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RADIOPATHOLOGICAL ASPECTS OF PULMONARY PROTON MINIBEAM RADIATION THERAPY
Abstract
Background and Aims
Proton minibeam radiation therapy (pMBRT) is a novel therapeutic approach which employs narrow (< 1 mm), spatially modulated proton beams [Prezado et al, 2013]. pMBRT has shown a remarkable reduction in neurotoxicity [Lamirault et al, 2020], and equivalent or superior tumor control [Prezado et al, 2018; Bertho et al, 2020] over conventional proton therapy (PT).
While the majority of pMBRT studies focused on brain or skin irradiations [Sammer et al, 2020; Girts et al, 2015; Bertho et al, 2020], this work reports on the first evaluation of the pulmonary response to pMBRT. Pulmonary irradiations are challenging as cardiorespiratory motion can blur the spatial fractionation of the dose. We compared the radiopathological consequences of pulmonary pMBRT versus conventional PT in mice.
Methods
Pulmonary irradiations, delivering a mean dose of 17Gy in both modalities, were performed in C57BL/6 mice. The development of radiation-induced pulmonary fibrosis was monitored thanks to the on-board cone-beam computed tomography (CBCT) system of the Small Animal Radiation Research Platform.
Results
CBCT images revealed a significant increase in lung density following conventional PT, corresponding to the development of radiation-induced lung fibrosis which ultimately impacted the survival of the animals (6/8 reached the endpoints 5 months post-irradiation). Comparatively, the increase in lung tissue density observed in the CBCT images of the pMBRT group was only mild 6 months post-irradiation. All the animals of this group survived until the end of the study without clinical symptoms. Histopathological analysis is ongoing and will be used to characterize the response of the lung parenchyma and cellular actors involved in the development of radiation-induced fibrosis.
Conclusions
These preliminary results suggest that the gain of normal tissue tolerance after pMBRT is also present in lung irradiation. Indeed, compared to conventional PT, pMBRT minimizes the development of radiation-induced lung fibrosis. This opens the door for pMBRT in moving targets.