Neutrophil-to-lymphocyte ratio is correlated to driver gene mutations in surgically-resected non-small cell lung cancer and its post-operative evolution impacts outcomes.

Background: We sought to evaluate prognostic value of neutrophil-to-lymphocyte ratio (NLR) in surgically resected non-small cell lung cancer (NSCLC) and its correlation to oncogenic drivers. We retrospectively reviewed data of patients who underwent anatomic lung resection for NSCLC and whose mutational status was known, from 4 department of thoracic surgery, over the period 2008 to 2019. Primary endpoints were overall survival (OS) and time to recurrence (TTR). Clinical and molecular factors were investigated in the univariate and multivariate analysis for their association with the primary endpoints.

Results: 2027 patients were included in the analysis. Correlations between NLR and OS (R=0.21), NLR and TTR (R=0.085) were significant (P<0.0001), with corresponding Pearson R of -0.46 (P<0.0001) and -0.292 (P<0.001), respectively. ROC curve analysis defined NLR cut-off value at 4.07. In the univariable analysis, the median OS was 66 months (95% CI: 62.94 - 69.06) in case of pre-operative NLR ≤ 4.07 and 38 months (95% CI: 36.73 - 39.27) in case of pre-operative NLR > 4.07 (P<0.0001), with corresponding 5-y OS of 72% and 29% respectively. Median TTR was associated with pre-operative NLR. Median TTR was 25 months (95% CI: 21.52 - 28.48) in case of pre-operative NLR ≤ 4.07 and 17 months (95% CI: 16.04 - 17.96) in case of pre-operative NLR > 4.07 (P<0.0001), with corresponding 5-years TTR of 18% and 9% respectively. Significant correlations between NLR >4.07 and KRAS (Cramer's V = 0.082, P < 0.0001) and EGFR mutations (Cramer's V = 0.064, P = 0.004) were observed.

Conclusions: Low pre-operative NLR is associated with longer OS in patients with resected NSCLC. Low pre-operative NLR is not associated with longer TTR in multivariate analysis. Correlation between the high NLR and KRAS/EGFR mutations were observed.