Factors affecting overall survival in early-onset gastroenteropancreatic neuroendocrine tumours (GEP-NETs): A multicenter database study using TriNetX.

626 Background: The incidence of early-onset gastroenteropancreatic neuroendocrine tumors (EO GEP-NETs), defined as diagnosis before age 50, is on the rise. Given their heterogeneous disease course, we aimed to identify clinical and demographic factors associated with overall survival (OS) in this population. Methods: We conducted a multicenter retrospective study using the TriNetX research platform, a federated network of de-identified electronic medical records. Adults diagnosed with EO GEP-NETs between January 1 st 2010 and January 1 st 2025 were identified, and effect of covariates on OS was evaluated using Cox proportional hazards model. Covariates included age at index, sex, race, marital status, obesity, type 2 diabetes mellitus, nicotine and alcohol dependence, depression, and metastatic sites (liver, bone, peritoneum, brain, lymph nodes, lung, retroperitoneum). Results: A total of 17,476 patients with EO GEP-NETs were identified; 42.3% were female and 65.3% were white. Factors associated with worse prognosis and increased mortality included male sex [HR 1.35, 95% CI 1.24–1.46; p<0.0001], nicotine dependence [HR 1.35, 95% CI 1.19–1.54; p<0.0001], type 2 diabetes mellitus [HR 1.21, 95% CI 1.05–1.39; p=0.008], and older age at diagnosis [HR 1.02 per year, 95% CI 1.02–1.03; p<0.0001]. Metastatic sites significantly associated with worse OS included liver [HR 2.53, 95% CI 2.18–2.93; p<0.0001], bone [HR 2.41, 95% CI 1.95–2.97; p<0.0001], peritoneum [HR 2.27, 95% CI 1.81–2.84; p<0.0001], brain [HR 2.23, 95% CI 1.69–2.94; p<0.0001], lymph nodes [HR 2.05, 95% CI 1.74–2.41; p<0.0001], and lung [HR 1.68, 95% CI 1.33–2.11; p<0.0001]. Protective factors included obesity [HR 0.84, 95% CI 0.74–0.96; p=0.01] and "married" status [HR 0.73, 95% CI 0.66–0.81; p<0.0001]. Race, alcohol dependence, and depression were not significantly associated with OS. Conclusions: Among patients with EO GEP-NETs, adverse prognostic factors include male sex, nicotine dependence, type 2 diabetes, older age at diagnosis, and metastatic involvement of the liver, bone, peritoneum, brain, lymph nodes, or lung. In contrast, marital status and obesity were associated with improved survival. These findings highlight prognostic heterogeneity in EO GEP-NETs and may help inform risk stratification and patient counseling. Cox proportional hazard model for overall survival. Covariate Hazard ratio P value 95% confidence interval Male 1.345 <0.0001 (1.238, 1.462) Alcohol dependence 1.033 0.862 (0.718, 1.486) Nicotine dependence 1.354 <0.0001 (1.189, 1.541) Overweight and obesity 0.843 0.010 (0.740, 0.961) Married 0.731 <0.0001 (0.660, 0.809) Depression, unspecified 0.838 0.118 (0.671, 1.046) Type 2 diabetes mellitus 1.209 0.008 (1.052, 1.389) Age at Index 1.021 <0.0001 (1.015, 1.026)