Trastuzumab with trimodality treatment for oesophageal adenocarcinoma with HER2 overexpression (NRG Oncology/RTOG 1010): a multicentre, randomised, phase 3 trial.

BACKGROUND: Trastuzumab is a monoclonal antibody against HER2 (also known as ERBB2). The primary objective of the NRG Oncology/RTOG-1010 trial was to establish whether trastuzumab improves disease-free survival when combined with trimodality treatment (paclitaxel plus carboplatin and radiotherapy, followed by surgery) for patients with untreated HER2-overexpressing oesophageal adenocarcinoma. METHODS: NRG Oncology/RTOG-1010 was an open label, randomised, phase 3 trial for which patients were accrued from 111 NRG-affiliated institutions in the USA. Eligible patients were adults (aged ≥18 years) with newly diagnosed pathologically confirmed oesophageal adenocarcinoma, American Joint Committee on Cancer 7th edition T1N1-2 or T2-3N0-2 stage disease, and a Zubrod performance status of 0-2. Patients were stratified by adenopathy (no vs yes [coeliac absent] vs yes [coeliac present ≤2 cm]) and randomly assigned (1:1) to receive weekly intravenous paclitaxel (50 mg/m2 intravenously over 1 h) and carboplatin (area under the curve 2, intravenously over 30-60 min) for 6 weeks with radiotherapy 50·4 Gy in 28 fractions (chemoradiotherapy) followed by surgery, with or without intravenous trastuzumab (4 mg/kg in week one, 2 mg/kg per week for 5 weeks during chemoradiotherapy, 6 mg/kg once presurgery, and 6 mg/kg every 3 weeks for 13 treatments starting 21-56 days after surgery). The primary endpoint, disease-free survival, was defined as the time from randomisation to death or first of locoregional disease persistence or recurrence, distant metastases, or second primary malignancy. Analyses were done by modified intention to treat. This study is registered with Clinicaltrials.gov, NCT01196390; it is now closed and in follow-up. FINDINGS: 606 patients were entered for HER2 assessment from Dec 30, 2010 to Nov 10, 2015, and 203 eligible patients who were HER2-positive were enrolled and randomly assigned to chemoradiotherapy plus trastuzumab (n=102) or chemoradiotherapy alone (n=101). Median duration of follow-up was 2·8 years (IQR 1·4-5·7). Median disease-free survival was 19·6 months (95% CI 13·5-26·2) with chemoradiotherapy plus trastuzumab compared with 14·2 months (10·5-23·0) for chemoradiotherapy alone (hazard ratio 0·99 [95% CI 0·71-1·39], log-rank p=0·97). Grade 3 treatment-related adverse events occurred in 41 (43%) of 95 patients in the chemoradiotherapy plus trastuzumab group versus 52 (54%) of 96 in the chemoradiotherapy group and grade 4 events occurred in 20 (21%) versus 21 (22%). The most common grade 3 or worse treatment-related adverse events for both groups were haematological (53 [56%] of 95 patients in the chemoradiotherapy plus trastuzumab group vs 55 [57%] of 96 patients in the chemotherapy group) or gastrointestinal disorders (28 [29%] vs 20 [21 %]). 34 (36%) of 95 patients in the chemoradiotherapy plus trastuzumab group and 27 (28%) of 96 patients in the chemoradiotherapy only group had treatment-related serious adverse events. There were eight treatment-related deaths: five (5%) of 95 patients in the chemoradiotherapy plus trastuzumab group (bronchopleural fistula, oesophageal anastomotic leak, lung infection, sudden death, and death not otherwise specified), and three (3%) of 96 in the chemoradiotherapy group (two multiorgan failure and one sepsis). INTERPRETATION: The addition of trastuzumab to neoadjuvant chemoradiotherapy for HER2-overexpressing oesophageal cancer was not effective. Trastuzumab did not lead to increased toxicities, suggesting that future studies combining it with or using other agents targeting HER2 in oesophageal cancer are warranted. FUNDING: National Cancer Institute and Genentech.

Long-Term Outcomes of NRG Oncology/RTOG 0529: A Phase 2 Evaluation of Dose-Painted Intensity Modulated Radiation Therapy in Combination With 5-Fluorouracil and Mitomycin-C for the Reduction of Acute Morbidity in Anal Canal Cancer.

