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

Annaïg Bertho; Ramon Ortiz; Mathieu Maurin; Marjorie Juchaux; Cristèle Gilbert; Julie Espenon; Gabriel Ramasamy; Annalisa Patriarca; Ludovic De Marzi; Frédéric Pouzoulet; Yolanda Prezado

doi:10.1016/j.ijrobp.2024.04.011

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

Int J Radiat Oncol Biol Phys. 2024 Apr 13:S0360-3016(24)00510-8. doi: 10.1016/j.ijrobp.2024.04.011. Online ahead of print.

Affiliations

¹ Institut Curie, Université PSL, CNRS UMR3347, Inserm, U1021 Signalisation Radiobiologie et Cancer, 91400, Orsay, France; Université Paris-Saclay, CNRS UMR3347, Inserm, U1021 Signalisation Radiobiologie et Cancer, 91400, Orsay, France.
² Institut Curie, PSL Research University, INSERM U932, 75005, Paris, France.
³ Institut Curie, PSL Research University, Département de Recherche Translationnelle, CurieCoreTech-Experimental Radiotherapy (RadeXp), 75005, Paris, France.
⁴ Centre de Protonthérapie d'Orsay, Radiation Oncology Department, Campus Universitaire, Institut Curie, PSL University, Orsay, 91898, France.
⁵ Centre de Protonthérapie d'Orsay, Radiation Oncology Department, Campus Universitaire, Institut Curie, PSL University, Orsay, 91898, France; Institut Curie, Campus Universitaire, PSL University, University Paris Saclay, CNRS UMR 9187, INSERM U1196, Orsay.
⁶ Institut Curie, PSL Research University, Département de Recherche Translationnelle, CurieCoreTech-Experimental Radiotherapy (RadeXp), 75005, Paris, France; Institut Curie, PSL University, Université Paris-Saclay, Inserm U1288, Laboratoire de Recherche Translationnelle en Oncologie, 91400, Orsay, France.
⁷ Institut Curie, Université PSL, CNRS UMR3347, Inserm, U1021 Signalisation Radiobiologie et Cancer, 91400, Orsay, France; Université Paris-Saclay, CNRS UMR3347, Inserm, U1021 Signalisation Radiobiologie et Cancer, 91400, Orsay, France. Electronic address: yolanda.prezado@curie.fr.

PMID: 38621606
DOI: 10.1016/j.ijrobp.2024.04.011

Abstract

Purpose: Proton 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 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. 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.

Results: pMBRT 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.

Conclusion: pMBRT appears suitable to treat moving targets, holding a significant ability to preserve healthy lung tissue, even without respiratory control or precise targeting.

Keywords: Proton Minibeam Radiation Therapy; normal tissue preservation; proton therapy; radiation-induced lung fibrosis; thoracic irradiation.