Are unsatisfactory outcomes after concurrent chemoradiotherapy for locally advanced non-small cell lung cancer due to treatment-related immunosuppression?

Abstract

We test the hypothesis that unsatisfactory outcomes after concurrent chemoradiotherapy (RT) for locally advanced non-small cell lung cancer (LA-NSCLC) are due to treatment-related immunosuppression. White blood cells (WBCs) data were retrospectively collected for all stage IIIA/B LA-NSCLC patients before and after (after RT: two weeks, two months, four months) concurrent chemotherapy and intensity-modulated RT in which patients were treated to a median of 63 Gy (1.8-2.0 Gy/fractions) in 2004-2014 (N = 155). Nine WBC variables were generated from pre-RT normalized absolute number of lymphocytes and neutrophils (L, N) and the N/L thereof. A WBC variable was considered a predictor for overall survival and recurrence (distant/local/nodal/regional) if p ≤ 0.006 (corrected for 9 variables) from Cox regression and competing risk analyses, respectively; both conducted using bootstrap resampling. Finally, a WBC variable predicting any of the outcomes was linearly associated with each of eleven disease/patient/treatment characteristics (p ≤ 0.005; corrected for 11 characteristics). At the three post-RT time points both L and N significantly decreased (p < 0.0003). Overall survival was associated with N and N/L four months post-RT (p = 0.00001, 0.0003); regional recurrence was associated with L two months post-RT (p < 0.0001). None of the disease/patient/treatment characteristics was significantly associated with any of the three WBC variables that predicted OS or recurrence (lowest p-value: p = 0.006 for tumour stage,). Significantly lower WBC levels after concurrent chemo-RT for LA-NSCLC are associated with worse long-term outcomes. The mechanism behind this treatment-related immunosuppression requires further analysis likely including other characteristics as no statistically significant association was established between any WBC variable and the disease/patient/treatment characteristics.