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Sample records for survival locoregional control

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

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    Grossberg, Aaron J; Chamchod, Sasikarn; Fuller, Clifton D; Mohamed, Abdallah S R; 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

    2016-06-01

    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. To determine whether lean body mass before and after RT for HNSCC predicts survival and locoregional control. 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. 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. 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 SM depletion did not affect outcomes. Post-RT SM depletion was more substantive in

  2. Salivary gland carcinoma : Independent prognostic factors for locoregional control, distant metastases, and overall survival: Results of the Dutch Head and Neck Oncology Cooperative Group

    NARCIS (Netherlands)

    Terhaard, CHJ; Lubsen, H; Van der Tweel, [No Value; Hilgers, FJM; Eijkenboom, WMH; Marres, HAM; Tjho-Heslinga, RE; de Jong, JMA; Roodenburg, JLN

    Background. We analyzed the records of patients with malignant salivary gland tumors, as diagnosed in centers of the Dutch Head and Neck Oncology Cooperative Group, in search of independent prognostic factors for locoregional control, distant metastases, and overall survival. Methods. In 565

  3. Loco-regional treatment in metastatic breast cancer patients: is there a survival benefit?

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    Ly, Bevan H; Nguyen, Nam P; Vinh-Hung, Vincent; Rapiti, Elisabetta; Vlastos, Georges

    2010-02-01

    A number of studies have recently demonstrated a survival benefit in stage IV breast cancer patients following surgical resection of the primary tumor. Here, we investigate the relationship between loco-regional treatment and survival in patients with metastatic breast cancer and evaluate the impact of different loco-regional treatments. We conducted a systematic review of the literature using PubMed to analyze studies with the following criteria: Type of loco-regional treatment (surgery alone or combined with radiation, radiotherapy), overall survival, progression-free survival, selection factors for local treatment, and complication rates. Thirteen studies evaluated the effect of loco-regional treatment on overall survival with overall median survival increasing from a range of 12.6-28.3 months among patients without surgery to a range of 25-42 months among patients with surgery. In addition, six studies reported a 3-year survival benefit of 28-95% and 17-79% in women with and without locoregional therapy respectively. Two studies did not find any improvement in overall survival. One study found an improvement in 5-year breast cancer-specific survival of 27% with negative surgical margins versus 12% with no surgery. Three studies reported an advantage in progression-free survival in the treatment group compared with the non-treatment group. Loco-regional treatment for breast cancer patients with distant metastases at diagnosis is an important issue because of possible improvement of survival or disease-free survival. The possibility of surgery and/or radiotherapy following induction chemotherapy should be weighed and left to individual practice. Participation in randomized controlled trials should be encouraged.

  4. Early FDG PET at 10 or 20 Gy under chemoradiotherapy is prognostic for locoregional control and overall survival in patients with head and neck cancer

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    Hentschel, Maria [Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, Clinic and Polyclinic of Nuclear Medicine, Dresden (Germany); Appold, Steffen; Baumann, Michael [Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, Clinic and Polyclinic of Radiotherapy and Radiation Oncology, Dresden (Germany); Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, OncoRay, National Center for Radiation Research in Oncology Dresden, Dresden (Germany); Schreiber, Andreas [Hospital Dresden-Friedrichstadt, Department of Radiotherapy, Dresden (Germany); Abolmaali, Nasreddin [Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, OncoRay, National Center for Radiation Research in Oncology Dresden, Dresden (Germany); Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, Institute and Polyclinic of Diagnostic Radiology, Dresden (Germany); Abramyuk, Andrij [Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, OncoRay, National Center for Radiation Research in Oncology Dresden, Dresden (Germany); Doerr, Wolfgang [Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, Clinic and Polyclinic of Radiotherapy and Radiation Oncology, Dresden (Germany); Kotzerke, Joerg; Zoephel, Klaus [Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, Clinic and Polyclinic of Nuclear Medicine, Dresden (Germany); Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, OncoRay, National Center for Radiation Research in Oncology Dresden, Dresden (Germany)

    2011-07-15

    Our study aimed to explore the optimal timing as well as the most appropriate prognostic parameter of {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG PET) during chemoradiotherapy (CRT) for an early prediction of outcome for patients with head and neck squamous cell carcinoma (HNSCC). Serial PET data (before and three times during CRT) of 37 patients with advanced stage HNSCC, receiving combined CRT between 2005 and 2009, were evaluated. The maximum standardized uptake value (SUV{sub max}), the average SUV (SUV{sub mean}) and the gross tumour volume determined by FDG PET (GTV PET), based on a source to background algorithm, were analysed. Stratified actuarial analysis was performed for overall survival (OS), disease-free survival (DFS) and locoregional control (LRC). The median follow-up time was 26 months (range 8-50). For all patients, OS was 51%, DFS 44% and LRC 55% after 2 years. The 2-year OS (88%) and 2-year LRC (88%) were higher for patients whose SUV{sub max} of the primary tumour decreased 50% or more from the beginning (0 Gy) to week 1 or 2 (10 or 20 Gy) of CRT ({delta}SUV{sub max10/20} {>=} 50%) than for patients with {delta}SUV{sub max20} < 50% (2-year OS = 38%; p = 0.02; 2-year LRC 40%; p = 0.06). A pretreatment GTV PET below the median of 10.2 ml predicted a better 2-year OS (34% for GTV PET {>=} 10.2 ml vs 83% for GTV PET < 10.2 ml; p = 0.02). The decrease of SUV{sub max} from before (0 Gy) to week 1 or 2 (10 or 20 Gy) of CRT is a potential prognostic marker for patients with HNSCC. Because GTV PET depends on the applied method of analysis, we suggest the use of SUV{sub max}, especially {delta}SUV{sub max10/20}, for an early estimation of therapy outcome. Confirmatory studies are warranted. (orig.)

  5. Loco-regional control after postoperative radiotherapy for patients with regional nodal metastases from melanoma.

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    Conill, Carlos; Valduvieco, Izaskun; Domingo-Domènech, Josep; Arguis, Pedro; Vidal-Sicart, Sergi; Vilalta, Antonio

    2009-10-01

    The role of adjuvant radiation therapy (RT) following nodal surgery in malignant melanoma remains controversial. There are no published randomised trials comparing surgery alone to surgery with postoperative RT. The purpose of the present retrospective study was to review the results of loco-regional control after postoperative RT in patients with nodal metastases of melanoma. Seventy-seven patients with high-risk disease (lymph nodes > or =3 cm, more than three lymph nodes involved, extracapsular extension and recurrent disease) were treated with adjuvant RT. Hypofractionation was used in 65 patients and conventional fractionation in 12 patients. Seventy-seven patients with nodal metastases from melanoma were managed with lymphadenectomy and radiation, with or without systemic therapy. The median age was 56 years old (range: 21-83). There were 47 males (61%) and 30 females (39%). Loco-regional control was observed in 95% of patients (73/77). The actuarial 5-year in-field loco-regional control rate was 90% (mean: 105 months; CI95%: 96-115 months). Median metastasis disease- free survival (MDFS) was 16 months (CI95%: 13-18 months). Median survival time (MST) for the entire group was 26 months (CI95%: 18-34 months). MST according to the localisation of node metastases (groin, axilla and cervical) was also analysed, without statistically significant differences (p=0.08). Concerning the number of risk factors score, analysis of survival did not show statistically significant differences (p=0.055). Despite the high incidence of distant metastases, loco-regional control remains an important goal in the management of melanoma. Surgery and adjuvant RT provides excellent loco-regional control, although distant metastases remain the major cause of mortality.

  6. Predictors of Locoregional Failure and Impact on Overall Survival in Patients With Resected Exocrine Pancreatic Cancer

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    Merrell, Kenneth W.; Haddock, Michael G. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Quevedo, J. Fernando [Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota (United States); Harmsen, William S. [Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota (United States); Kendrick, Michael L. [Department of General Surgery, Mayo Clinic, Rochester, Minnesota (United States); Miller, Robert C. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Hallemeier, Christopher L., E-mail: hallemeier.christopher@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States)

    2016-03-01

    Purpose: Resection of exocrine pancreatic cancer is necessary for cure, but locoregional and distant relapse is common. We evaluated our institutional experience to better understand risk factors for locoregional failure (LRF) and its impact on overall survival (OS). Methods and Materials: We reviewed 1051 consecutive patients with nonmetastatic exocrine pancreatic cancer who underwent resection at our institution between March 1987 and January 2011. Among them, 458 had adequate follow-up and evaluation for study inclusion. All patients received adjuvant chemotherapy (n=80 [17.5%]) or chemoradiation therapy (n=378 [82.5%]). Chemotherapy and chemoradiation therapy most frequently consisted of 6 cycles of gemcitabine and 50.4 Gy in 28 fractions with concurrent 5-fluorouracil, respectively. Locoregional control (LRC) and OS were estimated with the Kaplan-Meier method. Univariate and multivariate analyses were performed with Cox proportional hazards regression models incorporating propensity score. Results: Median patient age was 64.5 years (range: 29-88 years). Median follow-up for living patients was 84 months (range: 6-300 months). Extent of resection was R0 (83.8%) or R1 (16.2%). Overall crude incidence of LRF was 17% (n=79). The 5-year LRC for patients with and without radiation therapy was 80% and 68%, respectively (P=.003; hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.28-0.76). Multivariate analysis, incorporating propensity score, indicated radiation therapy (P<.0001; HR: 0.23; 95% CI: 0.12-0.42) and positive lymph node ratio of ≥0.2 (P=.02; HR: 1.78; 95% CI: 1.10-2.9) were associated with LRC. In addition, LRF was associated with worse OS (P<.0001; HR: 5.0; 95% CI: 3.9-6.3). Conclusions: In our analysis of 458 patients with resected pancreatic cancer, positive lymph node ratio of ≥0.2 and no adjuvant chemoradiation therapy were associated with increased LRF risk. LRF was associated with poor OS. Radiation therapy should be considered as

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

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    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

    2016-08-01

    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.

  8. Survival benefit of adding chemotherapy to intensity modulated radiation in patients with locoregionally advanced nasopharyngeal carcinoma.

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    Xuemei Ji

    Full Text Available BACKGROUND: To evaluate the contribution of chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma (NPC treated by intensity modulated radiotherapy (IMRT and to identify the optimal combination treatment strategy. PATIENTS AND METHODS: Between 2006 and 2010, 276 patients with stage II-IVb NPC were treated by IMRT alone or IMRT plus chemotherapy. Cisplatin-based chemotherapy included neoadjuvant or concurrent, or neoadjuvant plus concurrent protocols. The IMRT alone and chemoradiotherapy groups were well-matched for prognostic factors, except N stage, with more advanced NPC in the chemoradiotherapy arm. RESULTS: With a mean follow-up of 33.8 months, the 3-year actuarial rates of overall survival (OS, metastasis-free survival (MFS, relapse-free survival (RFS, and disease-free survival (DFS were 90.3%, 84.2%, 80.3%, and 69.2% for all of the patients, respectively. Compared with the IMRT alone arm, patients treated by concurrent chemoradiotherapy had a significantly better DFS (HR = 2.64; 95% CI, 1.12-6.22; P = 0.03, patients with neoadjuvant-concurrent chemoradiotherapy had a significant improvement in RFS and DFS (HR = 4.03; 95% CI, 1.35-12.05; P = 0.01 and HR = 2.43; 95% CI, 1.09-5.44; P = 0.03, neoadjuvant chemoradiotherapy provided no significant benefit in OS, MFS, RFS, and DFS. Stage group and alcohol consumption were prognostic factors for OS and N stage was a significant predictor for DFS. CONCLUSIONS: Addition of concurrent or neoadjuvant-concurrent chemotherapy to IMRT is available to prolong RFS or DFS for locoregionally advanced NPC. Such work could be helpful to guide effective individualized therapy.

  9. Radiographic response to locoregional therapy in hepatocellular carcinoma predicts patient survival times.

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    Memon, Khairuddin; Kulik, Laura; Lewandowski, Robert J; Wang, Edward; Riaz, Ahsun; Ryu, Robert K; Sato, Kent T; Marshall, Karen; Gupta, Ramona; Nikolaidis, Paul; Miller, Frank H; Yaghmai, Vahid; Senthilnathan, Seanthan; Baker, Talia; Gates, Vanessa L; Abecassis, Michael; Benson, Al B; Mulcahy, Mary F; Omary, Reed A; Salem, Riad

    2011-08-01

    It is not clear whether survival times of patients with hepatocellular carcinoma (HCC) are associated with their response to therapy. We analyzed the association between tumor response and survival times of patients with HCC who were treated with locoregional therapies (LRTs) (chemoembolization and radioembolization). Patients received LRTs over a 9-year period (n = 463). Patients with metastases, portal venous thrombosis, or who had received transplants were excluded; 159 patients with Child-Pugh B7 or lower were analyzed. Response (based on European Association for the Study of the Liver [EASL] and World Health Organization [WHO] criteria) was associated with survival times using the landmark, risk-of-death, and Mantel-Byar methodologies. In a subanalysis, survival times of responders were compared with those of patients with stable disease and progressive disease. Based on 6-month data, in landmark analysis, responders survived longer than nonresponders (based on EASL but not WHO criteria: P = .002 and .0694). The risk of death was also lower for responders (based on EASL but not WHO criteria: P = .0463 and .707). Landmark analysis of 12-month data showed that responders survived longer than nonresponders (P < .0001 and .004, based on EASL and WHO criteria, respectively). The risk of death was lower for responders (P = .0132 and .010, based on EASL and WHO criteria, respectively). By the Mantel-Byar method, responders had longer survival than nonresponders, based on EASL criteria (P < .0001; P = .596 with WHO criteria). In the subanalysis, responders lived longer than patients with stable disease or progressive disease. Radiographic response to LRTs predicts survival time. EASL criteria for response more consistently predicted survival times than WHO criteria. The goal of LRT should be to achieve a radiologic response, rather than to stabilize disease. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  10. Prognostic factors for locoregional recurrence and survival in stage IIIC breast carcinoma: impact of adjuvant radiotherapy.

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    Kuru, B

    2011-04-01

    The aims of the present study were to define the prognostic factors for locoregional recurrence (LRR) and survival in stage IIIC breast carcinoma as well as to examine the impact of adjuvant radiotherapy on the outcome of the disease. The records of 586 consecutive patients with stage IIIC breast carcinoma who underwent modified radical mastectomy were evaluated, and the prognostic factors for LRR and survival were analysed. Survival curves were generated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard model. Five-year LRR and survival of stage IIIC breast carcinoma were 15 percent and 41.3 percent, respectively. Five-year LRR was significantly lower and five-year survival was significantly higher for all patients as well as for T1-2 patients with one to three apical node involvements who were treated with adjuvant radiotherapy. In multivariate analysis, apical node involvement, age below 35 years, T4 tumour, grade 3, extracapsular extension and lymphovascular invasion decreased survival, whereas adjuvant tamoxifen and adjuvant radiotherapy (risk ratio [RR] 0.51, 95 percent confidence interval [CI] 0.39-0.67) increased survival. Adjuvant radiotherapy was the sole independent factor that was found to be significantly associated with decreased LRR (RR 0.25, 95 percent CI 0.16-0.38). Radiotherapy decreased LRR and increased survival significantly in all stage IIIC patients and in the subgroup of T1-2 patients with one to three apical node involvements. Thus, it should be considered in the treatment of stage IIIC breast carcinoma.

  11. Bridging Locoregional Therapy Prolongs Survival in Patients Listed for Liver Transplant with Hepatocellular Carcinoma

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    Xing, Minzhi [Yale School of Medicine, Interventional Radiology, Department of Radiology and Biomedical Imaging (United States); Sakaria, Sonali [Emory University School of Medicine, Division of Digestive Diseases, Department of Medicine (United States); Dhanasekaran, Renumathy [Stanford University School of Medicine, Division of Gastroenterology and Hepatology (United States); Parekh, Samir; Spivey, James [Emory University School of Medicine, Division of Digestive Diseases, Department of Medicine (United States); Knechtle, Stuart J. [Duke University School of Medicine, Division of Transplant Surgery, Department of Surgery (United States); Zhang, Di [University of Pittsburgh, Department of Biostatistics, Graduate School of Public Health (United States); Kim, Hyun S., E-mail: kevin.kim@yale.edu [Yale School of Medicine, Interventional Radiology, Department of Radiology and Biomedical Imaging (United States)

    2017-03-15

    Background and AimsTo evaluate the long-term survival benefit of bridging locoregional therapy (LRT) prior to orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC) within Milan criteria.MethodsOur transplant center registry was studied for all HCC patients within the Milan criteria who were listed for OLT from 1998 to 2013. Baseline clinical characteristics and median overall survival (OS) were calculated and stratified by LRT, OLT status, and wait times. Survival analysis was conducted using Kaplan–Meier estimation and log-rank test.ResultsOf 265 listed, 205 underwent OLT (mean follow-up 7.6 years). Of 205, 111 received bridging LRT (A), and 94 did not (B). Both were similar in demographics and tumor characteristics (p > 0.05). Median OS from HCC for A/B were 86.4 vs. 68.9 months (p = 0.01). Median OS from OLT for A/B were 74.6 vs. 63.6 months (p = 0.03). On multivariate analysis, independent predictors for survival from HCC were bridging LRT (p = 0.002) and high wait time (p = 0.008); independent predictors for survival from OLT were bridging LRT (p = 0.005) and high wait time (p = 0.005). Of 60 who were listed but did not undergo transplant, 44 received LRT (C) and 16 received best supportive care (D). Median OS from HCC for C/D were 37.1 vs. 24.8 months (p = 0.03).ConclusionsBridging LRT and high wait times were independent positive prognostic factors for survival from HCC diagnosis and OLT.

  12. Postoperative radiotherapy appeared to improve the disease free survival rate of patients with extrahepatic bile duct cancer at high risk of loco-regional recurrence

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    Kim, Mi Young; Kim, Jin Hee; Kim, Yong Hoon [Keimyung University Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of); Byun, Sang Jun [Dept. of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2016-12-15

    To investigate the outcomes of postoperative radiotherapy (RT), in patients with extrahepatic bile duct (EHBD) cancer by comparing the survival rate between patients undergoing surgery alone or surgery plus postoperative RT, and to identify the prognostic factors affecting survival. Between 2000 and 2013, 52 patients with EHBD cancer underwent surgical resection. Of these, 33 patients did not receive postoperative RT (group I), and 19 patients did (group II). R1 resection was significantly more frequent in group II. The median radiation dose was 5,040 cGy. The 3-year overall survival (OS) rate for group I and group II was 38% and 56%, respectively (p = 0.274). The 3-year disease free survival (DFS) rate for group I and group II was 20% and 31%, respectively (p = 0.049), and the 3-year loco-regional recurrence free survival (LRFS) rates were 19% and 58%, respectively (p = 0.002). Multivariate analyses showed that postoperative RT and lymphovascular invasion were independent prognostic factors for DFS and LRFS. Overall, 42 patients (80%) experienced treatment failure. Distant metastasis was the predominant pattern of failure in group II. Postoperative RT after surgical resection appeared to improve the loco-regional control and DFS rate. More effort is needed to reduce distant metastasis, the major pattern of failure, in patients who receive postoperative RT.

  13. Postoperative radiotherapy appeared to improve the disease free survival rate of patients with extrahepatic bile duct cancer at high risk of loco-regional recurrence.

    Science.gov (United States)

    Kim, Mi Young; Kim, Jin Hee; Kim, Yonghoon; Byun, Sang Jun

    2016-12-01

    To investigate the outcomes of postoperative radiotherapy (RT), in patients with extrahepatic bile duct (EHBD) cancer by comparing the survival rate between patients undergoing surgery alone or surgery plus postoperative RT, and to identify the prognostic factors affecting survival. Between 2000 and 2013, 52 patients with EHBD cancer underwent surgical resection. Of these, 33 patients did not receive postoperative RT (group I), and 19 patients did (group II). R1 resection was significantly more frequent in group II. The median radiation dose was 5,040 cGy. The 3-year overall survival (OS) rate for group I and group II was 38% and 56%, respectively (p = 0.274). The 3-year disease free survival (DFS) rate for group I and group II was 20% and 31%, respectively (p = 0.049), and the 3-year loco-regional recurrence free survival (LRFS) rates were 19% and 58%, respectively (p = 0.002). Multivariate analyses showed that postoperative RT and lymphovascular invasion were independent prognostic factors for DFS and LRFS. Overall, 42 patients (80%) experienced treatment failure. Distant metastasis was the predominant pattern of failure in group II. Postoperative RT after surgical resection appeared to improve the loco-regional control and DFS rate. More effort is needed to reduce distant metastasis, the major pattern of failure, in patients who receive postoperative RT.

  14. Postoperative radiotherapy dose correlates with locoregional control in patients with extra-hepatic bile duct cancer

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    Im, Jung Ho; Seong, Jinsil; Lee, Jeong Shim; Kim, Yong Bae; Kim, Kyung Sik; Lee, Woo Jung [Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Lee, Ik Jae; Park, Jun Sung; Yoon, Dong Sup [Sangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2013-12-15

    To evaluate the results of postoperative radiotherapy in patients with extra-hepatic bile duct cancer (EHBDC) and identify the prognostic factors for local control and survival. Between January 2001 and December 2010, we retrospectively reviewed the cases of 70 patients with EHBDC who had undergone curative resection and received postoperative radiotherapy. The median radiation dose was 50.4 Gy (range, 41.4 to 54 Gy). The resection margin status was R0 in 30 patients (42.9%), R1 in 25 patients (35.7%), and R2 in 15 patients (21.4%). The 5-year rates of overall survival (OS), event-free survival (EFS), and locoregional control (LRC) for all patients were 42.9%, 38.3%, and 61.2%, respectively. The major pattern of failure was distant relapses (33 patients, 47.1%). A multivariate analysis showed that the postradiotherapy CA19-9 level, radiation dose (≥50 Gy), R2 resection margins, perineural invasion, and T stage were the significant prognostic factors for OS, EFS, and LRC. OS was not significantly different between the patients receiving R0 and R1 resections, but was significantly lower among those receiving R2 resection (54.6%, 56.1%, and 7.1% for R0, R1, and R2 resections, respectively). In patients with EHBDC who had undergone curative resection, a postoperative radiotherapy dose less than 50 Gy was suboptimal for OS and LRC. Higher radiation doses may be needed to obtain better LRC. Further investigation of novel therapy or palliative treatment should be considered for patients receiving R2 resection.

  15. A nomogram to predict loco-regional control after re-irradiation for head and neck cancer.

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    Riaz, Nadeem; Hong, Julian C; Sherman, Eric J; Morris, Luc; Fury, Matthew; Ganly, Ian; Wang, Tony J C; Shi, Weji; Wolden, Suzanne L; Jackson, Andrew; Wong, Richard J; Zhang, Zhigang; Rao, Shyam D; Lee, Nancy Y

    2014-06-01

    Loco-regionally recurrent head and neck cancer (HNC) in the setting of prior radiotherapy carries significant morbidity and mortality. The role of re-irradiation (re-RT) remains unclear due to toxicity. We determined prognostic factors for loco-regional control (LRC) and formulated a nomogram to help clinicians select re-RT candidates. From July 1996 to April 2011, 257 patients with recurrent HNC underwent fractionated re-RT. Median prior dose was 65 Gy and median time between RT was 32.4 months. One hundred fifteen patients (44%) had salvage surgery and 172 (67%) received concurrent chemotherapy. Median re-RT dose was 59.4 Gy and 201 (78%) patients received IMRT. Multivariate Cox proportional hazards were used to identify independent predictors of LRC and a nomogram for 2-year LRC was constructed. Median follow-up was 32.6 months. Two-year LRC and overall survival (OS) were 47% and 43%, respectively. Recurrent stage (P=0.005), non-oral cavity subsite (P50 Gy (P=0.006) were independently associated with improved LRC. We generated a nomogram with concordance index of 0.68. Re-RT can be curative, and our nomogram can help determine a priori which patients may benefit. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Alpha-fetoprotein response after locoregional therapy for hepatocellular carcinoma: oncologic marker of radiologic response, progression, and survival.

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    Riaz, Ahsun; Ryu, Robert K; Kulik, Laura M; Mulcahy, Mary F; Lewandowski, Robert J; Minocha, Jeet; Ibrahim, Saad M; Sato, Kent T; Baker, Talia; Miller, Frank H; Newman, Steven; Omary, Reed; Abecassis, Michael; Benson, Al B; Salem, Riad

    2009-12-01

    Alpha-fetoprotein (AFP) is considered to be an indicator of tumor activity in hepatocellular carcinoma (HCC). We present a novel correlation of AFP response to radiologic response, time-to-progression (TTP), progression-free survival (PFS), and overall survival (OS) in patients treated with locoregional therapies. Four hundred sixty-three patients with HCC were treated with chemoembolization or radioembolization at our institution. One hundred twenty-five patients with baseline AFP higher than 200 ng/mL were studied for this analysis. AFP response was defined as more than 50% decrease from baseline. One hundred nineteen patients with follow-up imaging were studied for the AFP imaging correlation analysis. AFP response was correlated to radiologic response, TTP, PFS, and OS. Multivariate analyses were performed. Eighty-one patients (65%) showed AFP response. AFP response was seen in 26 (55%) of 47 and 55 (70%) of 78 of patients treated with chemoembolization and radioembolization, respectively (P = .12). WHO response was seen in 41 (53%) of 77 and 10 (24%) of 42 of AFP responders and nonresponders, respectively (P = .002). The hazard ratio (HR) for TTP in AFP nonresponders compared with responders was 2.8 (95% CI, 1.5 to 5.1). The HR for PFS was 4.2 (95% CI, 2.4 to 7.2) in AFP nonresponders compared with responders. The HR for OS in AFP nonresponders compared with responders was 5.5 (95% CI, 3.1 to 9.9) and 2.7 (95% CI, 1.6 to 4.6) on univariate and multivariate analyses, respectively. The data presented support the use of AFP response seen after locoregional therapy as an ancillary method of assessing tumor response and survival, as well as an early objective screening tool for progression by imaging.

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

    Science.gov (United States)

    Dilling, Thomas J.; Bae, Kyounghwa; Paulus, Rebecca; Watkins-Bruner, Deborah; Garden, Adam S.; Forastiere, Arlene; Ang, K. Kian; Movsas, Benjamin

    2011-01-01

    PURPOSE We investigated the impact of race, in conjunction with gender and partner status, on both locoregional control (LRC) and overall survival (OS) in three head and neck trials conducted by the Radiation Therapy Oncology Group (RTOG). METHODS AND MATERIALS Patients from RTOG 9003, 9111, and 9703 were included. Patients were stratified by treatment arms. Covariates of interest were partner status (partnered/non-partnered), race (white/non-white), and sex (female/male). Chi-square testing demonstrated homogeneity across treatment arms. Hazards ratio (HR) was used to estimate time to event outcome. Unadjusted and adjusted HRs were calculated for all covariates with associated 95% confidence intervals (CIs) and p-values. RESULTS 1736 patients were analyzed. Unpartnered males had inferior OS to partnered females (adjusted HR=1.22, 95% CI=(1.09, 1.36)), partnered males (adjusted HR=1.20, 95% CI=(1.09, 1.28)), and unpartnered females (adjusted HR=1.20, 95% CI=(1.09, 1.32)). White females had superior OS compared with white males, non-white females, and non-white males. Non-white males had inferior OS compared to white males. Partnered whites had improved OS relative to partnered non-white, unpartnered white, and unpartnered non-white patients. Unpartnered males had inferior LRC than partnered males (adjusted HR=1.26, 95% CI=(1.09, 1.46)) and unpartnered females (adjusted HR=1.30, 95% CI=(1.05, 1.62)). White females had superior LRC to non-white males and females. White males had improved LRC than non-white males. Partnered whites had improved LRC than partnered and unpartnered non-white patients. Unpartnered whites had improved LRC than unpartnered non-whites. CONCLUSIONS Race, gender, and partner status impacted on both overall survival and locoregional failure, both singly and in combination. PMID:21549515

  18. Disease-specific survival and locoregional control in tonsillar carcinoma

    NARCIS (Netherlands)

    MakKregar, S; Hilgers, FJM; Levendag, PC; Manni, JJ; Hart, AAM; Visser, O; Knegt, PPM; Marres, HAM; TenBroek, FW; Burlage, FR; VanderBeek, JMH; DeJong, RJB

    1996-01-01

    In a nationwide survey on oropharyngeal carcinoma in the Netherlands (1986-1990), 380 patients with a tonsillar carcinoma were retrospectively studied. The records of 268 (71%) men and 112 (29%) women with a median age of 59 yr (range 31-91), who had squamous cell carcinoma (272 patients, 98%) or

  19. Surrogate End Points for Overall Survival in Loco-Regionally Advanced Nasopharyngeal Carcinoma: An Individual Patient Data Meta-analysis.

    Science.gov (United States)

    Rotolo, Federico; Pignon, Jean-Pierre; Bourhis, Jean; Marguet, Sophie; Leclercq, Julie; Tong Ng, Wai; Ma, Jun; Chan, Anthony T C; Huang, Pei-Yu; Zhu, Guopei; Chua, Daniel T T; Chen, Yong; Mai, Hai-Qiang; Kwong, Dora L W; Soong, Yoke Lim; Moon, James; Tung, Yuk; Chi, Kwan-Hwa; Fountzilas, George; Zhang, Li; Hui, Edwin Pun; Lee, Anne W M; Blanchard, Pierre; Michiels, Stefan

    2017-04-01

    Our objective was to evaluate progression-free survival (PFS) and distant metastasis-free survival (DMFS) as surrogate end points for overall survival (OS) in randomized trials of chemotherapy in loco-regionally advanced nasopharyngeal carcinomas (NPCs). Individual patient data were obtained from 19 trials of the updated Meta-Analysis of Chemotherapy in Nasopharyngeal Carcinoma (MAC-NPC) plus one additional trial (total = 5144 patients). Surrogacy was evaluated at the individual level using a rank correlation coefficient ρ and at the trial level using a correlation coefficient R2 between treatment effects on the surrogate end point and OS. A sensitivity analysis was performed with two-year PFS/DMFS and five-year OS. PFS was strongly correlated with OS at the individual level (ρ = 0.93, 95% confidence interval [CI] = 0.93 to 0.94) and at the trial level (R2 = 0.95, 95% CI = 0.47 to 1.00). For DMFS, too, the individual-level correlation with OS was strong (ρ = 0.98, 95% CI = 0.98 to 0.98); at trial level, the correlation was high but the regression adjusted for measurement error could not be computed (unadjusted R2 = 0.96, 95% CI = 0.94 to 0.99). In the sensitivity analysis, two-year PFS was highly correlated with five-year OS at the individual level (ρ = 0.89, 95% CI = 0.88 to 0.90) and at the trial level (R2 = 0.85, 95% CI = 0.46 to 1.00); two-year DMFS was highly correlated with five-year OS at the individual level (ρ = 0.95, 95% CI = 0.94 to 0.95) and at the trial level (R2 = 0.78, 95% CI = 0.33 to 1.00). PFS and DMFS are valid surrogate end points for OS to assess treatment effect of chemotherapy in loco-regionally advanced NPC, while PFS can be measured earlier. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Postmastectomy radiotherapy improves disease-free survival of high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes.

    Directory of Open Access Journals (Sweden)

    Zhen-Yu He

    Full Text Available 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.We retrospectively reviewed the file records of 79 patients receiving PMRT and not receiving PMRT (618 patients.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.PMRT is beneficial in patients with high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes.

  1. Submandibular gland-sparing intensity modulated radiotherapy in the treatment of head and neck cancer. Sites of locoregional relapse and survival

    Energy Technology Data Exchange (ETDEWEB)

    Collan, Juhani; Kapanen, Mika; Nyman, Heidi; Joensuu, Heikki; Tenhunen, Mikko; Saarilahti, Kauko [Dept. of Oncology, Helsinki Univ. Central Hospital, Helsinki (Finland)], e-mail: kauko.saarilahti@hus.fi; Maekitie, Antti [Dept. of Otorhinolaryngology, Head and Neck Surgery, Helsinki Univ. Central Hospital, Helsinki (Finland)

    2012-07-15

    Background and purpose: To evaluate the patterns of locoregional relapse and survival following submandibular gland (SMG)-sparing intensity modulated radiotherapy (IMRT). Patients and methods: Eighty patients with laryngeal (n = 15), oropharyngeal (n = 50), hypopharyngeal (n = 11) or nasopharyngeal cancer (n = 4) were treated by submandibular gland-sparing IMRT for head and neck squamous cell cancer between July 2000 and December 2008. All patients were treated by bilateral IMRT. Thirty-nine (49%) received definitive radiotherapy (RT) and 41 (51%) postoperative RT. The contralateral parotid gland (PG) and SMG were included in the dose optimization planning program with intent to keep the mean doses for PG and SMG below 23 Gy and 28-30 Gy, respectively. The ipsilateral glands were also spared when considered feasible. Results: During a median follow-up time of 51 months (range, 24-117 months) nine local recurrent tumors were observed. Four of these nine patients were salvaged by surgery with no further recurrence. All local recurrences were located within the high-dose CTVs. None of the locally recurrent cancers were located at the vicinity of the spared PGs or SMGs. No recurrent tumors were observed in the contralateral neck. The Kaplan-Meier estimate for local control at five years following IMRT was 88 % for the whole cohort and the corresponding figure for local control following salvage surgery was 94 %. The estimates for five-year overall survival and disease-specific survival were 85 % and 90 %, respectively. Conclusion. In selected head and neck cancer patients who are estimated to have a low risk of cancer recurrence at the nodal levels I-II and who are treated with SMG-sparing IMRT the risk of cancer recurrence at the vicinity of the spared salivary glands is low.

  2. Loco-regional control after neo-adjuvant chemotherapy and conservative treatment for locally advanced breast cancer patients.

    Science.gov (United States)

    Levy, Antonin; Borget, Isabelle; Bahri, Manel; Arnedos, Monica; Rivin, Eleonor; Vielh, Philippe; Balleyguier, Corinne; Rimareix, Françoise; Bourgier, Céline

    2014-01-01

    Breast-conserving treatment (BCT) has been validated for breast cancer patients receiving adjuvant chemotherapy. Our objective was to evaluate the difference in loco-regional recurrence (LRR) rates between BCT and mastectomy in patients receiving radiation therapy after neo-adjuvant chemotherapy (NCT). A retrospective data base was used to identify all patients with breast cancer undergoing NCT from 2002 to 2007. Patients with initial metastatic disease were excluded from this analysis. LRR was compared between those undergoing BCT and mastectomy. Individual variables associated with LRR were evaluated. Two hundred eighty-four patients were included, 111 (39%) underwent BCT and 173 (61%) mastectomy. Almost all patients (99%) in both groups received postoperative radiation. Pathologic complete response was seen in 37 patients, of which 28 underwent BCT (p loco-regional control rate was 91% (95% CI: 86-94%). The 10-year LRR rate was similar in the BCT group (9.2% [95% CI: 4.9-16.7%]) and in the mastectomy group (10.7% [95% CI: 5.9-15.2%]; p = 0.8). Ten-year overall survival (OS) rates (63% [95% CI: 46-79%] in the BCT group; 60% [95% CI: 47-73%] in the mastectomy group, p = 0.8) were not statistically different between the two patient populations. Multivariate analysis showed that AJCC stage ≥ III (HR: 2.6; 95% CI: 1.2-5.8; p = 0.02), negative PR (HR: 6; 95% CI: 1.2-30.6, p = 0.03), and number of positive lymph nodes ≥3 (HR: 2.5; 95% CI: 1.1-5.9; p = 0.03) were independent predictors of LRR. Ten-year OS was similar in the BCT and in the mastectomy group (p = 0.1). The rate of LRR was low and did not significantly differ between the BCT and the mastectomy group after NCT. Randomized trials assessing whether mastectomy can be safely omitted in selected breast cancer patients (nonstage III tumors or those which do not require adjuvant hormone suppression) which respond to NCT are required. © 2014 Wiley Periodicals, Inc.

  3. Risk of recurrence and conditional survival in complete responders treated with TKIs plus or less locoregional therapies for metastatic renal cell carcinoma

    Science.gov (United States)

    Santini, Daniele; Santoni, Matteo; Conti, Alessandro; Procopio, Giuseppe; Verzoni, Elena; Galli, Luca; di Lorenzo, Giuseppe; De Giorgi, Ugo; De Lisi, Delia; Nicodemo, Maurizio; Maruzzo, Marco; Massari, Francesco; Buti, Sebastiano; Altobelli, Emanuela; Biasco, Elisa; Ricotta, Riccardo; Porta, Camillo; Vincenzi, Bruno; Papalia, Rocco; Marchetti, Paolo; Burattini, Luciano; Berardi, Rossana; Muto, Giovanni; Montironi, Rodolfo; Cascinu, Stefano; Tonini, Giuseppe

    2016-01-01

    PURPOSE We retrospectively analyzed the risk of recurrence and conditional Disease-Free Survival (cDFS) in 63 patients with complete remission during treatment with tirosin kinase inhibitor (TKI), alone or with local treatment in metastatic renal cell carcinoma. RESULTS 37% patients achieve CR with TKI alone, while 63% with additional loco-regional treatments. 49% patients recurred after CR, with a median Disease free survival of 28.2 months. Patients treated with multimodal approaches present lower rate of recurrence (40% vs 61%) and longer Disease free survival compared to patient treated with TKI alone (16.5 vs 41.9 months, p=0.039).Furthermore the rate of recurrence was higher in patients with brain (88%), pancreatic (71%) and bone metastasis (50%). Patients who continued TKI therapy after complete response had a longer disease free survival than patients who stopped therapy, although the difference was not significant (42.1 vs 25.1 months, p=0.254). 2y-cDFS was better in patients treated with multimodal treatment and who continued TKIs than the other patient arms. CONCLUSIONS The prognostic value of CR depends on the site where was obtained and how was obtained (with or without locoregional treatment). Cessation of TKI should be carefully considered in complete responder patients. PMID:27027342

  4. Risk of recurrence and conditional survival in complete responders treated with TKIs plus or less locoregional therapies for metastatic renal cell carcinoma.

    Science.gov (United States)

    Santini, Daniele; Santoni, Matteo; Conti, Alessandro; Procopio, Giuseppe; Verzoni, Elena; Galli, Luca; di Lorenzo, Giuseppe; De Giorgi, Ugo; De Lisi, Delia; Nicodemo, Maurizio; Maruzzo, Marco; Massari, Francesco; Buti, Sebastiano; Altobelli, Emanuela; Biasco, Elisa; Ricotta, Riccardo; Porta, Camillo; Vincenzi, Bruno; Papalia, Rocco; Marchetti, Paolo; Burattini, Luciano; Berardi, Rossana; Muto, Giovanni; Montironi, Rodolfo; Cascinu, Stefano; Tonini, Giuseppe

    2016-05-31

    We retrospectively analyzed the risk of recurrence and conditional Disease-Free Survival (cDFS) in 63 patients with complete remission during treatment with tirosin kinase inhibitor (TKI), alone or with local treatment in metastatic renal cell carcinoma. 37% patients achieve CR with TKI alone, while 63% with additional loco-regional treatments. 49% patients recurred after CR, with a median Disease free survival of 28.2 months. Patients treated with multimodal approaches present lower rate of recurrence (40% vs 61%) and longer Disease free survival compared to patient treated with TKI alone (16.5 vs 41.9 months, p=0.039).Furthermore the rate of recurrence was higher in patients with brain (88%), pancreatic (71%) and bone metastasis (50%). Patients who continued TKI therapy after complete response had a longer disease free survival than patients who stopped therapy, although the difference was not significant (42.1 vs 25.1 months, p=0.254). 2y-cDFS was better in patients treated with multimodal treatment and who continued TKIs than the other patient arms. The prognostic value of CR depends on the site where was obtained and how was obtained (with or without locoregional treatment). Cessation of TKI should be carefully considered in complete responder patients.

  5. HPV16 DNA status is a strong prognosticator of loco-regional control after postoperative radiochemotherapy of locally advanced oropharyngeal carcinoma: results from a multicentre explorative study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG).

    Science.gov (United States)

    Lohaus, Fabian; Linge, Annett; Tinhofer, Inge; Budach, Volker; Gkika, Eleni; Stuschke, Martin; Balermpas, Panagiotis; Rödel, Claus; Avlar, Melanie; Grosu, Anca-Ligia; Abdollahi, Amir; Debus, Jürgen; Bayer, Christine; Belka, Claus; Pigorsch, Steffi; Combs, Stephanie E; Mönnich, David; Zips, Daniel; von Neubeck, Cläre; Baretton, Gustavo B; Löck, Steffen; Thames, Howard D; Krause, Mechthild; Baumann, Michael

    2014-12-01

    To investigate the impact of HPV status in patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received surgery and cisplatin-based postoperative radiochemotherapy. For 221 patients with locally advanced squamous cell carcinoma of the hypopharynx, oropharynx or oral cavity treated at the 8 partner sites of the German Cancer Consortium, the impact of HPV DNA, p16 overexpression and p53 expression on outcome were retrospectively analysed. The primary endpoint was loco-regional tumour control; secondary endpoints were distant metastases and overall survival. In the total patient population, univariate analyses revealed a significant impact of HPV16 DNA positivity, p16 overexpression, p53 positivity and tumour site on loco-regional tumour control. Multivariate analysis stratified for tumour site showed that positive HPV 16 DNA status correlated with loco-regional tumour control in patients with oropharyngeal carcinoma (p=0.02) but not in the oral cavity carcinoma group. Multivariate evaluation of the secondary endpoints in the total population revealed a significant association of HPV16 DNA positivity with overall survival (ploco-regional tumour control after postoperative cisplatin-based radiochemotherapy of locally advanced oropharyngeal carcinoma and is now being explored in a prospective validation trial. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Survivability via Control Objectives

    Energy Technology Data Exchange (ETDEWEB)

    CAMPBELL,PHILIP L.

    2000-08-11

    Control objectives open an additional front in the survivability battle. A given set of control objectives is valuable if it represents good practices, it is complete (it covers all the necessary areas), and it is auditable. CobiT and BS 7799 are two examples of control objective sets.

  7. Locoregional Control of Non-Small Cell Lung Cancer in Relation to Automated Early Assessment of Tumor Regression on Cone Beam Computed Tomography

    Energy Technology Data Exchange (ETDEWEB)

    Brink, Carsten, E-mail: carsten.brink@rsyd.dk [Institute of Clinical Research, University of Southern Denmark (Denmark); Laboratory of Radiation Physics, Odense University Hospital (Denmark); Bernchou, Uffe [Institute of Clinical Research, University of Southern Denmark (Denmark); Laboratory of Radiation Physics, Odense University Hospital (Denmark); Bertelsen, Anders [Laboratory of Radiation Physics, Odense University Hospital (Denmark); Hansen, Olfred [Institute of Clinical Research, University of Southern Denmark (Denmark); Department of Oncology, Odense University Hospital (Denmark); Schytte, Tine [Department of Oncology, Odense University Hospital (Denmark); Bentzen, Soren M. [Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center, and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD (United States)

    2014-07-15

    Purpose: Large interindividual variations in volume regression of non-small cell lung cancer (NSCLC) are observable on standard cone beam computed tomography (CBCT) during fractionated radiation therapy. Here, a method for automated assessment of tumor volume regression is presented and its potential use in response adapted personalized radiation therapy is evaluated empirically. Methods and Materials: Automated deformable registration with calculation of the Jacobian determinant was applied to serial CBCT scans in a series of 99 patients with NSCLC. Tumor volume at the end of treatment was estimated on the basis of the first one third and two thirds of the scans. The concordance between estimated and actual relative volume at the end of radiation therapy was quantified by Pearson's correlation coefficient. On the basis of the estimated relative volume, the patients were stratified into 2 groups having volume regressions below or above the population median value. Kaplan-Meier plots of locoregional disease-free rate and overall survival in the 2 groups were used to evaluate the predictive value of tumor regression during treatment. Cox proportional hazards model was used to adjust for other clinical characteristics. Results: Automatic measurement of the tumor regression from standard CBCT images was feasible. Pearson's correlation coefficient between manual and automatic measurement was 0.86 in a sample of 9 patients. Most patients experienced tumor volume regression, and this could be quantified early into the treatment course. Interestingly, patients with pronounced volume regression had worse locoregional tumor control and overall survival. This was significant on patient with non-adenocarcinoma histology. Conclusions: Evaluation of routinely acquired CBCT images during radiation therapy provides biological information on the specific tumor. This could potentially form the basis for personalized response adaptive therapy.

  8. Conditional Survival: An Assessment of the Prognosis of Patients at Time Points After Initial Diagnosis and Treatment of Locoregional Melanoma Metastasis.

    Science.gov (United States)

    Haydu, Lauren E; Scolyer, Richard A; Lo, Serigne; Quinn, Michael J; Saw, Robyn P M; Shannon, Kerwin F; Spillane, Andrew J; Stretch, Jonathan R; McCarthy, William H; Thompson, John F

    2017-05-20

    Purpose Standard cancer staging and prognostic estimates are determined at the time of the patient's initial disease presentation. Conditional survival is an alternative, dynamic assessment from follow-up time points after the initial disease diagnosis and is based on the condition of survivorship. Estimates of conditional survival can provide critical prognostic information for patients and clinicians, guide subsequent cancer follow-up schedules, and influence decisions regarding treatments. The current study presents conditional survival estimates developed from a cohort of 4,540 patients diagnosed with stage III melanoma treated at a single institution. Methods Patients with stage III disease at first melanoma diagnosis (initial; n = 2,042), or who developed locoregional metastasis as a first recurrence some time after primary diagnosis (recurrent; n = 2,498), were assessed. Conditional melanoma-specific survival (MSS) estimates up to 5 years after diagnosis were adjusted for age, sex, and 8th edition American Joint Committee on Cancer (AJCC) stage. Results Older age at diagnosis of stage III disease conveyed a worse prognosis at each conditional survival time point. Males had significantly worse MSS outcomes for up to 2 years of conditional survival, after which males and females had similar MSS. For patients with AJCC stage IIIB and stage IIIC disease, MSS outcomes were similar to those of patients with stage IIIA disease after 3 and 5 years of survivorship, respectively. Conclusion Adjuvant systemic treatments may have the greatest benefit when administered within the first 2 years of stage III melanoma diagnosis, during which period prognosis is significantly worse for male patients of increasing age and AJCC substage. Conditional survival estimates illustrate improved survival prospects for patients with cancer returning for follow-up and may define a finite period of increased risk after diagnosis.

  9. Impact on Loco-regional Control of Radiochemotherapeutic Sequence and Time to Initiation of Adjuvant Treatment in Stage II/III Rectal Cancer Patients Treated with Postoperative Concurrent Radiochemotherapy.

    Science.gov (United States)

    Kim, Haeyoung; Chie, Eui Kyu; Ahn, Yong Chan; Kim, Kyubo; Park, Won; Yoon, Won Sup; Huh, Seung Jae; Ha, Sung W

    2014-04-01

    This study was designed to evaluate the impact of radiochemotherapeutic sequence and time to initiation of adjuvant treatment on loco-regional control for resected stage II and III rectal cancer. Treatment outcomes for rectal cancer patients from two hospitals with different sequencing strategies regarding adjuvant concurrent radiochemotherapy (CRCT) were compared retrospectively. Pelvic radiotherapy was administered concurrently on the first (early CRCT, n=180) or the third cycle of chemotherapy (late CRCT, n=180). During radiotherapy, two cycles of fluorouracil were provided to patients in both groups. In the early CRCT group, median six cycles of fluorouracil and leucovorin were prescribed during the post-CRCT period. In the late CRCT group, two cycles of fluorouracil were administered in the pre- and post-CRCT periods. No significant differences in the 5-year loco-regional recurrence-free survival (LRRFS) (92.5% vs. 95.6%, p=0.43) or overall survival and disease-free survival were observed between groups. Patients who began receiving adjuvant treatment later than five weeks after surgery had lower LRRFS than patients who received adjuvant treatment within five weeks following surgery (79% vs. 91%, ploco-regional recurrence increased as the time to initiation of adjuvant treatment was delayed. In the current study, treatment outcomes were not significantly influenced by the sequence of adjuvant treatment but by the delay of adjuvant treatment for more than five weeks. Timely administration of adjuvant treatment is deemed important in achieving loco-regional tumor control for stage II/III rectal cancer patients.

  10. Pattern of loco-regional failure after definitive radiotherapy for non-small cell lung cancer

    DEFF Research Database (Denmark)

    Schytte, Tine; Nielsen, Tine Bjørn; Brink, Carsten

    2014-01-01

    Non-small cell lung cancer (NSCLC) is associated with poor survival even though patients are treated with curatively intended radiotherapy. Survival is affected negatively by lack of loco-regional tumour control, but survival is also influenced by comorbidity caused by age and smoking......, and occurrence of distant metastasis. It is challenging to evaluate loco-regional control after definitive radiotherapy for NSCLC since it is difficult to distinguish between radiation-induced damage to the lung tissue and tumour progression/recurrence. In addition it may be useful to distinguish between...... had loco-regional failure only. Of these patients, 68 had intrapulmonary failure only, one patient had failure in mediastinum only, and 24 patients had intrapulmonary failure as well as mediastinal failure. Of the patients which had lung failure only, 78% had mediastinal involvement at treatment start...

  11. Dose-Escalated Intensity-Modulated Radiotherapy Is Feasible and May Improve Locoregional Control and Laryngeal Preservation in Laryngo-Hypopharyngeal Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Miah, Aisha B.; Bhide, Shreerang A.; Guerrero-Urbano, M. Teresa [Head and Neck Unit, The Royal Marsden National Health Service (NHS) Foundation Trust, London (United Kingdom); Institute of Cancer Research, London (United Kingdom); Clark, Catharine; Bidmead, A. Margaret [Institute of Cancer Research, London (United Kingdom); Department of Physics, The Royal Marsden NHS Foundation Trust, London (United Kingdom); St Rose, Suzanne; Barbachano, Yolanda; A' Hern, Roger [Department of Statistics, The Royal Marsden NHS Foundation Trust, London (United Kingdom); Tanay, Mary; Hickey, Jennifer; Nicol, Robyn; Newbold, Kate L. [Head and Neck Unit, The Royal Marsden National Health Service (NHS) Foundation Trust, London (United Kingdom); Harrington, Kevin J. [Head and Neck Unit, The Royal Marsden National Health Service (NHS) Foundation Trust, London (United Kingdom); Institute of Cancer Research, London (United Kingdom); Nutting, Christopher M., E-mail: chris.nutting@rmh.nhs.uk [Head and Neck Unit, The Royal Marsden National Health Service (NHS) Foundation Trust, London (United Kingdom); Institute of Cancer Research, London (United Kingdom)

    2012-02-01

    Purpose: To determine the safety and outcomes of induction chemotherapy followed by dose-escalated intensity-modulated radiotherapy (IMRT) with concomitant chemotherapy in locally advanced squamous cell cancer of the larynx and hypopharynx (LA-SCCL/H). Methods and Materials: A sequential cohort Phase I/II trial design was used to evaluate moderate acceleration and dose escalation. Patients with LA-SCCL/H received IMRT at two dose levels (DL): DL1, 63 Gy/28 fractions (Fx) to planning target volume 1 (PTV1) and 51.8 Gy/28 Fx to PTV2; DL2, 67.2 Gy/28 Fx and 56 Gy/28 Fx to PTV1 and PTV2, respectively. Patients received induction cisplatin/5-fluorouracil and concomitant cisplatin. Acute and late toxicities and tumor control rates were recorded. Results: Between September 2002 and January 2008, 60 patients (29 DL1, 31 DL2) with Stage III (41% DL1, 52% DL2) and Stage IV (52% DL1, 48% DL2) disease were recruited. Median (range) follow-up for DL1 was 51.2 (12.1-77.3) months and for DL2 was 36.2 (4.2-63.3) months. Acute Grade 3 (G3) dysphagia was higher in DL2 (87% DL2 vs. 59% DL1), but other toxicities were equivalent. One patient in DL1 required dilatation of a pharyngeal stricture (G3 dysphagia). In DL2, 2 patients developed benign pharyngeal strictures at 1 year. One underwent a laryngo-pharyngectomy and the other a dilatation. No other G3/G4 toxicities were reported. Overall complete response was 79% (DL1) and 84% (DL2). Two-year locoregional progression-free survival rates were 64.2% (95% confidence interval, 43.5-78.9%) in DL1 and 78.4% (58.1-89.7%) in DL2. Two-year laryngeal preservation rates were 88.7% (68.5-96.3%) in DL1 and 96.4% (77.7-99.5%) in DL2. Conclusions: At a mean follow-up of 36 months, dose-escalated chemotherapy-IMRT at DL2 has so far been safe to deliver. In this study, DL2 delivered high rates of locoregional control, progression-free survival, and organ preservation and has been selected as the experimental arm in a Cancer Research UK Phase III

  12. Buccal mucosa carcinoma: surgical margin less than 3 mm, not 5 mm, predicts locoregional recurrence

    Directory of Open Access Journals (Sweden)

    Chiou Wen-Yen

    2010-09-01

    Full Text Available Abstract Background Most treatment failure of buccal mucosal cancer post surgery is locoregional recurrence. We tried to figure out how close the surgical margin being unsafe and needed further adjuvant treatment. Methods Between August 2000 and June 2008, a total of 110 patients with buccal mucosa carcinoma (25 with stage I, 31 with stage II, 11 with stage III, and 43 with Stage IV classified according to the American Joint Committee on Cancer 6th edition were treated with surgery alone (n = 32, surgery plus postoperative radiotherapy (n = 38 or surgery plus adjuvant concurrent chemoradiotherapy (n = 40. Main outcome measures: The primary endpoint was locoregional disease control. Results The median follow-up time at analysis was 25 months (range, 4-104 months. The 3-year locoregional control rates were significantly different when a 3-mm surgical margin (≤3 versus >3 mm, 71% versus 95%, p = 0.04 but not a 5-mm margin (75% versus 92%, p = 0.22 was used as the cut-off level. We also found a quantitative correlation between surgical margin and locoregional failure (hazard ratio, 2.16; 95% confidence interval, 1.14 - 4.11; p = 0.019. Multivariate analysis identified pN classification and surgical margin as independent factors affecting disease-free survival and locoregional control. Conclusions Narrow surgical margin ≤3 mm, but not 5 mm, is associated with high risk for locoregional recurrence of buccal mucosa carcinoma. More aggressive treatment after surgery is suggested.

  13. Combined heavy smoking and drinking predicts overall but not disease-free survival after curative resection of locoregional esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sun P

    2016-07-01

    Full Text Available Peng Sun,1,2,* Cui Chen,3,* Fei Zhang,1,2,* Hang Yang,1,2 Xi-Wen Bi,1,2 Xin An,1,2 Feng-Hua Wang,1,2 Wen-Qi Jiang1,2 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 2Department of Medical Oncology, Sun Yat-Sen University Cancer Center, 3Department of Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China *These authors contributed equally to this work Introduction: The prognostic impact of smoking and drinking on esophageal squamous cell carcinoma (ESCC was scarcely discussed. We investigated the prognostic value of smoking and drinking and their relationships with clinicopathological characteristics in a large cohort of patients with locoregional ESCC.Patients and methods: We retrospectively analyzed 488 patients who underwent curative treatment at a single institution between January 2007 and December 2008. A chi-square test was used to evaluate the relationships between smoking and drinking and clinicopathological variables, the Kaplan–Meier method was used for 5-year overall survival (OS and disease-free survival, and Cox proportional hazards models were applied for univariate and multivariate analyses of variables with respect to OS and disease-free survival.Results: Heavy smokers were more likely to have advanced Tumor-Node-Metastases (TNM stage and higher neutrophil/lymphocyte ratio at diagnosis (P<0.05. Drinkers were more likely to have advanced TNM stage, to present with a larger tumor, and to undergo multidisciplinary treatment (P<0.05. For patients who used neither heavy tobacco nor alcohol, used either tobacco or alcohol, and used both, the 5-year OS rates and OS times were 57.4%, 46.4%, and 39.1% (P<0.05 and not reached, 55.2 months, and 41.2 months (P<0.05, respectively. On multivariate analysis, patients who both heavily smoked and drank had 1.392 times the risk of dying during follow-up compared with

  14. Efficacy of neck dissection for locoregional failures versus isolated nodal failures in nasopharyngeal carcinoma.

    Science.gov (United States)

    Tsang, Raymond King Yin; Chung, Joseph Chun Kit; Ng, Yiu Wing; To, Victor Shing Howe; Ho, Ambrose Chung Wai; Chan, Jimmy Yu Wai; Ho, Wai Kuen; Wei, William Ignace

    2012-05-01

    Neck dissection has been shown to be effective in controlling nodal failures in nasopharyngeal carcinoma. Its efficacy in controlling the disease in patients with synchronous locoregional failure is, however, not documented. A retrospective review of all patients who underwent neck dissection for nodal failures with or without treated local failure within 6 months was conducted for this study. The survivals of these 2 groups of patients were analyzed. The 5-year overall survival of the whole cohort was 58%. There was no difference in 5-year disease specific survival (68% vs 40%; p = .121) and 5-year progression free survival (44% vs 36%; p = .334) when comparing patients with isolated nodal failures and synchronous locoregional failures. Multivariate analysis showed that only the initial N classification affects survival. Neck dissection is efficacious in patients with nasopharyngeal carcinoma with nodal failure, with or without synchronous local failures. Copyright © 2011 Wiley Periodicals, Inc.

  15. Loco-Regional Control With Complete Resection and Tongue Reconstruction on the Malignant Melanoma in the Tongue.

    Science.gov (United States)

    Alkaff, Tuqa; Jeong, Woo Shik; Nam, Soon Yuhl; Choi, Jong Woo

    2017-07-01

    Primary malignant melanoma in the tongue is very uncommon disease that is considered low in comparison to cutaneous melanoma. In this report, the authors described a case of the hemitongue reconstruction with fasciocutaneous free flap on the patient who suffered from the malignant melanoma primarily originating from the base of the tongue that was treated with surgery and radiotherapy but developed a lung metastasis. A 76-year-old man was referred to the otorhinolaryngology clinic after complaining of a painful mass present for 3 months on the right side of the tongue. A punch biopsy was revealed atypical cells with pigmentation that is consistent with malignant melanoma. After wide excision and bilateral neck dissection performed, hemipartial tongue reconstruction was done using a radial forearm free flap. The patient had an uneventful recovery and received a course of radiotherapy along with follow-up examinations for 3 years. The authors report this rare patient for providing the other surgeons with the useful information regarding the management of the malignant melanoma on the tongue with free flap reconstruction which turned out to be successful in loco-regional control.

  16. Pretreatment quality of life predicts for locoregional control in head and neck cancer patients : A radiation therapy oncology group analysis

    NARCIS (Netherlands)

    Siddiqui, Farzan; Pajak, Thomas F.; Watkins-Bruner, Deborah; Konski, Andre A.; Coyne, James C.; Gwede, Clement K.; Garden, Adam S.; Spencer, Sharon A.; Jones, Christopher; Movsas, Benjamin

    2008-01-01

    Purpose: To analyze the prospectively collected health-related quality-of-life (HRQOL) data from patients enrolled in two Radiation Therapy Oncology Group randomized Phase III head and neck cancer trials (90-03 and 91-11) to assess their value as an independent prognostic factor for locoregional

  17. Definitive Reirradiation for Locoregionally Recurrent Non-Small Cell Lung Cancer With Proton Beam Therapy or Intensity Modulated Radiation Therapy: Predictors of High-Grade Toxicity and Survival Outcomes

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    McAvoy, Sarah; Ciura, Katherine; Wei, Caimiao; Rineer, Justin; Liao, Zhongxing; Chang, Joe Y.; Palmer, Matthew B.; Cox, James D.; Komaki, Ritsuko; Gomez, Daniel R., E-mail: DGomez@mdanderson.org

    2014-11-15

    Purpose: Intrathoracic recurrence of non-small cell lung cancer (NSCLC) after initial treatment remains a dominant cause of death. We report our experience using proton beam therapy and intensity modulated radiation therapy for reirradiation in such cases, focusing on patterns of failure, criteria for patient selection, and predictors of toxicity. Methods and Materials: A total of 102 patients underwent reirradiation for intrathoracic recurrent NSCLC at a single institution. All doses were recalculated to an equivalent dose in 2-Gy fractions (EQD2). All patients had received radiation therapy for NSCLC (median initial dose of 70 EQD2 Gy), with median interval to reirradiation of 17 months and median reirradiation dose of 60.48 EQD2 Gy. Median follow-up time was 6.5 months (range, 0-72 months). Results: Ninety-nine patients (97%) completed reirradiation. Median local failure-free survival, distant metastasis-free survival (DMFS), and overall survival times were 11.43 months (range, 8.6-22.66 months), 11.43 months (range, 6.83-23.84 months), and 14.71 (range, 10.34-20.56 months), respectively. Toxicity was acceptable, with rates of grade ≥3 esophageal toxicity of 7% and grade ≥3 pulmonary toxicity of 10%. Of the patients who developed local failure after reirradiation, 88% had failure in either the original or the reirradiation field. Poor local control was associated with T4 disease, squamous histology, and Eastern Cooperative Oncology Group performance status score >1. Concurrent chemotherapy improved DMFS, but T4 disease was associated with poor DMFS. Higher T status, Eastern Cooperative Oncology Group performance status ≥1, squamous histology, and larger reirradiation target volumes led to worse overall survival; receipt of concurrent chemotherapy and higher EQD2 were associated with improved OS. Conclusions: Intensity modulated radiation therapy and proton beam therapy are options for treating recurrent non-small cell lung cancer. However, rates of

  18. Association of Locoregional Control With High Body Mass Index in Women Undergoing Breast Conservation Therapy for Early-Stage Breast Cancer

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    Bergom, Carmen; Kelly, Tracy; Bedi, Meena; Saeed, Hina; Prior, Phillip [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Rein, Lisa E.; Szabo, Aniko [Division of Biostatistics, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Wilson, J. Frank; Currey, Adam D. [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); White, Julia, E-mail: Julia.White@osumc.edu [Department of Radiation Oncology, James Cancer Hospital, Ohio State University Comprehensive Cancer Center, Columbus, Ohio (United States)

    2016-09-01

    Purpose: Obesity, as measured by the body mass index (BMI), is a risk factor for distant recurrence and decreased survival in breast cancer. We sought to determine whether the BMI correlated with local recurrence and reduced survival in a cohort of predominantly obese women treated with breast conservation therapy. Methods and Materials: From 1998 to 2010, 154 women with early-stage invasive breast cancer and 39 patients with ductal carcinoma in situ underwent prone whole breast irradiation. Cox proportional hazards regression, Kaplan-Meier methods with the log-rank test, and multivariate analysis were used to explore the association of the outcomes with the BMI. Results: The median patient age was 60 years, and the median follow-up duration was 73 months. The median BMI was 33.2 kg/m{sup 2}; 91% of the patients were overweight (BMI ≥25 kg/m{sup 2}) and 69% of the patients were clinically obese (BMI ≥30 kg/m{sup 2}). The BMI was significantly associated with the locoregional recurrence-free interval for patients with invasive cancer and ductal carcinoma in situ (hazard ratio [HR], 1.09; P=.047). Also, a trend was seen for increased locoregional recurrence with a higher BMI (P=.09) for patients with invasive disease, which was significant when examining the outcomes with a BMI stratified by the median value of 33.2 kg/m{sup 2} (P=.008). A greater BMI was also significantly associated with decreased distant recurrence-free interval (HR, 1.09; P=.011) and overall survival (HR, 1.09; P=.004); this association remained on multivariate analysis (distant recurrence-free interval, P=.034; overall survival, P=.0007). Conclusions: These data suggest that the BMI might affect the rate of locoregional recurrence in breast cancer patients. A higher BMI predicted a worse distant recurrence-free interval and overall survival. The present investigation adds to the increasing evidence that BMI is an important prognostic factor in early-stage breast cancer treated with

  19. Survivability of SCADA Control Loop

    NARCIS (Netherlands)

    Camacho, José; de Boer, Pieter-Tjerk; Remke, Anne Katharina Ingrid

    2009-01-01

    The endorsement of information technologies for critical infrastructures control introduces new threats in their security and surveillance. Along with certain level of protection against attacks, it is desirable for critical processes to survive even if they succeed. A stochastic Petri Nets-based

  20. Dose-Response Relationship between Radiation Dose and Loco-regional Control in Patients with Stage II-III Esophageal Cancer Treated with Definitive Chemoradiotherapy.

    Science.gov (United States)

    Kim, Hyun Ju; Suh, Yang-Gun; Lee, Yong Chan; Lee, Sang Kil; Shin, Sung Kwan; Cho, Byung Chul; Lee, Chang Geol

    2017-07-01

    The correlation between radiation dose and loco-regional control (LRC) was evaluated in patients with stage II-III esophageal cancer treated with definitive concurrent chemoradiotherapy (CRT). Medical records of 236 stage II-III esophageal cancer patients treated with definitive CRT at Yonsei Cancer Center between 1994 and 2013 were retrospectively reviewed. Among these, 120 received a radiation dose of 60 Gy) is associated with increased LRC, PFS, and OS in patients with stage II-III esophageal cancer treated with definitive CRT.

  1. Intensity-modulated radiation therapy for T4 nasopharyngeal carcinoma. Treatment results and locoregional

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    Chen, J.L.Y.; Tsai, C.L.; Chen, W.Y.; Wang, C.W. [National Taiwan Univ. Hospital, Taipei (China). Div. of Radiation Oncology; Huang, Y.S.; Chen, Y.F. [National Taiwan Univ. Hospital, Taipei (China). Dept. of Medical Imaging; Kuo, S.H. [National Taiwan Univ. Hospital, Taipei (China). Div. of Radiation Oncology; National Taiwan Univ. College of Medicine, Taipei (China). Graduate Inst. of Clinical Medicine; Hong, R.L. [National Taiwan Univ. Hospital, Taipei (China). Div. of Medical Oncology; Ko, J.Y.; Lou, P.J. [National Taiwan Univ. Hospital, Taipei (China). Dept. of Otolaryngology

    2013-12-15

    Purpose: The purpose of this work was to examine outcomes in patients with T4 nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). Methods and materials: Between 2007 and 2010, 154 patients with nonmetastatic T4 NPC were treated with IMRT to a total dose of 70 Gy in 33-35 fractions. In addition, 97 % of patients received concurrent platinum-based chemotherapy. The median follow-up time was 52.8 months. Results: The rates of 5-year actuarial locoregional control, distant metastasis-free survival, progression free-survival, and overall survival (OS) were 81.2, 72.2, 61.9, and 78.1 %, respectively. A total of 27 patients had locoregional recurrence: 85.2 % in-field failures, 11.1 % marginal failures, and 3.7 % out-of-field failures. Fourteen patients with locoregional recurrence received aggressive treatments, including nasopharyngectomy, neck dissection, or re-irradiation, and the 5-year OS rate tended to be better (61.9 %) compared to those receiving conservative treatment (32.0 %, p = 0.051). In patients treated with 1 course of radiotherapy, grade {>=} 3 toxicities of ototoxicity, neck fibrosis, xerostomia, epistaxis, and radiographic temporal lobe necrosis occurred in 18.2, 9.8, 6.3, 2.1, and 5.6 % of patients, respectively. Increased ototoxicity, osteonecrosis, severe nasal bleeding, and temporal necrosis were observed in patients treated by re-irradiation. Conclusion: IMRT offers good locoregional control in patients with T4 NPC. For patients with locoregional recurrence after definitive radiotherapy, aggressive local treatment may be considered for a better outcome. (orig.)

  2. Pattern of loco-regional failure after definitive radiotherapy for non-small cell lung cancer.

    Science.gov (United States)

    Schytte, Tine; Nielsen, Tine Bjørn; Brink, Carsten; Hansen, Olfred

    2014-03-01

    Non-small cell lung cancer (NSCLC) is associated with poor survival even though patients are treated with curatively intended radiotherapy. Survival is affected negatively by lack of loco-regional tumour control, but survival is also influenced by comorbidity caused by age and smoking, and occurrence of distant metastasis. It is challenging to evaluate loco-regional control after definitive radiotherapy for NSCLC since it is difficult to distinguish between radiation-induced damage to the lung tissue and tumour progression/recurrence. In addition it may be useful to distinguish between intrapulmonary failure and mediastinal failure to be able to optimize radiotherapy in order to improve loco-regional control even though it is not easy to discriminate between the two sites of failure. This study is a retrospective analysis of 331 NSCLC patients treated with definitive radiotherapy from 2002 to 2011. The patients were treated consecutively at the Department of Oncology, Odense University Hospital, Denmark with at least 60 Gy. All patients were followed in a planned follow-up schedule and no patients were lost for follow-up. At the time of the analysis 93 patients had loco-regional failure only. Of these patients, 68 had intrapulmonary failure only, one patient had failure in mediastinum only, and 24 patients had intrapulmonary failure as well as mediastinal failure. Of the patients which had lung failure only, 78% had mediastinal involvement at treatment start. The only covariate with significant impact on developing intrapulmonary failure only was gross tumour volume. Median survival for the total group of 331 patients was 19 months. The median survival for patients with intrapulmonary failure only was 19 months, and it was 20 months for the patients with mediastinal relapse. We conclude that focus should be on increasing doses to intrapulmonary tumour volume, when dose escalation is applied to improve local tumour control in NSCLC patients treated with definitive

  3. [Postoperative external beam radiotherapy for medullary thyroid carcinoma with high risk of locoregional relapse].

    Science.gov (United States)

    Compagnon, F; Zerdoud, S; Rives, M; Laprie, A; Sarini, J; Grunenwald, S; Chaltiel, L; Graff, P

    2016-07-01

    To assess the outcome of locally advanced medullary thyroid carcinoma treated with surgery and adjuvant external beam radiotherapy. Twenty-nine consecutive patients with non-metastatic medullary thyroid carcinoma treated in our institution between January 1995 and December 2012 were retrospectively evaluated. All underwent curative-intended optimal surgery, followed by external beam radiotherapy because of high risk of locoregional relapse. Twelve patients were stage III, 16 IVa and 1 IVb. Positive surgical margins were present in 11 cases (10 R1 and 1 R2). Median and average preradiotherapy serum calcitonin were 141pg/mL and 699pg/mL, respectively. Fourteen patients received 3D-conformal radiotherapy and 15 received intensity-modulated radiotherapy. Median prescribed dose was 63Gy to the high-risk volumes and 54Gy to the low-risk volumes. Treatment was delivered in 30 fractions. The median gap between surgery and radiotherapy was 1.9months. Median follow-up was 76.4months. Kaplan-Meier estimates of 5-year locoregional relapse-free survival and overall survival were 79 and 96 %, respectively. Among the five locoregional relapses, two were related to a macroscopic metastatic cervical lymph node that was unfortunately not removed during the lymphadenectomy. Eight of ten patients with microscopic positive margins (R1) were controlled regarding the thyroidectomy bed. Eight patients had normal serum calcitonin after external beam radiotherapy, of whom only one developed a locoregional relapse during follow-up. Regarding the 21 patients with persistent positive serum calcitonin after treatment, only ten developed a macroscopic locoregional or distant relapse. One grade III and no grade IV acute morbidity were reported. Fifteen patients reported grade II chronic morbidity and no grade III/IV. Maximal surgery followed by adjuvant external beam radiotherapy as a treatment for locally advanced medullary thyroid carcinoma provides a high rate of long

  4. Role of tumour-free margin distance for loco-regional control in vulvar cancer-a subset analysis of the Arbeitsgemeinschaft Gynakologische Onkologie CaRE-1 multicenter study

    NARCIS (Netherlands)

    Woelber, Linn; Griebel, Lis-Femke; Eulenburg, Christine; Sehouli, Jalid; Jueckstock, Julia; Hilpert, Felix; de Gregorio, Nikolaus; Hasenburg, Annette; Ignatov, Atanas; Hillemanns, Peter; Fuerst, Sophie; Strauss, Hans-Georg; Baumann, Klaus H.; Thiel, Falk C.; Mustea, Alexander; Meier, Werner; Harter, Philipp; Wimberger, Pauline; Hanker, Lars Christian; Schmalfeldt, Barbara; Canzler, Ulrich; Fehm, Tanja; Luyten, Alexander; Hellriegel, Martin; Kosse, Jens; Heiss, Christoph; Hantschmann, Peer; Mallmann, Peter; Tanner, Berno; Pfisterer, Jacobus; Richter, Barbara; Neuser, Petra; Mahner, Sven

    2016-01-01

    Aim of the study: A tumour-free pathological resection margin of >= 8 mm is considered state-of-the-art. Available evidence is based on heterogeneous cohorts. This study was designed to clarify the relevance of the resection margin for loco-regional control in vulvar cancer. Methods: AGO-CaRE-1 is a

  5. Breast radiotherapy as part of loco-regional treatments in stage IV breast cancer patients with oligometastatic disease.

    Science.gov (United States)

    Bourgier, Céline; Khodari, Wassim; Vataire, Anne-Lise; Pessoa, Eduardo Lima; Dunant, Ariane; Delaloge, Suzette; Uzan, Catherine; Balleyguier, Corinne; Mathieu, Marie-Christine; Marsiglia, Hugo; Arriagada, Rodrigo

    2010-08-01

    Local treatments seem to improve metastasis progression-free survival (MPFS) and overall survival (OS) when added to systemic therapies in stage IV breast cancer. From 1990 to 2003, we reviewed 9138 cases treated and registered in the Institut Gustave-Roussy breast cancer database. Among them, 308 had presented with stage IV disease. Eighty percent of patients (n=239) had received a loco-regional treatment and they were categorized into two groups: loco-regional radiotherapy (LRRT) alone (Group 1; n=147) or breast and axillary surgery+/-LRRT (Group 2; n=92). The median follow-up was 6.5 years. LRRT obtained a long-standing loco-regional clinical response in 85% of patients. The 3-year MPFS rates were 20% in Group 1 and 39% in Group 2; the 3-year OS rates were 39% and 57%, respectively. However, no significant differences in MPFS or OS were observed between the two groups when adjusted on prognostic factors. Radiation therapy alone provides long-standing local control and yields MPFS and OS rates equivalent to those obtained when radiation therapy is combined with surgery, whatever the prognostic factors. Loco-regional therapies, especially radiation therapy alone, may have an important role to play in the treatment of selected patients with stage IV breast cancer. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  6. Tumor volume as a prognostic factor for local control and overall survival in advanced larynx cancer.

    Science.gov (United States)

    Timmermans, Adriana J; Lange, Charlotte A H; de Bois, Josien A; van Werkhoven, Erik; Hamming-Vrieze, Olga; Hilgers, Frans J M; van den Brekel, Michiel W M

    2016-02-01

    Tumor volume has been postulated to be an important prognostic factor for oncological outcome after radiotherapy or chemoradiotherapy. This postulate was retrospectively investigated in a consecutively treated cohort of T3-T4 larynx cancer patients. Retrospective cohort study. For 166 patients with T3-T4 larynx cancer (1999-2008), pretreatment computed tomography and magnetic resonance imaging scans were available for tumor volume delineation. Patients were treated with radiotherapy, chemoradiotherapy, or total laryngectomy with postoperative radiotherapy. Both a dedicated head and neck radiologist and the first author determined all tumor volumes. Statistical analysis was by Kaplan-Meier plots and Cox proportional hazard models. Patients with T3 larynx cancer had significantly smaller tumor volumes than patients with T4 larynx cancer (median = 8.1 cm(3) and 15.8 cm(3), respectively; P < .0001). In the group treated with total laryngectomy and postoperative radiotherapy, no association was found between tumor volume and local or locoregional control or overall survival. In the group treated with radiotherapy, a nonsignificant trend was observed between local control and tumor volume. In the chemoradiotherapy group, however, a significant impact of tumor volume was found on local control (hazard ratio = 1.07; 95% confidence interval = 1.01-1.13; P = .028). Tumor volume was not significantly associated with local control, locoregional control, or overall survival in the surgically treated group. In the group treated with radiotherapy, there was no statistically significant association, but a trend was observed between local control and tumor volume. Only in patients treated with concurrent chemoradiotherapy was a significant impact of tumor volume on local control found. 4. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  7. Embryologically based radical hysterectomy as peritoneal mesometrial resection (PMMR) with pelvic and para-aortic lymphadenectomy for loco-regional tumor control in endometrial cancer: first evidence for efficacy.

    Science.gov (United States)

    Kimmig, Rainer; Iannaccone, Antonella; Aktas, Bahriye; Buderath, Paul; Heubner, Martin

    2016-07-01

    To evaluate the feasibility and efficacy of embryologically based compartmental surgery for locoregional tumor control in intermediate and high risk endometrial cancer: peritoneal mesometrial resection with therapeutic pelvic and para-aortic lymphadenectomy by robotically assisted laparoscopy. 75 consecutive surgically treated patients with uterine malignancies have been analyzed. 68 patients with histologically proven endometrial cancer and complete robotically assisted surgery have been included in this study on morbidity and oncological outcome. 56 % of the patients were at intermediate/high risk with either stage IAG3 or IB (n = 22) or stage II-IV (n = 16). Adjuvant EBRT was offered to three patients only (4 %), whereas five received isolated vaginal brachytherapy (7 %). Indocyanine-green (ICG) fluorescence lymphography is demonstrated being useful for additional intraoperative visualization of the compartment borders and lymphatic drainage to the postponed lymph compartments. After a mean follow-up of 32 months, there were only two loco-regional recurrences (2.9 %). Both recurrences were apparently cured by salvage therapy. 9 patients died; 6 (8.8 %) from metastatic disease (5) or unknown cause (1), 3 (4.4 %) from intercurrent disease without evidence of disease. One patient (1.4 %) experienced a peritoneal carcinosis and is alive. There were 8/68 perioperative complications (12 %). No perioperative mortality was observed. Embryologically defined compartmental surgery by robotically assisted laparoscopy seems to be feasible and safe in endometrial cancer. The low loco-regional recurrence rate of 2.9 % in spite of a very low percentage of adjuvant radiotherapy and 56 % of intermediate/high risk tumors should stimulate to initiate a multicentre trial to evaluate the value of compartmental surgery for prevention of locoregional recurrence in endometrial cancer.

  8. Comparative Long-term Study of a Large Series of Patients with Invasive Ductal Carcinoma and Invasive Lobular Carcinoma. Loco-Regional Recurrence, Metastasis, and Survival.

    Science.gov (United States)

    García-Fernández, Antonio; Lain, Josep María; Chabrera, Carol; García Font, Marc; Fraile, Manel; Barco, Israel; Torras, Merçe; Reñe, Asumpta; González, Sonia; González, Clarissa; Piqueras, Mercedes; Veloso, Enrique; Cirera, Lluís; Pessarrodona, Antoni; Giménez, Nuria

    2015-01-01

    Our aim was to compare histologic and immunohistochemical features, surgical treatment and clinical course, including disease recurrence, distant metastases, and mortality between patients with invasive ductal carcinoma (IDC) or invasive lobular carcinoma (ILC). We included 1,745 patients operated for 1,789 breast tumors, with 1,639 IDC (1,600 patients) and 145 patients with ILC and 150 breast tumors. The median follow-up was 76 months. ILC was significantly more likely to be associated with a favorable phenotype. Prevalence of contralateral breast cancer was slightly higher for ILC patients than for IDC patients (4.0% versus 3.2%; p = n.s). ILC was more likely multifocal, estrogen receptor positive, Human Epidermal Growth Factor Receptor-2 (HER2) negative, and with lower proliferative index compared to IDC. Considering conservative surgery, ILC patients required more frequently re-excision and/or mastectomy. Prevalence of stage IIB and III stages were significantly more frequent in ILC patients than in IDC patients (37.4% versus 25.3%, p = 0.006). Positive nodes were significantly more frequent in the ILC patients (44.6% versus 37.0%, p = 0.04). After adjustment for tumor size and nodal status, frequencies of recurrence/metastasis, disease-free and specific survival were similar among patients with IDC and patients with ILC. In conclusion, women with ILC do not have worse clinical outcomes than their counterparts with IDC. Management decisions should be based on individual patient and tumor biologic characteristics rather than on lobular versus ductal histology. © 2015 Wiley Periodicals, Inc.

  9. Elective nodal irradiation is not necessary in chemoradiotherapy for postoperative loco-regional recurrent esophageal cancer.

    Science.gov (United States)

    Jingu, Keiichi; Umezawa, Rei; Yamamoto, Takaya; Matsushita, Haruo; Ishikawa, Youjirou; Kozumi, Maiko; Kubozono, Masaki; Takahashi, Noriyoshi; Kadoya, Noriyuki; Takeda, Ken

    2017-03-01

    The purposes of the present study were to evaluate prognostic factors for patients with postoperative loco-regional recurrent esophageal cancer treated with chemoradiotherapy by multivariate analysis and to determine which irradiation is better, involved field irradiation or elective nodal irradiation, by matched-pair analysis. We reviewed records for 80 patients with postoperative loco-regional recurrent esophageal cancer treated by chemoradiotherapy between 2000 and 2014. The median follow-up period was 62.0 months. Thirty-one cases were treated with elective nodal irradiation and were randomly matched by risk factors to 49 cases treated with involved field irradiation (1:1). Fifty-one patients had disease recurrence again, and irradiated-field failure was observed in 26 patients. The 5-year overall survival rate was 30.5% with a median survival period of 26.5 months. Grade 3 or higher late toxicity was observed in only one patient. In multivariate analysis, short disease-free interval and anastomotic recurrence were statistically significant unfavorable prognostic factors for overall survival (hazard ratios: 2.1 and 2.5, respectively). Matched-pair analysis including disease-free interval, pattern of recurrence and number of recurrent regions revealed that overall survival rate and irradiated-field control rate in patients treated with involved field irradiation were significantly better than those in patients treated with elective nodal irradiation (P = 0.016 and P = 0.014, respectively). Short disease-free interval and anastomotic recurrence are unfavorable factors and elective nodal irradiation is not necessary in chemoradiotherapy for patients with postoperative loco-regional recurrent esophageal cancer.

