Unexpectedly High Incidence of Immune-Related Adverse Events in Gastric Cancer Patients Who Received Conversion Surgery After Nivolumab-Including Chemotherapy

Sep 28, 2026

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Background: Nivolumab-including chemotherapy (nivo-CTX) for stage IV gastric cancer may increase the chance of conversion surgery, yet perioperative immune-related adverse events (irAEs) are not well characterized. Methods: irAEs were assessed in 36 patients with marginally resectable gastric cancer receiving nivo-CTX followed by surgery from November 2021 to March 2024. Results: irAEs occurred in 12 patients (33.3%), spanning chemotherapy, admission-to-surgery, and after surgery, with grade 2-4 events observed. Conclusions: irAEs were frequently seen beyond chemotherapy, requiring heightened perioperative awareness by surgeons.

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Introduction

Annals of Gastroenterological Surgery JSGS PAPER OPEN ACCESS Unexpectedly High Incidence of Immune-Related Adverse Events in Gastric Cancer Patients Who Received Conversion Surgery After Nivolumab-Including Chemotherapy Masashi Nishino1,2 | Takaki Yoshikawa1 | Hirokazu Shoji3 | Yuki Takenaka1 | Maho Takuwa1 | Yurina Fujisaki1 | Rei Ogawa1 | Takeyuki Wada1 | Tsutomu Hayashi1 | Yukinori Yamagata1 | Nobuyoshi Hiraoka2,4 | Yasuyuki Seto1 1Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan | 2Department of Molecular Oncology, Jikei University Graduate School of Medicine, Tokyo, Japan | 3Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan | 4Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo, Japan Correspondence: Takaki Yoshikawa ([tayoshik@ncc.go.jp](tayoshik@ncc.go.jp)) Received: 13 August 2025 | Revised: 15 September 2025 | Accepted: 22 September 2025 Funding: The authors received no specific funding for this work. Keywords: conversion surgery | gastric cancer | immune-related adverse events ABSTRACT Background: Nivolumab-including chemotherapy (nivo-CTX) for stage IV gastric cancer (GC) may increase the chance of conversion surgery but risk of immune-related adverse events (irAEs) during perioperative period remains unclear. Methods: We examined irAEs in 36 patients with marginally resectable GC who received nivo-CTX followed by surgery between November 2021 and March 2024. Results: Marginally resectable factors were para-aortic lymph node in 23, liver in 3, esophageal intramural metastasis in 2, mediastinal lymph node in 1, peribiliary lymph node in 1, P1b in 2, Bulky N in 5, and T4b in 1. IrAE was observed in 12 patients (33.3%). Among 12 patients, irAE was detected during chemotherapy in 6 patients (50%), after chemotherapy to admission to surgery in 2 (16.7%), and after surgery in 4 (33.3%). Grade 2 irAE was found in 6 patients (16.7%); rash in 6 and thyroiditis in 2, grade 3 was in 3 (8.3%); adrenal insufficiency in 1, hepatitis in 1, and pituitary insufficiency in 1, grade 4 was in 3 (8.3%); type 1 diabetes mellitus in 2, pemphigus in 1, and encephalitis in 1. Grade 3 or 4 irAE was found in 6 patients (16.7%). Among the patients who had irAE, grade 3 or 4 was detected in 2 of 6 during chemotherapy (33.3%) but was in 3 of 4 (75%) after surgery. Conclusions: IrAE was frequently observed not only during chemotherapy but also during perioperative period. Surgeons must pay special attention to unfamiliar irAE events during perioperative period. 1 | Introduction Gastric cancer remains a major global health concern, ranking as the fifth most diagnosed malignancy and the fourth leading cause of cancer-related death worldwide [1] . Although its incidence has declined in some Western countries, the disease burden remains particularly high in the East Asian nations, including Japan [2] . For patients with unresectable or metastatic gastric or gastroesophageal junction (EGJ) adenocarcinoma, prognosis has been poor. However, recent advances in systemic therapy have significantly improved clinical outcomes, particularly with the introduction of immune checkpoint inhibitors (ICIs) . Nivolumab, a PD-1 inhibitor, demonstrated survival benefits in combination with chemotherapy in the CheckMate 649 trial, leading to its approval as a new first-line treatment for HER2-negative unresectable or metastatic gastric and EGJ cancer [3] . This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2025 The Author(s). Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery. 6 Annals of Gastro

FAQs

How many marginally resectable gastric cancer patients were included, and what treatment sequence was used?

The study included 36 patients who received nivolumab-including chemotherapy (nivo-CTX) followed by conversion surgery. Surgeries occurred between November 2021 and March 2024.

What proportion of patients experienced immune-related adverse events (irAEs)?

irAEs were observed in 12 patients, representing 33.3% of the cohort. The events occurred during chemotherapy, between chemotherapy and admission to surgery, and after surgery.

When did irAEs most often occur, and what did the study conclude for perioperative care?

Grade 3 or 4 irAEs were detected in 2 of 6 patients during chemotherapy, but in 3 of 4 after surgery. The study concludes that irAEs frequently occur during perioperative periods, so surgeons must pay special attention to unfamiliar irAE events.

Sep 28, 2026

Uploaded by dabgoudw