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Background: We performed an analysis of the National Cancer Database to determine optimal doses of conventionally-fractionated adjuvant radiotherapy for patients with stage I/II or III Merkel cell carcinoma., Methods: The cohort included 2735 patients with resected Merkel cell carcinoma of the head and neck, trunk or extremities receiving radiotherapy. Exclusion criteria included doses of radiotherapy <30 or >80 Gy, or dose per fraction >200 or <180 cGy. Recursive partitioning analysis and spline models were used to select dose thresholds. Multivariable Cox regression was performed to validate thresholds with respect to overall survival., Results: Recursive partitioning analysis models defined a threshold of 57 Gy for stage I/II Merkel cell carcinoma, above which 3-year overall survival rate was decreased (P < 0.0001). The 3-year overall survival rate for patients receiving 50.0-57.0 Gy (81.2%) was greater compared to doses of 30.0-49.9 Gy (75.3%) or >57.0 Gy (70%, P < 0.0001). Doses > 57.0 Gy were associated with an increased hazard of death (1.31, confidence interval 1.07-1.60) with respect to doses of 50.0-57.0 Gy. Doses < 50.0 Gy for stage III Merkel cell carcinoma were associated with worsened 3-year overall survival (P < 0.0001) and increased hazard of death (2.01, confidence interval 1.43-2.82) with respect to doses between 50.0 and 57.0 Gy., Conclusions: Our results support doses of 50-57 Gy for most patients with stage I/II Merkel cell carcinoma receiving conventionally-fractionated adjuvant radiotherapy. In contrast to a prior National Cancer Database analysis, our results suggest doses ≥ 50 Gy should be strongly considered for patients with stage III Merkel cell carcinoma regardless of anatomic subsite., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

This study compares the outcomes of different postoperative radiation fields for locoregionally advanced thoracic esophageal squamous cell carcinoma (ESCC) patients. This is a multi-institution randomized phase II trial and noninferior study. Patients with ESCC who had undergone esophagectomy (stage T3-4N0-3M0) were enrolled and randomized into the large-field irradiation arm (LFI; tumor bed and elective lymph node region) and small-field irradiation arm (SFI; tumor bed only). The primary endpoint was whether the disease-free survival (DFS) of SFI was not inferior to LFI. The secondary endpoint was to evaluate the rationality of the radiation target volume by analyzing failure patterns. One hundred twenty-one patients (64 patients for LFI and 57 patients for SFI, respectively) were eligible in this mid-time analysis. The 1- and 3-year DFS was 79.9%, 46.2% for LFI and 67.6%, 44.3% for SFI, respectively (P = 0.414). The locoregional recurrence-free survival (LRFS) of LFI was significantly better than that of SFI (P = 0.003). However, there were no significant differences in the distant metastasis-free survival and overall survival between the two arms (P = 0.332, P = 0.405, respectively). The failure patterns of the two arms were significantly different (P = 0.002). For pT3-4N0-3M0 ESCC patients, postoperative radiotherapy with SFI showed a similar survival outcome to LFI. However, the LRFS of patients with SFI was worse than that of patients with LFI., (© The Author(s) 2019. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Adrenocortical carcinoma (ACC) is a rare malignancy with high rates of recurrence and poor prognosis. The role of radiotherapy (RT) in localized ACC has been controversial, and RT is not routinely offered., Objective: To evaluate the benefit of adjuvant RT on outcomes in ACC., Design: This is a retrospective propensity-matched analysis., Setting: All patients were seen through the University of Michigan's Endocrine Oncology program, and all those who underwent RT were treated at the University of Michigan., Participants: Of 424 patients with ACC, 78 were selected; 39 patients underwent adjuvant radiation., Intervention: Adjuvant RT to the tumor bed and adjacent lymph nodes., Main Outcomes Measures: Time to local failure, distant failure, or death., Results: Median follow-up time was 4.21 years (95% CI, 2.79 to 4.94). The median radiation dose was 55 Gy (range, 45 to 60). The 3-year overall survival estimate for patients improved from 48.6% for patients without RT (95% CI, 29.7 to 65.2) to 77.7% (95% CI, 56.3 to 89.5) with RT, with a hazard ratio (HR) of 3.59 (95% CI, 1.60 to 8.09; P = 0.002). RT improved local recurrence-free survival (RFS) from 34.2% (95% CI, 18.8 to 50.3) to 59.5% (95% CI, 39.0 to 75.0), with an HR of 2.67 (95% CI, 1.38 to 5.19; P = 0.0035). RT improved all RFS from 18.3% (95% CI, 6.7 to 34.3) to 46.7% (95% CI, 26.9 to 64.3), with an HR 2.59 (95% CI, 1.40 to 4.79; P = 0.0024)., Conclusions: In the largest single institution study to date, adjuvant RT after gross resection of ACC improved local RFS, all RFS, and overall survival in this propensity-matched analysis. Adjuvant RT should be considered a part of multidisciplinary management for patients with ACC., (Copyright © 2019 Endocrine Society.)

