ESTRO 2025 - Abstract Book

S2402

Interdisciplinary – Other

ESTRO 2025

3645

Proffered Paper Exploring the Systemic Immunological Impact of Stereotactic Radiotherapy: A Flow Cytometry-based Investigation (iDOSE study) Nora D. Purcell 1 , Linda R. Beeloo 1 , Idris I. Bahce 2 , Tanja D. deGruijl 3 , Suresh Senan 1 , Famke L. Schneiders 1 1 Radiation Oncology, VUMC, Amsterdam, Netherlands. 2 Pulmonary Medicine, VUMC, Amsterdam, Netherlands. 3 Medical Oncology, VUMC, Amsterdam, Netherlands Purpose/Objective For early-stage non-small cell lung cancer (ES-NSCLC), patients unfit for or declining surgery, stereotactic ablative body radiotherapy (SABR) is the standard of care, offering ~90% local control. However, 12% experience regional recurrences and 20% develop distant metastases. Attempts to enhance outcomes by combining SABR with immunotherapy yielded mixed results. While a phase-II trial showed SABR benefits (1), recent phase-III trials ended early due to lack of efficacy (2,3). SABR employs risk-adapted fractionation based on tumor proximity to organs-at risk: typical regimens include one 34Gy fraction, three 18Gy fractions, or five 11Gy fractions. Exploring the immunologic effects of these schemes enables optimization of SABR-immunotherapy combinations. We analyzed systemic immune responses across three routine SABR schedules in ES-NSCLC patients. This prospective study examines how three SABR fractionation schedules influence immune responses and guide SABR immunotherapy combination strategies. Material/Methods Approved by the Amsterdam UMC institutional review board [2018.548], the study enrolled 28 ES-NSCLC patients, with planned cohorts of 10 each. SABR schedules, based on tumor size and location, were: three fractions of 18Gy, five fractions of 11Gy, or one 34Gy fraction. Immune responses were analyzed using flow cytometry, assessing peripheral blood mononuclear cells (PBMCs) at five timepoints—pre-, during, and post-treatment. Immunophenotyping included 8–12 immune cell markers to evaluate lineage and activation profiles across timepoints. Results Systemic immune modulatory effects of radiotherapy were most prominent one week post-treatment across all fractionation schemes, with some effects persisting up to one month post-treatment. A significant decrease in circulating B cells was observed 1 week post-SABR, alongside significant increase in proliferation of CD4, CD8, T regulatory, and Natural Killer (NK) cells. Within the different fractionation regimens, a positive correlation was found between the number of fractions and the magnitude of immune modulation. The 5 × 11 Gy regimen exhibited the most significant immune effects, characterized by increased proliferation of CD4, CD8, and NK effector cells, whereas the 1 × 34Gy regimen showed less pronounced modulation.