Prognostic Value of Neutrophil-to-Lymphocyte Ratio and Location in Patients With EGFR Mutant Metastatic Non-Small Cell Lung Cancer Treated with TKIs

Abstract

Background: Targeted therapy with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has improved the field of metastatic non-small cell lung cancer treatment. Higher neutrophil-to-lymphocyte ratio (NLR) and lower relative lymphocyte counts as inflammatory indicators and associated with worse overall survival and progression free survival (PFS) in several tumor types. Few studies focused on these inflammation markers in field of TKIs eras. Methods: Patients with advanced EGFR mutation NSCLC treated with TKIs were included. Pre-treatment NLR means neutrophil to lymphocyte ratio measured in peripheral blood within one week before treating with TKIs. The baseline clinical characteristics of each group were compared by chi-square and t tests. Cox regression analyses were used to evaluate prognostic value of peripheral blood parameters on progression free survival (PFS). All prognostic factors were explored with multivariable regression. Results: We retrospectively analyzed 221 patients with metastatic NSCLC harboring exon 19 deletion, 21 L858R or rare mutation and receiving TKIs. Finally, a total of 190 patients were analyzed. The optimal cutoff values for pretreatment absolute lymphocyte count (Lym), lymphocyte percentage (Lym%), absolute neutrophil count (Neu), the percentage of neutrophil granulocytes (Neu%) and NLR were 1.625 B, 18.8%, 3.675a, 51.8% and 4.965, respectively. Patients with high neutrophil percent (18.8 months vs 13.0 months, P=0.003), absolute neutrophil counts (12.0 months vs 14.5 months, P=0.014) and NLR (7.0 months vs 15.2 months, P<0.001, one year PFS Rate, 38.4%, respectively) had worse PFS. In contrast, patients with high absolute lymphocyte counts (16.5 months vs 13.0 months, P=0.012) and lymphocyte percent (15.3 months vs 8.8 months, P<0.001) had a better progression-free-survival. Besides, tumor location is also an important factor for prognosis (14.3 months vs 11.6 months, P=0.003). On multivariate analysis, NLR and primary tumor location were both identified as independent and significantly risk indicators for worse PFS. Conclusion: NLR and primary location are both independent prognostic factors for PFS in patients with metastatic EGFR mutated lung tumor. Whether or not NLR and primary location could be useful markers in efficacy prediction of TKIs in advanced NSCLC calls for further investigation.