Electron FLASH platform for pre-clinical research: LINAC modification, simplification of pulse control and dosimetry

Background: FLASH radiotherapy is a treatment regime that delivers therapeutic dose to tumors at an ultra-high dose rate while maintaining adequate normal tissue sparing. However, a comprehensive understanding of the underlying mechanisms, potential late toxicities, and optimal fractionation schemes is important for successful clinical translation. This has necessitated extensive pre-clinical investigations, leading several research institutions to initiate dedicated FLASH research programs. Purpose: This work describes a workflow for establishing an easily accessible electron FLASH (eFLASH) platform. The platform incorporates simplified pulse control, optimized dose rate delivery, and validated Monte Carlo (MC) dose engine for accurate in vivo dosimetry dedicated to FLASH pre-clinical studies. Methods: Adjustment of the automatic frequency control (AFC) module allowed us to optimize the LINAC pulse form to achieve a uniform dose rate. A MC model for the 6 MeV FLASH beam was commissioned to ensure accurate dose calculation necessary for reproducible in vivo studies. Results: Optimizing the AFC module enabled the generation of a uniform pulse form, ensuring consistent dose per pulse and a uniform dose rate throughout FLASH irradiation. The MC model closely agreed with film measurements. MC dose calculations indicated that 6 MeV FLASH is adequate to achieve a uniform dose distribution for mouse whole brain irradiation but may not be optimal for the spinal cord study. Conclusions: We present a novel workflow for establishing a LINAC-based eFLASH research platform, incorporating techniques for optimized dose rate delivery, a simplified pulse control system, and validated MC engine. This work provides researchers with valuable new approaches to facilitate the development of robust and accessible LINAC-based system for FLASH studies.
Comment: 29 pages, 6 figures