Time-Dependent Oxygen Modulation of LQ Parameters Enables Microdosimetric Flash Modeling for Ion Beams
Abstract
Purpose
The combination of FLASH and ion-beam therapy could potentially enhance the therapeutic index of radiation therapy. The goal of this study was to establish a FLASH effect modeling approach for ion beams based on microdosimetry.
Methods
Microdosimetric lineal-energy spectra were calculated for various ion beams (proton, helium, lithium, beryllium, boron, and carbon) using the GATE Monte Carlo software package. An analytical framework was developed that uses microdosimetric dose-mean lineal energy (ȳ_D) together with a time-dependent oxygen depletion–recovery model to modulate linear–quadratic (LQ) parameters (α, β) as a function of oxygen tension during irradiation. Quantifications of the LQ parameter α, the FLASH protection effect (FSE), and their dependence on dose rate (0.1–1000 Gy/s), ȳ_D/LET, oxygen concentration, ion species, and radiosensitivity were performed.
Results
The microdosimetry-based ion-beam FLASH model quantified the FLASH effect across oxygen concentrations, dose rates, ion species, and radiosensitivities. The LQ parameter α showed a dependence on oxygen concentration for all ion species with various dose rates and saturated at high-oxygen-concentration levels. FSE increased with increasing environmental oxygen concentration and decreased after reaching a dose-rate-dependent maximum. FSE increased with an increasing dose rate. With the increasing LET or ȳ_D, FSE increased and then decreased, and finally tended to approach unity in the high-LET or ȳ_D region. The FSE–LET relationship showed a dependence on ion species, especially at high LET.
Conclusion
A microdosimetry-based framework was established to quantitatively evaluate the FLASH effect for ion-beam therapies at the clonogenic cell-survival level. The model results indicated that certain experimental conditions are required for FLASH irradiation with ion beams to achieve optimal normal tissue protection. The proposed microdosimetry-based approach took energy deposition at the micrometer scale into account and revealed ion-species dependence of the FSE–LET relationship.