Supplementary Material for: The Role of Perioperative Systemic Therapy in Localized Pancreatic Neuroendocrine Neoplasms

Background: The role of perioperative systemic therapy (PST) in the management of localized pancreatic neuroendocrine neoplasms (PanNEN) is unclear. Objectives: We aimed to evaluate the benefit of PST compared to surgery alone (SA) in patients with localized PanNEN. Method: We selected patients with stages I–III PanNEN who underwent curative-intent surgical resection in National Cancer Database from 2006 to 2014. Patients who had both PST and surgical resection were matched with patients who received SA by propensity score at 1-to-1 ratio with nearest neighbor method. Results: Four thousand eight hundred and ninety-two patients were included in this study with median age of 60 years. Factors associated with significant more use of PST compared to SA included age <65 years, community medical facilities, grade 3 tumor, tumor in the pancreatic head, T34 tumor, and N1 tumor. Three hundred and one PST patients were matched with 301 SA patients. In the matched cohort, the PST group had significantly shorter overall survival (OS) compared to the SA group (median overall both not reached, p = 0.037). This finding was confirmed by multivariable Cox proportional hazards regression in the original cohort (hazard ratio [HR] 1.45, 95% CI 1.11–1.89, p = 0.006). Subgroup analyses showed that adjuvant therapy was not associated with improved OS in grades 1–2 PanNEN (HR 2.03, 95% CI 1.31–3.16, p = 0.002). Conclusions: PST stratified by grade and neoadjuvant or adjuvant therapy compared to SA was not associated with improved OS in patients with localized PanNEN. PST for localized PanNEN should be used with caution until prospective data are available.