LAUSR

Introduction: Angiotensin system inhibitors (ASI) are widely used to manage hypertension. Laboratory and retrospective clinical data suggests that ASIs can improve cancer prognosis. The aim of this study is to investigate the effect of ASIs on overall survival in pancreatic ductal adenocarcinoma (PDAC) patients. Methods: We performed a retrospective review of the clinicopathologic records of patients with PDAC seen at the Massachusetts General Hospital (MGH) between 1/2006 - 12/2010. Patients on angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) were included as ASI users. We performed RNAseq and Gene Set Enrichment Analysis (GSEA) of primary tumor samples from patients with or without chronic ASI use. We also identified a surrogate signature of differentially expressed genes and we measured the extent of angiotensin inhibition in GEO and TCGA datasets. The extent of inhibition was used to correlate with survival. Statistical analysis was performed using Kaplan-Meier estimator and Cox proportional hazards ratio model. Results: A total of 794 consecutive PDAC patients were included, of whom 297 (37.4%) were on ASIs and 183 (23.0%) were on non-ASI antihypertensive drug therapy. In resected patients, ASI users had a significantly longer overall survival on univariate (median OS: 36.3 vs. 19.3 months, p=0.011) and multivariate analysis (HR, 0.49; 95%CI, 0.333-0.734; p Conclusion: In patients with PDAC, ASI use is associated with longer overall survival in resected patients and may benefit patients with locally advanced disease. These findings suggest the need for a prospective study to determine the efficacy of ASI in PDAC patients. Citation Format: Hao Liu, Matthias Pinter, Joao Incio, Hang Lee, William Ho, Jonathan Crain, Kamila Naxerova, Mengyang Di, Alex Jacobson, Daniella Dias Santos, Andrea Zanconato, Vikram Deshpande, Keith Lillemoe, Carlos Fernandez del Castillos, Michael Downes, Ronald Evans, James Michaelson, Cristina Ferrone, Yves Boucher, Jain K. Rakesh. Use of angiotensin system inhibitors is associated with longer overall survival in pancreatic ductal adenocarcinoma patients who underwent pancreatectomy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 957. doi:10.1158/1538-7445.AM2017-957