hiroko; Obana, Mina; Sako, Mayumi; Nozu, Kandai; Tanaka, Ryojiro; Iijima, Kazumoto

    2008-01-01

    Since the beginning of the 1990s, Japanese medical practitioners have extensively prescribed angiotensin-converting enzyme (ACE) inhibitors for children with mild IgA nephropathy (IgA-N) and steriods for those with severe IgA-N. We have performed a retrospective cohort study to clarify whether the long-term outcome has improved in Japanese children with IgA-N. Renal survival was defined as the time from onset to end-stage renal disease (ESRD). We divided the study period into two time periods based on the occurrence of the initial renal biopsy:1976–1989 and 1990–2004. Actuarial survivals were calculated by Kaplan–Meier method, and comparisons were made with the logrank test. The Cox proportional hazard model was used for multivariate analysis. Between 1976 and 2004, 500 children were diagnosed as having IgA-N in our hospitals. The actuarial renal survival from the time of apparent disease onset was 96.4% at 10 years, 84.5% at 15 years and 73.9% at 20 years. Renal survival in the 1990–2004 period was significantly better than that in 1976–1989 (p = 0.008), and a marked improvement in renal survival in patients with severe IgA-N was also observed (p = 0.0003). Multivariate analysis indicated that diagnosis year was a significant factor for ESRD-free survival independently of baseline characteristics. The results of this study show that there has been an improvement in terms of renal survival in Japanese children with IgA-N. PMID:18224344

  4. Improvement in survival end points of patients with metastatic renal cell carcinoma through sequential targeted therapy.

    PubMed

    Calvo, Emiliano; Schmidinger, Manuela; Heng, Daniel Y C; Grünwald, Viktor; Escudier, Bernard

    2016-11-01

    Survival of patients with metastatic renal cell carcinoma (mRCC) has improved since the advent of targeted therapy. Approved agents include the multi-targeted tyrosine kinase inhibitors (TKIs) sunitinib, sorafenib, axitinib, pazopanib, cabozantinib, and lenvatinib (approved in combination with everolimus), the anti-VEGF monoclonal antibody bevacizumab, the mammalian target of rapamycin (mTOR) inhibitors everolimus and temsirolimus, and the programmed death-1 (PD-1) targeted immune checkpoint inhibitor nivolumab. The identification of predictive and prognostic factors of survival is increasing, and both clinical predictive factors and pathology-related prognostic factors are being evaluated. Serum-based biomarkers and certain histologic subtypes of RCC, as well as clinical factors such as dose intensity and the development of some class effect adverse events, have been identified as predictors of survival. Expression levels of microRNAs, expression of chemokine receptor 4, hypermethylation of certain genes, VEGF polymorphisms, and elevation of plasma fibrinogen or d-dimer have been shown to be prognostic indicators of survival. In the future, prognosis and treatment of patients with mRCC might be based on genomic classification, especially of the 4 most commonly mutated genes in RCC (VHL, PBRM1, BAP1, and SETD2). Median overall survival has improved for patients treated with a first-line targeted agent compared with survival of patients treated with first-line interferon-α, and results of clinical trials have shown a survival benefit of sequential treatment with targeted agents. Prognosis of patients with mRCC will likely improve with optimization and individualization of current sequential treatment with targeted agents.

  5. Dosimetric evaluation of a simple planning method for improving intensity-modulated radiotherapy for stage III lung cancer

    PubMed Central

    Lu, Jia-Yang; Lin, Zhu; Zheng, Jing; Lin, Pei-Xian; Cheung, Michael Lok-Man; Huang, Bao-Tian

    2016-01-01

    This study aimed to evaluate the dosimetric outcomes of a base-dose-plan-compensation (BDPC) planning method for improving intensity-modulated radiotherapy (IMRT) for stage III lung cancer. For each of the thirteen included patients, three types of planning methods were applied to obtain clinically acceptable plans: (1) the conventional optimization method (CO); (2) a split-target optimization method (STO), in which the optimization objectives were set higher dose for the target with lung density; (3) the BDPC method, which compensated for the optimization-convergence error by further optimization based on the CO plan. The CO, STO and BDPC methods were then compared regarding conformity index (CI), homogeneity index (HI) of the target, organs at risk (OARs) sparing and monitor units (MUs). The BDPC method provided better HI/CI by 54%/7% on average compared to the CO method and by 38%/3% compared to the STO method. The BDPC method also spared most of the OARs by up to 9%. The average MUs of the CO, STO and BDPC plans were 890, 937 and 1023, respectively. Our results indicated that the BDPC method can effectively improve the dose distribution in IMRT for stage III lung cancer, at the expense of more MUs. PMID:27009235

  6. Improving survival of disassociated human embryonic stem cells by mechanical stimulation using acoustic tweezing cytometry.