The survival advantage of radiotherapy (RT) for patients with metastatic esophagus cancer has not been adequately evaluated. This study aims to find out the role of RT for metastatic esophagus cancer and to find the different effect for RT to esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). This study included 5,970 metastatic esophagus cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database, registered from January 2004 to December 2013. Propensity score (PS) analysis with 1:1 nearest neighbor matching method was used to ensure well-balanced characteristics of all comparison groups by histological types. The Kaplan-Meier and Cox proportional hazardous models were used to evaluate the overall survival (OS), cancer-specific survival (CSS), and corresponding 95% confidence interval (CI). Generally speaking, EAC did not get survival benefit from RT (median OS for RT group vs. no-RT group-8.0, 7.6-8.4 vs. 9.0, 8.5-9.5, P = 0.073), whereas RT for metastatic ESCC did significantly improve OS (median OS for RT group vs. no-RT group-8.0, 7.4-8.6 vs. 7.0, 6.4-7.6, P = 0.044). Therefore, compared with adenocarcinoma, ESCC could get more survival benefit from RT.

Background: Lateral nodal disease in rectal cancer remains a subject of debate and is treated differently in the East and the West. The predictive value of lateral lymph node and MRI-detected extramural vascular invasion (mrEMVI) features on oncological outcomes was assessed in this study., Methods: In this retrospective cohort study, data on patients with cT3-4 rectal cancer within 8 cm from the anal verge were considered over a 5-year period (2009-2013). Lateral lymph node size, malignant features and mrEMVI features were evaluated and related to oncological outcomes., Results: In total, 192 patients were studied, of whom 30 (15·6 per cent) underwent short-course radiotherapy and 145 (75·5 per cent) received chemoradiotherapy. A lateral lymph node short-axis size of 10 mm or more was associated with a significantly higher 5-year lateral/presacral local recurrence rate of 37 per cent, compared with 7·7 per cent in nodes smaller than 10 mm (P = 0·041). Enlarged nodes did not result in a higher 5-year rate of distant metastasis (23 per cent versus 27·7 per cent in nodes smaller than 10 mm; P = 0·563). However, mrEMVI positivity was related to more metastatic disease (5-year rate 43 versus 26·3 per cent in the mrEMVI-negative group; P = 0·014), but not with increased lateral/presacral recurrence. mrEMVI occurred in 46·6 per cent of patients with nodes smaller than 10 mm, compared with 29 per cent in patients with nodes of 10 mm or larger (P = 0·267)., Conclusion: Although lateral nodal disease is more a local problem, mrEMVI mainly predicts distant recurrence. The results of this study showed an unacceptably high local recurrence rate in patients with a short axis of 10 mm or more, despite neoadjuvant (chemo)radiotherapy., (© 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Background: The prognostic equivalence between mastectomy and breast-conserving surgery (BCS) followed by radiotherapy was shown in pivotal trials conducted decades ago. Since then, detection and treatment of breast cancer have improved substantially and recent retrospective analyses point towards a survival benefit for less extensive breast surgery. Evidence for the association of such survival data with locoregional recurrence rates is largely lacking., Methods: The Swedish Multicentre Cohort Study prospectively included clinically node-negative patients with breast cancer who had planned sentinel node biopsy between 2000 and 2004. Axillary lymph node dissection was undertaken only in patients with sentinel node metastases. For the present investigation, adjusted survival analyses were used to compare patients who underwent BCS and postoperative radiotherapy with those who received mastectomy without radiotherapy., Results: Of 3518 patients in the Swedish Multicentre Cohort Study, 2767 were included in the present analysis; 2338 had BCS with postoperative radiotherapy and 429 had mastectomy without radiotherapy. Median follow-up was 156 months. BCS followed by whole-breast irradiation was superior to mastectomy without irradiation in terms of both overall survival (79·5 versus 64·3 per cent respectively at 13 years; P < 0·001) and breast cancer-specific survival (90·5 versus 84·0 per cent at 13 years; P < 0·001). The local recurrence rate did not differ between the two groups. The axillary recurrence-free survival rate at 13 years was significantly lower after mastectomy without irradiation (98·3 versus 96·2 per cent; P < 0·001)., Conclusion: The present data support the superiority of BCS with postoperative radiotherapy over mastectomy without radiotherapy. The axillary recurrence rate differed significantly, and could be one contributing factor in a complex explanatory model., (© 2018 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.)

