Hypoxia hype.

FLASH-RT is exciting, but no one really understands why it appears to confer such an advantage in normal tissue sequelae. A dominating hypothesis, popular since the 1960s when alpha-beta ratios were being calculated on chalkboards, is that such rapid delivery of ionizing radiation (in milliseconds) could result in a radiochemical depletion of oxygen, thus sparing tissue from excess free radical formation at the precise moment it’s being bombarded by photons. Here’s a modern exploration of tissue oxygen kinetics in the context of actually being able to clinically deliver FLASH-RT. TBL: Dose-rate dependent changes in the oxygen enhancement ratio predict outcomes compatible with those of recent in vivo studies leaving oxygen depletion a viable explanation for the unprecedented therapeutic index achieved by FLASH-RT in preclinical models. | Petersson, Int J Radiat Oncol Biol Phys 2020