  10. P-cadherin as prognostic factor for loco-regional relapse in breast cancer.

    Science.gov (United States)

    Faria, Gil; Cardoso, Maria João; Martins, Diana; Bettencourt, Herberto; Amendoeira, Isabel; Schimitt, Fernando

    2012-01-01

    Breast cancer is the most frequent malignant tumor and the leading cause of cancer death in women in Portugal. Due to its relation to an increase in distant metastasis and subsequent death, loco-regional relapse is one major concern in breast cancer women. Several classic prognostic factors as tumour size, nodal stage, histological grade, HER2 status and hormonal receptors have been identified as the most important factors for determining loco-regional relapse, disease free and overall survival. However, there is heterogeneity in prognosis and tumor behaviour in patients with identical disease staging and a similar pattern of expression of known molecular markers, hence the need to discover new prognostic factors. One of the possibilities is P-cadherin, already described by researchers as a possible independent marker of prognosis in breast cancer. The aim of this work was to study in a retrospective series of patients the correlation of P-cadherin expression with loco-regional recurrence in breast cancer women. We analyzed the clinical records of 1432 consecutive patients with breast cancer and treated in a University Hospital over a 10 year period. Patients with loco-regional relapse (n=101) without prior or simultaneous distant disease were selected as case group. Control group consisted of patients with more than 10 years follow-up and without disease progression. For both groups demographic, clinical, pathological and molecular markers were analyzed. Tissue micro-arrays were constructed to study P-cadherin expression from 86 tumors with available paraffin embedded blocks. Mean time to recurrence was 41 months and mean survival time after recurrence was 33 months, with a 5-year survival rate of 55%. Tumour size, nodal status and histological grade were identified as independent markers of prognosis. P-cadherin was associated with higher histological grades and hormone negative tumours. P-cadherin was identified as an independent prognostic marker for disease

  11. Comparison of detection methods for HPV status as a prognostic marker for loco-regional control after radiochemotherapy in patients with HNSCC.

    Science.gov (United States)

    Linge, Annett; Schötz, Ulrike; Löck, Steffen; Lohaus, Fabian; Neubeck, Cläre von; Gudziol, Volker; Nowak, Alexander; Tinhofer, Inge; Budach, Volker; Sak, Ali; Stuschke, Martin; Balermpas, Panagiotis; Rödel, Claus; Bunea, Hatice; Grosu, Anca-Ligia; Abdollahi, Amir; Debus, Jürgen; Ganswindt, Ute; Lauber, Kirsten; Pigorsch, Steffi; Combs, Stephanie E; Mönnich, David; Zips, Daniel; Baretton, Gustavo B; Buchholz, Frank; Krause, Mechthild; Belka, Claus; Baumann, Michael

    2017-12-30

    To compare six HPV detection methods in pre-treatment FFPE tumour samples from patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who received postoperative (N = 175) or primary (N = 90) radiochemotherapy. HPV analyses included detection of (i) HPV16 E6/E7 RNA, (ii) HPV16 DNA (PCR-based arrays, A-PCR), (iii) HPV DNA (GP5+/GP6+ qPCR, (GP-PCR)), (iv) p16 (immunohistochemistry, p16 IHC), (v) combining p16 IHC and the A-PCR result and (vi) combining p16 IHC and the GP-PCR result. Differences between HPV positive and negative subgroups were evaluated for the primary endpoint loco-regional control (LRC) using Cox regression. Correlation between the HPV detection methods was high (chi-squared test, p < 0.001). While p16 IHC analysis resulted in several false positive classifications, A-PCR, GP-PCR and the combination of p16 IHC and A-PCR or GP-PCR led to results comparable to RNA analysis. In both cohorts, Cox regression analyses revealed significantly prolonged LRC for patients with HPV positive tumours irrespective of the detection method. The most stringent classification was obtained by detection of HPV16 RNA, or combining p16 IHC with A-PCR or GP-PCR. This approach revealed the lowest rate of recurrence in patients with tumours classified as HPV positive and therefore appears most suited for patient stratification in HPV-based clinical studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Concurrent chemotherapy and intensity-modulated radiotherapy for organ preservation of locoregionally advanced oral cavity cancer.

    Science.gov (United States)

    Pederson, Aaron W; Salama, Joseph K; Witt, Mary Ellen; Stenson, Kerstin M; Blair, Elizabeth A; Vokes, Everett E; Haraf, Daniel J

    2011-08-01

    To report outcomes of oral cavity cancer patients treated with concurrent chemotherapy and intensity-modulated radiotherapy (chemoIMRT). Between 2001 and 2004, 21 patients with oral cavity squamous cell carcinoma underwent definitive chemoIMRT. Sites included were oral tongue (n = 9), floor of mouth (n = 6), buccal mucosa (n = 3), retromolar trigone (n = 2), and hard palate (n = 1). Most had stage III-IV disease (n = 20). The most common regimen was 5 days infusional 5-fluorouracil (600 mg/m(2)/d × 5 days), hydroxyurea (500 mg, PO BID), and 1.5 Gy twice-daily irradiation to 72 to 75 Gy. The median follow-up for surviving patients was 60 months. Treatment failure occurred as follows: local-1, regional-1, and distant metastases-2. The 2- and 5-year estimates of locoregional progression-free survival, disease-free survival, and overall survival were 90% and 90%, 71% and 71%, and 76% and 76%, respectively. Late complications included osteoradionecrosis (3 patients, 14%). Concurrent chemoIMRT results in promising locoregional control for oral cavity squamous cell carcinomas with acceptable toxicity.

  13. Loco-regional recurrence from colon cancer: a population-based study.

    Science.gov (United States)

    Sjövall, Annika; Granath, Fredrik; Cedermark, Björn; Glimelius, Bengt; Holm, Torbjörn

    2007-02-01

    The survival after colon cancer surgery has not improved to the same extent as after rectal cancer treatment and studies on loco-regional recurrence after colon cancer surgery are scarce. The aim of this study was to assess the problem of loco-regional recurrence after potentially curative resections for colon cancer, regarding incidence, risk factors, management, and outcome. All 1,856 patients submitted to potentially curative surgery for colon cancer in the Stockholm/Gotland region in Sweden between 1996 and 2000 were followed until January 2005 or until death. Follow-up data were prospectively collected. Risk factors for loco-regional recurrences were analyzed, treatment and outcome for patients with recurrence was studied. The cumulative 5-year incidence of loco-regional recurrence was 11.5%. Tumor locations in the right flexure and in the sigmoid colon, bowel perforation and emergent surgery were identified as independent risk factors for loco-regional recurrence. The risk also increased with increasing T- and N-stage. The median survival for all 192 patients with loco-regional recurrence was 9 months. Surgery was performed in 110 (57%) patients. In 23 (12%) patients a complete tumor clearance was achieved and the estimated 5-year survival in this group was 43%. Loco-regional recurrence from colon cancer is a significant clinical problem. A multidisciplinary treatment approach, including preoperative staging, a complete resection of the recurrence and more effective adjuvant treatments may improve the outcome.

  14. Locoregionally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy plus concurrent weekly cisplatin with or without neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Wee, Chan Woo; Keam, Bhum Suk; Heo, Dae Seog; Sung, Myung Whun; Won, Tae Bin; Wu, Hong Gyun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2015-06-15

    The outcomes of locoregionally advanced nasopharyngeal carcinoma patients treated with concurrent chemoradiation (CCRT) using intensity-modulated radiotherapy (IMRT) with/without neoadjuvant chemotherapy (NCT) were evaluated. Eighty-three patients who underwent NCT followed by CCRT (49%) or CCRT with/without adjuvant chemotherapy (51%) were reviewed. To the gross tumor, 67.5 Gy was prescribed. Weekly cisplatin was used as concurrent chemotherapy. With a median follow-up of 49.4 months, the 5-year local control, regional control, distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival rates were 94.7%, 89.3%, 77.8%, 68.0%, and 81.8%, respectively. In multivariate analysis, the American Joint Committee on Cancer stage (p = 0.016) and N stage (p = 0.001) were negative factors for DMFS and DFS, respectively. Overall, NCT demonstrated no benefit and an increased risk of severe hematologic toxicity. However, compared to patients treated with CCRT alone, NCT showed potential of improving DMFS in stage IV patients. CCRT using IMRT resulted in excellent local control and survival outcome. Without evidence of survival benefit from phase III randomized trials, NCT should be carefully administered in locoregionally advanced nasopharyngeal carcinoma patients who are at high-risk of developing distant metastasis and radiotherapy-related mucositis. The results of ongoing trials are awaited.

  15. Predictors of loco-regional recurrence and cancer-related death after breast cancer surgery.

    Science.gov (United States)

    Rausei, Stefano; Rovera, Francesca; Dionigi, Gianlorenzo; Tornese, Deborah; Fachinetti, Anna; Boni, Luigi; Dionigi, Renzo

    2010-01-01

    To determine which tumor-related factors might predispose the patient to loco-regional recurrence or death and the impact of these factors on the different types of events. We retrospectively analyzed the data of 1991 women between January 1998 and March 2010 for a first primary nonmetastatic breast cancer and treated with surgery and neo-adjuvant/adjuvant therapy. The overall survival distribution was estimated using the Kaplan-Meier method. The prognostic impact of several factors on cumulative overall and loco-regional recurrence free survival was evaluated by univariate (log-rank test) and multivariate analysis (Cox regression). At log-rank test, pT, nodal status, histotype, grading, lymphangioinvasive growth, tumor diameter, estrogen receptors (ER) status, progesterone receptors (PR) status, expression of Ki67, and expression of Her2/neu had a prognostic value on loco-regional recurrence or overall survival. In the multivariate analysis grading remained the only independent predictor of loco-regional recurrences. With regard to overall survival, the Cox model selected grading along with nodal status and PR status. Loco-regional recurrences after breast cancer surgery are not frequent events. They are markers of tumor aggressiveness and predictor of an increased likelihood of cancer-related death. However, loco-regional recurrence and systemic tumor progression are partially independent events, since some prognostic factors differ. © 2010 Wiley Periodicals, Inc.

  16. Role of tumour-free margin distance for loco-regional control in vulvar cancer-a subset analysis of the Arbeitsgemeinschaft Gynäkologische Onkologie CaRE-1 multicenter study.

    Science.gov (United States)

    Woelber, Linn; Griebel, Lis-Femke; Eulenburg, Christine; Sehouli, Jalid; Jueckstock, Julia; Hilpert, Felix; de Gregorio, Nikolaus; Hasenburg, Annette; Ignatov, Atanas; Hillemanns, Peter; Fuerst, Sophie; Strauss, Hans-Georg; Baumann, Klaus H; Thiel, Falk C; Mustea, Alexander; Meier, Werner; Harter, Philipp; Wimberger, Pauline; Hanker, Lars Christian; Schmalfeldt, Barbara; Canzler, Ulrich; Fehm, Tanja; Luyten, Alexander; Hellriegel, Martin; Kosse, Jens; Heiss, Christoph; Hantschmann, Peer; Mallmann, Peter; Tanner, Berno; Pfisterer, Jacobus; Richter, Barbara; Neuser, Petra; Mahner, Sven

    2016-12-01

    A tumour-free pathological resection margin of ≥8 mm is considered state-of-the-art. Available evidence is based on heterogeneous cohorts. This study was designed to clarify the relevance of the resection margin for loco-regional control in vulvar cancer. AGO-CaRE-1 is a large retrospective study. Patients (n = 1618) with vulvar cancer ≥ FIGO stage IB treated at 29 German gynecologic-cancer-centres 1998-2008 were included. This subgroup analysis focuses on solely surgically treated node-negative patients with complete tumour resection (n = 289). Of the 289 analysed patients, 141 (48.8%) had pT1b, 140 (48.4%) pT2 and 8 (2.8%) pT3 tumours. One hundred twenty-five (43.3%) underwent complete vulvectomy, 127 (43.9%) partial vulvectomy and 37 (12.8%) radical local excision. The median minimal resection margin was 5 mm (1 mm-33 mm); all patients received groin staging, in 86.5% with full dissection. Median follow-up was 35.1 months. 46 (15.9%) patients developed recurrence, thereof 34 (11.8%) at the vulva, after a median of 18.3 months. Vulvar recurrence rates were 12.6% in patients with a margin <8 mm and 10.2% in patients with a margin ≥8 mm. When analysed as a continuous variable, the margin distance had no statistically significant impact on local recurrence (HR per mm increase: 0.930, 95% CI: 0.849-1.020; p = 0.125). Multivariate analyses did also not reveal a significant association between the margin and local recurrence neither when analysed as continuous variable nor categorically based on the 8 mm cutoff. Results were consistent when looking at disease-free-survival and time-to-recurrence at any site (HR per mm increase: 0.949, 95% CI: 0.864-1.041; p = 0.267). The need for a minimal margin of 8 mm could not be confirmed in the large and homogeneous node-negative cohort of the AGO-CaRE database. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Inverse Planned High-Dose-Rate Brachytherapy for Locoregionally Advanced Cervical Cancer: 4-Year Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Tinkle, Christopher L.; Weinberg, Vivian [Department of Radiation Oncology, University of California, San Francisco, California (United States); Chen, Lee-May [Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, California (United States); Littell, Ramey [Gynecologic Oncology, The Permanente Medical Group, San Francisco, California (United States); Cunha, J. Adam M.; Sethi, Rajni A. [Department of Radiation Oncology, University of California, San Francisco, California (United States); Chan, John K. [Gynecologic Oncology, California Pacific Medical Center, San Francisco, California (United States); Hsu, I-Chow, E-mail: ichow.hsu@ucsf.edu [Department of Radiation Oncology, University of California, San Francisco, California (United States)

    2015-08-01

    Purpose: Evaluate the efficacy and toxicity of image guided brachytherapy using inverse planning simulated annealing (IPSA) high-dose-rate brachytherapy (HDRB) boost for locoregionally advanced cervical cancer. Methods and Materials: From December 2003 through September 2009, 111 patients with primary cervical cancer were treated definitively with IPSA-planned HDRB boost (28 Gy in 4 fractions) after external radiation at our institution. We performed a retrospective review of our experience using image guided brachytherapy. Of the patients, 70% had a tumor size >4 cm, 38% had regional nodal disease, and 15% had clinically evident distant metastasis, including nonregional nodal disease, at the time of diagnosis. Surgical staging involving pelvic lymph node dissection was performed in 15% of patients, and 93% received concurrent cisplatin-based chemotherapy. Toxicities are reported according to the Common Terminology Criteria for Adverse Events version 4.0 guidelines. Results: With a median follow-up time of 42 months (range, 3-84 months), no acute or late toxicities of grade 4 or higher were observed, and grade 3 toxicities (both acute and late) developed in 8 patients (1 constitutional, 1 hematologic, 2 genitourinary, 4 gastrointestinal). The 4-year Kaplan-Meier estimate of late grade 3 toxicity was 8%. Local recurrence developed in 5 patients (4 to 9 months after HDRB), regional recurrence in 3 (6, 16, and 72 months after HDRB), and locoregional recurrence in 1 (4 months after HDR boost). The 4-year estimates of local, locoregional, and distant control of disease were 94.0%, 91.9%, and 69.1%, respectively. The overall and disease-free survival rates at 4 years were 64.3% (95% confidence interval [CI] of 54%-73%) and 61.0% (95% CI, 51%-70%), respectively. Conclusions: Definitive radiation by use of inverse planned HDRB boost for locoregionally advanced cervical cancer is well tolerated and achieves excellent local control of disease. However, overall

  18. Local field radiotherapy without elective nodal irradiation for postoperative loco-regional recurrence of esophageal cancer.

    Science.gov (United States)

    Kimoto, Takuya; Yamazaki, Hideya; Suzuki, Gen; Aibe, Norihiro; Masui, Koji; Tatekawa, Kotoha; Sasaki, Naomi; Fujiwara, Hitoshi; Shiozaki, Atsushi; Konishi, Hirotaka; Nakamura, Satoaki; Yamada, Kei

    2017-09-01

    Radiotherapy is an effective treatment for the postoperative loco-regional recurrence of esophageal cancer; however, the optimal treatment field remains controversial. This study aims to evaluate the outcome of local field radiotherapy without elective nodal irradiation for postoperative loco-regional recurrence of esophageal cancer. We retrospectively investigated 35 patients treated for a postoperative loco-regional recurrence of esophageal cancer with local field radiotherapy between December 2008 and March 2016. The median irradiation dose was 60 Gy (range: 50-67.5 Gy). Thirty-one (88.6%) patients received concurrent chemotherapy. The median follow-up period was 18 months (range: 5-94 months). The 2-year overall survival was 55.7%, with a median survival time of 29.9 months. In the univariate analysis, the maximal diameter ≤20 mm (P = 0.0383), solitary lesion (P = 0.0352), and the complete remission after treatment (P = 0.00411) had a significantly better prognosis. A total of 27 of 35 patients (77.1%) had progressive disease (loco-regional failure [n = 9], distant metastasis [n = 7], and both loco-regional failure and distant metastasis [n = 11]). No patients had Grade 3 or greater mucositis. Local field radiotherapy is a considerable treatment option for postoperative loco-regional recurrence of esophageal cancer.

  19. Predicting loco-regional recurrence risk in T1, T2 breast cancer with 1-3 positive axillary nodes postmastectomy: Development of a predictive nomogram.

    Science.gov (United States)

    Wadasadawala, T; Kannan, S; Gudi, S; Rishi, A; Budrukkar, A; Parmar, V; Shet, T; Desai, S; Gupta, S; Badwe, R; Sarin, R

    2017-01-01

    Role of postmastectomy radiotherapy (PMRT) in early breast cancer with 1-3 positive axillary nodes is still controversial. Hence, there is a need to identify subgroup of patients who have sufficiently high risk of disease recurrence to benefit from PMRT. The aim is to evaluate clinical outcomes of patients postmastectomy having pathological T1-T2 tumors with 1-3 positive axillary lymph nodes (LNs) treated with adjuvant systemic therapy and develop a predictive nomogram. Data collected retrospectively from eligible patients from 2005 to 2011. Kaplan-Meier survival analysis was used for all time-to-event analysis. Various known clinical and pathological risk factors were correlated with outcome using uni- and multi-variable analysis in SPSS version 21. All comparisons were two-tailed and P loco-regional control (LRC) was developed using least absolute shrinkage and selection operator shrinkage model in hdnom.io software. 38/242 (15.7%) patients had recurrent disease at loco-regional (10 patients), distant sites (22 patients) and simultaneous loco-regional and distant sites (6 patients) at a median follow-up 59.5 (range 4-133) months. Five years estimate of LRC, distant disease-free survival (DFS), DFS, cause-specific survival and overall survival was 87.8%, 85.4%, 84.2%, 93.1%, and 91.5%, respectively. Pathological tumor size, margin status, LN ratio as continuous variables and grade and triple negative breast cancer status as categorical variables were the risk factors included in the model for building nomogram. The nomogram developed based on institutional data can be a valuable tool in guiding adjuvant PMRT depending on the risk of 5 years loco-regional recurrence.

  20. Incidence, natural history, and patterns of locoregional recurrence in gastric cancer patients treated with preoperative chemoradiotherapy.

    Science.gov (United States)

    Reed, Valerie K; Krishnan, Sunil; Mansfield, Paul F; Bhosale, Priya R; Kim, Michelle; Das, Prajnan; Janjan, Nora A; Delclos, Marc E; Lowy, Andrew M; Feig, Barry W; Pisters, Peter W T; Ajani, Jaffer A; Crane, Christopher H

    2008-07-01

    To retrospectively determine the incidence and patterns (in-field, marginal, or out-of-field) of locoregional gastric cancer recurrence in patients who received preoperative chemoradiotherapy and to determine the outcome in these patients. Between 1994 and 2004, 149 patients with gastric carcinoma were treated according to institutional protocols with preoperative chemoradiotherapy. Ultimately, 105 patients had an R0 resection. Of these 105 patients, 65 received preoperative chemotherapy followed by chemoradiotherapy and 40 received preoperative chemoradiotherapy. Most (96%) of these patients received 5-fluorouracil-based chemotherapy during radiotherapy, and the median radiation dose was 45 Gy. We retrospectively identified and classified the patterns of locoregional recurrence. The 3-year actuarial incidence of locoregional recurrence was 13%, with locoregional disease recurring as any part of the failure pattern in 14 patients. Most (64%) of the evaluable locoregional recurrences were in-field. Of the 4 patients with a marginal recurrence, 2 had had inadequate coverage of the regional nodal volumes on their oblique fields. The pathologic complete response rate was 23%. A pathologic complete response was the only statistically significant predictor of locoregional control. Patients with gastric cancer who received preoperative chemoradiotherapy had low rates of locoregional recurrence. This strategy merits prospective multi-institutional and randomized evaluation.

  1. SERCA control of cell death and survival.

    Science.gov (United States)

    Chemaly, Elie R; Troncone, Luca; Lebeche, Djamel

    2018-01-01

    Intracellular calcium (Ca2+) is a critical coordinator of various aspects of cellular physiology. It is increasingly apparent that changes in cellular Ca2+ dynamics contribute to the regulation of normal and pathological signal transduction that controls cell growth and survival. Aberrant perturbations in Ca2+ homeostasis have been implicated in a range of pathological conditions, such as cardiovascular diseases, diabetes, tumorigenesis and steatosis hepatitis. Intracellular Ca2+ concentrations are therefore tightly regulated by a number of Ca2+ handling enzymes, proteins, channels and transporters located in the plasma membrane and in Ca2+ storage organelles, which work in concert to fine tune a temporally and spatially precise Ca2+ signal. Chief amongst them is the sarco/endoplasmic reticulum (SR/ER) Ca2+ ATPase pump (SERCA) which actively re-accumulates released Ca2+ back into the SR/ER, therefore maintaining Ca2+ homeostasis. There are at least 14 different SERCA isoforms encoded by three ATP2A1-3 genes whose expressions are species- and tissue-specific. Altered SERCA expression and activity results in cellular malignancy and induction of ER stress and ER stress-associated apoptosis. The role of SERCA misregulation in the control of apoptosis in various cell types and disease setting with prospective therapeutic implications is the focus of this review. Ca2+ is a double edge sword for both life as well as death, and current experimental evidence supports a model in which Ca2+ homeostasis and SERCA activity represent a nodal point that controls cell survival. Pharmacological or genetic targeting of this axis constitutes an incredible therapeutic potential to treat different diseases sharing similar biological disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Low rates of loco-regional recurrence following extended lymph node dissection for gastric cancer.

    Science.gov (United States)

    Muratore, A; Zimmitti, G; Lo Tesoriere, R; Mellano, A; Massucco, P; Capussotti, L

    2009-06-01

    The study by MacDonald et al. [Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001;345:725-30] has reported low loco-regional recurrence rates (19%) after gastric cancer resection and adjuvant radiotherapy. However, the lymph node dissection was often "inadequate". The aim of this retrospective study is to analyse if an extended lymph node dissection (D2) without adjuvant radiotherapy may achieve comparable loco-regional recurrence rates. A prospective database of 200 patients who underwent a curative resection for gastric carcinoma from January 2000 to December 2006 was analysed. D2 lymph node dissection was standard. Recurrences were categorized as loco-regional, peritoneal, or distant. No patients received neoadjuvant or adjuvant radiotherapy. The in-hospital mortality rate was 1% (2 patients). The mean number of dissected lymph nodes was 25.9. Overall and disease-free survival at 5years were 60.7% and 61.2% respectively. During the follow-up, 60 patients (30%) have recurred at 76 sites: 38 (50%) distant metastases, 25 (32.9%) peritoneal metastases, and 13 (17.1%) loco-regional recurrences. The loco-regional recurrence was isolated in 6 patients and associated with peritoneal or distant metastases in 7 patients. The mean time to the first recurrence was 18.9 (95% confidence interval: 15.0-21.9) months. Extended lymph node dissection is safe and warrants low loco-regional recurrence rates.

  3. Long-term results of radiotherapy combined with nedaplatin and 5-fluorouracil for postoperative loco-regional recurrent esophageal cancer: update on a phase II study.

    Science.gov (United States)

    Jingu, Keiichi; Matsushita, Haruo; Takeda, Ken; Umezawa, Rei; Takahashi, Chiaki; Sugawara, Toshiyuki; Kubozono, Masaki; Abe, Keiko; Tanabe, Takaya; Shirata, Yuko; Yamamoto, Takaya; Ishikawa, Youjirou; Nemoto, Kenji

    2012-11-22

    In 2006, we reported the effectiveness of chemoradiotherapy for postoperative recurrent esophageal cancer with a median observation period of 18 months. The purpose of the present study was to update the results of radiotherapy combined with nedaplatin and 5-fluorouracil (5-FU) for postoperative loco-regional recurrent esophageal cancer. Between 2000 and 2004, we performed a phase II study on treatment of postoperative loco-regional recurrent esophageal cancer with radiotherapy (60 Gy/30 fractions/6 weeks) combined with chemotherapy consisting of two cycles of nedaplatin (70 mg/m2/2 h) and 5-FU (500 mg/m2/24 h for 5 days).The primary endpoint was overall survival rate, and the secondary endpoints were progression-free survival rate, irradiated-field control rate and chronic toxicity. A total of 30 patients were enrolled in this study. The regimen was completed in 76.7% of the patients. The median observation period for survivors was 72.0 months. The 5-year overall survival rate was 27.0% with a median survival period of 21.0 months. The 5-year progression-free survival rate and irradiated-field control rate were 25.1% and 71.5%, respectively. Grade 3 or higher late toxicity was observed in only one patient. Two long-term survivors had gastric tube cancer more than 5 years after chemoradiotherapy.Pretreatment performance status, pattern of recurrence (worse for patients with anastomotic recurrence) and number of recurrent lesions (worse for patients with multiple recurrent lesions) were statistically significant prognostic factors for overall survival. Radiotherapy combined with nedaplatin and 5-FU is a safe and effective salvage treatment for postoperative loco-regional recurrent esophageal cancer. However, the prognosis of patients with multiple regional recurrence or anastomotic recurrence is very poor.

  4. Long-term bresults of radiotherapy combined with nedaplatin and 5-fluorouracil for postoperative loco-regional recurrent esophageal cancer: update on a phase II study

    Science.gov (United States)

    2012-01-01

    Background In 2006, we reported the effectiveness of chemoradiotherapy for postoperative recurrent esophageal cancer with a median observation period of 18 months. The purpose of the present study was to update the results of radiotherapy combined with nedaplatin and 5-fluorouracil (5-FU) for postoperative loco-regional recurrent esophageal cancer. Methods Between 2000 and 2004, we performed a phase II study on treatment of postoperative loco-regional recurrent esophageal cancer with radiotherapy (60 Gy/30 fractions/6 weeks) combined with chemotherapy consisting of two cycles of nedaplatin (70 mg/m2/2 h) and 5-FU (500 mg/m2/24 h for 5 days). The primary endpoint was overall survival rate, and the secondary endpoints were progression-free survival rate, irradiated-field control rate and chronic toxicity. Results A total of 30 patients were enrolled in this study. The regimen was completed in 76.7% of the patients. The median observation period for survivors was 72.0 months. The 5-year overall survival rate was 27.0% with a median survival period of 21.0 months. The 5-year progression-free survival rate and irradiated-field control rate were 25.1% and 71.5%, respectively. Grade 3 or higher late toxicity was observed in only one patient. Two long-term survivors had gastric tube cancer more than 5 years after chemoradiotherapy. Pretreatment performance status, pattern of recurrence (worse for patients with anastomotic recurrence) and number of recurrent lesions (worse for patients with multiple recurrent lesions) were statistically significant prognostic factors for overall survival. Conclusions Radiotherapy combined with nedaplatin and 5-FU is a safe and effective salvage treatment for postoperative loco-regional recurrent esophageal cancer. However, the prognosis of patients with multiple regional recurrence or anastomotic recurrence is very poor. PMID:23171077

  5. Controlling chaotic transients: Yorke's game of survival

    DEFF Research Database (Denmark)

    Aguirre, Jacobo; D'ovidio, Francesco; Sanjuán, Miguel A. F.

    2004-01-01

    . This problem is focused as a two-person, mathematical game between two players called "the protagonist" and "the adversary." The protagonist's goal is to survive. He can lose but cannot win; the best he can do is survive to play another round, struggling ad infinitum. In the absence of actions by either player...... knows the action of the adversary in choosing his response and is permitted to choose the initial point x(0) of the game. We use the "slope 3" tent map in an example of this problem. We show that it is possible for the protagonist to survive....

  6. Magnetic resonance imaging of the liver after loco-regional and systemic therapy.

    Science.gov (United States)

    Corona-Villalobos, Celia Pamela; Zhang, Yan; Zhang, Wei-Dong; Kamel, Ihab R

    2014-08-01

    Assessment of tumor response is crucial in determining the effectiveness of loco-regional and systemic therapy, and for determining the need for subsequent treatment. The ultimate goal is to improve patient's survival. Changes in tumor size and enhancement after therapy may not be detected early by the traditional response criteria. Tumor response is better assessed in the entire tumor volume rather than in a single axial plane. The purpose of this article is to familiarize the reader with early treatment response assessed by anatomic and volumetric functional magnetic resonance imaging metrics of the liver after loco-regional and systemic therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Radical radiotherapy with concurrent weekly cisplatin in loco-regionally advanced squamous cell carcinoma of the head and neck: a single-institution experience.

    Science.gov (United States)

    Gupta, Tejpal; Agarwal, Jai Prakash; Ghosh-Laskar, Sarbani; Parikh, Purvish M; D'Cruz, Anil K; Dinshaw, Ketayun A

    2009-06-15

    The dominant pattern of failure for squamous cell carcinoma of head and neck remains loco-regional, although distant metastases are now being increasingly documented. Radical radiotherapy with concurrent chemotherapy is contemporary standard of care in the non-surgical management of these loco-regionally advanced cancers, based on large randomized controlled trials utilizing high-dose cisplatin (80-100 mg/m2) cycled every three-weekly during definitive radiotherapy. Although efficacious, this is associated with high acute morbidity necessitating intensive supportive care with attendant resource implications. The aim of this retrospective study was to assess the efficacy and acute toxicity of an alternative schedule i.e. concurrent weekly cisplatin-based radical radiotherapy and it's potential to be an optimal regimen in advanced head and neck cancers. Outcome data of patients with Stage III & IV head and neck squamous cell carcinoma, excluding nasopharynx, planned for radical radiotherapy (66-70 Gy) with concurrent weekly cisplatin (30 mg/m2) treated in a single unit between 1996-2004 was extracted. The dataset consisted of 264 patients with a median age of 54 years. The median radiotherapy dose was 70 Gy (range 7.2-72 Gy) and median number of chemotherapy cycles was 6 (range 1-7). Two-thirds (65%) of patients received > or = 85% of planned cisplatin dose. With a mean follow-up of 19 months, the 5-year local control; loco-regional control; and disease free survival was 57%; 46%; and 43% respectively. Acute grade 3 or worse mucositis and dermatitis was seen in 77 (29%) and 92 (35%) patients respectively, essentially in patients receiving doses > or = 66 Gy and 6 or more cycles of chemotherapy. Other toxicities (hematologic, nausea and vomiting) were mild and self-limiting. Overall, the acute toxicity of this concurrent weekly chemo-radiation regimen though mildly increased did not mandate intensive supportive care. Stage grouping, primary site, and intensity of

  8. Concurrent radiotherapy and taxane chemotherapy in patients with locoregional recurrence of breast cancer. A retrospective analysis

    Energy Technology Data Exchange (ETDEWEB)

    Semrau, S.; Klautke, G.; Fietkau, R. [Dept. of Radiotherapy, Univ. of Rostock (Germany); Gerber, B.; Reimer, T. [Dept. of Gynecology and Obstetrics, Univ. of Rostock. Suedstadt Hospital, Rostock (Germany)

    2006-10-15

    Background and purpose: locoregional breast cancer recurrence is characterized by a high rate of systemic and local re-recurrence. Data on concurrent radiochemotherapy (RCT) in these cases are scarce. The purpose of this study was to evaluate feasibility, toxicity and efficacy of local control of a radiotherapy combined with a chemotherapy containing a taxane. Patients and methods: between May 1999 and November 2004, 36 women referred to the authors' clinic because of locoregional breast cancer recurrence that was either inoperable (n = 29) or resected (n = 7) received concurrent irradiation and taxane monotherapy weekly (TAX/RT; n = 28: paclitaxel 90 mg/m{sup 2} n = 24, or docetaxel 35 mg/m{sup 2}, n = 4) or taxane + cisplatin therapy (TAX/CIS/RT; n = 8; paclitaxel 135 mg/m{sup 2} d1 and cisplatin 20 mq/m{sup 2} d1-5 q28). Results: comparing TAX/RT with TAX/CIS/RT, the complete remission rate in patients with macroscopic tumor prior to RCT was significantly higher for TAX/RT than for TAX/CIS/RT (7/19 vs. 0/8; p = 0.046), but overall remission rates were comparable, i.e., partial remission: 11/20 versus 6/8 cases, stable disease (no change): 1/20 versus 2/8 cases, and response rate: 95% versus 75%, respectively. The cumulative local recurrence-free survival rate at 1 and 2 years post-treatment was 83% and 68% and that of systemic recurrence-free survival 56% and 29%, respectively. The main toxic reactions of third-degree and higher were dermatitis in TAX/RT (57% vs. 11% for TAX/CIS/RT) and leukocytopenia in TAX/CIS/RT (62% vs. 7% for TAX/RT). Conclusion: concurrent irradiation and taxane chemotherapy weekly, in particular with paclitaxel, is recommended due to response and acceptable side effects for treatment of inoperable locoregional breast cancer recurrence. (orig.)

  9. Salvage radiotherapy for locoregionally recurrent extrahepatic bile duct cancer after radical surgery.

    Science.gov (United States)

    Kim, Eunji; Kim, Yi-Jun; Kim, Kyubo; Song, Changhoon; Kim, Jae-Sung; Oh, Do-Youn; Nam, Eun Mi; Chie, Eui Kyu

    2017-12-01

    This study evaluated the outcome of salvage radiotherapy for locoregionally recurrent extrahepatic bile duct cancer. We performed a retrospective review of 23 extrahepatic bile duct cancer patients who underwent radiotherapy with or without concomitant chemotherapy for isolated locoregional recurrence after radical surgery between August 2001 and September 2013. The median disease-free interval was 11.8 months. Salvage radiotherapy was delivered to the recurrent tumour with or without initial operation bed up to a median dose of 54 Gy (range, 45-60). 18 patients received concomitant chemotherapy. The median follow-up period was 14.2 months for all patients, and 48.8 months for survivors. The median overall survival and progression-free survival (PFS) were 18.4 (range, 4.4-114.6) and 15.5 months (range, 1.6-114.6), respectively. On multivariate analysis, the use of concomitant chemotherapy was a favourable prognostic factor for PFS (p = 0.027), and prolonged disease-free interval (≥1 year) was associated with a significantly poor overall survival (p = 0.047). Grade 3 or higher toxicities did not occur in follow-up period. Salvage radiotherapy showed promising survival outcomes in locoregional recurrence of extrahepatic bile duct cancer. Our results indicated that concomitant chemotherapy was associated with improved PFS. Concurrent chemoradiotherapy can be a viable salvage treatment option in selected patients. Advances in knowledge: Locoregional recurrence is the most common pattern of failure after radical resection in extrahepatic bile duct cancer. In this study, salvage radiotherapy showed favourable survival outcomes without severe complications in locoregionally recurrent extrahepatic bile duct cancer patients.

  10. Critical analysis of locoregional failures following intensity-modulated radiotherapy for nasopharyngeal carcinoma.

    Science.gov (United States)

    Orlandi, Ester; Tomatis, Stefano; Potepan, Paolo; Bossi, Paolo; Mongioj, Valeria; Carrara, Mauro; Palazzi, Mauro; Franceschini, Marzia; Bergamini, Cristiana; Locati, Laura; Iannacone, Eva; Guzzo, Marco; Ibba, Tullio; Crippa, Flavio; Licitra, Lisa; Pignoli, Emanuele; Fallai, Carlo

    2013-01-01

    To analyze the patterns of locoregional failure following intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) at our institution, as part of an internal quality assurance program. We aimed to investigate the potential existence of a correlation between any part of the IMRT process and clinical outcome. A total of 106 non-metastatic NPC patients consecutively treated with IMRT (with or without chemotherapy) were analyzed. Radiotherapy was administered using a sequential or simultaneous integrated boost approach at the total prescribed dose of 66-70 Gy (2.00-2.12 Gy per fraction). MRI studies of recurrences were recorded with the planning computed tomography studies to identify volume of failure. Recurrence-related characteristics were analyzed with respect to the original treatment. Failures were classified as 'in-field', 'marginal' or 'out-field' if at least 95, 20-95 or less than 20% of the volume of failure, respectively, was within 95% of the total prescription dose. With a median follow-up of 43.4 months, 5-years local control, regional control, locoregional control and overall survival rates were 87.7, 88.0, 83.5 and 81.3% respectively. A total of 21 failures were registered in 15 patients. In particular, ten failures (47.6%) were classified as 'in-field' (seven local failures and three regional failures [RFs]), nine failures (42.9%) as 'marginal' (five local failures and four RFs) and only two failures (9.5%) as 'out-field' (both RFs). The most relevant causes of failures were suboptimal target definition and target coverage as well as a longer than planned overall treatment time. IMRT determines excellent outcome in NPC patients. However, great attention in all IMRT steps is necessary to reduce potential causes of failure.

  11. Long term outcomes after salvage radiotherapy for postoperative locoregionally recurrent non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Ji; Song, Chang Hoon; Kim, Jae Sung [Dept. of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Mi Young [Dept. of Radiation Oncology, Kyungpook National University Medical Center, Daegu (Korea, Republic of)

    2017-03-15

    The outcomes and toxicities of locoregionally recurrent non-small-cell lung cancer (NSCLC) patients treated with curative radiotherapy were evaluated in the modern era. Fifty-seven patients receiving radical radiotherapy for locoregionally recurrent NSCLC without distant metastasis after surgery from 2004 to 2014 were reviewed. Forty-two patients were treated with concurrent chemoradiotherapy (CCRT), and 15 patients with radiotherapy alone. The median radiation dose was 66 Gy (range, 45 to 70 Gy). Lung function change after radiotherapy was evaluated by comparing pulmonary function tests before and at 1, 6, and 12 months after radiotherapy. Median follow-up was 53.6 months (range, 12.0 to 107.5 months) among the survivors. The median overall survival (OS) and progression-free survival (PFS) were 54.8 months (range, 3.0 to 116.9 months) and 12.2 months (range, 0.8 to 100.2 months), respectively. Multivariate analyses revealed that single locoregional recurrence focus and use of concurrent chemotherapy were significant prognostic factors for OS (p = 0.048 and p = 0.001, respectively) and PFS (p = 0.002 and p = 0.026, respectively). There was no significant change in predicted forced expiratory volume in one second after radiotherapy. Although diffusing lung capacity for carbon monoxide decreased significantly at 1 month after radiotherapy (p < 0.001), it recovered to pretreatment levels within 12 months. Acute grade 3 radiation pneumonitis and esophagitis were observed in 3 and 2 patients, respectively. There was no chronic complication observed in all patients. Salvage radiotherapy showed good survival outcomes without severe complications in postoperative locoregionally recurrent NSCLC patients. A single locoregional recurrent focus and the use of CCRT chemotherapy were associated with improved survival. CCRT should be considered as a salvage treatment in patients with good prognostic factors.

  12. Intensity-modulated radiation therapy with simultaneous integrated boost technique following neoadjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma.

    Science.gov (United States)

    Kim, Kyubo; Wu, Hong-Gyun; Kim, Hak Jae; Sung, Myung-Whun; Kim, Kwang Hyun; Lee, Se-Hoon; Heo, Dae Seog; Kim, Hee Jung; Park, Charn Il

    2009-09-01

    Our aim was to evaluate the feasibility and efficacy of intensity-modulated radiation therapy (IMRT) with simultaneous integrated boost (SIB) technique following neoadjuvant chemotherapy for locoregionally advanced nasopharyngeal cancer (NPC). Between April 2004 and December 2006, 25 patients with stage IIB to IVB NPC underwent 3 cycles of neoadjuvant chemotherapy followed by IMRT using SIB technique. Neoadjuvant chemotherapeutic regimens were 5-fluorouracil and cisplatin in 11 patients; docetaxel, 5-fluorouracil, and cisplatin in 8; and paclitaxel and cisplatin in 6. Dose prescription of IMRT was as follows: 67.5 Gy at 2.25 Gy/fraction to postchemotherapy gross tumor, 54 to 60 Gy at 1.8 to 2 Gy/fraction to subclinical disease, and 48 Gy at 1.6 Gy/fraction to elective neck. Seventeen patients received weekly cisplatin during the course of radiation therapy as well. With a median follow-up of 29 months for survivors (range, 14-39), the 3-year local progression-free, regional progression-free, and distant metastasis-free survival rates were 89.6%, 87.2%, and 80.4%, respectively. Treatment was well tolerated despite the grade 3 mucositis (16%) and/or pharyngitis (16%). With follow-up, the frequency of xerostomia decreased. At 3 months after IMRT, the proportions of Radiation Therapy Oncology Group grades 0, 1, and 2 xerostomia were 13%, 38%, and 50%, respectively. At 24 months, the corresponding figures were 36%, 46%, and 18%, respectively. IMRT with SIB technique for locoregionally advanced NPC was feasible and effective regarding locoregional control and development of xerostomia, even after neoadjuvant chemotherapy. Definition of gross tumor volume by postchemotherapy extent of disease was also feasible.

  13. Survival trial design and monitoring using historical controls.

    Science.gov (United States)

    Wu, Jianrong; Xiong, Xiaoping

    2016-09-01

    In this paper, we propose a multistage group sequential procedure to design survival trials using historical controls. The formula for the number of events required for historical control trial designs is derived. Furthermore, a transformed information time is proposed for trial monitoring. An example is given to illustrate the application of the proposed methods to survival trial designs using historical controls. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  14. Microscopic disease extensions as a risk factor for loco-regional recurrence of NSCLC after SBRT.

    Science.gov (United States)

    Salguero, Francisco J; Belderbos, Jose S A; Rossi, Maddalena M G; Blaauwgeers, Johannes L G; Stroom, Joep; Sonke, Jan-Jakob

    2013-10-01

    Stereotactic body radiotherapy (SBRT) is a highly conformal technique that allows a more accurate irradiation of lung tumors. However, a highly conformal dose distribution may underdose undetected microscopic disease extensions (MDE) near the tumor leading to loco-regional failure in tumor control. The purpose of the current work is to assess the risk of loco-regional failure in SBRT by analyzing pre-treatment scans. A model to predict the risk of occurrence of MDE from pretreatment images was developed based on pathology samples of 47 lung cancer patients. This model was used to assess the outcome of 238 SBRT treatments. Patients with high risk of MDE presence showed significantly lower 2-year loco-regional control (82.0% vs. 91.8%) and shorter time to loco-regional failure (8.4 months vs. 20.7 months) than low risk patients. The minimum dose delivered in the volume surrounding the GTV affected the model predictive power. The model remained predictive for patients who received less than 31 Gy in that volume. For patients who received larger doses, the MDE risk classification was not significant. The results show that MDEs are, at least partially, responsible of loco-regional failure in highly conformal radiotherapy. This information could be used to optimize dose distributions. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. Loco-regional cancer drug therapy: present approaches and rapidly reversible hydrophobization (RRH) of therapeutic agents as the future direction.

    Science.gov (United States)

    Budker, Vladimir G; Monahan, Sean D; Subbotin, Vladimir M

    2014-12-01

    Insufficient drug uptake by solid tumors remains the major problem for systemic chemotherapy. Many studies have demonstrated anticancer drug effects to be dose-dependent, although dose-escalation studies have resulted in limited survival benefit with increased systemic toxicities. One solution to this has been the idea of loco-regional drug treatments, which offer dramatically higher drug concentrations in tumor tissues while minimizing systemic toxicity. Although loco-regional delivery has been most prominent in cancers of the liver, soft tissues and serosal peritoneal malignancies, survival benefits are very far from desirable. This review discusses the evolution of loco-regional treatments, the present approaches and offers rapidly reversible hydrophobization of drugs as the new future direction. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Higher Chest Wall Dose Results in Improved Locoregional Outcome in Patients Receiving Postmastectomy Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Panoff, Joseph E.; Takita, Cristiane [Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States); Hurley, Judith [Department of Medicine, Division of Hematology and Oncology, Miller School of Medicine, University of Miami, Miami, Florida (United States); Department of Surgery, Division of Surgical Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States); Reis, Isildinha M. [Department of Epidemiology and Public Health and Sylvester Division of Biostatistics, University of Miami Miller School of Medicine, Miami, Florida (United States); Sylvester Division of Biostatistics and Bioinformatics Core, University of Miami Miller School of Medicine, Miami, Florida (United States); Zhao, Wei [Sylvester Division of Biostatistics and Bioinformatics Core, University of Miami Miller School of Medicine, Miami, Florida (United States); Rodgers, Steven E. [Department of Medicine, Division of Hematology and Oncology, Miller School of Medicine, University of Miami, Miami, Florida (United States); Department of Surgery, Division of Surgical Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States); Gunaseelan, Vijayalakshmi [Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States); Wright, Jean L., E-mail: Jwright3@med.miami.edu [Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States)

    2012-03-01

    Purpose: Randomized trials demonstrating decreased locoregional recurrence (LRR) and improved overall survival (OS) in women receiving postmastectomy radiation therapy (PMRT) used up to 50 Gy to the chest wall (CW), but in practice, many centers boost the CW dose to {>=}60 Gy, despite lack of data supporting this approach. We evaluated the relationship between CW dose and clinical outcome. Methods and Materials: We retrospectively reviewed medical records of 582 consecutively treated patients who received PMRT between January 1999 and December 2009. We collected data on patient, disease, treatment characteristics, and outcomes of LRR, progression-free survival (PFS) and OS. Results: Median follow-up from the date of diagnosis was 44.7 months. The cumulative 5-year incidence of LRR as first site of failure was 6.2%. CW dose for 7% (43 patients) was {<=}50.4 Gy (range, 41.4-50.4 Gy) and 93% received >50.4 Gy (range, 52.4-74.4 Gy). A CW dose of >50.4 Gy vs. {<=}50.4 Gy was associated with lower incidence of LRR, a 60-month rate of 5.7% (95% confidence interval [CI], 3.7-8.2) vs. 12.7% (95% CI, 4.5-25.3; p = 0.054). Multivariate hazard ratio (HR) for LRR controlling for race, receptor status, and stage was 2.62 (95% CI, 1.02-7.13; p = 0.042). All LRR in the low-dose group occurred in patients receiving 50 to 50.4 Gy. Lower CW dose was associated with worse PFS (multivariate HR, 2.73; 95% CI, 1.64-4.56; p < 0.001) and OS (multivariate HR, 3.88; 95% CI, 2.16-6.99; p < 0.001). Conclusions: The addition of a CW boost above 50.4 Gy resulted in improved locoregional control and survival in this cohort patients treated with PMRT for stage II-III breast cancer. The addition of a CW boost to standard-dose PMRT is likely to benefit selected high-risk patients. The optimal technique, target volume, and patient selection criteria are unknown. The use of a CW boost should be studied prospectively, as has been done in the setting of breast conservation.

  17. Outcomes after curative or palliative surgery for locoregional recurrent breast cancer

    DEFF Research Database (Denmark)

    Juhl, Alexander Andersen; Mele, Marco; Damsgaard, Tine Engberg

    2014-01-01

    Background Locoregional recurrence (LRR) after breast cancer is an independent predictor for later systemic disease and poor long-term outcome. As the surgical treatment is complex and often leaves the patient with extensive defects, reconstructive procedures involving flaps, and thus plastic...... surgical assistance, are often required. The aim of the present study was to evaluate our institution’s approach to surgical treatment for locoregional recurrence of a breast cancer. Methods In the present retrospective, single-centre study, we evaluate our experience with 12 patients who underwent surgery...... occurred in four (33 %) of the patients. Median overall survival was 22 months, regardless of the surgery being curative or palliative. A median disease-free survival of 18 months was achieved for patients having achieved radicality. Conclusions Both wide local excision and full thickness chest wall...

  18. Radiation dose escalation for loco-regional recurrence of breast cancer after mastectomy

    Directory of Open Access Journals (Sweden)

    Skinner Heath D

    2013-01-01

    Full Text Available Abstract Background Radiation is a standard component of treatment for patients with locoregional recurrence (LRR of breast cancer following mastectomy. The current study reports the results of a 10% radiation dose escalation in these patients. Methods 159 patients treated at MD Anderson Cancer Center between 1994-2006 with isolated LRR after mastectomy alone were reviewed. Patients in the standard treatment group (65 pts, 40.9% were treated to 50 Gy comprehensively plus a boost of 10 Gy. The dose escalated group (94 pts, 59.1% was treated to 54 Gy comprehensively and a minimum 12 Gy boost. Median dose in the standard dose and dose escalated group was 60 Gy (±1 Gy, 95% CI and 66 Gy (±0.5 Gy, 95% CI respectively. Median follow up for living patients was 94 months from time of recurrence. Results The actuarial five year locoregional control (LRC rate was 77% for the entire study population. The five year overall survival and disease-free survival was 55% and 41%, respectively. On multivariate analysis, initial tumor size (p = 0.03, time to initial LRR (p = 0.03, absence of gross tumor at the time of radiation (p = 0.001 and Her2 status (p = 0.03 were associated with improved LRC. Five year LRC rates were similar in patients with a complete response to chemotherapy without surgery and patients with a complete surgical excision (77% vs 83%, p = NS, compared to a 63% LRC rate in patients with gross disease at the time of radiation (p = 0.024. LRC rates were 80% in the standard dose group and 75% in the dose escalated group (p = NS. Conclusions While LRR following mastectomy is potentially curable, distant metastasis and local control rates remain suboptimal. Radiation dose escalation did not appear to improve LRC. Given significant local failure rates, these patients are good candidates for additional strategies to improve their outcomes.

  19. Treatment results of breast cancer patients with locoregional recurrence after mastectomy

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Yuri; Gong, Gyun Gyub; Lee, Hee Jin [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); and others

    2013-09-15

    To analyze the results of locoregional and systemic therapy in the breast cancer patients with locoregional recurrence (LRR) after mastectomy. Seventy-one patients who received radiotherapy for isolated LRR after mastectomy between January 1999 and December 2009 were retrospectively reviewed. Among the 71 patients, 59 (83.1%) underwent wide excision and radiotherapy and 12 (16.9%) received radiotherapy alone. Adjuvant hormonal therapy was given to 45 patients (63.4%). Oncologic outcomes including locoregional recurrence-free survival, disease-free survival (DFS), and overall survival (OS) and prognostic factors were analyzed. Median follow-up time was 49.2 months. Of the 71 patients, 5 (7%) experienced second isolated LRR, and 40 (56%) underwent distant metastasis (DM). The median DFS was 35.6 months, and the 3- and 5-year DFS were 49.1% and 28.6%, respectively. The median OS was 86.7 months, and the 5-year OS was 62.3%. Patients who received hormone therapy together showed better 5-year DFS and OS than the patients treated with locoregional therapy only (31.6% vs. 22.1%, p = 0.036; 66.5% vs. 55.2%, p = 0.022). In multivariate analysis, higher N stage at recurrence was a significant prognostic factor for DFS and OS. Disease free interval (≤ 30 months vs. >30 months) from mastectomy to LRR was also significant for OS. The patients who received hormone therapy showed superior DFS and showed trend to better OS. DM was a major pattern of failure after the treatment of LRR after mastectomy. The role of systemic treatment for LRR after mastectomy should be investigated at prospective trials.

  20. Cutaneous Angiosarcoma of Head and Neck: A New Predictive Score for Locoregional Metastasis

    Directory of Open Access Journals (Sweden)

    J.E.H. Gründahl

    2015-06-01

    Full Text Available OBJECTIVES: Cutaneous angiosarcoma of head and neck (cAS-HN is a malignant neoplasm with deficient data on prognostic factors. The aim of this study is to present our monocenter database on cAS-HN so far and a new predictive score for locoregional metastasis (LRM. METHODS: Retrospectively, tumor characteristics and outcome of 103 consecutive patients with cAS-HN were analyzed. The main predictors of LRM (identified by univariate and multivariate statistics were combined to a LRM risk score. The prognostic values of stratification into high-, medium-, and low-risk groups concerning disease-specific survival (DSS, distant metastasis (DM, and progression-free survival (PFS were evaluated. RESULTS: LRM (n = 29 and control (n = 74 groups differed significantly concerning several tumor characteristics and outcome (DM, PFS, and DSS. Patients developing LRM showed 3-, 5-, and 10-year survival rates of 32%, 16%, and 11% (mean DSS time of 36.7 months [95% confidence interval (CI 20.5-52.8] compared to 81%, 73%, and 69% (mean DSS time of 292.4 months [95% CI 208.4-376.5] in controls without LRM (P < .001. The main predictors were American Joint Committee on Cancer (AJCC stage, tumor extent, and origin of the primary tumor. The LRM risk score revealed significant higher values for the LRM group [7.14 (SD 1.46 vs 4.88 (SD 1.89, P < .001]. The high-risk group showed significantly higher risk for DM and more unfavorable DSS and PFS. CONCLUSION: The LRM risk score is a simple way to estimate the risk for LRM and DM, to stage patients, and to determine treatment options.

  1. Locoregional therapy with α-emitting trastuzumab against peritoneal metastasis of human epidermal growth factor receptor 2-positive gastric cancer in mice.

    Science.gov (United States)

    Li, Huizi Keiko; Morokoshi, Yukie; Nagatsu, Kotaro; Kamada, Tadashi; Hasegawa, Sumitaka

    2017-08-01

    Peritoneal metastasis of gastric cancer (PMGC) is incurable and thus has an extremely poor prognosis. We have found, however, that locoregionally administered trastuzumab armed with astatine-211 ((211) At-trastuzumab) is effective against human epidermal growth factor receptor 2 (HER2)-positive PMGC in a xenograft mouse model. We first observed that (211) At-trastuzumab can specifically bind and effectively kill NCI-N87 (N87) cells, which are HER2-positive human metastatic GC cells, both in vitro and in s.c. tumors. We established a PMGC mouse model using N87 xenografts stably expressing luciferase to test α-particle radioimmunotherapy with (211) At-trastuzumab against PMGC. Biodistribution analysis in this PMGC mouse model revealed that the i.p. administration of (211) At-trastuzumab (1 MBq) was a more efficient means of delivery of (211) At into metastatic tumors than i.v. injection; the maximum tumor uptake with i.p. administration was over 60% injected dose per gram of tissue (%ID/g) compared to approximately 18%ID/g with i.v. injection. Surprisingly, a single i.p. injection of (211) At-trastuzumab (1 MBq) was sufficient to completely eradicate intraperitoneally disseminated HER2-positive GC xenografts in two of six treated mice by inducing DNA double-strand breaks, and to drastically reduce the tumor burden in another three mice. No bodyweight loss, leukocytopenia, or significant biochemical changes in liver or kidney function were observed in the treatment group. Accordingly, locoregionally administered (211) At-trastuzumab significantly prolonged the survival time of HER2-positive PMGC mice compared with control treatments. Our results provide a proof-of-concept demonstration that locoregional therapy with (211) At-trastuzumab may offer a new treatment option for HER2-positive PMGC. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  2. CX3CR1-dependent renal macrophage survival promotes Candida control and host survival

    Science.gov (United States)

    Lionakis, Michail S.; Swamydas, Muthulekha; Fischer, Brett G.; Plantinga, Theo S.; Johnson, Melissa D.; Jaeger, Martin; Green, Nathaniel M.; Masedunskas, Andrius; Weigert, Roberto; Mikelis, Constantinos; Wan, Wuzhou; Lee, Chyi-Chia Richard; Lim, Jean K.; Rivollier, Aymeric; Yang, John C.; Laird, Greg M.; Wheeler, Robert T.; Alexander, Barbara D.; Perfect, John R.; Gao, Ji-Liang; Kullberg, Bart-Jan; Netea, Mihai G.; Murphy, Philip M.

    2013-01-01

    Systemic Candida albicans infection causes high morbidity and mortality and is associated with neutropenia; however, the roles of other innate immune cells in pathogenesis are poorly defined. Here, using a mouse model of systemic candidiasis, we found that resident macrophages accumulated in the kidney, the main target organ of infection, and formed direct contacts with the fungus in vivo mainly within the first few hours after infection. Macrophage accumulation and contact with Candida were both markedly reduced in mice lacking chemokine receptor CX3CR1, which was found almost exclusively on resident macrophages in uninfected kidneys. Infected Cx3cr1–/– mice uniformly succumbed to Candida-induced renal failure, but exhibited clearance of the fungus in all other organs tested. Renal macrophage deficiency in infected Cx3cr1–/– mice was due to reduced macrophage survival, not impaired proliferation, trafficking, or differentiation. In humans, the dysfunctional CX3CR1 allele CX3CR1-M280 was associated with increased risk of systemic candidiasis. Together, these data indicate that CX3CR1-mediated renal resident macrophage survival is a critical innate mechanism of early fungal control that influences host survival in systemic candidiasis. PMID:24177428

  3. Management of inflammatory breast cancer after neo-adjuvant chemotherapy; Traitement locoregional du cancer du sein inflammatoire apres chimiotherapie neo-adjuvante

    Energy Technology Data Exchange (ETDEWEB)

    Abrous-Anane, S.; Daveau, C.; Dendale, R.; Campana, F.; Kirova, Y.; Fourquet, A.; Bollet, M.A. [Service d' onco-radiotherapie, institut Curie, 26, rue d' Ulm, 75005 Paris cedex 05 (France); Savignoni, A.; Gautier, C. [Service de biostatistique, institut Curie, 26, rue d' Ulm, 75248 Paris cedex 05 (France); Pierga, J.Y. [Service d' oncologie medicale, institut Curie, 26, rue d' Ulm, 75248 Paris cedex 05 (France); Reyal, F. [Service de chirurgie, institut Curie, 26, rue d' Ulm, 75248 Paris cedex 05 (France)

    2011-12-15

    Purpose. - To assess the benefit of breast surgery for inflammatory breast cancer. Patients and methods. - This retrospective series was based on 232 patients treated for inflammatory breast cancer. All patients received primary chemotherapy followed by either exclusive radiotherapy (118 patients, 51%) or surgery with or without radiotherapy (114 patients, 49%). The median follow-up was 11 years. Results. - The two groups were comparable apart from fewer tumors smaller than 70 mm (43% vs 33%, P = 0.003), a higher rate of clinical stage N2 (15% vs 5%, P = 0.04) and fewer histopathological grade 3 tumors (46% vs 61%, P < 0.05) in the no-surgery group. The addition of surgery was associated with a significant improvement in locoregional disease control (P = 0.04) but with no significant difference in overall survival rates or disease-free intervals. Late toxicities were not significantly different between the two treatment groups except for a higher rate of fibrosis in the no-surgery group (P < 0.0001), and more lymphedema in the surgery group (P = 0.002). Conclusion. - Our data suggest an improvement in locoregional control in patients treated by surgery, in conjunction with chemotherapy and radiotherapy, for inflammatory breast cancer. (authors)

  4. [Outcome and prognostic factors of 125 loco-regionally advanced head and neck squamous cell carcinoma treated with multi-modality treatment].

    Science.gov (United States)

    Qian, Wei; Zhu, Guopei; Ji, Qinghai; Guo, Ye; Wang, Yu; Wang, Yulong

    2014-03-01

    To investigate the treatment outcome of loco-regionally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) after been treated with multi-modality approach since 2005 in our hospital and to explore the prognostic factors for treatment outcomes. Clinical data of 125 postoperative LA-SCCHN patients treated in our department with radiotherapy/chemoradiotherapy from May 2005 to December 2011 were collected and reviewed in this study. The radiotherapy technique was intensity-modulated radiotherapy (IMRT) (93.6%) and a minority of patients received 3D-conformal radiotherapy (3D-CRT). Up to January 6th, 2013, 124 patients were followed up with a median follow-up duration of 25 months. The 3-year overall survival (OS), disease-free survival (DFS), loco-regional control (LRC), distant metastasis-free survival (DMFS) were 69.7%, 56.1%, 80.8%, and 73.1%, respectively. A total of 37 patients died during the follow-up period. Among the 43 patients presented with treatment failure, 13 patients had loco-regional relapse, 20 patients had distant metastasis and 10 patients presented with both loco-regional and distant relapses. Distant metastasis accounted for the predominant cause of death. Lung and mediastinal lymph nodes are the most common sites involved by distant metastasis.Univariate analysis indicated that patients who underwent non-radical surgery, with larger size of invaded lymph nodes, higher N stage (N2b and above) and vascular tumor embolism had a lower OS (P = 0.001, 0.000, 0.032, 0.007, respectively). Patients who underwent neck dissection only, or those with higher N stage (N2b and above) or higher TNM stage or vascular tumor thrombi had higher distant metastasis rates (P = 0.017, 0.002, 0.008, 0.001, respectively). The multivariate analysis showed that non-radical surgery was an independent prognostic factor for OS (P = 0.001), larger size of invaded lymph nodes was an independent prognostic factor for poorer LRC (P = 0.001); higher N stage (N2b and

  5. Survival

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — These data provide information on the survival of California red-legged frogs in a unique ecosystem to better conserve this threatened species while restoring...

  6. Clinical results of proton-beam therapy for locoregionally advanced esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mizumoto, Masashi; Sugahara, Shinji; Nakayama, Hidetsugu; Okumura, Toshiyuki; Tsuboi, Koji; Sakurai, Hideyuki [Proton Medical Research Center, Univ. of Tsukuba, Ibaraki (Japan); Dept. of Radiation Oncology, Univ. of Tsukuba, Ibaraki (Japan); Hashii, Haruko [Dept. of Radiation Oncology, Univ. of Tsukuba, Ibaraki (Japan); Nakahara, Akira [Dept. of Gastroenterological Medicine, Univ. of Tsukuba, Ibaraki (Japan); Terashima, Hideo [Dept. of Surgery, Univ. of Tsukuba, Ibaraki (Japan); Tokuuye, Koichi [Proton Medical Research Center, Univ. of Tsukuba, Ibaraki (Japan); Dept. of Radiology, Tokyo Medical Univ., Shinkuku, Tokyo (Japan)

    2010-09-15

    Purpose: To evaluate the efficacy and safety of proton-beam therapy for locoregionally advanced esophageal cancer. Patients and Methods: The subjects were 51 patients with esophageal cancer who were treated between 1985 and 2005 using proton beams with or without X-rays. All but one had squamous cell carcinoma. Of the 51 patients, 33 received combinations of X-rays (median 46 Gy) and protons (median 36 GyE) as a boost. The median total dose of combined X-rays and proton radiation for these 33 patients was 80 GyE (range 70-90 GyE). The other 18 patients received proton-beam therapy alone (median 79 GyE, range 62-98 GyE). Results: Treatment interruption due to radiation-induced esophagitis or hematologic toxicity was not required for any patient. The overall 5-year actuarial survival rate for the 51 patients was 21.1% and the median survival time was 20.5 months (95% confidence interval 10.9-30.2). Of the 51 patients, 40 (78%) showed a complete response within 4 months after completing treatment and seven (14%) showed a partial response, giving a response rate of 92% (47/51). The 5-year local control rate for all 51 patients was 38.0% and the median local control time was 25.5 months (95% confidence interval 14.6-36.3). Conclusion: The results suggest that proton-beam therapy is an effective treatment for patients with locally advanced esophageal cancer. Further studies are required to determine the optimal total dose, fractionation schedules, and best combination of proton therapy with chemotherapy. (orig.)

  7. Prognostic factors in patients with loco-regionally advanced gastric cancer.

    Science.gov (United States)

    Hultman, Bo; Gunnarsson, Ulf; Nygren, Peter; Sundbom, Magnus; Glimelius, Bengt; Mahteme, Haile

    2017-09-15

    The aim of this study was to investigate epidemiologic and prognostic factors relevant to the treatment of loco-regionally advanced gastric cancer (GC). Two hundred and fifty-five patients with GC were identified in Uppsala County between 2000 and 2009. Patient records were analyzed for loco-regionally advanced GC defined as tumor with peritoneal involvement, excluding serosal invasion from the primary tumor only, at primary diagnosis or during follow-up. The presence or not of distant metastasis (DM), including hematogenous metastases (e.g., liver, lung, and bone) and/or distant lymph node metastases, was also analyzed. The Cox proportional hazard model was used for multivariate analysis of factors influencing survival. One hundred and twenty patients (47% of all patients with GC; median age 70.5 years) had loco-regionally advanced disease, corresponding to an incidence of 3.8 per 100,000 person-years. Forty-one percent of these also had DM. Median overall survival (mOS) from the time of the diagnosis of loco-regionally advanced disease was 4.8 months for the total patient cohort, 5.1 months for the subgroup of patients without DM, and 4.7 months for the subgroup with DM. There was no significant difference in mOS between the subgroups with synchronous versus metachronous loco-regionally advanced GC: 4.8 months (range 0.0-67.4) versus 4.7 months (range 0.0-28.3). Using multivariate Cox analysis, positive prognostic factors for survival were good performance status at diagnosis and treatment with palliative chemotherapy and/or radiotherapy. Synchronous DM was a negative prognostic factor. The mOS did not differ when comparing the time period 2000-2004 (5.1 months, range 0-67.4) with the period 2005-2009 (4.0 months, range 0.0-28.3). Peritoneal involvement occurred in almost half of the patients with GC in this study and was associated with short life expectancy. New treatment strategies are warranted.

  8. Prognostic Factors for Local, Loco-regional and Systemic Recurrence in Early-stage Breast Cancer.

    Science.gov (United States)

    Kümmel, A; Kümmel, S; Barinoff, J; Heitz, F; Holtschmidt, J; Weikel, W; Lorenz-Salehi, F; du Bois, A; Harter, P; Traut, A; Blohmer, J U; Ataseven, B

    2015-07-01

    Aim: The risk of recurrence in breast cancer depends on factors such as treatment but also on the intrinsic subtype. We analyzed the risk factors for local, loco-regional and systemic recurrence, evaluated the differences and analyzed the risk of recurrence for different molecular subtypes. Material and Methods: A total of 3054 breast cancer patients who underwent surgery followed by adjuvant treatment at HSK hospital or Essen Mitte Hospital between 1998 and 2011 were analyzed. Based on immunohistochemical parameters, cancers were divided into the following subgroups: luminal A, luminal B (HER2-), luminal B (HER2+), HER2+ and TNBC (triple negative breast cancer). Results: 67 % of tumors were classified as luminal A, 13 % as luminal B (HER2-), 6 % as luminal B (HER2+), 3 % as HER2+ and 11 % as TNBC. After a median follow-up time of 6.6 years there were 100 local (3.3 %), 32 loco-regional (1 %) and 248 distant recurrences (8 %). Five-year recurrence-free survival for the overall patient collective was 92 %. On multivariate analysis, positive nodal status, TNBC subtype and absence of radiation therapy were found to be independent risk factors for all forms of recurrence. Age loco-regional recurrence was low. In addition to nodal status, subgroup classification was found to be an important factor affecting the risk of recurrence.

  9. Matched survival data in a co-twin control design

    DEFF Research Database (Denmark)

    Gerster, Mette; Madsen, Mia; Andersen, Per Kragh

    2014-01-01

    When using the co-twin control design for analysis of event times, one needs a model to address the possible within-pair association. One such model is the shared frailty model in which the random frailty variable creates the desired within-pair association. Standard inference for this model......-effects models for survival in matched pairs. Fitting this model to data generated from the frailty model provides consistent and asymptotically normal estimates of regression coefficients, no matter whether the independence assumption is met....

  10. Tumor markers for early diagnosis for brain metastasis of hepatocellular carcinoma: A case series and literature review for effective loco-regional treatment.

    Science.gov (United States)

    Kamimura, Kenya; Kobayashi, Yuji; Takahashi, Yoshifumi; Abe, Hiroyuki; Kumaki, Daisuke; Yokoo, Takeshi; Kamimura, Hiroteru; Sakai, Norihiro; Sakamaki, Akira; Abe, Satoshi; Takamura, Masaaki; Kawai, Hirokazu; Yamagiwa, Satoshi; Terai, Shuji

    2017-02-01

    Intrahepatic lesions of hepatocellular carcinoma (HCC) have been controlled by significant advances in treatment using loco-regional therapies, including, surgery, ablative therapy, catheter-based chemotherapy, and embolization. Consequently, the number of patients with extrahepatic metastatic lesions has increased. Their prognosis remains poor with approximately loco-regional treatment, including surgical resection and radiation therapy should be performed for better prognosis by preventing re-bleeding from the tumors.

  11. Anaesthesia for carotid endarterectomy - general or loco-regional?

    Science.gov (United States)

    Zdrehuş, Claudiu

    2015-04-01

    Carotid endarterectomy has been widely used for the surgical treatment of carotid stenosis, and may be performed under either general or loco-regional anaesthesia. The greatest risks of carotid endarterectomy are the neurologic complications and the myocardial infarction. Anaesthetic and surgical techniques are constantly under scrutiny to try to reduce the relatively high incidence of morbidity and mortality of an operation which in itself is only preventative. Loco-regional anaesthesia is an alternative to general anaesthesia which has attracted considerable attention amid claims of a reduction in operative morbidity and mortality. This review describes the problems and some solutions for providing loco-regional or general anaesthesia for carotid endarterectomy.

  12. Relationship between the prognostic and predictive value of the intrinsic subtypes and a validated gene profile predictive of loco-regional control and benefit from post-mastectomy radiotherapy in patients with high-risk breast cancer.

    Science.gov (United States)

    Tramm, Trine; Kyndi, Marianne; Myhre, Simen; Nord, Silje; Alsner, Jan; Sørensen, Flemming Brandt; Sørlie, Therese; Overgaard, Jens

    2014-10-01

    Breast cancer is characterized by great molecular heterogeneity demonstrated, e.g. by the intrinsic subtypes. Administration of post-mastectomy radiotherapy (PMRT) does, however, not reflect this heterogeneity. A gene profile (DBCG-RT profile) has recently been developed and validated, and has shown prognostic impact in terms of loco-regional failure and predictive impact for PMRT. Reports have also shown predictive value in terms of benefit of PMRT from intrinsic subtypes and derived approximations. The aim of this study was to examine: 1) the agreement between various methods for determining the intrinsic subtypes; and 2) the relationship between the prognostic and predictive impact of the DBCG-RT profile and the intrinsic subtypes. Intrinsic subtypes and the DBCG-RT profile was determined from microarray analysis based on fresh frozen tissue from 191 patients included in the Danish Breast Cancer Cooperative Group (DBCG) 82bc trial. Corresponding formalin-fixed, paraffin-embedded tissue was available from 146 of these patients and from another 890 DBCG82bc patients. Estrogen receptor, progesterone receptor, HER2, CK5/6, Ki-67 and EGFR were combined into immunohistochemical approximations of the intrinsic subtypes. Endpoint considered was loco-regional recurrence (LRR). The DBCG-RT profile identified a group of patients with low risk of LRR and no additional benefit from PMRT among all subtypes. Combining six immunohistochemical markers identified a subgroup of triple negative patients with high risk of LRR and significant benefit from PMRT. Agreement in the different assignments of tumors to the subtypes was suboptimal, and the clinical outcome and predicted benefit from PMRT varied according to the method used for assignment. The prognostic and predictive information obtained from the DBCG-RT profile cannot be substituted by any approximation of the tumors intrinsic subtype. The predictive value of the intrinsic subtypes in terms of PMRT was influenced by the

  13. Missed Opportunities for Loco-Regional Treatment of Elderly Women with Breast Cancer.

    Science.gov (United States)

    Bhoo-Pathy, Nirmala; Balakrishnan, Nanthini; See, Mee-Hoong; Taib, Nur Aishah; Yip, Cheng-Har

    2016-12-01

    Factors associated with surgery, adjuvant radiotherapy, and chemotherapy and whether there were missed opportunities for treatment in elderly patients were determined in an Asian setting. All 5616 patients, diagnosed with breast cancer in University Malaya Medical Centre from 1999 to 2013 were included. In 945 elderly patients (aged 65 years and above), multivariable logistic regression was performed to identify factors associated with treatment, following adjustment for age, ethnicity, tumor, and other treatment characteristics. The impact of lack of treatment on survival of the elderly was assessed while accounting for comorbidities. One in five elderly patients had comorbidities. Compared to younger patients, the elderly had more favorable tumor characteristics, and received less loco-regional treatment and chemotherapy. Within stage I-IIIa elderly breast cancer patients, 10 % did not receive any surgery. These patients were older, more likely to be Malays, have comorbidities, and bigger tumors. In elderlies with indications for adjuvant radiotherapy, no irradiation (30 %) was associated with increasing age, comorbidity, and the absence of systemic therapy. Hormone therapy was optimal, but only 35 % of elderly women with ER negative tumors received chemotherapy. Compared to elderly women who received adequate treatment, those not receiving surgery (adjusted hazard ratio: 2.30, 95 %CI: 1.10-4.79), or radiotherapy (adjusted hazard ratio: 1.56, 95 %CI: 1.10-2.19), were associated with higher mortality. Less than 25 % of the survival discrepancy between elderly women receiving loco-regional treatment and no treatment were attributed to excess comorbidities in untreated patients. While the presence of comorbidities significantly influenced loco-regional treatment decisions in the elderly, it was only able to explain the lower survival rates in untreated patients up to a certain extent, suggesting missed opportunities for treatment.

  14. Ultrasound-guided locoregional anaesthesia for carotid endarterectomy

    DEFF Research Database (Denmark)

    Martusevicius, Robertas; Swiatek, F; Joergensen, L G

    2012-01-01

    Ultrasound guidance is increasingly used for invasive anaesthetic procedures to improve efficacy, facilitate performance and reduce risk of complications. Herein, we present a simple approach to ultrasound-guided locoregional anaesthesia for patients undergoing eversion carotid endarterectomy....

  15. DEGRO practical guidelines for radiotherapy of breast cancer VI: therapy of locoregional breast cancer recurrences

    Energy Technology Data Exchange (ETDEWEB)

    Harms, Wolfgang [St. Claraspital, Abteilung fuer Radioonkologie, Basel (Switzerland); Budach, W. [Heinrich-Heine-University, Duesseldorf (Germany); Dunst, J. [University Hospital Schleswig-Holstein, Kiel (Germany); Feyer, P. [Vivantes Hospital Neukoelln, Berlin (Germany); Fietkau, R.; Sauer, R. [University Hospital Erlangen, Erlangen (Germany); Krug, D. [University Hospital Heidelberg, Heidelberg (Germany); Piroth, M.D. [Witten/Herdecke University, HELIOS-Hospital Wuppertal, Wuppertal (Germany); Sautter-Bihl, M.L. [Municipal Hospital, Karlsruhe (Germany); Sedlmayer, F. [Paracelsus Medical University Hospital, Salzburg (Austria); Wenz, F. [University of Heidelberg, University Medical Center Mannheim, Medical Faculty Mannheim, Mannheim (Germany); Haase, W.; Souchon, R.; Collaboration: Breast Cancer Expert Panel of the German Society of Radiation Oncology (DEGRO)

    2016-04-15

    To update the practical guidelines for radiotherapy of patients with locoregional breast cancer recurrences based on the current German interdisciplinary S3 guidelines 2012. A comprehensive survey of the literature using the search phrases ''locoregional breast cancer recurrence'', ''chest wall recurrence'', ''local recurrence'', ''regional recurrence'', and ''breast cancer'' was performed, using the limits ''clinical trials'', ''randomized trials'', ''meta-analysis'', ''systematic review'', and ''guidelines''. Patients with isolated in-breast or regional breast cancer recurrences should be treated with curative intent. Mastectomy is the standard of care for patients with ipsilateral breast tumor recurrence. In a subset of patients, a second breast conservation followed by partial breast irradiation (PBI) is an appropriate alternative to mastectomy. If a second breast conservation is performed, additional irradiation should be mandatory. The largest reirradiation experience base exists for multicatheter brachytherapy; however, prospective clinical trials are needed to clearly define selection criteria, long-term local control, and toxicity. Following primary mastectomy, patients with resectable locoregional breast cancer recurrences should receive multimodality therapy including systemic therapy, surgery, and radiation +/- hyperthermia. This approach results in high local control rates and long-term survival is achieved in a subset of patients. In radiation-naive patients with unresectable locoregional recurrences, radiation therapy is mandatory. In previously irradiated patients with a high risk of a second local recurrence after surgical resection or in patients with unresectable recurrences, reirradiation should be strongly considered. Indication and dose concepts

  16. Effect of HPV-associated p16INK4A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck

    DEFF Research Database (Denmark)

    Lassen, Pernille; Eriksen, Jesper G; Hamilton-Dutoit, Stephen

    2009-01-01

    with improved locoregional tumor control (5-year actuarial values 58% v 28%; P = .0005), improved disease-specific survival (72% v 34%; P = .0006), and improved overall survival (62% v 26%; P = .0003). In multivariate analysis, p16(INK4A) remained a strong independent prognostic factor for locoregional failure......PURPOSE: A subset of head and neck cancers is associated with the human papillomavirus (HPV). Viral infection is closely correlated with expression of p16(INK4A) in these tumors. We evaluated p16(INK4A) as a prognostic marker of treatment response and survival in a well-defined and prospectively...... collected cohort of patients treated solely with conventional radiotherapy in the Danish Head and Neck Cancer Group (DAHANCA) 5 trial. PATIENTS AND METHODS: Immunohistochemical expression of p16(INK4A) was analyzed in pretreatment paraffin-embedded tumor blocks from 156 patients treated with conventional...

  17. Electrochemotherapy - Supplementary Treatment for Loco-regional Metastasized Breast Carcinoma Administered to Concomitant Systemic Therapy.

    Science.gov (United States)

    Grischke, Eva-Maria; Röhm, Carmen; Stauß, Eva; Taran, Florin-Andrei; Brucker, Sara Y; Wallwiener, Diethelm

    2017-09-01

    Electrochemotherapy (ECT) is an established procedure for treating breast cancer loco-regional recurrences following surgical intervention and/or radiotherapy. Limited information is available on ECT application as a concomitant procedure to systemic therapy in recurrent breast cancer. The primary objective of this study was to determine if the application of ECT in close temporal relation to systemic chemotherapy could lead to increased local and/or systemic side effects. For this purpose we evaluated the safety of ECT as a supplemental local therapy to systemic therapy. ECT local and systemic toxicity and side effects were recorded and whether the anticipated local therapeutic effect of ECT would be influenced by the concomitant use of systemic therapies was investigated. This is an observational study. Thirty three patients with loco-regional metastasized breast carcinoma were treated and observed over a period of three years with 46 ECT applications for local tumour control in addition to established systemic therapy. A specific timeline for ECT administration was not fixed up, but was generally performed one week before the following chemotherapy administration with the aim to avoid the so called nadir, this means the peak period with risk of neutropenia. Data was collected over a period of three years on a population of 33 metastatic patients. Fifteen patients, received neo-adjuvant therapy as part of their primary treatment, but still had an advanced stage tumour. Some patients received repeated ECT applications. Objective tumour response was observed in 90% of the treated patients. Patients showed no increased local toxicity, especially no higher dermal toxicity, e.g. formation of local necrosis. ECT proved to be an effective supplement to a cytotoxic systemic therapy, especially for high-risk patients who did not respond well to systemic therapy of loco-regional metastases, without creating any greater systemic or loco-regional toxicities.

  18. Electrochemotherapy – Supplementary Treatment for Loco-regional Metastasized Breast Carcinoma Administered to Concomitant Systemic Therapy

    Science.gov (United States)

    Röhm, Carmen; Stauß, Eva; Taran, Florin-Andrei; Brucker, Sara Y.; Wallwiener, Diethelm

    2017-01-01

    Abstract Background Electrochemotherapy (ECT) is an established procedure for treating breast cancer loco-regional recurrences following surgical intervention and/or radiotherapy. Limited information is available on ECT application as a concomitant procedure to systemic therapy in recurrent breast cancer. The primary objective of this study was to determine if the application of ECT in close temporal relation to systemic chemotherapy could lead to increased local and/or systemic side effects. For this purpose we evaluated the safety of ECT as a supplemental local therapy to systemic therapy. ECT local and systemic toxicity and side effects were recorded and whether the anticipated local therapeutic effect of ECT would be influenced by the concomitant use of systemic therapies was investigated. Patients and methods This is an observational study. Thirty three patients with loco-regional metastasized breast carcinoma were treated and observed over a period of three years with 46 ECT applications for local tumour control in addition to established systemic therapy. A specific timeline for ECT administration was not fixed up, but was generally performed one week before the following chemotherapy administration with the aim to avoid the so called nadir, this means the peak period with risk of neutropenia. Results Data was collected over a period of three years on a population of 33 metastatic patients. Fifteen patients, received neo-adjuvant therapy as part of their primary treatment, but still had an advanced stage tumour. Some patients received repeated ECT applications. Objective tumour response was observed in 90% of the treated patients. Patients showed no increased local toxicity, especially no higher dermal toxicity, e.g. formation of local necrosis. Conclusions ECT proved to be an effective supplement to a cytotoxic systemic therapy, especially for high-risk patients who did not respond well to systemic therapy of loco-regional metastases, without creating any

  19. Minimal impact of postmastectomy radiation therapy on locoregional recurrence for breast cancer patients with 1 to 3 positive lymph nodes in the modern treatment era.

    Science.gov (United States)

    Miyashita, Minoru; Tada, Hiroshi; Suzuki, Akihiko; Watanabe, Gou; Hirakawa, Hisashi; Amari, Masakazu; Kakugawa, Yoichiro; Kawai, Masaaki; Furuta, Akihiko; Sato, Kaoru; Yoshida, Ryuichi; Ebata, Akiko; Sasano, Hironobu; Jingu, Keiichi; Ohuchi, Noriaki; Ishida, Takanori

    2017-06-01

    Given modern treatment strategies, controversy remains regarding whether postmastectomy radiation therapy (PMRT) is necessary for breast cancer patients with 1-3 positive axillary lymph nodes (ALN). Our aim was to assess the significance of PMRT in the modern treatment era for these patients. We have conducted the retrospective multicenter study and identified 658 patients with 1-3 positive ALN who were treated with mastectomy and ALN dissection between 1999 and 2012. Propensity score weighting was used to minimize the influence of confounding factors between the PMRT and no-PMRT groups. The variables including tumor size, lymph nodes status, skin and/or muscle invasion, histological grade, lymphovascular invasion and ER positivity which were statistically unbalanced between the groups were used to define the propensity scores. The median follow-up time was 7.3 years. In the modern era (2006-2012), no significant difference in locoregional recurrence (LRR)-free survival was noted between the PMRT and no-PMRT groups (P = 0.3625). The 8-year LRR-free survival rates of the PMRT and no-PMRT groups were 98.2% and 95.3%, respectively. After matching patients by propensity scores, the PMRT group, compared to the no-PMRT group, exhibited significantly better locoregional control (P = 0.0366) in the entire cohort. The 10-year LRR-free survival rates were 97.8% and 88.4% in the PMRT and no-PMRT groups, respectively. In contrast, no significant difference in LRR-free survival was noted between the PMRT and no-PMRT groups in the modern era (P = 0.5298). The 8-year LRR-free survival rates of patients treated in the modern era were approximately the same between the groups (98.0% and 95.7% in the PMRT and no-PMRT groups, respectively). Particularly, LRR-free survival of HER2 positive breast cancer significantly improved in the modern treatment era, compared with that of the old treatment era (P = 0.0349). PMRT had minimal impact on LRR for breast cancer patients with 1

  20. Prognostic value of primary gross tumor volume and standardized uptake value of 18F-FDG in PET/CT for distant metastasis in locoregionally advanced nasopharyngeal carcinoma.