PURPOSE: A multi-institutional phase 2 trial assessed long-term outcomes of dose-painted intensity modulated radiation therapy (IMRT) with 5-fluorouracil (5FU) and mitomycin-C (MMC) for anal canal cancer. METHODS AND MATERIALS: T2-4N0-3M0 anal cancers received 5FU (1000 mg/m2/d, 96-hour infusion) and MMC (10 mg/m2 bolus) on days 1 and 29 of dose-painted IMRT prescribed as follows: T2N0 = 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes, 28 fractions; T3-4N0-3 = 45Gy elective nodal, 50.4 Gy ≤3 cm and 54 Gy >3cm metastatic nodal and 54 Gy anal tumor planning target volumes, 30 fractions. Local-regional failures, distant metastases, and colostomy failures were assessed using the cumulative incidence method, and disease-free survival, overall survival, and colostomy-free survival were assessed using the Kaplan-Meier method. Late effects were scored using National Cancer Institute-Common Terminology Criteria for Adverse Events v3. RESULTS: Of 52 patients, 54% were stage II, 25% were stage IIIA, and 21% were stage IIIB. Median follow-up was 7.9 years (min-max, 0.02-9.2 years). Local-regional failure, colostomy failures, distant metastases, overall survival, disease-free survival, and colostomy-free survival at 5 years are 16% (95% confidence interval [CI], 7%-27%), 10% (95% CI, 4%-20%), 16% (95% CI, 7%-27%), 76% (95% CI, 61%-86%), 70% (95% CI, 56%-81%), and 74% (95% CI, 59%-84%); and at 8 years they are 16% (95% CI, 7%-27%), 12% (95% CI, 5%-23%), 22% (95% CI, 12%-34%), 68% (95% CI, 53%-79%), 62% (95% CI, 47%-74%) and 66% (95% CI, 51%-77%), respectively. Eight patients experienced local-regional failure, with 5 patients having persistent disease at 12 weeks. No isolated nodal failures occurred in the microscopic elective nodal volumes. Six patients required colostomy-5 for local-regional salvage and 1 for a temporary ostomy for anorectal dysfunction. Rates of late adverse events included: 28 patients (55%) with grade 2, 8 patients (16%) with grade 3, 0 patients with grade 4, and 2 patients (4%) with grade 5 events (sinus bradycardia and myelodysplasia, possibly owing to chemotherapy). Only 11 patients reported grade 1 to 3 sexual dysfunction. CONCLUSIONS: Dose-painted IMRT with 5FU/MMC for the treatment of anal canal cancer yields comparable long-term efficacy as conventional radiation cohorts. Enhanced normal tissue protection lowered rates of grade 3 and higher late effects without compromising pelvic tumor control.

Modulation of the Human Pancreatic Ductal Adenocarcinoma Immune Microenvironment by Stereotactic Body Radiotherapy.

PURPOSE: Stereotactic body radiotherapy (SBRT) is an emerging treatment modality for pancreatic ductal adenocarcinoma (PDAC), which can effectively prime cytotoxic T cells by inducing immunogenic tumor cell death in preclinical models. SBRT effects on human PDAC have yet to be thoroughly investigated; therefore, this study aimed to characterize immunomodulation in the human PDAC tumor microenvironment following therapy. EXPERIMENTAL DESIGN: Tumor samples were obtained from patients with resectable PDAC. Radiotherapy was delivered a median of 7 days prior to surgical resection, and sections were analyzed by multiplex IHC (mIHC), RNA sequencing, and T-cell receptor sequencing (TCR-seq). RESULTS: Analysis of SBRT-treated tumor tissue indicated reduced tumor cell density and increased immunogenic cell death relative to untreated controls. Radiotherapy promoted collagen deposition; however, vasculature was unaffected and spatial analyses lacked evidence of T-cell sequestration. Conversely, SBRT resulted in fewer tertiary lymphoid structures and failed to lessen or reprogram abundant immune suppressor populations. Higher percentages of PD-1+ T cells were observed following SBRT, and a subset of tumors displayed more clonal T-cell repertoires. CONCLUSIONS: These findings suggest that SBRT augmentation of antitumor immunogenicity may be dampened by an overabundance of refractory immunosuppressive populations, and support the continued development of SBRT/immunotherapy combination for human PDAC.

