E. Gkika1,2, E. Firat3, S. Adebahr4, E. Graf5, I. Popp6, A. Eichhorst7, G. Radicioni8, S. K. B. Spohn9, N. H. Nicolay10, A. Rimner11, S. S. Lo12, U. Nestle6, G. Niedermann13, G. D. Duda14, and A. Grosu13; 1Department of Radiation Oncology, University Medical Center Freiburg, Freiburg, Germany, 2Department of Radiation Oncology, University Hospital Bonn, Bonn, Germany, 3Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, Freiburg, Germany, 4Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg and German Cancer Consortium (DKTK) Partner Site Freiburg and German Cancer Research Center (DKFZ) Heidelberg, Freiburg, Germany, 5Institute of Medical Biometry and Statistics, Medical Center-University of Freiburg, Faculty of Medicine, Freiburg, Germany, 6Department of Radiation Oncology, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany, 71 Department of Radiation Oncology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, DKTK-Partner Site Freiburg, Germany, Feriburg, Germany, 8Department of Radiation Oncology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg,, Freiburg, Germany, 9Department of Radiation Oncology – University Medical Center Freiburg, Freiburg, Germany, 10Department of Radiation Oncology, Medical Center – University of Freiburg, Faculty of Medicine, Freiburg, Germany, 11Department of Radiation Oncology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, German Cancer Consortium (DKTK), partner site DKTK-Freiburg, Freiburg, Germany, 12Department of Radiation Oncology, University of Washington/ Fred Hutchinson Cancer Center, Seattle, WA, 13German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany, 14E. L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, USA, Boston, MA
Purpose/Objective(s): The study aimed to evaluate the influence of ablative SBRT fractionation on radiotherapy-induced lymphopenia, T cell proliferation and effector T cell function in patients with early-stage NSCLC or oligoprogressive or oligometastatic lung disease, using different dose and fractionation regimes (in 3, 5, 8 or 12 fractions) aiming at a BED of 100 Gy, with or without systemic treatment (chemotherapy or immunotherapy). Materials/
Methods: Patients with lung SBRT, either in the primary or the metastatic setting with or without concurrent systemic treatment, were included in the prospective LAPIS studies. To evaluate the effects of SBRT, immunoprofiling of peripheral blood was performed at first SBRT fraction (pre-treatment), during and at the end of SBRT as well as at first (FU1) and second (FU2) follow-up by flow cytometry. Results: The LAPIS studies accrued 156 patients between 2016-2021, of whom 130 were evaluable by flow cytometric analysis. With a median follow-up of 30 months, the median overall survival (OS) was 38 months from SBRT, and the median progression-free survival (PFS) was 14 months, while the 3– and 5-year PFS were 33% and 23%, respectively. For patients with an increase (yes vs no) in circulating CD8+ CTLs at FU1 (the primary study endpoint), the median PFS from FU1 was favorable (not reached versus 21 months), although the difference was not statistically significant (HR=0.653, 95% CI: 0.25-1.74, p=0,4). For patients treated with 8-12 fractions, SBRT induced stronger lymphopenia compared to 3-5 fractions at the end of treatment, but a significant increase in proliferation of CD8+ and CD4+ T cells (at the end of treatment. PD-1+/- T cell proliferation was also higher in the 8-12 fraction group. Effector T cell function, indicated by IFN-g expression, was comparable in both fractionation groups. These increases were durable and were observed at follow-up, especially in the subgroup of patients with metastatic disease who had not received concurrent systemic treatment. Conclusion: These data show that prolonged regimes given in moderate RT doses seem to better induce a polyfunctional T cell response compared to 3-5 fractions given in higher RT doses per fraction.
