Early Neutrophil-to-lymphocyte Ratio Reduction As a Surrogate Marker of Prognosis in Never Smokers with Advanced Lung Adenocarcinoma Receiving Gefitinib or Standard Chemotherapy As First-line Therapy

Purpose: An inflammatory-immunological marker, neutrophil-to-lymphocyte ratio (NLR), was evaluated as a surrogate indicator for prognosis of advanced lung adenocarcinoma patients.

Methods: The subjects of this study were 199 never smokers with advanced lung adenocarcinoma, who were enrolled in a prospective randomized phase III study (First-SIGNAL) comparing gefitinib with gemcitabine plus cisplatin as first-line therapy. The values of NLR were assessed at two time points: at baseline (pretreatment) and on day 1 of the second cycle (posttreatment).

Results: A higher posttreatment NLR was associated with a worse tumor response (median posttreatment NLR, 1.56 for partial response, 1.64 for stable disease, and 2.70 for progressive disease; P < 0.001). The risk of progression was higher when the posttreatment NLR was higher [hazard ratio (HR) = 1.23, 95 % confidence interval (CI) 1.15-1.31; P < 0.001]. A high posttreatment NLR was associated with an increased risk of death (HR = 1.13, 95 % CI 1.06-1.21; P < 0.001). These associations did not differ according to treatment arms. When total patients were divided into four groups according to the cutoff points of pre- and posttreatment NLRs, those with a high pretreatment NLR that declined substantially after treatment showed improved survival compared with those with a high pretreatment NLR that remained high even after treatment (median overall survival, 22.0 and 15.8 months, respectively; P < 0.001).

Conclusions: A high posttreatment NLR is associated with poor prognosis. An early reduction in the NLR after effective treatment may indicate survival improvement in the patients with poor prognosis.