Are unsatisfactory outcomes after concurrent chemoradiotherapy for locally advanced non-small cell lung cancer due to treatment-related immunosuppression?. (February 2020)

• Record Type: Journal Article
• Authors: Thor, Maria; Montovano, Margaret; Hotca, Alexandra; Luo, Leo; Jackson, Andrew; Wu, Abraham J.; Deasy, Joseph O.; Rimner, Andreas
• Is Part Of: Radiotherapy and oncology. Volume 143(2020)
• Page Start: 51
• Page End: 57
• Publication Date: 2020-02
• Subjects: Radiotherapy -- Lung cancer -- Immune -- Dose -- Toxicity -- Survival; Oncology -- Periodicals; Radiotherapy -- Periodicals; Tumors -- Periodicals; Medical Oncology -- Periodicals; Neoplasms -- radiotherapy -- Periodicals; Radiotherapy -- Periodicals; Radiothérapie -- Périodiques; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9940642
• DOI: 10.1016/j.radonc.2019.07.016
• Languages: English
• ISSNs: 0167-8140

Abstract

Highlights: The number of white blood cells (WBCs) significantly decreases within four months after concurrent chemo-RT of LA-NSCLC. The treatment-induced neutrophil decrease and the ratio between the decreased neutrophil and lymphocyte decreases is associated with worse overall survival. No investigated disease/patient/treatment characteristics was significantly associated with the WBC drop. Abstract: Background and Purpose: 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. Materials and Methods: 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). Results: 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, ). Conclusion: 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.