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

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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.

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