Shining a FLASHlight on Ultrahigh Dose-Rate Radiation and Possible Late Toxicity

Abstract

A recent study reported results from a clinical trial in cats and from experiments in mini-pigs in which a single dose of radiotherapy was delivered at ultrahigh dose rates (FLASH). There was acceptable acute toxicity; however, some animals suffered severe late toxicity, raising caution in the design of future trials. See related article by Rohrer Bley et al., p. 3814.

Trial registration: ClinicalTrials.gov NCT04986696 NCT04592887.

Conflict of interest statement

Conflicts: C.K. is a member of the Conformal FLASH Alliance sponsored by IBA (Ion Beam Applications; Louvain-la-Neuve, Belgium) which sells proton therapy machines. He is also a recipient of a Sponsored Research Agreement on FLASH proton radiation from IBA. Both A.M. and C.K have supervised experiments using FLASH radiation generated by an IBA proton machine.

©2022 American Association for Cancer Research.

Figures

Figure 1

A. Hypothetical FLASH-RT regimens for delivery of a dose of 30 Gy at FLASH dose rates. 30Gy x 1 (single dose regimen) may be too toxic to bone/soft tissues, as suggested by data in this study. 3 Gy x 10 (fractionated regimen) may be below minimal threshold required to see FLASH-associated sparing of late toxicity. 10 Gy x 3 (hypofractionation regimen) may take advantage of both the ability of FLASH dose rate and fractionation to spare late tissue toxicity. Note that these 3 regimens were chosen for the purposes of illustration. They are numerically equivalent in dose but not equivalent in terms of biological effectiveness. B. Sequence of events leading to radiation-induced osteoradionecrosis. Arrows indicate biologically linked processes. Diagram is based on review by Pacheco and Stock (17).