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Background: The optimal perioperative treatment for adenocarcinoma of gastroesophageal junction (GEJ) tumor remains uncertain. The systematic review aims to assess the best neoadjuvant modality, namely chemotherapy (CT) versus chemoradiotherapy (CRT) based on randomized controlled trials (RCTs) for resectable gastric, esophageal and GEJ tumors., Methods: We performed a comprehensive PubMed database and Cochrane Library search to identify relevant RCTs related to neoadjuvant treatment for resectable GEJ adenocarcinoma. We included all published RCTs (phase 2 or 3) that tested specific neoadjuvant therapies (CT or CRT) if the patient population included GEJ tumors. We applied the Version 2 Cochrane risk-of-bias tool (RoB 2) to all the eligible studies. Outcomes examined included R0 resection and pathological response based on intention-to-treat (ITT) analysis, surgical outcomes, notable adverse events, and overall survival (OS). Each randomized group of every study was noted to be neoadjuvant CRT, CT, or surgery alone in order to compare the outcomes among these treatment approaches., Results: We identified 25 RCTs with 7,855 patients published from 1996 to 2019. Seven studies tested preoperative CT versus surgery alone, 7 tested preoperative radiotherapy (RT) or CRT versus surgery alone, 4 tested preoperative RT or CRT versus preoperative CT, and 7 tested other combinations. The R0 resection ranged 47-100% and the 3-year OS ranged 6-66.1% in all the study arms. In an exploratory analysis, CRT strategies showed a superior R0 resection rate [80.2%; 95% confidence interval (CI): 79.8-80.6%] to surgery alone (60.9%; 95% CI: 60.4-61.3%; P<0.01) and to preoperative CT (63.9%; 95% CI: 63.6-64.2%; P<0.01). When comparing 3- and 5-year OS, improvement was noted when comparing CRT to surgery alone (P<0.01), and perioperative CT to surgery alone (P<0.01), but no definite difference was noted between CRT versus CT., Discussion: Preoperative CRT showed improvement in R0 resection rate to surgery alone and preoperative CT. However, there is no significant difference in OS between CRT and CT. Both neoadjuvant strategies remain clinically meaningful options for patients with resectable GEJ tumors. Lack of patient-level data and inconsistent reporting of key outcomes across studies were the main limitations of our study., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-22-29/coif). EYC reports research support from Taiho Oncology, Inc. for investigator initiated trial as co-investigator, and Honoraria for lectures from Horizon CME. The other authors have no conflicts of interest to declare., (2022 Journal of Gastrointestinal Oncology. All rights reserved.)

Background: In locally-advanced esophageal cancer (LAEC), providers' concerns regarding eventual surgical candidacy can persuade physicians to defer to definitive doses of 50 Gy or higher preoperatively. We report the successful completion rate of tri-modality therapy (TMT) (documented at the outset) and reasons for TMT non-adherence at a large multi-disciplinary esophageal program., Methods: LAEC patients diagnosed 2007-2016 from a prospective institutional database were subdivided into CRT/S+ [completed chemoradiation (CRT) and surgery] and CRT/S- (CRT and no subsequent surgery) groups. Chart review provided surgery non-adherence reasons., Results: A total of 283 patients met planned TMT criteria: 164 (58.0%) patients received 50 or 50.4 Gy CRT, 27 patients (9.5%) received greater than 50.4 Gy, and 92 patients received less than 50 Gy (32.5%, only 8 patients received CRT to 41.4 Gy); 221 (78.1%) completed surgery (CRT/S+), while 62 (21.9%) failed to advance to surgery (CRT/S-): 25 of 62 CRT/S- patients (40.3%) evidenced metastatic progression before surgery, 4 (6.5%) were deemed unresectable intraoperatively, 4 (6.5%) expired prior to planned surgery (3 from unknown causes, 1 suicide), 8 (12.9%) experienced significant CRT-related medical decompensation and were withdrawn from surgical consideration, 16 (25.8%) voluntarily declined surgery post-CRT (largely due to long-term quality of life concerns), and 5 (8.1%) failed to advance for unknown reasons. Four of the 16 patients who voluntarily declined surgery after CRT received less than 50 Gy. The 22.2% of CRT/S+ patients achieved pathologic complete response (21.6% for adenocarcinoma and 29.0% for squamous cell carcinoma)., Conclusions: Our institution's 78% surgery completion rate among TMT-indicated patients highlights the benefits of upfront multidisciplinary care. Metastatic disease development most commonly truncated TMT with a low rate failing due to medical decompensation. Given the number of patients who voluntarily declined surgery following CRT, TMT counseling and involvement of a patient advocate are paramount prior to treatment planning., Competing Interests: Conflicts of Interest: Previous presentation: digital poster presentation at ASTRO Annual Meeting 2018 in San Antonio, TX, USA.

Background: Watchful waiting in rectal cancer patients with a complete clinical response (cCR) to chemoradiation therapy (CRT) forgo upfront resection has been proposed. Growing evidence suggests that a watch-and-wait approach using resection for salvage of local recurrence may improve quality of life without jeopardizing outcomes. The current acceptance of watch-and-wait by US radiation oncologists (ROs) is unknown., Methods: US ROs completed our IRB-approved anonymous e-survey regarding non-surgical management of patients who achieved a cCR to neoadjuvant CRT. Self-ranked knowledge of the OnCoRe Project-UK prospective observational study of watch-and-wait-was tested for its association with ROs' attitudes using the Chi-squared or Fisher's test, as indicated. Supporters of observation are self-identified., Results: Of the 220 respondents, 48% (n=106) of respondents support watchful waiting and 48% claimed familiarity with the OnCoRe Project. Respondents supporting observation were more likely to be familiar with the publication (P=0.029). Among watch-and-wait supporters, 59% (n=62) felt comfortable discussing this approach and 41% preferred the conversation be initiated by other specialists. There was no association between comfort level in discussing watch-and-wait and familiarity with the OnCoRe Project. ROs treating more than 10 locally advanced rectal cancer (LARC) patients annually felt more comfortable discussing watch-and-wait (P=0.015) compared to ROs seeing fewer patients., Conclusions: Almost half of surveyed US ROs support watch-and-wait, though many do not feel comfortable discussing this paradigm with patients. Knowledge of the OnCoRe Project is associated with support of watch-and-wait, yet not comfort level in leading the discussion. These results inform provider attitudes toward future clinical study participation., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.