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether the addition of postoperative radiotherapy (PORT) to adjuvant chemotherapy offers any benefit in patients undergoing curative resection for non-small cell lung cancer found to harbour mediastinal lymphadenopathy. A total of 77 papers were identified using the reported search, of which 11 represented the best evidence to answer the clinical question. Only studies reporting on survival data of patients receiving adjuvant chemotherapy with and without PORT were included in this analysis. The authors, date, journal, country, study type, population, outcomes and key results are tabulated. Six studies reported a statistically significant positive impact of PORT on long-term or disease-free survival (DFS) (P = 0.048-0.0001). Five more studies found no difference in terms of survival between patients receiving and not receiving PORT. Among the 11 studies, only two were randomized controlled, with one of them reporting improved disease-free (P = 0.041) but not overall survival (P = 0.073), while the other finding no difference in survival. Furthermore, three more studies reported on DFS and/or locoregional recurrence of the disease. One of these studies reported a significantly improved DFS among patients receiving PORT (P = 0.003), while two of them reported a reduced rate of locoregional recurrence in this group (P = 0.032-0.009). Many studies report a positive effect of PORT when combined in parallel or sequentially with adjuvant chemotherapy in terms of long-term, disease free survival or locoregional control of the disease in patients who have undergone surgical resection of NSCLC and are found to harbour N2 disease. However, these reports are counterbalanced by an almost equal number of studies which show no difference between PORT and no PORT. Only one study reported significantly increased radiation related adverse effects in patients undergoing chemotherapy and PORT., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Although chemotherapy is used routinely in pediatric medulloblastoma (MB) patients, its benefit for adult MB is unclear. We evaluated the survival impact of adjuvant chemotherapy in adult MB., Methods: Using the National Cancer Data Base, we identified patients aged 18 years and older who were diagnosed with MB in 2004-2012 and underwent surgical resection and adjuvant craniospinal irradiation (CSI). Patients were divided into those who received adjuvant CSI and chemotherapy (CRT) or CSI alone (RT). Predictors of CRT compared with RT were evaluated with univariable and multivariable logistic regression. Survival analysis was limited to patients receiving CSI doses between 23 and 36 Gy. Overall survival (OS) was evaluated using the Kaplan-Meier estimator, log-rank test, multivariable Cox proportional hazards modeling, and propensity score matching., Results: Of the 751 patients included, 520 (69.2%) received CRT, and 231 (30.8%) received RT. With median follow-up of 5.0 years, estimated 5-year OS was superior in patients receiving CRT versus RT (86.1% vs 71.6%, P < .0001). On multivariable analysis, after controlling for risk factors, CRT was associated with superior OS compared with RT (HR: 0.53; 95%CI: 0.32-0.88, P = .01). On planned subgroup analyses, the 5 year OS of patients receiving CRT versus RT was improved for M0 patients (P < .0001), for patients receiving 36 Gy CSI (P = .0007), and for M0 patients receiving 36 Gy CSI (P = .0008)., Conclusions: This national database analysis demonstrates that combined postoperative chemotherapy and radiotherapy are associated with superior survival for adult MB compared with radiotherapy alone, even for M0 patients who receive high-dose CSI., (© The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Background: Histological subtype influences both prognosis and patterns of treatment failure in retroperitoneal sarcoma. Previous studies on the efficacy of neoadjuvant radiotherapy (NRT) have incorporated multiple histological types with heterogeneous tumour biology. The survival impact of NRT specifically for patients with retroperitoneal liposarcoma is poorly defined., Methods: Patients who underwent resection with curative intent for retroperitoneal liposarcoma and who received NRT or surgery alone were identified in the US National Cancer Data Base (2004-2013). Cox regression was used to identify co-variables associated with overall survival. NRT and surgery-alone cohorts were matched 1 : 1 by propensity scores based on the survival hazard on Cox modelling. Overall survival was compared by Kaplan-Meier estimates., Results: A total of 2082 patients with retroperitoneal liposarcoma were identified; 1908 underwent surgery alone and 174 received NRT before surgical resection. Median tumour size was 22·0 cm and 34·9 per cent of tumours were high grade. In the unmatched cohort, NRT was not associated with improved overall survival (χ 2  = 3·49, P = 0·062). In the propensity score-matched cohort, NRT was associated with an improvement in survival (median overall survival 129·2 versus 84·3 months; P = 0·046; hazard ratio (HR) 1·54, 95 per cent c.i. 1·01 to 2·36). This effect appeared most pronounced for tumours with adjacent organ invasion (median