Impact of Pre-treatment Immunologic Parameters on the Outcomes of Early-Stage Non-Small Cell Lung Cancer (NSCLC)

Abstract

Evaluate the association of pre-treatment immunologic parameters on the outcomes of early-stage non-small-cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT). All early-stage NSCLC treated with SBRT between Jan 2010 and Dec 2017 were included for analysis. Patients with a history of malignancy apart from skin malignancy (excluding melanoma) were excluded. The pre-treatment neutrophil-lymphocyte ratio (NLR), monocyte lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) were calculated. Overall survival (OS) and recurrence-free survival (RFS) were calculated. Univariate and multivariate analyses were performed accounting for NLR, PLR, MLR, ECOG, ITV volume, age and gender as covariates. Stepwise Cox regression analyses were used and results were considered significant if the p-value was less than 0.05. Multivariable models including ECOG and ITV volume as predictors were constructed and the Akaike Information Criteria (AIC) values were captured. NLR, PLR, and MLR were added separately to the multivariable model and the delta AIC between the two models were calculated. A total of 61 patients were identified in the current cohort and 41(67%) were females. The median age was 77.5 years, with an interquartile range (IQR) of 72-82 years. The median tumor size was 2.1 cm, with an IQ range of 1.6-2.8 cm. The median ITV and PTV volumes were 11.15 and 35.6 cm3, respectively. The median neutrophil count at baseline was 5.4 ×109/L (IQR: 4.17 – 7.05 ×109/L). Median lymphocyte count was 1.63 ×109/L (IQR: 1.29 – 2.10 ×109/L), median monocyte count was 0.65 ×109/L (IQR: 0.54 – 0.83 ×109/L), median platelet count was 260.0 ×109/L (IQR: 211.0 – 302.0 ×109/L). The median NLR was 3.42 (IQR: 2.38 – 5.04), median MLR was 0.39 (IQR: 0.31 – 0.53), and median PLR was 156.4 (IQR: 117.2 – 197.5). Univariate and multivariate analysis was performed for NLR, PLR, MLR, ECOG, ITV volume, age and gender. On univariate analysis, higher NLR was associated poorer OS (P = 0.009; HR-1.27; 95% CI 1.06-1.53) and poorer RFS (P = 0.01; HR-1.08; 95% CI 1.01-1.1.17). Multivariable models including ECOG and ITV volume showed higher NLR was associated with poorer OS (P = 0.01; HR-1.26; 95% CI 1.04-1.53). The delta AIC between the two multivariable models was 3.4, suggesting a moderate impact on OS. The relationship between NLR and RFS was nonlinear and a polynomial function was used. In multivariable analysis, higher NLR was associated with poor RFS (P = 0.001; NLRˆ1 HR 0.36; 0.17-0.78; NLRˆ2 HR-1.16; 95% CI 1.06-1.26). The delta AIC between the two multivariable models was 16.2, suggesting a strong impact on RFS. In our cohort MLR and PLR were not associated with RFS or OS in multivariable models. For MLR and PLR the delta AIC was less than 2, suggesting weak or no impact. Elevated NLR predicts poorer RFS and OS. Further validation could help identify patients at the risk of early failures.