Early recovery of leukocyte subsets is associated with progression-free survival in patients with inoperable stage III NSCLC after multimodal treatment: a prospective explorative study

Background We explored the dynamic changes of major leukocyte subsets during definitive treatment of patients with inoperable stage III NSCLC lung cancer and correlated it to survival to identify subpopulations associated with maximal patient benefit. Methods We analyzed peripheral blood of 20 patients, either treated with thoracic radiotherapy (RT), concurrent chemo-radiotherapy (cCRT), or cCRT with additional immune-checkpoint inhibition therapy. Blood samples were collected at 9 timepoints before, during, and up to 1 year post treatment and analyzed by multi-color flow cytometry. Statistical analysis was conducted for leukocyte subpopulations, IL-6, progression-free survival (PFS) and overall survival (OS). Results Increase of absolute lymphocyte counts (ALC) after the end of RT until 6 months thereafter was a predictor of PFS. Baseline lymphocyte counts showed no significant correlation to PFS or OS. Early recovery of absolute counts (AC) at 3 weeks after RT, total CD3+ T-cells, and CD8+ cytotoxic T-cells distinguished those patients with favorable PFS (≥12 months) from all other patients. Discriminant analysis identified B-cells, neutrophil-lymphocyte-ratio (NLR), CD4+ T-helper-cells, and NK-cells as predictors of favorable PFS. High variability in IL-6 plasma concentration of consecutive measurements within 6 months after the end of RT correlated negatively with PFS. Conclusion Our results suggest that two parameters commonly assessed in clinical routine, can be used to predict patient outcome. These are: early increase in CD8+ T-cell lymphocyte-count and variability in IL-6 plasma concentration, that are correlated to patients with favorable, respectively, poor outcome after definitive therapy independent of treatment regimen. Highlights Early increase within 3 weeks after thoracic radiation therapy (TRT) of CD8+ T cells is associated with favorable progression free survival (PFS). Low standard deviation in IL-6 plasma concentration in consecutive measurements after TRT is associated with favorable PFS. Absolute lymphocyte counts at treatment begin had no predictive value for treatment outcome. Funding statement none