Impact of Thoracic Vertebral Body Dose on Post-Treatment Neutrophil Lymphocyte Ratio in Locally Advanced Non-Small Cell Lung Cancer

Abstract

Neutrophil-lymphocyte ratio (NLR) has been associated with mortality for non-small cell lung cancer (NSCLC), but its association with recurrence in locally advanced NSCLC, specifically, is less established. We hypothesized that pre- and post-treatment NLR would be associated with increased recurrence and mortality and further that increasing radiation dose to the thoracic vertebral bodies (TVB) during chemoradiation would be associated with increased post-treatment NLR. We used Cox proportional hazards and Kaplan-Meier analysis to study the association of pre- and post-treatment NLR with overall survival and recurrence in patients with locally advanced NSCLC treated with chemoradiation. Pre- and post-NLR were analyzed as continuous and dichotomized variables. Pre-treatment NLR was dichotomized by a value of 5, an a priori cutoff previously shown to be prognostic in locally advanced NLR. Post-treatment NLR was dichotomized by the median. We subsequently performed linear and logistic regression to correlate TVB dose with NLR at 3 months post treatment. We identified 144 patients with available survival data (88 with recurrence data) treated with chemoradiation for locally advanced NSCLC between 2007 and 2016. Median follow up for living patients was 14.9 months. On multivariable analysis, pre-treatment NLR ≥ 5 was associated with worse overall survival (HR = 2.56; 95% CI 1.53 – 4.30; p < 0.001), any recurrence (HR = 2.13; 95% CI 1.10 – 4.12; p = 0.026) and locoregional recurrence (HR = 2.64; 95% CI 1.12 – 6.23; p = 0.026), but not distant recurrence (HR = 1.85; 95% CI 0.76 – 4.51; p = 0.18). There was a statistically significant increase in NLR after treatment (p < 0.001). Three-month median post-treatment NLR ≥ 6.6 was associated with worse overall survival (HR = 3.16; 95% CI 1.70 – 5.86; p < 0.001), any recurrence (HR = 2.96; 95% CI 1.54 – 5.69; p = 0.001), and locoregional recurrence (HR = 6.53; 95% CI 2.44 – 17.44; p < 0.001). There was a trend toward significant association with distant recurrence (HR = 2.16; 95% CI 0.92 – 5.05; p = 0.077). On linear regression, there was a statistically significant correlation of post-treatment NLR at 3 months with thoracic vertebral body volume receiving 5, 10, 20, 30, 40, and 50 Gy. On logistic regression, there was a direct correlation of 3-month post-treatment NLR ≥ 6.6 with V5 (p = 0.13), V10 (p = 0.023), V50 (p = 0.045), and V60 (p = 0.042). We found that both pre-treatment NLR and post-treatment NLR are associated with worse overall survival and locoregional recurrence. Additionally, we found that post-treatment NLR is correlated with TVB. These findings suggest that limiting dose to the TVB is important for not only reducing acute hematologic toxicity but also for improving disease outcomes, and these results should be validated in an independent, ideally prospectively studied cohort.