A Modified Lethal and Potentially Lethal Model With Explicit Oxygen Tension Dependence for FLASH RT

Abstract

To modify Curtis Lethal and Potentially Lethal (LPL) model to extend it from conventional (CONV) to ultra-high dose rate (FLASH) Radiotherapy (RT) domain with explicit intracellular oxygen tension dependence.After combining radiation-induced oxygen depletion, oxygen fixation hypothesis, and the Oxygen Enhancement Ratio (OER) concept, we incorporate intracellular oxygen tension dependence into the coefficients of the ordinary differential equations describing the original Curtis LPL model. Two biochemical pre-lesion states for the LPL lesions are amended into the model to explain the oxygen post-effect on the cell radiation survival fraction (SF). We perform analytical and numerical analyses for the solutions of the average numbers of LPL lesions. Using Poisson statistics, we can use the average number of LPL lesions to predict the cell SF for FLASH RT.Our modified LPL model maintains all original LPL model characteristics at fixed intracellular oxygen tension. For variable intracellular oxygen tensions, our new model extends prediction capabilities to FLASH RT. The comparisons of the two models are summarized below: CONCLUSION: Our modified LPL model has the potential to explain the observed FLASH phenomena, i.e., FLASH RT provides better normal tissue sparing while maintaining similar tumor control compared with CONV RT. Future studies are necessary to quantitatively validate our model predictions in systematically conducted FLASH irradiation experiments.