overall survival not reached versus 63·8 months; P = 0·044; HR 1·79, 1·01 to 3·19)., Conclusion: NRT improved survival in patients undergoing surgery for retroperitoneal liposarcoma, particularly those with high-risk pathological features., (© 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Background: The significance of extracapsular lymph node involvement (LNI) is unclear in patients with oesophageal cancer who have undergone neoadjuvant treatment followed by oesophagectomy. The aim of this study was to assess the incidence and prognostic significance of extracapsular LNI in a large multicentre series of consecutive patients with oesophageal cancer treated by neoadjuvant chemotherapy or chemoradiotherapy and surgery., Methods: Data from a consecutive series of patients treated at two European centres were analysed. All patients with squamous cell carcinoma or adenocarcinoma of the oesophagus or gastro-oesophageal junction, who received neoadjuvant chemotherapy or chemoradiation followed by transthoracic oesophagectomy and two-field lymphadenectomy with curative intent, were included., Results: Between January 2000 and September 2013, 704 patients underwent oesophagectomy after neoadjuvant therapy. A median of 28 (range 5-77) nodes per patient was recovered. Some 347 patients (49·3 per cent) had no LNI (ypN0). Of the remaining 357 patients (50·7 per cent) with LNI (ypN1-3), extracapsular LNI was found in 190 (53·2 per cent). Five-year overall survival rates were 62·7 per cent for patients with N0 disease, 44·9 per cent for patients without extracapsular spread and 14·0 per cent where extracapsular LNI was identified (P < 0·001). Multivariable analyses demonstrated the presence of extracapsular LNI as an independent prognostic factor., Conclusion: The presence of extracapsular LNI after neoadjuvant therapy carries a poor prognosis., (© 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.)

The conditions and outcomes of Japanese patients with prostate cancer who developed PSA failure after radical prostatectomy (RP), and who were treated via salvage radiotherapy (S-RT), were surveyed. Clinical data on S-RT were gathered in questionnaires completed by facilities participating in the Japanese Radiation Oncology Study Group. S-RT was defined as external-beam radiotherapy delivered to the prostate beds of patients with prostate cancer who had eventually developed PSA failure, although their PSA values had at one stage attained levels <0.2 ng/ml following RP. Hormonal therapy was combined with S-RT in ∼40% of cases. Outcomes were evaluated in 186 cases treated via S-RT alone. The nadir PSA level after RP, and the level upon initiation of S-RT, were 0.0135 ng/ml and 0.292 ng/ml, respectively. The median period between RP and S-RT was 18.6 months. The median follow-up period was 58 months. The 5-year PSA recurrence-free survival (PRFS) and clinical failure-free survival (CFFS) rates were 50.1% (95% CI: 42.8-57.9%) and 90.1% (95% CI: 86.4-95.7%), respectively. PRFS was significantly superior in patients with PSA values ≤0.3 ng/ml upon initiation of S-RT than in those with PSA values >0.3 ng/ml (57.5% vs 40.5%, P = 0.027). In Japan, hormonal therapy is combined with S-RT in ∼40% of cases. The 5-year PRFS and CFFS rates of cases treated via S-RT alone were 50.1% and 90.1%, respectively. A PSA value of 0.3 ng/ml served as a significant cut-off for prediction of PRFS., (© The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: The purpose of this study was to analyse retrospectively the pooled results after pelvic exenteration for locally advanced T4 rectal cancer. Historically, patients with T4 rectal cancers requiring pelvic exenteration have been offered only palliative surgery or no operation., Methods: The basic treatment principle was preoperative (chemo)radiotherapy, radical surgery and, in some patients, adjuvant chemotherapy. Risk factors for local recurrence, distant metastases and overall survival were studied in univariable and multivariable analyses., Results: Ninety-five patients with T4 rectal cancer who underwent pelvic exenteration in two tertiary referral centres up to 2013 were studied. Clear margins (R0) were achieved in 87 per cent of patients. Adjuvant chemotherapy was administered in 33 per cent, independent of the resection margin, lymph node status and postoperative T category. The 5-year local recurrence rate was 17 per cent, with a distant metastasis rate of 16 per cent and overall survival rate of 62 per cent. In multivariable analysis the only factor associated with death was omission of adjuvant chemotherapy (P = 0.016). The effect of adjuvant chemotherapy was more pronounced in the elderly: patients aged over 70 years who had chemotherapy had a 5-year overall survival rate of 80 per cent, compared with 39 per cent of elderly patients who did not receive chemotherapy (P = 0.019)., Conclusion: Pelvic exenteration led to an R0 resection rate of 87 per cent for T4 rectal cancer, giving good local control and overall survival comparable to population-based colorectal cancer survival rates. Adjuvant chemotherapy may improve overall survival further, even in the elderly., (© 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.)