    Science.gov (United States)

    Jin, Ya-Nan; Yao, Ji-Jin; Wang, Si-Yang; Zhang, Wang-Jian; Zhou, Guan-Qun; Zhang, Fan; Cheng, Zhi-Bin; Ma, Jun; Mo, Hao-Yuan; Sun, Ying

    2017-07-01

    Distant metastasis has become the predominant model of treatment failures in patients with locoregionally advanced nasopharyngeal carcinoma. Effort should therefore be made to stratify locoregionally advanced nasopharyngeal carcinoma patients into different groups based on the risk of metastasis to improve prognosis and tailor individualized treatments. This study aims to assess the value of primary gross tumor volume and the maximum standardized uptake value for predicting distant metastasis-free survival of patients with locoregionally advanced nasopharyngeal carcinoma. A total of 294 locoregionally advanced nasopharyngeal carcinoma patients who were identified from prospectively maintained database and underwent fluor-18-fluorodeoxyglucose positron emission tomography/computed tomography imaging before treatment were included. The maximum standardized uptake value was recorded for the primary tumor (SUVmax-P) and neck lymph nodes (SUVmax-N). Computed tomography-derived primary gross tumor volume was measured using the summation-of-area technique. At 5 years, the distant metastasis-free survival rate was 83.7%. The cut-off of the SUVmax-P, SUVmax-N, and primary gross tumor volume for distant metastasis-free survival was 8.95, 5.75, and 31.3 mL, respectively, by receiver operating characteristic curve. In univariate analysis, only SUVmax-N (hazard ratio: 7.01; 95% confidence interval: 1.70-28.87; p carcinoma. Combining SUVmax-N with clinical stage gives a more precise picture in predicting distant metastasis.

  1. Control of neural stem cell survival by electroactive polymer substrates.

    Directory of Open Access Journals (Sweden)

    Vanessa Lundin

    Full Text Available Stem cell function is regulated by intrinsic as well as microenvironmental factors, including chemical and mechanical signals. Conducting polymer-based cell culture substrates provide a powerful tool to control both chemical and physical stimuli sensed by stem cells. Here we show that polypyrrole (PPy, a commonly used conducting polymer, can be tailored to modulate survival and maintenance of rat fetal neural stem cells (NSCs. NSCs cultured on PPy substrates containing different counter ions, dodecylbenzenesulfonate (DBS, tosylate (TsO, perchlorate (ClO(4 and chloride (Cl, showed a distinct correlation between PPy counter ion and cell viability. Specifically, NSC viability was high on PPy(DBS but low on PPy containing TsO, ClO(4 and Cl. On PPy(DBS, NSC proliferation and differentiation was comparable to standard NSC culture on tissue culture polystyrene. Electrical reduction of PPy(DBS created a switch for neural stem cell viability, with widespread cell death upon polymer reduction. Coating the PPy(DBS films with a gel layer composed of a basement membrane matrix efficiently prevented loss of cell viability upon polymer reduction. Here we have defined conditions for the biocompatibility of PPy substrates with NSC culture, critical for the development of devices based on conducting polymers interfacing with NSCs.

  2. Non-intubated video-assisted thoracoscopic surgery under loco-regional anaesthesia for thoracic surgery: a meta-analysis.

    Science.gov (United States)

    Deng, Han-Yu; Zhu, Zi-Jiang; Wang, Yun-Cang; Wang, Wen-Ping; Ni, Peng-Zhi; Chen, Long-Qi

    2016-07-01

    The short-term feasibility and safety of non-intubated video-assisted thoracoscopic surgery under loco-regional anaesthesia for thoracic surgery remains unknown. Therefore, we conducted a meta-analysis to provide evidence for the short-term efficacy and safety profile of non-intubated video-assisted thoracoscopic surgery under loco-regional anaesthesia for thoracic surgery. We performed a systematic literature search in PubMed, Embase, Cochrane Library databases and Google Scholar, as well as American Society of Clinical Oncology to identify relevant studies comparing non-intubated video-assisted thoracoscopic surgery under loco-regional anaesthesia with conventionally intubated video-assisted thoracoscopic surgery under general anaesthesia, dated up to 31 August 2015. Data concerning global in-operating room time, hospital stays, rate of postoperative complications and perioperative mortality were extracted and analysed. We conducted a meta-analysis of the overall results and two subgroup analyses based on study design (a meta-analysis of randomized controlled trials and a second meta-analysis of observational studies). Four randomized controlled trials and six observational studies with a total of 1283 patients were included. We found that in the overall analysis, patients treated with non-intubated video-assisted thoracoscopic surgery under loco-regional anaesthesia achieved significantly shorter global in-operating room time [weighted mean difference = -41.96; 95% confidence interval (CI) = (-57.26, -26.67); P loco-regional anaesthesia. Non-intubated video-assisted thoracoscopic surgery under loco-regional anaesthesia for thoracic surgery proved to be feasible and safe. Future multicentre and well-designed randomized controlled trials with longer follow-up are needed to confirm and update the findings of our study, as well as the long-term efficacy of non-intubated video-assisted thoracoscopic surgery under loco-regional anaesthesia. © The Author 2016

  3. Anaesthesia for carotid endarterectomy – general or loco-regional?

    Science.gov (United States)

    Zdrehuş, Claudiu

    2015-01-01

    Carotid endarterectomy has been widely used for the surgical treatment of carotid stenosis, and may be performed under either general or loco-regional anaesthesia. The greatest risks of carotid endarterectomy are the neurologic complications and the myocardial infarction. Anaesthetic and surgical techniques are constantly under scrutiny to try to reduce the relatively high incidence of morbidity and mortality of an operation which in itself is only preventative. Loco-regional anaesthesia is an alternative to general anaesthesia which has attracted considerable attention amid claims of a reduction in operative morbidity and mortality. This review describes the problems and some solutions for providing loco-regional or general anaesthesia for carotid endarterectomy. PMID:28913451

  4. Coyote removal, understory cover, and survival of white-tailed deer neonates: Coyote Control and Fawn Survival

    Energy Technology Data Exchange (ETDEWEB)

    Kilgo, John C. [USDA Forest Service; Southern Research Station, New Ellenton, SC (United States); Vukovich, Mark [USDA Forest Service; Southern Research Station, New Ellenton, SC (United States); Ray, H. Scott [USDA Forest Service, Savannah River; New Ellenton, SC (United States); Shaw, Christopher E. [USDA Forest Service; Southern Research Station, New Ellenton, SC (United States); Ruth, Charles [South Carolina Dept. of Natural Resources, Columbia, SC (United States)

    2014-09-01

    Predation by coyotes (Canis latrans) on white-tailed deer (Odocoileus virginianus) neonates has led to reduced recruitment in many deer populations in southeastern North America. This low recruitment combined with liberal antlerless deer harvest has resulted in declines in some deer populations, and consequently, increased interest in coyote population control. We investigated whether neonate survival increased after coyote removal, whether coyote predation on neonates was additive to other mortality sources, and whether understory vegetation density affected neonate survival. We monitored neonate survival for 4 years prior to (2006–2009) and 3 years during (2010–2012) intensive coyote removal on 3 32-km2 units on the United States Department of Energy’s Savannah River Site, South Carolina. We removed 474 coyotes (1.63 coyotes/km2 per unit per year), reducing coyote abundance by 78% from pre-removal levels. The best model (wi = 0.927) describing survival probability among 216 radio-collared neonates included a within-year quadratic time trend variable, date of birth, removal treatment, and a varying removal year effect. Under this model, survival differed between pre-treatment and removal periods and it differed among years during the removal period, being >100% greater than pre-treatment survival (0.228) during the first removal year (0.513), similar to pre-treatment survival during the second removal year (0.202), and intermediate during the third removal year (0.431). Despite an initial increase, the overall effect of coyote removal on neonate survival was modest. Mortality rate attributable to coyote predation was lowest during the first removal year (0.357) when survival was greatest, but the mortality rate from all other causes did not differ between the pretreatment period and any year during removals, indicating that coyote predation acted as an additive source of mortality. Survival probability was not related to

  5. Risk Factors Associated with Loco-Regional Failure after Surgical Resection in Patients with Resectable Pancreatic Cancer.

    Science.gov (United States)

    Kim, Hyun Ju; Lee, Woo Jung; Kang, Chang Moo; Hwang, Ho Kyoung; Bang, Seung Min; Song, Si Young; Seong, Jinsil

    2016-01-01

    To evaluate the risk factors associated with loco-regional failure after surgical resection and to identify the subgroup that can obtain benefits from adjuvant radiotherapy (RT). We identified patients treated with surgical resection for resectable pancreatic cancer at Severance hospital between January 1993 and December 2014. Patients who received any neoadjuvant or adjuvant RT were excluded. A total of 175 patients were included. Adjuvant chemotherapy was performed in 107 patients with either a gemcitabine-based regimen (65.4%) or 5-FU based one (34.9%). The median loco-regional failure-free survival (LRFFS) and overall survival (OS) were 23.9 and 33.6 months, respectively. A recurrence developed in 108 of 175 patients (61.7%). The predominant pattern of the first failure was distant (42.4%) and 47 patients (26.9%) developed local failure as the first site of recurrence. Multivariate analysis identified initial CA 19-9 ≥ 200 U/mL, N1 stage, perineural invasion (PNI), and resection margin as significant independent risk factors for LRFFS. Patients were divided into four groups according to the number of risk factors, including initial CA 19-9, N stage, and PNI. Patients exhibiting two risk factors had 3.2-fold higher loco-regional failure (P < 0.001) and patients with all risk factors showed a 6.5-fold increase (P < 0.001) compared with those with no risk factors. In the analysis for OS, patients with more than two risk factors also had 3.3- to 6-fold higher risk of death with statistical significance. The results suggest that patients who exhibit more than two risk factors have a higher risk of locoregional failure and death. This subgroup could be benefited by the effective local adjuvant treatment.

  6. Comparison of Locoregional Recurrence with Mastectomy vs. Breast Conserving Surgery in Pregnancy Associated Breast Cancer (PABC

    Directory of Open Access Journals (Sweden)

    Paniti Sukumvanich

    2009-12-01

    Full Text Available We have compared outcomes, including the locoregional recurrence, between mastectomy and breast conserving therapy in PABC. Patients were divided into those who were treated with mastectomies (group 1 and those with breast conserving surgery (group 2. The groups were comparable except for lower mean age in group 2 and more patients with stage III disease and higher number of nodes positive in the group 1. Five-year actuarial LRR, distant metastases free survival and overall survival in group 1 vs. 2 were 10% vs. 37%, 73% vs. 81% and 57% vs. 59% respectively. The patients with PABC treated with breast conserving therapy, despite having lower stage disease, have a higher risk of local regional recurrence in comparison with those treated with mastectomy.

  7. Target volume definition for intensity-modulated radiotherapy after induction chemotherapy and patterns of treatment failure after sequential chemoradiotherapy in locoregionally advanced oropharyngeal squamous cell carcinoma.

    Science.gov (United States)

    Loo, S W; Geropantas, K; Wilson, P; Martin, W M C; Roques, T W

    2013-03-01

    To validate our approach to target volume definition for intensity-modulated radiotherapy (IMRT) after induction chemotherapy and to analyse the pattern of treatment failure in patients with locoregionally advanced oropharyngeal squamous cell carcinoma (SCC) after sequential chemoradiotherapy (SCRT). We studied all patients with locoregionally advanced oropharyngeal SCC treated with SCRT, definitive IMRT and no prior surgery between December 2004 and February 2010. SCRT consisted of three cycles of induction chemotherapy followed by IMRT with concurrent weekly chemotherapy. Our approach to IMRT tumour volume definition after induction chemotherapy was similar to recommendations from published clinical practice guidelines. Volumetric expansion was used to create the high-dose clinical target volume with a margin of 10 mm. The high-dose planning target volume (PTV) was treated to 65 Gy, whereas the prophylactic-dose PTV received 54 Gy over 30 fractions using the simultaneous integrated boost technique. The location and extent of each treatment failure was recorded, reconstructed on the planning computed tomography images and analysed using the dose distribution of the IMRT plan. Fifty-two patients were included. The median follow-up was 32.2 months (range 5.0-67.1 months). There were seven local failures, no regional recurrences and one with distant disease. None of the patients required post-treatment neck dissection. All local failures were in-field and occurred within the high-dose PTV. There were no marginal recurrences. Actuarial recurrence-free, disease-specific and overall survival rates at 3 years were 83.9, 85.9 and 79.7%, respectively. The absence of marginal recurrences validated the approach to IMRT target volume definition after induction chemotherapy proposed by clinical practice guidelines and practised at our institution. It suggested a lack of benefit with the use of larger geometric margins and additional anatomical expansion for the high

  8. Gall bladder carcinoma: Aggressive malignancy with protean loco-regional and distant spread.

    Science.gov (United States)

    Dwivedi, Amit Nandan Dhar; Jain, Shivi; Dixit, Ruhi

    2015-03-16

    The most common malignancy of biliary tract is gallbladder cancer (GBC) which is the third most common cancer in gastrointestinal tract. It is a lethal disease for most patients in spite of growing awareness and improved diagnostic techniques. GBC has a very poor prognosis and the 5 year survival rate is loco-regional rather than distant. It spreads by lymphatic, vascular, neural, intraperitoneal, and intraductal routes. Sonography is usually the most common imaging test to evaluate symptoms of biliary tract disease including suspected GC. With recent advances in imaging modalities like multi-detector computed tomography (CT) scanners, magnetic resonance imaging-positron emission tomography/CT diagnosis of gallbladder cancer has improved. Studies have also targeted molecular and genetic pathways. Treatment options have included extended and radical surgeries and adjuvant chemotherapy. This review article deals in detail with important aspects of carcinoma gallbladder and its manifestations and challenges. Role of various imaging modalities in characterization and accurate staging has been discussed. The loco-regional spread of this aggressive malignancy is dealt explicitly.

  9. Surgical resection of late solitary locoregional gastric cancer recurrence in stomach bed.

    Science.gov (United States)

    Watanabe, Masanori; Suzuki, Hideyuki; Maejima, Kentaro; Komine, Osamu; Mizutani, Satoshi; Yoshino, Masanori; Bo, Hideki; Kitayama, Yasuhiko; Uchida, Eiji

    2012-07-01

    Late-onset and solitary recurrence of gastric signet ring cell (SRC) carcinoma is rare. We report a successful surgical resection of late solitary locoregional recurrence after curative gastrectomy for gastric SRC carcinoma. The patient underwent total gastrectomy for advanced gastric carcinoma at age 52. Seven years after the primary operation, he visited us again with sudden onset of abdominal pain and vomiting. We finally decided to perform an operation, based on a diagnosis of colon obstruction due to the recurrence of gastric cancer by clinical findings and instrumental examinations. The laparotomic intra-abdominal findings showed that the recurrent tumor existed in the region surrounded by the left diaphragm, colon of splenic flexure, and pancreas tail. There was no evidence of peritoneal dissemination, and peritoneal lavage fluid cytology was negative. We performed complete resection of the recurrent tumor with partial colectomy, distal pancreatectomy, and partial diaphragmectomy. Histological examination of the resected specimen revealed SRC carcinoma, identical in appearance to the previously resected gastric cancer. We confirmed that the intra-abdominal tumor was a locoregional gastric cancer recurrence in the stomach bed. The patient showed a long-term survival of 27 months after the second operation. In the absence of effective alternative treatment for recurrent gastric carcinoma, surgical options should be pursued, especially for late and solitary recurrence.

  10. Locoregional cancer therapy using polymer-based drug depots

    NARCIS (Netherlands)

    Ramazani, F.; van Nostrum, C.F.; Storm, Gerrit; Kiessling, F.; Lammers, Twan Gerardus Gertudis Maria; Hennink, W.E.; Kok, R.J.

    2016-01-01

    Locoregional delivery of anticancer drugs is an attractive approach to minimize adverse effects associated with intravenous chemotherapy. Polymer-based drug depots injected or implanted intratumorally or adjacent to the tumor can provide long-term local drug exposure. This review highlights studies

  11. Ophthalmic loco-regional anaesthesia: Reducing discomfort during ...

    African Journals Online (AJOL)

    Loco-regional anaesthesia is commonly used for both intraocular and extraocular surgical procedures, although the provision and use of the anaesthetic technique varies worldwide. Injection techniques (retrobulbar, peribulbar and sub-Tenon's blocks) are associated with significant pain; indeed, many patients have a fear ...

  12. Can Locoregional Treatment of the Primary Tumor Improve Outcomes for Women With Stage IV Breast Cancer at Diagnosis?

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, David H.A., E-mail: dhanguyen@yahoo.com [British Columbia Cancer Agency, Department of Radiation Oncology, BC (Canada); Departement de Radio-Oncologie, Hopital Maisonneuve-Rosemont, Montreal, Quebec (Canada); Truong, Pauline T. [British Columbia Cancer Agency, Department of Radiation Oncology, BC (Canada); Breast Cancer Outcomes Unit, British Columbia Cancer Agency, BC (Canada); University of British Columbia, BC (Canada); Alexander, Cheryl; Walter, Caroline V.; Hayashi, Emily; Christie, Jennifer [Breast Cancer Outcomes Unit, British Columbia Cancer Agency, BC (Canada); Lesperance, Mary [Department of Mathematics and Statistics, University of Victoria, BC (Canada)

    2012-09-01

    Purpose: To examine the effect of locoregional treatment (LRT) of the primary tumor on survival in patients with Stage IV breast cancer at diagnosis. Methods and Materials: The study cohort comprised 733 women referred to the British Columbia Cancer Agency between 1996 and 2005 with newly diagnosed clinical or pathologic M1 breast cancer. Tumor and treatment characteristics, overall survival (OS), and locoregional progression-free survival were compared between patients treated with (n = 378) and without (n = 355) LRT of the primary disease. Multivariable analysis was performed with Cox regression modeling. Results: The median follow-up time was 1.9 years. LRT consisted of surgery alone in 67% of patients, radiotherapy alone in 22%, and both in 11%. LRT was used more commonly in women with age <50 years, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, Stage T1-2 tumors, N0-1 disease, limited M1 burden, and asymptomatic M1 disease (all p < 0.05). Systemic therapy was used in 92% of patients who underwent LRT and 85% of patients who did not. In patients treated with LRT compared with those without LRT, the 5-year OS rates were 21% vs. 14% (p < 0.001), and the rates of locoregional progression-free survival were 72% vs. 46% (p < 0.001). Among 378 patients treated with LRT, the rates of 5-year OS were higher in patients with age <50, ECOG performance status 0-1, estrogen receptor-positive disease, clear surgical margins, single subsite, bone-only metastasis, and one to four metastatic lesions (all p < 0.003). On multivariable analysis, LRT was associated with improved OS (hazard ratio, 0.78; 95% confidence interval, 0.64-0.94, p = 0.009). Conclusion: Locoregional treatment of the primary disease is associated with improved survival in some women with Stage IV breast cancer at diagnosis. Among those treated with LRT, the most favorable rates of survival were observed in subsets with young age, good performance status, estrogen receptor-positive disease

  13. Long-term results of paclitaxel plus cisplatin with concurrent radiotherapy for loco-regional esophageal squamous cell carcinoma.

    Science.gov (United States)

    Zhu, Han-Ting; Ai, Da-Shan; Tang, Hua-Rong; Badakhshi, Harun; Fan, Jian-Hong; Deng, Jia-Ying; Zhang, Jun-Hua; Chen, Yun; Zhang, Zhen; Xia, Yi; Guo, Xiao-Mao; Jiang, Guo-Liang; Zhao, Kuai-Le

    2017-01-21

    To evaluate the long-term effectiveness and late toxicities of paclitaxel (PTX) plus cisplatin (DDP) with concurrent radiotherapy for locally advanced esophageal squamous cancer. Between 2008 and 2011, 76 patients were enrolled in a phase II study on the treatment of loco-regionally advanced esophageal cancer with radiotherapy (68.4 Gy/44 fractions or 61.2 Gy/34 fractions) combined with 4-cycle chemotherapy consisting of DDP (25 mg/m2 per day for 3 d) and PTX (175 mg/m2 for 3 h). The primary endpoints were overall survival and progression-free survival, and the secondary endpoints were toxicity and the treatment failure pattern. A total of 76 patients were enrolled in this study, of whom 63.2% finished the whole regimen. The 5-year survival rates for the per-protocol population and intent-to-treat population were 25.4% and 26.4%, respectively, and the median survival rates were 23.7 mo and 28.5 mo, respectively. Grade 3 or 4 late toxicity was observed in only one patient (heart failure). In log-rank analysis, the pretreatment stage (stage II + III: 36.1 mo vs stage IV: 14.9 mo) and the completed cycle (1-3 cycles: 16.1 mo vs 4 cycles: 35.5 mo) were significant prognostic factors (P = 0.037 loco-regionally advanced esophageal squamous cancer.

  14. Survival of egg-laying controlling neuroendocrine cells during reproductive senescence of a mollusc

    NARCIS (Netherlands)

    Janse, C.

    2004-01-01

    During brain aging neuronal degradation occurs. In some neurons this may result in degeneration and cell death, still other neurons may survive and maintain their basic properties. The present study deals with survival of the egg-laying controlling neuroendocrine caudodorsal cells (CDCs) during

  15. Molecular predictors of locoregional and distant metastases in oropharyngeal squamous cell carcinoma.

    Science.gov (United States)

    Barber, Brittany R; Biron, Vincent L; Klimowicz, Alexander C; Puttagunta, Lakshmi; Côté, David W J; Seikaly, Hadi

    2013-10-16

    The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing due to fundamental changes in oncogenesis related to effects of the human papilomavirus (HPV). Virally-mediated tumours behave and respond to treatment differently than their classic, carcinogenically-mediated counterparts despite similar stage and grade of disease. This difference in behaviour has lead to investigation of etiologies of OPSCC at the molecular level. This study was designed to identify biomarker profiles predictive of locoregional and distant metastases and recurrence in OPSCC. Cross-sectional study of a prospectively-collected oropharyngeal tumour database was undertaken. All patients with OPSCC presenting to the University of Alberta Hospital from 2002-2009 were included in the study. Data collection from the Alberta Cancer Registry, including demographics, nodal status, distant metastases, treatment, recurrence, and survival, was undertaken. Tissue micro-arrays (TMAs) were constructed for each tumour specimen using triplicate cores (0.6mm) of formalin-fixed, paraffin-embedded (FFPE) pre-treatment tumour tissue. TMAs were processed using immunohistochemistry for p16, EGFR, Ki67, p53, and Bcl-XL. Positivity for each biomarker was determined using quantified AQUAnalysis ® scores on histoplots. Multivariate statistics were utilized to assess the relationship between each biomarker and locoregional and distant metastases, as well as recurrence-free survival (RFS). High expression of p16 (p=0.000) and Bcl-XL (p=0.039) independently demonstrated a significant association with nodal disease at presentation. Kaplan-Meier analysis demonstrated improved RFS in patients with high p16 and decreased RFS in patients with high p53 expression. Cox regression analysis supported p16 as an independent prognosticator for improved RFS. p53 demonstrated an association with recurrence, but when compared to p16 status, nodal status, and staging, was not an independent predictor of recurrence

  16. [Intra-arterial regional chemotherapy and intensive loco-regional radiotherapy in the treatment of locally advanced cancer of the breast].

    Science.gov (United States)

    Nicolato, A

    1990-09-01

    A multimodal treatment combining intra-arterial chemotherapy and intensive loco-regional radiotherapy was administered to 55 patients with locally advanced breast cancer. Adjuvant polychemotherapy followed, and eventually endocrino-therapy. Combined intra-arterial chemotherapy and intensive radiotherapy gave excellent results in both primary and lymph node lesions, with 90.9% and 92.2% complete/partial response rates. Three-year and 5-year actuarial survival rates were 69% and 59%, respectively. Patients showing better local responses to combined intra-arterial chemotherapy and intensive radiotherapy had longer survival and less frequent local recurrences. Combined intra-arterial chemotherapy and intensive loco-regional radiotherapy seems to be an effective modality for the treatment of locally advanced breast cancer.

  17. The orphan nuclear hormone receptor ERRβ controls rod photoreceptor survival

    Science.gov (United States)

    Onishi, Akishi; Peng, Guang-Hua; Poth, Erin M.; Lee, Daniel A.; Chen, Jichao; Alexis, Uel; de Melo, Jimmy; Chen, Shiming; Blackshaw, Seth

    2010-01-01

    Mutation of rod photoreceptor-enriched transcription factors is a major cause of inherited blindness. We identified the orphan nuclear hormone receptor estrogen-related receptor β (ERRβ) as selectively expressed in rod photoreceptors. Overexpression of ERRβ induces expression of rod-specific genes in retinas of wild-type as well as Nrl−/− mice, which lack rod photoreceptors. Mutation of ERRβ results in dysfunction and degeneration of rods, whereas inverse agonists of ERRβ trigger rapid rod degeneration, which is rescued by constitutively active mutants of ERRβ. ERRβ coordinates expression of multiple genes that are rate-limiting regulators of ATP generation and consumption in photoreceptors. Furthermore, enhancing ERRβ activity rescues photoreceptor defects that result from loss of the photoreceptor-specific transcription factor Crx. Our findings demonstrate that ERRβ is a critical regulator of rod photoreceptor function and survival, and suggest that ERRβ agonists may be useful in the treatment of certain retinal dystrophies. PMID:20534447

  18. Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation for Locoregionally Advanced Head and Neck Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Seiwert, Tanguy Y., E-mail: tseiwert@medicine.bsd.uchicago.edu [Departments of Medicine, University of Chicago, Chicago, Illinois (United States); Melotek, James M. [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Blair, Elizabeth A. [Department of Otolaryngology, University of Chicago, Chicago, Illinois (United States); Stenson, Kerstin M. [Department of Otolaryngology, Rush University, Chicago, Illinois (United States); Salama, Joseph K. [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Witt, Mary Ellyn [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Brisson, Ryan J.; Chawla, Apoorva; Dekker, Allison [Departments of Medicine, University of Chicago, Chicago, Illinois (United States); Lingen, Mark W. [Department of Pathology, University of Chicago, Chicago, Illinois (United States); Kocherginsky, Masha [Department of Public Health Sciences, University of Chicago, Chicago, Illinois (United States); Villaflor, Victoria M. [Departments of Medicine, University of Chicago, Chicago, Illinois (United States); Cohen, Ezra E.W. [Moores Cancer Center, University of California, San Diego, San Diego, California (United States); Haraf, Daniel J. [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Vokes, Everett E. [Departments of Medicine, University of Chicago, Chicago, Illinois (United States)

    2016-09-01

    Purpose: The role of cetuximab in the treatment of locoregionally advanced head and neck squamous cell cancer (LA-HNSCC) remains poorly defined. In this phase 2 randomized study, we investigated the addition of cetuximab to both induction chemotherapy (IC) and hyperfractionated or accelerated chemoradiation. Methods and Materials: Patients with LA-HNSCC were randomized to receive 2 cycles of weekly IC (cetuximab, paclitaxel, carboplatin) and either Cetux-FHX (concurrent cetuximab, 5-fluorouracil, hydroxyurea, and 1.5 Gy twice-daily radiation therapy every other week to 75 Gy) or Cetux-PX (cetuximab, cisplatin, and accelerated radiation therapy with delayed concomitant boost to 72 Gy in 42 fractions). The primary endpoint was progression-free survival (PFS), with superiority compared with historical control achieved if either arm had 2-year PFS ≥70%. Results: 110 patients were randomly assigned to either Cetux-FHX (n=57) or Cetux-PX (n=53). The overall response rate to IC was 91%. Severe toxicity on IC was limited to rash (23% grade ≥3) and myelosuppression (38% grade ≥3 neutropenia). The 2-year rates of PFS for both Cetux-FHX (82.5%) and Cetux-PX (84.9%) were significantly higher than for historical control (P<.001). The 2-year overall survival (OS) was 91.2% for Cetux-FHX and 94.3% for Cetux-PX. With a median follow-up time of 72 months, there were no significant differences in PFS (P=.35) or OS (P=.15) between the treatment arms. The late outcomes for the entire cohort included 5-year PFS, OS, locoregional failure, and distant metastasis rates of 74.1%, 80.3%, 15.7%, and 7.4%, respectively. The 5-year PFS and OS were 84.4% and 91.3%, respectively, among human papillomavirus (HPV)-positive patients and 65.9% and 72.5%, respectively, among HPV-negative patients. Conclusions: The addition of cetuximab to IC and chemoradiation was tolerable and produced long-term control of LA-HNSCC, particularly among poor-prognosis HPV-negative patients. Further

  19. Prognostic factors for local control and survival after radiotherapy of metastatic spinal cord compression

    NARCIS (Netherlands)

    Rades, Dirk; Fehlauer, Fabian; Schulte, Rainer; Veninga, Theo; Stalpers, Lukas J. A.; Basic, Hiba; Bajrovic, Amira; Hoskin, Peter J.; Tribius, Silke; Wildfang, Ingeborg; Rudat, Volker; Engenhart-Cabilic, Rita; Karstens, Johann H.; Alberti, Winfried; Dunst, Juergen; Schild, Steven E.

    2006-01-01

    To evaluate potential prognostic factors for local control and survival after radiotherapy of metastatic spinal cord compression (MSCC). The following potential prognostic factors were investigated retrospectively in 1,852 patients irradiated for MSCC: age, sex, performance status, primary tumor,

  20. Children with cancer with different survival perspectives: defensiveness, control strategies, and psychological adjustment

    NARCIS (Netherlands)

    Grootenhuis, M. A.; Last, B. F.

    2001-01-01

    The main objective of the present study was to investigate whether children with cancer with different survival perspectives differ in their psychological adjustment, defensiveness and their use of cognitive control strategies. Furthermore, the study investigated which variables predict emotional

  1. The influence of circumferential resection margin status on loco-regional recurrence in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Park, Hae Jin; Kim, Hak Jae; Chie, Eui Kyu; Kang, Chang Hyun; Kim, Young Tae

    2013-06-01

    To analyze treatment outcomes and patterns of recurrence, and to examine the impact of adjuvant postoperative radiotherapy (PORT) after esophagectomy in esophageal squamous cell carcinoma (SqCC) regarding the status of circumferential resection margin (CRM). We performed a retrospective review of esophageal cancer patients operated in Seoul National University Hospital between 2003 and 2010. Pathologically proven T3 SqCC patients with written reports mentioning the status of CRM were selected. Fifty-nine out of 71 patients (83.1%) had CRM+. Twenty-eight patients had radiotherapy in CRM+ and CRM-, respectively. The median follow-up period was 17.1 months (range: 5.2-63.1). Median survival and 2-year overall survival were 13.8 months and 41.9% in CRM+, and 27.3 months and 74.1% in CRM-, respectively. Loco-regional relapse-free survival (LRRFS) rate at 2 years was 33.6% and 74.1% in each groups (P = 0.029). Loco-regional recurrence was the major pattern of failure in CRM+. PORT did not improve LRRFS. The esophageal SqCC patients with CRM+ after resection showed worse LRRFS. This finding validated the prognostic value of CRM status. Nevertheless, we failed to demonstrate the benefits of adjuvant PORT in CRM+. This might suggest the necessity of neoadjuvant therapy to decrease the CRM+ rate after esophagectomy. Copyright © 2012 Wiley Periodicals, Inc.

  2. CEA Level, Radical Surgery, CD56 and CgA Expression Are Prognostic Factors for Patients With Locoregional Gastrin-Independent GNET.

    Science.gov (United States)

    Li, Yuan; Bi, Xinyu; Zhao, Jianjun; Huang, Zhen; Zhou, Jianguo; Li, Zhiyu; Zhang, Yefan; Li, Muxing; Chen, Xiao; Hu, Xuhui; Chi, Yihebali; Zhao, Dongbing; Zhao, Hong; Cai, Jianqiang

    2016-05-01

    Gastrin-independent gastric neuroendocrine tumors (GNETs) are highly malignant. Radical resections and lymphadenectomy are considered to be the only possible curative treatment for these tumors. However, the prognosis of gastrin-independent GNETs is not well defined. In this study, we identified prognostic factors of locoregional gastrin-independent GNETs.All patients diagnosed with locoregional gastrin-independent GNETs between 2000 and 2014 were included in this retrospective study. Clinical characteristics, blood tests, pathological characteristics, treatments, and follow-up data of the patients were collected and analyzed.Of the 66 patients diagnosed with locoregional gastrin-independent GNETs, 57 (86.4%) received radical resections, 7 (10.6%) with palliative resection, 1 (1.5%) with gastrojejunostomy, and 1 (1.5%) with exploration surgeries. The median survival time for these patients was 19.0 months (interquartile range, 11.0-38.0). The 1-, 3-, and 5-year survival rates were 72%, 34%, and 28%, respectively. Multivariate analysis indicated that carcinoembryonic antigen (CEA) level (P = 0.04), radical resection (P = 0.04), and positive Cluster of Differentiation 56 (CD56) expression (P = 0.016) were significant prognostic factors on overall survival rate. Further univariate and multivariate analysis of 57 patients who received radical resections found that CgA expression (P = 0.35) and CEA level (P = 0.33) are independent prognostic factors.Gastrin-independent GNETs had poor prognosis. Serum CEA level, radical surgery, CD56 and CgA expression are markers to evaluate the survival of patients with locoregional gastrin-independent GNETs.

  3. A prognostic index for locoregional recurrence after neoadjuvant chemotherapy

    OpenAIRE

    Herrero-Vicent, C; Guerrero-Zotano, A; Gavil?-Gregori, J; Hern?ndez-Blanquisett, A; Sandiego-Contreras, S; Samper-Hiraldo, JM; Guillem-Porta, V; Ruiz-Sim?n, A

    2016-01-01

    Background The appropriate selection criteria for breast-conserving surgery (BCS) or mastectomy after neoadjuvant chemotherapy (NAC) are poorly defined. The aim of this study is to analyse the incidence and prognostic factors for locoregional recurrence (LRR) in patients with breast cancer (BC) treated with NAC to develop a prognostic score to help with clinical decision-making. Materials and methods Using our retrospective maintained BC database, we identified 730 patients treated with NAC (...

  4. Locoregional IL-2 low dose applications for gastrointestinal tumors

    Science.gov (United States)

    Krastev, Zachary; Koltchakov, V; Tomova, R; Deredjian, S; Alexiev, A; Popov, D; Tomov, B; Koten, Jan-Willem; Jacobs, John; Otter, Willem Den

    2005-01-01

    AIM: To explore the feasibility of local interleukin 2 (IL-2) in patients with different forms of abdominal cancer. This required experimentation with the time interval between IL-2 applications and the methods of application. METHODS: Sixteen patients with stages III and IV of gastrointestinal malignancies (primary or metastatic) who were admitted to our Department of Gastroenterology were treated with locoregionally applied IL-2 in low doses. RESULTS: No major problems applying locoregional IL-2 were encountered. In 6 out of 16 patients, a modest but clinically worthwhile improvement was obtained. Adverse effects were minimal. The therapeutic scheme was well tolerated, even in patients in a poor condition. CONCLUSION: This study demonstrates the feasibility of low dose locoregional IL-2 application in advanced abdominal cancer. Local IL-2 therapy gives only negligible adverse effects. The results suggest that it is important to apply intratumorally. Local IL-2 may be given adjunct to standard therapeutic regimes and does not imply complex surgical interventions. These initial results are encouraging. PMID:16222748

  5. Biochemical Control With Radiotherapy Improves Overall Survival in Intermediate and High-Risk Prostate Cancer Patients Who Have an Estimated 10-Year Overall Survival of >90%

    Energy Technology Data Exchange (ETDEWEB)

    Herbert, Christopher, E-mail: cherbert@bccancer.bc.ca [Department of Radiation Oncology, British Columbia Cancer Agency, Vancouver Centre, Vancouver, BC (Canada); Liu, Mitchell; Tyldesley, Scott; Morris, W. James [Department of Radiation Oncology, British Columbia Cancer Agency, Vancouver Centre, Vancouver, BC (Canada); Joffres, Michel [Department of Health Sciences, Simon Fraser University, Surrey, BC (Canada); Khaira, Mandip; Kwan, Winkle [Department of Radiation Oncology, British Columbia Cancer Agency, Fraser Valley Centre, Surrey, BC (Canada); Moiseenko, Vitali [Department of Medical Physics, British Columbia Cancer Agency, Vancouver Centre, Vancouver, BC (Canada); Pickles, Thomas [Department of Radiation Oncology, British Columbia Cancer Agency, Vancouver Centre, Vancouver, BC (Canada)

    2012-05-01

    Purpose: To identify subgroups of patients with carcinoma of the prostate treated with radical radiotherapy that have improved overall survival when disease is biochemically controlled. Methods and Materials: A cohort of 1,060 prostate cancer patients treated with radical radiotherapy was divided into nine subgroups based on National Comprehensive Cancer Network risk category and estimated 10-year overall survival (eOS 10y) derived from the age adjusted Charlson Comorbidity Index. Patients with and without biochemical control were compared with respect to overall survival. Actuarial estimates of overall survival were calculated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used for analysis of overall survival. Results: Median follow-up was 125 months (range, 51-176 months). Only the subgroups with high or intermediate risk disease and an eOS 10y of >90% had a statistically significantly improved overall survival when prostate cancer was biochemically controlled. In all other groups, biochemical control made no significant difference to overall survival. In the subgroup with high-risk disease and eOS 10y >90%, actuarial overall survival was 86.3% (95% confidence interval [CI] 78.5%-94.1%) and 62.1% (95% CI 52.9%-71.3%) for patients with biochemical control and biochemical relapse respectively (p = 0.002). In the intermediate risk group with eOS >90%, actuarial overall survival was 95.3% (95% CI 89.0%-100%) and 79.8% (95% CI 68.0%-91.6%) for biochemically controlled and biochemically relapsed patients (p = 0.033). On multivariate analysis, National Comprehensive Cancer Network risk group (p = 0.005), biochemical control (p = 0.033) and eOS 10y (p < 0.001) were statistically significant. Conclusion: Biochemical control translates into improved overall survival in patients with high or intermediate risk disease and an estimated 10-year overall survival of >90%.

  6. Prognosis after treatment for loco-regional recurrence after mastectomy or breast conserving therapy in two randomised trials (EORTC 10801 and DBCG-82TM). EORTC Breast Cancer Cooperative Group and the Danish Breast Cancer Cooperative Group

    NARCIS (Netherlands)

    van Tienhoven, G.; Voogd, A. C.; Peterse, J. L.; Nielsen, M.; Andersen, K. W.; Mignolet, F.; Sylvester, R.; Fentiman, I. S.; van der Schueren, E.; van Zijl, K.; Blichert-Toft, M.; Bartelink, H.; van Dongen, J. A.

    1999-01-01

    The aim of this study was to investigate and compare the prognosis after treatment for loco-regional recurrences (LR) after (modified) radical mastectomy (MRM) or breast conserving therapy (BCT), in terms of overall survival and time to subsequent LR, in patients originally treated in two European

  7. Tribally Controlled Community College Libraries: A Paradigm for Survival.

    Science.gov (United States)

    Patterson, Lotsee; Taylor, Rhonda Harris

    1996-01-01

    This study reports on the results of a mail survey administered to tribally controlled college libraries during 1993, just before the colleges were granted federal land-grant college status. Highlights include the historical development of the institutions operated by Native American Indian tribes; budgets; staff; services; computer utilization;…

  8. Damage control resuscitation in combination with damage control laparotomy: a survival advantage.

    Science.gov (United States)

    Duchesne, Juan C; Kimonis, Katerina; Marr, Alan B; Rennie, Kelly V; Wahl, Georgia; Wells, Joel E; Islam, Tareq M; Meade, Peter; Stuke, Lance; Barbeau, James M; Hunt, John P; Baker, Christopher C; McSwain, Norman E

    2010-07-01

    Damage control laparotomy (DCL) improves outcomes when used in patients with severe hemorrhage. Correction of coagulopathy with close ratio resuscitation while limiting crystalloid forms a new methodology known as damage control resuscitation (DCR). We hypothesize a survival advantage in DCL patients managed with DCR when compared with DCL patients managed with conventional resuscitation efforts (CRE). This study is a 4-year retrospective study of all DCL patients who required >or=10 units of packed red blood cells (PRBC) during surgery. A 2-year period after institution of DCR (DCL and DCR) was compared with the preceding 2 years (DCL and CRE). Univariate analysis of continuous data was done with Student's t test followed by multiple logistic regression. One Hundred twenty-four and 72 patients were managed during the DCL and CRE and DCL and DCR time periods, respectively. Baseline patient characteristics of age, Injury Severity Score, % penetrating, blood pressure, hemoglobin, base deficit, and INR were similar between groups. There was no difference in quantity of intraoperative PRBC utilization between DCL and CRE and DCL and DCR study periods: 21.7 units versus 25.5 units (p = 0.53); however, when compared with DCL and CRE group, patients in the DCL and DCR group received less intraoperative crystalloids, 4.7 L versus 14.2 L (p = 0.009); more fresh frozen plasma (FFP), 18.2 versus 6.4 (p = 0.002); a closer FFP to PRBC ratio, 1 to 1.2 versus 1 to 4.2 (p = 0.002); platelets to PRBC ratio, 1:2.3 versus 1:5.9 (0.002); shorter mean trauma intensive care unit length of stay, 11 days versus 20 days (p = 0.01); and greater 30-day survival, 73.6% versus 54.8% (p ratio; 95% confidence interval: 0.19 (0.05-0.33), p = 0.005). This is the first civilian study that analyses the impact of DCR in patients managed with DCL. During the DCL and DCR study period more PRBC, FFP, and platelets with less crystalloid solution was used intraoperatively. DCL and DCR were associated with

  9. Controlling Redox Status for Stem Cell Survival, Expansion, and Differentiation

    Directory of Open Access Journals (Sweden)

    Sébastien Sart

    2015-01-01

    Full Text Available Reactive oxygen species (ROS have long been considered as pathological agents inducing apoptosis under adverse culture conditions. However, recent findings have challenged this dogma and physiological levels of ROS are now considered as secondary messengers, mediating numerous cellular functions in stem cells. Stem cells represent important tools for tissue engineering, drug screening, and disease modeling. However, the safe use of stem cells for clinical applications still requires culture improvements to obtain functional cells. With the examples of mesenchymal stem cells (MSCs and pluripotent stem cells (PSCs, this review investigates the roles of ROS in the maintenance of self-renewal, proliferation, and differentiation of stem cells. In addition, this work highlights that the tight control of stem cell microenvironment, including cell organization, and metabolic and mechanical environments, may be an effective approach to regulate endogenous ROS generation. Taken together, this paper indicates the need for better quantification of ROS towards the accurate control of stem cell fate.

  10. Induction Chemotherapy Has No Prognostic Value in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma and Chronic Hepatitis B Infection in the IMRT Era

    Directory of Open Access Journals (Sweden)

    Lu-Lu Zhang

    2017-10-01

    Full Text Available BACKGROUND: The effectiveness of induction chemotherapy (IC followed by concurrent chemoradiotherapy (CCRT over CCRT alone in patients with locoregionally advanced nasopharyngeal carcinoma (NPC and chronic hepatitis B infection in the intensity-modulated radiotherapy (IMRT era is unknown. PATIENTS AND METHODS: A total of 249 patients with stage T1-2 N2-3 or T3-4 N1-3 NPC and chronic hepatitis B infection treated with IMRT were retrospectively reviewed. Propensity score matching (PSM was employed to balance covariates; 140 patients were propensity-matched (1:1 basis. Survival outcomes in the IC + CCRT and CCRT groups were compared using the Kaplan–Meier method, log-rank test and Cox proportional hazards model. RESULTS: No significant survival differences were observed between IC + CCRT and CCRT (5-year overall survival, 88.3% vs. 82.2%; P = .484; disease-free survival, 73.9% vs. 75.2%; P = .643; distant metastasis-free survival, 84.1% vs. 85.1%; P = .781; and locoregional failure-free survival, 87.9% vs. 85.1%; P = .834. After adjusting for known prognostic factors in multivariate analysis, IC was not an independent prognostic factor for any outcome (all P > .05; subgroup analysis based on T category (T1-2/T3-4, N category (N0-1/N2-3, and overall stage (III/IV confirmed these results. The incidence of hepatic function damage in the IC + CCRT and CCRT groups was not significantly different. CONCLUSION: IC + CCRT leads to comparable survival outcomes and hepatic function damage compared to CCRT alone in patients with locoregionally advanced NPC with chronic hepatitis B infection in the IMRT era. Further investigations are warranted.

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

    Science.gov (United States)

    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. Copyright © 2015. Published by Elsevier Ltd.

  12. Cancer of the anal canal and local control.

    Science.gov (United States)

    Valentini, V; Mantello, G; Luzi, S; Macchia, G; Manfrida, S; Smaniotto, D

    1998-01-01

    Concomitant radiochemotherapy is the standard treatment of squamous cell carcinoma of the anal canal. It can afford a high local control rate though the same impact has not been observed on survival. A few reports have concerned the impact of local control on distant metastases and survival. From 1988 to 1998 at the "Divisione di Radioterapia" of the "Università Cattolica del S. Cuore" of Rome 30 patients with squamous cell carcinoma of the anal canal were treated for cure. Treatment consisted of two cycles of radiotherapy (23.4 Gy) with a 4-5 week split in each cycle. 5FU (100 mg/sqm/24 h) was administered in continuous infusion for the first 4 days of therapy; mitomycin C (10 mg/sqm bolus) was administered on day 1, 4-6 weeks after the end of cycle 2 of concomitant radiochemotherapy, patients received a boost of interstitial brachytherapy. Local control on T of all patients was 84% at 5 years. Six patients showed locoregional recurrence: 3 recurrences on T and 4 disease progressions in locoregional lymph nodes. 3 of 6 patients underwent salvage surgery. The initial extent of the disease, the patient's age and brachytherapy boost did not have a statistically significant influence on local control. Two of the 30 patients showed liver metastases, and at their appearance, one patient was free of local disease while the other showed locoregional progression after Miles' operation for salvage. The metastasis-free interval was not significantly influenced by local control, although at 5 years, 96% of patients with local control of T were free of metastases vs 75% of those with recurrence on T (p = 0.22). Overall actuarial survival at 5 years was 75%. The behavior of survival in our experience seemed to be significantly influenced by local control: in the group with local control, 5-year survival was 85% vs 40% of patients with local recurrence (p = 0.01).

  13. [Loco-regional treatments of the metastatic sites for patients with pauci-metastatic cutaneous melanoma (without brain metastasis): French national guidelines].

    Science.gov (United States)

    Sassolas, Bruno; Mourrégot, Anne; Thariat, Juliette; Tiffet, Olivier; Dygai-Cochet, Inna; Mirabel, Xavier; Truc, Gilles; Cupissol, Didier; Modiano, Philippe; Combemale, Patrick; Bedane, Christophe; Derrey, Stéphane; Lamant, Laurence; Lubrano, Vincent; Siegrist, Sophie; Rougé-Bugat, Marie-Ève; Mazeau-Woynar, Valérie; Verdoni, Laëtitia; Planchamp, François; Leccia, Marie-Thérèse

    2014-01-01

    The last years are marked by the emergence of new molecules for the treatment of metastatic cutaneous melanoma with a significant benefit on the survival. Besides, some techniques are in development for the loco-regional treatment of the metastatic sites, bringing new therapeutic perspectives. However, their respective use and place in the therapeutic strategy are debated by healthcare professionals. The French National Cancer Institute leads a national clinical practice guidelines project since 2008. It realized a review of these modalities of treatment and developed recommendations. The clinical practice guidelines development process is based on systematic literature review and critical appraisal by a multidisciplinary expert workgroup. The recommendations are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines are reviewed by independent practitioners in cancer care delivery. This article presents recommendations for loco-regional treatments of the pulmonary, bone, cutaneous, hepatic and digestive metastatic sites for patients with pauci-metastatic cutaneous melanoma.

  14. Clinical Outcomes of Volume-Modulated Arc Therapy in 205 Patients with Nasopharyngeal Carcinoma: An Analysis of Survival and Treatment Toxicities.

    Directory of Open Access Journals (Sweden)

    Rui Guo

    Full Text Available To investigate the clinical efficacy and treatment toxicity of volume-modulated arc therapy (VMAT for nasopharyngeal carcinoma (NPC.205 VMAT-treated NPC patients from our cancer center were prospectively entrolled. All patients received 68-70 Gy irradiation based on the planning target volume of the primary gross tumor volume. Acute and late toxicities were graded according to the Common Terminology Criteria for Adverse Events v3.0 and Radiation Therapy Oncology Group Late Radiation Morbidity Scoring Criteria.The median follow-up period was 37.3 months (range, 6.3-45.1 months. The 3-year estimated local failure-free survival, regional failure-free survival, locoregional failure-free survival, distant metastasis-free survival, disease-free survival and overall survival were 95.5%, 97.0%, 94.0%, 92.1%, 86.8% and 97.0%, respectively. Cox regression analysis showed primary gross tumor volume, N stage and EBV-DNA to be independent predictors of VMAT outcomes (P < 0.05. The most common acute and late side effects were grade 2-3 mucositis (78% and xerostomia (83%, 61%, 34%, and 9% at 3, 6, 12 and 24 months after VMAT, respectively.VMAT for the primary treatment of NPC achieved very high locoregional control with a favorable toxicity profile. The time-saving benefit of VMAT will enable more patients to receive precision radiotherapy.

  15. Cancer with diabetes: prevalence, metabolic control, and survival in an academic oncology practice.

    Science.gov (United States)

    Karlin, Nina J; Dueck, Amylou C; Cook, Curtiss B

    2012-01-01

    To determine the prevalence of diabetes mellitus, glycemic control, and impact of diabetes on overall survival in an academic oncology practice. Data on cancer patients (1999 to 2008) were retrieved from the institutional cancer registry and linked to electronic files to obtain diabetes status and hemoglobin A1c (A1C) values within the first 6 months of cancer diagnosis. Overall survival by cancer type with and without diabetes was compared using Cox regression. Excluding skin and hematologic malignancies, 15,951 cancer cases were identified. Overall diabetes prevalence was 6.8% (n = 1,090), declining over time (Pcancers (7.6% [68 of 899]). Patients with diabetes were older (mean age, 70 versus 66 years; Pcancer patients was 6.8% and did not differ across cancer types (P = 0.80). Only 58.6% (331 of 565) of diabetic cancer patients had all A1C cancer diagnosis. Pancreatic cancer patients with coexisting diabetes had better overall survival than pancreatic cancer patients without diabetes (hazard ratio, 0.60; 95% confidence interval 0.44 to 0.80; Pcancer patients had worse overall survival than prostate cancer patients without diabetes (hazard ratio, 1.36; 95% confidence interval 1.05 to 1.76; P = 0.02). In this academic oncology practice, diabetes was common, glycemic control often was suboptimal, and survival varied by cancer type. Additional study is needed to optimize glucose management and investigate mechanisms underlying age, sex, and survival differences.

  16. Distributed Sharing of Functionalities and Resources in Survivable GMPLS-controlled WSONs

    DEFF Research Database (Denmark)

    Fagertun, Anna Manolova; Cerutti, I.; Muñoz, R.

    2012-01-01

    at the physical layer (i.e., quality of transmission, QoT) and at the upper layer also in the case of a failure (i.e., survivability). This paper aims to apply the sharing concept to a WSON with QoT and survivability requirements (against single-link failures). QoT is guaranteed by resorting to regeneration...... is exploited to ensure survivability against single-link failures and make the sharing of network resources (regenerators and wavelengths) possible. The paper presents a novel distributed scheme (DISTR) for reservation of regenerators and wavelengths in generalized multi-protocol label switching controlled...... WSONs, in order to ensure the required level of QoT and survivability. Novel objects and selection strategies for the resource reservation protocol with traffic engineering extensions are proposed and evaluated. The DISTR scheme effectively combines regeneration and WC points, leading to a noticeable...

  17. Melanoma targeting with the loco-regional chemotherapeutic, Melphalan: From cell death to immunotherapeutic efficacy.

    Science.gov (United States)

    Dudek-Perić, Aleksandra Maria; Gołąb, Jakub; Garg, Abhishek D; Agostinis, Patrizia

    2015-12-01

    All immunoregulatory chemotherapeutics are chiefly applied in a systemic setting for anticancer therapy. However, immune responses following loco-regional application of chemotherapy may differ from those after systemic application. We recently found that Melphalan, a prototypical loco-regionally applied chemotherapeutic agent, exhibits the ability to increase the immunogenicity of dying melanoma cells.

  18. IMRT With Simultaneous Integrated Boost and Concurrent Chemotherapy for Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck

    Energy Technology Data Exchange (ETDEWEB)

    Montejo, Michael E.; Shrieve, Dennis C. [Department of Radiation Oncology, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah (United States); Bentz, Brandon G.; Hunt, Jason P.; Buchman, Luke O. [Division of Otolaryngology-Head Neck Surgery, Department of Surgery, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah (United States); Agarwal, Neeraj [Department of Internal Medicine, Oncology Division, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah (United States); Hitchcock, Ying J., E-mail: ying.hitchcock@hci.utah.edu [Department of Radiation Oncology, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah (United States)

    2011-12-01

    Purpose: To evaluate the efficacy and toxicity of accelerated radiotherapy with concurrent chemotherapy in advanced head-and-neck squamous cell carcinoma. Methods and Materials: Between April 2003 and May 2008, 43 consecutive patients with advanced head-and-neck squamous cell carcinoma received accelerated chemoradiation with concurrent cisplatin or cetuximab. The doses for intensity-modulated radiotherapy with simultaneous integrated boost were 67.5, 60.0, and 54 Gy in 30 daily fractions of 2.25, 2.0, and 1.8 Gy to the planning target volumes for gross disease, high-risk nodes, and low-risk nodes, respectively. Results: Of the patients, 90.7% completed chemoradiotherapy as prescribed. The median treatment duration was 43 days (range, 38-55 days). The complete response rate was 74.4%. With median follow-up of 36.7 months (range, 16.8-78.1 months) in living patients, the estimated 1-, 2-, and 5-year locoregional control, overall survival, and disease-free survival rates were 82%, 82%, and 82%; 73%, 65%, and 61%; and 73%, 73%, and 70%, respectively. One treatment-related death occurred from renal failure. Grade 3 mucositis and dermatitis occurred in 13 patients (30.2%) and 3 patients (6.9%), respectively. Grade 2 xerostomia occurred in 12 patients (27.9%). In patients with adequate follow-up, 82% were feeding tube free by 6 months after therapy; 13% remained feeding tube dependent at 1 year. Grade 3 soft-tissue fibrosis, esophageal stricture, osteoradionecrosis, and trismus occurred in 3 patients (6.9%), 5 patients (11.6%), 1 patient (2.3%), and 3 patients (6.9%), respectively. Conclusions: Our results show that intensity-modulated radiotherapy with simultaneous integrated boost with concurrent chemotherapy improved local and regional control. Acute and late toxicities were tolerable and acceptable. A prospective trial of this fractionation regimen is necessary for further assessment of its efficacy and toxicity compared with other approaches.

  19. Chemoradiotherapy of Anal Carcinoma: Survival and Recurrence in an Unselected National Cohort

    Energy Technology Data Exchange (ETDEWEB)

    Bentzen, Anne Gry, E-mail: anne.gry.bentzen@unn.no [Department of Oncology, University Hospital of Northern Norway, Tromso (Norway); Institute of Clinical Medicine, University of Tromso, Tromso (Norway); Guren, Marianne G.; Wanderas, Eva H. [Department of Oncology, Oslo University Hospital, Oslo (Norway); Frykholm, Gunilla [Department of Oncology, St. Olav' s University Hospital, Trondheim, Norway and The Norwegian Radiation Protection Authority (NRPA), Osteras (Norway); Tveit, Kjell M. [Department of Oncology, Oslo University Hospital, Oslo (Norway); Faculty of Medicine, University of Oslo, Oslo (Norway); Wilsgaard, Tom [Department of Community Medicine, University of Tromso, Tromso (Norway); Dahl, Olav [Section of Oncology, Institute of Medicine, University of Bergen and Department of Oncology, Haukeland University Hospital, Bergen (Norway); Balteskard, Lise [Department of Oncology, University Hospital of Northern Norway, Tromso (Norway); Centre for Clinical Documentation and Evaluation, Northern Norway Regional Health Authority, Tromso (Norway)

    2012-06-01

    Purpose: To evaluate treatment results, elucidate whether national guidelines were followed, and identify areas demanding further treatment optimization. Methods and Material: Between July 2000 and June 2007, 328 patients were treated with curatively intended chemoradiotherapy (CRT) for nonmetastatic squamous cell carcinoma of the anal region, according to national treatment guidelines based on tumor stage. Results: Complete response after CRT was obtained in 87% of patients, rising to 93% after salvage surgery. Chemotherapy, elective irradiation of the groin and salvage surgery were performed to a lesser extent in elderly patients, mainly because of frailty and comorbidity. Recurrence occurred in 24% of the patients, resulting in a 3- and 5-year recurrence-free survival (RFS) of 79% and 74%, respectively. Locoregional recurrences dominated, most commonly in the primary tumor site. Recurrence was treated with curative intent in 45% of the cases. The 3- and 5-year overall survival were 79% and 66%, and cancer-specific survival (CSS) were 84% and 75%, respectively. The risk of adverse outcome increased significantly with more locally advanced tumors and for male gender in multivariable analyses for RFS and CSS. Conclusions: The treatment results are in accordance with similar cohorts. The primary treatment control rate was high, but there was a significant risk of locoregional recurrence in advanced tumors. The loyalty to national guidelines was broad, although individual adjustments occurred. However, caution to avoid toxicity must not lead to inadequate treatment. Male gender seems to have inferior outcome.

  20. Barcelona Clinic Liver Cancer staging system and survival of untreated hepatocellular carcinoma in a hepatitis B virus endemic area.

    Science.gov (United States)

    Lee, Jeong-Hoon; Kim, Hwi Young; Kim, Yoon Jun; Yoon, Jung-Hwan; Chung, Jin Wook; Lee, Hyo-Suk

    2015-04-01

    A uniform staging system for hepatocellular carcinoma (HCC) is needed. In this study, the discrimination abilities of HCC staging systems (American Joint Committee on Cancer [AJCC], Barcelona Clinic Liver Cancer [BCLC], Cancer of the Liver Italian Program, and Okuda stage) were compared during the course of untreated HCC. We included consecutive 80 patients diagnosed with HCC, but were not treated for HCC, at a single medical center in Korea. In addition, 177 treated patients matched by prognostic factors were included to evaluate the survival gain owing to locoregional treatment. The mean age of untreated patients was 58.7 years. During the observation period (median = 41.1 months), 72 patients died (median survival = 2.1 months; range = 1.6-33.7 months). Among various staging systems, the BCLC system had the best discrimination ability (linear trend χ2  = 16.35). Multivariate analysis indicated that the intrahepatic tumor classification (AJCC T classification) was an independent predictor of overall survival (OS) (P = 0.001). However, either node or metastasis classification failed to affect the OS significantly (both P > 0.05). Patients undergoing intrahepatic tumor control with locoregional therapy showed prolonged survival in those patients with nodal involvement (hazard ratio = 0.315; P = 0.004) and extrahepatic metastasis (hazard ratio = 0.658; P = 0.258), respectively, after adjustment for independent prognostic factors. Compared with untreated patients, BCLC stage A and B patients had > 1 year of survival gain but those with stage C and D did not, owing to locoregional therapy. The BCLC system had the best discrimination among untreated HCC patients. However, re-evaluation of the clinical importance of nodal and metastasis classification might be required. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  1. Strategy of Using Intratreatment Hypoxia Imaging to Selectively and Safely Guide Radiation Dose De-escalation Concurrent With Chemotherapy for Locoregionally Advanced Human Papillomavirus–Related Oropharyngeal Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Nancy, E-mail: leen2@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Schoder, Heiko [Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Beattie, Brad [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Lanning, Ryan; Riaz, Nadeem; McBride, Sean [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Katabi, Nora [Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Li, Duan [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Yarusi, Brett; Chan, Susie; Mitrani, Lindsey [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Zhang, Zhigang [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Pfister, David G.; Sherman, Eric; Baxi, Shrujal [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Boyle, Jay; Morris, Luc G.T.; Ganly, Ian; Wong, Richard [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Humm, John [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2016-09-01

    Purpose: To report a small substudy of an ongoing large, multi-arm study using functional imaging to assess pre-/intratreatment hypoxia for all head and neck cancer, in which we hypothesized that pre- and early-treatment hypoxia assessment using functional positron emission tomography (PET) imaging may help select which human papillomavirus (HPV)-positive (HPV{sup +}) oropharyngeal cancer (OPC) patients can safely receive radiation de-escalation without jeopardizing treatment outcomes. Methods and Materials: Patients with HPV{sup +} oropharyngeal carcinoma were enrolled on an institutional review board–approved prospective study of which de-escalation based on imaging response was done for node(s) only. Pretreatment {sup 18}F-fluorodeoxyglucose and dynamic {sup 18}F-FMISO (fluoromisonidazole) positron emission tomography (PET) scans were performed. For patients with pretreatment hypoxia on{sup 18}F-FMISO PET (defined as a >1.2 tumor to muscle standard uptake value ratio), a repeat scan was done 1 week after chemoradiation. Patients without pretreatment hypoxia or with resolution of hypoxia on repeat scan received a 10-Gy dose reduction to metastatic lymph node(s). The 2-year local, regional, distant metastasis–free, and overall survival rates were estimated using the Kaplan-Meier product-limit method. A subset of patients had biopsy of a hypoxic node done under image guidance. Results: Thirty-three HPV{sup +} OPC patients were enrolled in this pilot study. One hundred percent showed pretreatment hypoxia (at primary site and/or node[s]), and among these, 48% resolved (at primary site and/or node[s]); 30% met criteria and received 10-Gy reduction to the lymph node(s). At the median follow-up of 32 months (range, 21-61 months), the 2-year locoregional control rate was 100%. One patient failed distantly with persistence of hypoxia on {sup 18}F-FMISO PET. The 2-year distant metastasis–free rate was 97%. The 2-year OS rate was 100%. Hypoxia on imaging was

  2. Loco-regional therapies for patients with hepatocellular carcinoma awaiting liver transplantation: Selecting an optimal therapy.

    Science.gov (United States)

    Byrne, Thomas J; Rakela, Jorge

    2016-06-24

    Hepatocellular carcinoma (HCC) is a common, increasingly prevalent malignancy. For all but the smallest lesions, surgical removal of cancer via resection or liver transplantation (LT) is considered the most feasible pathway to cure. Resection - even with favorable survival - is associated with a fairly high rate of recurrence, perhaps since most HCCs occur in the setting of cirrhosis. LT offers the advantage of removing not only the cancer but the diseased liver from which the cancer has arisen, and LT outperforms resection for survival with selected patients. Since time waiting for LT is time during which HCC can progress, loco-regional therapy (LRT) is widely employed by transplant centers. The purpose of LRT is either to bridge patients to LT by preventing progression and waitlist dropout, or to downstage patients who slightly exceed standard eligibility criteria initially but can fall within it after treatment. Transarterial chemoembolization and radiofrequency ablation have been the most widely utilized LRTs to date, with favorable efficacy and safety as a bridge to LT (and for the former, as a downstaging modality). The list of potentially effective LRTs has expanded in recent years, and includes transarterial chemoembolization with drug-eluting beads, radioembolization and novel forms of extracorporal therapy. Herein we appraise the various LRT modalities for HCC, and their potential roles in specific clinical scenarios in patients awaiting LT.

  3. Monte Carlo based protocol for cell survival and tumour control probability in BNCT.

    Science.gov (United States)

    Ye, S J

    1999-02-01

    A mathematical model to calculate the theoretical cell survival probability (nominally, the cell survival fraction) is developed to evaluate preclinical treatment conditions for boron neutron capture therapy (BNCT). A treatment condition is characterized by the neutron beam spectra, single or bilateral exposure, and the choice of boron carrier drug (boronophenylalanine (BPA) or boron sulfhydryl hydride (BSH)). The cell survival probability defined from Poisson statistics is expressed with the cell-killing yield, the 10B(n,alpha)7Li reaction density, and the tolerable neutron fluence. The radiation transport calculation from the neutron source to tumours is carried out using Monte Carlo methods: (i) reactor-based BNCT facility modelling to yield the neutron beam library at an irradiation port; (ii) dosimetry to limit the neutron fluence below a tolerance dose (10.5 Gy-Eq); (iii) calculation of the 10B(n,alpha)7Li reaction density in tumours. A shallow surface tumour could be effectively treated by single exposure producing an average cell survival probability of 10(-3)-10(-5) for probable ranges of the cell-killing yield for the two drugs, while a deep tumour will require bilateral exposure to achieve comparable cell kills at depth. With very pure epithermal beams eliminating thermal, low epithermal and fast neutrons, the cell survival can be decreased by factors of 2-10 compared with the unmodified neutron spectrum. A dominant effect of cell-killing yield on tumour cell survival demonstrates the importance of choice of boron carrier drug. However, these calculations do not indicate an unambiguous preference for one drug, due to the large overlap of tumour cell survival in the probable ranges of the cell-killing yield for the two drugs. The cell survival value averaged over a bulky tumour volume is used to predict the overall BNCT therapeutic efficacy, using a simple model of tumour control probability (TCP).

  4. Population-based cancer survival in the United States: Data, quality control, and statistical methods.

    Science.gov (United States)

    Allemani, Claudia; Harewood, Rhea; Johnson, Christopher J; Carreira, Helena; Spika, Devon; Bonaventure, Audrey; Ward, Kevin; Weir, Hannah K; Coleman, Michel P

    2017-12-15

    Robust comparisons of population-based cancer survival estimates require tight adherence to the study protocol, standardized quality control, appropriate life tables of background mortality, and centralized analysis. The CONCORD program established worldwide surveillance of population-based cancer survival in 2015, analyzing individual data on 26 million patients (including 10 million US patients) diagnosed between 1995 and 2009 with 1 of 10 common malignancies. In this Cancer supplement, we analyzed data from 37 state cancer registries that participated in the second cycle of the CONCORD program (CONCORD-2), covering approximately 80% of the US population. Data quality checks were performed in 3 consecutive phases: protocol adherence, exclusions, and editorial checks. One-, 3-, and 5-year age-standardized net survival was estimated using the Pohar Perme estimator and state- and race-specific life tables of all-cause mortality for each year. The cohort approach was adopted for patients diagnosed between 2001 and 2003, and the complete approach for patients diagnosed between 2004 and 2009. Articles in this supplement report population coverage, data quality indicators, and age-standardized 5-year net survival by state, race, and stage at diagnosis. Examples of tables, bar charts, and funnel plots are provided in this article. Population-based cancer survival is a key measure of the overall effectiveness of services in providing equitable health care. The high quality of US cancer registry data, 80% population coverage, and use of an unbiased net survival estimator ensure that the survival trends reported in this supplement are robustly comparable by race and state. The results can be used by policymakers to identify and address inequities in cancer survival in each state and for the United States nationally. Cancer 2017;123:4982-93. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. Published 2017. This article is a U

  5. Chemotherapy for Isolated Locoregional Recurrence of Breast Cancer: The CALOR Randomised Trial

    Science.gov (United States)

    Aebi, Stefan; Gelber, Shari; Anderson, Stewart J.; Láng, István; Robidoux, André; Martín, Miguel; Nortier, Johan W.R.; Paterson, Alexander H.G.; Rimawi, Mothaffar F.; Cañada, José Manuel Baena; Thürlimann, Beat; Murray, Elizabeth; Mamounas, Eleftherios P.; Geyer, Charles E.; Price, Karen N.; Coates, Alan S.; Gelber, Richard D.; Rastogi, Priya; Wolmark, Norman; Wapnir, Irene L.

    2014-01-01

    BACKGROUND Patients with isolated locoregional recurrences (ILRR) of breast cancer have a high risk of distant metastasis and death from breast cancer. We investigated adjuvant chemotherapy for such patients in a randomised clinical trial. METHODS The CALOR trial (clinicaltrials.gov NCT00074152) accrued patients 2003-2010. The 162 patients with resected ILRR were centrally randomised using permuted blocks and stratified by prior chemotherapy, ER/PgR status, and location of ILRR. Eighty-five were allocated to chemotherapy (type selected by the investigator; multidrug for at least four courses recommended) and 77 to no chemotherapy. Patients with oestrogen receptor-positive ILRR received adjuvant endocrine therapy; radiation therapy was mandated for patients with microscopically involved surgical margins, and anti-HER2 therapy was optional. The primary endpoint was disease-free survival (DFS). All analyses were by intention to treat. FINDINGS At a median follow up of 4·9 (IQR 3.6,6.0) years we observed 24 DFS events and nine deaths in the chemotherapy group compared with 34 DFS events and 21 deaths in the no chemotherapy group. Five-year DFS was 69% vs. 57%, (hazard ratio for chemotherapy versus no chemotherapy, 0·59; 95% confidence interval 0·35 to 0·99; P=0·046) and five-year overall survival was 88% vs. 76%, (hazard ratio, 0·41; 95% CI, 0·19 to 0·89; P=0·02). Adjuvant chemotherapy was significantly more effective for women with oestrogen receptor-negative disease measured in the recurrence (interaction P=0·04), but analyses of DFS based on the oestrogen receptor status of the primary tumour were not statistically significant (interaction P=0·43). Among the 85 patients who received standard chemotherapy, 12 reported SAEs. INTERPRETATION Adjuvant chemotherapy should be recommended for patients with completely resected isolated locoregional recurrences of breast cancer, especially if the recurrence is oestrogen receptor negative. FUNDING Public Service

  6. High Dose Involved Field Radiation Therapy as Salvage for Loco-Regional Recurrence of Non-Small Cell Lung Cancer

    Science.gov (United States)

    Bae, Sun Hyun; Nam, Heerim; Park, Hee Chul; Pyo, Hong Ryull; Shim, Young Mog; Kim, Jhingook; Kim, Kwhanmien; Ahn, Jin Seok; Ahn, Myung-Ju; Park, Keunchil

    2012-01-01

    Purpose To determine the effectiveness of salvage radiation therapy (RT) in patients with loco-regional recurrences (LRR) following initial complete resection of non-small cell lung cancer (NSCLC) and assess prognostic factors affecting survivals. Materials and Methods Between 1994 and 2007, 64 patients with LRR after surgery of NSCLC were treated with high dose RT alone (78.1%) or concurrent chemo-radiation therapy (CCRT, 21.9%) at Samsung Medical Center. Twenty-nine patients (45.3%) had local recurrence, 26 patients (40.6%) had regional recurrence and 9 patients (14.1%) had recurrence of both components. The median RT dose was 54 Gy (range, 44-66 Gy). The radiation target volume included the recurrent lesions only. Results The median follow-up time from the start of RT in survivors was 32.0 months. The rates of in-field failure free survival, intra-thoracic failure free survival and extra-thoracic failure free survival at 2 years were 52.3%, 33.9% and 59.4%, respectively. The median survival after RT was 18.5 months, and 2-year overall survival (OS) rate was 47.9%. On both univariate and multivariate analysis, the interval from surgery till recurrence and CCRT were significant prognostic factors for OS. Conclusion The current study demonstrates that involved field salvage RT is effective for LRR of NSCLC following surgery. PMID:23074111

  7. Pelvis Ewing sarcoma: Local control and survival in the modern era.

    Science.gov (United States)

    Ahmed, Safia K; Robinson, Steven I; Arndt, Carola A S; Petersen, Ivy A; Haddock, Michael G; Rose, Peter S; Issa Laack, Nadia N

    2017-09-01

    Local control for Ewing sarcoma (ES) has improved in modern studies. However, it is unclear if these gains have also been achieved for pelvis tumors. The purpose of this study is to evaluate local control and survival in pelvis ES patients treated in the modern era. All pelvis ES patients diagnosed from 1990 to 2012 and seen at Mayo Clinic were identified. Factors relevant to survival and local control were analyzed. The cohort consisted of 48 patients. Fifty-two percent had metastatic disease at diagnosis. The 5-year overall survival and event-free survival was 73% and 65%, respectively, for localized disease. The 5-year cumulative incidence of local recurrence was 19%, with a 26% incidence for radiation, 13% for surgery, and 0% for surgery + radiation (P = 0.54). All local failures occurred in-field. Sacral involvement by tumor trended toward a higher incidence of local recurrence (hazard ratio 3.06, P = 0.09). Patients treated with definitive radiation doses ≥5,600 cGy had a lower incidence of local recurrence (17% vs. 28%, P = 0.61). Our study demonstrates excellent survival for localized tumors in the modern era. Anatomical localization within the pelvis likely correlates with outcomes. Local control remains problematic, especially for patients treated with definitive radiation. Though statistically not significant, surgery + radiation and definitive radiation dose ≥5,600 cGy were associated with the lowest incidence of local failure, suggesting treatment intensification may improve local control for pelvis ES. © 2017 Wiley Periodicals, Inc.

  8. Impact of Postmastectomy Radiation on Locoregional Recurrence in Breast Cancer Patients With 1-3 Positive Lymph Nodes Treated With Modern Systemic Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Tendulkar, Rahul D., E-mail: tendulr@ccf.org [Department of Radiation Oncology, Cleveland Clinic Foundation, Cleveland, Ohio (United States); Rehman, Sana; Shukla, Monica E.; Reddy, Chandana A. [Department of Radiation Oncology, Cleveland Clinic Foundation, Cleveland, Ohio (United States); Moore, Halle; Budd, G. Thomas [Department of Solid Tumor Oncology, Cleveland Clinic Foundation, Cleveland, Ohio (United States); Dietz, Jill; Crowe, Joseph P. [Department of General Surgery, Cleveland Clinic Foundation, Cleveland, Ohio (United States); Macklis, Roger [Department of Radiation Oncology, Cleveland Clinic Foundation, Cleveland, Ohio (United States)

    2012-08-01

    Purpose: Postmastectomy radiation therapy (PMRT) remains controversial for patients with 1-3 positive lymph nodes (LN+). Methods and Materials: We conducted a retrospective review of all 369 breast cancer patients with 1-3 LN+ who underwent mastectomy without neoadjuvant systemic therapy between 2000 and 2007 at Cleveland Clinic. Results: We identified 271 patients with 1-3 LN+ who did not receive PMRT and 98 who did receive PMRT. The median follow-up time was 5.2 years, and the median number of LN dissected was 11. Of those not treated with PMRT, 79% received adjuvant chemotherapy (of whom 70% received a taxane), 79% received hormonal therapy, and 5% had no systemic therapy. Of the Her2/neu amplified tumors, 42% received trastuzumab. The 5-year rate of locoregional recurrence (LRR) was 8.9% without PMRT vs 0% with PMRT (P=.004). For patients who did not receive PMRT, univariate analysis showed 6 risk factors significantly (P<.05) correlated with LRR: estrogen receptor/progesterone receptor negative (hazard ratio [HR] 2.6), lymphovascular invasion (HR 2.4), 2-3 LN+ (HR 2.6), nodal ratio >25% (HR 2.7), extracapsular extension (ECE) (HR 3.7), and Bloom-Richardson grade III (HR 3.1). The 5-year LRR rate was 3.4% (95% confidence interval [CI], 0.1%-6.8%] for patients with 0-1 risk factor vs 14.6% [95% CI, 8.4%-20.9%] for patients with {>=}2 risk factors (P=.0006), respectively. On multivariate analysis, ECE (HR 4.3, P=.0006) and grade III (HR 3.6, P=.004) remained significant risk factors for LRR. The 5-year LRR was 4.1% in patients with neither grade III nor ECE, 8.1% with either grade III or ECE, and 50.4% in patients with both grade III and ECE (P<.0001); the corresponding 5-year distant metastasis-free survival rates were 91.8%, 85.4%, and 59.1% (P=.0004), respectively. Conclusions: PMRT offers excellent control for patients with 1-3 LN+, with no locoregional failures to date. Patients with 1-3 LN+ who have grade III disease and/or ECE should be strongly considered

  9. The Impact of Preradiation Residual Disease Volume on Time to Locoregional Failure in Cutaneous Merkel Cell Carcinoma—A TROG Substudy

    Energy Technology Data Exchange (ETDEWEB)

    Finnigan, Renee [Division of Cancer Services, Princess Alexandra Hospital, University of Queensland, Brisbane (Australia); Hruby, George [Department of Radiation Oncology, Sydney Cancer Centre, University of Sydney, Sydney (Australia); Wratten, Chris [Calvary Mater Newcastle Hospital, Newcastle (Australia); Keller, Jacqui; Tripcony, Lee; Dickie, Graeme [Cancer Care Services, Royal Brisbane and Women' s Hospital, Brisbane (Australia); Rischin, Danny [Department of Medical Oncology, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne (Australia); Poulsen, Michael, E-mail: michael_poulsen@health.qld.gov.au [Division of Cancer Services, Princess Alexandra Hospital, University of Queensland, Brisbane (Australia)

    2013-05-01

    Purpose: This study evaluated the impact of margin status and gross residual disease in patients treated with chemoradiation therapy for high-risk stage I and II Merkel cell cancer (MCC). Methods and Materials: Data were pooled from 3 prospective trials in which patients were treated with 50 Gy in 25 fractions to the primary lesion and draining lymph nodes and 2 schedules of carboplatin based chemotherapy. Time to locoregional failure was analyzed according to the burden of disease at the time of radiation therapy, comparing patients with negative margins, involved margins, or macroscopic disease. Results: Analysis was performed on 88 patients, of whom 9 had microscopically positive resection margins and 26 had macroscopic residual disease. The majority of gross disease was confined to nodal regions. The 5-year time to locoregional failure, time to distant failure, time to progression, and disease-specific survival rates for the whole group were 73%, 69%, 62%, and 66% respectively. The hazard ratio for macroscopic disease at the primary site or the nodes was 1.25 (95% confidence interval 0.57-2.77), P=.58. Conclusions: No statistically significant differences in time to locoregional failure were identified between patients with negative margins and those with microscopic or gross residual disease. These results must, however, be interpreted with caution because of the limited sample size.

  10. MiR-422a promotes loco-regional recurrence by targeting NT5E/CD73 in head and neck squamous cell carcinoma.

    Science.gov (United States)

    Bonnin, Nathalie; Armandy, Emma; Carras, Julien; Ferrandon, Sylvain; Battiston-Montagne, Priscillia; Aubry, Marc; Guihard, Sébastien; Meyronet, David; Foy, Jean-Philippe; Saintigny, Pierre; Ledrappier, Sonia; Jung, Alain; Rimokh, Ruth; Rodriguez-Lafrasse, Claire; Poncet, Delphine

    2016-07-12

    At the time of diagnosis, 60% of patients with head and neck squamous cell carcinoma (HNSCC) present tumors in an advanced stage (III-IV) of disease and 80% will relapse within the first two years post-treatment, due to their frequent radio(chemo)resistance. To identify new molecular targets and companion biomarkers, we have investigated the miRNome of 75 stage III-IV oropharynx tumors without relapse (R) or with loco-regional relapse (non-responder, NR) within two years post-treatment. Interestingly, miR-422a was significantly downregulated in NR tumors, in agreement with the increase in cell proliferation and adhesion induced by miR-422a inhibition in vitro. Furthermore, we identified CD73/NT5E oncogene as target of miR-422a. Indeed, modulation of the endogenous level of miR-422a inversely influences the expression and the enzymatic activity of CD73. Moreover, knocking down CD73 mimics the effects of miR-422a upregulation. Importantly, in tumors, miR-422a and CD73 expression levels are inversely correlated, and both are predictive of relapse free survival - especially considering loco(regional) recurrence - in vitro two independent cohorts of advanced oropharynx or HNSCC (N=255) tumors. In all, we reported, for the first time, that MiR-422a and its target CD73 are involved in early loco(regional) recurrence of HNSCC tumors and are new targets for personalized medicine.

  11. Prostate cancer control and survival in Vietnam veterans exposed to Agent Orange.

    Science.gov (United States)

    Everly, Lydia; Merrick, Gregory S; Allen, Zachariah A; Butler, Wayne M; Wallner, Kent; Lief, Jonathan H; Galbreath, Robert W; Adamovich, Edward

    2009-01-01

    In this study, we evaluated the impact of Agent Orange exposure on survival in Vietnam Veterans undergoing prostate brachytherapy. From May 1995 to January 2005, 81 Vietnam veterans (29 with Agent Orange exposure and 52 without) and 433 nonveterans of comparable age (mean age, 58 years) underwent prostate brachytherapy. The mean follow-up was 5.0 years. Biochemical progression-free survival (bPFS) was defined as a prostate-specific antigen (PSA)Agent Orange-exposed men were least likely to remain biochemically controlled (89.5%, 100%, and 97.2% in Agent Orange-exposed, nonexposed veterans, and nonveterans, respectively, p=0.012). No significant differences in cause-specific (CSS) (p=0.832) or overall survival (OS) (p=0.363) were discerned. In multivariate analysis, CSS was best predicted by Gleason Score and day 0 D(90), whereas Gleason Score, % positive biopsies, and D(90) predicted for bPFS. None of the evaluated parameters predicted for OS, however, a trend was identified for better OS in younger patients and those with a higher D(90). In addition, Agent Orange exposure did not predict for any of the survival parameters. To date, 22 patients have died (metastatic prostate cancer two, second malignancies nine, cardiovascular disease eight, trauma two, and pulmonary one). In this cohort of prostate brachytherapy patients, Agent Orange exposure did not statistically impact survival in multivariate analysis.

