Insulin-dependence as a Predictor of Shortened Cancer-specific Survival in Pancreatic Neuroendocrine Tumors: A Multi-Institutional Study from the United States Neuroendocrine Study Group

Introduction: PNETs are rare pancreatic malignancies originating from islet cells and exhibit a strong co-occurrence with Diabetes Mellitus (DM), associated with worse survival outcomes. However, studies have yet to delineate the impact of insulin dependent (IDDM) and non -insulin dependent (NIDDM) on poor oncological outcomes. Methods: Utilizing the U.S. Neuroendocrine Tumor Study Group database (1999-2016), we performed a retrospective cohort study of adult patients who underwent primary surgical resection of PNETs. Patients were categorized based on preoperative diagnosis into non-DM, NIDDM, and IDDM cohorts. We used the Kaplan-Meier method and log-rank test to study cancer-specific survival (CSS). Cox proportional Hazards models were used to assess the impact of IDDM on CSS. Results: Of the 1,122 patients included in the analysis, 870 (77%) were non-DM, 168 (15%) were NIDDM, and 84 (8%) were IDDM. The groups were similar in tumor stage and grade. However, they differed in sex, BMI, age, ASA class, tumor location, preoperative HbA1c and serum glucose (p-value <0.05). Patients with IDDM had significantly decreased 5-year CSS compared to patients without IDDM (CSS: IDDM 85%, NIDDM 94%, non-DM 93%, NIDDM + non-DM 93%; P <0.01). On multivariate analysis, IDDM was independently associated with worse CSS (HR 2.27, 95% Confidence Interval 1.15-4.45, P=0.02). Conclusion: Insulin dependence is associated with worse cancer-specific survival in PNET patients following surgical resection compared to PNET patients with NIDDM or without DM.