Short-course preoperative radiotherapy (SCPRT) is an alternative method to chemoirradiation for patients with Stage II and III rectal cancer when no downsizing is needed, but there is still widespread reluctance to use this method because of fear of side effects from high-fraction doses. This paper reports on a single institution patient cohort of operated rectal cancer patients after SCPRT, evaluated for chronic adverse effects, local control, progression-free survival and overall survival. Altogether, 257 patients were treated with SCPRT and surgery including total mesorectal excision (92% total mesorectal excision = TME) between 2002 and 2009. Local control and survival were analyzed. Chronic adverse effects for 154 patients without local relapse were evaluated according to the NCI-CTCAE version 4.0 classification, with a median follow-up of 48 months. We found a 5-year disease-free survival (DFS) and overall survival (OS) of 71%. The 5-year estimated local control (LC) rate was 94%. A positive resection margin was found in 4% of the patients and was significantly correlated with decreased DFS, OS and LC. Chronic adverse effects were reported by 58% of the patients, of which 10% were Grade 3 toxicities. The most frequent Grade 2 toxicity was stool incontinence (13%). Sexual dysfunction was found in 36% of the patients (31% Grade 1 or 2, and only 5% Grade 3). SCPRT combined with TME produced excellent LC rates together with a low rate of high-grade chronic adverse effects., (© The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: The impact of adjuvant radiation in patients with atypical meningioma remains poorly defined. We sought to determine the impact of adjuvant radiation therapy in this population., Methods: We identified 91 patients with World Health Organization grade II (atypical) meningioma managed at Dana-Farber/Brigham and Women's Cancer Center between 1997 and 2011. A propensity score model incorporating age at diagnosis, gender, Karnofsky performance status, tumor location, tumor size, reason for diagnosis, and era of treatment was constructed using logistic regression for the outcome of receipt versus nonreceipt of radiation therapy. Propensity scores were then used as continuous covariates in a Cox proportional hazards model to determine the adjusted impact of adjuvant radiation therapy on both local recurrence and the combined endpoint of use of salvage therapy and death due to progressive meningioma., Results: The median follow-up in patients without recurrent disease was 4.9 years. After adjustment for pertinent confounding variables, radiation therapy was associated with decreased local recurrence in those undergoing gross total resection (hazard ratio, 0.25; 95% CI, 0.07-0.96; P = .04). No differences in overall survival were seen in patients who did and did not receive radiation therapy., Conclusion: Patients who have had a gross total resection of an atypical meningioma should be considered for adjuvant radiation therapy given the improvement in local control. Multicenter, prospective trials are required to definitively evaluate the potential impact of radiation therapy on survival in patients with atypical meningioma., (© The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In Japan, the use of adjuvant radiotherapy after prostatectomy for prostate cancer has not increased compared with the use of salvage radiotherapy. We retrospectively evaluated the outcome of adjuvant radiotherapy together with prognostic factors of outcome in Japan. Between 2005 and 2007, a total of 87 patients were referred for adjuvant radiotherapy in 23 institutions [median age: 64 years (54-77 years), median initial prostate-specific antigen: 11.0 ng/ml (2.9-284 ng/ml), Gleason score (GS): 6, 7, 8, 9, 10 = 13.8, 35.6, 23.0, 27.6, 0%, respectively]. Rates of positive marginal status, seminal vesicle invasion (SVI) and extra-prostatic extension (EPE) were 74%, 26% and 64%, respectively. Median post-operative PSA nadir: 0.167 ng/ml (0-2.51 ng/ml). Median time from surgery to radiotherapy was 3 months (1-6 months). A total dose of ≥ 60 Gy and <65 Gy was administered to 69% of patients. The median follow-up time was 62 months. The 3- and 5-year biochemical relapse-free survival (bRFS) rates for all patients were 66.5% and 57.1%, respectively. The GS and marginal status (P = 0.019), GS and SVI (P = 0.001), marginal status and EPE (P = 0.017), type of hormonal therapy and total dose (P = 0.026) were significantly related. The 5-year bRFS rate was significantly higher in SVI-negative patients than SVI-positive patients (P = 0.001), and significantly higher in patients with post-operative PSA nadir ≤ 0.2 than in patients with post-operative PSA nadir >0.2 (P = 0.02), and tended to be more favorable after radiotherapy ≤ 3 months from surgery than >3 months from surgery (P = 0.069). Multivariate analysis identified SVI and post-operative PSA nadir as independent prognostic factors for bRFS (P = 0.001 and 0.018, respectively).