  12. Survival Outcomes in Patients with T2N0M0 (Stage II) Squamous Cell Carcinoma of the Larynx.

    Science.gov (United States)

    Gainor, Danielle L; Marchiano, Emily; Bellile, Emily; Spector, Matthew E; Taylor, Jeremy M G; Wolf, Gregory T; Hogikyan, Norman D; Prince, Mark E; Bradford, Carol R; Eisbruch, Avraham; Worden, Francis; Shuman, Andrew G

    2017-10-01

    Objective Emerging data have demonstrated suboptimal outcomes among patients with stage II larynx cancer. Our objective is to report survival outcomes for T2N0M0 larynx cancer and to determine the cause-specific survival. Study Design Case series with planned data collection. Setting Tertiary academic center. Subjects Adults with T2N0M0 squamous cell carcinoma of the larynx treated with curative intent. Methods A head and neck cancer epidemiology database was queried for eligible subjects from 2003 to 2014. Data were extracted from the electronic medical record and research database, and survival analyses were performed. Results Thirty-four patients with previously untreated stage II larynx cancer were identified (median follow-up 48 months). Patients included 27 males and 7 females with a mean age of 59 years. The majority of tumors arose from the glottis (59%). Of the cohort, 12% were treated with surgery, 65% radiation therapy, and 24% chemoradiation therapy. The estimated 2-year overall survival was 81%, (95% confidence interval [CI], 59%-92%), disease-specific survival was 91% (95% CI, 69%-98%), and recurrence-free survival was 84% (95% CI, 65%-93%). Four of 5 patients with persistent or recurrent disease posttreatment were successfully salvaged with total laryngectomy with 100% locoregional control. There were 11 mortalities (2 disease related, 2 due to metachronous primaries, 3 treatment related, and 4 from other/unknown causes). Conclusion Stage II laryngeal cancer has suboptimal survival outcomes. This appears to be a reflection of medical comorbidities, propensity for metachronous primaries, and the sequelae of late treatment effects rather than poor locoregional control.

  13. Steroid hormone control of cell death and cell survival: molecular insights using RNAi.

    Directory of Open Access Journals (Sweden)

    Suganthi Chittaranjan

    2009-02-01

    Full Text Available The insect steroid hormone ecdysone triggers programmed cell death of obsolete larval tissues during metamorphosis and provides a model system for understanding steroid hormone control of cell death and cell survival. Previous genome-wide expression studies of Drosophila larval salivary glands resulted in the identification of many genes associated with ecdysone-induced cell death and cell survival, but functional verification was lacking. In this study, we test functionally 460 of these genes using RNA interference in ecdysone-treated Drosophila l(2mbn cells. Cell viability, cell morphology, cell proliferation, and apoptosis assays confirmed the effects of known genes and additionally resulted in the identification of six new pro-death related genes, including sorting nexin-like gene SH3PX1 and Sox box protein Sox14, and 18 new pro-survival genes. Identified genes were further characterized to determine their ecdysone dependency and potential function in cell death regulation. We found that the pro-survival function of five genes (Ras85D, Cp1, CG13784, CG32016, and CG33087, was dependent on ecdysone signaling. The TUNEL assay revealed an additional two genes (Kap-alpha3 and Smr with an ecdysone-dependent cell survival function that was associated with reduced cell death. In vitro, Sox14 RNAi reduced the percentage of TUNEL-positive l(2mbn cells (p<0.05 following ecdysone treatment, and Sox14 overexpression was sufficient to induce apoptosis. In vivo analyses of Sox14-RNAi animals revealed multiple phenotypes characteristic of aberrant or reduced ecdysone signaling, including defects in larval midgut and salivary gland destruction. These studies identify Sox14 as a positive regulator of ecdysone-mediated cell death and provide new insights into the molecular mechanisms underlying the ecdysone signaling network governing cell death and cell survival.

  14. Repetitive transarterial chemoembolization (TACE) of liver metastases from gastric cancer: Local control and survival results

    Energy Technology Data Exchange (ETDEWEB)

    Vogl, Thomas J., E-mail: T.Vogl@em.uni-frankfurt.de [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Gruber-Rouh, Tatjana; Eichler, Katrin [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Nour-Eldin, Nour-Eldin A. [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Department of Radiology, Faculty of Medicine, Cairo University, Cairo (Egypt); Trojan, Jörg [Department of Internal Medicine I, Johann Wolfgang Goethe-University Frankfurt (Germany); Zangos, Stephan [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Naguib, Nagy N.N. [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Radiology Department, Faculty of Medicine, Alexandria University, Alexandria (Egypt)

    2013-02-15

    Objective: To evaluate the local tumor control and survival data after transarterial chemoembolization with different drug combinations in the palliative treatment of patients with liver metastases of gastric cancer. Materials and methods: The study was retrospectively performed. 56 patients (mean age, 52.4) with unresectable liver metastases of gastric cancer who did not respond to systemic chemotherapy were repeatedly treated with TACE in 4-week intervals. In total, 310 chemoembolization procedures were performed (mean, 5.5 sessions per patient). The local chemotherapy protocol consisted of mitomycin alone (30.4%), mitomycin and gemcitabine (33.9%), or mitomycin, gemcitabine and cisplatin (35.7%). Embolization was performed with lipiodol and starch microspheres. Local tumor response was evaluated by MRI according to RECIST. Survival data from first chemoembolization were calculated according to the Kaplan–Meier method. Results: The local tumor control was: complete response in 1.8% (n = 1), partial response in 1.8% (n = 1), stable disease in 51.8% (n = 29) and progressive disease in 44.6% (n = 25) of patients. The 1-, 2-, and 3-year survival rate from the start of chemoembolization were 58%, 38%, and 23% respectively. The median and mean survival times were 13 and 27.1 months. A Statistically significant difference between patients treated with different chemotherapy protocols was noted (ρ = 0.045) with the best survival time in the mitomycin, gemcitabine and cisplatin group. Conclusion: Transarterial chemoembolization is a minimally invasive therapy option for palliative treatment of liver metastases in patients with gastric cancer.

  15. Controls on Arctic sea ice from first-year and multi-year survival rates

    Energy Technology Data Exchange (ETDEWEB)

    Hunke, Jes [Los Alamos National Laboratory

    2009-01-01

    The recent decrease in Arctic sea ice cover has transpired with a significant loss of multi year ice. The transition to an Arctic that is populated by thinner first year sea ice has important implications for future trends in area and volume. Here we develop a reduced model for Arctic sea ice with which we investigate how the survivability of first year and multi year ice control the mean state, variability, and trends in ice area and volume.

  16. Two-year survival of ART restorations placed in elderly patients: A randomised controlled clinical trial.

    Science.gov (United States)

    da Mata, Cristiane; Allen, P Finbarr; McKenna, Gerald; Cronin, Michael; O'Mahony, Denis; Woods, Noel

    2015-04-01

    Older dentate adults are a high caries risk group who could potentially benefit from the use of the atraumatic restorative treatment (ART). This study aimed to compare the survival of ART and a conventional restorative technique (CT) using rotary instruments and a resin-modified glass-ionomer for restoring carious lesions as part of a preventive and restorative programme for older adults after 2 years. In this randomised controlled clinical trial, 99 independently living adults (65-90 years) with carious lesions were randomly allocated to receive either ART or conventional restorations. The survival of restorations was assessed by an independent and blinded examiner 6 months, 1 year and 2 years after restoration placement. Ninety-six (67.6%) and 121 (76.6%) restorations were assessed in the ART and CT groups, respectively, after 2 years. The cumulative restoration survival percentages after 2 years were 85.4% in the ART and 90.9% in the CT group. No statistically significant between group differences were detected (p=0.2050, logistic regression analysis). In terms of restoration survival, ART was as effective as a conventional restorative approach to treat older adults after 2 years. This technique could be a useful tool to provide dental care for older adults particularly in the non-clinical setting. ( ISRCTN 76299321). The results of this study show that ART presented survival rates similar to conventional restorations in older adults. ART appears to be a cost-effective way to provide dental care to elderly patients, particularly in out of surgery facilities, such as nursing homes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Targeting glucose metabolism in cancer: new class of agents for loco-regional and systemic therapy of liver cancer and beyond?

    Science.gov (United States)

    Savic, Lynn Jeanette; Chapiro, Julius; Duwe, Gregor; Geschwind, Jean-François

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the most prevalent cancers and the third leading cause of cancer-related deaths worldwide. In patients with unresectable disease, loco-regional catheter-based intra-arterial therapies (IAT) can achieve selective tumor control while minimizing systemic toxicity. As molecular features of tumor growth and microenvironment are better understood, new targets arise for selective anticancer therapy. Particularly, antiglycolytic drugs that exploit the hyperglycolytic cancer cell metabolism - also known as the 'Warburg effect' - have emerged as promising therapeutic options. Thus, future developments will combine the selective character of loco-regional drug delivery platforms with highly specific molecular targeted antiglycolytic agents. This review will exemplify literature on antiglycolytic approaches and particularly focus on intra-arterial delivery methods.

  18. Survival of Batrachochytrium dendrobatidis in Water: Quarantine and Disease Control Implications

    Science.gov (United States)

    Speare, Richard

    2003-01-01

    Amphibian chytridiomycosis is an emerging infectious disease of amphibians thought to be moved between countries by trade in infected amphibians. The causative fungus, Batrachochytrium dendrobatidis, produces aquatic, motile zoospores; infections have been achieved in experiments by exposing amphibians to water containing zoospores. However, the ability of this fungus to survive in the environment in the absence of an amphibian host is unknown. We show that B. dendrobatidis will survive in tap water and in deionized water for 3 and 4 weeks, respectively. In lake water, infectivity was observed for 7 weeks after introduction. The knowledge that water can remain infective for up to 7 weeks is important for the formulation of disease control and quarantine strategies for the management of water that has been in contact with amphibians. PMID:12967488

  19. Results of radiation therapy with or without surgery for loco-regional recurrences of adenocarcinoma of the rectum; Rechutes locoregionales d`adenocarcinomes du rectum traitees par irradiation associee ou non a une chirurgie d`exerese

    Energy Technology Data Exchange (ETDEWEB)

    Touboul, E.; Minne, J.F.; Ganansia, V.; Mitry, E.; Balosso, J.; Schlienger, M.; Laugier, A.; Housset, M.; Buffat, L. [Hopital Tenon, 75 - Paris (France). Service d`oncologie-radiotherapie; Breteau, N. [Centre Hospitalier Regional, 45 - Orleans (France). Service d`oncologie et de radiotherapie; Gallot, D. [Hopital Rothschild, 75 - Paris (France). Service de chirurgie viscerale; Parc, R. [Hopital Saint Antoine, 75 - Paris (France). Service de chirurgie digestive

    1999-01-01

    Retrospective study to analyze the results of external beam radiation treatment with or without surgery for loco--regional recurrence of adenocarcinoma of the rectum following previous surgery without pre- or post- operative radiotherapy. Between March 1973 and November 1991, 211 patients with loco-regional recurrence of rectum cancer were treated with external beam radiation treatment. Radical surgery was the only initial treatment modality. Surgical resection of local recurrence was done in 36 patients and only 17 patients could undergo complete resection. Forty-seven patients underwent radiotherapy (RT) combined with surgery and 164 received external beam radiation treatment alone to a mean total dose of 46 Gy. Among the 151 patients whose recurrence was revealed by pain, 64 (42 %) were considered to have a symptomatic response after loco-regional treatment with radiosurgery or RT alone. The mean duration of response was 12 months. The 3-year overall survival rate was 16 %. Five prognostic factors decreased the overall survival rate in multivariate analysis: high age, sex (male), concomitant distant metastasis, no tumor resection, and low total radiation dose with external beam radiation treatment alone. The 3-year survival rate for patients with completely resected recurrence was 9%. External beam RT treatment can only be considered a palliative symptomatic treatment. New techniques of early detection of local recurrence and new combined modalities approaches (radiation sensitizers or intra-operative radiotherapy) with surgical resection in some favorable cases should be studied. (authors)

  20. Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): a randomised trial.

    Science.gov (United States)

    Aebi, Stefan; Gelber, Shari; Anderson, Stewart J; Láng, István; Robidoux, André; Martín, Miguel; Nortier, Johan W R; Paterson, Alexander H G; Rimawi, Mothaffar F; Cañada, José Manuel Baena; Thürlimann, Beat; Murray, Elizabeth; Mamounas, Eleftherios P; Geyer, Charles E; Price, Karen N; Coates, Alan S; Gelber, Richard D; Rastogi, Priya; Wolmark, Norman; Wapnir, Irene L

    2014-02-01

    Patients with isolated locoregional recurrences (ILRR) of breast cancer have a high risk of distant metastasis and death from breast cancer. We aimed to establish whether adjuvant chemotherapy improves the outcome of such patients. The CALOR trial was a pragmatic, open-label, randomised trial that accrued patients with histologically proven and completely excised ILRR after unilateral breast cancer who had undergone a mastectomy or lumpectomy with clear surgical margins. Eligible patients were enrolled from hospitals worldwide and were centrally randomised (1:1) to chemotherapy (type selected by the investigator; multidrug for at least four courses recommended) or no chemotherapy, using permuted blocks, and stratified by previous chemotherapy, oestrogen-receptor and progesterone-receptor status, and location of ILRR. Patients with oestrogen-receptor-positive ILRR received adjuvant endocrine therapy, radiation therapy was mandated for patients with microscopically involved surgical margins, and anti-HER2 therapy was optional. The primary endpoint was disease-free survival. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00074152. From Aug 22, 2003, to Jan 31, 2010, 85 patients were randomly assigned to receive chemotherapy and 77 were assigned to no chemotherapy. At a median follow-up of 4·9 years (IQR 3·6-6 ·0), 24 (28%) patients had disease-free survival events in the chemotherapy group compared with 34 (44%) in the no chemotherapy group. 5-year disease-free survival was 69% (95% CI 56-79) with chemotherapy versus 57% (44-67) without chemotherapy (hazard ratio 0·59 [95% CI 0·35-0·99]; p=0·046). Adjuvant chemotherapy was significantly more effective for women with oestrogen-receptor-negative ILRR (pinteraction=0·046), but analyses of disease-free survival according to the oestrogen-receptor status of the primary tumour were not statistically significant (pinteraction=0·43). Of the 81 patients who

  1. Environmental control of phase transition and polyp survival of a massive-outbreaker jellyfish.

    Directory of Open Access Journals (Sweden)

    Laura Prieto

    Full Text Available A number of causes have been proposed to account for the occurrence of gelatinous zooplankton (both jellyfish and ctenophore blooms. Jellyfish species have a complex life history involving a benthic asexual phase (polyp and a pelagic sexual phase (medusa. Strong environmental control of jellyfish life cycles is suspected, but not fully understood. This study presents a comprehensive analysis on the physicochemical conditions that control the survival and phase transition of Cotylorhiza tuberculata; a scyphozoan that generates large outbreaks in the Mediterranean Sea. Laboratory experiments indicated that the influence of temperature on strobilation and polyp survival was the critical factor controlling the capacity of this species to proliferate. Early life stages were less sensitive to other factors such as salinity variations or the competitive advantage provided by zooxanthellae in a context of coastal eutrophication. Coherently with laboratory results, the presence/absence of outbreaks of this jellyfish in a particular year seems to be driven by temperature. This is the first time the environmental forcing of the mechanism driving the life cycle of a jellyfish has been disentangled via laboratory experimentation. Projecting this understanding to a field population under climatological variability results in a pattern coherent with in situ records.

  2. Social equity in perinatal survival: a case-control study at hospitals in Kigali, Rwanda.

    Science.gov (United States)

    Musafili, Aimable; Essén, Birgitta; Baribwira, Cyprien; Selling, Katarina Ekholm; Persson, Lars-Åke

    2015-12-01

    Rwanda has invested heavily in improving maternal and child health, but knowledge is limited regarding social equity in perinatal survival. We analysed whether perinatal mortality risks differed between social groups in hospitals in the country's capital. A case-control study was carried out on singleton births aged at least 22 weeks of gestation and born in district or tertiary referral hospitals in Kigali from July 2013 to May 2014. Perinatal deaths were recorded as they occurred, with the next two surviving neonates born in the same hospital selected as controls. Conditional logistic regression was used to determine social determinants of perinatal death after adjustments for potential confounders. We analysed 234 perinatal deaths and 468 controls. Rural residence was linked to an increased risk of perinatal death (OR = 3.31, 95% CI 1.43-7.61), but maternal education or household asset score levels were not. Having no health insurance (OR = 2.11, 95% CI 0.91-4.89) was associated with an increased risk of perinatal death, compared to having community health insurance. Living in a rural area and having no health insurance were associated with an increased risk of perinatal mortality rates in the Rwandan capital, but maternal education and household assets were not. ©2015 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.

  3. IMRT for Sinonasal Tumors Minimizes Severe Late Ocular Toxicity and Preserves Disease Control and Survival

    Energy Technology Data Exchange (ETDEWEB)

    Duprez, Frederic, E-mail: frederic.duprez@ugent.be [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium); Madani, Indira; Morbee, Lieve [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium); Bonte, Katrien; Deron, Philippe; Domjan, Vilmos [Department of Head and Neck Surgery, Ghent University Hospital, Ghent (Belgium); Boterberg, Tom; De Gersem, Werner; De Neve, Wilfried [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium)

    2012-05-01

    Purpose: To report late ocular (primary endpoint) and other toxicity, disease control, and survival (secondary endpoints) after intensity-modulated radiotherapy (IMRT) for sinonasal tumors. Methods and Materials: Between 1998 and 2009, 130 patients with nonmetastatic sinonasal tumors were treated with IMRT at Ghent University Hospital. Prescription doses were 70 Gy (n = 117) and 60-66 Gy (n = 13) at 2 Gy per fraction over 6-7 weeks. Most patients had adenocarcinoma (n = 82) and squamous cell carcinoma (n = 23). One hundred and one (101) patients were treated postoperatively. Of 17 patients with recurrent tumors, 9 were reirradiated. T-stages were T1-2 (n = 39), T3 (n = 21), T4a (n = 38), and T4b (n = 22). Esthesioneuroblastoma was staged as Kadish A, B, and C in 1, 3, and 6 cases, respectively. Results: Median follow-up was 52, range 15-121 months. There was no radiation-induced blindness in 86 patients available for late toxicity assessment ({>=}6 month follow-up). We observed late Grade 3 tearing in 10 patients, which reduced to Grade 1-2 in 5 patients and Grade 3 visual impairment because of radiation-induced ipsilateral retinopathy and neovascular glaucoma in 1 patient. There was no severe dry eye syndrome. The worst grade of late ocular toxicity was Grade 3 (n = 11), Grade 2 (n = 31), Grade 1 (n = 33), and Grade 0 (n = 11). Brain necrosis and osteoradionecrosis occurred in 6 and 1 patients, respectively. Actuarial 5-year local control and overall survival were 59% and 52%, respectively. On multivariate analysis local control was negatively affected by cribriform plate and brain invasion (p = 0.044 and 0.029, respectively) and absence of surgery (p = 0.009); overall survival was negatively affected by cribriform plate and orbit invasion (p = 0.04 and <0.001, respectively) and absence of surgery (p = 0.001). Conclusions: IMRT for sinonasal tumors allowed delivering high doses to targets at minimized ocular toxicity, while maintaining disease control and survival

  4. Prognostic impact of H3K27me3 expression on locoregional progression after chemoradiotherapy in esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Liao Yi-Ji

    2009-12-01

    Full Text Available Abstract Background Trimethylation of lysine 27 on histone H3 (H3K27me3 by enhancer of zeste homolog 2 (EZH2 is an epigenetic mark that mediates gene silencing. EZH2 is overexpressed and correlates with poor prognosis in many cancers. However, the clinical implication of H3K27me3 in human malignancies has not been well established. We wished to ascertain whether a correlation exists between the expression of H3K27me3 and clinical outcome in a group of patients with esophageal squamous cell carcinoma (ESCC treated with definitive chemoradiotherapy (CRT. Methods The method of immunohistochemistry (IHC was utilized to examine the protein expression of H3K27me3 in 98 pretreatment biopsy specimens of ESCC and in 30 samples of normal esophageal mucosa. The clinical/prognostic significance of H3K27me3 expression was statistically analyzed. Results The expression frequency and expression levels of H3K27me3 were significantly higher in ESCCs than in normal tissues. There was a positive correlation between H3K27me3 expression and WHO grade (P = 0.016, tumor size (P = 0.019, T status (P = 0.024, locoregional progression (P = 0.009 and EZH2 expression (P = 0.036. High H3K27me3 expression was associated with poor locoregional progression-free survival (LPFS (P = 0.010 in ESCC. Further analysis demonstrated that H3K27me3 could stratify patient outcome in T2-3 (P = 0.048, N0 (P = 0.005 and M0 (P = 0.018 stages as well as in CRT effective group (P = 0.022. Conclusions Our data suggests that H3K27me3 expression examined by IHC might be useful for stratifying LPFS for different subsets of ESCC patients treated with definitive CRT.

  5. Role of salvage stereotactic body radiation therapy in post-surgical loco-regional recurrence in a selected population of non-small cell lung cancer patients.

    Science.gov (United States)

    Agolli, Linda; Valeriani, Maurizio; Carnevale, Alessia; Falco, Teresa; Bracci, Stefano; De Sanctis, Vitaliana; Minniti, Giuseppe; Enrici, Riccardo Maurizi; Osti, Mattia Falchetto

    2015-03-01

    This is a retrospective analysis of a selected series of high-risk non-small cell lung cancer (NSCLC) patients with post-surgical loco-regional relapse treated with salvage stereotactic body radiotherapy (SBRT). Outcome and toxicity profiles were assessed. Twenty-eight patients (unfit for surgery or systemic therapy) with 30 lesions underwent salvage SBRT as an alternative therapy because of advanced age, co-morbid conditions or no response obtained from other treatments. Complete and partial responses were 16% and 70%, respectively. Local progression was observed in 3 patients. Regional relapse occurred in 5 patients. Distant progression occurred in 10 patients. The 2-year overall survival (OS) and disease-free survival (DFS) were 57.5% and 36.6%, respectively. Radiation acute pneumonitis occurred as follows: three patients developed grade 1, two patients experienced grade 2 and one patient experienced grade 3 toxicity. Stereotactic body radiotherapy could have an alternative role in isolated loco-regional relapse in patients unfit or resistant to other therapies. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  6. Control of Homeostasis and Dendritic Cell Survival by the GTPase RhoA

    DEFF Research Database (Denmark)

    Li, Shuai; Dislich, Bastian; Brakebusch, Cord H

    2015-01-01

    Tissues accommodate defined numbers of dendritic cells (DCs) in highly specific niches where different intrinsic and environmental stimuli control DC life span and numbers. DC homeostasis in tissues is important, because experimental changes in DC numbers influence immunity and tolerance toward...... various immune catastrophes and inflammation. However, the precise molecular mechanisms regulating DC life span and homeostasis are unclear. We report that the GTPase RhoA controls homeostatic proliferation, cytokinesis, survival, and turnover of cDCs. Deletion of RhoA strongly decreased the numbers of CD...... findings identify RhoA as a central regulator of DC homeostasis, and its deletion decreases DC numbers below critical thresholds for immune protection and homeostasis, causing aberrant compensatory DC proliferation....

  7. Outcomes of Locoregional Tumor Therapy for Patients with Hepatocellular Carcinoma and Transjugular Intrahepatic Portosystemic Shunts

    Energy Technology Data Exchange (ETDEWEB)

    Padia, Siddharth A., E-mail: spadia@uw.edu; Chewning, Rush H., E-mail: rchewnin@uw.edu; Kogut, Matthew J., E-mail: kogutm@uw.edu; Ingraham, Christopher R., E-mail: cringa@uw.edu; Johnson, Guy E., E-mail: gej@uw.edu [University of Washington Medical Center, Section of Interventional Radiology, Department of Radiology (United States); Bhattacharya, Renuka, E-mail: renuka@uw.edu [University of Washington Medical Center, Division of Gastroenterology and Hepatology, Department of Medicine (United States); Kwan, Sharon W., E-mail: shakwan@uw.edu; Monsky, Wayne L., E-mail: wmonsky@uw.edu; Vaidya, Sandeep, E-mail: svaidya@uw.edu [University of Washington Medical Center, Section of Interventional Radiology, Department of Radiology (United States); Hippe, Daniel S., E-mail: dhippe@uw.edu [University of Washington Medical Center, Department of Radiology (United States); Valji, Karim, E-mail: kvalji@uw.edu [University of Washington Medical Center, Section of Interventional Radiology, Department of Radiology (United States)

    2015-08-15

    PurposeLocoregional therapy for hepatocellular carcinoma (HCC) can be challenging in patients with a transjugular intrahepatic portosystemic shunt (TIPS). This study compares safety and imaging response of ablation, chemoembolization, radioembolization, and supportive care in patients with both TIPS and HCC.MethodsThis retrospective study included 48 patients who had both a TIPS and a diagnosis of HCC. Twenty-nine of 48 (60 %) underwent treatment for HCC, and 19/48 (40 %) received best supportive care (i.e., symptomatic management only). While etiology of cirrhosis and indication for TIPS were similar between the two groups, treated patients had better baseline liver function (34 vs. 67 % Child-Pugh class C). Tumor characteristics were similar between the two groups. A total of 39 ablations, 17 chemoembolizations, and 10 yttrium-90 radioembolizations were performed on 29 patients.ResultsAblation procedures resulted in low rates of hepatotoxicity and clinical toxicity. Post-embolization/ablation syndrome occurred more frequently in patients undergoing chemoembolization than ablation (47 vs. 15 %). Significant hepatic dysfunction occurred more frequently in the chemoembolization group than the ablation group. Follow-up imaging response showed objective response in 100 % of ablation procedures, 67 % of radioembolization procedures, and 50 % of chemoembolization procedures (p = 0.001). When censored for OLT, patients undergoing treatment survived longer than patients receiving supportive care (2273 v. 439 days, p = 0.001).ConclusionsAblation appears to be safe and efficacious for HCC in patients with TIPS. Catheter-based approaches are associated with potential increased toxicity in this patient population. Chemoembolization appears to be associated with increased toxicity compared to radioembolization.

  8. Analysis of loco-regional failures in head and neck cancer after radical radiation therapy.

    Science.gov (United States)

    De Felice, Francesca; Thomas, Christopher; Barrington, Sally; Pathmanathan, Angela; Lei, Mary; Urbano, Teresa Guerrero

    2015-11-01

    To investigate the anatomical distribution of loco-regional treatment failures (LRF) in patients with head and neck squamous cell carcinoma (HNSCC) in relation to clinical target volume (CTV) delineation. 56 patients with LRF were retrospectively identified. Patients were previously treated with radical intensity modulated radiotherapy (IMRT) +/- chemotherapy. Target volumes include gross tumour volume (GTV), its volumetric expansion of 10mm (GTV-HD), CTV high dose (CTV-HD) delineated by anatomic expansion from GTV and CTV low dose (CTV-LD) defined to receive a prophylactic dose. LRF were evaluated by PET-CT or CT scan. We analysed the association between sites of LRF and target volumes and dosimetry, using image co-registration. Based on percentage of volume that received 95% of prescribed dose, LRF were classified as in-field, marginal or out-field. Median interval time from end of treatment to LRF was 186days. 65 (95.6%) LRF were classified as in-field. Considering primary target volumes, 40 (58.8%) LRF occurred inside GTV, 13 (19.1%) in GTV-HD and 7 (10.3%) in CTV-HD. The overall 1-year and 2-year post-failure survival (PFS) was 45.8% and 24.2%, respectively. Post radiation LRF managed with salvage surgery had a significantly higher median PFS when compared with palliative treatments (p=0.003). The majority of LRF occurred within GTV/GTV-HD, suggesting it is safe to reduce the CTV to a volumetric expansion. Given the low incidence of geographical misses, future studies should be directed towards dose escalation of high-risk volumes. Potential reduction of RT-related toxicity with volumetric expansion could facilitate salvage surgery. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Multi-modality management for loco-regionally advanced laryngeal and hypopharyngeal cancer: balancing the benefit of efficacy and functional preservation.

    Science.gov (United States)

    Qian, Wei; Zhu, Guopei; Wang, Yulong; Wang, Xiaoshen; Ji, Qinghai; Wang, Yu; Dou, Shengjin

    2014-09-01

    The 5-year overall survival (OS) of loco-regionally advanced laryngeal and hypopharyngeal carcinoma (LA-LHC) has declined over the past two decades following the wide application of non-surgical approaches. We aimed to define the new role of open surgery combined with adjuvant chemoradiotherapy in the treatment of LA-LHC for improving survival while maintaining a functional larynx. In the current study, 90 LA-LHC patients treated with open surgery followed by postoperative RT/CRT in our institute from May 2005 to December 2012 were retrospectively analyzed. OS, disease-free survival (DFS), loco-regional failure-free survival (LRFFS) and distant metastasis-free survival (DMFS) were calculated, and prognostic factors were analyzed. Functional larynx preservation results were evaluated according to the head and neck quality of life (QoL) Scale. With a median follow-up period of 37 months, the 3- and 5-year OS, DFS, LRFFS and DMFS were 71.3, 63.7, 85.9, 73.7 and 55.9, 53.0, 81.6, 71.9 %, respectively. Vascular embolism and extracapsular extension (ECE) of the lymph nodes were prognostic factors for poorer OS (p = 0.045 and 0.046, respectively). Vascular embolism was the only prognostic factor for poorer DMFS (p = 0.005). Patients who underwent a conservative partial laryngectomy (CPL) experienced a higher QoL in the domains of speech, swallowing and emotion. Functional larynx preservation was achieved in 36/45 patients (80 %) who received CPL. The results of our study demonstrated that CPL followed by adequate adjuvant therapy could achieve superior oncological results compared with non-surgical approaches in LA-LHC patients while also maintaining satisfactory functional larynx in a majority of patients.

  10. Comparative Effectiveness of Cancer Control and Survival after Robot-Assisted versus Open Radical Prostatectomy.

    Science.gov (United States)

    Hu, Jim C; O'Malley, Padraic; Chughtai, Bilal; Isaacs, Abby; Mao, Jialin; Wright, Jason D; Hershman, Dawn; Sedrakyan, Art

    2017-01-01

    Robot-assisted surgery has been rapidly adopted in the U.S. for prostate cancer. Its adoption has been driven by market forces and patient preference, and debate continues regarding whether it offers improved outcomes to justify the higher cost relative to open surgery. We examined the comparative effectiveness of robot-assisted vs open radical prostatectomy in cancer control and survival in a nationally representative population. This population based observational cohort study of patients with prostate cancer undergoing robot-assisted radical prostatectomy and open radical prostatectomy during 2003 to 2012 used data captured in the SEER (Surveillance, Epidemiology, and End Results)-Medicare linked database. Propensity score matching and time to event analysis were used to compare all cause mortality, prostate cancer specific mortality and use of additional treatment after surgery. A total of 6,430 robot-assisted radical prostatectomies and 9,161 open radical prostatectomies performed during 2003 to 2012 were identified. The use of robot-assisted radical prostatectomy increased from 13.6% in 2003 to 2004 to 72.6% in 2011 to 2012. After a median followup of 6.5 years (IQR 5.2-7.9) robot-assisted radical prostatectomy was associated with an equivalent risk of all cause mortality (HR 0.85, 0.72-1.01) and similar cancer specific mortality (HR 0.85, 0.50-1.43) vs open radical prostatectomy. Robot-assisted radical prostatectomy was also associated with less use of additional treatment (HR 0.78, 0.70-0.86). Robot-assisted radical prostatectomy has comparable intermediate cancer control as evidenced by less use of additional postoperative cancer therapies and equivalent cancer specific and overall survival. Longer term followup is needed to assess for differences in prostate cancer specific survival, which was similar during intermediate followup. Our findings have significant quality and cost implications, and provide reassurance regarding the adoption of more

  11. [The results and toxicity of organ preservation treatment for locoregionally advanced laryngeal and hypopharyngeal cancer].

    Science.gov (United States)

    Kiprian, Dorota; Kawecki, Andrzej; Jarząbski, Andrzej; Michalski, Wojciech; Pawłowska-Sendułka, Beata

    2011-01-01

    The most frequent malignant tumor of the head and neck region is a squamous cell cancer of the larynx. Squamous cell cancer of the hypopharynx is diagnosed rarely, but it has poorer prognosis than laryngeal cancer. The surgical treatment, especially in advanced disease, is a laryngectomy with the definitive tracheostomy, what negatively influenced the quality of life. Therefore, oncologists have been interested in new alternative methods of conservative treatment from many years. The evaluation of efficacy and toxicity of the organ preservation treatment in patients with locally advanced laryngeal and hypopharyngeal cancer. The patients with diagnosed squamous cell laryngeal and hypopharyngeal cancer in III and IVa clinical status were treated with concomitant radiochemotherapy with intention of the organ preservation. Conformal 3D radiotherapy and SIB-IMRT technique was applied in all cases. Concomitant chemotherapy consisted of cisplatin in daily dose100mg/m(2) given two times during irradiation (1 and 22 day of treatment) or once weekly in dose 40mg/m(2). Between January 2004 and November 2008 146 patients were treated with this method. There were 83 patients diagnosed with laryngeal cancer and 62 patients with hypopharyngeal cancer in this group. The median follow up is 42 months. Five years overall survival is 75% and disease free survivak is 63%. Three years laryngectomy free survival (LFS) is 82% and 5-years LFS is 76%. This group of patients is alive with larynx preservations. In 17.3% patients local recurrence was observed (4.5% regional recurrence and 1.8% locoregional). Those patients underwent salvage surgery or were treated with palliative chemotherapy. No severe life risking early and late complications were observed. Only 7% of patients have required temporary tracheostomy because of difficulties in breathing due to larynx edema. We can conclude that organ preservation treatment is a valuable alternative to surgical procedure in patients diagnosed

  12. Prognostic Relevance of Objective Response According to EASL Criteria and mRECIST Criteria in Hepatocellular Carcinoma Patients Treated with Loco-Regional Therapies: A Literature-Based Meta-Analysis.

    Science.gov (United States)

    Vincenzi, Bruno; Di Maio, Massimo; Silletta, Marianna; D'Onofrio, Loretta; Spoto, Chiara; Piccirillo, Maria Carmela; Daniele, Gennaro; Comito, Francesca; Maci, Eliana; Bronte, Giuseppe; Russo, Antonio; Santini, Daniele; Perrone, Francesco; Tonini, Giuseppe

    2015-01-01

    The European Association for the Study of the Liver (EASL) criteria and the modified Response Evaluation Criteria in Solid Tumors (mRECIST) are currently adopted to evaluate radiological response in patients affected by HCC and treated with loco-regional procedures. Several studies explored the validity of these measurements in predicting survival but definitive data are still lacking. To conduct a systematic review of studies exploring mRECIST and EASL criteria usefulness in predictive radiological response in HCC undergoing loco-regional therapies and their validity in predicting survival. A comprehensive search of the literature was performed in electronic databases EMBASE, MEDLINE, COCHRANE LIBRARY, ASCO conferences and EASL conferences up to June 10, 2014. Our overall search strategy included terms for HCC, mRECIST, and EASL. Loco-regional procedures included transarterial embolization (TAE), transarterial chemoembolization (TACE) and cryoablation. Inter-method agreement between EASL and mRECIST was assessed using the k coefficient. For each criteria, overall survival was described in responders vs. non-responders patients, considering all target lesions response. Among 18 initially found publications, 7 reports including 1357 patients were considered eligible. All studies were published as full-text articles. Proportion of responders according to mRECIST and EASL criteria was 62.4% and 61.3%, respectively. In the pooled population, 1286 agreements were observed between the two methods (kappa statistics 0.928, 95% confidence interval 0.912-0.944). HR for overall survival (responders versus non responders) according to mRECIST and EASL was 0.39 (95% confidence interval 0.26-0.61, ploco-regional treatments. Objective response according to both criteria confirms a strong prognostic value in terms of overall survival. This prognostic value appears to be very similar between the two criteria.

  13. Well-differentiated thyroid cancer with aerodigestive tract invasion: Long-term control and functional outcomes.

    Science.gov (United States)

    Su, Shirley Y; Milas, Zvonimir L; Bhatt, Neel; Roberts, Dianna; Clayman, Gary L

    2016-01-01

    Well-differentiated thyroid cancer (WDTC) invading the aerodigestive tract is an uncommon entity associated with significant morbidity and reduced survival. We reviewed the surgical treatment, oncologic control, and functional outcomes of 69 consecutive patients with WDTC invading the upper aerodigestive tract. Complete tumor excision with negative margins was achieved in 62% of patients. Tracheostomy dependence (27%) and permanent hypoparathyroidism (49%) were present or the result of surgery. Seventy-one percent of patients ate a regular diet, 59% had normal speech, and the majority (62%) reported normal activities of daily living. The local, regional, and distant recurrence was 1%, 14%, and 23%, respectively. The 5-year overall survival (OS) and disease-free survival (DFS) was 71% and 45%, respectively. Surgical resection and appropriate adjuvant treatment can achieve excellent locoregional control while preserving function and quality of life. Long-term survival is limited by the high incidence of distant metastasis. © 2015 Wiley Periodicals, Inc.

  14. Survival of pathogenic enterohemorrhagic Escherichia coli (EHEC) and control with calcium oxide in frozen meat products.

    Science.gov (United States)

    Ro, Eun Young; Ko, Young Mi; Yoon, Ki Sun

    2015-08-01

    This study investigated both the level of microbial contamination and the presence of enterohemorrhagic Escherichia coli (EHEC) in frozen meat products, followed by the evaluation of its survival over 180 days under frozen temperature. We also examined the effect of calcium oxide on the populations of EHEC, E. coli O157:H7 and EPEC under both 10 °C and -18 °C storage conditions. Afterward, the morphological changes occurring in EHEC cells in response to freezer storage temperature and calcium oxide (CaO) treatments were examined using transmission electron microscopy. Among the frozen meat products tested, the highest contamination levels of total aerobic counts, coliforms and E. coli were observed in pork cutlets. Examination showed that 20% of the frozen meat products contained virulence genes, including verotoxin (VT) 1 and 2. Over 180 days of frozen storage and after 3 freeze-thaw cycles, the population of EHEC did not change regardless of the type of products or initial inoculated concentration, indicating the strong survival ability of EHEC. Subsequent testing revealed that the growth of three pathogenic E. coli strains was completely inhibited in meat patties prepared with 1% CaO, stored at 10 °C. However, the addition of 2% CaO was necessary to control the survival of EHEC, E. coli O157:H7 and EPEC in meat patties stored at -18 °C. CaO reduced the population of E. coli O157:H7 more effectively than the other EHEC and EPEC strains at both 10 °C and -18 °C. Transmission electron microscopy analysis revealed that exposed EHEC cells were resistant to the freezer storage temperature, although some cells incurred injury and death after several freeze-thaw cycles. Most of the cells exposed to CaO were found to have died or lost their cellular integrity and membranes, indicating that CaO has the potential to be used as a powerful antimicrobial agent for manufacturing frozen meat products. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Prognosis and determinants of outcome following locoregional or distant recurrence in patients with cutaneous melanoma

    NARCIS (Netherlands)

    Francken, Anne Brecht; Accortt, Neil A.; Shaw, Helen M.; Wiener, Martin; Soong, Seng-jaw; Hoekstra, Harald J.; Thompson, John F.

    Objective: Information on prognosis for patients with cutaneous melanoma after locoregional or distant recurrence is sparse and controversial. The aim of this study was to analyze factors influencing outcome after the development of a first relapse. Methods: Information was extracted from the Sydney

  16. Analysis of loco-regional and distant recurrences in breast cancer after conservative surgery.

    Science.gov (United States)

    Elsayed, Mostafa; Alhussini, Mahmoud; Basha, Ahmed; Awad, A T

    2016-05-14

    A number of patients treated conservatively for breast cancer will develop loco-regional and distant recurrences. Our aim was to determine how their occurrence may be linked to the evolution of the disease. We analyzed 238 women treated by conservative breast surgery and breast irradiation in a single institution. We evaluated the prognostic factors associated with loco-regional and distant recurrences and the prognostic value of local and regional recurrences on systemic progression. After a median follow-up of 5 year (range 1-10), 16 (6.72%) patients in the breast conservative surgery (BCS) groups had loco-regional recurrence. For distant recurrence, 10 (4.2%) patients had experienced distant recurrence. Lympho-vascular invasion (HR 2.55; 95% CI, 076 to 8.49) and an extensive intraductal component (HR, 2.22; 95% CI, 0.69 to 7.15) and nodal status are risk factors for loco-regional recurrence (LRR) after breast conservative therapy (BCT). Tumor size, nodal status, high histologic grade, and breast cancer diagnosed at a young age (≤35 years) are correlated with higher distant recurrence rates after BCT. Risk factors for LRR after BCS include lympho-vascular invasion, extensive inraductal component, and high nodal status, where as risk factors for distant recurrence include tumor size, nodal status, high histologic grade, and breast cancer diagnosed at a young age (≤35 years).

  17. Combined modality treatment improves tumor control and overall survival in patients with early stage Hodgkin's lymphoma: a systematic review

    DEFF Research Database (Denmark)

    Herbst, Christine; Rehan, Fareed A; Brillant, Corinne

    2010-01-01

    . We thus performed a systematic review with meta-analysis of randomized controlled trials comparing chemotherapy alone with CMT in patients with early stage Hodgkin's lymphoma with respect to response rate, tumor control and overall survival (OS). We searched Medline, EMBASE and the Cochrane Library....... These trials underlined the results of the main analysis. In conclusion, adding radiotherapy to chemotherapy improves tumor control and OS in patients with early stage Hodgkin's lymphoma....

  18. A prognostic index for locoregional recurrence after neoadjuvant chemotherapy.

    Science.gov (United States)

    Herrero-Vicent, C; Guerrero-Zotano, A; Gavilá-Gregori, J; Hernández-Blanquisett, A; Sandiego-Contreras, S; Samper-Hiraldo, J M; Guillem-Porta, V; Ruiz-Simón, A

    2016-01-01

    The appropriate selection criteria for breast-conserving surgery (BCS) or mastectomy after neoadjuvant chemotherapy (NAC) are poorly defined. The aim of this study is to analyse the incidence and prognostic factors for locoregional recurrence (LRR) in patients with breast cancer (BC) treated with NAC to develop a prognostic score to help with clinical decision-making. Using our retrospective maintained BC database, we identified 730 patients treated with NAC (327 patients treated with BCS and 403 patients treated with mastectomy) between 1998 and 2014. To identify variables associated with an increased LRR rate, we performed firstly Kaplan-Meier curves, with comparisons among groups using log-rank test, and then, significant variables were included in a multivariate analysis using Cox proportional hazards. The prognostic index was developed by assigning score 0 (favourable) or score 1 (unfavourable) for each significant variable of multivariate analysis and was created separately for patients with BCS and mastectomy. At a median follow-up of 72 months, the 6-year cumulative incidence of LRR was 7.2% ( ± 3%) for BCS and 7.9% ( ± 3%) for mastectomy. By univariate analysis, variables associated with an increased LRR were for BCS: HER2 positive, grade III, ductal carcinoma in situ (DCIS), No-pCR (ypTis, ypN0), and age < 40 years; and for mastectomy, HER2-positive, DCIS, No-pCR, and LVI. By multivariate analysis, variables associated with an increased LRR were for BCS: HER2 positive (HR: 11.1, p = 0.001), DCIS (HR: 3.1, p = 0.005), and age < 40 years (HR: 2.8, p = 0.02); and for mastectomy: HER2 positive (HR: 9.5, p = 0.03), DCIS (HR: 2.7, p = 0.01), No-pCR (HR: 11.4, p = 0.01), and age < 40 years (HR: 2.8, p = 0.006). The score stratified patients into three subsets with statistically different levels of risk for LRR. For BCS, the six-year LRR rates were 3%, 13%, and 33% for the low (score 0, n = 120), intermediate (score 1, n = 95) and high (score 2-3, n = 27) risk

  19. Survival of Listeria monocytogenes on fresh blueberries (Vaccinium corymbosum) stored under controlled atmosphere and ozone.

    Science.gov (United States)

    Concha-Meyer, Anibal; Eifert, Joseph; Williams, Robert; Marcy, Joseph; Welbaum, Gregory

    2014-05-01

    Listeria monocytogenes is a foodborne pathogen that represents a high risk for consumers because it can grow under refrigeration conditions and can also develop acid tolerance. Fresh blueberries are hand-picked, packed, and transported under refrigeration without receiving a microbial inactivation treatment. The aim of this work was to study the survival of L. monocytogenes in fresh highbush blueberries stored at 4 or 12 °C under different controlled atmosphere conditions, including air (control); 5% O2, 15% CO2, 80% N2 (controlled atmosphere storage [CAS]); or ozone gas (O3), 4 ppm at 4 °C or 2.5 ppm at 12 °C, at high relative humidity (90 to 95%) for a total of 10 days. Fresh blueberries inside a plastic clamshell were spot inoculated with the bacteria and were stored at 4 or 12 °C in isolated cabinets under air, CAS, and O3 atmospheric conditions. Samples were evaluated on days 0, 1, 4, 7, and 10 for microbial growth using modified Oxford agar. CAS did not delay or inhibit L. monocytogenes growth in fresh blueberries after 10 days. O3 achieved 3- and 2-log reductions when compared with air treatment at 4 and 12 °C, respectively. Low concentrations of O3 together with proper refrigeration temperature can ensure product safety throughout transportation. O3 is a strong antimicrobial that safely decomposes to oxygen and water without leaving residues and can be used as an alternative method to prevent bacterial growth during a long transport period.

  20. Outcomes of patients with loco-regionally recurrent or new primary squamous cell carcinomas of the head and neck treated with curative intent reirradiation at Mayo Clinic.

    Science.gov (United States)

    Curtis, Kelly K; Ross, Helen J; Garrett, Ashley L; Jizba, Theresa A; Patel, Ajay B; Patel, Samir H; Wong, William W; Halyard, Michele Y; Ko, Stephen J; Kosiorek, Heidi E; Foote, Robert L

    2016-04-09

    We reviewed outcomes of patients with loco-regionally recurrent (LRR) or new primary (NP) squamous cell carcinoma of the head and neck (SCCHN) treated at our institution with reirradiation (RRT). Patients received definitive RRT (DRRT) or post-operative RRT following salvage surgery (PRRT) from 2003 to 2011. Measured survival outcomes included loco-regional relapse free survival (LRFS) and overall survival (OS). Among 81 patients (PRRT, 42; DRRT, 39), median PRRT and DRRT doses were 60 Gy (12-70 Gy) and 69.6 Gy (48-76.8 Gy). The majority of patients received IMRT-based RRT (n = 77, 95 %). With median follow-up of 78.1 months (95 % CI, 56-96.8 months), 2-year OS was 53 % with PRRT and 48 % with DRRT (p = 0.12); 23 % of patients were alive at last follow-up. LRFS at 2 years was 60 %, and did not differ significantly between PRRT and DRRT groups. A trend toward inferior LRFS was noted among patients receiving chemotherapy with RRT versus RRT alone (p = 0.06). Late serious toxicities were uncommon, including osteoradionecrosis (2 patients) and carotid artery bleeding (1 patient, non-fatal). OS of PRRT- and DRRT-treated patients in this series appears superior to the published literature. We used IMRT for the majority of patients, in contrast to several series and trials previously reported, which may account in part for this difference. Future studies should seek to improve outcomes among patients with LRR/NP SCCHN via alternative therapeutic modalities such as proton radiotherapy and by incorporating novel systemic agents.

  1. c-Myb regulates NOX1/p38 to control survival of colorectal carcinoma cells.

    Science.gov (United States)

    Pekarčíková, Lucie; Knopfová, Lucia; Beneš, Petr; Šmarda, Jan

    2016-08-01

    The c-Myb transcription factor is important for maintenance of immature cells of many tissues including colon epithelium. Overexpression of c-Myb occurring in colorectal carcinomas (CRC) as well as in other cancers often marks poor prognosis. However, the molecular mechanism explaining how c-Myb contributes to progression of CRC has not been fully elucidated. To address this point, we investigated the way how c-Myb affects sensitivity of CRC cells to anticancer drugs. Using CRC cell lines expressing exogenous c-myb we show that c-Myb protects CRC cells from the cisplatin-, oxaliplatin-, and doxorubicin-induced apoptosis, elevates reactive oxygen species via up-regulation of NOX1, and sustains the pro-survival p38 MAPK pathway. Using pharmacological inhibitors and gene silencing of p38 and NOX1 we found that these proteins are essential for the protective effect of c-Myb and that NOX1 acts upstream of p38 activation. In addition, our result suggests that transcription of NOX1 is directly controlled by c-Myb and these genes are strongly co-expressed in human tumor tissue of CRC patients. The novel c-Myb/NOX1/p38 signaling axis that protects CRC cells from chemotherapy described in this study could provide a new base for design of future therapies of CRC. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Transition from LDR to HDR brachytherapy for cervical cancer: Evaluation of tumor control, survival, and toxicity.

    Science.gov (United States)

    Romano, K D; Pugh, K J; Trifiletti, D M; Libby, B; Showalter, T N

    In 2012, our institution transitioned from low-dose-rate (LDR) brachytherapy to high dose-rate (HDR) brachytherapy. We report clinical outcomes after brachytherapy for cervical cancer at our institution over a continuous 10-year period. From 2004 to 2014, 258 women (184 LDR and 74 HDR) were treated with tandem and ovoid brachytherapy in the multidisciplinary management of International Federation of Gynecology and Obstetrics Stages IA-IVB cervical cancer. Clinical and treatment-related prognostic factors including age, stage, smoking status, relevant doses, and toxicity data were recorded. Median followup for the LDR and HDR groups was 46 months and 12 months, respectively. The majority of patients (92%) received external beam radiotherapy as well as concurrent chemotherapy (83%) before the start of brachytherapy. For all stages, the 1-year local control and overall survival (OS) rates were comparable between the LDR and HDR groups (87% vs. 81%, p = 0.12; and 75% vs. 85%, p = 0.16), respectively. Factors associated with OS on multivariate analysis include age, stage, and nodal involvement. On multivariate analysis, severe toxicity (acute or chronic) was higher with HDR than LDR (24% vs. 10%, p = 0.04). Additional prognostic factors associated with increased severe toxicity include former/current smokers and total dose to lymph nodes. This comparative retrospective analysis of a large cohort of women treated with brachytherapy demonstrates no significant difference in OS or local control between the LDR and HDR. Acute and chronic toxicity increased shortly after the implementation of HDR, highlighting the importance of continued refinement of HDR methods, including integrating advanced imaging. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  3. Fecundity, survival, and growth of the seahorse Hippocampus ingens (Pisces: Syngnathidae under semi-controlled conditions

    Directory of Open Access Journals (Sweden)

    A.A Ortega-Salas

    2006-12-01

    Full Text Available Estudiamos la fecundidad, supervivencia, y crecimiento del caballito de mar, Hippocampus ingens en condiciones semi-controladas. Tres machos reproductores silvestres de 14.8, 24.5 y 32.0 g produjeron 1 598, 1 703 y 1 658 jóvenes. La densidad utilizada fue de 12 jóvenes por acuario de 60 l. Se agruparon en 1, 12 y 20 días de nacidos por acuario. La supervivencia fue de 78.5, 38.1 y 41.0 % en 35 días. Se les alimentó con una mezcla de rotíferos B. plicatilis y nauplios de Artemia para después transferirlos a estanques de 100 000 l a una densidad de 50/1 000 l, donde se les alimentó con Artemia adulta durante 60 días más. Crecieron de un promedio de 0.7, 1.5, y 2.7 a 4.5, 5.4 6.7 cm, respectivamente, en 95 días. La temperatura del agua marina utilizada varió de 17 a 23 ºC.We studied fecundity, survival, and growth of the seahorse Hippocampus ingens under semi-controlled conditions. Three wild brood stock mature males of 14.8, 24.5, and 32.0 g released 1 598, 1 703, and 1 658 juveniles. Juvenile stocking densities of 12 were settled in 60-l aquariums in groups of 1, 12, and 20 days old organisms. The rate of survival was 21.5, 61.9, and 59.0 %, respectively, in 35 days. Juveniles were fed a mix diet of rotifers B. plicatilis and Artemia nauplii, then they were transferred to a cement tank of 100 000 l at a density of 50/1 000 l and fed with live adult Artemia for 60 days more. They grew from an average of 0.7, 1.5, and 2.7 to 4.5, 5.4, and 6.7 cm, respectively, in 95 days. The seawater temperature varied from 17 to 23 ºC. Rev. Biol. Trop. 54 (4: 1099-1102. Epub 2006 Dec. 15.

  4. Factors predicting long-term survival in low-risk diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Møller, Michael B; Pedersen, Niels T; Christensen, Bjarne E

    2003-01-01

    -based combination chemotherapy (92%) or loco-regional radiotherapy/surgery (8%) with curative intent were included. The median age was 50 years and 170 achieved complete remission. The median follow-up time was 11 years. Twenty-six patients relapsed, with a median time to relapse of 12.1 months. Overall survival...

  5. Dental Implant Survival and Complication Rate over 2 Years for Individuals with Poorly Controlled Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Eskow, Caroline C; Oates, Thomas W

    2017-06-01

    Emerging evidence suggests that implant therapy may be a viable option for diabetic individuals with elevated glycemic levels. The purpose of this 2 year observational study was to evaluate survival and clinical complications of dental implants following placement in type 2 diabetes individuals having poor glycemic control. Adult participants (n = 24) with poorly controlled type 2 diabetes (8.0% ≤ HbA1c ≤ 12.0%) received two or more transgingival dental implants. Survival was evaluated after 1 (23 participants, 72 implants) and 2 (20 participants, 59 implants) years. Clinical complications were evaluated in 18 participants (52 implants) after 21-34 months. Relationships between complications and stratified HbA1c levels were assessed using Pearson's correlation test. Survival rates were 98.6% (71/72 implants) after 1 year and 96.6% (57/59 implants) after 2 years. Complications were identified in 29% of participants with peri-implant mucositis, the most common event. Complications correlated directly with number of implants across HbA1c strata (0.42, R2  = 0.66). There was no correlation between HbA1c and the occurrences of complications or mucositis. This 2-year evaluation supports the broader application of implant therapy in type 2 diabetes individuals with poor glycemic control in demonstrating high survival rates with limited complications. © 2016 Wiley Periodicals, Inc.

  6. An overview of loco-regional treatments in patients and mouse models for hepatocellular carcinoma.

    Science.gov (United States)

    Bimonte, Sabrina; Barbieri, Antonio; Palaia, Raffaele; Leongito, Maddalena; Albino, Vittorio; Piccirillo, Mauro; Arra, Claudio; Izzo, Francesco

    2015-01-01

    Hepatocellular carcinoma is a highly aggressive malignancy and is the third leading cause of cancer-related deaths worldwide. Although surgery is currently considered the most effective curative treatment for this type of cancer, it is note that most of patients have a poor prognosis due to chemioresistence and tumor recurrence. Loco-regional therapies, including radiofrequency ablation, surgical resection and transcatheter arterial chemoembolization play a major role in the clinical management of hepatocellular carcinoma. In order to improve the treatment outcome of patients diagnosed with this disease, several in vivo studies by using different techniques on cancer mouse models have been performed. This review will focus on the latest papers on the efficacy of loco-regional therapy and combined treatments in patients and mouse models of hepatocellular carcinoma.

  7. Protecting and rescuing the effectors: roles of differentiation and survival in the control of memory T cell development

    Directory of Open Access Journals (Sweden)

    Sema eKurtulus

    2013-01-01

    Full Text Available Vaccines, arguably the single most important intervention in improving human health, have exploited the phenomenon of immunological memory. The elicitation of memory T cells is often an essential part of successful long-lived protective immunity. Our understanding of T cell memory has been greatly aided by the development of TCR Tg mice and MHC tetrameric staining reagents that have allowed the precise tracking of antigen-specific T cell responses. Indeed, following acute infection or immunization, naïve T cells undergo a massive expansion culminating in the generation of a robust effector T cell population. This peak effector response is relatively short-lived and, while most effector T cells die by apoptosis, some remain and develop into memory cells. Although the molecular mechanisms underlying this cell fate decision remain incompletely defined, substantial progress has been made, particularly with regards to CD8+ T cells. For example, the effector CD8+ T cells generated during a response are heterogeneous, consisting of cells with more or less potential to develop into full-fledged memory cells. Development of CD8+ T cell memory is regulated by the transcriptional programs that control the differentiation and survival of effector T cells. While the type of antigenic stimulation and level of inflammation control effector CD8+ T cell differentiation, availability of cytokines and their ability to control expression and function of Bcl-2 family members governs their survival. These distinct differentiation and survival programs may allow for finer therapeutic intervention to control both the quality and quantity of CD8+ T cell memory. Effector to memory transition of CD4+ T cells is less well characterized than CD8+ T cells, emerging details will be discussed. This review will focus on the recent progress made in our understanding of the mechanisms underlying the development of T cell memory with an emphasis on factors controlling survival of

  8. Thermal Ablative Therapies and Immune Checkpoint Modulation: Can Locoregional Approaches Effect a Systemic Response?

    Directory of Open Access Journals (Sweden)

    Amol Mehta

    2016-01-01

    Full Text Available Percutaneous image-guided ablation is an increasingly common treatment for a multitude of solid organ malignancies. While historically these techniques have been restricted to the management of small, unresectable tumors, there is an expanding appreciation for the systemic effects these locoregional interventions can cause. In this review, we summarize the mechanisms of action for the most common thermal ablation modalities and highlight the key advances in knowledge regarding the interactions between thermal ablation and the immune system.

  9. Higher locoregional recurrence rate for triple-negative breast cancer following neoadjuvant chemotherapy, surgery and radiotherapy

    OpenAIRE

    Zhang, Chi; Wang, Shuang; Israel, Hayley P; Yan, Sherry X; HOROWITZ, DAVID P.; Crockford, Seth; Gidea-Addeo, Daniela; K. S. Clifford Chao; Kalinsky, Kevin; Connolly, Eileen P.

    2015-01-01

    Background Breast cancer subtype, determined by expression of estrogen/progesterone receptor (ER/PR) and human epidermal growth factor receptor (HER)-2, is predictive for prognosis. The importance of subtype to locoregional recurrence (LRR) following neoadjuvant chemotherapy (NAC) is unknown, particularly after adjuvant radiotherapy (RT). Methods We retrospectively identified 160-breast cancer patients registered at Columbia University Medical Center from 1999 to 2012 treated with NAC, surger...

  10. Nomograms to predict isolated loco-regional or distant recurrence among women with uterine cancer.

    Science.gov (United States)

    Kondalsamy-Chennakesavan, Srinivas; Yu, Changhong; Kattan, Michael W; Leung, Yee; Sykes, Peter; Nascimento, Marcelo; Nicklin, James; Perrin, Lewis; Crandon, Alex; Chetty, Naven; Land, Russell; Garrett, Andrea; Obermair, Andreas

    2012-06-01

    While there is ample literature on prognostic factors for uterine cancer, currently there are nomeans to estimate an individual's risk for recurrence or to differentiate the risk of loco-regional recurrence from distant recurrence. We addressed this gap by developing nomograms to individualize the risk of recurrence. A total of 2097 consecutive patients who underwent primary surgery between 1997 and 2007 were included. Sixteen covariates were evaluated for their prognostic significance and modeled using multivariable competing risks regression to predict three-year outcomes as part of a nomogram. Each covariate in the nomogram is assigned a value, and a sum of these values form the overall risk score from which three-year incidence probabilities can be predicted for each individual. Predictive accuracy was assessed with concordance index and then corrected for optimism. The median follow-up time (inter-quartile range, IQR) was 50.0 (28.3-77.5) months and 221 patients developed a recurrence (127 patients with isolated loco-regional recurrence, 94 patients with distant recurrence). The nomograms included the following covariates: age at diagnosis, FIGO stage (2009), grade, lymphovascular invasion, histological type, depth of myometrial invasion, and peritoneal cytology. Concordance indices for isolated loco-regional and distant recurrences were 0.73 and 0.86, respectively. Our nomograms quantify an individual patient's risk of isolated loco-regional and distant recurrence, using factors that are routinely collected. They may assist clinicians to assess an individual's prognosis, individualize treatment and also assist in the risk stratification in prospective randomized clinical trials evaluating the effectiveness of treatments for uterine cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Prevention of Intra-operative Cerebral Ischemia during Carotid Endarterectomy, Loco-regional versus General Anesthesia

    Science.gov (United States)

    Tawfic, Qutaiba A.; Ismaili, Mohamed Al; Ahmed, Mooyad A.

    2012-01-01

    Carotid endarterectomy (CEA), as a prophylactic operation is becoming more popular. It is performed in patients who are at risk of stroke from dislodged atheromatous plaque at the carotid bifurcation. The major concern during CEA is the detection of cerebral hypoperfusion or ischemia during carotid cross clamping. Some studies have shown that the introduction of loco-regional anesthesia has lowered the incidence of major complications compared with general anesthesia since ischemia detection is easier in conscious patient. PMID:22811781

  12. Intraocular pressure control and corneal graft survival after implantation of Ahmed valve device in high-risk penetrating keratoplasty.

    Science.gov (United States)

    Almousa, Radwan; Nanavaty, Mayank A; Daya, Sheraz M; Lake, Damian B

    2013-08-01

    To analyze the control of intraocular pressure (IOP) and corneal graft survival after implantation of Ahmed glaucoma device (AGD) in eyes that had high-risk penetrating keratoplasty (PK). This is a retrospective noncomparative case series of 59 eyes that had high-risk PK and underwent AGD insertion. The primary outcome measures are the control of IOP between 6 and 21 mm Hg and corneal graft survival. The secondary outcome measures are risk factors associated with IOP control and corneal graft survival. The mean IOP reduced significantly after the AGD procedure (26.45 ± 6.8 mm Hg preoperatively vs. 16.85 ± 7.4 mm Hg, 16.95 ± 4.6 mm Hg, 17.97 ± 5.7 mm Hg, 15.78 ± 5.2 mm Hg, and 15.59 ± 5.5 mm Hg, at 1 month, 6 months, 1 year, 2 years, and at the last follow-up postoperatively; P IOP control was successful in 44 eyes (75.8%). IOP control was successful in 96% of the eyes at 1 year, 87% at 2 years, 83% at 3 years, and 83% at 5 years. The percentage of clear corneal grafts after 1, 2, 3, and 5 years following the AGD insertion were 87%, 77%, 65%, and 47%, respectively. Further surgery after AGD insertion was associated with 1.79 times greater risk of failure of IOP control. AGD was effective in controlling the IOP associated with high-risk PK over a 5-year period. Postvalve surgery doubles the risk of failure of IOP control.

  13. Locoregional Anesthesia for Carotid Endarterectomy: Identification of Patients with Intolerance to Cross-Clamping.

    Science.gov (United States)

    Dellaretti, Marcos; de Vasconcelos, Laura T; Dourado, Jules; de Souza, Renata F; Fontoura, Renato R; de Sousa, Atos A

    2016-03-01

    During carotid endarterectomy (CEA), carotid cross-clamping is performed to allow for artery incision and plaque removal. A small subgroup of patients can tolerate carotid occlusion for only a few seconds, if at all, without presenting neurologic deficit. These patients are described as having ''cross-clamp intolerance.'' The purpose of this study was to demonstrate the safety of locoregional anesthesia in identifying patients with cross-clamp intolerance and factors associated with this condition. From August 2008 to May 2010, 115 consecutive patients were submitted to CEA under locoregional anesthesia at the Santa Casa de Belo Horizonte; the procedure was performed by the main author. Patients who showed intolerance to internal carotid artery (ICA) occlusion for intolerance. Among the 115 participating patients, 9.6% (11 patients) showed intolerance to ICA occlusion and developed deficits in intolerance). The factor that was associated with cross-clamp intolerance was the mean degree of contralateral carotid stenosis, which was 57.5% for those who presented intolerance and 27.8% for those who tolerated ICA occlusion. Locoregional anesthesia is a safe method for identifying patients with cross-clamp intolerance. Patients with cross-clamp intolerance present contralateral stenosis that is greater on average than patients who readily tolerate carotid artery occlusion. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Personalization of loco-regional care for primary breast cancer patients (part 2).

    Science.gov (United States)

    Toi, Masakazu; Winer, Eric P; Benson, John R; Inamoto, Takashi; Forbes, John F; von Minckwitz, Gunter; Robertson, John F R; Grobmyer, Stephen R; Jatoi, Ismail; Sasano, Hironobu; Kunkler, Ian; Ho, Alice Y; Yamauchi, Chikako; Chow, Louis W C; Huang, Chiun-Sheng; Han, Wonshik; Noguchi, Shinzaburo; Pegram, Mark D; Yamauchi, Hideko; Lee, Eun-Sook; Larionov, Alexey A; Bevilacqua, Jose L B; Yoshimura, Michio; Sugie, Tomoharu; Yamauchi, Akira; Krop, Ian E; Noh, Dong Young; Klimberg, V Suzanne

    2015-01-01

    Kyoto Breast Cancer Consensus Conference, Kyoto, Japan, 18-20 February 2014 The loco-regional management of breast cancer is increasingly complex with application of primary systemic therapies, oncoplastic techniques and genetic testing for breast cancer susceptibility. Personalization of loco-regional treatment is integral to optimization of breast cancer care. Clinical and pathological tumor stage, biological features and host factors influence loco-regional treatment strategies and extent of surgical procedures. Key issues including axillary staging, axillary treatment, radiation therapy, primary systemic therapy (PST), preoperative hormonal therapy and genetic predisposition were identified and discussed at the Kyoto Breast Cancer Consensus Conference (KBCCC2014). In the second of a two part conference scene, consensus recommendations for radiation treatment, primary systemic therapies and management of genetic predisposition are reported and focus on the following topics: influence of both clinical response to PST and stage at presentation on recommendations for postmastectomy radiotherapy; use of regional nodal irradiation in selected node-positive patients and those with adverse pathological factors; extent of surgical resection following downstaging of tumors with PST; use of preoperative hormonal therapy in premenopausal women with larger, node-negative luminal A-like tumors and managing increasing demands for contralateral prophylactic mastectomy in patients with a unilateral sporadic breast cancer.

  15. Personalization of loco-regional care for primary breast cancer patients (part 1).

    Science.gov (United States)

    Toi, Masakazu; Winer, Eric P; Benson, John R; Inamoto, Takashi; Forbes, John F; von Minckwitz, Gunter; Robertson, John F R; Grobmyer, Stephen R; Jatoi, Ismail; Sasano, Hironobu; Kunkler, Ian; Ho, Alice Y; Yamauchi, Chikako; Chow, Louis W C; Huang, Chiun-Sheng; Han, Wonshik; Noguchi, Shinzaburo; Pegram, Mark D; Yamauchi, Hideko; Lee, Eun-Sook; Larionov, Alexey A; Bevilacqua, Jose L B; Yoshimura, Michio; Sugie, Tomoharu; Yamauchi, Akira; Krop, Ian E; Noh, Dong Young; Klimberg, V Suzanne

    2015-01-01

    ABSTRACT  Kyoto Breast Cancer Consensus Conference, Kyoto, Japan, 18-20 February 2014 The loco-regional management of breast cancer is increasingly complex with application of primary systemic therapies, oncoplastic techniques and genetic testing for breast cancer susceptibility. Personalization of loco-regional treatment is integral to optimization of breast cancer care. Clinical and pathological tumor stage, biological features and host factors influence loco-regional treatment strategies and extent of surgical procedures. Key issues including axillary staging, axillary treatment, radiation therapy, primary systemic therapy (PST), preoperative hormonal therapy and genetic predisposition were identified and discussed at the Kyoto Breast Cancer Consensus Conference (KBCCC2014). In the first of a two part conference scene, consensus recommendations for axillary management are presented and focus on the following topics: indications for completion axillary lymph node dissection in primary surgical patients with ≤2 macrometastases or any sentinel nodal deposits after PST; the timing of sentinel lymph node biopsy in the context of PST; use of axillary irradiation as a component of primary treatment plans and the role of intraoperative node assessment in the post-Z0011 era.

  16. Survival analysis of postoperative nausea and vomiting in patients receiving patient-controlled epidural analgesia

    Directory of Open Access Journals (Sweden)

    Shang-Yi Lee

    2014-11-01

    Conclusion: Survival analysis using Cox regression showed that the average consumption of opioids played an important role in postoperative nausea and vomiting, a result not found by logistic regression. Therefore, the incidence of postoperative nausea and vomiting in patients cannot be reliably determined on the basis of a single visit at one point in time.

  17. Modulated electro-hyperthermia induced loco-regional and systemic tumor destruction in colorectal cancer allografts.

    Science.gov (United States)

    Vancsik, Tamas; Kovago, Csaba; Kiss, Eva; Papp, Edina; Forika, Gertrud; Benyo, Zoltan; Meggyeshazi, Nora; Krenacs, Tibor

    2018-01-01

    Background: Modulated electro-hyperthermia (mEHT), a non-invasive intervention using 13.56 MHz radiofrequency, can selectively target cancers due to their elevated glycolysis (Warburg-effect), extracellular ion concentration and conductivity compared to normal tissues. We showed earlier that mEHT alone can provoke apoptosis and damage associated molecular pattern (DAMP) signals in human HT29 colorectal cancer xenografts of immunocompromised mice. Materials: Here we tested the mEHT induced stress and immune responses in C26 colorectal cancer allografts of immunocompetent (BALB/c) mice between 12-72 h post-treatment. The right side of the symmetrical tumors grown in both femoral regions of mice were treated for 30 minutes, while the left side tumors served for untreated controls. Results: Loco-regional mEHT treatment induced an ongoing and significant tumor damage with the blockade of cell cycle progression indicated by the loss of nuclear Ki67 protein. Nuclear shrinkage, apoptotic bodies and DNA fragmentation detected using TUNEL assay confirmed apoptosis. Cleaved/activated-caspase-8 and -caspase-3 upregulation along with mitochondrial translocation of bax protein and release of cytochrome-c were consistent with the activation of both the extrinsic and intrinsic caspase-dependent programmed cell death pathways. The prominent release of stress-associated Hsp70, calreticulin and HMGB1 proteins, relevant to DAMP signaling, was accompanied by the significant tumor infiltration by S100 positive antigen presenting dendritic cells and CD3 positive T-cells with only scant FoxP3 positive regulatory T-cells. In addition, mEHT combined with a chlorogenic acid rich T-cell promoting agent induced significant cell death both in the treated and the untreated contralateral tumors indicating a systemic anti-tumor effect. Conclusions: mEHT induced caspase-dependent programmed cell death and the release of stress associated DAMP proteins in colorectal cancer allografts can provoke

  18. Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma. A matched-pair multicenter analysis of outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Yi-Yuan [Affiliated Hospital of Guilin Medical University, Department of Radiation Oncology, Guilin (China); Guilin Medical University Affiliated Hospital, Department of Otorhinolaryngology, Guilin (China); Xiang, Chun [Nan Xishan Hospital, Department of Otorhinolaryngology, Guilin (China); Lu, Jian-Xun [Affiliated Hospital of Youjiang Medical University for Nationalities, Department of Oncology, Baise (China); Su, Yi-Xin [Lingshan People' s Hospital, Department of Radiation Oncology, Lingshan (China); Pan, Yu-Fei [Nan Xishan Hospital, Department of Radiation Oncology, Guilin (China); Cai, Rui; Zhang, Rong-Jun; He, Zhuo-Kai; Liu, Mei-Lian; Huang, Hui; Bai, Xue; Tang, Hua-Ying; Shi, Yun-Hua; Wang, Yan; Jiang, Wei [Affiliated Hospital of Guilin Medical University, Department of Radiation Oncology, Guilin (China)

    2016-06-15

    The benefit of adjuvant chemotherapy (AC) in locoregionally advanced nasopharyngeal carcinoma (NPC) is controversial. This study compared concurrent chemoradiotherapy plus AC (CCRT/AC) with CCRT. Pair-matched analysis based on eight clinicopathological features of 244 patients treated with platinum-based CCRT/AC or CCRT alone was performed. Survival outcomes were assessed using the Kaplan-Meier method and log-rank test. Toxicities and response rates were compared using Fisher's exact test. Four-year overall survival, progression-free survival, distant failure-free survival, and locoregional failure-free survival were 72 %, 61 %, 71 %, and 81 %, respectively, for the CCRT arm, compared to 74 % (hazard ratio, HR 0.89; 95 % confidence interval, CI 0.64-1.23; P = 0.474), 62 % (HR 0.91, 95 % CI 0.68-1.20, P = 0.489), 73 % (HR 0.84, 95 % CI 0.59-1.18, P = 0.316), and 84 % (HR 0.84, 95 % CI 0.52-1.24, P = 0.323), respectively, for the CCRT/AC arm. Cox multivariate regression analysis demonstrated AC was not an independent prognostic factor. Overall, there was a higher incidence of grade 3-4 toxicities in the CCRT/AC arm. The most common grade 3-4 adverse events in the CCRT/AC arm were vomiting (27 %), nausea (43 %), leukopenia/neutropenia (23 %), thrombocytopenia (8.8 %), and anemia (6.2 %). Addition of AC to CCRT increased toxicities but did not improve survival in locoregionally advanced NPC. (orig.) [German] Der Nutzen der adjuvanten Chemotherapie (AC) bei lokoregional fortgeschrittenem nasopharyngealem Karzinom (NPC) ist kontrovers. In dieser Studie wurde die simultane Radiochemotherapie (''concurrent chemoradiotherapy'', CCRT) plus adjuvante Chemotherapie (AC) mit einer alleinigen CCRT verglichen. Die Matched-pair-Analyse basiert auf acht klinisch-pathologischen Merkmalen von 244 Patienten, die mit platinbasierter CCRT/AC oder alleiniger CCRT behandelt wurden. Die Ueberlebensendpunkte wurden mit der Kaplan-Meier-Methode und dem Log

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. Effect of pathologic fractures on survival in multiple myeloma patients: a case control study

    Directory of Open Access Journals (Sweden)

    Yilmaz Mustafa

    2008-06-01

    Full Text Available Abstract Background Multiple Myeloma (MM is a B cell neoplasm characterized by the clonal proliferation of plasma cells. Skeletal complications are found in up to 80% of myeloma patients at presentation and are major cause of morbidity. Methods 49 patients were enrolled with MM admitted to Black Sea Technical University Hospital between 2002–2005. Pathologic fractures (PFs were determined and the patients with or without PF were followed up minumum 3 years for survival analysis. Results PF was observed in 24 patients (49% and not observed in 25 patients (51%. The risk of death was increased in the patients with PF compared with patients who had no fractures. While overall survival was 17.6 months in the patients with PFs, it was 57.3 months in the patients with no PFs. Conclusion These findings suggest that PFs may induce reduced survival and increased mortality in the MM patients, however, larger sample size is essential to draw clearer conclusions added to these data.

  1. IIB osteosarcoma. Current management, local control, and survival statistics--São Paulo, Brazil.

    Science.gov (United States)

    Petrilli, S; Penna, V; Lopes, A; Figueiredo, M T; Gentil, F C

    1991-09-01

    Ninety-two patients with IIB osteosarcoma of the extremities were treated with intraarterial (IA) cisplatinum (CDDP) followed by surgery [amputation (61.6%) or resection with endoprosthesis (38.4%)]. Postoperative chemotherapy alternating adriamycin and CDDP was used. The total three-year survival was 62.1%, and the disease-free survival was 41.1%. The pathologic evaluation of the degree of tumor necrosis in response to the IA CDDP showed that in 53.2%, the necrosis was over 90%. The multivariate analysis of prognostic factors has shown that the highest survival was among females with tumors smaller than 15 cm. Patients with lesions equal to or larger than 15 cm were three times as likely to die of the disease. A second, more aggressive study is now underway, in which high dose methotrexate (HDMTX) is preoperatively combined with adriamycin and CDDP. Following operation, ifosfamide is added to the cases with a smaller degree of tumor necrosis, while the other group of patients will continue with HDMTX, in addition to CDDP and adriamycin (these last two drugs are used in both arms). Until now, complete remission has been achieved in 82% and 86%, respectively, with a follow-up examination varying from four to 26 months (average, 14 months). This is of extreme importance, because the majority of the authors' patients have tumors at initial evaluation larger than 10 cm in diameter.

  2. The Norwegian dietary guidelines and colorectal cancer survival (CRC-NORDIET) study: a food-based multicentre randomized controlled trial.

    Science.gov (United States)

    Henriksen, Hege Berg; Ræder, Hanna; Bøhn, Siv Kjølsrud; Paur, Ingvild; Kværner, Ane Sørlie; Billington, Siv Åshild; Eriksen, Morten Tandberg; Wiedsvang, Gro; Erlund, Iris; Færden, Arne; Veierød, Marit Bragelien; Zucknick, Manuela; Smeland, Sigbjørn; Blomhoff, Rune

    2017-01-30

    Colorectal cancer survivors are not only at risk for recurrent disease but also at increased risk of comorbidities such as other cancers, cardiovascular disease, diabetes, hypertension and functional decline. In this trial, we aim at investigating whether a diet in accordance with the Norwegian food-based dietary guidelines and focusing at dampening inflammation and oxidative stress will improve long-term disease outcomes and survival in colorectal cancer patients. This paper presents the study protocol of the Norwegian Dietary Guidelines and Colorectal Cancer Survival study. Men and women aged 50-80 years diagnosed with primary invasive colorectal cancer (Stage I-III) are invited to this randomized controlled, parallel two-arm trial 2-9 months after curative surgery. The intervention group (n = 250) receives an intensive dietary intervention lasting for 12 months and a subsequent maintenance intervention for 14 years. The control group (n = 250) receives no dietary intervention other than standard clinical care. Both groups are offered equal general advice of physical activity. Patients are followed-up at 6 months and 1, 3, 5, 7, 10 and 15 years after baseline. The study center is located at the Department of Nutrition, University of Oslo, and patients are recruited from two hospitals within the South-Eastern Norway Regional Health Authority. Primary outcomes are disease-free survival and overall survival. Secondary outcomes are time to recurrence, cardiovascular disease-free survival, compliance to the dietary recommendations and the effects of the intervention on new comorbidities, intermediate biomarkers, nutrition status, physical activity, physical function and quality of life. The current study is designed to gain a better understanding of the role of a healthy diet aimed at dampening inflammation and oxidative stress on long-term disease outcomes and survival in colorectal cancer patients. Since previous research on the role of diet for

  3. Predictive Value of Primary Tumor Site for Loco-regional Recurrence in Early Breast Cancer Patients with One to Three Positive Axillary Lymphadenophy.

    Science.gov (United States)

    Niu, Shaoqing; Wen, Ge; Ren, Yufeng; Li, Yiyang; Feng, Lingling; Wang, Chengtao; Huang, Xiaobo; Wen, Bixiu; Zhang, Yujing

    2017-01-01

    Introduction: It remains controversial on high risks for early breast cancer patients with one to three axillary nodes after mastectomy who is predisposition to locoregional recurrence. The present study is to investigate the relationship between primary tumor site and loco-regional recurrence (LRR) and explore the predictive value of clinicopathological characteristics in LRR for early breast cancer patients with one to three positive axillary lymph nodes after mastectomy. Methods: We reviewed the clinical data of 656 consecutively diagnosed patients with pT1-2N1M0 breast cancer who were treated in Sun Yat-sen University Cancer Center with radical operation without postoperative radiotherapy between March 1998 and December 2010. The primary tumor sites included outer quadrant in 455 patients (69.36%), inner quadrant in 156 patients (23.78%)and central quadrant in 45 patients (6.86%). LRR and LRR-free survival (LRFS) in combination with clinical and pathological features were analyzed to screen out patients with higher risk of LRR. Results: The median follow-up time was 64.9 months. The 5-, 10-year LRR for the cohort was 8.6% and 12.9%, respectively; the 5-, 10-year LRFS was 86.2% and 76.4%, respectively. Multivariate analyses showed that age of ≤35 years, inner quadrant tumor and non-luminal subtype were independent risk factors for LRR and LRFS. Patients with primary tumor in inner quadrant showed higher LRR and poorer LRFS when risk factors are ≥2 than those with tumors in other sites. Conclusions: Inner quadrant tumor was an independent predictor for LRR and LRFS in patients with early breast cancer and one to three positive axillary lymph nodes, which would be more accurate in combination with other prognostic indexes including patients' age, pathological T stage, Ki67 status, molecular subtypes.

  4. Radical Radiation Therapy After Lung-Sparing Surgery for Malignant Pleural Mesothelioma: Survival, Pattern of Failure, and Prognostic Factors

    Energy Technology Data Exchange (ETDEWEB)

    Minatel, Emilio [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Trovo, Marco, E-mail: marcotrovo33@hotmail.com [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Bearz, Alessandra [Department of Medical Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Di Maso, Matteo [Unit of Epidemiology and Biostatistics, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Baresic, Tania [Department of Nuclear Medicine, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Drigo, Annalisa; Barresi, Loredana [Department of Medical Physics, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Furlan, Carlo [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Del Conte, Alessandro [Department of Medical Oncology, Pordenone General Hospital, Pordenone (Italy); Bruschi, Gioia [Department of Pneumology, Pordenone General Hospital, Pordenone (Italy); Fontana, Paolo [Department of Thoracic Surgery, Mestre General Hospital, Mestre (Italy); Pagan, Vittore [Department of Surgery, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Franchin, Giovanni [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy)

    2015-11-01

    Purpose: To prospectively assess the survival, patterns of failure, and prognostic factors in a large cohort of patients with malignant pleural mesothelioma who had undergone a novel trimodal therapeutic approach, including lung-sparing surgery, chemotherapy, and subsequent treatment with high doses of intensity modulated radiation therapy (IMRT) to the whole hemithorax. Methods and Materials: The analysis was conducted on the data from 69 patients. Of the 69 patients, 35 underwent extended pleurectomy/decortication (P/D), with resection of the entire pleura, along with portions of the pericardium and diaphragm and 34, partial pleurectomy, defined as partial removal of parietal or visceral pleura for diagnostic purposes, leaving gross tumor behind in all cases. All patients received cisplatin/pemetrexed chemotherapy. Postoperative IMRT was delivered to the entire hemithorax, excluding the intact lung. The IMRT dose was 50 Gy in 25 fractions. Any fluorodeoxyglucose-avid areas or regions of particular concern for residual disease were given a simultaneous boost to 60 Gy. Results: The median follow-up duration was 19 months. No difference was seen in overall survival and locoregional control between the extended P/D group and the partial pleurectomy group. The 2-year overall survival was 65% and 58% in the extended P/D and partial pleurectomy groups, respectively (P=.94). Locoregional control at 2 years was 65% and 64% in the extended P/D and partial pleurectomy groups, respectively (P=.75). The predominant pattern of failure was distant: 19 patients (27.5%) developed distant metastases as the first site of relapse. Gross residual disease after surgery was significantly associated with overall survival (hazard ratio 3.45). One fatal pneumonitis was reported; 14 cases (20%) of grade 2 to 3 pneumonitis were documented. Conclusions: Radical IMRT after lung-sparing surgery and chemotherapy for malignant pleural mesothelioma leads to promising survival results and

  5. Radical Radiation Therapy After Lung-Sparing Surgery for Malignant Pleural Mesothelioma: Survival, Pattern of Failure, and Prognostic Factors.

