Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Advanced Pancreatic Ductal Adenocarcinoma: Impact of Baseline Fluctuation and Changes during Chemotherapy

AIMS AND BACKGROUND: Inflammation has been implicated in carcinogenesis and progression of pancreatic cancer. The neutrophil-to-lymphocyte ratio is an index of systemic inflammation. We examined the prognostic role of the neutrophil-to-lymphocyte ratio at baseline and the significance of intrapersonal variability of the ratio before and during chemotherapy. METHODS AND STUDY DESIGN: Advanced pancreatic adenocarcinoma patients who had received chemotherapy were included. Baseline clinical and biochemical parameters, including the neutrophil-to-lymphocyte ratio, were extracted and analyzed. The neutrophil-to-lymphocyte ratio threshold was determined via recursive partitioning and assessed at diagnosis, prior to chemotherapy and during treatment. Overall survival was estimated via the Kaplan-Meier method and compared between groups with the logrank test. RESULTS: Between 2005 and 2011, 85 patients with locally advanced (n = 38) and metastatic disease were identified: 68% with a neutrophil-to-lymphocyte ratio >3 had shorter median overall survival than patients with a neutrophil-to-lymphocyte ratio <3 (3.4 vs 9.4 months, P = 0.001). Pretreatment, 35% of repeat neutrophil-to-lymphocyte ratios crossed the threshold of 3. A persistently elevated neutrophil-to-lymphocyte ratio >3 suggested a worse overall survival than in patients with a decreasing, increasing or persistently low neutrophil-to-lymphocyte ratio (1.9 vs 8.2, 12.3 and 11.7 months, respectively, P <0.001). Twenty-three percent of patients had a >50% decrease in neutrophil-to-lymphocyte ratio following 4 weeks of chemotherapy, with a trend towards improvement in overall survival (12.5 vs 5.0 mo, P = 0.068). CONCLUSIONS: The baseline neutrophil-to-lymphocyte ratio is a validated marker for a poor prognosis. Multiple assessments of the pre-treatment neutrophil-to-lymphocyte ratio might be required. Reduction in the neutrophil-to-lymphocyte ratio during chemotherapy may be associated with improved survival.