We investigated the relationship between the time of radiotherapy (RT) and treatment outcomes in breast cancer. Patients with pathologic T1-2N0-1 breast cancer who received adjuvant RT in the morning (before 10:00 AM) or late afternoon (after 3:00 PM) were eligible for inclusion in this study. We retrospectively compared the clinicopathologic characteristics, acute skin reaction, and survival outcomes according to the time of RT. The median follow-up duration was 83 months (range, 10-131 months). From the 395 eligible patients, 190 (48.1%) and 205 (51.9%) patients were classified into the morning RT group and the afternoon RT group, respectively. The clinicopathologic characteristics were relatively well balanced between the treatment groups, except for pathologic N-stage (P = 0.0409). Grade 2 or higher acute skin reaction according to the Radiation Therapy Oncology Group criteria was observed in 39 (9.9%) patients, with a higher frequency in the afternoon RT group than the morning RT group (13.7% vs 5.8%, respectively; P = 0.0088). There was no difference in the failure patterns or survival outcomes between the treatment groups. RT in late afternoon was associated with increased Grade 2 or more skin reaction after RT for breast cancer patients, but treatment outcomes did not differ according to the time of RT. Individualized considerations for treatment should be taken into account to reduce the risk of skin reactions.

Objective: To assess the treatment outcomes and to explore the determinants of clinical outcome in breast cancer patients with 1-3 positive nodes who did or did not receive postmastectomy radiotherapy (PMRT) in a tertiary care referral cancer center in Northern Thailand., Methods: We investigated a retrospective cohort of registered breast cancer patients at the Faculty of Medicine, Chiang Mai University, Thailand from 2001-2007. Analysis was performed using Cox regression models to identify factors affecting the overall survival (OS) and relapse-free survival (RFS) rates. Comparisons were made between two cohorts: women who received adjuvant PMRT (74 patients) and women who did not receive adjuvant PMRT (81 patients)., Results: A total of 155 patients were included with a median follow-up period of 4.45 years. There was a statistically significant 4-year OS difference between the two groups of patients: 100% for the PMRT group and 93.1% for the non-PMRT group (P = 0.044). The 4-year RFS was 85.9% for patients receiving PMRT and 78.3% for patients who did not receive PMRT (P = 0.291). On multivariate analysis of OS, using hormonal treatment was the only significant independent factor associated with improved OS. On multivariate analysis of RFS, none of the variables were significantly associated with improved RFS. PMRT was notfound to be a prognostic variable related to the outcome of patients using a logistic regression model., Conclusion: Our retrospective, hospital-based analysis demonstrated that PMRT improved the treatment outcome in terms of OS for women with 1-3 node positive early-stage breast cancer.

The purpose of this study was to examine the safety and feasibility of a novel protocol of neoadjuvant short-course hyperfractionated accelerated radiotherapy (SC-HART) combined with S-1 for locally advanced rectal cancer. A total of 56 patients with lower rectal cancer of cT3N1M0 (Stage III b) was treated with SC-HART followed by radical surgery, and were analyzed in the present study. SC-HART was performed with a dose of 2.5 Gy twice daily, with an interval of at least 6 hours between fractions, up to a total dose of 25 Gy (25 Gy in 10 fractions for 5 days) combined with S-1 for 10 days. Radical surgery was performed within three weeks following the end of the SC-HART. The median age was 64.6 (range, 39-85) years. The median follow-up term was 16.3 (range, 2-53) months. Of the 56 patients, 53 (94.4%) had no apparent adverse events before surgery; 55 (98.2%) completed the full course of neoadjuvant therapy, while one patient stopped chemotherapy because of Grade 3 gastrointestinal toxicity (CTCAE v.3). The sphincter preservation rate was 94.6%. Downstaging was observed in 45 patients (80.4%). Adjuvant chemotherapy was administered to 43 patients (76.8%). The local control rate, disease-free survival rate and disease-specific survival rate were 100%, 91.1% and 100%, respectively. To conclude, SC-HART combined with S-1 for locally advanced rectal cancer was well tolerated and produced good short-term outcomes. SC-HART therefore appeared to have a good feasibility for use in further clinical trials.

