Review of Conventional and High Dose Rate Brain Radiation (FLASH): Neurobehavioural, Neurocognitive and Assessment Issues in Rodent Models.

Ionising radiation causes secondary tumours and/or enduring cognitive deficits, especially in children. Proton radiotherapy reduces exposure of the developing brain in children but may still cause some lasting effects. Recent observations show that ultra-high dose rate radiation treatment (≥40 Gy/s), called the FLASH effect, is equally effective at tumour control but less damaging to surrounding tissue compared with conventional dose rate protons (0.03-3 Gy/s). Most studies on the FLASH effect in brain and other tissues with different radiation modalities (electron and photon radiation), show FLASH benefits in these preclinical rodent models, but the data are limited, especially for proton FLASH, including for dose, dose rate and neurochemical and neurobehavioural outcomes. Tests of neurocognitive outcomes have been limited despite clinical evidence that this is the area of greatest concern. The FLASH effect in the context of proton exposure is promising, but a more systematic and comprehensive approach to outcomes is needed.