Results of the NRG Oncology/RTOG 0848 Adjuvant Chemotherapy Question-Erlotinib+Gemcitabine for Resected Cancer of the Pancreatic Head: A Phase II Randomized Clinical Trial.

PURPOSE: NRG/RTOG 0848 was designed to determine whether adjuvant radiation with fluoropyrimidine sensitization improved survival following gemcitabine-based adjuvant chemotherapy for patients with resected pancreatic head adenocarcinoma. In step 1 of this protocol, patients were randomized to adjuvant gemcitabine versus the combination of gemcitabine and erlotinib. This manuscript reports the final analysis of these step 1 data. METHODS: Eligibility-within 10 weeks of curative intent pancreaticoduodenectomy with postoperative CA19-9<180. Gemcitabine arm-6 cycles of gemcitabine. Gemcitabine+erlotinib arm-gemcitabine and erlotinib 100 mg/d. Two hundred deaths provided 90% power (1-sided α=0.15) to detect the hypothesized OS signal (hazard ratio=0.72) in favor of the arm 2. RESULTS: From November 17, 2009 to February 28, 2014, 163 patients were randomized and evaluable for arm 1 and 159 for arm 2. Median age was 63 (39 to 86) years. CA19-9 ≤90 in 93%. Arm 1: 32 patients (20%) grade 4 and 2 (1%) grade 5 adverse events; arm 2, 27 (17%) grade 4 and 3 (2%) grade 5. GI adverse events, arm 1: 22% grade ≥3 and arm 2: 28%, (P=0.22). The median follow-up (surviving patients) was 42.5 months (min-max: <1 to 75). With 203 deaths, the median and 3-year OS (95% confidence interval) are 29.9 months (21.7, 33.4) and 39% (30, 45) for arm 1 and 28.1 months (20.7, 30.9) and 39% (31, 47) for arm 2 (log-rank P=0.62). Hazard ratio (95% confidence interval) comparing OS of arm 2 to arm 1 is 1.04 (0.79, 1.38). CONCLUSIONS: The addition of adjuvant erlotinib to gemcitabine did not provide a signal for increased OS in this trial.

Hypofractionated Stereotactic Radiation Therapy for Metastatic Adenocarcinoma ex Goblet Cell Carcinoid of the Appendix: Case Report and Literature Review.

Adenocarcinoma ex-goblet carcinoid (ADA ex-GCC) is a rare and aggressive subtype of goblet cell carcinoid, a distinct tumor of the appendix characterized by both neuroendocrine and glandular differentiation. Patients often present with chronic abdominal pain or symptoms of acute appendicitis. Right hemicolectomy is the primary mode of treatment, and prophylactic salpingo-oophorectomy and hysterectomy is recommended in post-menopausal women due to the tumor's propensity of transcoelemic spread, especially to the ovaries. In this case report, we describe a patient with ADA ex-GCC who was found to have oligometastic disease in the pelvis and treated with hypofractionated stereotactic body radiation therapy (HSRT). She initially underwent a right hemicolectomy followed by adjuvant capecitabine four years prior when her tumor was incidentally discovered on colonoscopy. She subsequently had a salpingo-oophorectomy for gynecologic tract metastatic disease and declined further chemotherapy. The patient was again discovered to have oligometastatic disease in the right pelvis adjacent to the rectum on a Gallium-68 dotatate PET/MRI, and was subsequently treated with HSRT to 39 Gy in 6.5 Gy daily fractions. The patient tolerated her radiation course without notable radiation-related toxicity, and she remains without disease progression nine months later.

Short course radiation therapy for rectal cancer in the elderly: can radical surgery be avoided?