This study sought to investigate the clinical outcome and the role of postoperative radiotherapy for patients with salivary duct carcinoma (SDC) who had undergone surgery and postoperative radiotherapy. We performed a retrospective analysis of 25 SDC patients treated between 1998 and 2011 with surgery and postoperative radiotherapy. The median prescribed dose was 60 Gy (range, 49.5-61.4 Gy). The clinical target volume (CTV) was defined as the tumor bed in four patients, the tumor bed and ipsilateral neck in 14 patients, and the tumor bed and bilateral neck in six patients. Local control (LC), disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and prognostic variables were analyzed with the log-rank test. The 5-year LC, DFS and OS were 67%, 45% and 47%, respectively. Disease recurrence was found in 12 patients: seven as local, four as regional and eight as distant failure. Perineural and lymphovascular invasion was a significant prognostic factor for LC (P = 0.03). Local failure was common, and the presence of local recurrence significantly affected the OS (P < 0.05). We conclude that surgery and postoperative radiotherapy is expected to decrease the risk of local failure and contribute to good prognoses for patients with SDC. It might be advisable to have the CTV include the cranial nerves involved and the corresponding parts of the skull base in cases of pathologically positive perineural invasion.

Background: A positive circumferential resection margin (CRM) has been associated with a poorer prognosis in oesophageal and oesophagogastric junctional (OGJ) cancer. The College of American Pathologists defines the CRM as positive if tumour cells are present at the margin, whereas the Royal College of Pathologists also include tumour cells within 1 mm of this margin. The relevance of these differences is not clear and no study has investigated the impact of adjuvant therapy. The aim was to identify the optimal definition of an involved CRM in patients undergoing resection for oesophageal or OGJ cancer, and to determine whether adjuvant radiotherapy improved survival in patients with an involved CRM., Methods: This was a single-centre retrospective study of patients who had undergone attempted curative resection for a pathological T3 oesophageal or OGJ cancer. Clinicopathological variables and distance from the tumour to the CRM, measured to ± 0.1 mm, were correlated with survival., Results: A total of 226 patients were included. Sex (P = 0·018), tumour differentiation (P = 0·019), lymph node status (P < 0·001), number of positive nodes (P < 0·001), and CRM distance (P = 0·042) were independently predictive of prognosis. No significant survival difference was observed between positive CRM 0-mm and 0·1-0·9-mm groups after controlling for other prognostic variables. Both groups had poorer survival than matched patients with a CRM at least 1 mm clear of tumour cells. Among patients with a positive CRM of less than 1 mm, those undergoing observation alone had a median survival of 18·6 months, whereas survival was a median of 10 months longer in patients undergoing adjuvant radiotherapy, but otherwise matched for prognostic variables (P = 0·009)., Conclusion: A positive CRM of 1 mm or less should be regarded as involved. Adjuvant radiotherapy confers a significant survival benefit in selected patients with an involved CRM., (© 2013 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd.)

The purpose of this study was to evaluate the outcome prediction power of classical prognostic factors along with surrogate approximation of genetic signatures (AGS) subtypes in patients affected by localized breast cancer (BC) and treated with postoperative radiotherapy. We retrospectively analyzed 468 consecutive female patients affected by localized BC with complete immunohistochemical and pathological information available. All patients underwent surgery plus radiotherapy. Median follow-up was 59 months (range, 6-132) from the diagnosis. Disease recurrences (DR), local and/or distant, and contralateral breast cancer (CBC) were registered and analyzed in relation to subtypes (luminal A, luminal B, HER-2, and basal), and classical prognostic factors (PFs), namely age, nodal status (N), tumor classification (T), grading (G), estrogen receptors (ER), progesterone receptors and erb-B2 status. Bootstrap technique for variable selection and bootstrap resampling to test selection stability were used. Regarding AGS subtypes, HER-2 and basal were more likely to recur than luminal A and B subtypes, while patients in the basal group were more likely to have CBC. However, considering PFs along with AGS subtypes, the optimal multivariable predictive model for DR consisted of age, T, N, G and ER. A single-variable model including basal subtype resulted again as the optimal predictive model for CBC. In patients bearing localized BC the combination of classical clinical variables age, T, N, G and ER was still confirmed to be the best predictor of DR, while the basal subtype was demonstrated to be significantly and exclusively correlated with CBC.

