Proton minibeam radiation therapy: A promising alternative for brain re-irradiations.

Abstract

Re-irradiation remains a medical challenge due to the high toxicity risk. Proton minibeam radiation therapy (pMBRT), which has already demonstrated a remarkable neurotoxicity reduction, could minimize that risk in the central nervous system re-irradiations. The goal of this study was to perform the first evaluation of the anatomical and functional effects of pMBRT rat brain re-irradiations. Rats' brains were subjected to either a single conventional X-rays irradiation or additionally to a second irradiation with conventional RT or with pMBRT. Behavioral tests were carried out to assess the functional consequences of the different re-irradiation schemes. Histological evaluations were also performed to characterize tissue lesions, inflammation and astrogliosis. Re-irradiations with conventional RT led to a high skin lesion score (4) as compared to the mild lesion score (2) in the pMBRT re-irradiations, transitory altered locomotor and exploration activity, and had an important impact on cognitive functions such as memory abilities contrary to pMBRT re-irradiations. These results agree with the histological evaluations. Conventional RT re-irradiation resulted in necrosis of the fimbria, alveus necrosis, necrosis of CA1 to CA4 and/or gyrus dentatus, vasculopathy in the plexes in 88%, 25 %, 38 % and 50 % of the animals, respectively. The only histological finding in pMBRT re-irradiated animals was necrosis of the fimbria in 50% of the animals. Re-irradiation with pMBRT results in less neurotoxicity both from anatomical and functional point of view and it could be a safe alternative to current clinical practice.