The prognostic impact of neutrophil to lymphocyte ratio in advanced non-small-cell lung cancer patients treated with EGFR TKI

Thang Thanh Phan,1 Toan Trong Ho,1 Hue Thi Nguyen,1 Hang Thuy Nguyen,2 Thu Bich Tran,3 Son Truong Nguyen1 1Laboratory D Unit, Clinical Cancer Center, Cho Ray Hospital, Ho Chi Minh City, Vietnam; 2Pathology Department, Cho Ray Hospital, Ho Chi Minh City, Vietnam; 3Faculty of Biology and Biotechnology, University of Science, VNU-HCM, Ho Chi Minh City, Vietnam Purpose: To identify and clarify the roles of inflammatory markers in prognosis for advanced non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitor (TKI). Patients and methods: One hundred and twelve adenocarcinoma, clinical stage IV, NSCLC patients with either EGFR exon 19 deletion (E19del) or EGFR exon 21  L858R substitution mutation (L858R) were selected for this study. The blood cell count at different stages of treatment was used to calculate the inflammatory markers. The Kaplan–Meier statistics and Cox regression model were used to test the differences of progression-free survival (PFS) between groups by the optimal cutoff point of biomarkers. Results: The median values of white blood cell (WBC), neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR) and platelet to lymphocyte ratio (PLR) in NSCLC patients tended to be reduced after 3 months treated with EGFR TKI and increased conversely when the disease develops progression (P<0.001). With an optimal cutoff point of 2.96, NLR is the best prognostic marker in prediction of clinical response among the investigated markers (area under the curve [AUC]=0.873, 95% CI: 0.821–0.926, P<0.001), and it is an independent predictive marker (OR=3.52, 95% CI: 1.42–8.71, P<0.001). With optimal cutoff point of 0.38, MLR is also a predictive marker in response evaluation (AUC=0.762, 95% CI: 0.691–0.832). Univariate analyses have shown that the larger tumor size (>3cm) and the high level of pretreatment NLR were associated with the shortening of PFS (HR=2.24, 95% CI: 1.04–4.83, P=0.039 and HR=2.67, 95% CI: 1.41–5.03, P=0.006, respectively). Multivariate analysis has shown that the elevated NLR is an independent prognostic marker for worse PFS of NSCLC patients treated with EGFR TKI (HR=2.15, 95% CI: 1.15–3.99, P=0.016). Conclusion: NLR and MLR are valuable markers in response evaluation for NSCLC patients treated with EGFR TKI. The elevated NLR is also an independent prognostic factor for worse survival. Keywords: neutrophil to lymphocyte ratio, NLR, NSCLC, EGFR TK