Clinical Significance of Pancreatic Atrophy Induced by Immune-Checkpoint Inhibitors: A Case–Control Study

Abstract

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.

Two‐stage deep learning model for fully automated pancreas segmentation on computed tomography: Comparison with intra‐reader and inter‐reader reliability at full and reduced radiation dose on an external dataset

“…Multiple studies have shown that morphometric and radiomic metrics derived from morphologically normal pancreas can be biomarkers in diabetes, obesity, nonalcoholic fatty liver and pancreas disease, metabolic syndrome, and in patients undergoing immunotherapy for nonpancreatic malignancies. [1][2][3]8,[12][13][14] However, the quantitative changes in these metrics are beyond the perceptive abilities of the naked eye. Therefore, the pancreas appears morphologically normal on visual inspection in these subjects.…”

“…Our decision to develop a model for segmentation of morphologically normal pancreas was based on anticipated clinical applications. Multiple studies have shown that morphometric and radiomic metrics derived from morphologically normal pancreas can be biomarkers in diabetes, obesity, nonalcoholic fatty liver and pancreas disease, metabolic syndrome, and in patients undergoing immunotherapy for nonpancreatic malignancies 1–3,8,12–14 . However, the quantitative changes in these metrics are beyond the perceptive abilities of the naked eye.…”

“…4 On the other hand, obesity and metabolic syndrome are associated with increased pancreatic volumes. 1 Longitudinal change in pancreatic volume has been evaluated as a surrogate of improved glycemic control after bariatric surgery, 5 response to antidiabetic therapy in type 2 DM, 6 to predict outcomes after immunotherapy, 7,8 and to predict pancreatic function after partial pancreatectomy. 9,10 Pancreatic steatosis is another biomarker, which has been associated with pancreatic neoplasms, pancreatitis, nonalcoholic fatty liver and pancreas disease, metabolic syndrome, and DM.…”

Budesonide treatment for microscopic colitis from immune checkpoint inhibitors

“…Early endoscopy was associated with faster resolution of enterocolitis symptoms and shorter duration of glucocorticoid use in a retrospective analysis [20]. Endoscopy may be useful in identifying rare patients with CPI associated gastrointestinal symptoms that are not related to mucosal inflammation [21, 22], as well as patients with colonic ulceration who are more likely to fail initial management with glucocorticoids [10, 11]. Although mucosal changes are common in patients with CPI enterocolitis, a subset of patients have normal-appearing mucosa on endoscopy and lymphocyte-predominant inflammation [6, 23].…”

Pembrolizumab-induced diabetes

“…In our case, antibodies were absent. Several studies have reported mild elevations of serum amylase and serum lipase, without features of pancreatitis on imaging, although pancreatic atrophy may be seen [5,6].…”