Clinical significance of pancreatic atrophy induced by immune-checkpoint inhibitors: A case–control study

Yael Eshet, Erez Nissim Baruch, Ronnie Shapira-Frommer, Yael Steinberg-Silman, Teodor Kuznetsov, Guy Ben-Betzalel, Sameh Daher, Iris Gluck, Nethanel Asher, Sara Apter, Jacob Schachter, Jair Bar, Ben Boursi, Gal Markel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Immune-checkpoint inhibitor (ICI)–related diarrhea is attributed to inflammatory colitis, with no other drug-related differential diagnosis. Here, we investigated the occurrence of pancreatic atrophy (PA) in ICI-treated cancer patients and its correlation to exocrine pancreatic insufficiency (EPI). Metastatic melanoma, non–small cell lung carcinoma, and head and neck squamous cell carcinoma patients (n ¼ 403) treated with anti–PD-1 (n ¼ 356) or anti–CTLA-4 (n ¼ 47) were divided into a case group (radiologic evidence of PA); control group matched by age, gender, and previous lines of treatment; and colitis group (ICI-induced colitis). Quantitative pancreatic volumetry was used for calculation of the decrease in pancreatic volume over time (atrophy rate). Thirty-one patients (7.7%) developed PA compared with 41 matched controls (P ¼ 0.006). Four patients developed EPI, all from the anti–PD-1–treated group, which resolved with oral enzyme supplementation. The atrophy rate did not correlate with EPI (P ¼ 0.87). EPI-related diarrhea presented at a median of 9 months, whereas the diarrhea of anti–PD-1–induced colitis patients (n ¼ 22) was presented at a median of 2 months (P ¼ 0.029). ICI-induced PA is irreversible and can result in EPI. EPI should be suspected in cases of late-onset steroid-resistant diarrhea with features of steatorrhea and treated with oral enzyme supplements.

Original languageEnglish
Pages (from-to)1453-1458
Number of pages6
JournalCancer immunology research
Issue number12
StatePublished - Dec 2018


FundersFunder number
Israel Ministry of Economy60958
Saban Family Team Science Award
Joanne G. and Gary N. Owen Fund in Immunology Research
Ministry of Economy


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