Background: The aim was to determine the effect of the circumferential resection margin (CRM) on overall survival following surgical excision of rectal cancer., Methods: The effect of CRM on survival was examined by case mix-adjusted analysis of patients undergoing potentially curative excision of a rectal cancer between 1998 and 2002., Results: Of 1896 patients, 1561 (82.3 per cent) had recorded data on the CRM. In 232 patients (14.9 per cent) tumour was found 1 mm or less from the CRM. In 370 patients (23.7 per cent) it was over 1 mm but no more than 5 mm from the CRM, and in 288 (18.4 per cent) it was over 5 mm but no more than 10 mm from the CRM. The remaining 671 patients (43.0 per cent) had a CRM exceeding 10 mm. Overall 5-year survival rates for these groups were 43.2, 51.7, 66.6 and 66.0 per cent respectively. Compared with patients with a CRM exceeding 10 mm, the adjusted risk of death was significantly increased for patients with a CRM of 1 mm or less (hazard ratio (HR) 1.61, P < 0.001) and those with a margin greater than 1 mm but no larger than 5 mm (HR 1.35, P = 0.005). There was no added risk for patients with tumour more than 5 mm but 10 mm or less from the CRM (HR 1.02, P = 0.873). The adverse effect of a CRM greater than 1 mm but no larger than 5 mm was found particularly in mid-rectal cancers., Conclusion: A predicted CRM of 5 mm or less on preoperative staging should be considered for neoadjuvant treatment., (Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Background: Definitive chemoradiotherapy (dCRT) has been proposed as an alternative therapy for selected patients with oesophageal cancer. The aim of this study was to determine the outcomes of dCRT, surgery alone, and neoadjuvant chemotherapy followed by surgery (CS) in patients with oesophageal cancer., Methods: Consecutive patients diagnosed with oesophageal cancer and managed by a multidisciplinary team were staged by computed tomography and endoluminal ultrasonography. Those deemed unsuitable for surgery on the grounds of performance status, bulky local disease or personal choice received dCRT. The primary outcome measure was overall survival measured from date of diagnosis., Results: Of 417 patients, 173 received dCRT, 126 underwent surgery alone and 118 received CS. The incidence of grade III/IV toxicity after dCRT and CS was 39.3 and 60.2 per cent respectively. Operative morbidity rates were 42.9 and 44.4 per cent after surgery alone and CS respectively. Thirty-day mortality rates were zero, 7.9 and 0.8 per cent after dCRT, surgery alone and CS respectively. Overall 2-year survival rates were 44.3, 56.2 and 42.4 per cent (P = 0.422)., Conclusion: These findings support the need for a randomized trial of dCRT versus CS for resectable oesophageal cancer.

Background: Rectum-preserving endoscopic posterior mesorectal resection (EPMR) removes the local lymph nodes in a minimally invasive manner and completes tumour staging after transanal local excision (TE). The aim of this study was to compare the morbidity and mortality of TE and EPMR with those of low anterior resection (LAR) in patients with T1 rectal cancer., Methods: Between 1996 and 2006 EPMR was performed 6 weeks after TE in 18 consecutive patients with a T1 rectal cancer. Morbidity and mortality were recorded prospectively and compared with those in a group of 17 patients treated by LAR. Lymph node involvement and local recurrence rate were analysed in both groups., Results: Two major and three minor complications were noted after EPMR, and four major and four minor complications after LAR (P = 0.402 for major and P = 0.691 for minor complications). Median number of lymph nodes removed was 7 (range 1-22) for EPMR and 11 (range 2-36) for LAR (P = 0.132). Two of 25 patients with a low-risk rectal cancer were node positive. No patient developed locoregional recurrence., Conclusion: EPMR after TE is a safe option for T1 rectal cancer. This two-stage procedure has a lower morbidity than LAR and may reduce locoregional recurrence compared with TE alone., (2008 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)