Thoracic Proton Minibeam Radiation Therapy: Tissue Preservation and Survival Advantage Over Conventional Proton Therapy

Abstract

PurposeProton Minibeam Radiotherapy (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 to conventional radiotherapy 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 biological impact. Methods and materialsthe 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. Anatomopathological analysis was carried out at 9 months post-irradiation 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 (AT2) epithelial cells, club cells, and macrophages. ResultspMBRT has milder effects on survival, skin reactions, and lung fibrosis compared to CPT. The pMBRT-induced lung changes were more regional and less severe, with evidence of potential reactive proliferation of AT2 epithelial cells and less extensive depletion of club cells and macrophage invasion than the more damaging effects observed in CPT. ConclusionpMBRT appears suitable to treat moving targets, holding a significant ability to preserve healthy lung tissue, even without respiratory control or precise targeting.