Background To explore the impact of dynamic changes of leukocyte subsets during therapy on patient prognosis in inoperable stage III NSCLC, we compared in a prospective explorative single-center study the kinetics of major leukocyte subsets (absolute cell counts, ALC) before, during, and after definitive treatment and correlated it to survival to identify subpopulations associated with maximal patient benefit.

Materials and Methods We analyzed peripheral blood of 20 patients with inoperable stage III NSCLC, either treated with radiation therapy (RT), concurrent chemo-radiotherapy (cCRT), or cCRT with additional concurrent (nivolumab) or sequential (durvalumab) immune-checkpoint inhibition therapy. Blood samples were collected at 9 time points including before treatment begin (baseline), at the end of therapy, and during 1 y follow-up after treatment. Analysis included multi-color flow cytometry. Statistical analysis was conducted for leukocyte subpopulations (T cells, B cells, NK cells, neutrophils, thrombocytes), IL-6, progression-free survival (PFS) and overall survival (OS).

Results The increase of ALC after the end of thoracic radiotherapy (TRT) until 6 months thereafter was a predictor of PFS. Baseline lymphocyte counts showed no significant correlation to PFS or OS. Early recovery (within three months after TRT) of cell counts in lymphocytes, total CD3+ T cells, and CD8+ cytotoxic T cells were predictors of longer PFS. According to discriminant analysis, B cells, neutrophil-lymphocyte-ratio (NLR), CD4+ T helper cells, and NK cells contributed most to prolonged PFS.

Conclusions Our explorative results suggest that early recovery of absolute lymphocyte counts (ALC) of CD8+ T-cells, CD4+ T cells, and NK-cells after (chemo-) radiation-based definitive therapy of inoperable stage III NSCLC is associated with increased PFS. Immune checkpoint therapy showed a trend towards favorable PFS, OS, and fewer local tumor recurrences.

T. Hofer: None. A.E. Nieto: None. L. Kaesmann: B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); Modest; AstraZeneca. D. Speakers Bureau/Honoraria (speakers bureau, symposia, and expert witness); Modest; Amgen. C.J. Pelikan: None. J. Taugner: None. S. Mathur: None. C. Eze: None. C. Belka: B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); Modest; Brainlab, Elekta, ViewRay. D. Speakers Bureau/Honoraria (speakers bureau, symposia, and expert witness); Modest; ViewRay, Bristol Myers Squibb, Roche, Merck & Co, AstraZeneca. F. Consultant/Advisory Board; Modest; ViewRay, Bristol Myers Squibb, Roche, Merck & Co, AstraZeneca, European Society for Radiotherapy and Oncology. F. Manappov: B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); Modest; AstraZeneca. D. Speakers Bureau/Honoraria (speakers bureau, symposia, and expert witness); Modest; AstraZeneca, Novartis, Roche, Eli Lilly, Elekta, Brainlab. F. Consultant/Advisory Board; Modest; AstraZeneca, Novartis. E. Noessner: None.