Maria Thor1, Margaret Montovano2, Alexandra Hotca2, Leo Luo2, Andrew Jackson1, Abraham J Wu2, Joseph O Deasy3, Andreas Rimner2. 1. Dept of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, United States. 2. Dept of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, United States. 3. Dept of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, United States. Electronic address: deasyj@mskcc.org.
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.
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.
Authors: Maria Thor; Joseph O Deasy; Chen Hu; Elizabeth Gore; Voichita Bar-Ad; Clifford Robinson; Matthew Wheatley; Jung Hun Oh; Jeffrey Bogart; Yolanda I Garces; Vivek S Kavadi; Samir Narayan; Puneeth Iyengar; Jacob S Witt; James W Welsh; Cristopher D Koprowski; James M Larner; Ying Xiao; Jeffrey Bradley Journal: Clin Cancer Res Date: 2020-05-12 Impact factor: 12.531
Authors: Jamie E Chaft; Andreas Rimner; Walter Weder; Christopher G Azzoli; Mark G Kris; Tina Cascone Journal: Nat Rev Clin Oncol Date: 2021-04-28 Impact factor: 65.011