Association between genotype and long-term risk of reintervention and distant metastases in patients with multiple endocrine neoplasia type 1-associated duodenopancreatic neuroendocrine tumors.

MEN1

Truncating germline MEN1 variants, associated with a higher risk of reintervention and distant metastases after surgery for duodenopancreatic neuroendocrine tumors

Duodenal and pancreatic neuroendocrine tumors are the leading cause of mortality in multiple endocrine neoplasia type 1, due to distant metastasis. This single-centre retrospective study analysed 153 patients with genetically confirmed multiple endocrine neoplasia type 1 evaluated from 1985 to 2024, 94 (61%) of whom underwent resection of duodenopancreatic neuroendocrine tumors at a median age of 40 years. After a median follow-up of 16.4 years, 25 patients (27%) required reintervention, and a truncating MEN1 variant was independently associated with reintervention (HR 3.82; 95% CI: 1.25-16.68). Among 84 patients without metastases at surgery, 24 (28.6%) developed distant metastases, with truncating genotype predicting shorter distant metastasis-free survival (HR 5.55; 95% CI: 1.56-35.40). Of the patients who developed metastases, 37.5% had a largest resected tumor ≤2 cm.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The message is clinical: tumor size alone is not enough to stratify risk, and the type of germline MEN1 variant, known from the molecular diagnosis, could modulate the intensity of postoperative surveillance. The very wide confidence intervals (upper bound of 35.40 for metastases), however, reflect the small number of events in a single-centre series spanning nearly 40 years. Multicentre validation is needed before this becomes a decision criterion.

Analysis by Dr Thibaut Benquey