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Introduction: Perioperative chemotherapy improves overall survival (OS) and disease-free survival (DFS) compared with surgery alone in patients with resectable gastric adenocarcinoma (GA) or gastro-oesophageal junction adenocarcinoma (GEJA). The addition of trastuzumab to chemotherapy improves outcomes in patients with HER2-positive advanced gastric cancer (GC), and we aimed to explore its role in the perioperative setting., Material and Methods: This Spanish, multicentre, open-label phase II trial evaluated the efficacy and toxicity of perioperative capecitabine, oxaliplatin and trastuzumab (XELOX-T) in patients with HER2-positive resectable GA or GEJA. The primary end-point was 18-months DFS; and secondary end-points included pathological complete response (pCR) rate, R0 resection rate, OS and toxicity (NCT01130337)., Results: Thirty-six patients were included. After three cycles of preoperative treatment, 14 patients (38% of the intention-to-treat population) had partial response and 18 (50%) had stable disease. Surgery was performed in 31 patients: 28 (90%) had R0 resection, three (9.6%) had a pCR and three (9.6%) died due to surgical complications. A total of 24 patients received post-operative XELOX-T, 22 of whom completed trastuzumab maintenance. Main grade III/IV toxicities included diarrhoea (33%), nausea and vomiting (8%). After a median follow-up of 24.1 months, 18-month DFS was 71% (95% confidence interval [CI], 53-83%); and an update after 102 months of follow-up showed a median OS of 79.9 months and a 60-month OS of 58% (95% CI, 40-73%)., Conclusions: These data suggest that perioperative XELOX-T in patients with HER2-positive GA and GEJA is feasible and active. Further investigation in randomised studies is warranted., Competing Interests: Conflict of interest statement Paula Jimenez-Fonseca declares travel grants from Ipsen and consulting/advisory role for Roche, Celgene, Bristol, Mylan, Rovi, LeoPharma, all outside of the scope of this work. Maria Alsina declares disclosures in terms of scientific consultancy from Bristol Myers Squibb, Lilly, Merck Sharp and Dohme, and Servier; honoraria from Amgen, Bristol Myers Squibb, Lilly, Merck Sharp and Dohme, Roche, and Servier; and travel expenses (partial coverage) from Amgen, Lilly, and Roche. Enrique Aranda disclosures consultant or advisory role for Roche, Merck, Angem, Bayer and Sanofi. Carlos López disclosures Honoraria for Roche, Merck, Sanofi, Novartis, Pfizer, Eisai, Ipsen, Bayer, AstraZeneca, and Servier; Consulting or Advisory Role for Amgen, Roche, Sanofi, Merck, Servier, Pfizer, Ipsen, Bayer, Eisai; research funding from Amgen, Roche, Merck, Merck Sharp & Dohme, AstraZeneca, Sanofi, Bayer, Ipsen, Eisai, Celgene Travel, Accommodations, Expenses Roche, Pfizer, Merck, Servier, Amgen, Ipsen Fernando Rivera disclosures consultant or advisory role for Roche, Merck-Serono, Amgen, MSD, BMS, Lilly, Celgene, Sanofi-Aventis, Servier, Astra-Zeneca, and Bayer; research Funding from Roche, Merck-Serono, Amgen, MSD, Lilly, Celgene, Sanofi-Aventis, Bayer, Servier; speaker roles for Roche, Merck-Serono, Amgen, MSD, BMS, Lilly, Celgene, Sanofi-Aventis, Servier, and Bayer; and grant support from Amgen. The rest of the authors declare no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: The effect of surgery for metastases in patients with esophagogastric cancer is unknown, given the lack of randomized clinical trials; likewise, the criteria for selecting eligible patients remain to be determined., Methods: This registry evaluates the results of patients with advanced adenocarcinoma of the stomach, distal esophagus, or gastro-esophageal junction from 32 centers. To assess selection criteria and prognostic factors, a state arrival extended Markov proportional hazards (PH) model was used., Results: 1792 subjects were analyzed, 5% of whom (n = 92) underwent surgery for metastasis. The most common surgeries were peritoneal (29%), hepatic (24%), and distant lymph nodes (11%). Subjects chosen for metastasectomy had higher survival rates, HR 0.34 (95% CI, 0.06-0.80, p = 0.021). Patients who underwent surgery had a mOS since metastasectomy of 16.7 months (95% CI, 12.5-22.4). The 1- and 3-year relapse rates following R0 resection were 58% and 65%, respectively. Median time since R0 metastasectomy until relapse was 8.4 months (95% CI, 7.6-23.7). The 3-year OS after surgery was 30.6% (95% CI, 19.3-40.4). Duration of chemotherapy prior to surgery (months) increased mortality (HR 1.04 [95% CI, 1.01-1.07]), p = 0.009. The only significant interaction involved the use of anti-HER2 therapy., Conclusion: The AGAMENON registry suggests that subjects with limited metastatic disease, selected on a clinical basis, can benefit from early surgeries. Prospective trials are needed to confirm these data., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: To develop and validate a nomogram and web-based calculator to predict overall survival (OS) in Caucasian-advanced oesophagogastric adenocarcinoma (AOA) patients undergoing first-line combination chemotherapy., Methods: Nine hundred twenty-four AOA patients treated at 28 Spanish teaching hospitals from January 2008 to September 2014 were used as derivation cohort. The result of an adjusted-Cox proportional hazards regression was represented as a nomogram and web-based calculator. The model was validated in 502 prospectively recruited patients treated between October 2014 and December 2016. Harrell's c-index was used to evaluate discrimination., Results: The nomogram includes seven predictors associated with OS: HER2-positive tumours treated with trastuzumab, Eastern Cooperative Oncology Group performance status, number of metastatic sites, bone metastases, ascites, histological grade, and neutrophil-to-lymphocyte ratio. Median OS was 5.8 (95% confidence interval (CI), 4.5-6.6), 9.4 (95% CI, 8.5-10.6), and 14 months (95% CI, 11.8-16) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the derivation set and 4.6 (95% CI, 3.3-8.1), 12.7 (95% CI, 11.3-14.3), and 18.3 months (95% CI, 14.6-24.2) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the validation set. The nomogram is well-calibrated and reveals acceptable discriminatory capacity, with optimism-corrected c-indices of 0.618 (95% CI, 0.591-0.631) and 0.673 (95% CI, 0.636-0.709) in derivation and validation groups, respectively. The AGAMENON nomogram outperformed the Royal Marsden Hospital (c-index=0.583; P=0.00046) and Japan Clinical Oncology Group prognostic indices (c-index=0.611; P=0.03351)., Conclusions: We developed and validated a straightforward model to predict survival in Caucasian AOA patients initiating first-line polychemotherapy. This model can contribute to inform clinical decision-making and optimise clinical trial design.