Average Dose Rate is the Major Temporal Beam Structure Parameter for Preserving Murine Intestines with Pulsed Electron FLASH-RT

Veljko Grilj; Anet Valdes Zayas; Anouk Sesink; Preethi Devanand; David Repáraz; Ryan Paisley; K Sprengers; Katiuska Passelli; Julie Pernot; Till T Böhlen; Reiner W Geyer; Raphael Moeckli; Claude Bailat; Jean-Francois Germond; Julien Dagher; Francois Bochud; Jean Bourhis; Fernanda G Herrera

doi:10.1016/j.ijrobp.2025.04.021

Average Dose Rate is the Major Temporal Beam Structure Parameter for Preserving Murine Intestines with Pulsed Electron FLASH-RT

Int J Radiat Oncol Biol Phys. 2025 May 2:S0360-3016(25)00389-X. doi: 10.1016/j.ijrobp.2025.04.021. Online ahead of print.

Authors

Veljko Grilj¹, Anet Valdes Zayas², Anouk Sesink³, Preethi Devanand³, David Repáraz³, Ryan Paisley⁴, K Sprengers⁴, Katiuska Passelli³, Julie Pernot³, Till T Böhlen⁴, Reiner W Geyer⁴, Raphael Moeckli⁴, Claude Bailat⁴, Jean-Francois Germond⁴, Julien Dagher⁵, Francois Bochud⁴, Jean Bourhis³, Fernanda G Herrera⁶

Affiliations

¹ Department of Oncology, Radiation Oncology Service Lausanne University Hospital and University of Lausanne, Switzerland. Electronic address: Veljko.Grilj@chuv.ch.
² Department of Oncology, Radiation Oncology Service Lausanne University Hospital and University of Lausanne, Switzerland. Electronic address: Anet.Valdes-Zayas@chuv.ch.
³ Department of Oncology, Radiation Oncology Service Lausanne University Hospital and University of Lausanne, Switzerland.
⁴ Institute of Radiation Physics, Lausanne University Hospital and Lausanne University, Lausanne, Switzerland.
⁵ Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁶ Department of Oncology, Radiation Oncology Service, Service of Immuno Oncology, Ludwig Institute for Cancer Research, Agora Cancer Research Institute, Lausanne University Hospital and University of Lausanne, Switzerland.

PMID: 40319927
DOI: 10.1016/j.ijrobp.2025.04.021

Abstract

Purpose: The relationship between 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 radiotherapy (FLASH-RT), which is characterized by high average dose rates (DR_av) and large doses-per-pulse (DPP).

Materials and methods: The abdominal cavity of tumor free C57BL/6 mice was irradiated with a pulsed electron beam at 17 Gy, generated by an prototype electron LINAC. The time structure of the applied beams was varied by adjusting the pulse repetition frequency (PRF) 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 h post-irradiation and the number of regenerating crypts per unit length was evaluated.

Results: 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.

Conclusions: 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.

Keywords: FLASH; beam parameters; dose rate; mouse intestine; radiation; toxicity.