Impact of classical and basal-like molecular subtypes on overall survival in resected pancreatic cancer in the SPACIOUS-2 multicentre study.

BACKGROUND: The recently identified classical and basal-like molecular subtypes of pancreatic cancer impact on overall survival (OS). However, the added value of routine subtyping in both clinical practice and randomized trials is still unclear, as most studies do not consider clinicopathological parameters. This study examined the clinical prognostic value of molecular subtyping in patients with resected pancreatic cancer. METHODS: Subtypes were determined on fresh-frozen resected pancreatic cancer samples from three Dutch centres using the Purity Independent Subtyping of Tumours classification. Patient, treatment, and histopathological variables were compared between subtypes. The prognostic value of subtyping in (simulated) pre- and postoperative settings was assessed using Kaplan-Meier and Cox regression analyses. RESULTS: Of 199 patients with resected pancreatic cancer, 164 (82.4 per cent) were classified as the classical and 35 (17.6 per cent) as the basal-like subtype. Patients with a basal-like subtype had worse OS (11 versus 16 months (HR 1.49, 95 per cent c.i. 1.03 to 2.15; P = 0.035)) than patients with a classical subtype. In multivariable Cox regression analysis, including only clinical variables, the basal-like subtype was a statistically significant predictor for poor OS (HR 1.61, 95 per cent c.i. 1.11 to 2.34; P = 0.013). When histopathological variables were added to this model, the prognostic value of subtyping decreased (HR 1.49, 95 per cent c.i. 1.01 to 2.19; P = 0.045). CONCLUSION: The basal-like subtype was associated with worse OS in patients with resected pancreatic cancer. Adding molecular classification to inform on tumor biology may be used in patient stratification.

New onset non-alcoholic fatty liver disease after resection of pancreatic neuroendocrine tumors.

BACKGROUND AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatis (NASH) may occur after pancreatic resection due to exocrine pancreatic insufficiency (EPI). Patients with long-term survival, such as after pancreatic neuroendocrine tumor (pNET) resection, are at risk of NAFLD/NASH. We aimed to determine the incidence and risk factors for new onset NAFLD/NASH and EPI after pNET resection. METHODS: Retrospective monocenter cohort study. Patients who underwent pNET resection (1992-2016) were assessed for new onset NAFLD/NASH and EPI. Postoperative NAFLD/NASH was determined by a blinded abdominal radiologist, who compared pre- and postoperative imaging. RESULTS: Out of 235 patients with pNET, a total of 112 patients underwent resection and were included with a median follow-up of 54 months. New onset NAFLD/NASH occurred in 20% and EPI in 49% of patients. Multivariate analysis showed that the only risk factor for new onset NAFLD/NASH was recurrent disease (OR 4.4, 95% CI 1.1-16.8, P = 0.031), but not EPI (OR 0.94, 95% CI 0.3-2.8, P = 0.911). The only risk factor for EPI was pancreatoduodenectomy (OR 4.3, 95% CI 1.4-13.7, P = 0.012). CONCLUSIONS: New onset NAFLD/NASH is occasionally found after pNET resection, especially in patients with recurrent disease, but is not related to EPI.