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Purpose: Proton minibeam radiation therapy (pMBRT) is an innovative radiation therapy approach that highly modulates the spatial dimension of the dose delivery using narrow, parallel, and submillimetric proton beamlets. pMBRT has proven its remarkable healthy tissue preservation in the brain and skin. This study assesses the potential advantages of pMBRT for thoracic irradiations compared with conventional radiation therapy in terms of normal tissue toxicity. The challenge here was the influence of respiratory motion on the typical peak and valley dose patterns of pMBRT and its potential biologic effect., Methods and Materials: The whole thorax of naïve C57BL/6 mice received one fraction of high dose (18 Gy) pMBRT or conventional proton therapy (CPT) without any respiratory control. The development of radiation-induced pulmonary fibrosis was longitudinally monitored using cone beam computed tomography. Anatomopathologic analysis was carried out at 9 months postirradiation and focused on the reaction of the lungs' parenchyma and the response of cell types involved in the development of radiation-induced fibrosis and lung regeneration as alveolar type II epithelial cells, club cells, and macrophages., Results: pMBRT has milder effects on survival, skin reactions, and lung fibrosis compared with CPT. The pMBRT-induced lung changes were more regional and less severe, with evidence of potential reactive proliferation of alveolar type II epithelial cells and less extensive depletion of club cells and macrophage invasion than the more damaging effects observed in CPT., Conclusions: pMBRT appears suitable to treat moving targets, holding a significant ability to preserve healthy lung tissue, even without respiratory control or precise targeting., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: FLASH radiation therapy (FLASH-RT) is a promising radiation technique that uses ultrahigh doses of radiation to increase the therapeutic window of the treatment. FLASH-RT has been observed to provide normal tissue sparing at high dose rates and similar tumor control compared with conventional RT, yet the biological processes governing these radiobiological effects are still unknown. In this study, we sought to investigate the potential immune response generated by FLASH-RT in a high dose of proton therapy in an orthotopic glioma rat model., Methods and Materials: We cranially irradiated rats with a single high dose (25 Gy) using FLASH dose rate proton irradiation (257 ± 2 Gy/s) or conventional dose rate proton irradiation (4 ± 0.02 Gy/s). We first assessed the protective FLASH effect that resulted in our setup through behavioral studies in naïve rats. This was followed by a comprehensive analysis of immune cells in blood, healthy tissue of the brain, and tumor microenvironment by flow cytometry., Results: Proton FLASH-RT spared memory impairment produced by conventional high-dose proton therapy and induced a similar tumor infiltrating lymphocyte recruitment. Additionally, a general neuroinflammation that was similar in both dose rates was observed., Conclusions: Overall, this study demonstrated that FLASH proton therapy offers a neuro-protective effect even at high doses while mounting an effective lymphoid immune response in the tumor., (Copyright © 2022 Elsevier Inc. All rights reserved.)