Rectal cancer in elderly patients can be difficult to manage. Short course radiation therapy (SCRT) has shown to be effective when given immediately prior to surgery. Here we report outcomes of elderly patients who underwent SCRT either alone or prior to resection. Between 2010 and 2015, elderly patients with rectal cancer and no distant metastatic disease were identified. Symptoms at diagnosis, therapies, toxicities, and pathologic and clinical response were recorded from patient charts. The SCRT prescription dose was 5 Gy ×5 to the rectal tumor and 4 Gy ×5 to the mesorectum, omitting the iliac nodes. Twenty patients were identified with median age of 85 years (range, 71-93 years). No patient received systemic therapy. Sixty percent of patients were cT3 at diagnosis. Half underwent resection post SCRT and half received SCRT as definitive therapy. The 1- and 2-year overall survival was 75% and 54%. Overall survival did not differ between patients treated with SCRT and surgery compared to SCRT alone (P=0.8). Of the 10 surgical patients, 3 had a complete pathologic response at time of resection and 3 patients died within 2 weeks due to perioperative complications. Of patients treated with SCRT alone, 8 were symptomatic at presentation and 5 had a clinician defined symptomatic response. No patient treated with SCRT monotherapy required additional palliative measures for outflow obstruction, but 2 progressed locally and died. SCRT is well tolerated, results in pathologic complete responses in a small percentage of patients, and achieves 63% symptom improvement rate as monotherapy. A high peri-operative complication rate was observed in this small series. In elderly patients, SCRT as initial treatment with a watch and wait approach for surgery is feasible and should be evaluated prospectively.

Hypofractionated Stereotactic Radiotherapy for Non-breast or Prostate Cancer Oligometastases: A Tail of Survival Beyond 10 Years.

Purpose and Objective(s): We sought to analyze the long-term follow-up of patients treated with hypofractionated, stereotactic radiotherapy (HSRT) for oligometastases from malignancies other than breast or prostate cancer. Materials and Methods: From 2001 to 2006, 82 cancer patients with 1-5 radiographically apparent metastatic lesions (in 1-3 organs) from primary sites other than breast or prostate cancer, were enrolled on a prospective study of HSRT. Freedom from widespread metastasis (FFWM) was defined from date of enrollment until death, an event (i.e., widespread distant metastasis not amenable to local therapy), or last radiographic study. Local recurrence was scored as an event if pathologically confirmed or if a treated lesion increased by ≥20% using RECIST criteria. Prognostic variables were assessed using Cox regression analysis. Results: The mean age was 61 ± 11 years, with a male to female ratio of 46:36. The most common metastatic sites were liver (50%), lung (48%), thoracic lymph nodes (18%), and bone (5%). Sixty-one patients (74%) had 1 involved organ and 18 (22%) had 1 lesion treated. The preferred dose-fractionation scheduled was 50 Gy in 10 fractions (52 patients). The median follow-up was 1.7 years. Eleven patients lived >5 years, and 6 lived >10 years. The 5-year OS, PFS, FFWM, and LC rates were 13.4, 7.3, 18.3, and 63.4%, and the 10-years OS, PFS, FFWM, and patient LC rates were 7.3, 6.1, 13.4, and 62.2%, respectively. A greater net gross tumor volume (GTV) was significantly adverse for OS (p < 0.01) and LC (p < 0.01). For FFWM, net GTV was not a significant factor (p = 0.14). Four patients remain alive at >13 years from enrollment and treatment, without evidence of active disease. Conclusion: A small subset of select non-breast, non-prostate cancer patients with limited metastasis treated with HSRT are long-term survivors. Net GTV is a significant factor for tumor control and survival. Further research is needed to help better select patients most likely to benefit from local therapy for metastatic disease.

NRG Oncology/RTOG 0438: A Phase 1 Trial of Highly Conformal Radiation Therapy for Liver Metastases.

