Modeling for predicting survival fraction of cells after ultra-high dose rate irradiation

Abstract

Objective. FLASH radiotherapy (FLASH-RT) with ultra-high dose rate (UHDR) irradiation (i.e. > 40 Gy s−1) spares the function of normal tissues while preserving antitumor efficacy, known as the FLASH effect. The biological effects after conventional dose rate-radiotherapy (CONV-RT) with ≤0.1 Gy s−1 have been well modeled by considering microdosimetry and DNA repair processes, meanwhile modeling of radiosensitivities under UHDR irradiation is insufficient. Here, we developed an integrated microdosimetric-kinetic (IMK) model for UHDR-irradiation enabling the prediction of surviving fraction after UHDR irradiation. Approach. The IMK model for UHDR-irradiation considers the initial DNA damage yields by the modification of indirect effects under UHDR compared to CONV dose rate. The developed model is based on the linear-quadratic (LQ) nature with the dose and dose square coefficients, considering the reduction of DNA damage yields as a function of dose rate. Main results. The estimate by the developed model could successfully reproduce the in vitro experimental dose–response curve for various cell line types and dose rates. Significance. The developed model would be useful for predicting the biological effects under the UHDR irradiation.

Reply to comment on ‘Modeling for predicting survival fraction of cells after ultra-high dose rate irradiation’

“…Note that the experimental F DSB values reported by Buonanno et al were obtained by the linear fitting to the dose-response curves of γ-H2AX fluorescence in the literature. From figure 1, the value of F DSB at 800 Gy s −1 was 0.887 ± 0.049, which is almost the same as 0.866 ± 0.028, as reported in our previous paper (Shiraishi et al 2024a). Using the F DSB value (i.e.…”

“…The data accumulation on oxygen levels during irradiation is necessary for developing a mechanistic model for predicting the surviving fraction considering oxygen level. As for the data used to determine the parameters and to benchmark our model (Shiraishi et al 2024a), scientifically valid data were appropriately selected from the few previously published reports based on the definition of radiobiological hypoxia. As Liew and Mairani suggested, we reevaluated our model and demonstrated that it can reproduce the experimental survival data, even when using only the experimental DNA damage data measured reliably under normoxic conditions (Buonanno et al 2019, Fouillade et al 2020.…”

“…Concerning the data selection for determining the model parameters in equation (12) in our previous paper (Shiraishi et al 2024a), the available experimental data for the modelling study are limited. As Liew and Mairani pointed out, we used literature that does not provide detailed explanations of oxygen levels, but we also emphasized that the experimental data on DNA damage were selected based on the definition of hypoxia in radiation biology.…”

“…This reply is in response to the comment by Liew and Mairani on our proposed model for predicting the survival fraction of cells after ultra-high dose rate (UHDR) irradiation (Shiraishi et al 2024a). Focusing on low-LET radiation, we modelled the relationship between the dose rate and yield ratio of DNA double-strand breaks (DSBs).…”