2559 - First Report of FLASH Sparing Effect of Multifield Raster-Scanning Helium Ion Beams in Radiation Induced Lung Fibrosis Model
Presenter(s)
M. Moustafa1, M. Akbarpour1, H. Hassan1, J. Furkel1, M. Knoll1, N. Abdallah2, A. Osama2, S. Brons3, C. A. Assenmacher4, S. Magdeldin2, J. Debus1, and A. Abdollahi1; 1Division of Molecular and Translational Radiation Oncology, Department of Radiation Oncology, Heidelberg Faculty of Medicine (MFHD), Heidelberg University Hospital (UKHD) and Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg, Germany, 2Children Cancer Hospital Egypt 57357, Cairo, Egypt, 3Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany, 4Comparative Pathology Core (CPC), Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA
Purpose/Objective(s): Helium ion beams combine favorable biophysical characteristics, including increased linear energy transfer (LET) and markedly reduced lateral scattering, offering higher precision, dose conformality, and improved normal-tissue sparing for deep-seated tumors compared with state-of-the-art proton particle therapy. Building on this rationale, we sought to demonstrate the technical feasibility of whole-thoracic irradiation (WTI) using multifield raster-scanned FLASH helium ion beams (He) and to evaluate their normal-tissue sparing potential in a radiation-induced lung fibrosis (RILF) model as a paradigmatic endpoint of late normal-tissue radiotolerance.
Materials/Methods: C57BL/6 mice underwent whole-thoracic irradiation (WTI) with either standard dose-rate (SDR) or ultra-high dose-rate (FLASH) helium ion beams at the Heidelberg Ion-Beam Therapy Centre. WTI was delivered in four clockwise fields (81 spots per field, ~170 ms each) in the plateau region (LET ˜ 2.3 keV/µm), prescribing single doses of 10, 12.5, or 14.5 Gy. RILF was quantified 24 weeks post-irradiation by computed tomography using mean lung density, lung volume, and a validated radiomic fibrosis index. Imaging endpoints were correlated with blood gas and clinical chemistry, comprehensive histopathology, bulk RNA sequencing, single-cell RNA sequencing, and proteomics.
Results: Multifield FLASH helium WTI was technically feasible and robustly deliverable in a clinical-like configuration. Across all dose levels, FLASH significantly reduced radiological surrogates of fibrosis versus SDR, with lower mean lung density, preserved lung volume, and decreased fibrosis index, accompanied by more favorable blood gas profiles and attenuated histological fibrosis. Immunohistochemistry showed reduced TGFß expression and fewer senescent AECI/AECII, while single-cell transcriptomics indicated depletion of profibrotic M2-polarized lipofibroblasts.
Conclusion: This study demonstrates the feasibility and normal-tissue sparing effect of FLASH helium ion beams delivered by multifield WTI for the endpoint RILF, marking a critical step towards clinical translation of this innovative technology to mitigate late pulmonary toxicity.