Relationships between longitudinal neutrophil to lymphocyte ratios, body weight changes, and overall survival in patients with non-small cell lung cancer

Background: There is emerging evidence showing a significant relationship between overall survival (OS) in non-small cell lung cancer NSCLC patients and weight change during chemotherapy or chemoradiation. A high neutrophil/lymphocyte ratio (NLR) at baseline and at follow-up is associated with shorter survival in cancer patients and may be a surrogate for ongoing inflammation, implicated in cancer cachexia and tumor progression. The objective of this study is to explore potential relationships between OS, serial weights, and serial NLRs in advanced NSCLC patients receiving chemotherapy. Methods: One hundred thirty-nine patients with chemotherapy-naive NSCLC, predominantly with stage III/IV disease, were treated with first-line platinum doublets from June, 2011 to August, 2012. NLR, tumor response, and body weight were recorded at baseline, 6, and 12 weeks from initiation of therapy and correlated with OS. The association between NLR and OS was assessed using Cox PH (proportional hazards) analysis, the association between NLR and weight change was assessed using a simple regression analysis, and the association between NLR and tumor response was assessed using the Fisher's exact test. Results: One hundred thirty-nine patients with median age 68, PS 0-1/2 = 83/17%, male/female = 58%/42%. Median NLR at baseline was 3.6 (range 0.1898 to 30.910), at 6 weeks 3.11 (range 0.2703 to 42.11), and at 12 weeks 3.52 (range 0.2147 to 42.93). A Higher NLR at baseline, 6, and 12 weeks was associated with decreased OS (baseline: HR 1.06, p < 0.001; 6 weeks: HR 1.07, p = 0.001; 12 weeks: HR 1.05, p < 0.001), and longitudinal NLR, as a time-dependent covariate, was also associated with decreased OS (HR = 1.06, p < 0.001). Baseline weight and NLR were inversely related (cor = -0.267, p = 0.001), and weight change and NLR were inversely related at 12 weeks (cor = -0.371, p < 0.001). Longitudinal measurements of weight and NLR were also negatively associated (slope = -0.06, p < 0.001). Using a cutoff of NLR > 5, there was a significant association between progressive disease and NLR > 5 at 6 weeks (p = 0.02) and 12 weeks (p = 0.03). Conclusions: High baseline and progressive increases in NLRs are associated with progressive disease, inferior OS and weight loss in NSCLC patients. In addition to having prognostic significance, these observations suggest that studying molecular mediators of cachexia/ inflammation and their relationships to tumor progression may identify new therapeutic targets in the large subset of NSCLC patients who have cancer cachexia.