Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio associations with heart and body dose and their effects on patient outcomes in locally advanced non-small cell lung cancer treated with definitive radiotherapy

Background Inflammation plays a vital role in tumor growth and progression and can be affected by radiotherapy (RT) and chemotherapy. We sought to investigate the prognostic significance of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), and their associations with dosimetric factors in locally advanced non-small cell lung cancer (LA-NSCLC). Methods In this retrospective study, subjects consisted of 244 patients who had received definitive RT ± chemotherapy for LA-NSCLC between 2012 and 2016. Absolute lymphocyte count (ALC), NLR and PLR recorded at pretreatment, during RT and post-RT were analyzed. Multivariable analysis (MVA) was performed to correlate clinical factors and inflammatory biomarkers with progression-free survival (PFS) and overall survival (OS) using a Cox regression model. Relationships between NLR or PLR with OS and PFS were evaluated with Kaplan-Meier analysis and compared with log-rank test results. Multiple stepwise linear regression was used to assess the associations between dosimetric factors and NLR or PLR. Results The median PFS and OS for all patients were 8.6 and 15.8 months, respectively. On MVA for PFS and OS, higher 1-month post-RT start NLR [hazard ratio (HR) 1.049; 95% CI: 1.018-1.080; P=0.001] or higher 1-month post-RT start PLR (HR 1.001; 95% CI: 1.000-1.002; P<0.001) was associated with inferior PFS. Higher 1-month post-RT start NLR (HR 1.040; 95% CI: 1.013-1.069; P=0.004) or PLR (HR 1.001; 95% CI: 1.001-1.002; P<0.001) was also an independent predictor of OS. ALCmin, baseline NLR and PLR were not associated with treatment outcomes. Multiple stepwise linear regression analysis confirmed that baseline NLR (P<0.001), heart V20 (P<0.001), heart V40 (P<0.001), and mean body dose (MBD) were significantly associated with 1-month post-RT start NLR. Also, baseline PLR (P<0.001) and MBD (P<0.001) were significantly associated with 1-month post-RT start PLR. Conclusions Higher NLR and PLR during treatment were associated with worse patient outcomes, and heart dose or body dose was correlated with NLR or PLR in advanced NSCLC patients treated with definitive RT.