Increased neutrophil-to-lymphocyte ratio after neoadjuvant therapy is associated with worse survival after resection of borderline resectable pancreatic ductal adenocarcinoma

• Published in: Surgery Vol. 160; no. 5; pp. 1288 - 1293
• Main Authors: Glazer, Evan S., MD, PhD, Rashid, Omar M., MD, JD, Pimiento, Jose M., MD, Hodul, Pamela J., MD, FACS, Malafa, Mokenge P., MD, FACS
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-11-2016
• Subjects: Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adenocarcinoma - therapy; Adult; Aged; Biomarkers, Tumor - blood; Carcinoma, Pancreatic Ductal - mortality; Carcinoma, Pancreatic Ductal - pathology; Carcinoma, Pancreatic Ductal - therapy; Databases, Factual; Disease-Free Survival; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Leukocyte Count; Lymphocyte Count; Male; Middle Aged; Neoadjuvant Therapy - adverse effects; Neoadjuvant Therapy - methods; Neoplasm Invasiveness - pathology; Neoplasm Staging; Pancreatectomy - methods; Pancreatectomy - mortality; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - therapy; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Statistics, Nonparametric; Surgery; Survival Analysis; Time Factors; Treatment Outcome
• ISSN: 0039-6060; 1532-7361
• DOI: 10.1016/j.surg.2016.04.039

Background The neutrophil-to-lymphocyte ratio (neutrophil count divided by lymphocyte count) is a marker of inflammation associated with poor cancer outcomes. The role of neutrophil-to-lymphocyte ratio in borderline resectable pancreatic ductal adenocarcinoma is unknown. We hypothesized that increased neutrophil-to-lymphocyte ratio in patients with borderline resectable pancreatic ductal adenocarcinoma after neoadjuvant therapy is inversely associated with survival. Methods We used our borderline resectable pancreatic ductal adenocarcinoma database to identify patients who had completed neoadjuvant therapy and underwent resection. The neutrophil-to-lymphocyte ratio difference was calculated as the neutrophil-to-lymphocyte ratio after neoadjuvant therapy minus the neutrophil-to-lymphocyte ratio before neoadjuvant therapy. Patients were assigned to the increased neutrophil-to-lymphocyte ratio cohort if the difference was ≥2.5 units; all others were assigned to the stable neutrophil-to-lymphocyte ratio cohort. Statistical analyses were performed with t test and regression. Results Of 62 patients identified, 43 were assigned to the stable neutrophil-to-lymphocyte ratio cohort, and 19 to the increased neutrophil-to-lymphocyte ratio cohort. There were no differences in stage, age, or sex. The preneoadjuvant neutrophil-to-lymphocyte ratio was 3.1 ± 2.4, whereas the postneoadjuvant neutrophil-to-lymphocyte ratio was 4.4 ± 3.5 ( P  = .002). Overall survival was worse in the increased neutrophil-to-lymphocyte ratio cohort compared with the stable neutrophil-to-lymphocyte ratio cohort ( P  = .009) with a Cox hazard ratio of 2.9 ( P  = .02). N0 disease conferred a survival advantage over N1 disease (Cox hazard ratio = 0.3, P  = .01). On multivariate Cox hazard regression analysis, both increased neutrophil-to-lymphocyte ratio and N1 stage were associated with worse survival ( P  < .01). Conclusion This investigation shows an independent, inverse association between survival and decreased neutrophil-to-lymphocyte ratio in patients with borderline resectable pancreatic ductal adenocarcinoma. These findings support exploring predictive inflammatory biomarkers, such as neutrophil-to-lymphocyte ratio, to investigate inflammation and improve outcomes.