    Science.gov (United States)

    Minatel, Emilio; Trovo, Marco; Bearz, Alessandra; Di Maso, Matteo; Baresic, Tania; Drigo, Annalisa; Barresi, Loredana; Furlan, Carlo; Del Conte, Alessandro; Bruschi, Gioia; Fontana, Paolo; Pagan, Vittore; Franchin, Giovanni

    2015-11-01

    To prospectively assess the survival, patterns of failure, and prognostic factors in a large cohort of patients with malignant pleural mesothelioma who had undergone a novel trimodal therapeutic approach, including lung-sparing surgery, chemotherapy, and subsequent treatment with high doses of intensity modulated radiation therapy (IMRT) to the whole hemithorax. The analysis was conducted on the data from 69 patients. Of the 69 patients, 35 underwent extended pleurectomy/decortication (P/D), with resection of the entire pleura, along with portions of the pericardium and diaphragm and 34, partial pleurectomy, defined as partial removal of parietal or visceral pleura for diagnostic purposes, leaving gross tumor behind in all cases. All patients received cisplatin/pemetrexed chemotherapy. Postoperative IMRT was delivered to the entire hemithorax, excluding the intact lung. The IMRT dose was 50 Gy in 25 fractions. Any fluorodeoxyglucose-avid areas or regions of particular concern for residual disease were given a simultaneous boost to 60 Gy. The median follow-up duration was 19 months. No difference was seen in overall survival and locoregional control between the extended P/D group and the partial pleurectomy group. The 2-year overall survival was 65% and 58% in the extended P/D and partial pleurectomy groups, respectively (P=.94). Locoregional control at 2 years was 65% and 64% in the extended P/D and partial pleurectomy groups, respectively (P=.75). The predominant pattern of failure was distant: 19 patients (27.5%) developed distant metastases as the first site of relapse. Gross residual disease after surgery was significantly associated with overall survival (hazard ratio 3.45). One fatal pneumonitis was reported; 14 cases (20%) of grade 2 to 3 pneumonitis were documented. Radical IMRT after lung-sparing surgery and chemotherapy for malignant pleural mesothelioma leads to promising survival results and acceptable toxicity rates. The similarity of survival between

  6. Pedicled posteromedial thigh (pPMT) perforator flap and its application in loco-regional soft tissue reconstructions.

    Science.gov (United States)

    Scaglioni, Mario F; Franchi, Alberto; Giovanoli, Pietro

    2017-10-16

    The posteromedial thigh (PMT) perforator flap is a valuable reconstructive option. In its pedicled form, the experience is currently limited to a few case reports. The purpose of this article is to describe various clinical applications of the pedicled posteromedial thigh (pPMT) flap for reconstruction of loco-regional soft tissue defects. From 2014 to 2016, 15 patients underwent reconstruction with 15 pPMT flaps. The locations of the defects included the inguinal region (4 cases), the perineal and genital region (3 cases), the proximal and distal medial thigh (3 and 2 cases, respectively), and the popliteal fossa (3 cases). The perforator selected was a branch of the profunda femoris artery (PFA) in 12 cases and the medial circumflex fermoral artery (MCFA) in 3 cases. In all cases, the flap was harvested as a perforator-based island flap, while the mechanism of flap transfer varied between V-Y advancement, interpolation, or different degrees of axial pivoting around the skeletonized perforator (propeller flap design). The flap sizes varied from 5 × 4 cm2 to 29 × 8 cm2, and the pedicle could be skeletonized for up to 13 cm. All the flaps survived after surgery without complication. The donor sites were all primarily closed with minimal morbidity. Follow-up observations were conducted for 6 to 14 months, and all patients had good functional recovery. The pPMT perforator flap is a reconstructive option that can be considered when dealing with soft tissue defects located in body regions ranging from the groin down to the popliteal fossa. It avoids the need for a microsurgical transfer and easily fulfills the dictum of replacing "like tissue with like tissue." Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  7. Functional hepatic imaging as a biomarker of primary and secondary tumor response to loco-regional therapies.

    Science.gov (United States)

    Lewis, H L; Ghasabeh, M A; Khoshpouri, P; Kamel, I R; Pawlik, T M

    2017-12-01

    Objective criteria to measure tumor response are a key tenet for assessment of treatment efficacy when evaluating a therapeutic modality. Several response criteria have been proposed including the Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST (mRECIST), RECIST 1-1, and European Association for the Study of the Liver (EASL) guidelines. Response following loco-regional therapies (LRT) can be particularly difficult to assess as post-treatment changes may not always relate to changes in lesion size. As imaging modalities and solid tumor therapies continue to advance, there has been growing recognition that measurement of actual tumoricidal activity may not always be related to tumor size, and accurate assessment of treatment response may vary by therapeutic modality. As such, the objective change in the physical size characteristics of a tumor may not accurately reflect biological response to treatment. Functional imaging encompasses methods that are capable of detecting or measuring changes in tissue metabolism, blood flow, or composition. Conventional imaging modalities such as magnetic resonance imaging (MRI) and computed topography (CT) now include techniques such as diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) maps, dynamic contrast enhancement (DCE-MRI), and perfusion CT (pCT). Use of functional cross-sectional imaging is particularly relevant to assess primary and secondary hepatic malignancies treated with LRT, such as trans-arterial chemoembolization (TACE), radiofrequency ablation (RFA), yttrium-90 (Y-90), and hepatic arterial infusion (HAI) chemotherapy. We herein review the imaging techniques, as well as the methodologies for measuring tumor response and survival, among patients treated with LRT for primary and secondary hepatic malignancies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Carotid endarterectomy: review of 10 years of practice of general and locoregional anesthesia in a tertiary care hospital in Portugal

    Directory of Open Access Journals (Sweden)

    Mercês Lobo

    2015-08-01

    Full Text Available BACKGROUND: Retrospective and prospective randomized studies have compared general and locoregional anesthesia for carotid endarterectomy, but without definitive results.OBJECTIVES: Evaluate the incidence of complications (medical, surgical, neurological, and hospital mortality in a tertiary center in Portugal and review the literature.METHODS: Retrospective analysis of patients undergoing endarterectomy between 2000 and 2011, using a software for hospital consultation.RESULTS: A total of 750 patients were identified, and locoregional anesthesia had to be converted to general anesthesia in 13 patients. Thus, a total of 737 patients were included in this analysis: 74% underwent locoregional anesthesia and 26% underwent general anesthesia. There was no statistically significant difference between the two groups regarding per operative variables. The use of shunt was more common in patients undergoing general anesthesia, a statistically significant difference. The difference between groups of strokes and mortality was not statistically significant. The average length of stay was shorter in patients undergoing locoregional anesthesia with a statistically significant difference.CONCLUSIONS: We found that our data are overlaid with the literature data. After reviewing the literature, we found that the number of studies comparing locoregional and general anesthesia and its impact on delirium, cognitive impairment, and decreased quality of life after surgery is still very small and can provide important data to compare the two techniques. Thus, some questions remain open, which indicates the need for randomized studies with larger number of patients and in new centers.

  9. Novel Multisensor Probe for Monitoring Bladder Temperature During Locoregional Chemohyperthermia for Nonmuscle-Invasive Bladder Cancer: Technical Feasibility Study

    Science.gov (United States)

    Geijsen, Debby E.; Zum Vörde Sive Vörding, Paul J.; Schooneveldt, Gerben; Sijbrands, Jan; Hulshof, Maarten C.; de la Rosette, Jean; de Reijke, Theo M.; Crezee, Hans

    2013-01-01

    Abstract Background and Purpose: The effectiveness of locoregional hyperthermia combined with intravesical instillation of mitomycin C to reduce the risk of recurrence and progression of intermediate- and high-risk nonmuscle-invasive bladder cancer is currently investigated in clinical trials. Clinically effective locoregional hyperthermia delivery necessitates adequate thermal dosimetry; thus, optimal thermometry methods are needed to monitor accurately the temperature distribution throughout the bladder wall. The aim of the study was to evaluate the technical feasibility of a novel intravesical device (multi-sensor probe) developed to monitor the local bladder wall temperatures during loco-regional C-HT. Materials and Methods: A multisensor thermocouple probe was designed for deployment in the human bladder, using special sensors to cover the bladder wall in different directions. The deployment of the thermocouples against the bladder wall was evaluated with visual, endoscopic, and CT imaging in bladder phantoms, porcine models, and human bladders obtained from obduction for bladder volumes and different deployment sizes of the probe. Finally, porcine bladders were embedded in a phantom and subjected to locoregional heating to compare probe temperatures with additional thermometry inside and outside the bladder wall. Results: The 7.5 cm thermocouple probe yielded optimal bladder wall contact, adapting to different bladder volumes. Temperature monitoring was shown to be accurate and representative for the actual bladder wall temperature. Conclusions: Use of this novel multisensor probe could yield a more accurate monitoring of the bladder wall temperature during locoregional chemohyperthermia. PMID:24112045

  10. Brief reports: Controlling the survival of human pluripotent stem cells by small molecule-based targeting of topoisomerase II alpha.

    Science.gov (United States)

    Ben-David, Uri; Cowell, Ian G; Austin, Caroline A; Benvenisty, Nissim

    2015-03-01

    Pluripotent-specific inhibitors (PluriSIns) make a powerful tool to study the mechanisms controlling the survival of human pluripotent stem cells (hPSCs). Here, we characterize the mechanism of action of PluriSIn#2, a compound that selectively eliminates undifferentiated hPSCs, while sparing various other cell types derived from them. Toxicogenomic analysis predicts this compound to be a topoisomerase inhibitor. Gene expression analyses reveal that one of the human topoisomerase enzymes, topoisomerase II alpha (TOP2A), is uniquely expressed in hPSCs: TOP2A is highly expressed in undifferentiated cells, is downregulated during their differentiation, and its expression depends on the expression of core pluripotency transcription factors. Furthermore, siRNA-based knockdown of TOP2A in undifferentiated hPSCs results in their cell death, revealing that TOP2A expression is required for the survival of these cells. We find that PluriSIn#2 does not directly inhibit TOP2A enzymatic activity, but rather selectively represses its transcription, thereby significantly reducing TOP2A protein levels. As undifferentiated hPSCs require TOP2A activity for their survival, TOP2A inhibition by PluriSIn#2 thus causes their cell death. Therefore, TOP2A dependency can be harnessed for the selective elimination of tumorigenic hPSCs from culture. © 2014 AlphaMed Press.

  11. Altered G{sub 1} checkpoint control determines adaptive survival responses to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Boothman, David A.; Meyers, Mark; Odegaard, Eric; Wang, Meizhi [Department of Human Oncology, University of Wisconsin-Madison, Madison, WI (United States)

    1996-11-04

    Adaptive survival responses (ASRs) are observed when cells become more resistant to a high dose of a cytotoxic agent after repeated low dose exposures to that agent or another genotoxic agent. Confluent (G{sub 0}/G{sub 1}) human normal (GM2936B, GM2937A, AG2603, IMR-90), cancer-prone (XPV2359), and neoplastic (U1-Mel, HEp-2, HTB-152) cells were primed with repeated low doses of X-rays (ranging from 0.05-10 cGy/day for 4 days), then challenged with a high dose (290-450 cGy) on day 5. U1-Mel and HEp-2 cells showed greater than 2-fold transient survival enhancement when primed with 1-10 cGy. ASRs in U1-Mel or HEp-2 cells were blocked by cycloheximide or actinomycin D. Increases in cyclins A and D1 mRNAs were noted in primed compared to unirradiated U1-Mel and HEp-2 cells; however, only cyclin A protein levels increased. Cyclin D1 and proliferating cell nuclear antigen (PCNA) protein levels were constitutively elevated in HEp-2 and U1-Mel cells, compared to the other human normal and neoplastic cells examined, and were not altered by low or high doses of radiation. Low dose primed U1-Mel cells entered S-phase 4-6 h faster than unprimed U1-Mel cells upon low-density replating. Similar responses in terms of survival recovery, transcript and protein induction, and altered cell cycle regulation were not observed in the other human normal, cancer-prone or neoplastic cells examined. We hypothesize that only certain human cells can adapt to ionizing radiation by progressing to a point later in G{sub 1} (the A point) where DNA repair processes and radioresistance can be induced. ASRs in human cells correlated well with constitutively elevated levels of PCNA and cyclin D1, as well as inducibility of cyclin A. We propose that a protein complex composed of cyclin D1, PCNA, and possibly cyclin A may play a role in cell cycle regulation and DNA repair, which determine ASRs in human cells.

  12. Combination of immortalization and inducible death strategies to generate a human mesenchymal stromal cell line with controlled survival

    Directory of Open Access Journals (Sweden)

    Paul Bourgine

    2014-03-01

    By combining the opposite concepts of ‘induced-life’ and ‘inducible-death’, we generated a hMSCs line with defined properties and allowing for temporally controlled survival. The cell line represents a relevant tool for medical discovery in regenerative medicine and a potential means to address availability, standardization and safety requirements in cell & gene therapy. The concept of a hTERT-iCasp9 combination, here explored in the context of hMSCs, could be extended to other types of progenitor/stem cells.

  13. Damage control resuscitation is associated with a reduction in resuscitation volumes and improvement in survival in 390 damage control laparotomy patients.

    Science.gov (United States)

    Cotton, Bryan A; Reddy, Neeti; Hatch, Quinton M; LeFebvre, Eric; Wade, Charles E; Kozar, Rosemary A; Gill, Brijesh S; Albarado, Rondel; McNutt, Michelle K; Holcomb, John B

    2011-10-01

    To determine whether implementation of damage control resuscitation (DCR) in patients undergoing damage control laparotomy (DCL) translates into improved survival. DCR aims at preventing coagulopathy through permissive hypotension, limiting crystalloids and delivering higher ratios of plasma and platelets. Previous work has focused only on the impact of delivering higher ratios (1:1:1). A retrospective cohort study was performed on all DCL patients admitted between January 2004 and August 2010. Patients were divided into pre-DCR implementation and DCR groups and were excluded if they died before completion of the initial laparotomy. The lethal triad was defined as immediate postoperative temperature less than 95°F, international normalized ratio more than 1.5, or a pH less than 7.30. A total of 390 patients underwent DCL. Of these, 282 were pre-DCR and 108 were DCR. Groups were similar in demographics, injury severity, admission vitals, and laboratory values. DCR patients received less crystalloids (median: 14 L vs 5 L), red blood cells (13 U vs 7 U), plasma (11 U vs 8 U), and platelets (6 U vs 0 U) in 24 hours, all P lethal triad upon intensive care unit arrival (80% vs 46%, P < 0.001). 24-hour and 30-day survival was higher with DCR (88% vs 97%, P = 0.006 and 76% vs 86%, P = 0.03). Multivariate analysis controlling for age, injury severity, and emergency department variables, demonstrated DCR was associated with a significant increase in 30-day survival (OR: 2.5, 95% CI: 1.10-5.58, P = 0.028). In patients undergoing DCL, implementation of DCR reduces crystalloid and blood product administration. More importantly, DCR is associated with an improvement in 30-day survival.

  14. Data Acquistion Controllers and Computers that can Endure, Operate and Survive Cryogenic Temperatures Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Current and future NASA exploration flight missions require Avionics systems, Computers, Controllers and Data processing units that are capable of enduring extreme...

  15. Surgical Treatment with Locoregional Flap for the Nose

    Directory of Open Access Journals (Sweden)

    Marco Marcasciano

    2017-01-01

    Full Text Available Nonmelanotic skin cancers (NMSCs are the most frequent of all neoplasms and nasal pyramid represents the most common site for the presentation of such cutaneous malignancies, particularly in sun-exposed areas: ala, dorsum, and tip. Multiple options exist to restore functional and aesthetic integrity after skin loss for oncological reasons; nevertheless, the management of nasal defects can be often challenging and the best “reconstruction” is still to be found. In this study, we retrospectively reviewed a total of 310 patients who presented to our Department of Plastic and Reconstructive Surgery for postoncological nasal reconstruction between January 2011 and January 2016. Nasal region was classified into 3 groups according to the anatomical zones affected by the lesion: proximal, middle, and distal third. We included an additional fourth group for complex defects involving more than one subunit. Reconstruction with loco regional flaps was performed in all cases. Radical tumor control and a satisfactory aesthetic and functional result are the primary goals for the reconstructive surgeon. Despite tremendous technical enhancements in nasal reconstruction techniques, optimal results are usually obtained when “like is used to repair like.” Accurate evaluation of the patients clinical condition and local defect should be always considered in order to select the best surgical option.

  16. PRETREATMENT NUTRITIONAL STATUS AND LOCOREGIONAL FAILURE IN PATIENTS WITH HEAD AND NECK CANCER UNDERGOING DEFINITIVE CONCURRENT CHEMORADIATION THERAPY

    Science.gov (United States)

    Platek, Mary E.; Reid, Mary E.; Wilding, Gregory E.; Jaggernauth, Wainwright; Rigual, Nestor R.; Hicks, Wesley L.; Popat, Saurin R.; Warren, Graham W.; Sullivan, Maureen; Thorstad, Wade L.; Khan, Mohamed K.; Loree, Thom R.; Singh, Anurag K.

    2015-01-01

    Background This study was carried out to determine if markers of nutritional status predict for locoregional failure following intensity-modulated radiation therapy (IMRT) with concurrent chemoradiotherapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN). Methods We performed a retrospective chart review of 78 patients with SCCHN who received definitive CCRT. We compared patient factors, tumor characteristics, and nutritional status indicators between patients with and without locoregional failure. Results Fifteen of 78 patients (19%) experienced locoregional failure. Median follow-up for live patients was 38 months. On univariate analysis, pretreatment percentage of ideal body weight (%IBW) (p cancer undergoing definitive CCRT based on pre-treatment %IBW should be examined further. PMID:21990220

  17. Pretreatment nutritional status and locoregional failure of patients with head and neck cancer undergoing definitive concurrent chemoradiation therapy.

    Science.gov (United States)

    Platek, Mary E; Reid, Mary E; Wilding, Gregory E; Jaggernauth, Wainwright; Rigual, Nestor R; Hicks, Wesley L; Popat, Saurin R; Warren, Graham W; Sullivan, Maureen; Thorstad, Wade L; Khan, Mohamed K; Loree, Thom R; Singh, Anurag K

    2011-11-01

    This study was carried out to determine if markers of nutritional status predict for locoregional failure following intensity-modulated radiation therapy (IMRT) with concurrent chemoradiotherapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN). We performed a retrospective chart review of 78 patients with SCCHN who received definitive CCRT. We compared patient factors, tumor characteristics, and nutritional status indicators between patients with and without locoregional failure. Fifteen of 78 patients (19%) experienced locoregional failure. Median follow-up for live patients was 38 months. On univariate analysis, pretreatment percentage of ideal body weight (%IBW) (p cancer undergoing definitive CCRT based on pretreatment %IBW should be examined further. Copyright © 2010 Wiley Periodicals, Inc.

  18. Survival variability of controls and definition of imaging endpoints for longitudinal follow-up of pancreatic ductal adenocarcinoma in rats.

    Science.gov (United States)

    Akladios, Cherif; Ignat, Mihaela; Mutter, Didier; Aprahamian, Marc

    2017-01-01

    The 3Rs guideline is the gold standard for ethics in animal experimentation. Two of those rules, namely refinement and reduction, require further improvement. The objective of this study was to define pathways to better compliance with these prerequisites. Two methods which move us in this direction are: (1) using small animal imaging techniques for pancreatic ductal adenocarcinoma (PDAC) follow-up and (2) reduction of the number of control animals included in a study of PDAC progression under treatment. Firstly, we used MicroCT scan to diagnose events showing PDAC progression prior to any clinical symptoms to thereby define more humane endpoints identifiable before any painful phenomenon is observed. Secondly, in order to test the hypothesis of using a reference control group in all preclinical studies of a new treatment of PDAC, we investigated the stability of the results obtained with the control groups in three successive identical studies comparing placebo and gemcitabine in tumor-bearing Lewis rats. Two imaging endpoints were found. The first was the observation of a liver metastasis assessing PDAC diffusion and, earlier than liver metastasis, the presence of bands of fluid along the flanks, with more or less a medial displacement of bowel and solid viscera, reflecting a peritoneal ascites. Results of the longitudinal follow-up of rats in the gemcitabine study revealed heterogeneity in the survival rate in the three control groups, as opposed to the survival rate in the three treated groups which did not differ statistically. As a result, the significance of improved survival with chemotherapy varied greatly according to the control group used for the comparison, ranging from no impact to a highly significant effect. The early detection by the means of animal imaging of one or more signs indicating the onset of a critical step in the development of the disease (e.g., ascites or/and metastasis) allows the researcher to prevent the occurrence of animal pain

  19. The impact of prostate edema on cell survival and tumor control after permanent interstitial brachytherapy for early stage prostate cancers

    Science.gov (United States)

    (Jay Chen, Zhe; Roberts, Kenneth; Decker, Roy; Pathare, Pradip; Rockwell, Sara; Nath, Ravinder

    2011-08-01

    Previous studies have shown that procedure-induced prostate edema during permanent interstitial brachytherapy (PIB) can cause significant variations in the dose delivered to the prostate gland. Because the clinical impact of edema-induced dose variations strongly depends on the magnitude of the edema, the temporal pattern of its resolution and its interplay with the decay of radioactivity and the underlying biological processes of tumor cells (such as tumor potential doubling time), we investigated the impact of edema-induced dose variations on the tumor cell survival and tumor control probability after PIB with the 131Cs, 125I and 103Pd sources used in current clinical practice. The exponential edema resolution model reported by Waterman et al (1998 Int. J. Radiat. Oncol. Biol. Phys. 41 1069-77) was used to characterize the edema evolutions previously observed during clinical PIB for prostate cancer. The concept of biologically effective dose, taking into account tumor cell proliferation and sublethal damage repair during dose delivery, was used to characterize the effects of prostate edema on cell survival and tumor control probability. Our calculation indicated that prostate edema, if not appropriately taken into account, can increase the cell survival and decrease the probability of local control of PIB. The magnitude of an edema-induced increase in cell survival increased with increasing edema severity, decreasing half-life of radioactive decay and decreasing photon energy emitted by the source. At the doses currently prescribed for PIB and for prostate cancer cells characterized by nominal radiobiology parameters recommended by AAPM TG-137, PIB using 125I sources was less affected by edema than PIB using 131Cs or 103Pd sources due to the long radioactive decay half-life of 125I. The effect of edema on PIB using 131Cs or 103Pd was similar. The effect of edema on 103Pd PIB was slightly greater, even though the decay half-life of 103Pd (17 days) is longer than

  20. Vector control improves survival of three species of prairie dogs (Cynomys) in areas considered enzootic for plague

    Science.gov (United States)

    Biggins, Dean E.; Godbey, Jerry L.; Gage, Kenneth L.; Carter, Leon G.; Montenieri, John A.

    2010-01-01

    Plague causes periodic epizootics that decimate populations of prairie dogs (PDs) (Cynomys), but the means by which the causative bacterium (Yersinia pestis) persists between epizootics are poorly understood. Plague epizootics in PDs might arise as the result of introductions of Y. pestis from sources outside PD colonies. However, it remains possible that plague persists in PDs during interepizootic periods and is transmitted at low rates among highly susceptible individuals within and between their colonies. If this is true, application of vector control to reduce flea numbers might reduce mortality among PDs. To test whether vector control enhances PD survival in the absence of obvious plague epizootics, we reduced the numbers of fleas (vectors for Y. pestis) 96–98% (1 month posttreatment) on 15 areas involving three species of PDs (Cynomys leucurus, Cynomys parvidens in Utah, and Cynomys ludovicianus in Montana) during 2000–2004 using deltamethrin dust delivered into burrows as a pulicide. Even during years without epizootic plague, PD survival rates at dusted sites were 31–45% higher for adults and 2–34% higher for juveniles compared to survival rates at nondusted sites. Y. pestis was cultured from 49 of the 851 flea pools tested (6882 total fleas) and antibodies against Y. pestis were identified in serum samples from 40 of 2631 PDs. Although other explanations are possible, including transmission of other potentially fatal pathogens by fleas, ticks, or other ectoparasites, our results suggest that plague might be maintained indefinitely in PD populations in the absence of free epizootics and widespread mortality among these animals. If PDs and their fleas support enzootic cycles of plague transmission, there would be important implications for the conservation of these animals and other species.

  1. Survival time outcomes in randomized, controlled trials and meta-analyses: the parallel universes of efficacy and cost-effectiveness.

    Science.gov (United States)

    Guyot, Patricia; Welton, Nicky J; Ouwens, Mario J N M; Ades, A E

    2011-01-01

    Many regulatory agencies require that manufacturers establish both efficacy and cost-effectiveness. The statistical analysis of the randomized, controlled trial (RCT) outcomes should be the same for both purposes. The question addressed by this article is the following: for survival outcomes, what is the relationship between the statistical analyses used to support inference and the statistical model used to support decision making based on cost-effectiveness analysis (CEA)? We performed a review of CEAs alongside trials and CEAs based on a synthesis of RCT results, which were submitted to the National Institute for Health and Clinical Excellence (NICE) Technology Appraisal program and included survival outcomes. We recorded the summary statistics and the statistical models used in both efficacy and cost-effectiveness analyses as well as procedures for model diagnosis and selection. In no case was the statistical model for efficacy and CEA the same. For efficacy, relative risks or Cox regression was used. For CEA, the common practice was to fit a parametric model to the control arm, then to apply the hazard ratio from the efficacy analysis to predict the treatment arm. The proportional hazards assumption was seldom checked; the choice of model was seldom based on formal criteria, and uncertainty in model choice was seldom addressed and never propagated through the model. Both inference and decisions based on CEAs should be based on the same statistical model. This article shows that for survival outcomes, this is not the case. In the interests of transparency, trial protocols should specify a common procedure for model choice for both purposes. Further, the sufficient statistics and the life tables for each arm should be reported to improve transparency and to facilitate secondary analyses of results of RCTs. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  2. Effectiveness of routine visits and routine tests in detecting isolated locoregional recurrences after treatment for early-stage invasive breast cancer : A meta-analysis and systematic review

    NARCIS (Netherlands)

    de Bock, GH; Bonnema, J; van der Hage, J; Kievit, J; van de Velde, CJH

    2004-01-01

    Purpose To review the effectiveness of routine visits and routine tests in detecting isolated locoregional recurrences in asymptomatic patients after treatment for early-stage invasive breast cancer. Methods Systematic review and meta-analysis. The proportion of isolated locoregional recurrences

  3. ADF and Cofilin1 Control Actin Stress Fibers, Nuclear Integrity, and Cell Survival.

    Science.gov (United States)

    Kanellos, Georgios; Zhou, Jing; Patel, Hitesh; Ridgway, Rachel A; Huels, David; Gurniak, Christine B; Sandilands, Emma; Carragher, Neil O; Sansom, Owen J; Witke, Walter; Brunton, Valerie G; Frame, Margaret C

    2015-12-01

    Genetic co-depletion of the actin-severing proteins ADF and CFL1 triggers catastrophic loss of adult homeostasis in multiple tissues. There is impaired cell-cell adhesion in skin keratinocytes with dysregulation of E-cadherin, hyperproliferation of differentiated cells, and ultimately apoptosis. Mechanistically, the primary consequence of depleting both ADF and CFL1 is uncontrolled accumulation of contractile actin stress fibers associated with enlarged focal adhesions at the plasma membrane, as well as reduced rates of membrane protrusions. This generates increased intracellular acto-myosin tension that promotes nuclear deformation and physical disruption of the nuclear lamina via the LINC complex that normally connects regulated actin filaments to the nuclear envelope. We therefore describe a pathway involving the actin-severing proteins ADF and CFL1 in regulating the dynamic turnover of contractile actin stress fibers, and this is vital to prevent the nucleus from being damaged by actin contractility, in turn preserving cell survival and tissue homeostasis. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Autophagy controls an intrinsic host defense to bacteria by promoting epithelial cell survival: a murine model.

    Directory of Open Access Journals (Sweden)

    Sun-Young Chang

    Full Text Available Cell death is a critical host response to regulate the fate of bacterial infections, innate immune responses, and ultimately, disease outcome. Shigella spp. invade and colonize gut epithelium in human and nonhuman primates but adult mice are naturally resistant to intra-gastric Shigella infection. In this study, however, we found Shigella could invade the terminal ileum of the mouse small intestine by 1 hour after infection and be rapidly cleared within 24 h. These early phase events occurred shortly after oral infection resulting in epithelial shedding, degranulation of Paneth cells, and cell death in the intestine. During this process, autophagy proceeded without any signs of inflammation. In contrast, blocking autophagy in epithelial cells enhanced host cell death, leading to tissue destruction and to inflammation, suggesting that autophagic flow relieves cellular stress associated with host cell death and inflammation. Herein we propose a new concept of "epithelial barrier turnover" as a general intrinsic host defense mechanism that increases survival of host cells and inhibits inflammation against enteric bacterial infections, which is regulated by autophagy.

  5. Retinoblastoma protein controls growth, survival and neuronal migration in human cerebral organoids.

    Science.gov (United States)

    Matsui, Takeshi; Nieto-Estévez, Vanesa; Kyrychenko, Sergii; Schneider, Jay W; Hsieh, Jenny

    2017-03-15

    The tumor suppressor retinoblastoma protein (RB) regulates S-phase cell cycle entry via E2F transcription factors. Knockout (KO) mice have shown that RB plays roles in cell migration, differentiation and apoptosis, in developing and adult brain. In addition, the RB family is required for self-renewal and survival of human embryonic stem cells (hESCs). Since little is known about the role of RB in human brain development, we investigated its function in cerebral organoids differentiated from gene-edited hESCs lacking RB. We show that RB is abundantly expressed in neural stem and progenitor cells in organoids at 15 and 28 days of culture. RB loss promoted S-phase entry in DCX + cells and increased apoptosis in Sox2 + neural stem and progenitor cells, and in DCX + and Tuj1 + neurons. Associated with these cell cycle and pro-apoptotic effects, we observed increased CCNA2 and BAX gene expression, respectively. Moreover, we observed aberrant Tuj1 + neuronal migration in RB-KO organoids and upregulation of the gene encoding VLDLR, a receptor important in reelin signaling. Corroborating the results in RB-KO organoids in vitro , we observed ectopically localized Tuj1 + cells in RB-KO teratomas grown in vivo Taken together, these results identify crucial functions for RB in the cerebral organoid model of human brain development. © 2017. Published by The Company of Biologists Ltd.

  6. Hemodialysis versus peritoneal dialysis: a case control study of survival in patients with chronic kidney disease stage 5

    DEFF Research Database (Denmark)

    Maier, Alexandra; Stocks, Franziska; Pommer, Wolfgang

    2009-01-01

    It is still controversial whether the mode of dialysis or preexisting comorbidities may influence the prognosis of patients with chronic kidney disease stage 5. Therefore, we performed a prospective case control study to evaluate whether the mode of dialysis may influence outcome. We found 25 cases...... on peritoneal dialysis (PD) treatment and 75 age and sex-matched controls on hemodialysis (HD) treatment for more than 3 months. Analysis was by intention-to-treat. During the follow up of 58 months, 6 out of 25 patients (24%) died in the PD group, whereas in the HD group 26 out of 75 patients (35%) died......, predicted death in patients with chronic kidney disease. It is concluded that age and comorbidities but not mode of dialysis are important to predict survival in patients with chronic kidney disease stage 5....

  7. Treatment outcome and prognostic variables for local control and survival in patients receiving radical radiotherapy for urinary bladder cancer

    DEFF Research Database (Denmark)

    Fokdal, Lars; Høyer, Morten; von der Maase, Hans

    2004-01-01

    for the selection of patients for curative intended radiotherapy. During radiotherapy acute transient side effects were recorded in 78% of the patients; severe bowel complications were recorded in 9 patients (3%). Following radiotherapy, 10 patients (3%) developed intestinal reactions requiring surgery. Three......The aim of this retrospective study was to analyze the outcome of radical radiotherapy in 292 patients with bladder cancer and to identify prognostic factors for local control and survival. Median age was 72.3 years (range 45-83 years). Median follow up was 66 months (range 18-121 months). All...... patients were treated by use of a standard 3-field technique with 60 Gy in 30 fractions to the tumor and the bladder. The elective lymph nodes were treated with doses in the range from 46 Gy to 60 Gy. Complete response was obtained in 52% of the patients at 3-month control. However, 41% of all patients...

  8. Radiofrequency ablation to treat loco-regional recurrence of well-differentiated thyroid carcinoma.

    Science.gov (United States)

    Lee, Sun Jin; Jung, So Lyung; Kim, Bum Soo; Ahn, Kook Jin; Choi, Hyun Seok; Lim, Dong Jun; Kim, Min Hee; Bae, Ja Seong; Kim, Min Sik; Jung, Chan Kwon; Chong, Se Min

    2014-01-01

    To evaluate the efficacy of radiofrequency ablation (RFA) in the treatment of loco-regional, recurrent, and well-differentiated thyroid carcinoma. Thirty-five recurrent well-differentiated thyroid carcinomas (RTC) in 32 patients were treated with RFA, between March 2008 and October 2011. RTCs were detected by regular follow-up ultrasound and confirmed by biopsy. All patients had fewer than 3 RTCs in the neck and were at high surgical risk or refused to undergo repeated surgery. Average number of RFA sessions were 1.3 (range 1-3). Post-RFA biopsy and ultrasound were performed. The mean follow-up period was 30 months. Pre- and post-RFA serum thyroglobulin values were evaluated. Thirty-one patients with 33 RTCs were treated with RFA only, whereas 1 patient with 2 RTCs was treated with RFA followed by surgery. At the last follow-up ultrasound, 31 (94%) of the 33 RTCs treated with RFA alone completely disappeared and the remaining 2 (6%) RTCs showed decreased volume. The largest diameter and volume of the 33 RTCs were markedly decreased by 93.2% (from 8.1 ± 3.4 mm to 0.6 ± 1.8 mm, p loco-regional, recurrent, and well-differentiated thyroid carcinoma in patients at high surgical risk.

  9. Effects of a new outdoor mosquito control device, the mosquito landing box, on densities and survival of the malaria vector, Anopheles arabiensis, inside controlled semi-field settings.

    Science.gov (United States)

    Mmbando, Arnold S; Okumu, Fredros O; Mgando, Joseph P; Sumaye, Robert D; Matowo, Nancy S; Madumla, Edith; Kaindoa, Emmanuel; Kiware, Samson S; Lwetoijera, Dickson W

    2015-12-09

    The significance of malaria transmission occurring outdoors has risen even in areas where indoor interventions such as long-lasting insecticidal nets and indoor residual spraying are common. The actual contamination rates and effectiveness of recently developed outdoor mosquito control device, the mosquito landing box (MLB), on densities and daily survival of host-seeking laboratory Anopheles arabiensis, which readily bites humans outdoors was demonstrated. Experiments were conducted in large semi-field systems (SFS) with human volunteers inside, to mimic natural ecosystems, and using MLBs baited with natural or synthetic human odours and carbon dioxide. The MLBs were dusted with 10% pyriproxyfen (PPF) or entomopathogenic fungi (Metarhizium anisopliae) spores to mark mosquitoes physically contacting the devices. Each night, 400 laboratory-reared An. arabiensis females were released in one SFS chamber with two MLBs, and another chamber without MLBs (control). Mosquitoes were individually recaptured while attempting to bite volunteers inside SFS or by aspiration from SFS walls. Mosquitoes from chambers with PPF-treated MLBs and respective controls were individually dipped in water-filled cups containing ten conspecific third-instar larvae, whose subsequent development was monitored. Mosquitoes recaptured from chambers with fungi-treated MLBs were observed for fungal hyphal growth on their cadavers. Separately, effects on daily survival were determined by exposing An. arabiensis in chambers having MLBs treated with 5% pirimiphos methyl compared to chambers without MLBs (control), after which the mosquitoes were recaptured and monitored individually until they died. Up to 63% (152/240) and 43% (92/210) of mosquitoes recaptured inside treatment chambers were contaminated with pyriproxyfen and M. anisopliae, respectively, compared to 8% (19/240) and 0% (0/164) in controls. The mean number of larvae emerging from cups in which adults from chambers with PPF-treated MLBs

  10. Control of mitochondrial pH by uncoupling protein 4 in astrocytes promotes neuronal survival

    KAUST Repository

    Lambert, Hélène Perreten

    2014-09-18

    Brain activity is energetically costly and requires a steady and highly regulated flow of energy equivalents between neural cells. It is believed that a substantial share of cerebral glucose, the major source of energy of the brain, will preferentially be metabolized in astrocytes via aerobic glycolysis. The aim of this study was to evaluate whether uncoupling proteins (UCPs), located in the inner membrane of mitochondria, play a role in setting up the metabolic response pattern of astrocytes. UCPs are believed to mediate the transmembrane transfer of protons, resulting in the uncoupling of oxidative phosphorylation from ATP production. UCPs are therefore potentially important regulators of energy fluxes. The main UCP isoforms expressed in the brain are UCP2, UCP4, and UCP5. We examined in particular the role of UCP4 in neuron-astrocyte metabolic coupling and measured a range of functional metabolic parameters including mitochondrial electrical potential and pH, reactive oxygen species production, NAD/NADH ratio, ATP/ADP ratio, CO2 and lactate production, and oxygen consumption rate. In brief, we found that UCP4 regulates the intramitochondrial pH of astrocytes, which acidifies as a consequence of glutamate uptake, with the main consequence of reducing efficiency of mitochondrial ATP production. The diminished ATP production is effectively compensated by enhancement of glycolysis. This nonoxidative production of energy is not associated with deleterious H2O2 production. We show that astrocytes expressing more UCP4 produced more lactate, which is used as an energy source by neurons, and had the ability to enhance neuronal survival.

  11. Using copper sulfate on hybrid striped bass eggs to control fungus and increase survival

    Science.gov (United States)

    A major obstacle in fish hatcheries is the inevitable fungal growth on eggs. Copper sulfate (CuSO4) is commonly used for fungus control in channel catfish hatcheries that use troughs, but effectiveness on fish eggs hatched using different systems has only recently been investigated. Fish were spawn...

  12. Surviving or Thriving? Do Teachers Have Lower Perceived Control and Well-Being than Other Professions?

    Science.gov (United States)

    Grenville-Cleave, Bridget; Boniwell, Ilona

    2012-01-01

    Teaching is not what it used to be. The complexity and intensity of the pressures on teachers and the pace of education reform are unprecedented. The aim of this research was to explore perceived control and well-being in teachers and other professionals. A mixed methods design was selected. Phase 1 consisted of an online quantitative survey (298…

  13. Re-Irradiation of Locoregional NSCLC Recurrence Using Robotic Stereotactic Body Radiotherapy.

    Science.gov (United States)

    Ceylan, Cemile; Hamacı, Andaç; Ayata, Hande; Berberoglu, Kezban; Kılıç, Ayhan; Güden, Metin; Engin, Kayıhan

    2017-01-01

    We evaluated the efficacy, toxicity, and dose responses of re-irradiation with stereotactic body radiotherapy (SBRT) in patients with recurrent non- small cell lung cancer (NSCLC) after previous irradiation. 28 patients were included. Previous median radiation doses were 54 and 66 Gy. The median interval time between previous radiotherapy and SBRT was 14 months. The median follow-up time after SBRT was 9 months (range 3-93 months). To evaluate the effectiveness of SBRT, local control, overall survival, and treatment-related toxicity were reported. SBRT doses and fractionation ranged from 60 to 30 Gy and from 3 to 8, respectively, according to previous doses, location of the recurrence, and interval time. 65% of tumor recurrences overlapped with previous treatment, while 35% of tumors recurred outside of the previous treatment. 4 patients had local progression after SBRT at their first follow-up. The Kaplan-Meier estimates of the 1- and 2-year actuarial overall survival were 71 and 42%, respectively. The mean survival following SBRT was 32.8 months, and the median survival was 21 months. No grade 3 or higher toxicities were observed. Robotic SBRT is a tolerable treatment option with manageable toxicity which can be used with radical or palliative intent in carefully selected patients with locally recurrent tumors after previous irradiation. © 2017 S. Karger GmbH, Freiburg.

  14. Protein C concentrate controls leukocyte recruitment during inflammation and improves survival during endotoxemia after efficient in vivo activation.

    Science.gov (United States)

    Frommhold, David; Tschada, Julia; Braach, Natascha; Buschmann, Kirsten; Doerner, Axel; Pflaum, Johanna; Stahl, Marie-Sophie; Wang, Hongjie; Koch, Lutz; Sperandio, Markus; Bierhaus, Angelika; Isermann, Berend; Poeschl, Johannes

    2011-11-01

    Anti-inflammatory properties of protein C (PC) concentrate are poorly studied compared to activated protein C, although PC is suggested to be safer in clinical use. We investigated how PC interferes with the leukocyte recruitment cascade during acute inflammation and its efficacy during murine endotoxemia. We found that similar to activated protein infusion, intravenous PC application reduced leukocyte recruitment in inflamed tissues in a dose- and time-dependent manner. During both tumor necrosis factor-α induced and trauma-induced inflammation of the cremaster muscle, intravital microscopy revealed that leukocyte adhesion and transmigration, but not rolling, were profoundly inhibited by 100 U/kg PC. Moreover, PC blocked leukocyte emigration into the bronchoalveolar space during lipopolysaccharide (LPS) induced acute lung injury. PC was efficiently activated in a murine endotoxemia model, which reduced leukocyte infiltration of organs and strongly improved survival (75% versus 25% of control mice). Dependent on the inflammatory model, PC provoked a significant inhibition of leukocyte recruitment as early as 1 hour after administration. PC-induced inhibition of leukocyte recruitment during acute inflammation critically involves thrombomodulin-mediated PC activation, subsequent endothelial PC receptor and protease-activated receptor-1-dependent signaling, and down-regulation of intercellular adhesion molecule 1 leading to reduced endothelial inflammatory response. We conclude that during acute inflammation and sepsis, PC is a fast acting and effective therapeutic approach to block leukocyte recruitment and improve survival. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  15. The impact of loco-regional recurrences on metastatic progression in early-stage breast cancer : a multistate model

    NARCIS (Netherlands)

    de Bock, G. H.; Putter, H.; Bonnema, J.; van der Hage, J. A.; Bartelink, H.; van de Velde, C. J.

    To study whether the effects of prognostic factors associated with the occurrence of distant metastases (DM) at primary diagnosis change after the incidence of loco-regional recurrences (LRR) among women treated for invasive stage I or II breast cancer. The study population consisted of 3,601 women,

  16. [An analog-digital system of external pressure for loco-regional treatment of deep venous thrombosis with fibrinolytics].

    Science.gov (United States)

    Magallón Ortín, P; Fernández-Pavón, A; Jiménez Cossío, A J

    1990-01-01

    A new method, by external pressure, analogic-digital system, is presented to be used in loco-regional treatment of "Deep Venous Thrombosis" with fibrinolytic agents; in order to allow a great concentration of drug and a better derivation of it toward the deep venous system.

  17. Damage Control Surgery for Hepatocellular Cancer Rupture in an Elderly Patient: Survival and Quality of Life

    Directory of Open Access Journals (Sweden)

    Konstantinos Bouliaris

    2015-01-01

    Full Text Available Spontaneous rupture of hepatocellular carcinoma (HCC is a rare emergency condition with high mortality rate. Successful management depends on patients’ hemodynamic condition upon presentation and comorbidities, correct diagnosis, HCC status, liver function, and future liver remnant, as well as available sources. There is still a debate in the literature concerning the best approach in this devastating complication. Nevertheless, the primary goal should be a definitive bleeding arrest. In most cases, patients with spontaneous rupture of HCC present with hemodynamic instability, due to hemoperitoneum, necessitating an emergency treatment modality. In such cases, transcatheter arterial embolization (TAE should be the treatment of choice. Emergency liver resection is an option when TAE fails or in cases with preserved liver function and limited tumors. Otherwise, damage control strategies, as in liver trauma, are a reasonable alternative. We report a case of an elderly patient with hemoperitoneum and hypovolemic shock from spontaneous rupture of undiagnosed HCC, who was treated successfully by emergency surgery and damage control approach.

  18. Mosquito control pesticides and sea surface temperatures have differential effects on the survival and oxidative stress response of coral larvae.

    Science.gov (United States)

    Ross, Cliff; Olsen, Kevin; Henry, Michael; Pierce, Richard

    2015-04-01

    The declining health of coral reefs is intensifying worldwide at an alarming rate due to the combined effects of land-based sources of pollution and climate change. Despite the persistent use of mosquito control pesticides in populated coastal areas, studies examining the survival and physiological impacts of early life-history stages of non-targeted marine organisms are limited. In order to better understand the combined effects of mosquito pesticides and rising sea surface temperatures, we exposed larvae from the coral Porites astreoides to selected concentrations of two major mosquito pesticide ingredients, naled and permethrin, and seawater elevated +3.5 °C. Following 18-20 h of exposure, larvae exposed to naled concentrations of 2.96 µg L(-1) or greater had significantly reduced survivorship compared to controls. These effects were not detected in the presence of permethrin or elevated temperature. Furthermore, larval settlement, post-settlement survival and zooxanthellae density were not impacted by any treatment. To evaluate the sub-lethal stress response of larvae, several oxidative stress endpoints were utilized. Biomarker responses to pesticide exposure were variable and contingent upon pesticide type as well as the specific biomarker being employed. In some cases, such as with protein carbonylation and catalase gene expression, the effects of naled exposure and temperature were interactive. In other cases pesticide exposure failed to induce any sub-lethal stress response. Overall, these results demonstrate that P. astreoides larvae have a moderate degree of resistance against short-term exposure to ecologically relevant concentrations of pesticides even in the presence of elevated temperature. In addition, this work highlights the importance of considering the complexity and differential responses encountered when examining the impacts of combined stressors that occur on varying spatial scales.

  19. Decreasing loco-regional recurrence for oral cavity cancer with total Mohs margins technique.

    Science.gov (United States)

    Bergeron, Mathieu; Gauthier, Pierre; Audet, Nathalie

    2016-12-01

    The conventional technique for cancer resection margin analysis studies only 0.1% of the surgical margins. Complete frozen section margins - also known as Mohs margins - allows for analysis of 100% of the surgical margins. The objective of our study is to compare oral cavity cancer loco-regional recurrence rates when treated by total frozen sections technique (Total Mohs margins) versus conventional margins. We conducted a multicenter retrospective cohort chart review. Loco-regional oral cancer recurrence rates were compared between patients treated with total Mohs margins (2007-2013) and patients treated with conventional margins techniques (2002-2007). After applying inclusion criteria, a total of 60 patients treated by total Mohs margins and 57 patients with conventional margins were identified. Patients had similar baseline cancer stages, pathological types, past head and neck cancers and comorbidities (all p > 0.05). One-year recurrence rate was lower (10.0% vs 21.1%, p = 0.019) in favor of Mohs total margins and stayed significantly lower at 5 years of follow-up. When adjusted for T grade with N0 disease, Mohs technique was still beneficial in loco-regional recurrence for Tis-T4N0 up to 2 years (10.5% vs 25.7%, z-score 1.849, p = 0.032). The Number Needed to Treat at 2 years of follow-up for this subgroup of patients (Tis-T4N0) is 6.6. Margins had to be retaken more often intra-operatively in Mohs technique (68.3% vs 12.3%, p < 0.0001), mainly for positive deep margins (48.6% of all margins, p = 0.028). Duration of surgery was not increased with Mohs vs conventional technique (380 min vs 475 min respectively, p = 0.025). Mohs total margins may result in a significant reduction in cancer recurrence rate at 5 years compare to conventional surgery. Moreover, duration of surgery was not increased when using Mohs technique when judiciously performed.

  20. Breast cancer related lymphedema in patients with different loco-regional treatments.

    Science.gov (United States)

    Ozcinar, Beyza; Guler, Sertac Ata; Kocaman, Nazmiye; Ozkan, Mine; Gulluoglu, Bahadir M; Ozmen, Vahit

    2012-06-01

    Lymphedema, a sequela of breast cancer and breast cancer therapy, changes functional abilities and may affect a patient's psychosocial adjustment and overall quality of life. Aim of this prospective observational study was to determine the rate of mid-term and late time period lymphedema in breast cancer patients with different loco-regional treatments, and factors associated with lymphedema. Patients surgically treated for early-stage breast cancer were prospectively enrolled in the study. Demographic, clinical, pathological, and loco-regional treatments data of patients and lymphedema rates were recorded. Patients were divided into six groups regarding different loco-regional treatments. Pre- and postoperative (12 months, and median 64 months after surgery) circumferences of arms were recorded. 218 patients, all female with a median age of 48 (19-82) years, were included in the study. The numbers of patients in breast conservation surgery group (BCS) (N=104), mastectomy group (N=114), sentinel lymph node biopsy group (SLNB) (N=80), axillary lymph node dissection group (ALND) (N=138), group with radiotherapy (RT) (N=88) and group without radiotherapy (N=130). Incidence of lymphedema after surgery in mid-term period was 24.8%. The rate of lymphedema at 64 months median follow-up time was 7.3%. (BCS: 11.1%, 4.2% and 0.5%; Mastectomy: 15.0%, 3.2% and 1.4%; SLNB: 8.0%, 1.9% and 0.5%; ALND: 18.0%, 5.3% and 1.4%; RT: 14.7%, 6.3% and 1.4%; without RT: 11.4%, 2.1% and 0.5%). When we excluded patients with both mid-term and late term lymphedema, only four patients developed lymphedema at late time, then re-calculated late term lypmhedema rate was 1.8%. The factors affecting the lymphedema was ALND and radiotherapy (RT) and no lymphedema was detected in patients underwent breast conserving surgery and SLNB. Age and body mass index were not related to lymphedema at any time. The incidence of lymphedema gradually increased in time and a quarter of patients experienced the

  1. Parotid small cell carcinoma presenting with long-term survival after surgery alone: a case report

    Directory of Open Access Journals (Sweden)

    Kanazawa Takeharu

    2012-12-01

    Full Text Available Abstract Introduction Primary involvement of the salivary glands in small cell carcinoma is rare, and has one of the worst prognoses of salivary gland neoplasms. However, it has been reported that some cases have a favorable outcome, although the prognostic factors are still under consideration. Multidisciplinary therapy was usually required to achieve long-term survival. Recently, a resemblance of some small cell carcinomas of the salivary gland to cutaneous Merkel cell carcinoma was suggested; the latter have the potential for spontaneous regression, which is related to a favorable clinical outcome. Case presentation We present a locoregional advanced parotid small cell carcinoma with multiple lymph node metastases in an 87-year-old Asian woman. The tumor was controlled by surgery alone, and nine-year disease-free survival was achieved without any adjunctive therapy. To the best of our knowledge, this is the longest reported follow-up of head and neck small cell carcinoma. Conclusion We believe this to be the first case of small cell carcinoma with involvement of the salivary glands reported in the literature with a good outcome after surgery alone without any adjunctive therapy.

  2. Patterns of Loco-regional Treatment for Non-Metastatic Breast Cancer by Patient and Health Systems Factors

    Science.gov (United States)

    Anderson, Roger T.; Morris, Cyllene; Kimmick, Gretchen; Trentham-Dietz, Amy; Camacho, Fabian; Wu, Xiao-Cheng; Sabatino, Susan A.; Fleming, Steven T.; Lipscomb, Joseph

    2014-01-01

    Purpose To examine local definitive therapy for non-metastatic breast cancer using the Centers for Disease Control and Prevention’s National Program of Cancer Registries Patterns of Care Breast and Prostate Cancer (POCBP) study. Patients and Methods POCBP medical record data were re-abstracted in seven state/ regional registry systems (GA, NC, KY, LA, WI, MN and CA) to verify data quality and assess treatment patterns in the population. National Comprehensive Cancer Network clinical practice treatment guidelines were aligned with American Joint Committee on Cancer stage at diagnosis to appraise care. Results 6,505 of 9142 patients with registry confirmed breast cancer were coded as primary disease with 0-IIIA stage tumors and were included for study. Approximately 90% received guideline concordant loco-regional treatment; however this outcome varied by age group as 92.9% of women < 65 years and 85.2% ≥ 65 years received standard care (p <0.0001). Characteristics which best discriminated receipt of guideline concordant care in receiver operating curve (ROC) analyses (C-value) were receipt of BCS versus mastectomy (C = 0.70), patient age (C=0.62), greater tumor stage (C= 0.60), public insurance (C= 0.58) and presence of at least mild comorbidity (C = 0.55). RT following BCS was the most omitted treatment component causing non-concordance in the study population. In multivariable regression, effects of treatment facility, DCIS, race, and comorbidity on non-concordant care differed by age group. Conclusion Patterns of underuse of standard therapies for breast cancer vary by age group and BCS use, where omission of RT is at risk. PMID:25369150

  3. Common sole larvae survive high levels of pile-driving sound in controlled exposure experiments.

    Directory of Open Access Journals (Sweden)

    Loes J Bolle

    Full Text Available In view of the rapid extension of offshore wind farms, there is an urgent need to improve our knowledge on possible adverse effects of underwater sound generated by pile-driving. Mortality and injuries have been observed in fish exposed to loud impulse sounds, but knowledge on the sound levels at which (sub-lethal effects occur is limited for juvenile and adult fish, and virtually non-existent for fish eggs and larvae. A device was developed in which fish larvae can be exposed to underwater sound. It consists of a rigid-walled cylindrical chamber driven by an electro-dynamical sound projector. Samples of up to 100 larvae can be exposed simultaneously to a homogeneously distributed sound pressure and particle velocity field. Recorded pile-driving sounds could be reproduced accurately in the frequency range between 50 and 1000 Hz, at zero to peak pressure levels up to 210 dB re 1µPa(2 (zero to peak pressures up to 32 kPa and single pulse sound exposure levels up to 186 dB re 1µPa(2s. The device was used to examine lethal effects of sound exposure in common sole (Solea solea larvae. Different developmental stages were exposed to various levels and durations of pile-driving sound. The highest cumulative sound exposure level applied was 206 dB re 1µPa(2s, which corresponds to 100 strikes at a distance of 100 m from a typical North Sea pile-driving site. The results showed no statistically significant differences in mortality between exposure and control groups at sound exposure levels which were well above the US interim criteria for non-auditory tissue damage in fish. Although our findings cannot be extrapolated to fish larvae in general, as interspecific differences in vulnerability to sound exposure may occur, they do indicate that previous assumptions and criteria may need to be revised.

  4. Retrospective Analysis of the Survival Benefit of Induction Chemotherapy in Stage IVa-b Nasopharyngeal Carcinoma

    OpenAIRE

    Xiao-Wen Lan; Xue-Bin Zou; Yao Xiao; Jie Tang; Pu-Yun OuYang; Zhen Su; Fang-Yun Xie

    2016-01-01

    Purpose The value of adding induction chemotherapy to chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) remains controversial, yet high-risk patients with LA-NPC have poor outcomes after chemoradiotherapy. We aimed to assess the survival benefits of induction chemotherapy in stage IVa-b NPC. Patients and Methods A total of 602 patients with stage IVa-b NPC treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy with or without inducti...

  5. Cardiogenic shock associated with loco-regional anesthesia rescued with left ventricular assist device implantation

    Directory of Open Access Journals (Sweden)

    Droogan Christopher

    2010-12-01

    Full Text Available Abstract A healthy 53 year old man developed profound cardiogenic shock following instillation of bupivacaine-lidocaine-epinephrine solution as a locoregional anesthetic for elective outpatient shoulder surgery. Intubation, resuscitation, and transfer to the nearby hospital were done: echocardiography showed profound biventricular dysfunction; cardiac catheterization showed normal coronary arteries. Despite placement of an intra-aortic balloon pump and intravenous vasoactive drugs, the patient remained in shock. Stabilization was achieved with emergent institution of cardiopulmonary bypass and placement of a temporary left ventricular assist device (LVAD. Twenty-four hours later, cardiac function normalized and the LVAD was removed. The patient was discharged five days later and remained with normal heart function in three-year follow-up.

  6. Loco-regional administration of nanomedicines for the treatment of lung cancer.

    Science.gov (United States)

    Garrastazu Pereira, Gabriela; Lawson, Amanda Jane; Buttini, Francesca; Sonvico, Fabio

    2016-10-01

    Lung cancer poses one of the most significant challenges to modern medicine, killing thousands every year. Current therapy involves surgical resection supplemented with chemotherapy and radiotherapy due to high rates of relapse. Shortcomings of currently available chemotherapy protocols include unacceptably high levels of systemic toxicity and low accumulation of drug at the tumor site. Loco-regional delivery of nanocarriers loaded with anticancer agents has the potential to significantly increase efficacy, while minimizing systemic toxicity to anticancer agents. Local drug administration at the tumor site using nanoparticulate drug delivery systems can reduce systemic toxicities observed with intravenously administered anticancer drugs. In addition, this approach presents an opportunity for sustained delivery of anticancer drug over an extended period of time. Herein, the progress in the development of locally administered nanomedicines for the treatment of lung cancer is reviewed. Administration by inhalation, intratumoral injection and means of direct in situ application are discussed, the benefits and drawbacks of each modality are explored.

  7. Radiofrequency ablation to treat loco-regional recurrence of well-differentiated thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Jung, So Lyung; Kim, Bum Soo; Ahn, Kook Jin [Dept. of Radiology, eoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); and others

    2014-12-15

    To evaluate the efficacy of radiofrequency ablation (RFA) in the treatment of loco-regional, recurrent, and well-differentiated thyroid carcinoma. Thirty-five recurrent well-differentiated thyroid carcinomas (RTC) in 32 patients were treated with RFA, between March 2008 and October 2011. RTCs were detected by regular follow-up ultrasound and confirmed by biopsy. All patients had fewer than 3 RTCs in the neck and were at high surgical risk or refused to undergo repeated surgery. Average number of RFA sessions were 1.3 (range 1-3). Post-RFA biopsy and ultrasound were performed. The mean follow-up period was 30 months. Pre- and post-RFA serum thyroglobulin values were evaluated. Thirty-one patients with 33 RTCs were treated with RFA only, whereas 1 patient with 2 RTCs was treated with RFA followed by surgery. At the last follow-up ultrasound, 31 (94%) of the 33 RTCs treated with RFA alone completely disappeared and the remaining 2 (6%) RTCs showed decreased volume. The largest diameter and volume of the 33 RTCs were markedly decreased by 93.2% (from 8.1 +/- 3.4 mm to 0.6 +/- 1.8 mm, p < 0.001) and 96.4% (from 173.9 +/- 198.7 mm{sup 3} to 6.2 +/- 27.9 mm{sup 3}, p < 0.001), respectively. Twenty of the 21 RTCs evaluated with post-RFA biopsies (95%) were negative for malignancy. One (5%) showed remaining tumor that was removed surgically. The serum thyroglobulin was decreased in 19 of 26 patients (73%). Voice change developed immediately after RFA in 6 patients (19%) and was spontaneously recovered in 5 patients (83%). Radiofrequency ablation can be effective in treating loco-regional, recurrent, and well-differentiated thyroid carcinoma in patients at high surgical risk.

  8. Survival Outcome after Stereotactic Body Radiation Therapy and Surgery for Early Stage Non-Small Cell Lung Cancer: A Meta-Analysis.

    Science.gov (United States)

    Yu, Xiao-Jun; Dai, Wan-Rong; Xu, Yong

    2017-08-22

    Treatment modalities in medically compromised patients with early-stage non-small cell lung cancer (NSCLC) are controversial. Stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy has been increasingly recognized as a favorable alternative to surgical resection for early-stage NSCLC. Many retrospective analyses compared the efficacy of stereotactic body radiotherapy (SBRT) with surgery for early-stage non-small cell lung cancer (NSCLC). However, the efficacy between SBRT and surgery regimens for patients with early-stage NSCLC remains unclear. This study aimed to investigate the efficacy between SBRT and surgery. Publications on comparison SBRT with Surgery in treatment of early stage non-small cell lung cancer (NSCLC) from 2011 to 2017 were collected. Retrospective trials analyzed the summary hazard ratios (HRs) of overall survival (OS), disease-free survival (DFS), local control survival (LC), regional control survival (RC), loco-regional control survival (LRC), and distant control survival (DC) between SBRT and Surgery. The major outcomes measures were hazard ratios (HRs). Meta-analysis Revman 5.3 software was used to analyze the combined Pooled HRs using fixed- or random-effects models according to the heterogeneity. A systematic literature search was conducted including14 studies. In this meta-analysis, patients with SBRT achieved inferior OS, DFS, LC, RC, LRC and DC, compared with surgery. In this study we found more favorable outcomes with stage I NSCLC treated with SBRT. The surgery had no obvious advantages in this meta-analysis. Although surgery has become the recommended treatment at present, SBRT has potential to be an alternative treatment as a novel non-invasive radiation therapy modality in patients with stage I-II NSCLC.

  9. The influence of micrometastases on prognosis and survival in stage I-II colon cancer patients: the Enroute⊕ Study

    Directory of Open Access Journals (Sweden)

    Pruijt Hans FM

    2011-05-01

    Full Text Available Abstract Background The presence of lymph node metastases remains the most reliable prognostic predictor and the gold indicator for adjuvant treatment in colon cancer (CC. In spite of a potentially curative resection, 20 to 30% of CC patients testing negative for lymph node metastases (i.e. pN0 will subsequently develop locoregional and/or systemic metastases within 5 years. The presence of occult nodal isolated tumor cells (ITCs and/or micrometastases (MMs at the time of resection predisposes CC patients to high risk for disease recurrence. These pN0micro+ patients harbouring occult micrometastases may benefit from adjuvant treatment. The purpose of the present study is to delineate the subset of pN0 patients with micrometastases (pN0micro+ and evaluate the benefits from adjuvant chemotherapy in pN0micro+ CC patients. Methods/design EnRoute+ is an open label, multicenter, randomized controlled clinical trial. All CC patients (age above 18 years without synchronous locoregional lymph node and/or systemic metastases (clinical stage I-II disease and operated upon with curative intent are eligible for inclusion. All resected specimens of patients are subject to an ex vivo sentinel lymph node mapping procedure (SLNM following curative resection. The investigation for micrometastases in pN0 patients is done by extended serial sectioning and immunohistochemistry for pan-cytokeratin in sentinel lymph nodes which are tumour negative upon standard pathological examination. Patients with ITC/MM-positive sentinel lymph nodes (pN0micro+ are randomized for adjuvant chemotherapy following the CAPOX treatment scheme or observation. The primary endpoint is 3-year disease free survival (DFS. Discussion The EnRoute+ study is designed to improve prognosis in high-risk stage I/II pN0 micro+ CC patients by reducing disease recurrence by adjuvant chemotherapy. Trial Registration ClinicalTrials.gov: NCT01097265

  10. Meta-analyses of randomized controlled trials show suboptimal validity of surrogate outcomes for overall survival in advanced colorectal cancer.

    Science.gov (United States)

    Ciani, Oriana; Buyse, Marc; Garside, Ruth; Peters, Jaime; Saad, Everardo D; Stein, Ken; Taylor, Rod S

    2015-07-01

    To quantify and compare the treatment effects on three surrogate end points, progression-free survival (PFS), time to progression (TTP), and tumor response rate (TR) vs. overall survival (OS) based on a meta-analysis of randomized controlled trials (RCTs) of drug interventions in advanced colorectal cancer (aCRC). We systematically searched for RCTs of pharmacologic therapies in aCRC between 2003 and 2013. Trial characteristics, risk of bias, and outcomes were recorded based on a predefined form. Univariate and multivariate random-effects meta-analyses were used to estimate pooled summary treatment effects. The ratio of hazard ratios (HRs)/odds ratios (ORs) and difference in medians were used to quantify the degree of difference in treatment effects on the surrogate end points and OS. Spearman ρ, surrogate threshold effect (STE), and R(2) were also estimated across predefined trial-level covariates. We included 101 RCTs. In univariate and multivariate meta-analyses, we found larger treatment effects for the surrogates than for OS. Compared with OS, treatment effects were on average 13% higher when HRs were measured and 3% to 45% higher when ORs were considered; differences in median PFS/TTP were higher than on OS by an average of 0.5 month. Spearman ρ ranged from 0.39 to 0.80, mean R(2) from 0.06 to 0.65, and STE was 0.8 for HRPFS, 0.64 for HRTTP, or 0.28 for ORTR. The stratified analyses revealed high variability across all strata. None of the end points in this study were found to achieve the level of evidence (ie, mean R(2)trial > 0.60) that has been set to select high or excellent correlation levels by common surrogate evaluation tools. Previous surrogacy relationships observed between PFS and TTP vs. OS in selected settings may not apply across other classes or lines of therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Induction concurrent chemoradiotherapy using Paclitaxel and Carboplatin combination followed by surgery in locoregionally advanced non-small cell lung cancer--Asian experience.

    Science.gov (United States)

    Yap, Swee-Peng; Lim, Wan-Teck; Foo, Kian-Fong; Hee, Siew-Wan; Leong, Swan-Swan; Fong, Kam-Weng; Eng, Philip; Hsu, Anne Al; Wee, Joseph Ts; Agasthian, Thirugnanam; Koong, Heng-Nung; Tan, Eng-Huat

    2008-05-01

    It has been established that combined chemoradiotherapy treatment benefits selected patients with stage III Non Small Cell Lung Cancer (NSCLC). However, locoregional recurrence still poses a problem. The addition of surgery as the third modality may provide a possible solution. We report our experience of using the triple-modality approach in this group of patients. This is a retrospective review of 33 patients with stage III NSCLC treated between 1997 and 2005. Patients have good performance status and no significant weight loss. There were 26 males (79 %) with median age of 63 years (range, 43 to 74) and median follow-up of 49 months. Seventy-six percent had Stage IIIA disease. Chemotherapy consisted of paclitaxel at 175 mg/m2 over 3 hours followed by carboplatin at AUC of 5 over 1 hour. Thoracic radiotherapy was given concurrently with the second and third cycles of chemotherapy. All patients received 50 Gray in 25 fractions over 5 weeks. The main toxicities were grade 3/4 neutropenia (30%), grade 3 infection (15 %) and grade 3 oesophagitis (9%). Twenty-five patients (76%) underwent surgery. Of the 8 who did not undergo surgery, 1 was deemed medically unfit after induction chemoradiotherapy and 4 had progressive disease; 3 declined surgery. Nineteen patients (58 %) had lobectomy and 6 had pneumonectomy. The median overall survival was 29.9 months and 12 patients are still in remission. The use of the triplemodality approach is feasible, with an acceptable tolerability and resectability rate in this group of patients.

  12. Beta-blocker usage after malignant melanoma diagnosis and survival: a population-based nested case-control study.

    Science.gov (United States)

    McCourt, C; Coleman, H G; Murray, L J; Cantwell, M M; Dolan, O; Powe, D G; Cardwell, C R

    2014-04-01

    Beta-blockers have potential antiangiogenic and antimigratory activity. Studies have demonstrated a survival benefit in patients with malignant melanoma treated with beta-blockers. To investigate the association between postdiagnostic beta-blocker usage and risk of melanoma-specific mortality in a population-based cohort of patients with malignant melanoma. Patients with incident malignant melanoma diagnosed between 1998 and 2010 were identified within the U.K. Clinical Practice Research Datalink and confirmed using cancer registry data. Patients with malignant melanoma with a melanoma-specific death (cases) recorded by the Office of National Statistics were matched on year of diagnosis, age and sex to four malignant melanoma controls (who lived at least as long after diagnosis as their matched case). A nested case-control approach was used to investigate the association between postdiagnostic beta-blocker usage and melanoma-specific death and all-cause mortality. Conditional logistic regression was applied to generate odds ratios (ORs) and 95% confidence intervals (CIs) for beta-blocker use determined from general practitioner prescribing. Beta-blocker medications were prescribed after malignant melanoma diagnosis to 20·2% of 242 patients who died from malignant melanoma (cases) and 20·3% of 886 matched controls. Consequently, there was no association between beta-blocker use postdiagnosis and cancer-specific death (OR 0·99, 95% CI 0·68-1·42), which did not markedly alter after adjustment for confounders including stage (OR 0·87, 95% CI 0·56-1·34). No significant associations were detected for individual beta-blocker types, by defined daily doses of use or for all-cause mortality. Contrary to some previous studies, beta-blocker use after malignant melanoma diagnosis was not associated with reduced risk of death from melanoma in this U.K. population-based study. © 2014 British Association of Dermatologists.

  13. Survival of the fittest clone: Pro-apoptotic protein Noxa controls selection of lymphocytes under competitive conditions

    NARCIS (Netherlands)

    Wensveen, F.M.

    2010-01-01

    Darwinistic selection, or ‘survival of the fittest’, is based on intrinsic capacity, relative to that of its competitors in a given niche. This process drives the generation of species by allowing survival of organisms in with favorable, specialized characteristics for a certain niche. However, mere

  14. A mixed linear model controlling for case underascertainment across multiple cancer registries estimated time trends in survival.

    Science.gov (United States)

    Dahm, Stefan; Bertz, Joachim; Barnes, Benjamin; Kraywinkel, Klaus

    2018-01-10

    Large temporal and geographical variation in survival rates estimated from epidemiological cancer registries coupled with heterogeneity in death certificate only (DCO) notifications makes it difficult to interpret trends in survival. The aim of our study is to introduce a method for estimating such trends while accounting for heterogeneity in DCO notifications in a cancer site-specific manner. We used the data of 4.0 million cancer cases notified in 14 German epidemiological cancer registries. Annual 5-year relative survival rates from 2002 through 2013 were estimated, and proportions of DCO notifications were recorded. "DCO-excluded" survival rates were regressed on DCO proportions and calendar years using a mixed linear model with cancer registry as a random effect. Based on this model, trends in survival rates were estimated for Germany at 0% DCO. For most cancer sites and age groups, we estimated significant positive trends in survival. Age-standardized survival for all cancers combined increased by 7.1% units for women and 10.8% units for men. The described method could be used to estimate trends in cancer survival based on the data from epidemiological cancer registries with differing DCO proportions and with changing DCO proportions over time. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Effect of Brood Pheromone on Survival and Nutrient Intake of African Honey Bees (Apis mellifera scutellata) under Controlled Conditions.

    Science.gov (United States)

    Démares, Fabien J; Yusuf, Abdullahi A; Nicolson, Susan W; Pirk, Christian W W

    2017-05-01

    The influence of pheromones on insect physiology and behavior has been thoroughly reported for numerous aspects, such as attraction, gland development, aggregation, mate and kin recognition. Brood pheromone (BP) is released by honey bee larvae to indicate their protein requirements to the colony. Although BP is known to modulate pollen and protein consumption, which in turn can affect physiological and morphological parameters, such as hypopharyngeal gland (HPG) development and ovarian activation, few studies have focused on the effect of BP on nutritional balance. In this study, we exposed newly emerged worker bees for 14 d and found that BP exposure increased protein intake during the first few days, with a peak in consumption at day four following exposure. BP exposure decreased survival of caged honey bees, but did not affect either the size of the HPG acini or ovarian activation stage. The uncoupling of the BP releaser effect, facilitated by working under controlled conditions, and the presence of larvae as stimulating cues are discussed.

  16. The Changing Therapeutic Role of Chemo-radiotherapy for Loco-regionally Advanced Nasopharyngeal Carcinoma from Two/Three-Dimensional Radiotherapy to Intensity-Modulated Radiotherapy: A Network Meta-Analysis.

    Science.gov (United States)

    You, Rui; Cao, Ying-Shu; Huang, Pei-Yu; Chen, Lei; Yang, Qi; Liu, You-Ping; Zou, Xiong; Zhang, Yi-Nuan; Jiang, Rou; Zhang, Meng-Xia; Duan, Chong-Yang; Lin, Ai-Hua; Hong, Ming-Huang; Chen, Ming-Yuan

    2017-01-01

    Purpose: We used randomized trials of radiotherapy (RT) with or without chemotherapy in non-metastatic nasopharyngeal carcinoma to investigate the survival benefit of chemoradiotherapy regimens between two/three-dimensional radiotherapy (2D/3D RT) and intensity-modulated radiotherapy (IMRT). Methods: Overall, 27 trials and 7,940 patients were included. Treatments were grouped into seven categories including RT alone, induction chemotherapy (IC) followed by RT (IC-RT), RT followed by adjuvant chemotherapy (RT-AC), IC followed by RT followed by AC (IC-RT-AC), concurrent chemo-radiotherapy (CRT), IC followed by CRT (IC-CRT), and CRT followed by AC (CRT-AC). To distinguish between 2D/3D RT and IMRT, three categories in IMRT were newly added, including CRT in IMRT, IC-CRT in IMRT, and CRT-AC in IMRT. The P score was used to rank the treatments. Results: Both fixed- and random-effects frequentist and Bayesian network meta-analysis models were applied, which provided similar results and the same ranking. IC-CRT was the most effective regimen compared with CRT-AC and CRT in the IMRT era for overall survival (OS) (HR, 95% CI, IC-CRT vs. CRT-AC, 0.61 (0.45, 0.82); IC-CRT vs. CRT 0.65 (0.47, 0.91)), progression-free survival (PFS) (0.69 (0.54, 0.88); 0.63 (0.49, 0.80)), and distant metastasis-free survival (DMFS) (0.58 (0.28, 1.21); 0.60 (0.42, 0.85)). CRT-AC achieved the highest survival benefit compared with CRT, and IC-CRT for loco-regional relapse-free survival (LRRFS) (0.44 (0.15, 1.28); 0.72 (0.22, 2.33)). Among these 10 categories, after distinguishing between 2D/3D RT and IMRT, IC-CRT in IMRT ranked first for OS, PFS, and DMFS, and CRT-AC in IMRT ranked first for LRRFS. Conclusion: IC-CRT should be the most suitable regimen for loco-regionally advanced NPC in the IMRT era.

  17. Effect of multiple micronutrient supplementation on survival of HIV-infected children in Uganda: a randomized, controlled trial.

    Science.gov (United States)

    Ndeezi, Grace; Tylleskär, Thorkild; Ndugwa, Christopher M; Tumwine, James K

    2010-06-03

    Micronutrient deficiencies compromise the survival of HIV-infected children in low-income countries. We assessed the effect of multiple micronutrient supplementation on the mortality of HIV-infected children in Uganda. In a randomized, controlled trial, 847 children aged one to five years and attending HIV clinics in Uganda were stratified by antiretroviral therapy (ART, n = 85 versus no ART, n = 762). The children were randomized to six months of either: twice the recommended dietary allowance of 14 micronutrients as the intervention arm (vitamins A, B1, B2, niacin, B6, B12, C, D and E, folate, zinc, copper, iodine and selenium); or the standard recommended dietary allowance of six multivitamins (vitamins A, D2, B1, B2, C and niacin) as a comparative "standard-of-care" arm. Mortality was analyzed at 12 months of follow up using Kaplan Meier curves and the log rank test. Mortality at 12 months was 25 out of 426 (5.9%) children in the intervention arm and 28 out of 421 (6.7%) in the comparative arms: risk ratio 0.9 (95% CI 0.5 - 1.5). Two out of 85 (2.4%) children in the ART stratum died compared with 51 out of 762 (6.7%) in the non-ART stratum. Of those who died in the non-ART stratum, 25 of 383 (6.5%) were in the intervention arm and 26 of 379 (6.9%) in the comparative arm; risk ratio 1.0 (95% CI 0.6 - 1.6). There was no significant difference in survival at 12 months (p = 0.64, log rank test). In addition, there was no significant difference in mean weight-for-height at 12 months; 0.70 +/- 1.43 (95% CI 0.52 - 0.88) for the intervention versus 0.59 +/- 1.15 (95% CI 0.45 - 0.75) in the comparative arm. The mean CD4 cell count; 1024 +/- 592 (95% CI 942 - 1107) versus 1060 +/- 553 (95% CI 985 - 1136) was also similar between the two groups. Twice the recommended dietary allowance of 14 micronutrients compared with a standard recommended dietary allowance of six multivitamins for six months was well tolerated, but it did not significantly alter mortality, growth or CD

  18. A modified sentinel lymph node technique combined with endoluminal loco-regional resection for the treatment of rectal tumours: a 14-year experience.

    Science.gov (United States)

    Quaresima, S; Paganini, A M; D'Ambrosio, G; Ursi, P; Balla, A; Lezoche, E

    2017-12-01

    After endoluminal loco-regional resection (ELRR) by transanal endoscopic microsurgey (TEM) the N parameter may remain undefined. Nucleotide-guided mesorectal excision (NGME) improves the lymph node harvest. The aim of the present study is to evaluate the long-term oncological results after ELRR with NGME. A total of 57 patients were enrolled over the period January 2001 to June 2015. All patients underwent ELRR by TEM. Prior to surgery, 99 m-technetium-marked nanocolloid was injected into the peritumoural submucosa. After removal of the specimen, the residual defect was probed to detect any residual radioactivity and 'hot' mesorectal fat was excised. All patients were included in a 5-year follow-up programme. Significant radioactivity in the residual cavity was found in 28 out of 57 patients (49%). The mean number of lymph nodes harvest in irradiated and nonirradiated patients was 1.66 and 2.76, respectively. After 68.2 months' follow-up overall survival was 91.2%, disease-related mortality 3.5% and disease-free survival 89.5%. Two patients developed pulmonary metastases: one ypT3N0 patient underwent lung lobectomy after chemotherapy and one pT2N0 patient was managed with lung radiotherapy. Both patients are currently alive and disease-free at 48 months' follow-up. Two patients developed local recurrence 1 year after ELRR, both treated with neoadjuvant chemo-radiotherapy and total mesorectal excision. Comparing the present series with previous patients who did not undergo NGME, an increased number of harvested lymph nodes were observed, with a statistically significant difference (P = 0.0085). NGME during ELRR improves the lymph node harvest and staging accuracy. The long-term results showed satisfactory local (3.5%) and distant (7%) recurrence rates. Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.

  19. Comparison of the short-term efficacy between docetaxel plus carboplatin and 5-fluorouracil plus carboplatin in locoregionally advanced nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Lv X

    2016-08-01

    Full Text Available Xing Lv,1,2,* Wei-Xiong Xia,1,2,* Liang-Ru Ke,1,2 Jing Yang,1,2 Wen-Zhe Qiu,1,2 Ya-Hui Yu,1,2 Hu Liang,1,2 Xin-Jun Huang,1,2 Guo-Yin Liu,1,2 Qi Zeng,1,2 Xiang Guo,1,2 Yan-Qun Xiang1,2 1Key Laboratory of Oncology in South China, 2Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China *These authors contributed equally to this work Objective: Platinum-based chemotherapy in combination with radiotherapy is a standard treatment strategy for locoregionally advanced nasopharyngeal carcinoma (NPC. This study aimed to investigate the long-term efficacy and tolerability of inductive chemotherapy with docetaxel plus carboplatin (TC or 5-fluorouracil plus carboplatin (FC followed by concurrent radiation therapy in patients with NPC. Methods: Patients (N=88 were randomized to receive TC or FC as inductive therapy followed by concurrent radiotherapy (60–70 Gy with two cycles of carboplatin (area under the curve =5 mg·h/L. Patients were followed up for 8 years. Primary end point was progression-free survival (PFS. Secondary end points included overall survival (OS, toxicity, tumor response, distant metastasis-free survival, and local recurrence-free survival. Results: At the end of the follow-up period, 31 patients died, 32 had disease progression, eleven had cancer recurrence, and 25 had distant metastasis. Overall, there was no difference between treatment groups with regard to response or survival. We found that following induction and concurrent chemoradiotherapy, the majority of patients showed a complete response (~96%–98% for induction therapy and 82%–84% for comprehensive therapy to both therapies. PFS and OS were also similar between groups. The rate of PFS was 63.6% for both FC and TC and that of OS was 65.9% and 63.5%, respectively. The overall incidence of grade 3–4 adverse events in the TC group (20.5% was higher than in the FC group (10.7%. Neutropenia and leukopenia

  20. Issues Affecting the Loco-regional and Systemic Management of Patients with Invasive Lobular Carcinoma of the Breast.

    Science.gov (United States)

    Jacobs, Carmel; Clemons, Mark; Addison, Christina; Robertson, Susan; Arnaout, Angel

    2016-01-01

    Invasive lobular carcinoma (ILC) of the breast is the second most common type of invasive breast carcinoma accounting for 8-14% of all breast cancers. Traditional management of ILC has followed similar paradigms as that for invasive ductal carcinoma (IDC). However, ILC represents a pathologically, clinically and biologically unique variant of breast cancer with particular management challenges. These challenges are seen in both the loco-regional management of ILC; where ILC tumors tend to avoid detection and hence present as more clinically advanced and surgically challenging carcinomas, and the systemic management with a unique response pattern to standard systemic therapies. Because of these challenges, the outcome for patients with ILC has likely lagged behind the continued improvements seen in outcome for patients with IDC. Here, we discuss some of the unique challenges ILC presents and discuss possible management strategies to best overcome the difficulties in the loco-regional and systemic management of patients with ILC. © 2015 Wiley Periodicals, Inc.

  1. Self-rated health in the last 12 years of life compared to matched surviving controls: the Health and Retirement Study.

    Directory of Open Access Journals (Sweden)

    Sari Stenholm

    Full Text Available Self-rated health (SRH is a valid measure of health status and associated with mortality. Based on individual-level biannual repeat data on SRH we sought to characterize the natural history of poor SRH during the 12 years prior to death in men and women in different age groups. We conducted a retrospective analysis of the Health and Retirement Study participants who died between 1998 and 2010 and had at least two SRH measurements in the 12 years prior to death. We used a nested case-control design to compare SRH trajectories of deceased men and women aged 30-64, 65-79 and 80 years versus surviving participants. The cases comprised 3,350 deceased participants who were matched to surviving controls (n = 8,127. SRH was dichotomized into good vs. poor health. Men and women dying at age 65-79 and ≥ 80 years had 1.5 to 3 times higher prevalence of poor SRH already 11-12 years prior to death compared to surviving controls. The risk estimates remained statistically significant even after adjusting for life-style related risk factors and diagnosed diseases. Prevalence of poor SRH before death was lowest among those aged ≥ 80 years and highest in 30-64 year-olds. In conclusion, men and women who subsequently die perceive their health worse already 11-12 years prior to death compared to their surviving controls.

