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THE SPARING EFFECT OF FLASH-RT IS MAINTAINED WITH STANDARD FRACTIONATION REGIMEN
Abstract
Background and Aims
To date, single dose and hypo-fractionated regimens of whole brain FLASH-RT have been shown to reduce the adverse cognitive and pathological complications routinely observed after conventional dose rate radiotherapy (CONV-RT). In this study, our aim was to evaluate the impact of a standard fractionation regimen on brain function.
Methods
Whole brain 3Gy fractions were delivered daily using CONV and FLASH (eRT6/Oriatron) for two weeks (10x3Gy) and long-term potentiation (LTP) was used to provide direct readouts of neurotransmission. While behavioral testing remains the gold standard for validating the functional impact of cranial irradiation on the brain, electrophysiological assessments and LTP are direct measurements of synaptic plasticity.
Results
Our previous results in pediatric and adult mouse models showed that consistently with neurocognitive preservation, LTP was preserved after FLASH-RT when delivered in single and hypo-fractionated regimens but was significantly inhibited after CONV-RT. In this study, data collected from two regions of the brain (hippocampus, medial prefrontal cortex) confirmed significant inhibition of LTP after 10x3Gy CONV-RT. Remarkably, 10x3Gy FLASH-RT and controls were identical and exhibited normal LTP across each brain region.
Conclusions
While further work is ongoing to establish a causal link between LTP and behavioral outcomes and validate the anti-tumor effect, these results provide the first evidence that brain functionality is preserved after standard fractionation with FLASH-RT.