Characteristics and treatment options of glucagonomas: a national study from the French Group of Endocrine Tumors and ENDOCAN-RENATEN network.

Abstract

Glucagonoma is a very rare functional pancreatic neuroendocrine tumor (PanNET). We aimed to provide data on the diagnosis, prognosis, and management of patients with glucagonoma. In this retrospective national cohort, we included all patients with glucagonoma, defined by at least one major criterion (necrolytic migratory erythema (NME) and/or recent-onset diabetes and/or weight loss ≥ 5 kg) associated with either glucagonemia >2xULN or positive glucagon immunostaining. Antisecretory efficacy was defined as partial/complete resolution of glucagonoma symptoms. Antitumor efficacy was assessed according to the time to next treatment (TTNT). Thirty-eight patients were included with median age 58.7 yo, primary PanNET located in the tail (68.4%), synchronous metastases (63.2%). Median Ki-67 index was 3%. Most frequent glucagonomas symptoms at diagnosis were NME (86.8%), weight loss (68.4%) and diabetes (50%). Surgery of the primary PanNET was performed in 76.3% of cases, mainly with curative intent (61.5%). After surgery, complete resolution of NME was seen in 93.8% (n = 15/16). The secretory response rates were 85.7%, 85.7%, 75% and 60% with surgery of metastases (n = 6/7), chemotherapy (n = 6/7), liver-directed therapy (n = 6/8) and somatostatin analogues (n = 6/10), respectively. All lines combined, longer TTNT was reported with chemotherapy (20.2 months). Median overall survival was 17.3 years. The Ki-67 index >3% was associated with shorter OS (HR 5.27, 95%CI [1.11-24.96], p = 0.036). Patients with glucagonoma had prolonged survival, even in the presence of metastases at diagnosis. Curative-intent surgery should always be considered. Chemotherapy, PRRT or liver-directed therapy seem to provide both substantial antitumor and antisecretory efficacy.