Abstract
BackgroundThere 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.MethodsOne hundred thirty-nine patients with chemotherapy-naïve 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.ResultsOne 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).ConclusionsHigh 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.
Highlights
There is emerging evidence showing a significant relationship between overall survival (OS) in non-small cell lung cancer Non-small cell lung cancer (NSCLC) patients and weight change during chemotherapy or chemoradiation
Identifying and combating this phenomenon has taken on great importance in light of studies showing that weight change in advanced NSCLC patients receiving concurrent chemoradiation or chemotherapy alone is inversely associated with overall survival (OS) [5,6,7]
It is likely that neutrophil/lymphocyte ratio (NLR) is a surrogate for ongoing inflammation, and that inflammation may be a linchpin that links tumor progression with cachexia and overall survival
Summary
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. More recent evidence suggests that there are several other factors that contribute to cancer cachexia, which includes increased insulin resistance, hypogonadism, adrenergic activation, and activation of proinflammatory responses [4]. Identifying and combating this phenomenon has taken on great importance in light of studies showing that weight change in advanced NSCLC patients receiving concurrent chemoradiation or chemotherapy alone is inversely associated with overall survival (OS) [5,6,7]. Loss of muscle mass (regardless of BMI) is associated with worse functional status and OS [8]
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