Systematic analysis and modeling of the FLASH sparing effect as a function of dose and dose rate

Ultrahigh-dose-rate radiotherapy (FLASH-RT) is a revolutionary radiotherapy technology that can spare normal tissues without compromising tumor control. Although qualitative experimental results have been reported, quantitative and systematic analysis of data is necessary. Particularly, the FLASH effect response model to the dose or dose rate is still unclear. This study investigated the relationships between the FLASH effect and experimental parameters, such as dose, dose rate, and other factors by analyzing published in vivo experimental data from animal models. The data were modeled based on logistic regression analysis using the sigmoid function. The model was evaluated using prediction accuracy, receiver operating characteristic (ROC) curve, and area under the ROC curve. Results showed that the FLASH effect was closely related to the dose, mean dose rate, tissue type, and corresponding biological endpoints. The dose rate corresponding to a 50% probability of triggering cognitive protection in the brain was 45 Gy s \(^{-1}\) $_{}^{-1}$ . The dose rate corresponding to a 50% probability of triggering intestinal crypt survival and regeneration was 140 Gy s \(^{-1}\) $_{}^{-1}$ . For the skin toxicity effect, the dose corresponding to a 50% probability of triggering the FLASH effect was 24 Gy. This study helps to characterize the conditions underlying the FLASH effect and provides important information for optimizing experiments.