Ultrahigh-Dose-Rate Proton Irradiation Elicits Reduced Toxicity in Zebrafish Embryos.

Purpose: Recently, ultrahigh-dose-rate radiation therapy (UHDR-RT) has emerged as a promising strategy to increase the benefit/risk ratio of external RT. Extensive work is on the way to characterize the physical and biological parameters that control the so-called "Flash" effect. However, this healthy/tumor differential effect is observable in in vivo models, which thereby drastically limits the amount of work that is achievable in a timely manner.

Potential Molecular Mechanisms behind the Ultra-High Dose Rate "FLASH" Effect.

FLASH radiotherapy, or the delivery of a dose at an ultra-high dose rate (>40 Gy/s), has recently emerged as a promising tool to enhance the therapeutic index in cancer treatment. The remarkable sparing of normal tissues and equivalent tumor control by FLASH irradiation compared to conventional dose rate irradiation—the FLASH effect—has already been demonstrated in several preclinical models and even in a first patient with T-cell cutaneous lymphoma. However, the biological mechanisms responsible for the differential effect produced by FLASH irradiation in normal and cancer cells remain to be elucidated.