  2. Survival of patients with intermediate stage hepatocellular carcinoma treated with superselective transarterial chemoembolization using doxorubicin-loaded DC Bead under cone-beam computed tomography control

    Directory of Open Access Journals (Sweden)

    Popovic Peter

    2016-12-01

    Full Text Available The purpose of this retrospective study was to evaluate treatment response, adverse events and survival rates of patients with intermediate stage HCC treated with superselective doxorubicin-loaded DC Bead transarterial chemoembolization (DEBDOX under cone beam computed tomography (CBCT control.

  3. Histologic and systemic prognosticators for local control and survival in margin-negative transoral laser microsurgery treated oral cavity squamous cell carcinoma.

    Science.gov (United States)

    Sinha, Parul; Mehrad, Mitra; Chernock, Rebecca D; Lewis, James S; El-Mofty, Samir K; Wu, Ningying; Nussenbaum, Brian; Haughey, Bruce H

    2015-01-01

    Appreciable local recurrence rates observed in patients with margin-negative, transoral laser microsurgery (TLM)-treated oral cavity squamous cell carcinoma (SCC) necessitate identification of new prognosticators for local control and survival. A histopathologic index (Brandwein-Gensler score [BGS]) and intrinsic/iatrogenic/chronic conditions causing immune compromise are investigated. From a prospectively assembled database of TLM-treated oral cavity SCC, specimens for 60 patients with a minimum of 2-years follow-up could undergo BGS assignment. Local control, disease-specific survival (DSS), and overall survival (OS) were study endpoints. "Low-BGS" was recorded in 28 patients (47%) and "high-BGS" in 32 patients (53%), whereas immune compromise was observed in 18%. In multivariate analyses, immune compromise was the only predictor for local control. T classification and immune compromise were prognostic for DSS and OS. "High-BGS" was prognostic only for OS. "High-BGS" was associated with recurrences but immune compromise was the most significant predictor of local control and survival in margin-negative, TLM-treated oral cavity SCC. Strategies that maintain/restore tumor-specific immune responses in immune compromised oral cavity SCC hosts need to be developed. © 2014 Wiley Periodicals, Inc.

  4. A comparative study of machine learning methods for time-to-event survival data for radiomics risk modelling.

    Science.gov (United States)

    Leger, Stefan; Zwanenburg, Alex; Pilz, Karoline; Lohaus, Fabian; Linge, Annett; Zöphel, Klaus; Kotzerke, Jörg; Schreiber, Andreas; Tinhofer, Inge; Budach, Volker; Sak, Ali; Stuschke, Martin; Balermpas, Panagiotis; Rödel, Claus; Ganswindt, Ute; Belka, Claus; Pigorsch, Steffi; Combs, Stephanie E; Mönnich, David; Zips, Daniel; Krause, Mechthild; Baumann, Michael; Troost, Esther G C; Löck, Steffen; Richter, Christian

    2017-10-16

    Radiomics applies machine learning algorithms to quantitative imaging data to characterise the tumour phenotype and predict clinical outcome. For the development of radiomics risk models, a variety of different algorithms is available and it is not clear which one gives optimal results. Therefore, we assessed the performance of 11 machine learning algorithms combined with 12 feature selection methods by the concordance index (C-Index), to predict loco-regional tumour control (LRC) and overall survival for patients with head and neck squamous cell carcinoma. The considered algorithms are able to deal with continuous time-to-event survival data. Feature selection and model building were performed on a multicentre cohort (213 patients) and validated using an independent cohort (80 patients). We found several combinations of machine learning algorithms and feature selection methods which achieve similar results, e.g. C-Index = 0.71 and BT-COX: C-Index = 0.70 in combination with Spearman feature selection. Using the best performing models, patients were stratified into groups of low and high risk of recurrence. Significant differences in LRC were obtained between both groups on the validation cohort. Based on the presented analysis, we identified a subset of algorithms which should be considered in future radiomics studies to develop stable and clinically relevant predictive models for time-to-event endpoints.

  5. The importance of internal carotid artery occlusion tolerance test in carotid endarterectomy under locoregional anesthesia.

    Science.gov (United States)

    Dellaretti, Marcos; de Vasconcelos, Laura T; Dourado, Jules; de Souza, Renata F; Fontoura, Renato R; de Sousa, Atos A

    2016-06-01

    Carotid endarterectomy is considered a safe and effective method for preventing stroke in the short and long term in patients with severe carotid stenosis. The internal carotid artery (ICA) occlusion tolerance test was performed to evaluate cerebral tolerance during temporary carotid occlusion, defined as the capacity of the cerebral hemisphere to maintain adequate cerebral blood flow during occlusion of the ICA. Thus, the aim of the present study is to determine the importance of this test in patients undergoing carotid endarterectomy. From August 2008 to May 2015, 115 consecutive patients (39 female, 77 male) were referred for carotid endarterectomy at the Santa Casa de Belo Horizonte by the main author. Of the 115 patients who participated in the study, 107 were submitted to carotid endarterectomy. Morbi-mortality was 2.7 %. The presence of deficits during the ICA occlusion tolerance test in less than 30 s was associated with the presence of complications. Among the 104 patients who showed no deficits during the test, only one case (0.9 %) presented complications, while among the three cases that showed deficits during the test and who were submitted to carotid endarterectomy, two cases presented complications (p carotid endarterectomy under locoregional anesthesia is a safe surgical procedure. The internal carotid artery occlusion tolerance test can help identify high-risk patients who have been assigned this treatment.

  6. Preoperative locoregional staging of rectal carcinoma: comparison of MR, TRUS and Multislice CT. Personal experience.

    Science.gov (United States)

    Panzironi, Giuseppe; De Vargas Macciucca, Marina; Manganaro, Lucia; Ballesio, Laura; Ricci, Francesca; Casale, Alessandra; Campagnano, Deborah

    2004-04-01

    The aim of this study was to measure the sensitivity and clinical indications of Magnetic Resonance (MR) as compared to Transrectal Ultrasonography (TRUS) and spiral Computed Tomography (CT) in the preoperative staging and evaluation of rectal carcinoma. Twenty patients with histologically proven rectal carcinoma were examined with phased-array coil MRI. We used T1 and T2, spin-echo, turbo-spin-echo, flash2D sequences with and without fat suppression; FOV 180-280; 4-6 mm slice thickness; i.v. Gadolinium. The MR images were compared with TRUS, spiral CT and with the final histological diagnosis. MR showed a 92.3% sensitivity for rectal wall infiltration vs. 100% of TRUS and 75% of CT. The sensitivity for lymph node metastases was 76.4% vs. 72.2% for TRUS and 88% for CT. Locoregional staging of rectal cancer by MRI shows a high sensitivity and is also feasible in stenosing or proximal rectal lesions. TRUS, despite its limitations, is still the most sensitive method for the evaluation of wall infiltration. CT was less sensitive than the other two The sensitivity of MR and CT for lymph node metastases is comparable, but the former is more specific.

  7. Loco-regional extensions of central nervous system germ cell tumors: a retrospective radiological analysis of 100 patients.

    Science.gov (United States)

    Duron, Loïc; Sadones, Flavie; Thiesse, Philippe; Cellier, Cécile; Alapetite, Claire; Doz, François; Frappaz, Didier; Brisse, Hervé J

    2018-01-01

    The current staging system of central nervous system (CNS) germ cell tumors (GCT) includes a binary classification in "localized" or "metastatic" disease based on the absence or presence of leptomeningeal dissemination. Loco-regional tumor dissemination has been barely described whereas its accurate definition might be useful in terms of prognosis and treatment, especially for radiation therapy planning. Our purpose was therefore to describe MR patterns and prevalence of loco-regional extensions of these tumors. One hundred consecutive patients (median age 16.3 years, range 7-41 years, sex ratio 7:1) with a histologically or biologically proven CNS GCT were retrospectively included. Brain and spinal MRI at diagnosis were reviewed by two neuroradiologists focusing on MR patterns of primaries and loco-regional extensions. When available, follow-up MR exams were analyzed. Pure germinoma represented 84/100 cases. Primaries were unifocal pineal (n = 49/100), bifocal pineal and supra-sellar (n = 27/100), isolated supra-sellar (n = 21/100), isolated basal ganglia (n = 2/100) or trifocal pineal, supra-sellar, and basal ganglia (n = 1/100). Metastatic disease occurred in 6/100 patients (depicted by MRI in two and CSF cytology in four). Loco-regional extensions were observed in all patients and classified as follows: third ventricle (n = 88/100), thalamus (n = 47/100), midbrain (n = 42/100), distant sub-ependymal areas (n = 19/100), optic pathways (n = 19/100), lateral ventricles (n = 7/100), cavernous sinus (n = 6/100), corpus callosum (n = 4/100), and fourth ventricle (n = 3/100). CNS GCT present with specific loco-regional extensions at diagnosis. Improving their recognition will be helpful to further understand their prognostic value and potentially to optimize the treatment.

  8. Hyperthermia and Radiation Therapy in Locoregional Recurrent Breast Cancers: A Systematic Review and Meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Datta, Niloy R., E-mail: niloyranjan.datta@ksa.ch [Center for Radiation Oncology KSA-KSB, Kantonsspital Aarau, Aarau (Switzerland); Puric, Emsad [Center for Radiation Oncology KSA-KSB, Kantonsspital Aarau, Aarau (Switzerland); Klingbiel, Dirk [Swiss Group for Clinical Cancer Research, Coordinating Center, Bern (Switzerland); Gomez, Silvia [Center for Radiation Oncology KSA-KSB, Kantonsspital Aarau, Aarau (Switzerland); Bodis, Stephan [Center for Radiation Oncology KSA-KSB, Kantonsspital Aarau, Aarau (Switzerland); Department of Radiation Oncology, University Hospital Zurich, Zurich (Switzerland)

    2016-04-01

    Purpose: To conduct a systematic review and meta-analysis to evaluate the outcome of hyperthermia (HT) and radiation therapy (RT) in locally recurrent breast cancers (LRBCs). Methods and Materials: A total of 708 abstracts were screened from 8 databases according to the PRISMA guidelines. Single-arm and 2-arm studies, treating LRBCs with HT and RT but without surgery (for local recurrence) or concurrent chemotherapy were considered. The evaluated endpoint was complete response (CR). Results: Thirty-one full text articles, pertaining to 34 studies, were shortlisted for the meta-analysis. Eight were 2-arm (randomized, n=5; nonrandomized, n=3), whereas 26 were single-arm studies. In all, 627 patients were enrolled in 2-arm and 1483 in single-arm studies. Patients were treated with a median of 7 HT sessions, and an average temperature of 42.5°C was attained. Mean RT dose was 38.2 Gy (range, 26-60 Gy). Hyperthermia was most frequently applied after RT. In the 2-arm studies, a CR of 60.2% was achieved with RT + HT versus 38.1% with RT alone (odds ratio 2.64, 95% confidence interval [CI] 1.66-4.18, P<.0001). Risk ratio and risk difference were 1.57 (95% CI 1.25-1.96, P<.0001) and 0.22 (95% CI 0.11-0.33, P<.0001), respectively. In 26 single-arm studies, RT + HT attained a CR of 63.4% (event rate 0.62, 95% CI 0.57-0.66). Moreover, 779 patients had been previously irradiated (696 from single-arm and 83 from 2-arm studies). A CR of 66.6% (event rate 0.64, 95% CI 0.58-0.70) was achieved with HT and reirradiation (mean ± SD dose: 36.7 ± 7.7 Gy). Mean acute and late grade 3/4 toxicities with RT + HT were 14.4% and 5.2%, respectively. Conclusions: Thermoradiation therapy enhances the likelihood of CR rates in LRBCs over RT alone by 22% with minimal acute and late morbidities. For even those previously irradiated, reirradiation with HT provides locoregional control in two-thirds of the patients. Thermoradiation therapy could therefore be considered as an effective

  9. Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases. Local tumour control and survival

    Energy Technology Data Exchange (ETDEWEB)

    Oehlke, Oliver; Wucherpfennig, David; Prokic, Vesna [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); Fels, Franziska [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); St. Josefs Hospital, Department of Radiation Oncology, Offenburg (Germany); Frings, Lars [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); University Hospital Freiburg, Department of Geriatrics and Gerontology, Freiburg (Germany); University Medical Center Freiburg, Department of Nuclear Medicine, Freiburg (Germany); Egger, Karl [University Medical Center Freiburg, Department of Neuroradiology, Freiburg (Germany); Weyerbrock, Astrid [University Medical Center Freiburg, Department of Neurosurgery, Freiburg (Germany); Nieder, Carsten [Nordland Hospital, Department of Oncology and Palliative Medicine, Bodoe (Norway); University of Tromsoe, Institute of Clinical Medicine, Faculty of Health Sciences, Tromsoe (Norway); Grosu, Anca-Ligia [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); German Cancer Consortium (DKTK), Freiburg (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany)

    2015-01-16

    Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) for multiple brain metastases may prevent treatment-related cognitive decline, compared to standard WBRT. Additionally, simultaneous integrated boost (SIB) on individual metastases may further improve the outcome. Here, we present initial data concerning local tumour control (LTC), intracranial progression-free survival (PFS), overall survival (OS), toxicity and safety for this new irradiation technique. Twenty patients, enrolled between 2011 and 2013, were treated with HA-WBRT (30 Gy in 12 fractions, D{sub 98} {sub %} to hippocampus ≤ 9 Gy) and a SIB (51 Gy) on multiple (2-13) metastases using a volumetric modulated arc therapy (VMAT) approach based on 2-4 arcs. Metastases were evaluated bidimensionally along the two largest diameters in contrast-enhanced three-dimensional T1-weighed MRI. Median follow-up was 40 weeks. The median time to progression of boosted metastases has not been reached yet, corresponding to a LTC rate of 73 %. Median intracranial PFS was 40 weeks, corresponding to a 1-year PFS of 45.3 %. Median OS was 71.5 weeks, corresponding to a 1-year OS of 60 %. No obvious acute or late toxicities grade > 2 (NCI CTCAE v4.03) were observed. D{sub mean} to the bilateral hippocampi was 6.585 Gy ± 0.847 (α/β = 2 Gy). Two patients developed a new metastasis in the area of hippocampal avoidance. HA-WBRT (simultaneous integrated protection, SIP) with SIB to metastases is a safe and tolerable regime that shows favorable LTC for patients with multiple brain metastases, while it has the potential to minimize the side-effect of cognitive deterioration. (orig.) [German] Die Hippocampus-schonende Ganzhirnbestrahlung (HS-GHB) kann im Vergleich zur Standard-GHB die Verschlechterung der neurokognitiven Funktion verhindern. Zusaetzlich vermag ein simultan integrierter Boost (SIB) auf die Metastasen die Prognose der betroffenen Patienten weiter zu verbessern. In dieser Studie praesentieren wir erste Ergebnisse

  10. Definitive surgery and intraoperative photodynamic therapy: a prospective study of local control and survival for patients with pleural dissemination of non-small cell lung cancer.

    Science.gov (United States)

    Simone, Charles B; Cengel, Keith A

    2014-02-01

    Patients with non-small cell lung cancer (NSCLC) with pleural dissemination have very limited survivals often of just 6-9 months. Prior reports of aggressive surgical resection of pleural metastases have shown no consistent improvements in overall survival and very high rates of local recurrences. Based on this and the generally very diffuse pleural dissemination seen in patients, chemotherapy and palliative interventions are standard of care. By attempting to sterile microscopic residual disease after surgical resection, intraoperative photodynamic therapy (PDT) could improve local pleural control and overall survival compared with surgery alone for patients with NSCLC with pleural metastasis. Prior attempts to demonstrate an improvement in clinical outcomes with PDT as an intraoperative adjuvant combined with definitive surgery to treat pleural malignancies have not been successful, perhaps due, in part, to limited ability to perform real-time dosimetry and ensure adequate and even light distribution throughout the chest cavity. A stratified phase II trial assessed the efficacy of definitive surgery and intraoperative PDT with real-time dosimetry in patients with NSCLC with pleural dissemination demonstrated prolonged local control and a higher than expected 21.7-month median survival from the time of surgery and PDT among 22 enrolled patients. This is the first ever report describing optimal methods, techniques, and dosimetry that could be used to safely and reproducibly deliver intraoperative PDT to the chest cavity as part of multimodality therapy for NSCLC with pleural metastasis.

  11. Transrectal rigid-hybrid NOTES cholecystectomy can be performed without peritoneal contamination: a controlled porcine survival study.

    Science.gov (United States)

    Müller, Philip C; Senft, Jonas D; Gath, Philip; Steinemann, Daniel C; Nickel, Felix; Billeter, Adrian T; Müller-Stich, Beat P; Linke, Georg R

    2018-01-01

    The risk of infectious complications due to peritoneal contamination is a major concern and inhibits the widespread use of transrectal NOTES. A standardized rectal washout with a reversible colon occlusion device in situ has previously shown potential in reducing peritoneal contamination. The aim of this study was to compare the peritoneal contamination rate and inflammatory reaction for transrectal cholecystectomy after ideal rectal preparation (trCCE) and standard laparoscopic cholecystectomy (lapCCE) in a porcine survival experiment. Twenty pigs were randomized to trCCE (n = 10) or lapCCE (n = 10). Before trCCE, rectal washout was performed with saline solution. A colon occlusion device was then inserted and a second washout with povidone-iodine was performed. The perioperative course and the inflammatory reaction (leukocytes, C-reactive protein) were compared. At necropsy, 14 days after surgery the abdominal cavity was screened for infectious complications and peritoneal swabs were obtained for comparison of peritoneal contamination. Peritoneal contamination was lower after trCCE than after lapCCE (0/10 vs. 6/10; p = 0.003). No infectious complications were found at necropsy in either group and postoperative complications did not differ (p = 1.0). Immediately after the procedure, leukocytes were higher after lapCCE (17.0 ± 2.7 vs. 14.6 ± 2.3; p = 0.047). Leukocytes and C-reactive protein showed no difference in the further postoperative course. Intraoperative complications and total operation time (trCCE 114 ± 32 vs. 111 ± 27 min; p = 0.921) did not differ, but wound closure took longer for trCCE (31.5 ± 19 vs. 13 ± 5 min; p = 0.002). After standardized rectal washout with a colon occlusion device in situ, trCCE was associated without peritoneal contamination and without access-related infectious complications. Based on the findings of this study, a randomized controlled clinical study comparing clinical outcomes of trCCE with

  12. SW43-DOX ± loading onto drug-eluting bead, a potential new targeted drug delivery platform for systemic and locoregional cancer treatment - An in vitro evaluation.

    Science.gov (United States)

    Ludwig, Johannes M; Gai, Yongkang; Sun, Lingyi; Xiang, Guangya; Zeng, Dexing; Kim, Hyun S

    2016-08-01

    Treatment of unresectable primary cancer and their distant metastases, with the liver representing one of the most frequent location, is still plagued by insufficient treatment success and poor survival rates. The Sigma-2 receptor is preferentially expressed on many tumor cells making it an appealing target for therapy. Thus, we developed a potential targeted drug conjugate consisting of the Sigma-2 receptor ligand SW43 and Doxorubicin (SW43-DOX) for systemic cancer therapy and for locoregional treatment of primary and secondary liver malignancies when loaded onto drug-eluting bead (DEB) which was compared in vitro to the treatment with Doxorubicin alone. SW43-DOX binds specifically to the Sigma-2 receptor expressed on hepatocellular (Hep G2, Hep 3B), pancreatic (Panc-1) and colorectal (HT-29) carcinoma cell lines with high affinity and subsequent early specific internalization. Free SW43-DOX showed superior concentration and time depended cancer toxicity than treatment with Doxorubicin alone. Action mechanisms analysis revealed an apoptotic cell death with increased caspase 3/7 activation and reactive oxygen species (ROS) production. Only ROS scavenging with α-Tocopherol, but not the caspase inhibition (Z-VAD-FMK), partly reverted the effect. SW43-DOX could successfully be loaded onto DEB and showed prolonged eluting kinetics compared to Doxorubicin. SW43-DOX loaded DEB vs. Doxorubicin loaded DEB showed a significantly greater time dependent toxicity in all cell lines. In conclusion, the novel conjugate SW43-DOX ± loading onto DEB is a promising drug delivery platform for targeted systemic and locoregional cancer therapy. Copyright © 2016. Published by Elsevier B.V.

  13. The Preoperative Controlling Nutritional Status Score Predicts Survival After Curative Surgery in Patients with Pathological Stage I Non-small Cell Lung Cancer.

    Science.gov (United States)

    Shoji, Fumihiro; Haratake, Naoki; Akamine, Takaki; Takamori, Shinkichi; Katsura, Masakazu; Takada, Kazuki; Toyokawa, Gouji; Okamoto, Tatsuro; Maehara, Yoshihiko

    2017-02-01

    The prognostic Controlling Nutritional Status (CONUT) score is used to evaluate immuno-nutritional conditions and is a predictive factor of postoperative survival in patients with digestive tract cancer. We retrospectively analyzed clinicopathological features of patients with pathological stage I non-small cell lung cancer (NSCLC) to identify predictors or prognostic factors of postoperative survival and to investigate the role of preoperative CONUT score in predicting survival. We selected 138 consecutive patients with pathological stage I NSCLC treated from August 2005 to August 2010. We measured their preoperative CONUT score in uni- and multivariate Cox regression analyses of postoperative survival. A high CONUT score was positively associated with preoperative serum carcinoembryonic antigen level (p=0.0100) and postoperative recurrence (p=0.0767). In multivariate analysis, the preoperative CONUT score [relative risk (RR)=6.058; 95% confidence interval (CI)=1.068-113.941; p=0.0407), increasing age (RR=7.858; 95% CI=2.034-36.185; p=0.0029), and pleural invasion (RR=36.615; 95% CI=5.900-362.620; pcancer-specific survival (CS), and overall survival (OS), the group with high CONUT score had a significantly shorter RFS, CS, and OS than did the low-CONUT score group by log-rank test (p=0.0458, p=0.0104 and p=0.0096, respectively). The preoperative CONUT score is both a predictive and prognostic factor in patients with pathological stage I NSCLC. This immuno-nutritional score can indicate patients at high risk of postoperative recurrence and death. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  14. The influence of adjuvant radiotherapy on patterns of failure and survivals in uterine carcinosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hae Jin; Kim, Hak Jae; Wu, Hong Gyun; Kim, Hans; Ha, Sung Whan; Kang, Soon Beom; Song, Yong Sang; Park, Noh Hyun; Kim, Jae Won [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2011-12-15

    To evaluate the impact of postoperative radiotherapy (PORT) on patterns of failure and survivals in uterine carcinosarcoma patients treated with radical surgery. Between October 1998 and August 2010, 19 patients with stage I?III uterine carcinosarcoma received curative hysterectomy and bilateral salpingo-oophorectomy with or without PORT at Seoul National University Hospital. Their hospital medical records were retrospectively reviewed. PORT and non-PORT groups included 11 and 8 patients, respectively. They were followed for a mean of 22.7 months (range, 7.8 to 126.6 months). At 5 years, the overall survival rates were 51.9% for entire, 61.4% for PORT, and 41.7% for non-PORT groups, respectively. There was no statistical difference between PORT and non-PORT groups with regard to overall survival (p = 0.682). Seven out of 19 (36.8%) patients showed treatment failures, which all happened within 12 months. Although the predominant failures were distant metastasis in PORT group and loco-regional recurrence in non-PORT group, there was no statistically significant difference in loco-regional recurrence-free survival (LRRFS) (p = 0.362) or distant metastasis-free survival (DMFS) (p = 0.548). Lymph node metastasis was found to be a significant prognostic factor in predicting poor LRRFS (p = 0.013) and DMFS (p = 0.021), while the International Federation Gynecology and Obstetrics (FIGO) stage (p = 0.043) was associated with LRRFS. Considering that adjuvant radiotherapy after surgical resection was effective to decrease loco-regional recurrence and most treatment failures were distant metastasis, multimodal therapy including surgery, radiotherapy, and chemotherapy might be an optimal treatment for uterine carcinosarcoma patients.

  15. Survival in Malnourished Older Patients Receiving Post-Discharge Nutritional Support; Long-Term Results of a Randomized Controlled Trial

    NARCIS (Netherlands)

    Neelemaat, F; van Keeken, S; Langius, J A E; de van der Schueren, M A E; Thijs, A; Bosmans, J E

    2017-01-01

    BACKGROUND: Previous analyses have shown that a post-discharge individualized nutritional intervention had positive effects on body weight, lean body mass, functional limitations and fall incidents in malnourished older patients. However, the impact of this intervention on survival has not yet been

  16. The 3.5-year survival rates of primary molars treated according to three treatment protocols: a controlled clinical trial

    NARCIS (Netherlands)

    Mijan, M.; Amorim, R.G. de; Leal, S.C.; Mulder, J.; Oliveira, L.; Creugers, N.H.J.; Frencken, J.E.F.M.

    2014-01-01

    OBJECTIVES: This study aimed to test the hypothesis that there is no difference in the survival rates of molars treated according to the conventional restorative treatment (CRT) using amalgam, atraumatic restorative treatment (ART) using high-viscosity glass ionomer, and ultraconservative treatment

  17. Predictive factors of long-term colorectal cancer survival after ultrasound-controlled ablation of hepatic metastases.

    Science.gov (United States)

    Hernández-Socorro, Carmen Rosa; Saavedra, Pedro; Ramírez Felipe, José; Bohn Sarmiento, Uriel; Ruiz-Santana, Sergio

    2017-04-21

    The risk factors associated to long-term survival were assessed in patients with liver metastases of colorectal carcinoma undergoing ablative therapies. Single-centre cohort study, retrospectively analysed and prospectively collected consecutive patients with unresectable metastatic liver disease of colorectal carcinoma treated with ablative therapies between 1996 and 2013. Factors associated with survival time were identified using Cox's proportional hazard model with time-dependent covariates. A forward variable selection based on Akaike information criterion was performed. Relative risk and 95% confidence intervals for each factor were calculated. Statistical significance was set as P<.05. Seventy-five patients with liver metastases of colorectal cancer, with a mean age of 65.6 (10.3) underwent 106 treatments. Variables selected were good quality of life (RR 0.308, 95% CI 0.150-0.632) and tumour extension (RR 3.070, 95% CI 1.776-5.308). The median overall survival was 18.5 months (95% CI 17.4-24.4). The survival prognosis in median was 13.5 vs. 23.4 months for patients with and without tumour extension, and 23.0 vs. 12.8 months for patients with good and fair or poor quality of life, respectively. Good quality of life and tumour extension were the only statistically significant predictors of long-term survival in patients of colorectal carcinoma with liver metastatic disease undergoing ablative treatment with ultrasound. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  18. Effect of Low Temperature and Wheat Winter-Hardiness on Survival of Puccinia striiformis f. sp. tritici under Controlled Conditions.

    Directory of Open Access Journals (Sweden)

    Lijie Ma

    Full Text Available Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst, is one of the most important diseases of wheat worldwide. Understanding the survival of Pst during the overwintering period is critical for predicting Pst epidemics in the spring. Real-time quantitative PCR (qPCR methods quantifying Pst DNA and RNA (cDNA were developed and compared for the ability to quantify viable Pst in leaf tissues. Both qPCR of DNA and RNA can provide reliable measurement of viable Pst in plant tissues prior to the late sporulation stage for which qPCR of DNA gave a much higher estimate of fungal biomass than qPCR of RNA. The percentage of Pst biomass that was viable in detached and attached leaves under low temperatures decreased over time. Pst survived longer on attached leaves than on detached leaves. The survival of Pst in cultivars with strong winter-hardiness at 0°C and -5°C was greater than those with weak winter-hardiness. However, such differences in Pst survival among cultivars were negligible at -10, -15 and -20°C. Results indicated that Pst mycelia inside green leaves can also be killed by low temperatures rather than through death of green leaves under low temperatures. The relationship of Pst survival in attached leaves with temperature and winter-hardiness was well described by logistic models. Further field evaluation is necessary to assess whether inclusion of other factors such as moisture and snow cover could improve the model performance in predicting Pst overwintering potential, and hence the epidemic in spring.

  19. The 3.5-year survival rates of primary molars treated according to three treatment protocols: a controlled clinical trial.

    Science.gov (United States)

    Mijan, Maite; de Amorim, Rodrigo Guedes; Leal, Soraya Coelho; Mulder, Jan; Oliveira, Luciana; Creugers, Nico H J; Frencken, Jo E

    2014-05-01

    This study aimed to test the hypothesis that there is no difference in the survival rates of molars treated according to the conventional restorative treatment (CRT) using amalgam, atraumatic restorative treatment (ART) using high-viscosity glass ionomer, and ultraconservative treatment (UCT) protocol after 3.5 years. Cavitated primary molars were treated according to CRT, ART, and UCT (small cavities were restored with ART and medium/large cavities were daily cleaned with toothpaste/toothbrush under supervision). Molar extractions resulting from toothache, sepsis, or pulp exposure were failures. The Kaplan-Meier method was used to estimate the survival curves. The numbers of treated teeth, among the 302 6-7-year-old children, were 341 (CRT), 244 (ART), and 281 (for UCT group: 109 small ART, 166 open cavities, and 6 combinations). Protocol groups were similar at baseline regarding gender and mean decayed missing filled tooth score, but not regarding age and type of surface. The numbers of molars extracted were 22 (CRT), 16 (ART), and 26 (UCT). Fistulae were most often recorded. After 3.5 years, the cumulative survival rate ± standard error for all molars treated was 90.9 ± 2.0 % with CRT, 90.4 ± 2.4 % with ART, and 88.6 ± 1.9 % with UCT (p = 0.13). Only a type of surface effect was observed over the 3.5-year period: survival rates for molars were higher for single- than for multiple-surface cavities. There was no difference in the cumulative survival rates of primary molars treated according to the CRT, ART, and UCT protocols over a 3.5-year period. Keeping cavities in primary molars biofilm-free might be another treatment option alongside restoring such cavities through conventional and ART protocols.

  20. Aloin delivery on buccal mucosa: ex vivo studies and design of a new locoregional dosing system.

    Science.gov (United States)

    De Caro, Viviana; Scaturro, Anna Lisa; Di Prima, Giulia; Avellone, Giuseppe; Sutera, Flavia Maria; Di Fede, Olga; Campisi, Giuseppina; Giannola, Libero Italo

    2015-01-01

    Chemoprevention of potential malignant disorders or cancerous lesions that affect oral mucosae requires extended duration of treatment. Locoregional delivery of natural products could represent a promising strategy for this purpose. To investigate the aptitude of aloin to permeate through, or accumulate in, the buccal mucosa and to develop a new prolonged oro-mucosal drug delivery system. Permeation/accumulation of aloin from Curacao Aloe (containing 50% barbaloin) was evaluated ex vivo, using porcine buccal mucosa as the most useful model to simulate human epithelium. Oro-mucosal matrix tablets were prepared by dispersing aloin (10% w/w) in Eudragit® RS 100 as, biocompatible, low permeable, pH-independent, and non-swelling polymer. The prepared tablets were evaluated for drug-polymer compatibility, weight variation, drug uniformity content, diameter, thickness, hardness, friability, swelling, mucoadhesive strength, and drug release. Aloin has low tendency to cross buccal mucosa, permeation is marginal, and high drug amounts remain entrapped into the epithelium. Matrix tablets characteristics were in agreement with pharmacopoeial requirements. Drug release showed highly reproducible Higuchian profile. Delivery through matrix tablets promoted drug accumulation in the mucosal tissue. Following application of matrix tablets on porcine buccal mucosa, the amount of discharged drug recovered in the tissue should be sufficient to produce the desired effects, providing therapeutic drug levels directly at the site of action. Aloin-loaded tablets are valid candidates for prevention/treatment of potentially malignant disorders and oral cancer and could potentially lead to clinically relevant drug delivery system as coadjuvant of conventional chemotherapy/radiation therapy.

  1. Temperature measurements in a capacitive system of deep loco-regional hyperthermia.

    Science.gov (United States)

    Sahinbas, H; Rosch, M; Demiray, M

    2017-01-01

    Hyperthermia has been shown to be a medically useful procedure applicable for different indications. For the connection between clinical effects and heat, it is important to understand the actual temperatures achieved in the tissue. There are limited temperature data available when using capacitive hyperthermia devices even though this is worldwide the most widespread method for loco-regional heating. Hence, this study examines temperature measurements using capacitive heating. Bioequivalent phantoms were used for the measurements, which, however, do not consider perfusion in live tissue. In general, the required temperature impact for an effective cancer therapy should need an increase of 0.2°C/min, which has been achieved. In the described tests on the non-perfused dummy, on average, the temperature increases by approximately 2°C in the first 12 min. The temperature difference relative to the starting temperature was 10-12°C within a therapy time of 60 min (rising from the initial room temperature between 20-24°C and 32-34°C). The average deviation with three individual measurements each on different days in a specified localization was 2°C. The minimum temperature difference was 4.2°C, and the maximum value was reached in the liver with 10.5°C. These values were achieved with a moderate energy input of 60-150 watts, with much higher performance outputs still available. These results show that the tested capacitive device is capable of achieving quick temperature increase with a sufficient impact into the depth of a body.

  2. Failure-Free Survival and Radiotherapy in Patients With Newly Diagnosed Nonmetastatic Prostate Cancer: Data From Patients in the Control Arm of the STAMPEDE Trial.

    Science.gov (United States)

    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

    2016-03-01

    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. To describe survival and the impact on failure-free survival of RT by nodal involvement in these patients. 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. Long-term HT either alone or with RT, as per local standard. Planned RT use was recorded at entry. Failure-free survival (FFS) and overall survival. 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, 0.18-0.61]) and N+M0 disease (HR, 0.48 [95% CI, 0.29-0.79]). Survival for men entering the cohort with

  3. Comparison of MRI and PET-CT in detecting the loco-regional recurrence of soft tissue sarcomas during surveillance

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sun-Young [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, 88, Olympic-ro 43-gil, Songpa-gu, Seoul (Korea, Republic of); Hallym University Sacred Heart Hospital, Department of Radiology, Anyang-si, Gyeonggi-do (Korea, Republic of); Chung, Hye Won [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, 88, Olympic-ro 43-gil, Songpa-gu, Seoul (Korea, Republic of); Chae, Sun Young [University of Ulsan College of Medicine, Asan Medical Center, Department of Nuclear Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul (Korea, Republic of); Lee, Jong-Seok [University of Ulsan College of Medicine, Asan Medical Center, Department of Orthopedic Surgery, 88, Olympic-ro 43-gil, Songpa-gu, Seoul (Korea, Republic of)

    2016-10-15

    To investigate the diagnostic performance of MRI and PET-CT for the detection of loco-regional recurrences after soft tissue sarcoma (STS) excision. From Dec 2003 to Aug 2014, 394 patients with STSs, who were included in the electronic patient registry for initial or repeated surgery at our hospital, were retrospectively reviewed. We identified 152 patients who underwent regular postoperative follow-ups with both MRI and PET-CT, obtained within a 3 month period of each other. We analyzed differences in the performance of MRI and PET-CT for the diagnosis of loco-regional recurrences using McNemar's test. The receiver-operating characteristic curves and calculations of the area under the curve were used. Twenty patients were found to have a loco-regional recurrence after tumor excision. For MRI and PET-CT, the sensitivities were 90.0 and 95.0 %, and the specificities 97.7 and 95.5 %, respectively, with positive predictive values of 85.7 and 76.0 % and negative predictive values of 98.5 and 99.2 %, respectively. No significant difference was detected between the sensitivities of MRI and PET-CT (p = 0.125). The area under the receiver-operating characteristic curve for PET-CT (0.952) was not significantly greater than that for MRI (0.939; p = 0.6). MRI of the area of interest is recommended for evaluation of tumor recurrence after surgical excision of STS. PET-CT was shown to be effective for detection of STS recurrence, and comparable to MRI. However, if PET-CT or MRI findings are inconclusive, the other modality may be helpful in differentiating tumor recurrence from post-therapeutic tissue change. (orig.)

  4. Comparison of MRI and PET-CT in detecting the loco-regional recurrence of soft tissue sarcomas during surveillance.

    Science.gov (United States)

    Park, Sun-Young; Chung, Hye Won; Chae, Sun Young; Lee, Jong-Seok

    2016-10-01

    To investigate the diagnostic performance of MRI and PET-CT for the detection of loco-regional recurrences after soft tissue sarcoma (STS) excision. From Dec 2003 to Aug 2014, 394 patients with STSs, who were included in the electronic patient registry for initial or repeated surgery at our hospital, were retrospectively reviewed. We identified 152 patients who underwent regular postoperative follow-ups with both MRI and PET-CT, obtained within a 3 month period of each other. We analyzed differences in the performance of MRI and PET-CT for the diagnosis of loco-regional recurrences using McNemar's test. The receiver-operating characteristic curves and calculations of the area under the curve were used. Twenty patients were found to have a loco-regional recurrence after tumor excision. For MRI and PET-CT, the sensitivities were 90.0 and 95.0 %, and the specificities 97.7 and 95.5 %, respectively, with positive predictive values of 85.7 and 76.0 % and negative predictive values of 98.5 and 99.2 %, respectively. No significant difference was detected between the sensitivities of MRI and PET-CT (p = 0.125). The area under the receiver-operating characteristic curve for PET-CT (0.952) was not significantly greater than that for MRI (0.939; p = 0.6). MRI of the area of interest is recommended for evaluation of tumor recurrence after surgical excision of STS. PET-CT was shown to be effective for detection of STS recurrence, and comparable to MRI. However, if PET-CT or MRI findings are inconclusive, the other modality may be helpful in differentiating tumor recurrence from post-therapeutic tissue change.

  5. Treatment strategies and survival of older breast cancer patients - an international comparison between the Netherlands and Ireland.

    Science.gov (United States)

    Kiderlen, Mandy; Walsh, Paul M; Bastiaannet, Esther; Kelly, Maria B; Audisio, Riccardo A; Boelens, Petra G; Brown, Chris; Dekkers, Olaf M; de Craen, Anton J M; van de Velde, Cornelis J H; Liefers, Gerrit-Jan

    2015-01-01

    Forty percent of breast cancers occur among older patients. Unfortunately, there is a lack of evidence for treatment guidelines for older breast cancer patients. The aim of this study is to compare treatment strategy and relative survival for operable breast cancer in the elderly between The Netherlands and Ireland. From the Dutch and Irish national cancer registries, women aged ≥65 years with non-metastatic breast cancer were included (2001-2009). Proportions of patients receiving guideline-adherent locoregional treatment, endocrine therapy, and chemotherapy were calculated and compared between the countries by stage. Secondly, 5-year relative survival was calculated by stage and compared between countries. Overall, 41,055 patients from The Netherlands and 5,826 patients from Ireland were included. Overall, more patients received guideline-adherent locoregional treatment in The Netherlands, overall (80% vs. 68%, adjusted pIreland, where endocrine therapy was prescribed to 92% of hormone receptor-positive patients, compared to 59% in The Netherlands. In The Netherlands, only 6% received chemotherapy, as compared 24% in Ireland. But relative survival was poorer in Ireland (5 years relative survival 89% vs. 83%), especially in stage II (87% vs. 85%) and stage III (61% vs. 58%) patients. Treatment for older breast cancer patients differed significantly on all treatment modalities between The Netherlands and Ireland. More locoregional treatment was provided in The Netherlands, and more systemic therapy was provided in Ireland. Relative survival for Irish patients was worse than for their Dutch counterparts. This finding should be a strong recommendation to study breast cancer treatment and survival internationally, with the ultimate goal to equalize the survival rates for breast cancer patients across Europe.

  6. Tuber melanosporum spread within sub-optimal climatic zones is controlled by fruiting triggers and not mycorrhiza survival

    Directory of Open Access Journals (Sweden)

    Paul W. Thomas

    2014-07-01

    Full Text Available Tuber melanosporum is the most valuable of all cultivatable truffle species. Farming of this species spans every continent with the exception of Antarctica. Tuber aestivum (syn. T. uncinatum and Tuber brumale are truffle species that have similar host plant preference and a similar affinity for calcareous soils as T. melanosporum, but occur over a broader geographic zone. The geographic limit of T. melanosporum is thought to be climatically dictated but it is not known whether this is due to an impact on mycorrhizal survival or climatically-derived fruiting triggers. Here, data is compiled from five cultivated research sites in the climatically sub-optimal conditions of the UK in order to address this question. Here we show: (iTuber melanosporum mycorrhiza can survive and grow in sub-optimal climatic conditions. (iiIt is climatically-derived fruiting triggers and not ectomycorrhiza survival that dictate the climatic preferences and geographic spread of T. melanosporum. (iiiImportant climatic parameters for potential fruiting triggers are sunshine hours, summer rainfall and summer temperatures.   The data presented here not only aid our understanding of the ecological parameters of T. melanosporum but also have a practical application for truffle cultivators in choosing suitable locations for a plantation.

  7. Analysis of CT-verified loco-regional recurrences after definitive IMRT for HNSCC using site of origin estimation methods.

    Science.gov (United States)

    Zukauskaite, Ruta; Hansen, Christian R; Brink, Carsten; Johansen, Jørgen; Asmussen, Jon T; Grau, Cai; Overgaard, Jens; Eriksen, Jesper G

    2017-11-01

    A significant part of patients with head and neck squamous cell carcinoma (HNSCC) develop recurrent disease after curative radiotherapy. We aimed to analyze loco-regional recurrence pattern by identifying possible points of recurrence origin by three different methods in relation to treatment volumes. A total of 455 patients completed IMRT-based treatment for HNSCC from 2006 to 2012. A total of 159 patients had remaining cancer after IMRT, developed loco-regional recurrence or distant disease during follow-up. Among those, 69 patients with loco-regional recurrences had affirmative CT or PET/CT scan. Possible points of origin (POs) of the recurrences were identified on scans by two independent observers, estimated as center of mass and as maximum surface distance. The recurrence position was analyzed in relation to high-dose treatment volume (CTV1) and 95% of prescription dose. In total, 104 loco-regional recurrences (54 in T-site and 50 in N-site) were identified in 69 patients. Median time to recurrence for the 69 patients was 10 months. No clinically relevant difference was found between the four POs, with standard deviation between POs in x, y and z axes of 3, 3 and 6 mm. For recurrences inside CTV1, 0-5 mm and 5-10 mm outside CTV1 the standard deviation of dose differences between the POs were 1, 1.4 and 1 Gy, respectively. 56% and 25% of T-site and N-site recurrences were inside CTV1, respectively. Coverage by 95% prescription dose to high-dose treatment volume was achieved in 78% of T-site and 39% of N-site recurrences. For recurrences identified by possible points of recurrence origin, no significant difference between observer-based or mathematically estimated methods was found. More than half of T-site recurrences were inside high-dose treatment volume, whereas N-site recurrences were mainly outside.

  8. Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial.

    Science.gov (United States)

    Jacobs, Ian G; Finn, Judith C; Jelinek, George A; Oxer, Harry F; Thompson, Peter L

    2011-09-01

    There is little evidence from clinical trials that the use of adrenaline (epinephrine) in treating cardiac arrest improves survival, despite adrenaline being considered standard of care for many decades. The aim of our study was to determine the effect of adrenaline on patient survival to hospital discharge in out of hospital cardiac arrest. We conducted a double blind randomised placebo-controlled trial of adrenaline in out-of-hospital cardiac arrest. Identical study vials containing either adrenaline 1:1000 or placebo (sodium chloride 0.9%) were prepared. Patients were randomly allocated to receive 1 ml aliquots of the trial drug according to current advanced life support guidelines. Outcomes assessed included survival to hospital discharge (primary outcome), pre-hospital return of spontaneous circulation (ROSC) and neurological outcome (Cerebral Performance Category Score - CPC). A total of 4103 cardiac arrests were screened during the study period of which 601 underwent randomisation. Documentation was available for a total of 534 patients: 262 in the placebo group and 272 in the adrenaline group. Groups were well matched for baseline characteristics including age, gender and receiving bystander CPR. ROSC occurred in 22 (8.4%) of patients receiving placebo and 64 (23.5%) who received adrenaline (OR=3.4; 95% CI 2.0-5.6). Survival to hospital discharge occurred in 5 (1.9%) and 11 (4.0%) patients receiving placebo or adrenaline respectively (OR=2.2; 95% CI 0.7-6.3). All but two patients (both in the adrenaline group) had a CPC score of 1-2. Patients receiving adrenaline during cardiac arrest had no statistically significant improvement in the primary outcome of survival to hospital discharge although there was a significantly improved likelihood of achieving ROSC. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  9. Association with pregnancy increases the risk of local recurrence but does not impact overall survival in breast cancer: A case-control study of 87 cases.

    Science.gov (United States)

    Genin, A S; De Rycke, Y; Stevens, D; Donnadieu, A; Langer, A; Rouzier, R; Lerebours, F

    2016-12-01

    Pregnancy-associated breast cancer (PABC) constitutes 7% of all BCs in young women. The prognosis of PABC remains controversial. In this study, we evaluated the impact of the association of pregnancy with BC on the rates of overall survival (OS), disease free survival (DFS), and distant and local recurrence-free survival. We conducted a retrospective unicenter case-control study. We enrolled PABC patients treated at our institution between 1992 and 2009. For each case, 2 BC controls were matched for age and year of diagnosis. Univariate and multivariate analyses were performed to assess the parameters associated with prognosis. Eighty-seven PABC patients were enrolled and matched with 174 controls. The univariate analysis did not reveal any significant differences in OS, DFS or distant recurrence rates between the 2 groups. Pregnancy associated status, a tumor larger than T2 and neoadjuvant chemotherapy as the primary treatment were significantly associated with an increased risk of local relapse. The multivariate analysis showed that the pregnancy associated status and the tumor size were strong prognostic factors of local recurrence. Pregnancy associated status negates the prognostic value of tumor size, as both T0-T2 and T3-T4 PABC patients have the same poor prognosis as control BC patients with T3-T4 tumors. Interestingly, although PABC patients have more locally advanced tumors, they did not have a higher rate of radical surgery than the control BC patients. Pregnancy associated status is a strong prognostic factor of local relapse in BC. In PABC patients, when possible, radical surgery should be the preferred first treatment step. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Synergistic locoregional chemoradiotherapy using a composite liposome-in-gel system as an injectable drug depot.

    Science.gov (United States)

    GuhaSarkar, Shruti; Pathak, Kamal; Sudhalkar, Niyati; More, Prachi; Goda, Jayant Sastri; Gota, Vikram; Banerjee, Rinti

    The use of radiosensitizers in clinical radiotherapy is limited by systemic toxicity. The biopolymeric, biodegradable, injectable liposome-in-gel-paclitaxel (LG-PTX) system was developed for regional delivery of the radiosensitizer paclitaxel (PTX), and its efficacy was evaluated with concurrent fractionated radiation. LG-PTX is composed of nano-sized drug-loaded fluidizing liposomes, which are incorporated into a porous biodegradable gellan hydrogel. This allows enhanced drug permeation while maintaining a localization of the drug depot. LG-PTX had an IC50 of 325±117 nM in B16F10 melanoma cells, and cytotoxicity with concurrent doses of fractionated radiation showed significant increase in apoptotic cells (75%) compared to radiation (39%) or LG-PTX (43%) alone. Peri-tumoral injection in tumor-bearing mice showed PTX localization in the tumor 2 hours after administration, with no drug detected in plasma or other organs. LG-PTX administration with doses of focal radiation (5×3 Gy) significantly reduced tumor volumes compared to control (6.4 times) and radiation alone (1.6 times) and improved animal survival. LG-PTX thus efficiently localizes the drug at the tumor site and synergistically enhances the effect of concurrent radiotherapy. This novel liposome-in-gel system can potentially be used as a platform technology for the delivery of radiosensitizing drugs to enhance the efficacy of chemoradiotherapy.

  11. Survivability enhancement study for C/sup 3/I/BM (communications, command, control and intelligence/battle management) ground segments: Final report

    Energy Technology Data Exchange (ETDEWEB)

    1986-10-30

    This study involves a concept developed by the Fairchild Space Company which is directly applicable to the Strategic Defense Initiative (SDI) Program as well as other national security programs requiring reliable, secure and survivable telecommunications systems. The overall objective of this study program was to determine the feasibility of combining and integrating long-lived, compact, autonomous isotope power sources with fiber optic and other types of ground segments of the SDI communications, command, control and intelligence/battle management (C/sup 3/I/BM) system in order to significantly enhance the survivability of those critical systems, especially against the potential threats of electromagnetic pulse(s) (EMP) resulting from high altitude nuclear weapon explosion(s). 28 figs., 2 tabs.

  12. Transbronchial and transesophageal fine-needle aspiration using a single ultrasound bronchoscope in the diagnosis of locoregional recurrence of surgically-treated lung cancer.

    Science.gov (United States)

    Sanz-Santos, José; Serra, Pere; Andreo, Felipe; Torky, Mohamed; Centeno, Carmen; Morán, Teresa; Carcereny, Enric; Fernández, Esther; García-Reina, Samuel; Ruiz-Manzano, Juan

    2017-02-28

    The present study sought to evaluate the usefulness of EBUS-TBNA in the diagnosis of locoregional recurrence of lung cancer in a cohort of lung cancer patients who were previously treated surgically, and describe our initial experience of EUS-B-FNA in this clinical scenario. We retrospectively studied the clinical records of all patients with a previous surgically-treated lung cancer who were referred to our bronchoscopy unit after suspicion of locoregional recurrence. The diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall accuracy of EBUS-TBNA for the diagnosis of locoregional recurrence were evaluated. Seventy-three patients were included. EBUS-TBNA confirmed malignancy in 40 patients: 34 confirmed to have locoregional recurrence, six had metachronous tumours. Of the 33 patients with non-malignant EBUS-TBNA; 2 had specific non-malignant diseases, 26 underwent radiological follow up and 5 patients underwent surgery. Of the 26 patients who had radiological follow up; 18 remained stable, three presented thoracic radiological progression and 5 presented extrathoracic progression. Of the 5 patients who underwent surgery; 3 had metachronous tumours, one confirmed to be a true negative and one presented nodal invasion. Seven patients underwent EUS-B-FNA, four of them confirmed to have recurrence. The sensitivity, specificity, NPV, PPV and overall accuracy of EBUS-TBNA for the diagnosis of locoregional recurrence were 80.9, 100, 69.2, 100 and 86.6% respectively. EBUS-TBNA is an accurate procedure for the diagnosis of locoregional recurrence of surgically-treated lung cancer. EUS-B-FNA combined with EBUS-TBNA broads the diagnostic yield of EBUS-TBNA alone.

  13. The VrrA sRNA controls a stationary phase survival factor Vrp of Vibrio cholerae.

    Science.gov (United States)

    Sabharwal, Dharmesh; Song, Tianyan; Papenfort, Kai; Wai, Sun Nyunt

    2015-01-01

    Small non-coding RNAs (sRNAs) are emerging regulatory elements in bacteria. The Vibrio cholerae sRNA VrrA has previously been shown to down-regulate outer membrane proteins (OmpA and OmpT) and biofilm matrix protein (RbmC) by base-pairing with the 5' region of the corresponding mRNAs. In this study, we present an additional target of VrrA in V. cholerae, the mRNA coding for the ribosome binding protein Vrp. Vrp is homologous to ribosome-associated inhibitor A (RaiA) of Escherichia coli which facilitates stationary phase survival through ribosome hibernation. We show that VrrA down-regulates Vrp protein synthesis by base-pairing to the 5' region of vrp mRNA and that the regulation requires the RNA chaperone protein, Hfq. We further demonstrate that Vrp is highly expressed during stationary phase growth and associates with the ribosome of V. cholerae. The effect of the Vrp protein in starvation survival is synergistic with that of the VC2530 protein, a homolog of the E. coli hibernation promoting factor HPF, suggesting a combined role for these proteins in ribosome hibernation in V. cholerae. Vrp and VC2530 are important for V. cholerae starvation survival under nutrient deficient conditions. While VC2530 is down-regulated in cells lacking vrrA, mutation of vrp results in VC2530 activation. This is the first report indicating a regulatory role for an sRNA, modulating stationary factors involved in bacterial ribosome hibernation.

  14. Initial experience with locoregional radioimmunotherapy using {sup 131}I-labelled monoclonal antibodies against tenascin (BC-4) for treatment of glioma (WHO III and IV)

    Energy Technology Data Exchange (ETDEWEB)

    Poepperl, G.; Gildehaus, F.J.; Hahn, K.; Tatsch, K. [Klinik und Poliklinik fuer Nuklearmedizin, Klinikum Grosshadern, Muenchen (Germany); Goetz, C.; Reulen, H.J. [Klinik und Poliklinik fuer Neurochirurgie, Klinikum Grosshadern, Muenchen (Germany); Yousry, T.A. [Inst. fuer Neuroradiologie der LMU Muenchen, Klinikum Grosshadern, Muenchen (Germany)

    2002-06-01

    Aim: None of the established treatments (surgery, radiotherapy, chemotherapy) for malignant glioma has improved its very poor prognosis. Adjuvant locoregional radioimmunotherapy (RIT) represents a new therapeutic approach. We present our initial experience with this therapeutic tool with respect to adverse effects, biokinetics and clinical follow-up. Methods: Following surgery and radiotherapy, 12 patients with glioma (4, WHO stage III; 8, WHO stage IV) underwent 1-5 RIT-cycles (average dose 1100 MBq {sup 131}labelled monoclonal BC-4 antibodies) at six week intervals. Follow-up included serial FDG-PET and MRI investigations. Evaluation of biokinetics included whole body scans, together with analysis of blood, urine and fluid from the tumor cavity. Results: Following RIT, four patients experienced temporary seizures, which, in one case, were associated with temporary aphasia. Eight patients developed HAMA (human anti-mouse anti-bodies) during follow-up. Mean biologic half-life of the radiopharmaceutical in the resection cavity was 3.9 d (range: 1.0-10.2 d) and remained stable intraindividually during further RIT-cycles. The antibody/radionuclide conjugate remain stable in the tumor cavity for at least 5 d. Median survival presently stands at 18.5 months compared to 9.7 months in a historical patient group (n=89) undergoing conventional therapeutic strategies. Five patients show no signs of recurrence. In three patients with post-surgical evidence of residual tumor, one patient showed partial remission, one stable disease, and one progressive disease during RIT. Four patients without evidence of residual tumor mass at the beginning of RIT developed recurrence during therapy. Conclusions: Initial experience demonstrates that locoregional RIT is a well tolerated treatment modality that may represent a promising new approach in the management of patients with malignant glioma. Advantages of local application include passage of the blood-brain barrier, high concentration

  15. Preoperative chemoradiotherapy versus postoperative chemoradiotherapy for stage II–III resectable rectal cancer: a meta-analysis of randomized controlled trials

    Energy Technology Data Exchange (ETDEWEB)

    Song, Jin Ho [Gyeongsang National University School of Medicine, Jinju (Korea, Republic of); Jeong, Jae Uk [Chonnam National University School of Medicine, Gwangju (Korea, Republic of); Lee, Jong Hoon; Kim, Sung Hwan [The Catholic University of Korea, Suwon (Korea, Republic of); Cho, Hyeon Min [The Catholic University of Korea, Suwon (Korea, Republic of); Um, Jun Won [University Ansan Hospital, Ansan (Korea, Republic of); Jang, Hong Seok [The Catholic University of Korea, Seoul (Korea, Republic of)

    2017-09-15

    Whether preoperative chemoradiotherapy (CRT) is better than postoperative CRT in oncologic outcome and toxicity is contentious in prospective randomized clinical trials. We systematically analyze and compare the treatment result, toxicity, and sphincter preservation rate between preoperative CRT and postoperative CRT in stage II–III rectal cancer. We searched Medline, Embase, and Cochrane Library from 1990 to 2014 for relevant trials. Only phase III randomized studies performing CRT and curative surgery were selected and the data were extracted. Meta-analysis was used to pool oncologic outcome and toxicity data across studies. Three randomized phase III trials were finally identified. The meta-analysis results showed significantly lower 5-year locoregional recurrence rate in the preoperative-CRT group than in the postoperative-CRT group (hazard ratio, 0.59; 95% confidence interval, 0.41–0.84; p = 0.004). The 5-year distant recurrence rate (p = 0.55), relapse-free survival (p = 0.14), and overall survival (p = 0.22) showed no significant difference between two groups. Acute toxicity was significantly lower in the preoperativeCRT group than in the postoperative-CRT group (p < 0.001). However, there was no significant difference between two groups in perioperative and chronic complications (p = 0.53). The sphincter-saving rate was not significantly different between two groups (p = 0.24). The conversion rate from abdominoperineal resection to low anterior resection in low rectal cancer was significantly higher in the preoperative-CRT group than in the postoperative-CRT group (p < 0.001). As compared to postoperative CRT, preoperative CRT improves only locoregional control, not distant control and survival, with similar chronic toxicity and sphincter preservation rate in rectal cancer patients.

  16. Prospective prediction of resistance to neoadjuvant therapy in patients with locoregional esophageal adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Rosen DG

    2015-02-01

    Full Text Available Daniel G Rosen,1 Weiwei Shan,2 Natalie Lassen,2 Clare Johnson,2 Kristen Oelschlager,2 Yaeli Bierman-Harrar,1 Kenneth A Kesler,3 Derek Maetzold,2 Sunil Badve,3 Robert W Cook,2 Romil Saxena3 1Baylor College of Medicine, Houston TX, USA; 2Castle Biosciences, Incorporated, Friendswood, TX, USA; 3Indiana University, Indianapolis, IN, USA Background: To clinically validate a multianalyte algorithmic immunohistochemistry (IHC assay that has been previously shown to accurately identify patients with locoregional esophageal adenocarcinoma (EC who will exhibit extreme resistance to neoadjuvant chemoradiotherapy. Methods: Archived biopsy specimens of EC were subject to IHC examination of compartmentalized immunoreactivity of nuclear factor kappa B (NF-κB, Sonic Hedgehog (SHH, and GLI family zinc finger 1 (Gli-1, and a labeling index score was assigned to each biomarker. Test prediction was generated by logistic regression predictive modeling, using the labeling index scores for all three analytes from each sample, referring to a validated training set of 167 EC patients. Accuracy of the test was determined by comparing the predicted outcomes with pathologically determined College of American Pathologists tumor response grade. Analytical validity of the test was measured by comparing validation set prediction results obtained in two independent Clinical Laboratory Improvement Amendment-certified laboratories, and by measuring concordance between two trained labeling index readers. Results: Specimens from 64 patients that met specific criteria were collected. No technical failure was encountered during the IHC labeling procedures. The logistic regression algorithm generated an area under the curve of 0.96 and 0.85 for the 64 sample cohort in two independent clinical laboratories, respectively, comparing predictive results with the established training set. Positive predictive values of 88% and 82% were also achieved in each laboratory, respectively. A

  17. Radiation Therapy in Addition to Gross Total Resection of Retroperitoneal Sarcoma Results in Prolonged Survival: Results from a Single Institutional Study

    Directory of Open Access Journals (Sweden)

    Timothy M. Zagar

    2008-01-01

    Full Text Available Purpose. Typical treatment of retroperitoneal sarcomas (RPSs is surgery with or without radiation therapy for localized disease. With surgery alone, local failure rates are as high as 90%; this led to radiation therapy playing an important role in the treatment of RPSs. Methods. Thirty-one patients with retroperitoneal sarcoma treated with gross total resection and radiation therapy make up this retrospective analysis. Nineteen were treated preoperatively and 12 postoperatively (median dose, 59.4 Gy—sixteen also received intraoperative radiation therapy (IORT (median dose, 11 Gy. Patients were followed with stringent regimens, including frequent CT scans of the chest, abdomen, and pelvis. Results. With a median follow-up of 19 months (range 1–66 months, the 2-year overall survival (OS rate is 70% (median, 52 months. The 2-year locoregional control (LRC rate is 77% (median, 61.6 months. The 2-year distant disease free survival (DDFS rate is 70% (median not reached. There were no differences in radiation-related acute and late toxicities among patients treated pre- versus postoperatively, whether with or without IORT. Conclusions. Compared to surgery alone, neoadjuvant or adjuvant radiation therapy offers patients with RPS an excellent chance for long-term LRC, DDS, and OS. The integration of modern treatment planning for external beam radiation therapy and IORT allows for higher doses to be delivered with acceptable toxicities.

  18. Barhl1 regulates migration and survival of cerebellar granule cells by controlling expression of the neurotrophin-3 gene.

    Science.gov (United States)

    Li, Shengguo; Qiu, Feng; Xu, Anlong; Price, Sandy M; Xiang, Mengqing

    2004-03-24

    The neurons generated at the germinal rhombic lip undergo long distance migration along divergent pathways to settle in widely dispersed locations within the hindbrain, giving rise to cerebellar granule cells and precerebellar nuclei. Neurotrophin-3 (NT-3) signaling has been shown to be required for proper migration and survival of cerebellar granule cells. The molecular bases that govern NT-3 expression within the cerebellum, however, remain unknown at present. Here we report that, during early mouse neurogenesis, the Barhl1 homeobox gene is highly expressed by the rhombic lip and rhombic lip-derived migratory neurons. Its expression is later restricted to cerebellar granule cells and precerebellar neurons extending mossy fibers, two groups of neurons that synaptically connect in the adult cerebellar system. Loss of Barhl1 function causes cerebellar phenotypes with a striking similarity to those of NT-3 conditional null mice, which include attenuated cerebellar foliation as well as defective radial migration and increased apoptotic death of granule cells. Correlating with these defects, we find that NT-3 expression is dramatically downregulated in granule cells of the posterior lobe of Barhl1(-)/- cerebella. Moreover, in the precerebellar system of Barhl1(-/-) mice, all five nuclei that project mossy fibers fail to form correctly because of aberrant neuronal migration and elevated apoptosis. These results suggest that Barhl1 plays an essential role in the migration and survival of cerebellar granule cells and precerebellar neurons and functionally link Barhl1 to the NT-3 signaling pathway during cerebellar development.

  19. A randomized controlled trial of cognitive-behavioral stress management in breast cancer: survival and recurrence at 11-year follow-up.

    Science.gov (United States)

    Stagl, Jamie M; Lechner, Suzanne C; Carver, Charles S; Bouchard, Laura C; Gudenkauf, Lisa M; Jutagir, Devika R; Diaz, Alain; Yu, Qilu; Blomberg, Bonnie B; Ironson, Gail; Glück, Stefan; Antoni, Michael H

    2015-11-01

    Non-metastatic breast cancer patients often experience psychological distress which may influence disease progression and survival. Cognitive-behavioral stress management (CBSM) improves psychological adaptation and lowers distress during breast cancer treatment and long-term follow-ups. We examined whether breast cancer patients randomized to CBSM had improved survival and recurrence 8-15 years post-enrollment. From 1998 to 2005, women (N = 240) 2-10 weeks post-surgery for non-metastatic Stage 0-IIIb breast cancer were randomized to a 10-week, group-based CBSM intervention (n = 120) or a 1-day psychoeducational seminar control (n = 120). In 2013, 8-15 years post-study enrollment (11-year median), recurrence and survival data were collected. Cox Proportional Hazards Models and Weibull Accelerated Failure Time tests were used to assess group differences in all-cause mortality, breast cancer-specific mortality, and disease-free interval, controlling for biomedical confounders. Relative to the control, the CBSM group was found to have a reduced risk of all-cause mortality (HR = 0.21; 95 % CI [0.05, 0.93]; p = .040). Restricting analyses to women with invasive disease revealed significant effects of CBSM on breast cancer-related mortality (p = .006) and disease-free interval (p = .011). CBSM intervention delivered post-surgery may provide long-term clinical benefit for non-metastatic breast cancer patients in addition to previously established psychological benefits. Results should be interpreted with caution; however, the findings contribute to the limited evidence regarding physical benefits of psychosocial intervention post-surgery for non-metastatic breast cancer. Additional research is necessary to confirm these results and investigate potential explanatory mechanisms, including physiological pathways, health behaviors, and treatment adherence changes.

  20. Effect of a mentor-based, supportive-expressive program, Be Resilient to Breast Cancer, on survival in metastatic breast cancer: a randomised, controlled intervention trial.

    Science.gov (United States)

    Ye, Zeng Jie; Qiu, Hong Zhong; Liang, Mu Zi; Liu, Mei Ling; Li, Peng Fei; Chen, Peng; Sun, Zhe; Yu, Yuan Liang; Wang, Shu Ni; Zhang, Zhang; Liao, Kun Lun; Peng, Cai Fen; Huang, Hui; Hu, Guang Yun; Zhu, Yun Fei; Zeng, Zhen; Hu, Qu; Zhao, Jing Jing

    2017-11-07

    Because of medical advances, metastatic breast cancer (MBC) is now viewed as a chronic disease, rather than an imminent death sentence. Helping women live with this disease requires more than a medical approach to symptoms. Thus, a mentor-based and supportive-expressive program 'Be Resilient to Breast Cancer' (BRBC) was designed to help Chinese women with MBC enhance their resilience levels, biopsychosocial functions, and potentially extend their life span. A total of 226 women with MBC were randomly assigned, in a 1 : 1 ratio, to an intervention group (IG) that participated in BRBC or to a control group (CG) that received no intervention. Be Resilient to Breast Cancer was conducted for 120 min once a week. Primary outcomes were cancer-specific survival and secondary outcomes were resilience, Allostatic Load Index (ALI), anxiety, depression, and quality of life (QoL). The Cox proportional-hazards model was used for survival analysis and growth mixture models were performed for secondary outcomes. Be Resilient to Breast Cancer did not significantly prolong 3- or 5-year survival (median survival, 36.7 months in IG and 31.5 months in CG). The hazard ratio for death was 0.736 (95% CI, 0.525-1.133, P=0.076; univariate Cox model) and 0.837 (95% CI, 0.578-1.211, P=0.345; multivariate Cox analysis). The IG improved in anxiety (ES=0.85, Presilience (ES=0.67, Presilience, QoL, ALI, and emotional distress.

  1. Survival and Complications of Single Dental Implants in the Edentulous Mandible Following Immediate or Delayed Loading: A Randomized Controlled Clinical Trial.

    Science.gov (United States)

    Kern, M; Att, W; Fritzer, E; Kappel, S; Luthardt, R G; Mundt, T; Reissmann, D R; Rädel, M; Stiesch, M; Wolfart, S; Passia, N

    2018-02-01

    It was the aim of this 24-mo randomized controlled clinical trial to investigate whether the survival of a single median implant placed in the edentulous mandible to retain a complete denture is not compromised by immediate loading. Secondary outcomes were differences in prosthetic complications between the loading principles. Each of the 158 patients who received an implant was randomly assigned to the immediate loading group ( n = 81) or the delayed loading group ( n = 77). Recall visits were performed 1 mo after implant placement (for only the delayed loading group) and 1, 4, 12, and 24 mo after implant loading. Nine implants failed in the immediate loading group, all within the first 3 mo of implant loading, and 1 implant failed in the delayed loading group prior to loading. Noninferiority of implant survival of the immediate loading group, as compared with the delayed loading group, could not be shown ( P = 0.81). Consistent with this result, a secondary analysis with Fisher exact test revealed that the observed difference in implant survival between the treatment groups was indeed statistically significant ( P = 0.019). The most frequent prosthetic complications and maintenance interventions in the mandible were retention adjustments, denture fractures, pressure sores, and matrix exchanges. There was only 1 statistically significant difference between the groups regarding the parameter "fracture of the denture base in the ball attachment area" ( P = 0.007). The results indicate that immediate loading of a single implant in the edentulous mandible reveals inferior survival than that of delayed loading and therefore should be considered only in exceptional cases (German Clinical Trials Register: DRKS00003730).

  2. Edema control by cediranib, a vascular endothelial growth factor receptor-targeted kinase inhibitor, prolongs survival despite persistent brain tumor growth in mice

    DEFF Research Database (Denmark)

    Kamoun, Walid S; Ley, Carsten D; Farrar, Christian T

    2009-01-01

    by an increase in plasma collagen IV. These rapid changes in tumor vascular morphology and function led to edema alleviation -- as measured by MRI and by dry/wet weight measurement of water content -- but did not affect tumor growth. By immunohistochemistry, we found a transient decrease in macrophage...... infiltration and significant but minor changes in tumor cell proliferation and apoptosis. Systemically, cediranib increased plasma VEGF and placenta growth factor levels, and the number of circulating CXCR4(+)CD45(+) cells. However, by controlling edema, cediranib significantly increased survival of mice...

  3. Metabolic and protein interaction sub-networks controlling the proliferation rate of cancer cells and their impact on patient survival.

    Science.gov (United States)

    Feizi, Amir; Bordel, Sergio

    2013-10-24

    Cancer cells can have a broad scope of proliferation rates. Here we aim to identify the molecular mechanisms that allow some cancer cell lines to grow up to 4 times faster than other cell lines. The correlation of gene expression profiles with the growth rate in 60 different cell lines has been analyzed using several genome-scale biological networks and new algorithms. New possible regulatory feedback loops have been suggested and the known roles of several cell cycle related transcription factors have been confirmed. Over 100 growth-correlated metabolic sub-networks have been identified, suggesting a key role of simultaneous lipid synthesis and degradation in the energy supply of the cancer cells growth. Many metabolic sub-networks involved in cell line proliferation appeared also to correlate negatively with the survival expectancy of colon cancer patients.

  4. Survival Analysis

    CERN Document Server

    Miller, Rupert G

    2011-01-01

    A concise summary of the statistical methods used in the analysis of survival data with censoring. Emphasizes recently developed nonparametric techniques. Outlines methods in detail and illustrates them with actual data. Discusses the theory behind each method. Includes numerous worked problems and numerical exercises.

  5. Modelling survival

    DEFF Research Database (Denmark)

    Ashauer, Roman; Albert, Carlo; Augustine, Starrlight

    2016-01-01

    well GUTS, calibrated with short-term survival data of Gammarus pulex exposed to four pesticides, can forecast effects of longer-term pulsed exposures. Thirdly, we tested the ability of GUTS to estimate 14-day median effect concentrations of malathion for a range of species and use these estimates...

  6. Survival of Antibiotic Resistant Bacteria and Horizontal Gene Transfer Control Antibiotic Resistance Gene Content in Anaerobic Digesters

    Science.gov (United States)

    Miller, Jennifer H.; Novak, John T.; Knocke, William R.; Pruden, Amy

    2016-01-01

    Understanding fate of antibiotic resistant bacteria (ARB) vs. their antibiotic resistance genes (ARGs) during wastewater sludge treatment is critical in order to reduce the spread of antibiotic resistance through process optimization. Here, we spiked high concentrations of tetracycline-resistant bacteria, isolated from mesophilic (Iso M1-1—a Pseudomonas sp.) and thermophilic (Iso T10—a Bacillus sp.) anaerobic digested sludge, into batch digesters and monitored their fate by plate counts and quantitative polymerase chain reaction (QPCR) of their corresponding tetracycline ARGs. In batch studies, spiked ARB plate counts returned to baseline (thermophilic) or 1-log above baseline (mesophilic) while levels of the ARG present in the spiked isolate [tet(G)] remained high in mesophilic batch reactors. To compare results under semi-continuous flow conditions with natural influent variation, tet(O), tet(W), and sul1 ARGs, along with the intI1 integrase gene, were monitored over a 9-month period in the raw feed sludge and effluent sludge of lab-scale thermophilic and mesophilic anaerobic digesters. sul1 and intI1 in mesophilic and thermophilic digesters correlated positively (Spearman rho = 0.457–0.829, P digested sludge or thermophilic digested sludge (Spearman rho = 0.130–0.486, P = 0.075–0.612). However, in the thermophilic digester, the tet(O) and tet(W) ratios remained consistently low over the entire monitoring period. We conclude that the influent sludge microbial composition can influence the ARG content of a digester, apparently as a result of differential survival or death of ARBs or horizontal gene transfer of genes between raw sludge ARBs and the digester microbial community. Notably, mesophilic digestion was more susceptible to ARG intrusion than thermophilic digestion, which may be attributed to a higher rate of ARB survival and/or horizontal gene transfer between raw sludge bacteria and the digester microbial community. PMID:27014196

  7. Survival and local control rates of triple-negative breast cancer patients treated with boost-IOERT during breast-conserving surgery

    Energy Technology Data Exchange (ETDEWEB)

    Fastner, Gerd; Zehentmayr, Franz; Kopp, Peter; Fussl, Christoph; Sedlmayer, Felix [Landeskrankenhaus, Paracelsus Medical University, Department of Radiotherapy and Radio-Oncology, Salzburg (Austria); Hauser-Kronberger, Cornelia [Landeskrankenhaus, Paracelsus Medical University, Department of Pathology, Salzburg (Austria); Moder, Angelika [Landeskrankenhaus, Paracelsus Medical University, Institute of Inborn Errors in Metabolism, Salzburg (Austria); Reitsamer, Roland; Fischer, Thorsten [Landeskrankenhaus, Paracelsus Medical University, Department of Special Gynecology, Salzburg (Austria); Landeskrankenhaus, Paracelsus Medical University, Department of Gynecology, Salzburg (Austria); Deutschmann, Heinrich [Landeskrankenhaus, Paracelsus Medical University, Department of Radiotherapy and Radio-Oncology, Salzburg (Austria); Paracelsus Medical University, Institute for Research and Development of Advanced Radiation Technologies (radART), Salzburg (Austria)

    2016-01-15

    The purpose of this work was to retrospectively evaluate survival and local control rates of triple-negative breast cancer subtypes classified as five marker negative (5NP) and core basal (CB), respectively, after breast-conserving surgery and intraoperative boost radiotherapy with electrons (IOERT) followed by whole breast irradiation. A total of 71 patients with triple-negative breast cancer were enrolled, who were treated with lumpectomy, axillary lymph node dissection, and IOERT with 9.6 Gy (median D{sub max}) followed by normofractionated whole breast irradiation to median total doses of 54 Gy. Chemotherapy was applied in a neoadjuvant (12 %), adjuvant (75 %), or combinational setting (7 %). After a median follow-up of 97 months (range 4-170 months), 5 in-breast recurrences were detected (7.0 %). For all patients, 8-year actuarial rates for local control, metastases-free survival, disease-specific survival, and overall survival amounted to 89, 75, 80, and 69 %, respectively. All local recurrences occurred in grade 3 (G3) tumors irrespective of their specific immunohistochemical phenotype; thus, the local control rate for grades 1/2 (G1/2) was 100 % for both 5NP and CB, while for G3 it was 88 % for 5NP and 90 % for CB (p = 0.65 and 0.82, respectively, n.s.). For disease-specific survival, only the difference of the best-prognosis group 5-NP/G3 vs. the worst-prognosis cohort CB/G1/2 was statistically significant: 90 % vs. 54 % (p = 0.03). Boost-IOERT provides acceptable long-term in-breast control in triple negative breast cancer. The best subgroup in terms of disease-specific survival was represented by 5NP in combination with tumor grading G3. (orig.) [German] Ziel der Studie war es, im Rahmen einer retrospektiven Analyse Ueberlebens- und Lokalkontrollraten bei triple-negativen Mammakarzinomen zu untersuchen. Die Tumoren waren in 5NP(5-Marker-negative)- und CB(core basal)-Subtypen klassifiziert und die Patientinnen hatten nach brusterhaltender Operation und

  8. Impact of primary local treatment on the development of distant metastases or death through locoregional recurrence in young breast cancer patients

    NARCIS (Netherlands)

    Bantema-Joppe, E. J.; van den Heuvel, E. R.; de Munck, L.; de Bock, G. H.; Smit, W. G. J. M.; Timmer, P. R.; Dolsma, W. V.; Jansen, L.; Siesling, S.; Langendijk, J. A.; Maduro, J. H.; Schroder, Carolien; Schroder, Carolien

    In this study, we tested the hypothesis whether breast conserving therapy (BCT) compared with mastectomy is associated with a negative outcome in terms of distant metastases or death (DMD) and investigated the relation between locoregional recurrence (LRR) and DMD in young breast cancer (BC)

  9. Impact of primary local treatment on the development of distant metastases or death through locoregional recurrence in young breast cancer patients

    NARCIS (Netherlands)

    Bantema-Joppe, E.J.; van den Heuvel, E.R.; de Munck, L.; de Bock, G.H.; Smit, W.G.J.M.; Timmer, P.R.; Dolsma, W.V.; Jansen, L.; Schroder, C.P.; Siesling, Sabine; Langendijk, J.A.; Maduro, J.H.

    2013-01-01

    In this study, we tested the hypothesis whether breast conserving therapy (BCT) compared with mastectomy is associated with a negative outcome in terms of distant metastases or death (DMD) and investigated the relation between locoregional recurrence (LRR) and DMD in young breast cancer (BC)

  10. Pulmonary function after high-dose chemotherapy with autologous bone marrow transplantation and radiotherapy in patients with advanced loco-regional breast cancer

    NARCIS (Netherlands)

    Dolsma, WV; DeVries, EGE; VanderMark, TW; Sleijfer, DT; Willemse, PHB; VanderGraaf, WTA; Mulder, POM; Szabo, BG; Mulder, NH

    1997-01-01

    Our aim was to study the extent of pulmonary toxicity after high-dose chemotherapy and radiotherapy in breast cancer patients. In a retrospective study the pulmonary symptoms and chest X-rays were analysed before, during and after treatment in 17 patients, treated with loco-regional radiotherapy to

  11. A pilot study to investigate the role of the 26S proteasome in radiotherapy resistance and loco-regional recurrence following breast conserving therapy for early breast cancer.

    Science.gov (United States)

    Elfadl, Dalia; Hodgkinson, Victoria C; Long, Ervine D; Scaife, Lucy; Drew, Philip J; Lind, Michael J; Cawkwell, Lynn

    2011-08-01

    Breast conserving therapy is a currently accepted method for managing patients with early stage breast cancer. However, approximately 7% of patients may develop loco-regional tumour recurrence within 5 years. We previously reported that expression of the 26S proteasome may be associated with radio-resistance. Here we aimed to analyse the 26S proteasome in a pilot series of early breast cancers and correlate the findings with loco-regional recurrence. Fourteen patients with early breast cancer who developed loco-regional recurrence within 4 years of completing breast conserving therapy were selected according to strict criteria and compared with those from 14 patients who were disease-free at 10 years. Decreased expression of the 26S proteasome was significantly associated with radio-resistance, manifested as the development of a loco-regional recurrence within 4 years of breast conserving therapy (p = 0.018). This small pilot study provides further suggestion that the 26S proteasome may be associated with response to radiotherapy. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Towards personalized follow-up : a conditional prediction model and nomogram for risk of locoregional recurrence in early breast cancer patients

    NARCIS (Netherlands)

    Witteveen, Annemieke; Vliegen, Ingrid; Sonke, G.S.; Klaase, J.M.; IJzerman, Maarten Joost; Siesling, Sabine

    2015-01-01

    Background The objective of this study was to develop and validate a conditional logistic regression model for the prediction of locoregional recurrence (LRR) of breast cancer. To make a translation to clinical practice a web based nomogram was made. Methods Women first diagnosed with early breast

  13. Survival of antibiotic resistant bacteria and horizontal gene transfer control antibiotic resistance gene content in anaerobic digesters

    Directory of Open Access Journals (Sweden)

    Jennifer Hafer Miller

    2016-03-01

    Full Text Available Understanding fate of antibiotic resistant bacteria (ARB versus their antibiotic resistance genes (ARGs during wastewater sludge treatment is critical in order to reduce the spread of antibiotic resistance through process optimization. Here, we spiked high concentrations of tetracycline-resistant bacteria, isolated from mesophilic (Iso M1-1- a Pseudomonas sp. and thermophilic (Iso T10- a Bacillus sp. anaerobic digested sludge, into batch digesters and monitored their fate by plate counts and quantitative polymerase chain reaction (QPCR of their corresponding tetracycline ARGs. In batch studies, spiked ARB plate counts returned to baseline (thermophilic or 1-log above baseline (mesophilic while levels of the ARG present in the spiked isolate (tet(G remained high in mesophilic batch reactors. To compare results under semi-continuous flow conditions with natural influent variation, tet(O, tet(W, and sul1 ARGs, along with the intI1 integrase gene, were monitored over a 9-month period in the raw feed sludge and effluent sludge of lab-scale thermophilic and mesophilic anaerobic digesters. sul1 and intI1 in mesophilic and thermophilic digesters correlated positively (Spearman rho = 0.457 to 0.829, P<0.05 with the raw feed sludge. There was no correlation in tet(O or tet(W ratios in raw sludge and mesophilic digested sludge or thermophilic digested sludge (Spearman rho = 0.130 to 0.486, P = 0.075 to 0.612. However, in the thermophilic digester, the tet(O and tet(W ratios remained consistently low over the entire monitoring period. We conclude that the influent sludge microbial composition can influence the ARG content of a digester, apparently as a result of differential survival or death of ARBs or horizontal gene transfer of genes between raw sludge ARBs and the digester microbial community. Notably, mesophilic digestion was more susceptible to ARG intrusion than thermophilic digestion, which may be attributed to a higher rate of ARB survival and

  14. Evidence for Integrin - Venus Kinase Receptor 1 Alliance in the Ovary of Schistosoma mansoni Females Controlling Cell Survival.

    Science.gov (United States)

    Gelmedin, Verena; Morel, Marion; Hahnel, Steffen; Cailliau, Katia; Dissous, Colette; Grevelding, Christoph G

    2017-01-01

    In metazoan integrin signaling is an important process of mediating extracellular and intracellular communication processes. This can be achieved by cooperation of integrins with growth factor receptors (GFRs). Schistosoma mansoni is a helminth parasite inducing schistosomiasis, an infectious disease of worldwide significance for humans and animals. First studies on schistosome integrins revealed their role in reproductive processes, being involved in spermatogenesis and oogenesis. With respect to the roles of eggs for maintaining the parasite´s life cycle and for inducing the pathology of schistosomiasis, elucidating reproductive processes is of high importance. Here we studied the interaction of the integrin receptor Smβ-Int1 with the venus kinase receptor SmVKR1 in S. mansoni. To this end we cloned and characterized SmILK, SmPINCH, and SmNck2, three putative bridging molecules for their role in mediating Smβ-Int1/SmVKR1 cooperation. Phylogenetic analyses showed that these molecules form clusters that are specific for parasitic platyhelminths as it was shown for integrins before. Transcripts of all genes colocalized in the ovary. In Xenopus oocytes germinal vesicle breakdown (GVBD) was only induced if all members were simultaneously expressed. Coimmunoprecipitation results suggest that a Smβ-Int1-SmILK-SmPINCH-SmNck2-SmVKR1 complex can be formed leading to the phosphorylation and activation of SmVKR1. These results indicate that SmVKR1 can be activated in a ligand-independent manner by receptor-complex interaction. RNAi and inhibitor studies to knock-down SmILK as a representative complex member concurrently revealed effects on the extracellular matrix surrounding the ovary and oocyte localization within the ovary, oocyte survival, and egg production. By TUNEL assays, confocal laser scanning microscopy (CLSM), Caspase-3 assay, and transcript profiling of the pro-apoptotic BCL-2 family members BAK/BAX we obtained first evidence for roles of this signaling

  15. Evidence for Integrin - Venus Kinase Receptor 1 Alliance in the Ovary of Schistosoma mansoni Females Controlling Cell Survival.