PURPOSE: This study aimed to determine the feasibility and maximally tolerated dose of hypofractionated, conformal radiation therapy (RT) in patients with liver metastases. METHODS AND MATERIALS: Nonsurgical patients with ≤5 liver metastases (sum of maximal diameter of all lesions ≤8 cm) were included in the study. There were 4 dose levels: 35 Gy, 40 Gy (starting level), 45 Gy, and 50 Gy, in 10 fractions. The clinical target volume included metastases identified on contrast computed tomography or magnetic resonance imaging with a 5-mm margin within the liver. The planning target volume margin ranged from 4 to 30 mm, depending on breathing motion. Dose-limiting toxicities were defined as RT-related grade ≥4 hepatic or gastrointestinal toxicities or thrombocytopenia occurring within 90 days of the start of RT. RESULTS: A total of 26 patients with metastases from colorectal (8 patients), breast (7 patients) and other malignancies (11 patients) were enrolled between November 2005 and December 2010. Twenty-three patients were evaluable (8, 7, and 8 on the 40, 45, and 50 Gy dose levels, respectively). Two patients assigned to 50 Gy received 35 Gy owing to normal tissue limits, so 2 additional patients were treated to 50 Gy. There were no dose-limiting toxicities on any of the dose levels. On the 45 Gy dose level, 1 patient developed reversible grade 3 enteritis (37 days from RT start) and diarrhea (22 days); another patient developed grade 3 lymphopenia (23 days). At the 50 Gy dose level, 1 patient had grade 3 hyperglycemia (74 days), and another patient developed grade 3 lymphopenia (13 days), colonic hemorrhage (325 days), and colonic gastrointestinal obstruction (325 days). With a potential median follow-up of 66.1 months (range, 34.6-89.0 months), no other late toxicities were observed. CONCLUSIONS: Treatment of liver metastases with 50 Gy in 10 fractions was feasible and safe in a multi-institutional setting.

Oligometastatic breast cancer treated with hypofractionated stereotactic radiotherapy: Some patients survive longer than a decade.

BACKGROUND: The clinical state of oligometastases describes metastases limited in number and extent, amenable to metastasis-directed therapy. We sought to analyze long-term outcomes and characterize potential prognostic factors, in women with breast cancer (BC) oligometastases treated with hypofractionated stereotactic radiation (HSRT) therapy on a prospective phase II protocol. METHODS: Forty-eight women with 1-5 extracranial BC oligometastases received HSRT to all radiographically apparent sites of disease. Various dose-fractionation schedules were used. Most (n = 27) received 10 daily fractions, typically ≥50 Gy (n = 17). RESULTS: BC patients with bone-only oligometastases (BO, n = 12) vs. all other patients (non-BO; n = 36) were significantly younger, more likely to present with oligometastases at the time of primary BC diagnosis (i.e., synchronous), and significantly more likely to have had hormone receptor-positive disease. The 5-year and 10-year overall survival (OS) rates after HSRT were 83% and 75%, respectively, for BO patients vs. 31% and 17%, respectively, for non-BO patients (p = 0.002). BO patients experienced a significantly (p = 0.018) greater freedom from widespread metastases (FFWM). Among non-BO patients, net oligometastatic GTV >25 cc (reflecting disease burden) was a significant factor for freedom from local recurrence (p = 0.047) and FFWM (p = 0.028). The number of oligometastatic lesions (p = 0.007) and organs (p = 0.001) involved were also significant factors for FFWM in non-BO patients. CONCLUSIONS: Some patients with BC oligometastases treated with HSRT can survive >10 years. Tumor burden (volume and number of lesions) appears to impact risk of recurrence. Further research is needed to help better identify BC patients most likely to benefit from metastasis-directed radiotherapy.

Impact of Right-sided Primary Tumor Location Among Patients With Oligometastatic Colorectal Cancer Treated With Stereotactic Body Radiotherapy.

INTRODUCTION: Among patients with colorectal cancer, those with right-sided primary tumors have worse outcomes in both the primary and metastatic setting. Patients with oligometastatic colorectal cancer (OMCC) have improved prognosis relative to those with diffusely metastatic disease. We aimed to assess if the trend toward worse outcomes with right-sided tumors remained in the oligometastatic setting. PATIENTS AND METHODS: We analyzed 31 patients treated at a single institution with stereotactic body radiotherapy for OMCC from 2011 to 2014 to assess the impact that primary tumor location had on overall survival (OS) and progression-free survival (PFS). RESULTS: Overall, patient local control was fair (66% at 2 y); however, distant control was only 37.4% at 2 years. The median OS was 2.4 years; the median PFS was 6.5 months. Patients with right-sided primary tumors had numerically worse median OS than those with left-sided or rectal primary tumors (1.4 vs. 3.7 y, P=0.09). Median PFS was significantly worse among those with right-sided primaries (2.9 vs. 10.8 mo, P=0.05). This held on multivariate analysis. CONCLUSIONS: These results affirm that patients with OMCC have extended OS periods and that stereotactic body radiotherapy offers strong local control in these settings. We show that even in the oligometastatic setting those with right-sided primary tumors have worse outcomes relative to those with left-sided or rectal primary tumors. This suggests more aggressive treatment may be needed for those with oligometastatic right-sided colorectal cancer.

