Hirata Shoichiro, Kono Yoshiyasu, Tanaka Emi, Sue Masahiko, Takeuchi Yasuto, Yoshikawa Tomoki, Maki Yoshie, Kamio Tomohiro, Kametaka Daisuke, Matsueda Katsunori, Sakaguchi Chihiro, Hamada Kenta, Iwamuro Masaya, Kawano Seiji, Kawahara Yoshiro, Otsuka Motoyuki
Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
Department of Gastroenterology, Japanese Red Cross Society Himeji Hospital, 1-12-1 Shimoteno, Himeji 670-8540, Japan.
Cancers (Basel). 2025 Aug 12;17(16):2634. doi: 10.3390/cancers17162634.
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. 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. 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). 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.
胃肠道免疫相关不良事件（GI-irAEs）是免疫检查点抑制剂（ICIs）公认的并发症，但其预后相关性及相关危险因素仍不明确。本研究旨在评估使用预后营养指数（PNI）测量的基线营养状况是否会改变GI-irAEs的预后影响，并确定与其发生相关的临床因素。我们回顾性分析了在单一机构接受ICIs治疗的1104例癌症患者。GI-irAEs被定义为需要临床干预的胃肠道症状。患者按irAE类型和PNI（≥40 vs. <40）分层，并评估生存和治疗反应的差异。还检查了发生GI-irAEs的潜在危险因素。2.7%的患者发生了GI-irAEs，在PNI≥40的患者中，GI-irAEs与总生存期延长相关（中位数：28.7个月 vs. 14.0个月）。在PNI<40的患者中未观察到这种生存优势。PNI依赖的预后模式特定于GI-irAEs，在非GI irAEs中未观察到。在4周和8周的标志性分析中证实了类似趋势。PNI状态对客观缓解率和疾病控制率的差异在GI-irAEs患者中最为明显。使用抗CTLA-4抗体与GI-irAE的发生显著相关（比值比4.24；95%置信区间1.73-10.39）。GI-irAEs似乎主要在营养状况良好的患者中带来生存益处。PNI可能是一个有用的工具，用于阐明GI-irAEs的临床相关性，并有助于识别在ICI治疗期间最可能从免疫激活中获益的患者。
