May oxygen depletion explain the FLASH effect? A chemical track structure analysis

Highlights: • Bottom-up radiation chemistry study reproduced observed radiolytic oxygen depletion (ROD) with high accuracy. • Dynamical nature of oxygen depletion and its impact on OER taken into account for the first time. • Negligible impact of ROD on radiosensitivity through transient hypoxia in conditions of reported experiments. • ROD impact on therapeutic window occurs eventually in opposite direction. Recent observations in animal models show that ultra-high dose rate ("FLASH") radiation treatment significantly reduces normal tissue toxicity maintaining an equivalent tumor control. The dependence of this "FLASH" effect on target oxygenation has led to the assumption that oxygen "depletion" could be its major driving force.