Stereotactic Body Radiotherapy for Lung Metastases from Colorectal Cancer: Prognostic Factors for Disease Control and Survival.

OBJECTIVES: To evaluate disease control and survival after stereotactic body radiotherapy (SBRT) for lung metastases from colorectal cancer and to identify prognostic factors after treatment. METHODS: Patients with metastatic colorectal cancer to the lungs treated with SBRT from 2002 to 2013 were identified from a prospectively maintained database. Patients may have received prior systemic therapy, radiotherapy to nonthoracic sites and/or resection of thoracic and/or nonthoracic metastases. Endpoints were timed from end of SBRT and included overall survival (OS), progression-free survival, distant metastases-free survival, and local failure-free survival. Univariate and multivariate analysis using Cox proportional hazard modeling was used to identify prognostic factors. RESULTS: Sixty-five patients were identified. Before SBRT, 69.2% and 33.8% of patients received systemic therapy and lung-directed local therapy, respectively, for metastatic disease. At the time of SBRT, 64.6% had lung-only involvement. Median survivals were: OS of 20.3 months (95% confidence intervals [CI], 15.9-27.0 mo), progression-free survival of 5.7 months (95% CI, 3.2-7.0 mo), distant metastases-free survival of 5.8 months (95% CI, 3.2-7.6 mo), and local failure-free survival of 15.4 months (95% CI, 8.5-21.1 mo). Nearly all (98%) patients developed distant progression. Extra lung and liver involvement at the time of initial metastases (hazard ratios [HR] 2.10) and extra lung involvement at SBRT (HR 2.67) were the only independent predictors of OS. Net gross target volume of >14.1 mL (HR 2.49) was the only independent predictor of local failure-free survival. CONCLUSIONS: Reasonable survival and local control can be achieved with SBRT. We identified several prognostic factors testable in future prospective trials that may help improve patient selection.

SBRT for Hepatocellular Carcinoma: 8-Year Experience from a Regional Transplant Center.

PURPOSE: The study aimed to evaluate stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) in patients not eligible for liver transplant (LT). METHODS: We retrospectively identified transplant-ineligible HCC patients treated with SBRT to the liver between 2004 and 2013. Our primary endpoint was overall survival (OS). We also report treatment toxicities using CTCAE 3.0, radiographic response, and patterns of failure. RESULTS: We identified 93 patients with median age at SBRT of 65.8 years. Forty-six percent were classified as Child-Pugh B or C and 85% had an Eastern Cooperative Oncology Group performance status of 1-2. After SBRT, 86% of patients experienced no or mild treatment-related adverse events. Only 8% of patients experienced grade 3 and 2% of patients experienced grade 4 adverse events. Overall radiographic response was complete in 1.2%, partial in 35.4%, stable in 43.9%, and progressive disease in 19.5%. Median OS was 8.8 months with 1-, 2-, and 3-year OS rates of 38.0, 29.8 and 21.2%, respectively. The Cancer of the Liver Italian Program (CLIP) score was found to strongly correlate with survival. Median OS for patients with CLIP scores of 0, 1, 2, and 3 was 21.1, 8.5, 5.1, and 7.1 months, respectively (p = 0.003). CONCLUSION: Our series demonstrates that SBRT is generally safe for HCC patients, even those with advanced liver failure. Although survival is generally poor, we were able to identify a group of patients with good liver function and early tumor stage who can achieve median OS of close to 2 years with SBRT.

Patterns and Yearly Time Trends in the Use of Radiation Therapy During the Last 30 Days of Life Among Patients With Metastatic Rectal Cancer in the United States From 2004 to 2012.