    PubMed

    Chen, Di; Sun, Yubing; Deng, Cheri X; Fu, Jianping

    2015-03-24

    Dissociation-induced apoptosis of human embryonic stem cells (hESCs) hampers their large-scale culture. Herein we leveraged the mechanosensitivity of hESCs and employed, to our knowledge, a novel technique, acoustic tweezing cytometry (ATC), for subcellular mechanical stimulation of disassociated single hESCs to improve their survival. By acoustically actuating integrin-bound microbubbles (MBs) to live cells, ATC increased the survival rate and cloning efficiency of hESCs by threefold. A positive correlation was observed between the increased hESC survival rate and total accumulative displacement of integrin-anchored MBs during ATC stimulation. ATC may serve as a promising biocompatible tool to improve hESC culture. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  7. Starch filler and osmoprotectants improve the survival of rhizobacteria in dried alginate beads.

    PubMed

    Schoebitz, Mauricio; Simonin, Hélène; Poncelet, Denis

    2012-01-01

    This work deals with optimising the cell survival of rhizobacteria encapsulated in alginate beads filled with starch. Immobilisation of rhizobacteria was done by dripping alginate-starch solution mixed with rhizobacteria into a calcium solution. Beads were analysed based on matrix formulation, bacteria growth phase, osmoprotectants and nature of calcium solution. Maximum cell recovery was obtained on Raoultella terrigena grown in medium supplemented with trehalose and calcium gluconate as gelling agent. Furthermore, dried beads containing Azospirillum brasilense presented 76% of viable cells after one year of storage. The survival of rhizobacteria during the bioencapsulation process can be improved by incorporating starch on beads composition, varying the growth phase of cells and using trehalose in growth culture medium. This work provides a selection of appropriate methods to improve the surviving rate of encapsulated cells during their production and long-term storage (∼1 year at 4°C).

  8. Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial.

    PubMed

    van den Bent, Martin J; Carpentier, Antoine F; Brandes, Alba A; Sanson, Marc; Taphoorn, Martin J B; Bernsen, Hans J J A; Frenay, Marc; Tijssen, Cees C; Grisold, Wolfgang; Sipos, Laslo; Haaxma-Reiche, Hanny; Kros, Johannes M; van Kouwenhoven, Mathilde C M; Vecht, Charles J; Allgeier, Anouk; Lacombe, Denis; Gorlia, Thierry

    2006-06-20

    Anaplastic oligodendrogliomas are more responsive to chemotherapy than high-grade astrocytomas. We investigated, in a multicenter randomized controlled trial, whether adjuvant procarbazine, lomustine, and vincristine (PCV) chemotherapy improves overall survival (OS) in newly diagnosed patients with anaplastic oligodendrogliomas or anaplastic oligoastrocytomas. The primary end point of the study was OS; secondary end points were progression-free survival (PFS) and toxicity. Patients were randomly assigned to either 59.4 Gy of radiotherapy (RT) in 33 fractions only or to the same RT followed by six cycles of standard PCV chemotherapy (RT/PCV). 1p and 19q deletions were assessed with fluorescent in situ hybridization. A total of 368 patients were included. The median follow-up time was 60 months, and 59% of patients have died. In the RT arm, 82% of patients with tumor progression received chemotherapy. In 38% of patients in the RT/PCV arm, adjuvant PCV was discontinued for toxicity. OS time after RT/PCV was 40.3 months compared with 30.6 months after RT only (P = .23). RT/PCV increased PFS time compared with RT only (23 v 13.2 months, respectively; P = .0018). Twenty-five percent of patients were diagnosed with combined 1p/19q loss; 74% of this subgroup was still alive after 60 months. RT/PCV did not improve survival in the subgroup of patients with 1p/19q loss. Adjuvant PCV chemotherapy does not prolong OS but does increase PFS in anaplastic oligodendroglioma. Combined loss of 1p/19q identifies a favorable subgroup of oligodendroglial tumors. No genetic subgroup could be identified that benefited with respect to OS from adjuvant PCV.

  9. Melanoma: Last call for radiotherapy.

    PubMed

    Espenel, Sophie; Vallard, Alexis; Rancoule, Chloé; Garcia, Max-Adrien; Guy, Jean-Baptiste; Chargari, Cyrus; Deutsch, Eric; Magné, Nicolas

    2017-02-01

    Melanoma is traditionally c