    Directory of Open Access Journals (Sweden)

    Verena Gelmedin

    2017-01-01

    Full Text Available In metazoan integrin signaling is an important process of mediating extracellular and intracellular communication processes. This can be achieved by cooperation of integrins with growth factor receptors (GFRs. Schistosoma mansoni is a helminth parasite inducing schistosomiasis, an infectious disease of worldwide significance for humans and animals. First studies on schistosome integrins revealed their role in reproductive processes, being involved in spermatogenesis and oogenesis. With respect to the roles of eggs for maintaining the parasite´s life cycle and for inducing the pathology of schistosomiasis, elucidating reproductive processes is of high importance. Here we studied the interaction of the integrin receptor Smβ-Int1 with the venus kinase receptor SmVKR1 in S. mansoni. To this end we cloned and characterized SmILK, SmPINCH, and SmNck2, three putative bridging molecules for their role in mediating Smβ-Int1/SmVKR1 cooperation. Phylogenetic analyses showed that these molecules form clusters that are specific for parasitic platyhelminths as it was shown for integrins before. Transcripts of all genes colocalized in the ovary. In Xenopus oocytes germinal vesicle breakdown (GVBD was only induced if all members were simultaneously expressed. Coimmunoprecipitation results suggest that a Smβ-Int1-SmILK-SmPINCH-SmNck2-SmVKR1 complex can be formed leading to the phosphorylation and activation of SmVKR1. These results indicate that SmVKR1 can be activated in a ligand-independent manner by receptor-complex interaction. RNAi and inhibitor studies to knock-down SmILK as a representative complex member concurrently revealed effects on the extracellular matrix surrounding the ovary and oocyte localization within the ovary, oocyte survival, and egg production. By TUNEL assays, confocal laser scanning microscopy (CLSM, Caspase-3 assay, and transcript profiling of the pro-apoptotic BCL-2 family members BAK/BAX we obtained first evidence for roles of

  16. Evidence for Integrin – Venus Kinase Receptor 1 Alliance in the Ovary of Schistosoma mansoni Females Controlling Cell Survival

    Science.gov (United States)

    Gelmedin, Verena; Morel, Marion; Hahnel, Steffen; Cailliau, Katia; Dissous, Colette; Grevelding, Christoph G.

    2017-01-01

    In metazoan integrin signaling is an important process of mediating extracellular and intracellular communication processes. This can be achieved by cooperation of integrins with growth factor receptors (GFRs). Schistosoma mansoni is a helminth parasite inducing schistosomiasis, an infectious disease of worldwide significance for humans and animals. First studies on schistosome integrins revealed their role in reproductive processes, being involved in spermatogenesis and oogenesis. With respect to the roles of eggs for maintaining the parasite´s life cycle and for inducing the pathology of schistosomiasis, elucidating reproductive processes is of high importance. Here we studied the interaction of the integrin receptor Smβ-Int1 with the venus kinase receptor SmVKR1 in S. mansoni. To this end we cloned and characterized SmILK, SmPINCH, and SmNck2, three putative bridging molecules for their role in mediating Smβ-Int1/SmVKR1 cooperation. Phylogenetic analyses showed that these molecules form clusters that are specific for parasitic platyhelminths as it was shown for integrins before. Transcripts of all genes colocalized in the ovary. In Xenopus oocytes germinal vesicle breakdown (GVBD) was only induced if all members were simultaneously expressed. Coimmunoprecipitation results suggest that a Smβ-Int1-SmILK-SmPINCH-SmNck2-SmVKR1 complex can be formed leading to the phosphorylation and activation of SmVKR1. These results indicate that SmVKR1 can be activated in a ligand-independent manner by receptor-complex interaction. RNAi and inhibitor studies to knock-down SmILK as a representative complex member concurrently revealed effects on the extracellular matrix surrounding the ovary and oocyte localization within the ovary, oocyte survival, and egg production. By TUNEL assays, confocal laser scanning microscopy (CLSM), Caspase-3 assay, and transcript profiling of the pro-apoptotic BCL-2 family members BAK/BAX we obtained first evidence for roles of this signaling

  17. Effect of controlled atmosphere storage, modified atmosphere packaging and gaseous ozone treatment on the survival of Salmonella Enteritidis on cherry tomatoes.

    Science.gov (United States)

    Daş, Elif; Gürakan, G Candan; Bayindirli, Alev

    2006-08-01

    In recent years, outbreaks of infections associated with raw and minimally processed fruits and vegetables have been reported. The objective of this study was to analyse the growth/survival of Salmonella Enteritidis at spot-inoculated or stem-injected cherry tomatoes during passive modified atmosphere packaging (MAP), controlled atmosphere (CA) and to compare the results with those of air storage at 7 and 22 degrees C. During MAP, the gas composition equilibrated to 6% O2/4% CO2. CO2 level was maintained as 5% through the term of CA storage at 7 and 22 degrees C. The results demonstrate that S. Enteritidis can survive and/or grow during the storage of tomatoes depending on the location site of the pathogen on fruit, suspension cell density and storage temperature. During MAP, CA and air storage, S. Enteritidis with initial population of 7.0 log10 cfu/tomato survived on tomato surfaces with an approximate decrease of 4.0-5.0 log10 cfu/tomato in population within the storage period; however, in the case of initial population of 3.0 log10 cfu/tomato, cells died completely on day 4 during MAP storage and on day 6 during both CA and air storage. The death rate of S. Enteritidis on the surfaces of tomatoes that were stored in MAP was faster than that of stored in air and in CA. Storage temperature was effective on the survival of S. Enteritidis for the samples stored at ambient atmosphere; cells died completely on day 6 at 7 degrees C and on day 8 at 22 degrees C. Stem scars provided protective environments for Salmonella; an approximate increase of 1.0 log10 cfu/tomato in stem-scar population was observed during MAP, CA and air storage at 22 degrees C within the period of 20 days. Cells survived with no significant change in number at 7 degrees C. During the research, the effect of ozone treatment (5-30 mg/l ozone gas for 0-20 min) was also considered for surface sanitation before storage. Gaseous ozone treatment has bactericidal effect on S. Enteritidis, inoculated on

  18. c-Met PET Imaging Detects Early-Stage Locoregional Recurrence of Basal-Like Breast Cancer.

    Science.gov (United States)

    Arulappu, Appitha; Battle, Mark; Eisenblaetter, Michel; McRobbie, Graeme; Khan, Imtiaz; Monypenny, James; Weitsman, Gregory; Galazi, Myria; Hoppmann, Susan; Gazinska, Patrycja; Wulaningsih, Wulan; Dalsgaard, Grethe Tang; Macholl, Sven; Ng, Tony

    2016-05-01

    Locoregional recurrence of breast cancer poses significant clinical problems because of frequent inoperability once the chest wall is involved. Early detection of recurrence by molecular imaging agents against therapeutically targetable receptors, such as c-Met, would be of potential benefit. The aim of this study was to assess (18)F-AH113804, a peptide-based molecular imaging agent with high affinity for human c-Met, for the detection of early-stage locoregional recurrence in a human basal-like breast cancer model, HCC1954. HCC1954 tumor-bearing xenograft models were established, and (18)F-AH113804 was administered. Distribution of radioactivity was determined via PET at 60 min after radiotracer injection. PET and CT images were acquired 10 d after tumor inoculation, to establish baseline distribution and uptake, and then on selected days after surgical tumor resection. CT images and caliper were used to determine the tumor volume. Radiotracer uptake was assessed by (18)F-AH113804 PET imaging. c-Met expression was assessed by immunofluorescence imaging of tumor samples and correlated with (18)F-AH113804 PET imaging results. Baseline uptake of (18)F-AH113804, determined in tumor-bearing animals after 10 d, was approximately 2-fold higher in the tumor than in muscle tissue or the contralateral mammary fat pad. The tumor growth rate, determined from CT images, was comparable between the animals with recurrent tumors, with detection of tumors of low volume (tumor resection. (18)F-AH113804 PET detected local tumor recurrence as early as 6 d after surgery in the recurrent tumor-bearing animals and exhibited significantly higher (18)F-AH113804 uptake (in comparison to mammary fatty tissue), with a target-to-background (muscle) ratio of approximately 3:1 (P tumor samples, determined by immunofluorescence, correlated with the respective (18)F-AH113804 imaging signals (r = 0.82, P tumor and has potential utility for the detection of locoregional recurrence from an early

  19. Value of subtraction MRI in assessing treatment response following image-guided loco-regional therapies for hepatocellular carcinoma.

    Science.gov (United States)

    Winters, S D; Jackson, S; Armstrong, G A; Birchall, I W; Lee, K H Y; Low, G

    2012-07-01

    To compare contrast-enhanced subtraction magnetic resonance imaging (MRI) with contrast-enhanced standard MRI in assessing treatment response following loco-regional therapies for hepatocellular carcinoma (HCC). Institutional review board approval was obtained and informed consent was waived for this retrospective study. All patients were analysed from our institution's liver tumour database that had loco-regional HCC therapy and the following: (1) a contrast-enhanced MRI ≤6 weeks post-treatment, (2) an unenhanced T1-weighted high-signal treatment zone (TZ) ≥1 cm, (3) follow-up contrast-enhanced MRI performed ≥6 months post-treatment. Randomized standard and subtraction TZ datasets were independently assessed by three blinded radiology readers for either complete treatment necrosis or residual disease. The standard of reference (SOR) comprised a consensus read by two radiologists with knowledge of the follow-up MRI and all available clinical data. Statistical analyses were performed using receiver operating characteristics (ROC), t-test, and kappa statistic. Twenty-six patients (19 male and seven female patients; mean age 60 years, standard deviation 10.9 years, range 46-88 years) had a total of 45 corresponding HCCs and TZs. For ROC, the area under the curve (AUC) was 0.93 (subtraction protocol) versus 0.90 (standard protocol; p = 0.49). For the t-test, the mean reader confidence level was 4.4, 3.6, and 4.4 (subtraction protocol) versus 3, 3, and 3.7 (standard protocol; p ≤ 0.011). The kappa statistic for reader-to-SOR agreement was 0.83, 0.63, and 0.71 (subtraction protocol) versus 0.51, 0.36, and 0.64 (standard protocol). Subtraction MRI significantly improves the reader confidence level in the assessment of treatment response following loco-regional therapies for HCC. Copyright © 2012 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  20. Survival of Antibiotic Resistant Bacteria and Horizontal Gene Transfer Control Antibiotic Resistance Gene Content in Anaerobic Digesters.

    Science.gov (United States)

    Miller, Jennifer H; Novak, John T; Knocke, William R; Pruden, Amy

    2016-01-01

    Understanding fate of antibiotic resistant bacteria (ARB) vs. their antibiotic resistance genes (ARGs) during wastewater sludge treatment is critical in order to reduce the spread of antibiotic resistance through process optimization. Here, we spiked high concentrations of tetracycline-resistant bacteria, isolated from mesophilic (Iso M1-1-a Pseudomonas sp.) and thermophilic (Iso T10-a Bacillus sp.) anaerobic digested sludge, into batch digesters and monitored their fate by plate counts and quantitative polymerase chain reaction (QPCR) of their corresponding tetracycline ARGs. In batch studies, spiked ARB plate counts returned to baseline (thermophilic) or 1-log above baseline (mesophilic) while levels of the ARG present in the spiked isolate [tet(G)] remained high in mesophilic batch reactors. To compare results under semi-continuous flow conditions with natural influent variation, tet(O), tet(W), and sul1 ARGs, along with the intI1 integrase gene, were monitored over a 9-month period in the raw feed sludge and effluent sludge of lab-scale thermophilic and mesophilic anaerobic digesters. sul1 and intI1 in mesophilic and thermophilic digesters correlated positively (Spearman rho = 0.457-0.829, P horizontal gene transfer of genes between raw sludge ARBs and the digester microbial community. Notably, mesophilic digestion was more susceptible to ARG intrusion than thermophilic digestion, which may be attributed to a higher rate of ARB survival and/or horizontal gene transfer between raw sludge bacteria and the digester microbial community.

  1. Natural history definition and a suggested clinical approach to Buerger's disease: a case-control study with survival analysis.

    Science.gov (United States)

    Fazeli, Bahare; Ravari, Hassan; Assadi, Reza

    2012-08-01

    The aim of this study was first to describe the natural history of Buerger's disease (BD) and then to discuss a clinical approach to this disease based on multivariate analysis. One hundred eight patients who corresponded with Shionoya's criteria were selected from 2000 to 2007 for this study. Major amputation was considered the ultimate adverse event. Survival analyses were performed by Kaplan-Meier curves. Independent variables including gender, duration of smoking, number of cigarettes smoked per day, minor amputation events and type of treatments, were determined by multivariate Cox regression analysis. The recorded data demonstrated that BD may present in four forms, including relapsing-remitting (75%), secondary progressive (4.6%), primary progressive (14.2%) and benign BD (6.2%). Most of the amputations occurred due to relapses within the six years after diagnosis of BD. In multivariate analysis, duration of smoking of more than 20 years had a significant relationship with further major amputation among patients with BD. Smoking cessation programs with experienced psychotherapists are strongly recommended for those areas in which Buerger's disease is common. Patients who have smoked for more than 20 years should be encouraged to quit smoking, but should also be recommended for more advanced treatment for limb salvage.

  2. Ezh2 Controls an Early Hematopoietic Program and Growth and Survival Signaling in Early T Cell Precursor Acute Lymphoblastic Leukemia

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    Etienne Danis

    2016-03-01

    Full Text Available Early T cell precursor acute lymphoblastic leukemia (ETP-ALL is an aggressive subtype of ALL distinguished by stem-cell-associated and myeloid transcriptional programs. Inactivating alterations of Polycomb repressive complex 2 components are frequent in human ETP-ALL, but their functional role is largely undefined. We have studied the involvement of Ezh2 in a murine model of NRASQ61K-driven leukemia that recapitulates phenotypic and transcriptional features of ETP-ALL. Homozygous inactivation of Ezh2 cooperated with oncogenic NRASQ61K to accelerate leukemia onset. Inactivation of Ezh2 accentuated expression of genes highly expressed in human ETP-ALL and in normal murine early thymic progenitors. Moreover, we found that Ezh2 contributes to the silencing of stem-cell- and early-progenitor-cell-associated genes. Loss of Ezh2 also resulted in increased activation of STAT3 by tyrosine 705 phosphorylation. Our data mechanistically link Ezh2 inactivation to stem-cell-associated transcriptional programs and increased growth/survival signaling, features that convey an adverse prognosis in patients.

  3. TRPV6 calcium channel translocates to the plasma membrane via Orai1-mediated mechanism and controls cancer cell survival.

    Science.gov (United States)

    Raphaël, Maylis; Lehen'kyi, V'yacheslav; Vandenberghe, Matthieu; Beck, Benjamin; Khalimonchyk, Sergiy; Vanden Abeele, Fabien; Farsetti, Leonardo; Germain, Emmanuelle; Bokhobza, Alexandre; Mihalache, Adriana; Gosset, Pierre; Romanin, Christoph; Clézardin, Philippe; Skryma, Roman; Prevarskaya, Natalia

    2014-09-16

    Transient receptor potential vanilloid subfamily member 6 (TRPV6) is a highly selective calcium channel that has been considered as a part of store-operated calcium entry (SOCE). Despite its first discovery in the early 2000s, the role of this channel in prostate cancer (PCa) remained, until now, obscure. Here we show that TRPV6 mediates calcium entry, which is highly increased in PCa due to the remodeling mechanism involving the translocation of the TRPV6 channel to the plasma membrane via the Orai1/TRPC1-mediated Ca(2+)/Annexin I/S100A11 pathway, partially contributing to SOCE. The TRPV6 calcium channel is expressed de novo by the PCa cell to increase its survival by enhancing proliferation and conferring apoptosis resistance. Xenografts in nude mice and bone metastasis models confirmed the remarkable aggressiveness of TRPV6-overexpressing tumors. Immunohistochemical analysis of these demonstrated the increased expression of clinical markers such as Ki-67, prostate specific antigen, synaptophysin, CD31, and CD56, which are strongly associated with a poor prognosis. Thus, the TRPV6 channel acquires its oncogenic potential in PCa due to the remodeling mechanism via the Orai1-mediated Ca(2+)/Annexin I/S100A11 pathway.

  4. TRPV6 calcium channel translocates to the plasma membrane via Orai1-mediated mechanism and controls cancer cell survival

    Science.gov (United States)

    Raphaël, Maylis; Lehen’kyi, V’yacheslav; Vandenberghe, Matthieu; Beck, Benjamin; Khalimonchyk, Sergiy; Vanden Abeele, Fabien; Farsetti, Leonardo; Germain, Emmanuelle; Bokhobza, Alexandre; Mihalache, Adriana; Gosset, Pierre; Romanin, Christoph; Clézardin, Philippe; Skryma, Roman; Prevarskaya, Natalia

    2014-01-01

    Transient receptor potential vanilloid subfamily member 6 (TRPV6) is a highly selective calcium channel that has been considered as a part of store-operated calcium entry (SOCE). Despite its first discovery in the early 2000s, the role of this channel in prostate cancer (PCa) remained, until now, obscure. Here we show that TRPV6 mediates calcium entry, which is highly increased in PCa due to the remodeling mechanism involving the translocation of the TRPV6 channel to the plasma membrane via the Orai1/TRPC1-mediated Ca2+/Annexin I/S100A11 pathway, partially contributing to SOCE. The TRPV6 calcium channel is expressed de novo by the PCa cell to increase its survival by enhancing proliferation and conferring apoptosis resistance. Xenografts in nude mice and bone metastasis models confirmed the remarkable aggressiveness of TRPV6-overexpressing tumors. Immunohistochemical analysis of these demonstrated the increased expression of clinical markers such as Ki-67, prostate specific antigen, synaptophysin, CD31, and CD56, which are strongly associated with a poor prognosis. Thus, the TRPV6 channel acquires its oncogenic potential in PCa due to the remodeling mechanism via the Orai1-mediated Ca2+/Annexin I/S100A11 pathway. PMID:25172921

  5. One life saved by four prevented recurrencies? Update of the early breast cancer trialists confirms. Postoperative radiotherapy improves survival after breast conserving surgery

    Energy Technology Data Exchange (ETDEWEB)

    Sautter-Bihl, M.L. [Staedtisches Klinikum Karlsruhe (Germany). Klinik fuer Radioonkologie und Strahlentherapie; Sedlmayer, F. [Landeskrankenhaus Salzburg (Austria); Budach, W. [University Hospital Duesseldorf (DE)] (and others)

    2012-06-15

    The debate about the impact of local control on survival in early breast cancer patients is still going on, in spite of the continuously growing evidence that avoidance of locoregional disease reduces the risk of tumor-specific death. Recently, B. Fisher, one of the pioneers of breast conserving therapy claimed that during the last two decades, as a result of the use of systemic therapy in conjunction with breast conserving surgery and radiation, the incidence of locoregional recurrence has been reduced to a level where further reduction is likely to have little impact on survival. The penultimate meta-analysis of the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) reported the effect of radiotherapy in early breast cancer on recurrence and survival in 2005 and provided the essential message that four prevented local recurrences at 5 years would avoid one breast cancer death in 15 years. The scientific community has eagerly awaited the quinquennial update of the EBCTCG which has now been published. A total of 17 randomized studies comparing postoperative radiotherapy vs. none were analyzed and comprised 7 new studies in addition to follow-up data of from 9 previously reported trials. A total of 10,801 patients with pT1-2 tumors were included, the majority of whom (n=7,287) were node negative, while 1,050 were node positive (2,464 unknown). In contrast to the previous meta-analysis, all patients received breast conserving surgery, consisting of lumpectomy (n=8,422) or more extensive techniques like quadrantectomy or sectoral resection (n= 2,399). The effect of radiotherapy on 10-year recurrences of any type and their relation to the 15-year breast cancer death rate were studied in correlation to various prognostic parameters and treatment characteristics (e.g., surgery, tamoxifen use). Moreover, a subgroup analysis was performed according to low, intermediate, and high initial risk of recurrence, from which the expected absolute benefit was derived

  6. Survival After Retirement.

    Science.gov (United States)

    Holloway, Clark; Youngblood, Stuart A.

    1986-01-01

    Examined survival rates after retirement in a large corporation. A regression analysis was performed to control for age, sex, job status, and type of work differences that may influence longevity. Short-term suvivors seemed to undergo a different adjustment process than long-term survivors. (Author/ABL)

  7. Wear, bone density, functional outcome and survival in vitamin E-incorporated polyethylene cups in reversed hybrid total hip arthroplasty: design of a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    van der Veen Hugo C

    2012-09-01

    Full Text Available Abstract Background Aseptic loosening of total hip arthroplasties is generally caused by periprosthetic bone resorption due to tissue reactions on polyethylene wear particles. In vitro testing of polyethylene cups incorporated with vitamin E shows increased wear resistance. The objective of this study is to compare vitamin E-stabilized highly cross-linked polyethylene with conventional cross-linked polyethylene in “reversed hybrid” total hip arthroplasties (cemented all-polyethylene cups combined with uncemented femoral stems. We hypothesize that the adjunction of vitamin E leads to a decrease in polyethylene wear in the long-term. We also expect changes in bone mineral density, less osteolysis, equal functional scores and increased implant survival in polyethylene cemented cups incorporated with vitamin E in the long-term. Design A double-blinded randomized controlled trial will be conducted. Patients to be included are aged under 70, suffer from non-inflammatory degenerative joint disease of the hip and are scheduled for a primary total hip arthroplasty. The study group will receive a reversed hybrid total hip arthroplasty with a vitamin E-stabilized highly cross-linked polyethylene cemented cup. The control group will receive a reversed hybrid total hip arthroplasty with a conventional cross-linked polyethylene cemented cup. Radiological follow-up will be assessed at 6 weeks and at 1, 3, 5, 7 and 10 years postoperatively, to determine polyethylene wear and osteolysis. Patient-reported functional status (HOOS, physician-reported functional status (Harris Hip Score and patients’ physical activity behavior (SQUASH will also be assessed at these intervals. Acetabular bone mineral density will be assessed by dual energy X-ray absorptiometry (DEXA at 6 weeks and at 1 year and 2 years postoperatively. Implant survival will be determined at 10 years postoperatively. Discussion In vitro results of vitamin E-stabilized polyethylene are promising

  8. CASE-CONTROL SURVIVAL ANALYSIS WITH A GENERAL SEMIPARAMETRIC SHARED FRAILTY MODEL - A PSEUDO FULL LIKELIHOOD APPROACH.

    Science.gov (United States)

    Gorfine, Malka; Zucker, David M; Hsu, Li

    2009-01-01

    In this work we deal with correlated failure time (age at onset) data arising from population-based case-control studies, where case and control probands are selected by population-based sampling and an array of risk factor measures is collected for both cases and controls and their relatives. Parameters of interest are effects of risk factors on the failure time hazard function and within-family dependencies among failure times after adjusting for the risk factors. Due to the retrospective sampling scheme, large sample theory for existing methods has not been established. We develop a novel technique for estimating the parameters of interest under a general semiparametric shared frailty model. We also present a simple, easily computed, and non-iterative nonparametric estimator for the cumulative baseline hazard function. We provide rigorous large sample theory for the proposed method. We also present simulation results and a real data example for illustrating the utility of the proposed method.

  9. Identification of Risk Factors for Locoregional Recurrence in Breast Cancer Patients with Nodal Stage N0 and N1: Who Could Benefit from Post-Mastectomy Radiotherapy?

    Directory of Open Access Journals (Sweden)

    Eunjin Jwa

    Full Text Available The locoregional recurrence (LRR rate was reported as high as approximately 20% in stage I-II breast cancer following mastectomy. To investigate the risk factors for LRR in pT1-2N0-1 breast cancer patients treated with mastectomy but not radiation, and to define a subgroup of patients at high risk of LRR who may benefit from postmastectomy radiotherapy (PMRT.In total, 390 patients with pT1-2N0M0 (n = 307 and pT1-2N1M0 (n = 83 breast cancer who underwent total mastectomy without adjuvant radiotherapy from 2002 to 2011 were enrolled in the study.After a median follow-up period of 5.6 years (range, 0.6-11.3 years, 21 patients had 18 systemic relapses and 12 LRRs including six in the chest wall and eight in the regional nodal area. The 5-year LRR-free survival (LRRFS rates were 97.0% in pN0, 98.8% in pN1, and 97.4% in all patients. Multivariate analysis revealed that age < 50 years (Hazard Ratio, 11.4; p = 0.01 and no adjuvant chemotherapy (Hazard Ratio, 10.2; p = 0.04 were independent risk factors for LRR in pN0 patients. Using these factors, the 5-year LRRFS rates were 100% without any risk factors, 96.4% with one risk factor, and 86.7% with two risk factors. In pN1 patients, multivariate analysis revealed that having a hormone receptor negative tumor (Hazard Ratio, 18.3; p = 0.03 was the only independent risk factor for LRR. The 5-year LRRFS rates were 100.0% for luminal type, and 92.3% for non-luminal type cancer.Patients with pT1-2N0-1 breast cancer who underwent total mastectomy without PMRT could be stratified by nodal stage and risk factors for LRR. PMRT may have of value for node negative patients aged less than 50 years and who are not treated with adjuvant chemotherapy, and for non-luminal type patients with one to three positive nodes.

  10. Identification of Risk Factors for Locoregional Recurrence in Breast Cancer Patients with Nodal Stage N0 and N1: Who Could Benefit from Post-Mastectomy Radiotherapy?

    Science.gov (United States)

    Jwa, Eunjin; Shin, Kyung Hwan; Lim, Hyeon Woo; Jung, So-Youn; Lee, Seeyoun; Kang, Han-Sung; Lee, EunSook; Park, Young Hee

    2015-01-01

    The locoregional recurrence (LRR) rate was reported as high as approximately 20% in stage I-II breast cancer following mastectomy. To investigate the risk factors for LRR in pT1-2N0-1 breast cancer patients treated with mastectomy but not radiation, and to define a subgroup of patients at high risk of LRR who may benefit from postmastectomy radiotherapy (PMRT). In total, 390 patients with pT1-2N0M0 (n = 307) and pT1-2N1M0 (n = 83) breast cancer who underwent total mastectomy without adjuvant radiotherapy from 2002 to 2011 were enrolled in the study. After a median follow-up period of 5.6 years (range, 0.6-11.3 years), 21 patients had 18 systemic relapses and 12 LRRs including six in the chest wall and eight in the regional nodal area. The 5-year LRR-free survival (LRRFS) rates were 97.0% in pN0, 98.8% in pN1, and 97.4% in all patients. Multivariate analysis revealed that age risk factors for LRR in pN0 patients. Using these factors, the 5-year LRRFS rates were 100% without any risk factors, 96.4% with one risk factor, and 86.7% with two risk factors. In pN1 patients, multivariate analysis revealed that having a hormone receptor negative tumor (Hazard Ratio, 18.3; p = 0.03) was the only independent risk factor for LRR. The 5-year LRRFS rates were 100.0% for luminal type, and 92.3% for non-luminal type cancer. Patients with pT1-2N0-1 breast cancer who underwent total mastectomy without PMRT could be stratified by nodal stage and risk factors for LRR. PMRT may have of value for node negative patients aged less than 50 years and who are not treated with adjuvant chemotherapy, and for non-luminal type patients with one to three positive nodes.

  11. Are there patients with T1 to T2, lymph node-negative breast cancer who are "high-risk" for locoregional disease recurrence?

    Science.gov (United States)

    Mamtani, Anita; Patil, Sujata; Stempel, Michelle M; Morrow, Monica

    2017-07-15

    Indications for postmastectomy radiotherapy (PMRT) in patients with T1 to T2, lymph node-negative (N0) breast cancer with "high-risk" features are controversial. The European Organization for Research and Treatment of Cancer (EORTC) 22922 and National Cancer Institute of Canada Clinical Trials Group MA20 trials reporting improved 10-year disease-free survival with lymph node irradiation included patients with high-risk N0 disease, but, to the authors' knowledge, benefits in patients receiving modern systemic therapy are uncertain. The authors retrospectively identified patients with T1 to T2N0 disease who were treated with mastectomy from January 2006 through December 2011. High-risk features included age patients, only 15 received PMRT and were excluded. Of the remaining 657 patients, 187 (28%) had 1 high-risk feature and 449 patients (68%) had ≥ 2 high-risk features. A total of 36 patients with unknown tumor grade were excluded from risk analysis. Approximately 98% of patients underwent sentinel lymph node biopsy alone and 86% received adjuvant systemic therapy. At a median of 5.6 years of follow-up, the locoregional disease recurrence (LRR) rate was 4.7% (31 patients). Increasing tumor size was found to be associated with LRR (hazard ratio, 1.70; P = .006), whereas other high-risk features were not (all P > .05). Receipt of systemic therapy decreased the LRR rate (hazard ratio, 0.40; P = .03). Although crude LRR rates increased from 3.8% to 9.4% with 1 versus ≥ 4 high-risk features, the number of risk factors was not found to be significantly associated with LRR (P = .54). In the current study, a low crude LRR rate (4.7%) was observed in a large unselected cohort of patients with T1 to T2N0 breast cancer with high-risk features who were treated with mastectomy and systemic therapy without PMRT. Although increasing tumor size and the omission of systemic therapy were found to be predictive, other features did not confer a higher LRR

  12. MR imaging features associated with distant metastasis-free survival of patients with invasive breast cancer: a case-control study.

    Science.gov (United States)

    Song, Sung Eun; Shin, Sung Ui; Moon, Hyeong-Gon; Ryu, Han Suk; Kim, Kwangsoo; Moon, Woo Kyung

    2017-04-01

    Preoperative breast magnetic resonance (MR) imaging features of primary breast cancers may have the potential to act as prognostic biomarkers by providing morphologic and kinetic features representing inter- or intra-tumor heterogeneity. Recent radiogenomic studies reveal that several radiologist-annotated image features are associated with genes or signal pathways involved in tumor progression, treatment resistance, and distant metastasis (DM). We investigate whether preoperative breast MR imaging features are associated with worse DM-free survival in patients with invasive breast cancer. Of the 3536 patients with primary breast cancers who underwent preoperative MR imaging between 2003 and 2009, 147 patients with DM were identified and one-to-one matched with control patients (n = 147) without DM according to clinical-pathologic variables. Three radiologists independently reviewed the MR images of 294 patients, and the association of DM-free survival with MR imaging and clinical-pathologic features was assessed using Cox proportional hazard models. Of MR imaging features, rim enhancement (hazard ratio [HR], 1.83 [95% confidence interval, CI 1.29, 2.51]; p = 0.001) and peritumoral edema (HR, 1.48 [95% CI 1.03, 2.11]; p = 0.032) were the significant features associated with worse DM-free survival. The significant MR imaging features, however, were different between breast cancer subtypes and stages. Preoperative breast MR imaging features of rim enhancement and peritumoral edema may be used as prognostic biomarkers that help predict DM risk in patients with breast cancer, thereby potentially enabling improved personalized treatment and monitoring strategies for individual patients.

  13. Prolonged survival of a female patient with total pelvic exenteration

    Directory of Open Access Journals (Sweden)

    Ignjatović Dragan

    2005-01-01

    Full Text Available Background. To present a female patient who lived 5 years after total pelvic exenteration (TPE. Case report. The female patient underwent TPE due to retrovesicovaginal fistula as a consequence of locoregional irradiation after the operation for the malignoma of the vaginal part of the uterus. In the formation of Bricker conduit, the ureter antireflux was achieved by the application of the “tobacco sack muff” made of the intestines around the ureter. By the use of this technique, the occurrence of pyelonephritis, as the leading cause of death in such patients, was prevented. Conclusion. TPE is a hope for significantly prolonged survival of patients with advanced pelvic malignomas, or with a postirradiatiation fistula.

  14. Survival rate of one-piece dental implants placed with a flapless or flap protocol--a randomized, controlled study: 12-month results.

    Science.gov (United States)

    Froum, Stuart J; Cho, Sang Choon; Elian, Nicholas; Romanos, George; Jalbout, Ziad; Natour, Mazen; Norman, Robert; Neri, Dinah; Tarnow, Dennis P

    2011-01-01

    The purpose of this randomized controlled clinical study was to compare the survival of a one-piece anodically oxidized surface implant when placed with a flapless or flap protocol. Bone loss measurements on radiographs and changes in clinical probing depths 1 year post-definitive restoration placement were recorded and compared. Fifty-two of 60 patients (implants) remained in the study at the 1-year follow-up. At the time of final evaluation, no implant was lost in either group. At the time of placement of the definitive restoration, there was a mean mesial and distal bone gain in both groups compared to bone levels present at the time of implant insertion. There were no significant changes in bone levels between placement of the definitive restoration and those recorded 12 months later, and no significant differences in bone levels between the flap or flapless group at 6 or 12 months were noted. No significant differences were seen either in pocket depth or change in pocket depth at 6 and 12 months in the flapless and flap groups. It was therefore concluded that one-piece anodically oxidized surface implants, 1 year post-definitive restoration insertion, had high survival rates (100%) and stable marginal bone and probing depth levels whether a flapless or flap protocol was used for implant insertion.

  15. Survival of Betta splendens fish (Regan, 1910) in domestic water containers and its effectiveness in controlling Aedes aegypti larvae (Linnaeus, 1762) in Northeast Brazil.

    Science.gov (United States)

    de Oliveira Lima, José Wellington; de Góes Cavalcanti, Luciano Pamplona; Pontes, Ricardo José Soares; Heukelbach, Jörg

    2010-12-01

    In Northeast Brazil, large domestic containers used to store water are important breeding sites of Aedes aegypti, the main vector of dengue fever. The objective of this study was to estimate the survival of Betta splendens (Perciformes: Osphronemidae) fish in domestic containers in Fortaleza (Ceará State), as well as its effectiveness in the control of premature A. aegypti stages. The use of B. splendens was compared to Bacillus thuringiensis israelensis (Bti) in domestic containers. In a first home visit, B. splendens or Bti were applied to water containers. Two follow-up visits were conducted after 3-4 and 5-6 months to assess the presence of viable fish in the containers and infestation by larvae. Betta splendens fish were still present in 97.6% of containers 45-60 days after application. When the fish was present, the infestation rate was significantly higher (P containers, but that appropriate measures should be taken to assure prolonged survival and the presence of fish in the containers. © 2010 Blackwell Publishing Ltd.

  16. Effect of fish oil, arginine, and doxorubicin chemotherapy on remission and survival time for dogs with lymphoma: a double-blind, randomized placebo-controlled study.

    Science.gov (United States)

    Ogilvie, G K; Fettman, M J; Mallinckrodt, C H; Walton, J A; Hansen, R A; Davenport, D J; Gross, K L; Richardson, K L; Rogers, Q; Hand, M S

    2000-04-15

    Polyunsaturated n-3 fatty acids have been shown to inhibit the growth and metastasis of tumors. This double-blind, randomized study was designed to evaluate the hypothesis that polyunsaturated n-3 fatty acids can improve metabolic parameters, decrease chemical indices of inflammation, enhance quality of life, and extend disease free interval and survival time for dogs treated for lymphoblastic lymphoma with doxorubicin chemotherapy. Thirty-two dogs with lymphoma were randomized to receive one of two diets supplemented with menhaden fish oil and arginine (experimental diet) or an otherwise identical diet supplemented with soybean oil (control diet). Diets were fed before and after remission was attained with up to five dosages of doxorubicin. Parameters examined included blood concentrations of glucose, lactic acid, and insulin in response to glucose and diet tolerance tests; alpha-1 acid glycoprotein; tumor necrosis factor; interleukin-6; body weight; amino acid profiles; resting energy expenditure; disease free interval (DFI); survival time (ST); and clinical performance scores. Dogs fed the experimental diet had significantly (P diet tolerance testing. Increasing C22:6 levels were significantly (P dogs with Stage III lymphoma fed the experimental diet. Fatty acids of the n-3 series normalize elevated blood lactic acid in a dose-dependent manner, resulting in an increase in DFI and ST for dogs with lymphoma. Copyright 2000 American Cancer Society.

  17. Duration of adjuvant trastuzumab in HER2 positive breast cancer: Overall and disease free survival results from meta-analyses of randomized controlled trials.

    Science.gov (United States)

    Gyawali, Bishal; Niraula, Saroj

    2017-11-01

    One year of trastuzumab, chosen empirically, improves survival of women with early-stage, HER2-positive breast cancer but also adds substantially to cost, toxicity, and inconvenience. Longer treatment does not improve outcomes, but potentiates toxicities. Medline, Embase, and major conference proceedings were searched systematically in June 2017 to identify Randomized Controlled Trials (RCTs) comparing one year versus shorter durations of trastuzumab in adjuvant treatment of breast cancer. Reported Hazard-Ratios (HR) for Overall Survival (OS) and Disease-Free Survival (DFS), and Odds-Ratio for cardiac events, with respective 95% Confidence Intervals (CI) from each study was weighted using generic inverse-variance, and pooled in a meta-analysis. Inter-study heterogeneity and sub-group difference (based on hormone-receptors and node-positivity) were assessed using I 2 , and chi 2 statistics, respectively. Four studies (n=7614) satisfied inclusion criteria. Individual RCTs had diverse pre-specified upper-limits of 95% CI for declaring non-inferiority (range: <1.15 to <1.53). Pooled results demonstrated significant improvements in OS (HR 1.28, p=0.04), and DFS (HR 1.24, p=0.005) with 1year of trastuzumab compared to shorter durations. Absence of multiplicity argument allowed for declaring superiority of 1year of trastuzumab based on our results despite non-inferiority designs of individual trials. No influence on overall effect by duration of trastuzumab in experimental arm (9weeks versus 6months) was noted. No statistical interaction by hormone-receptor status and node-positivity on overall results was noticed [p(sub-group difference) 0.73, and 0.52, respectively]. Odds-Ratio for cardiac events was 2.65 (p<0.001) favoring shorter duration. One year of trastuzumab prolongs overall, and disease-free survivals in women with early-stage HER2 positive breast cancer compared to shorter durations and this should remain as the standard of care. Cardiotoxicity increased

  18. Innovations’ Survival

    Directory of Open Access Journals (Sweden)

    Jakub Tabas

    2016-01-01

    Full Text Available Innovations currently represent a tool of maintaining the going concern of a business entity and its competitiveness. However, effects of innovations are not infinite and if an innovation should constantly preserve a life of business entity, it has to be a continual chain of innovations, i.e. continual process. Effective live of a single innovation is limited while the limitation is derived especially from industry. The paper provides the results of research on innovations effects in the financial performance of small and medium-sized enterprises in the Czech Republic. Objective of this paper is to determine the length and intensity of the effects of technical innovations in company’s financial performance. The economic effect of innovations has been measured at application of company’s gross production power while the Deviation Analysis has been applied for three years’ time series. Subsequently the Survival Analysis has been applied. The analyses are elaborated for three statistical samples of SMEs constructed in accordance to the industry. The results obtained show significant differences in innovations’ survival within these three samples of enterprises then. The results are quite specific for the industries, and are confronted and discussed with the results of authors’ former research on the issue.

  19. TREATMENT OPTIONS FOR LOCOREGIONAL RECURRENCES OF ORAL AND OROPHARYNGEAL MUCOSAL SQUAMOUS CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    I. A. Zaderenko

    2014-01-01

    Full Text Available The study included 314 patients with recurrent squamous cell carcinoma of the oral cavity and oropharynx after radical treatment. Patients were divided into groups depending on the timing – patients with early recurrence (n = 162, and late recurrence (n = 152 , and depending on the type of treatment of recurrent tumors: conservative treatment group (n = 56 , surgical (n = 235 and combined treatment (n = 23 group. A comparative evaluation of the effectiveness of the treatment of these patients based on the results of treatment, survival rates, the frequency and severity of complications. The conservative therapy of recurrent tumors of the oral cavity if surgical treatment is impossible is effective, especially in cases of late recurrent tumors but only surgical or combined treatment may reach the five-year survival rate in patients with recurrent tumor, cancer of the oral cavity and oropharynx.

  20. Adaptive and innovative Radiation Treatment FOR improving Cancer treatment outcomE (ARTFORCE); a randomized controlled phase II trial for individualized treatment of head and neck cancer.

    Science.gov (United States)

    Heukelom, Jolien; Hamming, Olga; Bartelink, Harry; Hoebers, Frank; Giralt, Jordi; Herlestam, Teresa; Verheij, Marcel; van den Brekel, Michiel; Vogel, Wouter; Slevin, Nick; Deutsch, Eric; Sonke, Jan-Jakob; Lambin, Philippe; Rasch, Coen

    2013-02-22

    Failure of locoregional control is the main cause of recurrence in advanced head and neck cancer. This multi-center trial aims to improve outcome in two ways. Firstly, by redistribution of the radiation dose to the metabolically most FDG-PET avid part of the tumour. Hereby, a biologically more effective dose distribution might be achieved while simultaneously sparing normal tissues. Secondly, by improving patient selection. Both cisplatin and Epidermal Growth Factor Receptor (EGFR) antibodies like Cetuximab in combination with Radiotherapy (RT) are effective in enhancing tumour response. However, it is unknown which patients will benefit from either agent in combination with irradiation. We will analyze the predictive value of biological markers and (89)Zr-Cetuximab uptake for treatment outcome of chemoradiation with Cetuximab or cisplatin to improve patient selection. ARTFORCE is a randomized phase II trial for 268 patients with a factorial 2 by 2 design: cisplatin versus Cetuximab and standard RT versus redistributed RT. Cisplatin is dosed weekly 40 mg/m(2) for 6 weeks. Cetuximab is dosed 250 mg/m(2) weekly (loading dose 400 mg/m(2)) for 6 weeks. The standard RT regimen consists of elective RT up to 54.25 Gy with a simultaneous integrated boost (SIB) to 70 Gy in 35 fractions in 6 weeks. Redistributed adaptive RT consists of elective RT up to 54.25 Gy with a SIB between 64-80 Gy in 35 fractions in 6 weeks with redistributed dose to the gross tumour volume (GTV) and clinical target volume (CTV), and adaptation of treatment for anatomical changes in the third week of treatment.Patients with locally advanced, biopsy confirmed squamous cell carcinoma of the oropharynx, oral cavity or hypopharynx are eligible.Primary endpoints are: locoregional recurrence free survival at 2 years, correlation of the median (89)Zr-cetuximab uptake and biological markers with treatment specific outcome, and toxicity. Secondary endpoints are quality of life, swallowing function

  1. Local control and survival in patients with soft tissue sarcomas treated with limb sparing surgery in combination with interstitial brachytherapy and external radiation

    DEFF Research Database (Denmark)

    Muhic, A.; Hovgaard, D.; Mork, Petersen M.

    2008-01-01

    %. Nineteen (49%) patients suffered from some degree of decreased force or function of the affected extremity, 16 (41%) suffered from oedema, 12 (31%) had persistent pain, 8 (21%) suffered from wound complications, and in 4 (10%) of these patients plastic surgery were required. CONCLUSION: Limb sparing......PURPOSE: The purpose of this study was to evaluate local control, survival and complication rate after treatment of soft tissue sarcoma (STS) with limb-sparing surgery combined with pulsed-dose rate (PDR) interstitial brachytherapy (BRT) and external beam radiotherapy (EBRT). PATIENTS AND METHODS......: A retrospective review of 39 adult patients (female/male=25/14, mean age 51(range 21-78) years) with STS who underwent primary limb-sparing surgery combined with PDR BRT (20Gy) and additional post-operative EBRT (50Gy) during the years 1995-2004. RESULTS: Five patients developed local recurrence after a mean...

  2. Use of N-acetylcysteine during liver procurement: a prospective randomized controlled study.

    Science.gov (United States)

    D'Amico, Francesco; Vitale, Alessandro; Piovan, Donatella; Bertacco, Alessandra; Ramirez Morales, Rafael; Chiara Frigo, Anna; Bassi, Domenico; Bonsignore, Pasquale; Gringeri, Enrico; Valmasoni, Michele; Garbo, Greta; Lodo, Enrico; D'Amico, Francesco Enrico; Scopelliti, Michele; Carraro, Amedeo; Gambato, Martina; Brolese, Alberto; Zanus, Giacomo; Neri, Daniele; Cillo, Umberto

    2013-02-01

    Antioxidant agents have the potential to reduce ischemia/reperfusion damage to organs for liver transplantation (LT). In this prospective, randomized study, we tested the impact of an infusion of N-acetylcysteine (NAC) during liver procurement on post-LT outcomes. Between December 2006 and July 2009, 140 grafts were transplanted into adult candidates with chronic liver disease who were listed for first LT, and according to a sequential, closed-envelope, single-blinded procedure, these patients were randomly assigned in a 1/1 ratio to an NAC protocol (69 patients) or to the standard protocol without NAC [71 patients (the control group)]. The NAC protocol included a systemic NAC infusion (30 mg/kg) 1 hour before the beginning of liver procurement and a locoregional NAC infusion (300 mg through the portal vein) just before cross-clamping. The primary endpoint was graft survival. The graft survival rates at 3 and 12 months were 93% and 90%, respectively, in the NAC group and 82% and 70%, respectively, in the control group (P = 0.02). An adjusted Cox analysis showed a significant NAC effect on graft survival at both 3 months [hazard ratio = 1.65, 95% confidence interval (CI) = 1.01-2.93, P = 0.04] and 12 months (hazard ratio = 1.73, 95% CI = 1.14-2.76, P ≤ 0.01). The incidence of postoperative complications was lower in the NAC group (23%) versus the control group (51%, P 1.8), the incidence of primary dysfunction of the liver was lower (P = 0.09) for the NAC group (15%) versus the control group (32%). In conclusion, the NAC harvesting protocol significantly improves graft survival. The effect of NAC on early graft function and survival seems higher when suboptimal grafts are used. Copyright © 2012 American Association for the Study of Liver Diseases.

  3. B-cell receptor-associated protein 31 regulates human embryonic stem cell adhesion, stemness, and survival via control of epithelial cell adhesion molecule.

    Science.gov (United States)

    Kim, Won-Tae; Seo Choi, Hong; Min Lee, Hyun; Jang, Young-Joo; Ryu, Chun Jeih

    2014-10-01

    B-Cell receptor-associated protein 31 (BAP31) regulates the export of secreted membrane proteins from the endoplasmic reticulum (ER) to the downstream secretory pathway. Previously, we generated a monoclonal antibody 297-D4 against the surface molecule on undifferentiated human embryonic stem cells (hESCs). Here, we found that 297-D4 antigen was localized to pluripotent hESCs and downregulated during early differentiation of hESCs and identified that the antigen target of 297-D4 was BAP31 on the hESC-surface. To investigate the functional role of BAP31 in hESCs, BAP31 expression was knocked down by small interfering RNA. BAP31 depletion impaired hESC self-renewal and pluripotency and drove hESC differentiation into multicell lineages. BAP31 depletion hindered hESC proliferation by arresting cell cycle at G0/G1 phase and inducing caspase-independent cell death. Interestingly, BAP31 depletion reduced hESC adhesion to extracellular matrix (ECM). Analysis of cell surface molecules showed decreased expression of epithelial cell adhesion molecule (EpCAM) in BAP31-depleted hESCs, while ectopic expression of BAP31 elevated the expression of EpCAM. EpCAM depletion also reduced hESC adhesion to ECM, arrested cell cycle at G0/G1 phase and induced cell death, producing similar effects to those of BAP31 depletion. BAP31 and EpCAM were physically associated and colocalized at the ER and cell surface. Both BAP31 and EpCAM depletion decreased cyclin D1 and E expression and suppressed PI3K/Akt signaling, suggesting that BAP31 regulates hESC stemness and survival via control of EpCAM expression. These findings provide, for the first time, mechanistic insights into how BAP31 regulates hESC stemness and survival via control of EpCAM expression. © 2014 AlphaMed Press.

  4. Image guided brachytherapy in locally advanced cervical cancer: Improved pelvic control and survival in RetroEMBRACE, a multicenter cohort study.

    Science.gov (United States)

    Sturdza, Alina; Pötter, Richard; Fokdal, Lars Ulrik; Haie-Meder, Christine; Tan, Li Tee; Mazeron, Renaud; Petric, Primoz; Šegedin, Barbara; Jurgenliemk-Schulz, Ina Maria; Nomden, Christel; Gillham, Charles; McArdle, Orla; Van Limbergen, Erik; Janssen, Hilde; Hoskin, Peter; Lowe, Gerry; Tharavichitkul, Ekkasit; Villafranca, Elena; Mahantshetty, Umesh; Georg, Petra; Kirchheiner, Kathrin; Kirisits, Christian; Tanderup, Kari; Lindegaard, Jacob Christian

    2016-09-01

    Image guided brachytherapy (IGBT) for locally advanced cervical cancer allows dose escalation to the high-risk clinical target volume (HRCTV) while sparing organs at risk (OAR). This is the first comprehensive report on clinical outcome in a large multi-institutional cohort. From twelve centres 731 patients, treated with definitive EBRT±concurrent chemotherapy followed by IGBT, were analysed. Kaplan-Meier estimates at 3/5years were calculated for local control (LC, primary endpoint), pelvic control (PC), overall survival (OS), cancer specific survival (CSS). In 610 patients, G3-4 late toxicity (CTCAEv3.0) was reported. Median follow up was 43months, percent of patients per FIGO stage IA/IB/IIA 22.8%, IIB 50.4%, IIIA-IVB 26.8%. 84.8% had squamous cell carcinomas; 40.5% lymph node involvement. Mean EBRT dose was 46±2.5Gy; 77.4% received concurrent chemotherapy. Mean D90 HRCTV was 87±15Gy (EQD2 10 ), mean D2cc was: bladder 81±22Gy, rectum 64±9Gy, sigmoid 66±10Gy and bowel 64±9Gy (all EQD2 3 ). The 3/5-year actuarial LC, PC, CSS, OS were 91%/89%, 87%/84%, 79%/73%, 74%/65%. Actuarial LC at 3/5years for IB, IIB, IIIB was 98%/98%, 93%/91%, 79%/75%. Actuarial PC at 3/5years for IB, IIB, IIIB was 96%/96%, 89%/87%, 73%/67%. Actuarial 5-year G3-G5 morbidity was 5%, 7%, 5% for bladder, gastrointestinal tract, vagina. IGBT combined with radio-chemotherapy leads to excellent LC (91%), PC (87%), OS (74%), CSS (79%) with limited severe morbidity. Copyright © 2016. Published by Elsevier Ireland Ltd.

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

    Energy Technology Data Exchange (ETDEWEB)

    Eaton, Bree R.; Esiashvili, Natia [Departments of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, Georgia (United States); Kim, Sungjin [Department of Biostatistics and Bioinformatics, Cedars-Sinai Medical Center, Los Angeles, California (United States); Weyman, Elizabeth A.; Thornton, Lauren T. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Mazewski, Claire; MacDonald, Tobey [Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Atlanta, Georgia (United States); Ebb, David [Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts (United States); MacDonald, Shannon M.; Tarbell, Nancy J. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Yock, Torunn I., E-mail: tyock@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2016-01-01

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

  6. Surviving and thriving with cancer using a Web-based health behavior change intervention: randomized controlled trial.

    Science.gov (United States)

    Bantum, Erin O'Carrol; Albright, Cheryl L; White, Kami K; Berenberg, Jeffrey L; Layi, Gabriela; Ritter, Phillip L; Laurent, Diana; Plant, Katy; Lorig, Kate

    2014-02-24

    Given the substantial improvements in cancer screening and cancer treatment in the United States, millions of adult cancer survivors live for years following their initial cancer diagnosis and treatment. However, latent side effects can occur and some symptoms can be alleviated or managed effectively via changes in lifestyle behaviors. The purpose of this study was to test the effectiveness of a six-week Web-based multiple health behavior change program for adult survivors. Participants (n=352) were recruited from oncology clinics, a tumor registry, as well as through online mechanisms, such as Facebook and the Association of Cancer Online Resources (ACOR). Cancer survivors were eligible if they had completed their primary cancer treatment from 4 weeks to 5 years before enrollment. Participants were randomly assigned to the Web-based program or a delayed-treatment control condition. In total, 303 survivors completed the follow-up survey (six months after completion of the baseline survey) and participants in the Web-based intervention condition had significantly greater reductions in insomnia and greater increases in minutes per week of vigorous exercise and stretching compared to controls. There were no significant changes in fruit and vegetable consumption or other outcomes. The Web-based intervention impacted insomnia and exercise; however, a majority of the sample met or exceeded national recommendations for health behaviors and were not suffering from depression or fatigue at baseline. Thus, the survivors were very healthy and well-adjusted upon entry and their ability to make substantial health behavior changes may have been limited. Future work is discussed, with emphasis placed on ways in which Web-based interventions can be more specifically analyzed for benefit, such as in regard to social networking. Clinicaltrials.gov NCT00962494; http://www.clinicaltrials.gov/ct2/show/NCT00962494 (Archived by WebCite at http://www.webcitation.org/6NIv8Dc6Q).

  7. Survival outcome of malignant minor salivary tumors in Pakistani population

    Directory of Open Access Journals (Sweden)

    Hassan Iqbal

    2014-01-01

    Full Text Available Objective: Malignant tumors of minor salivary glands (MSG are rare. Survival outcome in Pakistani population with malignant MSG tumors remains to be defined. The objective of this study was to report the clinical presentation, treatment modalities, and survival outcome of radically treated malignant tumors of MSG in Pakistani population. Materials and Methods: Between April 2003 and March 2011, 45 patients with malignant tumors of MSG were treated at Shaukat Khanum Cancer Hospital and included in the study. Patient characteristics and treatment modalities were assessed and local, regional, and distant failures determined. Relapse-free (RFS and overall survival (OS was calculated using Kaplan-Meier curves, and log-rank test was used to determine significance. Results: Median age was 40 (17-83 years. Male to female ratio was 1.25:1. Most common site was hard palate in 31 (69% patients. Adenoid cystic carcinoma (51% was the most common histological diagnosis. Nine patients (20% underwent surgery as the only treatment modality, six patients received (13% radiotherapy alone, and 30 patients (67% had surgery followed by adjuvant radiotherapy. Eight patients developed recurrence (four local, two regional, one locoregional, and one distant. The 5-year actuarial overall OS and RFS was 77 and 66%, respectively. Age, T-stage, and treatment modality were significant for RFS, whereas T-stage and treatment modality were significant factors for OS. Conclusion: Surgery as single modality or combined with radiation therapy resulted in acceptable survival in Pakistani population with malignant minor salivary tumors.

  8. Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre, randomised trial.

    Science.gov (United States)

    Baud, Olivier; Maury, Laure; Lebail, Florence; Ramful, Duksha; El Moussawi, Fatima; Nicaise, Claire; Zupan-Simunek, Véronique; Coursol, Anne; Beuchée, Alain; Bolot, Pascal; Andrini, Pierre; Mohamed, Damir; Alberti, Corinne

    2016-04-30

    Bronchopulmonary dysplasia, a major complication of extreme prematurity, has few treatment options. Postnatal steroid use is controversial, but low-dose hydrocortisone might prevent the harmful effects of inflammation on the developing lung. In this study, we aimed to assess whether low-dose hydrocortisone improved survival without bronchopulmonary dysplasia in extremely preterm infants. In this double-blind, placebo-controlled, randomised trial done at 21 French tertiary-care neonatal intensive care units (NICUs), we randomly assigned (1:1), via a secure study website, extremely preterm infants inborn (born in a maternity ward at the same site as the NICU) at less than 28 weeks of gestation to receive either intravenous low-dose hydrocortisone or placebo during the first 10 postnatal days. Infants randomly assigned to the hydrocortisone group received 1 mg/kg of hydrocortisone hemisuccinate per day divided into two doses per day for 7 days, followed by one dose of 0·5 mg/kg per day for 3 days. Randomisation was stratified by gestational age and all infants were enrolled by 24 h after birth. Study investigators, parents, and patients were masked to treatment allocation. The primary outcome was survival without bronchopulmonary dysplasia at 36 weeks of postmenstrual age. We used a sequential analytical design, based on intention to treat, to avoid prolonging the trial after either efficacy or futility had been established. This trial is registered with ClinicalTrial.gov, number NCT00623740. 1072 neonates were screened between May 25, 2008, and Jan 31, 2014, of which 523 were randomly assigned (256 hydrocortisone, 267 placebo). 255 infants on hydrocortisone and 266 on placebo were included in analyses after parents withdrew consent for one child in each group. Of the 255 infants assigned to hydrocortisone, 153 (60%) survived without bronchopulmonary dysplasia, compared with 136 (51%) of 266 infants assigned to placebo (odds ratio [OR] adjusted for gestational age

  9. Standard versus atrial fibrillation-specific management strategy (SAFETY) to reduce recurrent admission and prolong survival: pragmatic, multicentre, randomised controlled trial.

    Science.gov (United States)

    Stewart, Simon; Ball, Jocasta; Horowitz, John D; Marwick, Thomas H; Mahadevan, Gnanadevan; Wong, Chiew; Abhayaratna, Walter P; Chan, Yih K; Esterman, Adrian; Thompson, David R; Scuffham, Paul A; Carrington, Melinda J

    2015-02-28

    Patients are increasingly being admitted with chronic atrial fibrillation, and disease-specific management might reduce recurrent admissions and prolong survival. However, evidence is scant to support the application of this therapeutic approach. We aimed to assess SAFETY--a management strategy that is specific to atrial fibrillation. We did a pragmatic, multicentre, randomised controlled trial in patients admitted with chronic, non-valvular atrial fibrillation (but not heart failure). Patients were recruited from three tertiary referral hospitals in Australia. 335 participants were randomly assigned by computer-generated schedule (stratified for rhythm or rate control) to either standard management (n=167) or the SAFETY intervention (n=168). Standard management consisted of routine primary care and hospital outpatient follow-up. The SAFETY intervention comprised a home visit and Holter monitoring 7-14 days after discharge by a cardiac nurse with prolonged follow-up and multidisciplinary support as needed. Clinical reviews were undertaken at 12 and 24 months (minimum follow-up). Coprimary outcomes were death or unplanned readmission (both all-cause), measured as event-free survival and the proportion of actual versus maximum days alive and out of hospital. Analyses were done on an intention-to-treat basis. The trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTRN 12610000221055). During median follow-up of 905 days (IQR 773-1050), 49 people died and 987 unplanned admissions were recorded (totalling 5530 days in hospital). 127 (76%) patients assigned to the SAFETY intervention died or had an unplanned readmission (median event-free survival 183 days [IQR 116-409]) and 137 (82%) people allocated standard management achieved a coprimary outcome (199 days [116-249]; hazard ratio 0·97, 95% CI 0·76-1·23; p=0·851). Patients assigned to the SAFETY intervention had 99·5% maximum event-free days (95% CI 99·3-99·7), equating to a median

  10. Induction chemotherapy with paclitaxel and cisplatin to concurrent radiotherapy and weekly paclitaxel in the treatment of loco-regionally advanced, stage IV (M0, head and neck squamous cell carcinoma. Mature results of a prospective study

    Directory of Open Access Journals (Sweden)

    Pergolizzi Stefano

    2011-11-01

    Full Text Available Abstract Background to evaluate activity and toxicity of a sequential treatment in advanced, non metastatic, mostly unresectable, head and neck squamous cell carcinoma. Methods Patients with loco-regionally advanced or unresectable, head and neck cancer, were prospectively treated with 3 courses of induction chemotherapy followed by concurrent chemoradiation. Induction chemotherapy consisted of paclitaxel 175 mg/m2 day 1 and cisplatin 75 mg/m2 day 2, given every 3 weeks, to a total of three courses. Curative radiotherapy started 4 weeks after the last cycle of chemotherapy with the goal of delivering a total dose ≥ 66 Gy. During RT weekly paclitaxel (40 mg/m2 was administered. Results The trial accrued 43 patients from January 1999 to December 2002. All patients received 3 courses of induction chemotherapy and the planned dose of radiotherapy. Thirty-eight patients were able to tolerate weekly paclitaxel during irradiation at least for 4 courses. After induction therapy there were 32 overall responses, 74.4% (23 partial and 9 complete; at completion of concomitant treatment overall responses were 42, 97.7% (20 partial and 22 complete. Median time to treatment failure was 20 months and the disease progression rate at 3 and 5 years was 33% and 23%, respectively. The median overall survival time was 24 months and 3 and 5 years overall survival rates were 37% and 26%, respectively. The major toxicity was mucositis. Conclusions This combined treatment was found to be feasible and active in advanced or unresectable, head and neck squamous cell carcinoma patients. Long-term results observed in this trial encourage to consider this approach in further investigation using newer radiation delivering technique and new molecularly agents.

  11. KINET: a social marketing programme of treated nets and net treatment for malaria control in Tanzania, with evaluation of child health and long-term survival.

    Science.gov (United States)

    Schellenberg, J R; Abdulla, S; Minja, H; Nathan, R; Mukasa, O; Marchant, T; Mponda, H; Kikumbih, N; Lyimo, E; Manchester, T; Tanner, M; Lengeler, C

    1999-01-01

    We present a large-scale social marketing programme of insecticide-treated nets in 2 rural districts in southwestern Tanzania (population 350,000) and describe how the long-term child health and survival impact will be assessed. Formative and market research were conducted in order to understand community perceptions, knowledge, attitudes and practice with respect to the products to be socially marketed. We identified Zuia Mbu (Kiswahili for 'prevent mosquitoes') as a suitable brand name for both treated nets and single-dose insecticide treatment sachets. A mix of public and private sales outlets is used for distribution. In the first stage of a stepped introduction 31 net agents were appointed and trained in 18 villages: 15 were shop owners, 14 were village leaders, 1 was a parish priest and 1 a health worker. For net treatment 37 young people were appointed in the same villages and trained as agents. Further institutions in both districts such as hospitals, development projects and employers were also involved in distribution. Promotion for both products was intense and used a variety of channels. A total of 22,410 nets and 8072 treatments were sold during the first year: 18 months after launching, 46% of 312 families with children aged under 5 years reported that their children were sleeping under treated nets. A strong evaluation component in over 50,000 people allows assessment of the long-term effects of insecticide-treated nets on child health and survival, anaemia in pregnancy, and the costs of the intervention. This evaluation is based on cross-sectional surveys, and case-control and cohort studies.

  12. Impact of insecticides used to control Spodoptera frugiperda (J.E. Smith in corn on survival, sex ratio, and reproduction of Trichogramma pretiosum Riley offspring

    Directory of Open Access Journals (Sweden)

    Jander R Souza

    2013-06-01

    Full Text Available Corn (Zea mays L. is cultivated in large areas and considered one of the world's major cereal crops. There are several arthropod pests that can reduce its production such as the fall armyworm, Spodoptera frugiperda (J.E. Smith (Lep.: Noctuidae, which is considered to be the main pest for corn. Fall armyworm is primarily controlled by insecticides. The use of biological control agents to manage this pest is growing with an emphasis on the egg parasitoid Trichogramma pretiosum Riley (Hym.: Trichogrammatidae. Thus, the aim of this research was to evaluate the impact of the following insecticides (g ai L-1 beta-cypermethrin (0.03, chlorfenapyr (0.60, chlorpyrifos (0.96, spinosad (0.16, etofenprox (0.10, triflumuron (0.08, alfa-cypermethrin/teflubenzuron (0.0425/0.0425, and lambda-cyhalothrin/thiamethoxam (0.11/0.083 on survival, sex ratio, reproduction, and T. pretiosum offspring. Distilled water was used as a control. Commercial insecticide formulations were diluted in distilled water. Bioassays used Anagasta kuehniella eggs treated with insecticides which were afterwards exposed to parasitism. Bioassays were conducted under controlled conditions at 25 ± 2 °C, 70 ± 10% RH, and 12:12 h photoperiod. Alfa-cypermethrin/teflubenzuron, beta-cypermethrin, chlorpyrifos, chlorfenapyr, spinosad, etofenprox, and lambda-cyhalothrin/thiamethoxam reduced parasitism capacity of maternal generation females as well as the percentage of insect emergence from the F1 generation. Only triflumuron was selective for T. pretiosum and can be recommended along with this parasitoid in fall armyworm management programs in corn.

  13. Preoperative nutritional status is an important predictor of survival in patients undergoing surgery for renal cell carcinoma.

    Science.gov (United States)

    Morgan, Todd M; Tang, Dominic; Stratton, Kelly L; Barocas, Daniel A; Anderson, Christopher B; Gregg, Justin R; Chang, Sam S; Cookson, Michael S; Herrell, S Duke; Smith, Joseph A; Clark, Peter E

    2011-06-01

    The role of malnutrition has not been well studied in patients undergoing surgery for renal cell carcinoma (RCC). Our aim was to evaluate whether nutritional deficiency (ND) is an important determinant of survival following surgery for RCC. A total of 369 consecutive patients underwent surgery for locoregional RCC from 2003 to 2008. ND was defined as meeting one of the following criteria: body mass index nutritional status preoperatively and counsel patients appropriately. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  14. Locoregional Prostate Cancer Treatment Pattern Variation in Independent Cancer Centers: Policy Effect, Patient Preference, or Physician Incentive?

    Directory of Open Access Journals (Sweden)

    Andrew S. Camarata

    2015-01-01

    Full Text Available Surveillance, Epidemiologic, and End Results (SEER registry data abstracted from a priority 2 or higher reporting source from 2006 to 2008 were used to compare treatment patterns in 45–64-year old men diagnosed with locoregional prostate cancer (LRPC across states with or without radiation therapy-directed certificate of need (CON laws and across independent cancer centers (ICCs compared to large multi-specialty groups (LMSGs. Adjusted treatment percentages for the five most common LRPC treatments (surgery, external beam radiation therapy (EBRT, combination brachytherapy with EBRT, brachytherapy, and observation were compared using cross-sectional logistic regression between CON-unregulated and -regulated states and between LMSGs and ICCs. LRPC EBRT rates were no different across CON regions, but are increased in ICCs compared to LMSGs (37.00% vs. 13.23%, P < 0.001. Variation in LRPC treatment patterns by reporting source merits further scrutiny under the Affordable Care Act of 2010, considering the intent of incentivized accountable care organizations (ACOs established by the Patient Protection and Affordable Care Act of 2010 (PPACA and the implications of early descriptions of these new healthcare provider organizations on prostate cancer treatment patterns.

  15. Diuretic {sup 18}F-FDG PET/CT imaging for detection and locoregional staging of urinary bladder cancer: prospective evaluation of a novel technique

    Energy Technology Data Exchange (ETDEWEB)

    Nayak, Brusabhanu; Dogra, Prem Nath [All India Institute of Medical Sciences, Department of Urology, New Delhi (India); Naswa, Niraj [All India Institute of Medical Sciences, Department of Nuclear Medicine, New Delhi (India); Kumar, Rakesh [All India Institute of Medical Sciences, Department of Nuclear Medicine, New Delhi (India); New Delhi (India)

    2013-03-15

    Positron emission tomography/computed tomography (PET/CT) with {sup 18}F-fluorodeoxyglucose (FDG) has been used with limited success in the past in primary diagnosis and locoregional staging of urinary bladder cancer, mainly because of the pharmacokinetics of renal excretion of {sup 18}F-FDG. In the present prospective study, we have evaluated the potential application of diuretic {sup 18}F-FDG PET/CT in improving detection and locoregional staging of urinary bladder tumours. Twenty-five patients suspected of having primary carcinoma of the urinary bladder were evaluated prospectively for diagnosis and staging. All of these 25 patients underwent conventional contrast-enhanced computed tomography (CECT) of the abdomen/pelvis and whole-body diuretic {sup 18}F-FDG PET/CT. In addition, pelvic PET/CT images were obtained using the special technique of forced diuresis using intravenous furosemide (20-40 mg). Of the 25 patients, 10 underwent radical cystectomy and 15 underwent transurethral resection of the bladder tumour (TURBT). Results of CECT and diuretic {sup 18}F-FDG PET/CT were compared considering histopathology as a reference standard. Of the 25 patients, CECT detected a primary tumour in 23 (sensitivity 92 %), while {sup 18}F-FDG PET/CT was positive in 24 patients (sensitivity 96 %). Mean size and maximum standardized uptake value of the bladder tumours were 3.33 cm (range 1.6-6.2) and 5.3 (range 1.3-11.7), respectively. Of the 25 patients, only 10 patients underwent radical cystectomy based on disease status on TURBT. Among those ten patients, nine had locoregional metastases. Among the nine patients who had positive lymph nodes for metastasis on histopathology, CECT and PET/CT scan had a sensitivity of 44 and 78 %, respectively. {sup 18}F-FDG PET/CT was found to be superior to CECT in the detection of the primary tumour and locoregional staging (p < 0.05). Diuretic {sup 18}F-FDG PET/CT is highly sensitive and specific and plays an important role in improving

  16. The impact of prenatal vitamin A and zinc supplementation on birth size and neonatal survival - a double-blind, randomized controlled trial in a rural area of Indonesia.

    Science.gov (United States)

    Prawirohartono, Endy P; Nyström, Lennarth; Nurdiati, Detty S; Hakimi, Mohammad; Lind, Torbjörn

    2013-01-01

    Prenatal supplementation with micronutrients may increase birth weight and thus improve infant health and survival in settings where infants and children are at risk of micronutrient deficiencies. To assess whether vitamin A and/or zinc supplementation given during pregnancy can improve birth weight, birth length, neonatal morbidity, or infant mortality. A double-blind, randomized controlled trial supplementing women (n = 2173) in Central Java, Indonesia throughout pregnancy with vitamin A, zinc, combined vitamin A+zinc, or placebo. Out of 2173 supplemented pregnant women, 1956 neonates could be evaluated. Overall, zinc supplementation improved birth length compared to placebo or combined vitamin A+zinc (48.8 vs. 48.5 cm, p = 0.04); vitamin A supplementation improved birth length compared to placebo or combined vitamin A+zinc (48.7 vs. 48.2 cm, p = 0.04). These effects remained after adjusting for maternal height, pre-pregnancy weight, and parity. There was no effect of supplementation on birth weight, the proportion of low birth weight, neonatal morbidity, or mortality. Prenatal zinc or vitamin A supplementation demonstrates a small but significant effect on birth length, but supplementation with zinc, vitamin A or a combination of zinc and vitamin A, have no effect on birth weight, neonatal morbidity, or mortality.

  17. Patterns of care and the survival of elderly patients with high-risk endometrial cancer: A case-control study from the FRANCOGYN group.

    Science.gov (United States)

    Rousselin, A; Bendifallah, S; Nyangoh Timoh, K; Ouldamer, L; Canlorbe, G; Raimond, E; Hudry, N; Coutant, C; Graesslin, O; Touboul, C; Collinet, P; Bricou, A; Huchon, C; Daraï, E; Ballester, M; Levêque, J; Lavoue, V

    2017-11-01

    The standard of care of endometrial cancer involves complex procedures such as pelvic and para-aortic lymphadenectomy and omentectomy, particularly for high-risk endometrial cancer. Few data are available about these complex surgical procedures and adjuvant therapy in elderly women. We aim to examine treatment and survival of elderly women diagnosed with high-risk endometrial cancer. We performed a case-control study of women diagnosed between 2001 and 2013 with high-risk endometrial cancers. Women older than 70 years (n = 198) were compared with patients Elderly patients had lymphadenectomies less frequently compared with younger patients (76% vs 96%, p elderly women had 57% increased risk of recurrence (hazard ratio 1.57, 95% CI 1.04-2.39) compared with younger patients. Although we found an independently significant lower DFS in elderly patients with high-risk endometrial cancer when compared with young patients, elderly women are less likely to be treated with lymphadenectomy and chemotherapy. Specific guidelines for management of elderly patients with high-risk endometrial cancer are required to improve their prognosis. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  18. Survival with Newly Diagnosed Metastatic Prostate Cancer in the "Docetaxel Era": Data from 917 Patients in the Control Arm of the STAMPEDE Trial (MRC PR08, CRUK/06/019).

    Science.gov (United States)

    James, Nicholas David; Spears, Melissa R; Clarke, Noel W; Dearnaley, David P; De Bono, Johann S; Gale, Joanna; Hetherington, John; Hoskin, Peter J; Jones, Robert J; Laing, Robert; Lester, Jason F; McLaren, Duncan; Parker, Christopher C; Parmar, Mahesh K B; Ritchie, Alastair W S; Russell, J Martin; Strebel, Räto T; Thalmann, George N; Mason, Malcolm D; Sydes, Matthew R

    2015-06-01

    Prostate cancer (PCa) is the second most common disease among men worldwide. It is important to know survival outcomes and prognostic factors for this disease. Recruitment for the largest therapeutic randomised controlled trial in PCa--the Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy: A Multi-Stage Multi-Arm Randomised Controlled Trial (STAMPEDE)--includes men with newly diagnosed metastatic PCa who are commencing long-term androgen deprivation therapy (ADT); the control arm provides valuable data for a prospective cohort. Describe survival outcomes, along with current treatment standards and factors associated with prognosis, to inform future trial design in this patient group. STAMPEDE trial control arm comprising men newly diagnosed with M1 disease who were recruited between October 2005 and January 2014. Overall survival (OS) and failure-free survival (FFS) were reported by primary disease characteristics using Kaplan-Meier methods. Hazard ratios and 95% confidence intervals (CIs) were derived from multivariate Cox models. A cohort of 917 men with newly diagnosed M1 disease was recruited to the control arm in the specified interval. Median follow-up was 20 mo. Median age at randomisation was 66 yr (interquartile range [IQR]: 61-71), and median prostate-specific antigen level was 112 ng/ml (IQR: 34-373). Most men (n=574; 62%) had bone-only metastases, whereas 237 (26%) had both bone and soft tissue metastases; soft tissue metastasis was found mainly in distant lymph nodes. There were 238 deaths, 202 (85%) from PCa. Median FFS was 11 mo; 2-yr FFS was 29% (95% CI, 25-33). Median OS was 42 mo; 2-yr OS was 72% (95% CI, 68-76). Survival time was influenced by performance status, age, Gleason score, and metastases distribution. Median survival after FFS event was 22 mo. Trial eligibility criteria meant men were younger and fitter than general PCa population. Survival remains disappointing in men presenting with M1 disease

  19. Comparative efficacy, tolerability, and survival outcomes of various radiopharmaceuticals in castration-resistant prostate cancer with bone metastasis: a meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Tunio M

    2015-09-01

    Full Text Available Mutahir Tunio,1 Mushabbab Al Asiri,1 Abdulrehman Al Hadab,1 Yasser Bayoumi2 1Radiation Oncology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia; 2Radiation Oncology, National Cancer Institute, Cairo University, Cairo, Egypt Background: A meta-analysis was conducted to assess the impact of radiopharmaceuticals (RPs in castration-resistant prostate cancer (CRPC on pain control, symptomatic skeletal events (SSEs, toxicity profile, quality of life (QoL, and overall survival (OS.Materials and methods: The PubMed/MEDLINE, CANCERLIT, EMBASE, Cochrane Library database, and other search engines were searched to identify randomized controlled trials (RCTs comparing RPs with control (placebo or radiation therapy in metastatic CRPC. Data were extracted and assessed for the risk of bias (Cochrane’s risk of bias tool. Pooled data were expressed as odds ratio (OR, with 95% confidence intervals (CIs; Mantel–Haenszel fixed-effects model.Results: Eight RCTs with a total patient population of 1,877 patients were identified. The use of RP was associated with significant reduction in pain intensity and SSE (OR: 0.63, 95% CI: 0.51–0.78, I2=27%, P<0.0001, improved QoL (OR: 0.71, 95% CI: 0.55–0.91, I2=65%, three trials, 1,178 patients, P=0.006, and a minimal improved OS (OR: 0.84, 95% CI: 0.64–1.04, I2=47%, seven trials, 1,845 patients, P=0.11. A subgroup analysis suggested an improved OS with radium-223 (OR: 0.68, 95% CI: 0.51–0.90, one trial, 921 patients and strontium-89 (OR: 0.21, 95% CI: 0.05–0.91, one trial, 49 patients. Strontium-89 (five trials was associated with increased rates of grade 3 and 4 thrombocytopenia (OR: 4.26, 95% CI: 2.22–8.18, P=0.01, leucopenia (OR: 7.98, 95% CI: 1.82–34.95, P=0.02, pain flare (OR: 6.82, 95% CI: 3.42–13.55, P=0.04, and emesis (OR: 3.61, 95% CI: 1.76–7.40, P=0.02.Conclusion: The use of RPs was associated with significant reduction in SSEs and improved QoL, while the radium-223

  20. The effects of hemoglobin levels and their interactions with cigarette smoking on survival in nasopharyngeal carcinoma patients.

    Science.gov (United States)

    Zeng, Qi; Shen, Lu-Jun; Li, Sheng; Chen, Ling; Guo, Xiang; Qian, Chao-Nan; Wu, Pei-Hong

    2016-05-01

    There is very little published information regarding the prognostic value of hemoglobin (Hb) levels combined with smoking on the survival of patients with nasopharyngeal carcinoma (NPC), and the interactions between them remain unclear. A total of 2440 NPC patients were confirmed, and multivariate analysis was performed to identify valuable prognostic Hb levels in the entire population and in the cohort of smokers. The survival differences were compared using log-rank tests. The multiplicative and additive interactions were assessed using Cox regression and a Microsoft Word Excel spreadsheet. Postradiotherapy (RT) Hb was an independent prognostic factor for overall survival (OS) (HR = 0.797; P = 0.006), failure-free survival (FFS) (HR=0.811; P = 0.010), and loco-regional failure-free survival (LR-FFS) (HR = 0.725; P = 0.000). In the cohort of smokers, pack-years was also an independent predictor of OS (HR = 0.673; P OS, with RERI = 5.616, AP = 0.665, and S = 4.078. Stratified analyses demonstrated that heavy smokers with low post-RT Hb had HRs of 2.295 (P < 0.001) for death, 2.222 (P < 0.001) for disease failure, and 2.267 (P < 0.001) loco-regional recurrence compared with light smokers with high post-RT Hb levels, and post-RT Hb level is an important predictor of survival in patients with NPC. The positive interaction between post-RT Hb level and pack-years contributes to the elevated risk of poor survival. Oncologists should devote particular attention to heavy smokers with low post-RT Hb levels in the future. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  1. Effect of continued tobacco smoking during radiotherapy on loco-regional control for carcinoma of the larynx

    DEFF Research Database (Denmark)

    Møller, P.; Primdahl, H.; C, A. Kristensen

    2015-01-01

    Purpose/Objective: Tobacco smoking impose a poor prognosis on cancer patients either from reduced treatment response, new primary cancers, or other tobacco-related diseases. The effect of tobacco cessation in smokers commencing radiation treatment for head and neck cancer has only been investigated...... were all active smokers at the date of diagnosis. Patients treated with primary radiotherapy > 60 Gy were included. No surgery was allowed. Tobacco consumption was recorded weekly during radiotherapy, and two and six weeks after, and any smoking during RT was considered active smoking. Follow-up data...... observed in smokers who continued smoking during radiotherapy compared to smokers who quit, however, the findings were statistically insignificant. Further exploration will seek to elucidate any local effect of smoking as well as to identify socioeconomic predictors of being a continuous smoker during...

  2. Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial

    DEFF Research Database (Denmark)

    Coombes, R C; Kilburn, L S; Snowdon, C F

    2007-01-01

    of aromatase inhibitors after treatment, and whether these early improvements lead to real gains in survival. METHODS: 4724 postmenopausal patients with unilateral invasive, oestrogen-receptor-positive or oestrogen-receptor-unknown breast cancer who were disease-free on 2-3 years of tamoxifen, were randomly...... patients with oestrogen-receptor-negative disease were excluded. CONCLUSIONS: Our results suggest that early improvements in disease-free survival noted in patients who switch to exemestane after 2-3 years on tamoxifen persist after treatment, and translate into a modest improvement in overall survival...