PURPOSE: Although radiation therapy (RT) can provide palliative benefits for patients with metastatic rectal cancer, its role at the end of life remains unclear. The objective of this study was to assess sociodemographic and clinical factors associated with the use of RT during the last 30 days of life and to evaluate yearly time trends in RT utilization among stage IV patients with rectal cancer. METHODS: The 2004 to 2012 National Cancer DataBase was queried for patients with metastatic rectal cancer who had a documented death during follow-up. A Bayesian multilevel logistic regression model was used to characterize predictive factors and yearly time trends associated with RT use in the last 30 days of life. RESULTS: Among 10 431 patients who met inclusion criteria, 345 (3%) received RT during the last 30 days of life. Factors independently associated with RT use included older age, female sex, African American race, nonprivate insurance, higher comorbidity burden, and worse grade. The odds of RT use at the end of life decreased by 28% between 2007 and 2009 (odds ratio [OR] = 0.72, 95% Credible Interval (CI) = 0.58-0.93), but then increased by 16% from 2010 to 2012 (OR = 1.16, 95% CI = 1.13-1.33), relative to 2004 to 2006. CONCLUSION: Radiation therapy use for patients with metastatic rectal cancer is beneficial, and efforts to optimize its appropriate use are important. Several factors associated with RT use during the last 30 days of life included disparities in sociodemographic and clinical subgroups. Research is needed to understand the underlying causes of these inequalities and the role of predictive models in clinical decision-making.

Comparison of outcomes between SBRT, yttrium-90 radioembolization, transarterial chemoembolization, and radiofrequency ablation as bridge to transplant for hepatocellular carcinoma.

PURPOSE: To evaluate and compare outcome of stereotactic body radiation therapy (SBRT), yttrium-90 radioembolization, radiofrequency ablation (RFA), or transarterial chemoembolization (TACE) as bridge to liver transplant (LT) in patients with hepatocellular carcinoma. METHODS AND MATERIALS: We retrospectively reviewed patients treated at our institution with SBRT, TACE, RFA, or yttrium-90 as bridge to LT between 2006 and 2013. We analyzed radiologic and pathologic response and rate of failure after bridge therapy. Toxicities were reported using Common Terminology Criteria for Adverse Events, 4.0. Kaplan-Meier method was used to calculate disease-free survival (DFS) and overall survival after LT. RESULTS: Sixty patients with a median age 57.5 years (range, 44-70) met inclusion criteria. Thirty-one patients (50.7%) had hepatitis C cirrhosis, 14 (23%) alcoholic cirrhosis, and 8 (13%) nonalcoholic steatohepatitis cirrhosis. Patients received a total of 79 bridge therapies: SBRT (n = 24), TACE (n = 37), RFA (n = 9), and Y90 (n = 9). Complete response (CR) was 25% for TACE, 8.6% for SBRT, 22% for RFA, and 33% for Y90. Grade 3 or 4 acute toxicity occurred following TACE (n = 4) and RFA (n = 2). Transplant occurred at a median of 7.4 months after bridge therapy. Pathological response among 57 patients was 100% necrosis (n = 23, 40%), >50% necrosis (n = 20, 35%), <50% necrosis (n = 9, 16%), and no necrosis (n = 5, 9%). Pathologic complete response was as follows: SBRT (28.5%), TACE (41%), RFA (60%), Y90 (75%), and multiple modalities (33%). At a median follow-up of 35 months, 7 patients had recurrence after LT. DFS was 85.8% and overall survival was 79% at 5 years. CONCLUSION: All bridge therapies demonstrated good pathological response and DFS after LT. SBRT and Y90 demonstrated significantly less grade ≥3 acute toxicity. Choice of optimal modality depends on tumor size, pretreatment bilirubin level, Child-Pugh status, and patient preference. Such a decision is best made at a multidisciplinary tumor board as is done at our institution.

Long-Term Survival of a Patient with Metastatic Small-Cell Carcinoma of the Stomach Treated with Radiation Therapy.

