MDPI AG Acta Medica Okayama 2072-6694 17 16 2025 Prognostic Impact of Gastrointestinal Immune-Related Adverse Events Depends on Nutritional Status in Cancer Patients Treated with Immune Checkpoint Inhibitors 2634 EN Shoichiro Hirata Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshiyasu Kono Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Emi Tanaka Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masahiko Sue Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuto Takeuchi Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoki Yoshikawa Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshie Maki Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiro Kamio Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisuke Kametaka Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Katsunori Matsueda Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chihiro Sakaguchi Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kenta Hamada Department of Practical Gastrointestinal Endoscopy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masaya Iwamuro Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Seiji Kawano Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshiro Kawahara Department of Practical Gastrointestinal Endoscopy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoyuki Otsuka Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Gastrointestinal immune-related adverse events (GI-irAEs) are recognized complications of immune checkpoint inhibitors (ICIs), but their prognostic relevance and associated risk factors remain unclear. This study aimed to assess whether baseline nutritional status, measured using the prognostic nutritional index (PNI), modifies the prognostic impact of GI-irAEs, and to identify clinical factors associated with their occurrence. Methods: We retrospectively analyzed 1104 cancer patients treated with ICIs at a single institution. GI-irAEs were defined as gastrointestinal symptoms requiring clinical intervention. Patients were stratified by irAE type and PNI (≥40 vs. <40), and differences in survival and treatment response were evaluated. Potential risk factors for developing GI-irAEs were also examined. Results: GI-irAEs occurred in 2.7% of patients and were associated with prolonged overall survival (median: 28.7 vs. 14.0 months) among those with PNI ≥ 40. This survival advantage was not observed in patients with PNI < 40. The PNI-dependent prognostic pattern was specific to GI-irAEs and not observed for non-GI irAEs. Similar trends were confirmed in 4- and 8-week landmark analyses. Differences in objective response rate and disease control rate by PNI status were most pronounced in patients with GI-irAEs. The use of anti-CTLA-4 antibodies was significantly associated with GI-irAE development (odds ratio 4.24; 95% confidence interval 1.73–10.39). Conclusions: GI-irAEs appear to confer a survival benefit primarily in patients with preserved nutritional status. PNI may serve as a useful tool to contextualize the clinical relevance of GI-irAEs and help identify patients most likely to benefit from immune activation during ICI therapy. No potential conflict of interest relevant to this article was reported.