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Shuo Li,1–4,* Huaxiang Xu,1–4,* Wenquan Wang,1–4 Heli Gao,1–4 Hao Li,1–4 Shirong Zhang,1–4 Jinzhi Xu,1–4 Wuhu Zhang,1–4 Shuaishuai Xu,1–4 Tianjiao Li,1–4 Quanxing Ni,1–4 Xianjun Yu,1–4 Chuntao Wu,1–4 Liang Liu1–41Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China; 3Shanghai Pancreatic Cancer Institute, Shanghai 200032, People’s Republic of China; 4Pancreatic Cancer Institute, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workPurpose: The systemic inflammation response index (SIRI), based on peripheral neutrophil, monocyte, and lymphocyte counts, was recently emerged and used as a novel tool in predicting prognosis in different types of cancer. Our aim was to investigate the clinical significance of preoperative SIRI in patients with resectable pancreatic ductal adenocarcinoma (PDAC).Materials and methods: The SIRI was developed in a training cohort of 371 PDAC patients undergoing radical surgery between 2010 and 2013 and validated in a validation cohort of 310 patients from 2014 to 2015. Baseline clinicopathologic characteristics, preoperative laboratory parameters and follow-up information were collected. The optimal cutoff value of SIRI was determined by receiver operating characteristic curve. Univariate and multivariate analysis were performed to analyze the prognostic value of SIRI.Results: The optimal cutoff value of SIRI stratified patients into low SIRI group (≤0.69) and high SIRI group (>0.69). Survival analysis showed that the median overall survival (OS) and recurrence-free survival (RFS) were significantly better in patients with low SIRI. The SIRI was an independent predictor of OS and RFS in multivariate analysis. In addition, SIRI remained its prognostic significance both in patients with early-stage diseases and in patients with normal carbohydrate antigen 19-9 levels. High SIRI indicated poor treatment response for patients who received postoperative adjuvant chemotherapy.Conclusion: Preoperative SIRI was an independent prognostic indicator of poor outcomes in PDAC patients after radical resection. It might assist clinicians to identify high-risk patients and choose the optimal individualized treatment strategy.Keywords: pancreatic ductal adenocarcinoma, systemic inflammation response index, overall survival, recurrence-free survival, prognosis