Small-cell carcinoma (SCC), or high-grade neuroendocrine carcinoma of the stomach, is a rare subtype of extra-pulmonary SCC which is almost invariably lethal. Gastric SCC often presents with local symptoms indistinguishable from other primary stomach cancers; however, both regional and distant spread are common at the initial presentation. Depending on symptoms and patient performance status, treatment typically consists of chemotherapy or resection followed by adjuvant chemotherapy, as even patients with limited stage gastric SCC likely have micrometastatic disease at the time of diagnosis. In this case report, we describe the long-term survival of a 75-year-old male with recurrent oligometastatic high-grade neuroendocrine carcinoma of the stomach treated with radiation therapy (RT) alone. He presented with abdominal pain and dyspepsia and was found to have a 6 cm locally invasive node-positive gastric SCC initially treated with extensive surgical resection. He was not a candidate for adjuvant chemotherapy, and surveillance imaging subsequently confirmed metachronous liver and local recurrences within 1 year after surgery, which were managed with stereotactic body RT and conventional radiation, respectively. An additional para-aortic nodal recurrence was treated with intensity-modulated radiotherapy 7 years after surgery with good response. He tolerated all RT courses without notable radiation-related toxicity and remains in complete remission 11 years after initial diagnosis.

Can Surgery be Avoided After Preoperative Chemoradiation for Rectal Cancer in the Era of Organ Preservation? Current Review of Literature.

Approximately 10% to 25% of patients have a pathologic complete response after neoadjuvant chemoradiation. There is a compelling argument for attempting to avoid surgery in carefully selected groups of patients. Although nerve-preserving surgical techniques are now standard, the rates of urinary and sexual dysfunction are significant. Also, although sphincter function and quality of life among patients undergoing an ultra-low anterior resection is acceptable, results are poorer than expected and may be disabling. Trials of omission of surgery for selected patients with complete response after preoperative chemoradiation, otherwise known as "Watch and Wait," have shown favorable long-term results. We review the current literature on accepted standards of care and identify areas of controversy and important ongoing clinical studies aiming to resolve these issues.

Stereotactic body radiation therapy as a bridge to transplantation and for recurrent disease in the transplanted liver of a patient with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer mortality worldwide. Despite orthotopic liver transplantation (OLT), recurrent HCC is a major cause of morbidity. In this case report, we evaluate the efficacy of stereotactic body radiation therapy (SBRT) as a bridge to OLT and for recurrence in the transplanted liver of a patient with HCC. A 52-year-old male with a history of chronic hepatitis C presented with a 1.7-cm liver lesion radiographically consistent with HCC, which was subsequently treated with a course of SBRT to 50 Gy in 5 fractions followed by OLT in 2009. The patient had a 2.2-cm recurrence in the transplanted liver in 2012, which was treated with SBRT to 62.5 Gy in 5 fractions. He tolerated the course of radiotherapy well with no significant radiation-related toxicity and remains in complete remission approximately 1 year after SBRT. SBRT is a safe and effective modality for the treatment of recurrent HCC in the transplanted liver of the same patient initially treated with SBRT as a bridge to OLT.

Multicentre results of stereotactic body radiotherapy for secondary liver tumours.

BACKGROUND: Surgical resection is the standard treatment for liver metastases, although for the majority of patients this is not possible. Stereotactic body radiotherapy (SBRT) is an alternative local-regional therapy. The purpose of this study was to evaluate the results of SBRT for secondary liver tumours from a combined multicentre database. METHODS: Variables from patients treated with SBRT from four Academic Medical Centres were entered into a common database. Local tumour control and 1-year survival rates were calculated. RESULTS: In total, 153 patients (91 women) 59 ± 8.4 years old with 363 metastatic liver lesions were treated with SBRT. The underlying primary tumour arose from gastrointestinal (GI), retroperitoneal and from extra-abdominal primaries in 56%, 8% and 36% of patients, respectively. Metastases, with a gross tumour volume (GTV) of 138.5 ± 126.8 cm(3) , were treated with a total radiation dose of 37.5 ± 8.2 Gy in 5 ± 3 fractions. The 1-year overall survival was 51% with an overall local control rate of 62% at a mean follow-up of 25.2 ± 5.9 months. A complete tumour response was observed in 32% of patients. Grade 3-5 adverse events were noted in 3% of patients. CONCLUSION: Secondary liver tumours treated with SBRT had a high rate of local control with a low incidence of adverse events.