Average Dose Rate is the Major Temporal Beam Structure Parameter for Preserving Murine Intestines With Pulsed Electron FLASH Radiation Therapy.

Abstract

The relationship between the physical parameters of pulsed beams and the FLASH effect remains largely unexplored. Our research aimed to investigate systematically the beam requirements necessary for pulsed electron FLASH radiation therapy, which is characterized by high average dose rates (DR_av) and large doses-per-pulse (DPP). The abdominal cavity of tumor-free C57BL/6 mice was irradiated with a pulsed electron beam at 17 Gy, generated by a prototype electron linear accelerator. The time structure of the applied beams was varied by adjusting the pulse repetition frequency and the DPP. The overall survival was assessed for each group irradiated with different configurations of beam parameters. For some groups, jejunum samples were harvested at 96 hours postirradiation and the number of regenerating crypts per unit length was evaluated. Decreasing both DPP and DR_av led to an increase in side effects and reduced overall survival. The observed toxicity was reduced by increasing DR_av while maintaining a constant DPP, achieving a maximum FLASH sparing effect at a minimum DR_av of 100 Gy/s. Conversely, lowering the DR_av while maintaining a high DPP (>1 Gy/pulse) increased side effects with the subsequent reduction in overall survival. This research provides evidence that the DR_av is the major temporal beam parameter for reproducing the FLASH normal tissue-sparing effect even in the case of pulsed radiation beams. A minimum dose rate of 100 Gy/s is necessary to maximize the sparing effect for intestines irradiated with 17 Gy.