Modification of the microstructure of the CERN- CLEAR-VHEE beam at the picosecond scale modifies ZFE morphogenesis but has no impact on hydrogen peroxide production.

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Abstract

BACKGROUND: FLASH radiotherapy has emerged as a promising advancement in radiation oncology, demonstrating the potential to minimize normal tissue toxicity while preserving tumoricidal efficacy. However, the precise beam parameters required for clinical translation remain to be fully defined.METHODS: To optimize beam parameters for clinical application, we employed Very High Energy Electrons (VHEE) at the CLEAR facility, capable of targeting deep-seated tumors. These were used alongside a FLASH-validated Intermediate Energy Electron (IIE) beam and a 160-225?keV X-ray beam, collectively delivering dose rates from 1?Gy/min to 1011 Gy/s. High-throughput chemical assays investigated the radiochemical effects across this dose range, while zebrafish embryos provided an in vivo model to evaluate biological responses and developmental outcomes. This study offers the first comprehensive analysis of FLASH effects across a wide spectrum of dose rates and temporal parameters, from early physico-chemical interactions to complex biological systems.RESULTS: Data from CLEAR demonstrated that beam intensity, particularly bunch charge, is a critical determinant of the FLASH effect, and uncovered an unforeseen biological response when electrons are delivered over the picosecond timescale.CONCLUSION: Our findings suggest that scanning strategies employing high intensity beamlets may be optimal for the clinical implementation of FLASH radiotherapy. These insights are pivotal for guiding the development of future FLASH protocols in radiation oncology.

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