  3. Bayesian Analysis of the Genetic Control of Survival in F3 Families of Common Bean Análisis Bayesiano del Control Genético de la Supervivencia en Familias F3 de Poroto

    Directory of Open Access Journals (Sweden)

    Freddy Mora

    2008-12-01

    Full Text Available The objectives of this study were to examine the genetic control of survival in segregant families F3 of the common bean (Phaseolus vulgaris L. in southern Brazil during the 2004-2005 growing season, to identify useful genotypes for the breeding program of this crop, and to determine the genetic association between survival and weight of 100 seeds (production trait; P100. A Bayesian approach was used to predict breeding values and to estimate variance components. Survival was recorded as a binary response: dead plant or live plant during harvest. The total population consisted of 11,520 individual plants. The difference in the magnitude between the best and the worst families was as high as 22%, and varied from 57 to 73%. Survival was found to be highly heritable, with an a posteriori heritability mean and Bayesian credible interval: H² = 53% (43-65%. The genetic advance by direct selection achieved a value of 18%, considering a selection intensity of 25%. Survival was not correlated with P100 (Pearson = 0.099; Spearman = 0.074, indicating that selection for this trait alone would have little impact on production from a breeding viewpoint. Bayesian analysis, using the Gibbs algorithm, was useful in the genetic evaluation of common bean families based on a binary response variable.El presente estudio tuvo como objetivos examinar el control genético de la supervivencia en familias segregantes (F3 de poroto (Phaseolus vulgaris L. en el sur de Brasil, durante la temporada agrícola 2004-2005, identificar genotipos útiles para el programa de mejoramiento del cultivo, y determinar la relación genética de la supervivencia con el peso de 100 semillas (característica de producción; P100. Se utilizó un análisis Bayesiano para la predicción de valores genéticos y la estimación de componentes de varianza. Se midió la supervivencia como una característica binaria (planta viva o muerta durante el período de cosecha. La población total

  4. Orthotopic liver transplantation after the combined use of locoregional therapy and sorafenib for advanced hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Yoo EJ

    2013-06-01

    Full Text Available Eun Jin Yoo,1,* Hye Sun Shin,1,* Seung Up Kim,1,2,7 Dong Jin Joo,3,4 Jun Yong Park,1,2,7 Gi Hong Choi,3 Do Young Kim,1,2,7 Sang Hoon Ahn,1,2,7 Jinsil Seong,5 Myung Joo Koh,6 Kwang-Hyub Han,1,2,7 Chae Yoon Chon1,2,7 1Department of Internal Medicine, 2Institute of Gastroenterology, 3Department of Surgery, 4Research Institute for Transplantation, 5Department of Radiation Oncology, 6Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea; 7Liver Cirrhosis Clinical Research Center, Seoul, South Korea *These authors contributed equally to this work Abstract: We herein report a patient with advanced hepatitis B virus-related hepatocellular carcinoma (HCC beyond the Milan criteria. He underwent orthotopic liver transplantation after successful HCC downstaging that satisfied the University of California, San Francisco criteria, using concurrent chemoradiation therapy with a combination of repeated hepatic arterial infusion chemotherapy (HAIC and sorafenib. A 52-year-old male was diagnosed with advanced hepatitis B virus-related HCC beyond the Milan criteria. He underwent concurrent chemoradiation therapy (50 Gy with 20 fractions over 5 weeks with HAIC using 5-fluorouracil at a dose of 500 mg/day, which was administered during the first and fifth weeks of radiation therapy as an initial treatment modality. This was followed by the combined use of HAIC using 5-fluorouracil (500 mg/m2 for 5 hours on days 1–3 and cisplatin (60 mg/m2 for 2 hours on day 2 every 4 weeks (twelve cycles and sorafenib (from the third to the twelfth cycle of HAIC to treat the remaining HCC. Because a remarkable decrease in the tumor burden that satisfied the University of California, San Francisco criteria was observed after these combination treatments, the patient underwent orthotopic liver transplantation with curative aim and survived for 11 months without evidence of HCC recurrence. Keywords: hepatocellular carcinoma, liver transplantation

  5. Methods for estimating the site of origin of locoregional recurrence in head and neck squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Due, A.K.; Vogelius, I.R.; Berthelsen, A.K.; Kristensen, C.A.; Specht, L. [Copenhagen Univ. (Denmark). Dept. of Radiation Oncology Section 3994; Aznar, M.C. [Copenhagen Univ. (Denmark). Dept. of Radiation Oncology Section 3994; Copenhagen Univ. (Denmark). Niels Bohr Institute; Bentzen, S.M. [Copenhagen Univ. (Denmark). Dept. of Radiation Oncology Section 3994; Wisconsin Univ., MD (United States). Depts. of Human Oncology and Medical Physics; Korreman, S.S. [Copenhagen Univ. (Denmark). Niels Bohr Institute; Roskilde Univ. (Denmark). Dept. of Science, Systems, and Models

    2012-08-15

    Purpose: Methods to estimate the likely origin of recurrences after radiation therapy for head and neck squamous cell carcinoma are compared. Methods and materials: A total of 25 patients meeting the following inclusion criteria were randomly selected: curatively intended intensity-modulated radiotherapy planned on a positron emission tomography-computed tomography (PET/CT) scan during the period 2005-2009; squamous cell carcinoma in the oral cavity, pharynx or larynx; complete clinical response followed by locoregional recurrence; and a CT scan at recurrence before any salvage therapy. Exclusion criteria were previous cancer in the area, surgery prior to radiotherapy, or a synchronous cancer. Three methods of estimating focal points of recurrence origin and two volume overlap methods assigning the recurrences to the most central target volumes encompassing at least 50% or 95% of the recurrence volumes were tested. Treatment planning and recurrence scans were rigid and deformable co-registered in order to transfer focal points to the treatment planning scan. Double determinations of all volumes, points, and co-registrations were made. Results: The volume overlap methods assigned the recurrences to significantly more peripheral target volumes than focal methods (p < 0.0001 for all comparisons of 95% overlap vs. focal methods, p < 0.028 for all comparisons of 50% overlap vs. focal methods). Repeated registrations of the same point had higher reproducibility with deformable registration than with rigid registration (median distance 0.31 vs. 0.35 cm, p = 0.015). No significant differences were observed among the focal methods. Conclusion: Significant differences between methods were found which may affect strategies to improve radiotherapy based on pattern of failure analyses. (orig.)

  6. Prognostic prediction across a gradient of total tumor volume in patients with hepatocellular carcinoma undergoing locoregional therapy

    Directory of Open Access Journals (Sweden)

    Lin Han C

    2010-12-01

    Full Text Available Abstract Background The size and number of tumors are important prognostic indicators for hepatocellular carcinoma (HCC. However, it is difficult to assess the prognosis for patients with a variable number and size of tumors. By combining these two factors, we investigated the role and prognostic accuracy of total tumor volume (TTV for HCC. Methods A total of 786 patients undergoing locoregional therapy (transarterial chemoembolization, percutaneous radiofrequency ablation and acetic acid or ethanol injection for HCC were prospectively evaluated. Results The mean and median TTV was 177 cm3 (range, 0.1-3,591 cm3 and 21 cm3, respectively. Of all, 38%, 29%, 15%, 7% and 11% of patients had TTV of 3, 10-50 cm3, 50-200 cm3, 200-500 cm3 and >500 cm3, respectively. TTV was significantly larger in patients with higher serum α-fetoprotein (AFP levels or with vascular invasion. The Child-Turcotte-Pugh score, performance status, vascular invasion, AFP level and TTV were significant independent prognostic predictors in the Cox proportional hazards model. After adjustment, patients with TTV 50-200 cm3 (relative risk [RR]: 1.74, p = 0.009, 200-500 cm3 (RR: 2.15, p = 0.006 and >500 cm3 (RR: 3.92, p 3. Conclusions TTV is a feasible prognostic predictor across a wide gradient and can be used to predict the mortality risk of HCC. Selecting appropriate cutoffs of TTV may help refine the design of cancer staging system and treatment planning. Future clinical trials of HCC may include this parameter for mortality risk stratification.

  7. Biological Subtype Predicts Risk of Locoregional Recurrence After Mastectomy and Impact of Postmastectomy Radiation in a Large National Database

    Energy Technology Data Exchange (ETDEWEB)

    Tseng, Yolanda D., E-mail: ydt2@uw.edu [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); Uno, Hajime [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Hughes, Melissa E. [Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Niland, Joyce C. [Department of Biostatistics, City of Hope Comprehensive Cancer Center, Duarte, California (United States); Wong, Yu-Ning [Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Theriault, Richard [Department of General Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Blitzblau, Rachel C. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Moy, Beverly [Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Breslin, Tara [Division of Surgical Oncology, Department of Surgery, Northwestern Lake Forest Hospital, Lake Forest, Illinois (United States); Edge, Stephen B. [Baptist Cancer Center, Memphis, Tennessee (United States); Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Hassett, Michael J. [Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Punglia, Rinaa S. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States)

    2015-11-01

    Purpose: To evaluate locoregional recurrence (LRR) after mastectomy and impact of postmastectomy radiation (PMRT) by breast cancer subtype. Methods and Materials: Between 2000 and 2009, 5673 patients with stage I to III breast carcinoma underwent mastectomy and nodal evaluation; 30% received PMRT. Isolated LRR (iLRR) and LRR were compared across groups defined by biological subtype and receipt of trastuzumab: luminal A (estrogen [ER]/progesterone [PR]+, HER2−, low/intermediate grade), luminal B (ER/PR+, HER2−, high grade), HER2 with trastuzumab, HER2 without trastuzumab, and triple negative (TN; ER−, PR−, HER2−). LRR hazard ratios (HR) were estimated with multivariable Fine and Gray models. The effect of PMRT on LRR was evaluated with Fine and Gray models stratified by propensity for PMRT. Results: With a median follow-up time of 50.1 months, there were 19 iLRR and 109 LRR events. HER2 patients with trastuzumab had no iLRR and only a single LRR. Compared with luminal A patients, TN patients had significantly greater adjusted risk of iLRR (HR 14.10; 95% CI 2.97%-66.90%), with a similar trend among luminal B (HR 4.94; 95% CI 0.94%-25.82%) and HER2 patients without trastuzumab (HR 4.41; 95% CI 0.61%-32.11%). Although PMRT reduced LRR, the effect of PMRT varied by subgroup, with the greatest and smallest effects seen among luminal A (HR 0.17; 95% CI 0.05%-0.62%) and TN patients (HR 0.59; 95% CI 0.25%-1.35%), respectively. Conclusions: TN patients had the highest risk of LRR and the least benefit from PMRT; these patients may benefit from alternative treatment strategies. In contrast, in the era of HER2-directed therapy, the role of local therapy may need to be reassessed among HER2 patients.

  8. Nomogram for Predicting the Risk of Locoregional Recurrence in Patients Treated With Accelerated Partial-Breast Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Wobb, Jessica L. [Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan (United States); Chen, Peter Y., E-mail: PChen@beaumont.edu [Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan (United States); Shah, Chirag [Department of Radiation Oncology, Summa Health System, Akron, Ohio (United States); Moran, Meena S. [Department of Therapeutic Radiology, Yale School of Medicine, Norwich, Connecticut (United States); Shaitelman, Simona F. [Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas (United States); Vicini, Frank A. [Department of Radiation Oncology, Michigan Healthcare Professionals/21st Century Oncology, Farmington, Michigan (United States); Mbah, Alfred K.; Lyden, Maureen [Biostat International Inc, Tampa, Florida (United States); Beitsch, Peter [Department of Surgery, Dallas Breast Center, Dallas, Texas (United States)

    2015-02-01

    Purpose: To develop a nomogram taking into account clinicopathologic features to predict locoregional recurrence (LRR) in patients treated with accelerated partial-breast irradiation (APBI) for early-stage breast cancer. Methods and Materials: A total of 2000 breasts (1990 women) were treated with APBI at William Beaumont Hospital (n=551) or on the American Society of Breast Surgeons MammoSite Registry Trial (n=1449). Techniques included multiplanar interstitial catheters (n=98), balloon-based brachytherapy (n=1689), and 3-dimensional conformal radiation therapy (n=213). Clinicopathologic variables were gathered prospectively. A nomogram was formulated utilizing the Cox proportional hazards regression model to predict for LRR. This was validated by generating a bias-corrected index and cross-validated with a concordance index. Results: Median follow-up was 5.5 years (range, 0.9-18.3 years). Of the 2000 cases, 435 were excluded because of missing data. Univariate analysis found that age <50 years, pre-/perimenopausal status, close/positive margins, estrogen receptor negativity, and high grade were associated with a higher frequency of LRR. These 5 independent covariates were used to create adjusted estimates, weighting each on a scale of 0-100. The total score is identified on a points scale to obtain the probability of an LRR over the study period. The model demonstrated good concordance for predicting LRR, with a concordance index of 0.641. Conclusions: The formulation of a practical, easy-to-use nomogram for calculating the risk of LRR in patients undergoing APBI will help guide the appropriate selection of patients for off-protocol utilization of APBI.

  9. Quality of Survival and Growth in Children and Young Adults in the PNET4 European Controlled Trial of Hyperfractionated Versus Conventional Radiation Therapy for Standard-Risk Medulloblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Kennedy, Colin, E-mail: crk1@soton.ac.uk [University of Southampton Faculty of Medicine and University Hospital Southampton National Health Service Foundation Trust, Southampton (United Kingdom); Bull, Kim [University of Southampton Faculty of Medicine and University Hospital Southampton National Health Service Foundation Trust, Southampton (United Kingdom); Chevignard, Mathilde [Hôpitaux de Saint Maurice, Saint Maurice (France); Neurophysiology, University of Pierre et Marie-Curie Paris 6, Paris (France); Culliford, David [University of Southampton Faculty of Medicine and University Hospital Southampton National Health Service Foundation Trust, Southampton (United Kingdom); Dörr, Helmuth G. [Kinder- und Jugendklinik der Universität Erlangen, Erlangen (Germany); Doz, François [Institut Curie and University Paris Descartes, Sorbonne Paris Cité (France); Kortmann, Rolf-Dieter [Department of Radiation Therapy, University of Leipzig, Leipzig (Germany); Lannering, Birgitta [Department of Pediatrics, The Sahlgren Academy, University of Gothenburg, Gothenburg (Sweden); Massimino, Maura [Fondazione Istituto di Ricovero e Cura a Carattere Scientifico IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Navajas Gutiérrez, Aurora [Hospital Universitario Cruces, Baracaldo-Vizcaya (Spain); Rutkowski, Stefan [University Medical Center Hamburg-Eppendorf, Hamburg (Germany); Spoudeas, Helen A. [Center for Pediatric Endocrinology, University College London, London (United Kingdom); Calaminus, Gabriele [Pediatric Oncology, University of Muenster, Muenster (Germany)

    2014-02-01

    Purpose: To compare quality of survival in “standard-risk” medulloblastoma after hyperfractionated radiation therapy of the central nervous system with that after standard radiation therapy, combined with a chemotherapy regimen common to both treatment arms, in the PNET4 randomised controlled trial. Methods and Materials: Participants in the PNET4 trial and their parents/caregivers in 7 participating anonymized countries completed standardized questionnaires in their own language on executive function, health status, behavior, health-related quality of life, and medical, educational, employment, and social information. Pre- and postoperative neurologic status and serial heights and weights were also recorded. Results: Data were provided by 151 of 244 eligible survivors (62%) at a median age at assessment of 15.2 years and median interval from diagnosis of 5.8 years. Compared with standard radiation therapy, hyperfractionated radiation therapy was associated with lower (ie, better) z-scores for executive function in all participants (mean intergroup difference 0.48 SDs, 95% confidence interval 0.16-0.81, P=.004), but health status, behavioral difficulties, and health-related quality of life z-scores were similar in the 2 treatment arms. Data on hearing impairment were equivocal. Hyperfractionated radiation therapy was also associated with greater decrement in height z-scores (mean intergroup difference 0.43 SDs, 95% confidence interval 0.10-0.76, P=.011). Conclusions: Hyperfractionated radiation therapy was associated with better executive function and worse growth but without accompanying change in health status, behavior, or quality of life.

  10. Effects of temperature on survival, development, longevity, and fecundity of Ophraella communa (Coleoptera: Chrysomelidae), a potential biological control agent against Ambrosia artemisiifolia (Asterales: Asteraceae).

    Science.gov (United States)

    Zhou, Zhong-Shi; Guo, Jian-Ying; Chen, Hong-Song; Wan, Fang-Hao

    2010-06-01

    Ophraella communa (Coleoptera: Chrysomelidae) is a leaf beetle that is unintentionally introduced in China. It is a potential biological control agent against common ragweed, Ambrosia artemisiifolia (Asterales: Asteraceae). The effects of temperature on the development and fecundity of O. communa were studied at eight constant temperature regimens (15, 20, 22, 25, 28, 30, 32, 36 degrees C) in the laboratory. The results showed that the developmental periods for egg, larva, pupa, and entire immature stages decreased in response to the increasing temperature, with the exception of 30 degrees C. The survival rates at different developmental stages were higher at 25 and 28 degrees C than at other temperatures. Ovipositional period and longevity of female shortened with the increasing temperature. The highest fecundity of female was observed to be 2,712.3 eggs/female at 28 degrees C. Life table of O. communa was constructed based on the data at 20-32 degrees C. The innate capacity for increase (r(m)), the net reproductive rate (R(0)), and the finite rate of increase (lambda) reached the maximum at 28 degrees C, with values of 0.247, 1,773.0, and 1.280, respectively. The shortest period of a generation (T) was 24.6 d at 32 degrees C, whereas the longest T value was recorded as 79.3 d at 20 degrees C. These results offer valuable insight on the establishment potential of O. communa in new environments with diverse temperature regimens and on its mass-rearing techniques in laboratory.

  11. Microencapsulation increases survival of the probiotic L .plantarum IS-10506, but not E. faecium IS-27526 in a dynamic, computer-controlled in vitro model of the upper gastrointestinal tract.

    Science.gov (United States)

    Surono, Ingrid; Verhoeven, Jessica; Verbruggen, Sanne; Venema, Koen

    2018-02-23

    to test the effect of microencapsulation on the survival of two probiotic strains isolated from Dadih, Indonesian fermented buffalo milk, in a dynamic, computer controlled in vitro model of the upper gastrointestinal (GI) tract (TIM-1), simulating human adults. Free or microencapsulated probiotics, L.plantarum IS-10506 or E.faecium IS-27526, resuspended in milk were studied for survival in the complete TIM-1 system (stomach + small intestine) or in the gastric compartment of TIM-1 only. Hourly samples collected after the ileal-cecal valve or after the pylorus were plated on MRS agar (for Lactobacillus) or S&B agar (for Enterococcus). Survival of the free cells after transit through the complete TIM-1 system was on average for the E. faecium and L. plantarum 15.0% and 18.5%, respectively. Survival of the microencapsulated E. faecium and L. plantarum was 15.7% and 84.5%, respectively. The free cells were further assessed in only the gastric compartment of TIM-1. E. faecium and L. plantarum showed an average survival of 39% and 32%, respectively, after gastric passage. There is similar sensitivity to gastric acid as well as survival after complete upper GI tract transit of free cells, but microencapsulation only protected L. plantarum. Survival of microencapsulated L. plantarum IS-10506 is increased compared to free cells in a validated in vitro model of the upper GI tract. It increases its use as ingredient of functional foods. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  12. Relationship Between Radiation Treatment Time and Overall Survival After Induction Chemotherapy for Locally Advanced Head-and-Neck Carcinoma: A Subset Analysis of TAX 324

    Energy Technology Data Exchange (ETDEWEB)

    Sher, David J., E-mail: dsher@partners.org [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, MA (United States); Posner, Marshall R. [Division of Hematology/Oncology, Mount Sinai School of Medicine, New York, NY (United States); Tishler, Roy B. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, MA (United States); Sarlis, Nicholas J. [Sanofi-Aventis US, Bridgewater, NJ (United States); Haddad, Robert I. [Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women' s Hospital, Boston, MA (United States); Holupka, Edward J. [Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, MA (Israel); Devlin, Phillip M. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, MA (United States)

    2011-12-01

    Purpose: To analyze the relationship between overall survival (OS) and radiation treatment time (RTT) and overall treatment time (OTT) in a well-described sequential therapy paradigm for locally advanced head-and-neck carcinoma (LAHNC). Methods and Materials: TAX 324 is a Phase III study comparing TPF (docetaxel, cisplatin, and fluorouracil) with PF (cisplatin and fluorouracil) induction chemotherapy (IC) in LAHNC patients; both arms were followed by carboplatin-based chemoradiotherapy (CRT). Prospective radiotherapy quality assurance was performed. This analysis includes all patients who received three cycles of IC and a radiation dose of {>=} 70 Gy. Radiotherapy treatment time was analyzed as binary ({<=} 8 weeks vs. longer) and continuous (number of days beyond 8 weeks) functions. The primary analysis assessed the relationship between RTT, OTT, and OS, and the secondary analysis explored the association between treatment times and locoregional recurrence (LRR). Results: A total of 333 (of 501) TAX 324 patients met the criteria for inclusion in this analysis. There were no significant differences between the treatment arms in baseline or treatment characteristics. On multivariable analysis, PF IC, World Health Organization performance status of 1, non-oropharynx site, T3/4 stage, N3 status, and prolonged RTT (hazard ratio 1.63, p = 0.006) were associated with significantly inferior survival. Performance status, T3/4 disease, and prolonged RTT (odds ratio 1.68, p = 0.047) were independently and negatively related to LRR on multivariable analysis, whereas PF was not. Overall treatment time was not independently associated with either OS or LRR. Conclusions: In this secondary analysis of the TAX 324 trial, TPF IC remains superior to PF IC after controlling for radiotherapy delivery time. Even with optimal IC and concurrent chemotherapy, a non-prolonged RTT is a crucial determinant of treatment success. Appropriate delivery of radiotherapy after IC remains essential

  13. Incremental Cancer Detection of Locoregional Restaging with Diagnostic Mammography Combined with Whole-Breast and Regional Nodal Ultrasound in Women with Newly Diagnosed Breast Cancer.

    Science.gov (United States)

    Candelaria, Rosalind P; Huang, Monica L; Adrada, Beatriz E; Bassett, Roland; Hunt, Kelly K; Kuerer, Henry M; Smith, Benjamin D; Chavez-MacGregor, Mariana; Yang, Wei Tse

    2017-02-01

    This study aims to determine if locoregional restaging with diagnostic mammography and ultrasound (US) of the whole breast and regional nodes performed for quality assurance in women with newly diagnosed breast cancer who were referred to a tertiary care center yields incremental cancer detection. An institutional review board-approved retrospective, single-institution database review was performed on the first 1000 women referred to our center in 2010 with a provisional breast cancer diagnosis. Locoregional restaging consisted of diagnostic full-field digital mammography combined with US of the whole breast and regional nodal basins. Bilateral whole-breast US was performed in women with contralateral mammographic abnormality or had heterogeneously or extremely dense parenchyma. Demographic, clinical, and pathologic factors were analyzed. Final analyses included 401 women. Of the 401 women, 138 (34%) did not have their outside images available for review upon referral. The median age was 54 years (range 21-92); the median tumor size was 2.9 cm (range 0.6-18.0) for women whose disease was upstaged and 2.2 cm (range 0.4-15.0) for women whose disease was not upstaged. Incremental cancer detection rates were 15.5% (62 of 401) in the ipsilateral breast and 3.9% (6 of 154) in the contralateral breast (P < 0.0001). The total upstage rate was 25% (100 of 401). Surgical management changed from segmentectomy to mastectomy in 12% (50 of 401). The re-excision rate after segmentectomy was 19% (35 of 189). Locoregional restaging with diagnostic mammography combined with whole-breast and regional nodal US that is performed for standardization of the imaging workup for newly diagnosed breast cancer patients can reduce underestimation of disease burden and impact therapeutic planning. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  14. [Physical activity and cancer survival].

    Science.gov (United States)

    Romieu, Isabelle; Touillaud, Marina; Ferrari, Pietro; Bignon, Yves-Jean; Antoun, Sami; Berthouze-Aranda, Sophie; Bachmann, Patrick; Duclos, Martine; Ninot, Grégory; Romieu, Gilles; Sénesse, Pierre; Behrendt, Jan; Balosso, Jacques; Pavic, Michel; Kerbrat, Pierre; Serin, Daniel; Trédan, Olivier; Fervers, Béatrice

    2012-10-01

    Physical activity has been shown in large cohort studies to positively impact survival in cancer survivors. Existing randomized controlled trials showed a beneficial effect of physical activity on physical fitness, quality of life, anxiety and self-esteem; however, the small sample size, the short follow-up and the lack of standardization of physical activity intervention across studies impaired definite conclusion in terms of survival. Physical activity reduces adiposity and circulating estrogen levels and increases insulin sensitivity among other effects. A workshop was conducted at the International Agency for Research on Cancer in April 2011 to discuss the role of physical activity on cancer survival and the methodology to develop multicentre randomized intervention trials, including the type of physical activity to implement and its association with nutritional recommendations. The authors discuss the beneficial effect of physical activity on cancer survival with a main focus on breast cancer and report the conclusions from this workshop.

  15. Foreign Ownership and Long-term Survival

    DEFF Research Database (Denmark)

    Kronborg, Dorte; Thomsen, Steen

    2006-01-01

    Does foreign ownership enhance or decrease a firm's chances of survival? Over the 100 year period 1895-2001 this paper compares the survival of foreign subsidiaries in Denmark to a control sample matched by industry and firm size. We find that foreign-owned companies have higher survival...... probability. On average exit risk for domestic companies is 2.3 times higher than for foreign companies. First movers like Siemens, Philips, Kodak, Ford, GM or Goodyear have been active in the country for almost a century. Relative foreign survival increases with company age. However, the foreign survival...

  16. [Basic Studies on Locoregional Injection of a Newly Designed Chitin Sol].

    Science.gov (United States)

    Chiba, Takehiro; Sugitachi, Akio; Kume, Kouhei; Segawa, Takenori; Nishinari, Yutaka; Ishida, Kaoru; Noda, Hironobu; Nishizuka, Satoshi; Kimura, Yusuke; Koeda, Keisuke; Sasaki, Akira

    2015-11-01

    Systemic chemotherapy in advanced cancer cases often provokes serious adverse events. We aimed to examine the fundamental properties and efficacy of a novel chitin sol, an anti-cancer agent with minor side effects designed to avoid the adverse effects of chemotherapy and enhance the QOL and ADL of patients. DAC-70 was used to create the novel agent termed DAC-70 sol. The anti-proliferative activity was assayed by the WST method using different types of cell lines. The anti-cancer efficacy of the novel agent was examined using cancer-bearing mice. DAC-70 sol was easily injectable through a 21-G needle. The sol suppressed proliferation of the cells in vitro. Intra-tumor injection of DAC-70 sol inhibited the rapid growth of solid tumors in the mice. CDDP-loaded DAC-70 sol, CDDP/DAC-70 sol, successfully controlled malignant ascites in the mice (psol and CDDP/DAC-70 sol is clinically useful as novel cancer chemotherapy for advanced cases. This warrants further clinical studies in cancer chemotherapy.

  17. Combined BTK and PI3Kδ inhibition with acalabrutinib and ACP-319 improves survival and tumor control in CLL mouse model

    DEFF Research Database (Denmark)

    Niemann, Carsten U; Mora-Jensen, Helena I; Dadashian, Eman L

    2017-01-01

    the effectiveness of combing PI3K-delta and BTK inhibitors. Experimental design: As CLL proliferation and survival depends on the microenvironment, we used murine models to assess the efficacy of the BTK inhibitor acalabrutinib combined with the PI3K-delta inhibitor ACP-319 in vivo We compared single......, combination therapy extended survival by over two weeks compared to either single agent. The combination reduced tumor proliferation, NF-KB signaling and expression of BCL-xL and MCL-1 more potently than single-agent therapy. Conclusion: The combination of acalabrutinib and ACP-319 was superior...

  18. Invasive micropapillary carcinoma of the breast has a better long-term survival than invasive ductal carcinoma of the breast in spite of its aggressive clinical presentations: a comparison based on large population database and case-control analysis.

    Science.gov (United States)

    Chen, Hongliang; Wu, Kejin; Wang, Maoli; Wang, Fuwen; Zhang, Mingdi; Zhang, Peng

    2017-12-01

    There are controversies in the comparison of overall survival between invasive micropapillary carcinoma of the breast (IMPC) and invasive ductal carcinoma (IDC). The objective of this study was to compare the long-term survival outcome between non-metastatic IMPC and IDC. The Surveillance, Epidemiology, and End Results database was searched to identify women with non-metastatic IMPC and IDC diagnosed between 2001 and 2013. Comparisons of patient and tumor characteristics were performed using Pearson's chi-square. The propensity score matching method was applied with each IMPC matched to one IDC. Breast cancer-specific survival (BCSS) and overall survival (OS) were estimated using the Kaplan-Meier product limit method and compared across groups using the log-rank statistic. Multivariate analysis was performed through Cox models. IMPC was presented with aggressive clinical presentations such as larger tumor, more positive lymph nodes, and more advanced stage compared with IDC. A higher rate of estrogen receptor (ER)/progesterone receptor (PR) positivity was also observed in IMPC. With a median follow-up of 64 months, IMPC had a better BCSS (P = 0.031) and OS (P = 0.012) compared with IDC. In a case-control analysis IMPC was still an independent favorable prognostic factor for BCSS (HR = 0.410, P analysis, IMPC always showed a better survival outcome compared with IDC except in AJCC stage I and histologic grade I disease. IMPC has a better long-term survival outcome compared with IDC in spite of its highly aggressive clinical presentation. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  19. Trastuzumab in the adjuvant treatment of HER2-positive early breast cancer patients: a meta-analysis of published randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Wenjin Yin

    Full Text Available BACKGROUND: Adjuvant trastuzumab therapy has yielded conflicting results for overall survival, concerns about central nervous system (CNS metastasis, and questions about optimal schedule. Therefore, we carried out a meta-analysis to assess the benefits of concurrent or sequential trastuzumab with adjuvant chemotherapy for early breast cancer patients with HER2-positive tumors. METHODS: Computerized and manual searches were performed to identify randomized clinical trials comparing adjuvant chemotherapy with or without trastuzumab in HER2-positive early breast cancer patients. Odds ratios were used to estimate the association between the addition of trastuzumab to adjuvant chemotherapy and various survival outcomes. The fixed-effects or random-effects model was used to combine data. FINDINGS: With six eligible studies identified, this analysis demonstrated that patients with HER2-positive breast cancer derived benefit in disease-free survival, overall survival, locoregional recurrence and distant recurrence (all P<0.001 from the addition of trastuzumab to adjuvant chemotherapy, whereas trastuzumab did worse in CNS recurrence as compared to the control group (P = 0.018. Furthermore, concomitant use of trastuzumab significantly lowered the hazard of death (P<0.001 but bore a higher incidence of CNS recurrence (P = 0.010, while statistical significance failed to be discerned for either overall survival (P = 0.069 or CNS metastasis (P = 0.374 between the sequential and observation arms. CONCLUSION: This analysis verifies the efficacy of trastuzumab in the adjuvant setting. Additionally, our findings indirectly corroborate the superiority of concurrent trastuzumab to sequential use and also illuminate that prolonged survival is the possible reason for the higher incidence of CNS with trastuzumab versus observation.

  20. Chemoradiotherapy, with adjuvant surgery for local control, confers a durable survival advantage in adenocarcinoma and squamous cell carcinoma of the oesophagus.

    LENUS (Irish Health Repository)

    Bass, G A

    2014-04-01

    Oesophageal cancer usually presents with systemic disease, necessitating systemic therapy. Neo-adjuvant chemoradiotherapy improves short-term survival, but its long-term impact is disputed because of limited accrual, treatment-protocol heterogeneity and a short follow-up of randomised trials.

  1. Randomized controlled clinical trial of the 24-months survival of composite resin restorations after one-step incomplete and complete excavation on primary teeth

    NARCIS (Netherlands)

    Franzon, R.; Opdam, N.J.; Guimaraes, L.F.; Demarco, F.F.; Casagrande, L.; Haas, A.N de; Araujo, F.B.

    2015-01-01

    OBJECTIVE: This randomized clinical trial aimed to compare the 24-months survival of composite restorations in primary molars after partial caries removal (PCR) and total caries removal (TCR). METHODS: Forty-eight children aged 3-8 years with at least one molar with a deep carious lesion were

  2. Identification of sigma factor SigmaB-controlled genes and their impact on acid stress, high hydrostatic pressure, and freeze survival in Listeria monocytogenes EGD-e

    NARCIS (Netherlands)

    Wemekamp-Kamphuis, H.H.; Wouters, J.A.; Leeuw, de P.P.L.A.; Hain, T.; Chakraborty, T.; Abee, T.

    2004-01-01

    The gene encoding the alternative sigma factor sigma(B) in Listeria monocytogenes is induced upon exposure of cells to several stresses. In this study, we investigated the impact of a sigB null mutation on the survival of L. monocytogenes EGD-e at low pH, during high-hydrostatic-pressure treatment,

  3. Internal and external validation of an ESTRO delineation guideline - dependent automated segmentation tool for loco-regional radiation therapy of early breast cancer.

    Science.gov (United States)

    Eldesoky, Ahmed R; Yates, Esben S; Nyeng, Tine B; Thomsen, Mette S; Nielsen, Hanne M; Poortmans, Philip; Kirkove, Carine; Krause, Mechthild; Kamby, Claus; Mjaaland, Ingvil; Blix, Egil S; Jensen, Ingelise; Berg, Martin; Lorenzen, Ebbe L; Taheri-Kadkhoda, Zahra; Offersen, Birgitte V

    2016-12-01

    To internally and externally validate an atlas based automated segmentation (ABAS) in loco-regional radiation therapy of breast cancer. Structures of 60 patients delineated according to the ESTRO consensus guideline were included in four categorized multi-atlas libraries using MIM Maestro™ software. These libraries were used for auto-segmentation in two different patient groups (50 patients from the local institution and 40 patients from other institutions). Dice Similarity Coefficient, Average Hausdorff Distance, difference in volume and time were computed to compare ABAS before and after correction against a gold standard manual segmentation (MS). ABAS reduced the time of MS before and after correction by 93% and 32%, respectively. ABAS showed high agreement for lung, heart, breast and humeral head, moderate agreement for chest wall and axillary nodal levels and poor agreement for interpectoral, internal mammary nodal regions and LADCA. Correcting ABAS significantly improved all the results. External validation of ABAS showed comparable results. ABAS is a clinically useful tool for segmenting structures in breast cancer loco-regional radiation therapy in a multi-institutional setting. However, manual correction of some structures is important before clinical use. The ABAS is now available for routine clinical use in Danish patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Locoregional Failure in Early-Stage Breast Cancer Patients Treated With Radical Mastectomy and Adjuvant Systemic Therapy: Which Patients Benefit From Postmastectomy Irradiation?

    Energy Technology Data Exchange (ETDEWEB)

    Trovo, Marco, E-mail: marcotrovo33@hotmail.com [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Durofil, Elena [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Polesel, Jerry [Department of Epidemiology and Biostatistics, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Roncadin, Mario [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Perin, Tiziana [Department of Pathology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Mileto, Mario; Piccoli, Erica [Department of Surgery, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Quitadamo, Daniela [Scientific Direction, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Massarut, Samuele [Department of Surgery, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Carbone, Antonino [Department of Pathology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Trovo, Mauro G. [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy)

    2012-06-01

    Purpose: To assess the locoregional failure in patients with Stage I-II breast cancer treated with radical mastectomy and to evaluate whether a subset of these patients might be at sufficiently high risk of locoregional recurrence (LRR) to benefit from postmastectomy irradiation (PMRT). Methods and Materials: Stage I-II breast cancer patients (n = 150) treated with radical mastectomy without adjuvant irradiation between 1999 and 2005 were analyzed. The pattern of LRR was reported. Kaplan-Meier analysis was used to calculate rates of LRR, and Cox proportional hazards methods were used to evaluate potential risk factors. Results: Median follow-up was 75 months. Mean patient age was 56 years. One-hundred forty-three (95%) patients received adjuvant systemic therapy: 85 (57%) hormonal therapy alone, 14 (9%) chemotherapy alone, and 44 (29%) both chemotherapy and hormonal therapy. Statistically significant factors associated with increased risk of LRR were premenopausal status (p = 0.004), estrogen receptor negative cancer (p = 0.02), pathologic grade 3 (p = 0.02), and lymphovascular invasion (p = 0.001). T and N stage were not associated with increased risk of regional recurrence. The 5-year LRR rate for patients with zero or one, two, three, and four risk factors was 1%, 10.3%, 24.2%, and 75%, respectively. Conclusions: A subset of patients with early-stage breast cancer is at high risk of LRR, and therefore PMRT might be beneficial.

  5. Clinical effect of a positive surgical margin after hepatectomy on survival of patients with intrahepatic cholangiocarcinoma.

    Science.gov (United States)

    Yeh, Chun-Nan; Hsieh, Feng-Jen; Chiang, Kun-Chun; Chen, Jen-Shi; Yeh, Ta-Sen; Jan, Yi-Yin; Chen, Miin-Fu

    2015-01-01

    Several unfavorable prognostic factors have been proposed for peripheral cholangiocarcinoma (PCC) in patients undergoing hepatectomy, including gross type of tumor, vascular invasion, lymph node metastasis, a high carbohydrate antigen 19-9 level, and a positive resection margin. However, the clinical effect of a positive surgical margin on the survival of patients with PCC after hepatectomy still needs to be clarified due to conflicting results. A total of 224 PCC patients who underwent hepatic resection with curative intent between 1977 and 2007 were retrospectively reviewed. Eighty-nine patients had a positive resection margin, with 62 having a microscopically positive margin and 27 a grossly positive margin (R2). The clinicopathological features, outcomes, and recurrence pattern were compared with patients with curative hepatectomy. PCC patients with hepatolithiasis, periductal infiltrative or periductal infiltrative mixed with mass-forming growth, higher T stage, and more advanced stage tended to have higher positive resection margin rates after hepatectomy. PCC patients who underwent curative hepatectomy had a significantly higher survival rate than did those with a positive surgical margin. When PCC patients underwent hepatectomy with a positive resection margin, the histological grade of the tumor, nodal positivity, and chemotherapy significantly affected overall survival. Locoregional recurrence was the most common pattern of recurrence. A positive resection margin had an unfavorable effect on overall survival in PCC patients undergoing hepatectomy. In these patients, the prognosis was determined by the biology of the tumor, including differentiation and nodal positivity, and chemotherapy increased overall survival.

  6. Revisit of 1997 TNM staging system--survival analysis of 1112 lung cancer patients in Taiwan.

    Science.gov (United States)

    Perng, Reury-Perng; Chen, Chih-Yi; Chang, Gee-Chen; Hsia, Te-Chun; Hsu, Nan-Yung; Tsai, Ying-Huang; Tsai, Chun-Ming; Yang, Chih-Hsin; Chen, Yuh-Min; Yu, Chong-Jen; Lee, Jen-Jyh; Hsu, Han-Shui; Yu, Chih-Teng; Kao, Eing-Long; Chiu, Chao-Hua

    2007-01-01

    There is neither a nation-wide nor a large-scale, multi-institutional lung cancer database available for stage-by-stage survival analysis in Taiwan at present. Using the data element provided by the International Association for the Study of Lung Cancer, the Taiwan Lung Cancer Society initiated a project to include native lung cancer patients into a global database. A total of 1112 Taiwan lung cancer patients treated in 7 medical centers were enrolled. In small cell lung cancer, patients with ipsilateral pleural effusion had a survival between those with locoregional disease alone and those with distant metastasis; however, the difference was not statistically significant (P = 0.204). In non-small cell lung cancer, tumor size had significant survival influence for patients as a whole (P < 0.001) but it did not support the further division of stage IA according to tumor size (P = 0.122). The survival was compatible in stage IIIB and IV patients and therefore, the survival impact of pleural effusion cannot be determined. In patients with pIIIA-N2 disease, those who had station 8 nodal metastasis had inferior survival (P = 0.020) and station 5 superior survival (P = 0.010). In patients with distant metastasis, bone, liver, or distant lymph node metastasis predicted an inferior survival (all P values < 0.05). The present study provides for comparison in this area a stage-by-stage reference for the survival of lung cancer patients. Some factors other than current TNM descriptors need to be further investigated in constructing the next version of the staging system.

  7. Mycobacterium tuberculosis Modulates miR-106b-5p to Control Cathepsin S Expression Resulting in Higher Pathogen Survival and Poor T-Cell Activation

    Directory of Open Access Journals (Sweden)

    David Pires

    2017-12-01

    Full Text Available The success of tuberculosis (TB bacillus, Mycobacterium tuberculosis (Mtb, relies on the ability to survive in host cells and escape to immune surveillance and activation. We recently demonstrated that Mtb manipulation of host lysosomal cathepsins in macrophages leads to decreased enzymatic activity and pathogen survival. In addition, while searching for microRNAs (miRNAs involved in posttranscriptional gene regulation during mycobacteria infection of human macrophages, we found that selected miRNAs such as miR-106b-5p were specifically upregulated by pathogenic mycobacteria. Here, we show that miR-106b-5p is actively manipulated by Mtb to ensure its survival in macrophages. Using an in silico prediction approach, we identified miR-106b-5p with a potential binding to the 3′-untranslated region of cathepsin S (CtsS mRNA. We demonstrated by luminescence-based methods that miR-106b-5p indeed targets CTSS mRNA resulting in protein translation silencing. Moreover, miR-106b-5p gain-of-function experiments lead to a decreased CtsS expression favoring Mtb intracellular survival. By contrast, miR-106b-5p loss-of-function in infected cells was concomitant with increased CtsS expression, with significant intracellular killing of Mtb and T-cell activation. Modulation of miR-106b-5p did not impact necrosis, apoptosis or autophagy arguing that miR-106b-5p directly targeted CtsS expression as a way for Mtb to avoid exposure to degradative enzymes in the endocytic pathway. Altogether, our data suggest that manipulation of miR-106b-5p as a potential target for host-directed therapy for Mtb infection.

  8. A novel schedule of accelerated partial breast radiation using intensity-modulated radiation therapy in elderly patients: survival and toxicity analysis of a prospective clinical trial

    Energy Technology Data Exchange (ETDEWEB)

    Sayan, Mutlay; Nelson, Carl; Gagne, Havaleh; Rubin, Deborah; Heimann, Ruth [Dept. of Radiation Oncology, University of Vermont Medical Center, Burlington (United States); Wilson, Karen [University of Vermont Cancer Center, Burlington (United States)

    2017-03-15

    Several accelerated partial breast radiation (APBR) techniques have been investigated in patients with early-stage breast cancer (BC); however, the optimal treatment delivery techniques remain unclear. We evaluated the feasibility and toxicity of APBR delivered using intensity-modulated radiation therapy (IMRT) in elderly patients with stage I BC, using a novel fractionation schedule. Forty-two patients aged ≥65 years, with stage I BC who underwent breast conserving surgery were enrolled in a phase I/II study evaluating APBR using IMRT. Forty eligible patients received 40 Gy in 4 Gy daily fractions. Patients were assessed for treatment related toxicities, and cosmesis, before APBR, during, and after completion of the treatment. The median age was 73 years, median tumor size 0.8 cm and the median follow-up was 54 months. The 5-year locoregional control was 97.5% and overall survival 90%. Erythema and skin pigmentation was the most common acute adverse event, reported by 27 patients (69%). Twenty-six patients (65%) reported mild pain, rated 1-4/10. This improved at last follow-up to only 2 (15%). Overall the patient and physician reported worst late toxicities were lower than the baseline and at last follow-up, patients and physicians rated cosmesis as excellent/good in 93% and 86 %, respectively. In this prospective trial, we observed an excellent rate of tumor control with daily APBR. The acceptable toxicity profile and cosmetic results of this study support the use of IMRT planned APBR with daily schedule in elderly patients with early stage BC.

  9. Psychology and survival.

    Science.gov (United States)

    Phillips, D P; Ruth, T E; Wagner, L M

    1993-11-06

    We examined the deaths of 28,169 adult Chinese-Americans, and 412,632 randomly selected, matched controls coded "white" on the death certificate. Chinese-Americans, but not whites, die significantly earlier than normal (1.3-4.9 yr) if they have a combination of disease and birthyear which Chinese astrology and medicine consider ill-fated. The more strongly a group is attached to Chinese traditions, the more years of life are lost. Our results hold for nearly all major causes of death studied. The reduction in survival cannot be completely explained by a change in the behaviour of the Chinese patient, doctor, or death-registrar, but seems to result at least partly from psychosomatic processes.

  10. Impact of 3-Monthly Vitamin D Supplementation Plus Exercise on Survival after Surgery for Osteoporotic Hip Fracture in Adult Patients over 50 Years: A Pragmatic Randomized, Partially Blinded, Controlled Trial.

    Science.gov (United States)

    Laiz, A; Malouf, J; Marin, A; Longobardi, V; de Caso, J; Farrerons, J; Casademont, J

    2017-01-01

    To determine whether 3-monthly supplementation of an oral vitamin D widely used in Spain (calcifediol) plus daily exercise could influence survival at one and four years after surgery for osteoporotic hip fracture. A pragmatic, randomized, partially single-blind placebo-controlled study. Patients admitted to a tertiary university hospital for acute hip fracture. 675 healthy adult patients undergoing surgery for osteoporotic hip fracture were recruited from January 2004 to December 2007. Patients were randomized to receive either 3-monthly oral doses of 3 mg calcifediol (Hidroferol Choque®) or placebo in the 12 months postsurgery. Patients who received calcifediol were also given an exercise programme. The placebo group received standard health recommendations only. The primary endpoint was survival at 1 year and at 4 year follow-up. We also recorded new fractures, medical complications and anti-osteoporotic treatment compliance. We included a total of 88 patients, aged 62 to 99 years. Mean age was 82 years and 88.6% were women. At 12 months, 10 (11.3%) patients had died, 9 of them, from the non-intervention group. At 4 years after surgery, 20 (22.7%) had died, 3 (3.4%) from the intervention group and 17 (19.3%) from the non-intervention group. At this time, survival curve analysis showed 93% survival in the intervention group and 62% in the non-intervention group (p=0.001). At 12-month follow up, there were 18 new fractures, 9 in each group. The non-intervention group had more medical complications, with significant differences at visit 2 (p = 0.04) and 3 (p = 0.02) but not at visit 4 (p = 0.18). No significant differences between groups were found regarding treatment compliance. 3-monthly, oral supplements of 3 mg calcifediol plus daily exercise improved survival at one-year and four-year follow up after surgery for an osteoporotic hip fracture.

  11. Examination of 12-lipoxygenase (12-LOX) as a therapeutic target in non-small cell lung cancer (NSCLC): Mechanisms controlling survival and induction of apoptosis following selective inhibition

    LENUS (Irish Health Repository)

    Cathcart, Mary Clare

    2011-06-01

    Background: Platelet-type 12-LOX is an arachidonic acid metabolising enzyme resulting in the formation of 12(S)-HETE, which stimulates tumour cell adhesion, invasion and metastasis. This study aimed to examine the expression profile and role of this enzyme in NSCLC, and determine if it is a potential target for intervention. Methods: A panel of retrospective resected lung tumours was stained for 12-LOX expression by IHC. Levels of the 12-LOX metabolite, 12(S)-HETE, were examined in 50 NSCLC serum samples, and correlated with serum VEGF. A panel of NSCLC cell lines were treated with baicalein (10 uM), a selective inhibitor of 12-LOX, or 12(S)-HETE (100 ng\\/ml) and cell survival\\/proliferation examined by BrdU. Apoptosis following 12-LOX inhibition was examined by HCS and validated by FACS and DNA laddering. The effect of 12-LOX inhibition on NSCLC tumour growth and survival was examined in-vivo using an athymic nude mouse model. Gene alterations following 12-LOX inhibition in NSCLC cell lines were assessed by qPCR arrays and validated by RT-PCR. Transient transfection methods were used to examine the effects of 12-LOX overexpression in NSCLC cells. Results: 12-LOX expression was observed to a varying degree in human lung cancers of varying histological subtypes. 12(S)-HETE levels were correlated (p<0.05) with those of VEGF. Baicalein inhibited proliferation\\/survival in all cell lines, while 12(S)-HETE increased proliferation. 12-LOX inhibition increased apoptosis, indicated by a reduction in f-actin content and mitochondrial mass potential. Treatment with baicalein significantly reduced the growth of NSCLC tumours and increased overall survival in athymic nude mice. qPCR array data implicated a number of apoptosis\\/angiogenesis genes regulating these effects, including bcl-2, VEGF, integrin A2 and A4. 12-LOX overexpression resulted in an increase in VEGF secretion, confirming qPCR observations. Conclusions: 12-LOX is a survival factor\\/potential target in

  12. Loco-regional morbidity after breast conservation and axillary lymph node dissection for early breast cancer with or without regional nodes radiotherapy, perspectives in modern breast cancer treatment: the Skagen Trial 1 is active

    DEFF Research Database (Denmark)

    Nielsen, Hanne Melgaard; Friis, Rasmus Blechingberg; Linnet, Søren

    2017-01-01

    BACKGROUND: Axillary lymph node dissection (ALND) and adjuvant radiotherapy (RT) in early breast cancer are associated with a risk of morbidity, including lymphedema and impaired shoulder mobility. The aim of this study was to evaluate loco-regional morbidity after breast conserving surgery (BCS...

  13. Isolated loco-regional recurrence of breast cancer is more common in young patients and following breast conserving therapy : Long-term results of European Organisation for Research and Treatment of Cancer studies

    NARCIS (Netherlands)

    de Bock, Truuske; van der Hage, J.A.; Putter, H.; Bonnema, J.; Bartelink, H.; van de Velde, C.J.

    The aim of this study was to evaluate prognostic factors for isolated loco-regional recurrence in patients treated for invasive stage I or H breast cancer. The study population comprised 3602 women who had undergone primary surgery for early stage breast cancer, who were enrolled in European

  14. Patterns of failure and prognostic factors in resected extrahepatic bile duct cancer: implication for adjuvant radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Koo, Tae Ryool; Eom, Keun Yong; Kim, In Ah; Cho, Jai Young; Yoon, Yoo Seok; Hwang, Dae Wook; Han, Ho Seong; Kim, Jae Sung [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2014-06-15

    To find the applicability of adjuvant radiotherapy for extrahepatic bile duct cancer (EBDC), we analyzed the pattern of failure and evaluate prognostic factors of locoregional failure after curative resection without adjuvant treatment. In 97 patients with resected EBDC, the location of tumor was classified as proximal (n = 26) and distal (n = 71), using the junction of the cystic duct and common hepatic duct as the dividing point. Locoregional failure sites were categorized as follows: the hepatoduodenal ligament and tumor bed, the celiac artery and superior mesenteric artery, and other sites. The median follow-up time was 29 months for surviving patients. Three-year locoregional progression-free survival, progression-free survival, and overall survival rates were 50%, 42%, and 52%, respectively. Regarding initial failures, 79% and 81% were locoregional failures in proximal and distal EBDC patients, respectively. The most common site was the hepatoduodenal ligament and tumor bed. In the multivariate analysis, perineural invasion was associated with poor locoregional progression-free survival (p = 0.023) and progression-free survival (p = 0.012); and elevated postoperative CA19-9 (> or =37 U/mL) did with poor locoregional progression-free survival (p = 0.002), progression-free survival (p < 0.001) and overall survival (p < 0.001). Both proximal and distal EBDC showed remarkable proportion of locoregional failure. Perineural invasion and elevated postoperative CA19-9 were risk factors of locoregional failure. In these patients with high risk of locoregional failure, adjuvant radiotherapy could be considered to improve locoregional control.

  15. Geometric analysis of loco-regional recurrences in relation to pre-treatment hypoxia in patients with head and neck cancer.

    Science.gov (United States)

    Boeke, Simon; Thorwarth, Daniela; Mönnich, David; Pfannenberg, Christina; Reischl, Gerald; La Fougère, Christian; Nikolaou, Konstantin; Mauz, Paul-Stefan; Paulsen, Frank; Zips, Daniel; Welz, Stefan

    2017-11-01

    A previous pattern-of-failure study has suggested that up to 50% of the loco-regional failures (LRF) in head and neck squamous cell carcinoma (HNSCC) occur outside the initial hypoxic volume determined by [18F]-fluoromisonidazole-PET ([18F]-FMISO-PET). The aim of the present analysis was to correlate spatial patterns of failure with respect to the pretherapeutic dynamic [18F]-FMISO-PET/CT in HNSCC after radiochemotherapy (RCT). Within a running phase 2 trial using [18F]-FMISO-PET imaging prior to RCT in HNSCC patients (n = 54), we have observed so far 11 LRF with a minimum follow-up of 12 months. For nine patients, LRF imaging (CT or [18F]-FDG-PET/CT) for pattern-of-failure analysis was available. Analysis included the static 4-h hypoxic subvolume (VH) as well as a M-parameter volume (VM), which is derived from modeling of dynamic PET. Deformable image registration of the CT scan with the recurrent tumor to the pre-treatment [18F]-FMISO-PET/CT and the planning CT was done to quantify the hypoxic subvolumes compared to the recurrent tumor volume. Moreover, a point-of-origin analysis was performed. A total of five local, two regional and two loco-regional recurrences were detected. After deformable image registration of the CT scan with the recurrent tumor to the pre-treatment [18F]-FMISO-PET/CT and the planning CT, a significant overlap of the recurrence volume with [18F]-FMISO-positive subvolumes in the initial gross tumor volume (GTV) was observed. Median overlap of 40.2%, range 9.4-100.0%, for VH and 49.0%, range 4.4-96.4%, for VM was calculated. The point-of-origin analysis showed median distances of 0.0 mm, range 0.0-11.3 mm to VH and 8.6 mm, range 0.0-15.5 mm to VM, respectively. Our data suggest that loco-regional recurrences after RCT originate from the initial GTV (primary tumor and/or lymph node metastases) containing hypoxic subvolumes, which supports the concept of hypoxia imaging-based dose escalation.

  16. Survival of Sami cancer patients

    Directory of Open Access Journals (Sweden)

    Leena Soininen

    2012-07-01

    Full Text Available Objectives. The incidence of cancer among the indigenous Sami people of Northern Finland is lower than among the Finnish general population. The survival of Sami cancer patients is not known, and therefore it is the object of this study. Study design. The cohort consisted of 2,091 Sami and 4,161 non-Sami who lived on 31 December 1978 in the two Sami municipalities of Inari and Utsjoki, which are located in Northern Finland and are 300–500 km away from the nearest central hospital. The survival experience of Sami and non-Sami cancer patients diagnosed in this cohort during 1979–2009 was compared with that of the Finnish patients outside the cohort. Methods. The Sami and non-Sami cancer patients were matched to other Finnish cancer patients for gender, age and year of diagnosis and for the site of cancer. An additional matching was done for the stage at diagnosis. Cancer-specific survival analyses were made using the Kaplan–Meier method and Cox regression modelling. Results. There were 204 Sami and 391 non-Sami cancer cases in the cohort, 20,181 matched controls without matching with stage, and 7,874 stage-matched controls. In the cancer-specific analysis without stage variable, the hazard ratio for Sami was 1.05 (95% confidence interval 0.85–1.30 and for non-Sami 1.02 (0.86–1.20, indicating no difference between the survival of those groups and other patients in Finland. Likewise, when the same was done by also matching the stage, there was no difference in cancer survival. Conclusion. Long distances to medical care or Sami ethnicity have no influence on the cancer patient survival in Northern Finland.

  17. Randomized controlled clinical trial of the 24-months survival of composite resin restorations after one-step incomplete and complete excavation on primary teeth.

    Science.gov (United States)

    Franzon, R; Opdam, N J; Guimarães, L F; Demarco, F F; Casagrande, L; Haas, A N; Araujo, F B

    2015-10-01

    This randomized clinical trial aimed to compare the 24-months survival of composite restorations in primary molars after partial caries removal (PCR) and total caries removal (TCR). Forty-eight children aged 3-8 years with at least one molar with a deep carious lesion were included (PCR; n=66; TCR; n=54). For PCR, excavation was stopped when dentine with a leathery consistency was achieved; in the TCR group, total absence of carious tissue was confirmed using a blunt-tipped probe. Pulpotomy was performed in cases of pulp exposure. Success was assessed by modified USPHS criteria with Alpha and Bravo scores recorded as success. Pulp exposure occurred in 1 and 15 of the teeth treated with PCR and TCR respectively (p<0.01). The restorations survival rate after 24 months was 66% (PCR) and 86% (TCR) (p=0.03). When teeth that received pulpotomy were analyzed separately, the survival rate was 92% (p=0.09). PCR performed in occlusoproximal restorations demonstrated the lowest success rate (p=0.002). PCR increases 2.90 times the probability of having a restorative failure compared to TCR (p=0.03), after adjusting for cavity type. When pulp exposure and restoration failure were considered as the outcome, there was no significant difference between the two groups (p=0.10) with success rates of 64% (PCR) and 61% (TCR). Collectively, deciduous teeth submitted to PCR prevented pulp exposure and, consequently, more invasive treatments; otherwise, PCR yielded lower longevity for composite restoration compared to TCR, suggesting that PCR restorations need to be followed over time, especially when multi-surface restorations are involved. Composite restorations on carious remaining tissue require monitoring over time, especially those performed in more than one surface. Even if the restorations present shortcomings over the time, the majority of them are subject to repair, allowing more conservative approaches for teeth with deep caries lesions. Copyright © 2015 Elsevier Ltd. All

  18. Program Cell Death Receptor-1-Mediated Invariant Natural Killer T-Cell Control of Peritoneal Macrophage Modulates Survival in Neonatal Sepsis

    Directory of Open Access Journals (Sweden)

    Eleanor A. Fallon

    2017-11-01

    Full Text Available We have shown that invariant natural killer T (iNKT cells mediate sepsis-induced end-organ changes and immune responses, including macrophage bacterial phagocytosis, a finding regulated by the check point protein program cell death receptor-1 (PD-1. Furthermore, PD-1 mediates mortality in both adult and neonatal murine sepsis as well as in surgical patients. Given our previous findings, we hypothesize that iNKT cells will also modulate neonatal sepsis survival, and that this effect is regulated in part through PD-1. We utilized a polymicrobial intra-peritoneal cecal slurry (CS sepsis model in wild type (WT, iNKT−/− or PD-1−/− 5–7 day old neonatal pups. Typically, tissues were harvested at 24 h for various bioassays/histology and, in some cases, survival was assessed for up to 7 days. Interestingly, similar to what we recently reported for PD-1−/− mice following CS, iNKT−/−-deficient animals exhibit a markedly improved survival vs. WT. Histologically, minor alterations in liver architectural, which were noted in WT pups, were attenuated in both iNKT−/− and PD-1−/− pups. Following CS, PECAM-1 expression was unchanged in the WT pups but increased in both iNKT−/− and PD-1−/− pups. In WT, following CS the emergence of a Ly6Clow subpopulation was noted among the influxed peritoneal macrophage population. Conversely, within iNKT−/− pups, there were fewer peritoneal macrophages and a greater percentage of Ly6Chigh macrophages. We show not only a key role for iNKT cells in affecting end-organ damage as well as alterations in phagocytes phenotypes in neonatal sepsis but that this iNKT cell mediated effect is driven by the central checkpoint protein PD-1.

  19. Comparison of survival rates between 3D conformal radiotherapy and intensity-modulated radiotherapy in patients with stage Ⅲ non–small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Kong M

    2016-11-01

    Full Text Available Moonkyoo Kong, Seong Eon Hong Department of Radiation Oncology, Kyung Hee University Medical Center, Kyung Hee University School of Medicine, Seoul, Republic of Korea Purpose: Randomized trials showing a clear survival benefit of intensity-modulated radiotherapy (IMRT over 3-dimensional conformal radiotherapy (3D-CRT in the treatment of lung cancer are lacking. This study compared the survival rates of patients with stage III non-small cell lung cancer who were treated with either 3D-CRT or IMRT and analyzed the prognostic factors for survival.Methods: From January 2008 to July 2015, 19 patients were treated with IMRT and 30 were treated with 3D-CRT in our institution. The choice between 3D-CRT and IMRT was determined by the physician based on tumor extent and general condition of the patients. The primary endpoint of this study was overall survival. The secondary endpoints were loco-regional recurrence-free survival, distant metastasis-free survival, and the incidence of radiation-induced lung and esophageal toxicities. Results: The 1- and 2-year overall survival rates were 94.7% and 77.1% in the IMRT group and 76.7% and 52.5% in the 3D-CRT group, respectively. The overall survival rates of the IMRT group were higher than those of the 3D-CRT group; however, these differences were not statistically significant (P=0.072. Gross tumor volume was significantly associated with the overall survival rate. The 1- and 2-year loco-regional recurrence-free survival rates were 63.2% and 51% in the IMRT group and 67.5% and 48.1% in the 3D-CRT group (P=0.897, respectively. The 1- and 2-year distant metastasis-free survival rates were 78.9% and 68.4% in the IMRT group and 62.6% and 40.9% in the 3D-CRT group (P=0.120, respectively. Chemotherapy and treatment interruption were significantly associated with distant metastasis-free survival.Conclusion: IMRT showed comparable or better overall survival compared with 3D-CRT in patients with stage III non-small cell

  20. Survival after definitive (chemo)radiotherapy in esophageal cancer patients: a population-based study in the north-East Netherlands.

    Science.gov (United States)

    Smit, Justin K; Muijs, Christina T; Burgerhof, Johannes G M; Paardekooper, Gabriel; Timmer, Paul R; Muller, Karin; Woutersen, Dankert; Mul, Véronique E; Beukema, Jannet C; Hospers, Geke A P; van Dijk, Boukje A C; Langendijk, Johannes A; Plukker, John Th M

    2013-06-01

    Definitive (chemo)radiotherapy is employed in esophageal cancer patients as an alternative for patients considered medically unfit for surgery or having unresectable tumors. We evaluated a population-based cohort to improve the selection for intensified nonsurgical strategies and to identify prognostic factors. Patients who had squamous cell carcinoma (SCC) or adenocarcinoma (AC) were treated in four referral centers in the north-east Netherlands with definitive chemoradiotherapy (dCRT) or radiotherapy (dRT) between 1996 and 2008. Of the 287 included patients, 110 were treated with dCRT and 177 with dRT. Median overall survival (OS) was 11 months (95 % confidence interval: 10-12 months), with OS of 22 and 8 % and disease-free survival (DFS) of 16 and 5 % at 2 and 5 years, respectively. DFS at 2 and 5 years was 24 and 9 % for SCC versus 10 and 2 % for AC patients (P = 0.006). OS after 2 and 5 years was 29 and 14 % for SCC patients versus 17 and 3 % for AC patients (P = 0.044). On multivariate Cox regression, SCC was an independent prognostic factor for DFS [P = 0.020, hazard ratio (HR) = 0.71] and OS (P = 0.047, HR = 0.76). On matched cohort analysis, DFS was higher in the dCRT group compared with dRT patients (P = 0.016). The locoregional failure rate was lower in the dCRT group and in SCC patients (P = 0.001 and 0.046). Long-term results and the local control rate in SCC patients were better after definitive (chemo)radiotherapy compared with in AC patients. SCC was an independent prognostic factor for survival. Definitive chemoradiotherapy leads to improved local control rate and DFS.

  1. Internal and external validation of an ESTRO delineation guideline - dependent automated segmentation tool for loco-regional radiation therapy of early breast cancer

    DEFF Research Database (Denmark)

    Eldesoky, Ahmed R; Yates, Esben S; Nyeng, Tine B

    2016-01-01

    BACKGROUND AND PURPOSE: To internally and externally validate an atlas based automated segmentation (ABAS) in loco-regional radiation therapy of breast cancer. MATERIALS AND METHODS: Structures of 60 patients delineated according to the ESTRO consensus guideline were included in four categorized......-regional radiation therapy in a multi-institutional setting. However, manual correction of some structures is important before clinical use. The ABAS is now available for routine clinical use in Danish patients....... and axillary nodal levels and poor agreement for interpectoral, internal mammary nodal regions and LADCA. Correcting ABAS significantly improved all the results. External validation of ABAS showed comparable results. CONCLUSIONS: ABAS is a clinically useful tool for segmenting structures in breast cancer loco...

  2. Hybrid {sup 18}F-FDG PET/MRI might improve locoregional staging of breast cancer patients prior to neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Goorts, Briete; Nijnatten, Thiemo J.A. van [Maastricht University Medical Center, GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Maastricht University Medical Center, Department of Surgery, P.O. Box 5800, Maastricht (Netherlands); Maastricht University Medical Center, Department of Radiology and Nuclear Medicine, Maastricht (Netherlands); Voeoe, Stefan; Wildberger, Joachim E.; Lobbes, Marc B.I. [Maastricht University Medical Center, Department of Radiology and Nuclear Medicine, Maastricht (Netherlands); Kooreman, Loes F.S. [Maastricht University Medical Center, GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Maastricht University Medical Center, Department of Pathology, Maastricht (Netherlands); Boer, Maaike de [Maastricht University Medical Center, Department of Medical Oncology, Maastricht (Netherlands); Keymeulen, Kristien B.M.I. [Maastricht University Medical Center, Department of Surgery, P.O. Box 5800, Maastricht (Netherlands); Aarnoutse, Romy; Smidt, Marjolein L. [Maastricht University Medical Center, GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Maastricht University Medical Center, Department of Surgery, P.O. Box 5800, Maastricht (Netherlands); Mottaghy, Felix M. [Maastricht University Medical Center, Department of Radiology and Nuclear Medicine, Maastricht (Netherlands); RWTH Aachen University Hospital, Department of Nuclear Medicine, Aachen (Germany)

    2017-10-15

    Our purpose in this study was to assess the added clinical value of hybrid {sup 18}F-FDG-PET/MRI compared to conventional imaging for locoregional staging in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). In this prospective study, primary invasive cT2-4 N0 or cT1-4 N+ breast cancer patients undergoing NAC were included. A PET/MRI breast protocol was performed before treatment. MR images were evaluated by a breast radiologist, blinded for PET images. PET images were evaluated by a nuclear physician. Afterwards, a combined PET/MRI report was written. PET/MRI staging was compared to conventional imaging, i.e., mammography, ultrasound and MRI. The proportion of patients with a modified treatment plan based on PET/MRI findings was analyzed. A total of 40 patients was included. PET/MRI was of added clinical value in 20.0% (8/40) of patients, changing the treatment plan in 10% and confirming the malignancy of suspicious lesions on MRI in another 10%. In seven (17.5%) patients radiotherapy fields were extended because of additional or affirmative PET/MRI findings being lymph node metastases (n = 5) and sternal bone metastases (n = 2). In one (2.5%) patient radiotherapy fields were reduced because of fewer lymph node metastases on PET/MRI compared to conventional imaging. Interestingly, all treatment changes were based on differences in number of lymph nodes suspicious for metastasis or number of distant metastasis, whereas differences in intramammary tumor extent were not observed. Prior to NAC, PET/MRI shows promising results for locoregional staging compared to conventional imaging, changing the treatment plan in 10% of patients and potentially replacing PET/CT or tissue sampling in another 10% of patients. (orig.)

  3. Mapping of failures after radiochemotherapy in patients with non-metastatic esophageal cancer: A posteriori analysis of the dose distribution in the sites of loco-regional relapse.

    Science.gov (United States)

    Bednarek, Coraline; Crehange, Gilles; Quivrin, Magali; Cueff, Adèle; Vulquin, Noémie; Chevalier, Cédric; Cerda, Thomas; Petegnief, Yolande; Mazoyer, Frédéric; Maingon, Philippe; Bosset, Jean François; Servagi Vernat, Stéphanie

    2015-08-01

    We aimed to evaluate the patterns of loco-regional failure (LRF) after exclusive chemoradiotherapy (eCRT) for esophageal cancer with respect to planned dose and/or the incidental (unplanned) dose outside target volumes. Co-image registration of CT or (18)F-FDG PET-CT at the time of failure (tf) and at the time of CRT (t0) was performed in 34 patients with LRF. Dosimetric parameters with regard to local failure (LF), nodal failure (NF) and involved nodal stations (NS) were derived. Twenty-two patients (64.7%) had LF, the majority of which (95.5%) were located at the epicenter of the GTV of the primary tumor. The mean doses recalculated to the NS at tf were more likely to be lower than the planned dose delivered to the PTV at t0: Dmean=33.9 ± 20.8 Gy vs 52.2 ± 8.5 Gy (p=0.0009), D95%=27.5 ± 21 Gy vs 46.1 ± 4.8 Gy (p=0.004). Among the 12 patients with NF outside the elective nodal irradiation (ENI) volume, Dmean of NS outside the ENI was significantly lower (19.4 ± 21.4 Gy) than the Dmean of NS with failure within the ENI (45.1 ± 6.1 Gy, p=0.01). Loco-regional failure after exclusive chemoradiotherapy for esophageal cancer may be due to an inadequately low dose. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Induction of VX2 para-renal carcinoma in rabbits: generation of animal model for loco-regional treatments of solid tumors.

    Science.gov (United States)

    Bimonte, Sabrina; Leongito, Maddalena; Piccirillo, Mauro; Tamma, Maria Luisa; Vallifuoco, Marianna; Bracco, Adele; Mancini, Antonio; Di Napoli, Daniele; Castaldo, Sigismondo; Cozzolino, Santolo; Iacobellis, Francesca; Grassi, Roberto; Granata, Vincenza; Lastoria, Secondo; Curley, Steven; Izzo, Francesco

    2016-01-01

    Animal models of para-renal cancer can provide useful information for the evaluation of tumor response to loco-regional therapy experiments in solid tumors. The aim of our study was to establish a rabbit para-renal cancer model using locally implanted VX2 tumors. In order to generate a rabbit model of para-renal cancer, we established four hind limb donor rabbits by using frozen VX2 tumor samples. Following inoculation, rabbits were monitored for appetite and signs of pain. Viable tumors appeared as palpable nodules within 2 weeks of inoculation. Tumor growth was confirmed in all rabbits by high-resolution ultrasound analysis and histology. Once tumor growth was established, hind limb tumors extraction was used for tumor line propagation and para-renal tumor creation. Twenty-one rabbit models bearing para-renal cancer were established by implanting VX2 tumor into the para-renal capsula. Tumors developed into discreet 2-3 cm nodules within 1-3 weeks of implantation. Serial renal ultrasonography follow-up, starting 1 week after tumor implantation, was performed. Two weeks after tumor implantation, rabbits were euthanized and tumors and other organs were collected for histopathology. Tumor growth after VX2 tumor fragment implantation was confirmed in all rabbits by high-resolution ultrasound (US) imaging examinations of the para-renal regions and was measured with digital caliper. The para-renal injection of VX2 tumor fragments, achieved tumor growth in 100% of cases. All data were confirmed by histological analysis. We generated for the first time, a model of para-renal cancer by surgical tumor implantation of VX2 frozen tumor fragments into rabbit's para-renal region. This method minimizes the development of metastases and the use of non-necrotic tumors and will optimize the evaluation of tumor response to loco-regional therapy experiments.

  5. Extrahepatic metastases occur in a minority of hepatocellular carcinoma patients treated with locoregional therapies: analyzing patterns of progression in 285 patients.

    Science.gov (United States)

    Senthilnathan, Seanthan; Memon, Khairuddin; Lewandowski, Robert J; Kulik, Laura; Mulcahy, Mary F; Riaz, Ahsun; Miller, Frank H; Yaghmai, Vahid; Nikolaidis, Paul; Wang, Edward; Baker, Talia; Abecassis, Michael; Benson, Al B; Omary, Reed A; Salem, Riad

    2012-05-01

    Although most cancers are considered predominantly systemic processes, this may not hold true for hepatocellular carcinoma (HCC). The literature regarding patterns of progression of HCC (local versus systemic) has been relatively sparse. Our objectives were to: (1) analyze patterns of progression in HCC patients presenting with intrahepatic disease from initial treatment until death, and (2) identify clinically relevant risk factors for the development of metastases. Over a 9-year period, 285 patients treated with transarterial locoregional therapies underwent scheduled imaging follow-up from treatment until death and were categorized by pattern of progression: (i) intrahepatic (increased tumor enhancement/size, development/progression of vascular invasion, new hepatic lesions) progression or (ii) extrahepatic (adrenal/bone/lung/lymph node) metastases. Uni/multivariate analyses assessing the risk factors for the development of metastases were performed. The median time from last scan to death was 2.4 months (interquartile range: 1.3-4.8 months). The time to development of metastases, vascular invasion, and/or new lesions was 13.8 months (confidence interval: 11.3-17.7 months). Of the 209 patients followed until death, only 50 developed extrahepatic metastases (24%). Multivariate analyses identified age 200 ng/mL (P = 0.04), and vascular invasion (P = 0.017) as significant predictors of metastases development. Knowledge of the risk factors associated with the development of metastases may help guide assessment of patient prognosis. Because 76% of patients presenting with local disease treated with locoregional therapies die without developing extrahepatic metastases, the notion of HCC as a systemic disease, as detected by imaging, may be reconsidered. Copyright © 2011 American Association for the Study of Liver Diseases.

  6. Accelerated partial breast irradiation using intensity-modulated radiotherapy versus whole breast irradiation: 5-year survival analysis of a phase 3 randomised controlled trial.

    Science.gov (United States)

    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

  7. Multinationals and plant survival

    DEFF Research Database (Denmark)

    Bandick, Roger

    2010-01-01

    The aim of this paper is twofold: first, to investigate how different ownership structures affect plant survival, and second, to analyze how the presence of foreign multinational enterprises (MNEs) affects domestic plants’ survival. Using a unique and detailed data set on the Swedish manufacturing...... sector, I am able to separate plants into those owned by foreign MNEs, domestic MNEs, exporting non-MNEs, and purely domestic firms. In line with previous findings, the result, when conditioned on other factors affecting survival, shows that foreign MNE plants have lower survival rates than non......-MNE plants. However, separating the non-MNEs into exporters and non-exporters, the result shows that foreign MNE plants have higher survival rates than non-exporting non-MNEs, while the survival rates of foreign MNE plants and exporting non-MNE plants do not seem to differ. Moreover, the simple non...

  8. Long-term safety of unopposed estrogen used by women surviving myocardial infarction: 14-year follow-up of the ESPRIT randomised controlled trial.

    Science.gov (United States)

    Cherry, N; McNamee, R; Heagerty, A; Kitchener, H; Hannaford, P

    2014-05-01

    To compare health outcomes during 14-year observational follow-up in women initially randomised to unopposed estrogen or placebo. At recruitment to the Estrogen for the Prevention of Re-Infarction Trial (ESPRIT) women were assigned to estradiol valerate: 2 mg or placebo treatment for 2 years. Women were recruited from 35 hospitals in the northwest of England and Wales in July 1996-February 2000. Women aged 50-69 surviving their first myocardial infarction. All women were followed by data linkage to UK mortality and cancer records; mean follow-up 14.1 and 12.6 years, respectively. In an intention-to-treat analysis, hazard ratios (HRs) were computed, overall and stratified by age at recruitment. Death (all-cause, cardiac disease, stroke or cancer) and cancer incidence (any, breast or endometrium). There were 418 deaths in 1017 women randomised. The all-cause mortality HR of 1.07 (95% CI 0.88-1.29) indicated no significant difference between treatment groups. Women aged 50-59 years at recruitment had lower HRs than women aged 60-69 years for all outcomes except ischaemic heart disease. Among 149 incident cancers there were seven cases of breast cancer in the intervention arm and 15 in the placebo; HR 0.47 (95% CI 0.19-1.15). There were no deaths from endometrial cancer but three incident cases, one in the active arm and two in placebo. These results suggest that unopposed estrogen may be used safely by women with an intact uterus surviving a first myocardial infarction. © 2014 Royal College of Obstetricians and Gynaecologists.

  9. Implant survival and marginal bone loss at turned and oxidized implants in periodontitis-susceptible smokers and never-smokers: a retrospective, clinical, radiographic case-control study.

    Science.gov (United States)

    Sayardoust, Shariel; Gröndahl, Kerstin; Johansson, Eva; Thomsen, Peter; Slotte, Christer

    2013-12-01

    Little is known about the long-term outcome of oxidized surface oral implants, especially in periodontitis-susceptible smokers. The aim of this study is to determine implant survival and marginal bone loss at turned and oxidized implants in smokers and never-smokers with periodontitis. Forty smokers and 40 never-smokers with experience of advanced periodontal disease, treated with implants 5 years previously, are included in this study. Groups were matched for sex, oral hygiene, and implant distribution, and patients were subgrouped by implant surface type (turned or oxidized). The overall implant survival rate was 96.9% in never-smokers and 89.6% in smokers. Compared with oxidized implants, turned implants failed more frequently in smokers. In smokers, mean (standard error of the mean) marginal bone loss at 5 years was 1.54 (0.21) mm at turned and 1.16 (0.24) mm at oxidized implants. In never-smokers, significantly greater bone loss was found at oxidized implants, 1.26 (0.15) mm, than at turned implants, 0.84 (0.14) mm. Oxidized implants demonstrated similar bone loss for both groups. Turned implants lost significantly more bone in smokers. Compared with never-smokers, the smokers' likelihood ratio for implant failure was 4.68, 6.40 for turned and 0.00 for oxidized implants. The results of the study underscore the need for prevention and cessation of smoking. Turned implants failed more frequently and lost more marginal bone in smokers. In contrast, oxidized implants showed similar failure rates and bone loss in smokers and never-smokers. Turned implants displayed less bone loss than oxidized implants in never-smokers. Oxidized surface implants are more suitable for patients susceptible to periodontitis who smoke.

  10. MicroRNA networks regulated by all-trans retinoic acid and Lapatinib control the growth, survival and motility of breast cancer cells

    Science.gov (United States)

    Kurosaki, Mami; Paroni, Gabriela; Zanetti, Adriana; Gianni, Maurizio; Bolis, Marco; Lupi, Monica; Tsykin, Anna; Goodall, Gregory J.; Garattini, Enrico

    2015-01-01

    SKBR3-cells, characterized by ERBB2/RARA co-amplification, represent a subgroup of HER2+ breast-cancers sensitive to all-trans retinoic acid (ATRA) and Lapatinib. In this model, the two agents alone or in combination modulate the expression of 174 microRNAs (miRs). These miRs and predicted target-transcripts are organized in four interconnected modules (Module-1 to -4). Module-1 and Module-3 consist of ATRA/Lapatinib up-regulated and potentially anti-oncogenic miRs, while Module-2 contains ATRA/Lapatinib down-regulated and potentially pro-oncogenic miRs. Consistent with this, the expression levels of Module-1/-3 and Module-2 miRs are higher and lower, respectively, in normal mammary tissues relative to ductal-carcinoma-in-situ, invasive-ductal-carcinoma and metastases. This indicates associations between tumor-progression and the expression profiles of Module-1 to -3 miRs. Similar associations are observed with tumor proliferation-scores, staging, size and overall-survival using TCGA (The Cancer Genome Atlas) data. Forced expression of Module-1 miRs, (miR-29a-3p; miR-874-3p) inhibit SKBR3-cell growth and Module-3 miRs (miR-575; miR-1225-5p) reduce growth and motility. Module-2 miRs (miR-125a; miR-193; miR-210) increase SKBR3 cell growth, survival and motility. Some of these effects are of general significance, being replicated in other breast cancer cell lines representing the heterogeneity of this disease. Finally, our study demonstrates that HIPK2-kinase and the PLCXD1-phospholipase-C are novel targets of miR-193a-5p/miR-210-3p and miR-575/miR-1225-5p, respectively. PMID:25961594

  11. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial

    Science.gov (United States)

    James, Nicholas D; Sydes, Matthew R; Clarke, Noel W; Mason, Malcolm D; Dearnaley, David P; Spears, Melissa R; Ritchie, Alastair W S; Parker, Christopher C; Russell, J Martin; Attard, Gerhardt; de Bono, Johann; Cross, William; Jones, Rob J; Thalmann, George; Amos, Claire; Matheson, David; Millman, Robin; Alzouebi, Mymoona; Beesley, Sharon; Birtle, Alison J; Brock, Susannah; Cathomas, Richard; Chakraborti, Prabir; Chowdhury, Simon; Cook, Audrey; Elliott, Tony; Gale, Joanna; Gibbs, Stephanie; Graham, John D; Hetherington, John; Hughes, Robert; Laing, Robert; McKinna, Fiona; McLaren, Duncan B; O'Sullivan, Joe M; Parikh, Omi; Peedell, Clive; Protheroe, Andrew; Robinson, Angus J; Srihari, Narayanan; Srinivasan, Rajaguru; Staffurth, John; Sundar, Santhanam; Tolan, Shaun; Tsang, David; Wagstaff, John; Parmar, Mahesh K B

    2016-01-01

    Summary Background Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone. Methods Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m2) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544). Findings 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60–71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6

  12. FBXW7/hCDC4 controls glioma cell proliferation in vitro and is a prognostic marker for survival in glioblastoma patients

    Directory of Open Access Journals (Sweden)

    Hagedorn Martin

    2007-02-01

    Full Text Available Abstract Background In the quest for novel molecular mediators of glioma progression, we studied the regulation of FBXW7 (hCDC4/hAGO/SEL10, its association with survival of patients with glioblastoma and its potential role as a tumor suppressor gene in glioma cells. The F-box protein Fbxw7 is a component of SCFFbxw7, a Skp1-Cul1-F-box E3 ubiquitin ligase complex that tags specific proteins for proteasome degradation. FBXW7 is mutated in several human cancers and functions as a haploinsufficient tumor suppressor in mice. Any of the identified targets, Cyclin E, c-Myc, c-Jun, Notch1/4 and Aurora-A may have oncogenic properties when accumulated in tumors with FBXW7 loss. Results We tested the expression of FBXW7 in human glioma biopsies by quantitative PCR and compared the transcript levels of grade IV glioma (glioblastoma, G-IV with those of grade II tumors (G-II. In more than 80% G-IV, expression of FBXW7 was significantly reduced. In addition, levels of FBXW7 were correlated with survival indicating a possible implication in tumor aggressiveness. Locus 4q31.3 which carries FBXW7 was investigated by in situ hybridization on biopsy touchprints. This excluded allelic loss as the principal cause for low expression of FBXW7 in G-IV tumors. Two targets of Fbxw7, Aurora-A and Notch4 were preferentially immunodetected in G-IV biopsies. Next, we investigated the effects of FBXW7 misregulation in glioma cells. U87 cells overexpressing nuclear isoforms of Fbxw7 lose the expression of the proliferation markers PCNA and Ki-67, and get counterselected in vitro. This observation fits well with the hypothesis that Fbxw7 functions as a tumor suppressor in astroglial cells. Finally, FBXW7 knockdown in U87 cells leads to defects in mitosis that may promote aneuploidy in progressing glioma. Conclusion Our results show that FBXW7 expression is a prognostic marker for patients with glioblastoma. We suggest that loss of FBXW7 plays an important role in glioma

  13. Breast conserving treatment of breast carcinoma T2 ({<=} 4 cm) and T3 by neoadjuvant chemotherapy, quadrantectomy, high dose rate brachytherapy as a boost, external beam radiotherapy and adjuvant chemotherapy: local control and overall survival analysis; Tratamento conservador do cancer de mama T2 ({<=} 4 cm) e T3 por quimioterapia neoadjuvante, quadrantectomia, braquiterapia com alta taxa de dose como reforco de dose, teleterapia complementar e quimioterapia adjuvante: analise de controle local e sobrevida global

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Celia Regina; Miziara Filho, Miguel Abrao; Fogaroli, Ricardo Cesar; Baraldi, Helena Espindola; Pellizzon, Antonio Cassio Assis; Pelosi, Edilson Lopes [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil). Servico de Radioterapia], e-mail: celiarsoares@terra.com.br; Fristachi, Carlos Elias [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil). Servico de Onco-Ginecologia e Mastologia; Paes, Roberto Pinto [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil)

    2008-12-15

    Objective: to assess the treatment of breast cancer T2 ({<=} 4 cm) and T3 through neoadjuvant chemotherapy, quadrantectomy and high dose rate brachytherapy as a boost, complementary radiotherapy and adjuvant chemotherapy, considering local control and overall survival. Material and method: this clinical prospective descriptive study was based on the evaluation of 88 patients ranging from 30 to 70 years old, with infiltrating ductal carcinoma, clinical stage IIb and IIIa, responsive