Room: AAPM ePoster Library
Purpose: Remarkable normal tissue sparing and comparable tumor control with FLASH RT (ultrahigh dose-rate radiotherapy) effects were observed by in vivo animal studies with ultra-short radiation pulses but only at high repetition rates. In this study, we conducted a quantitative assessment of this effect based on the radiation-induced oxygen depletion (RIOD) hypothesis.
Methods: For cells irradiated by ultra-short radiation pulses at high pulse repetition rates, the intracellular oxygen level ([O2]) goes through ultra-fast physical, fast chemical, and slow oxygen diffusion stages. Due to the high radiation pulse repetition rate, cells do not have enough time to completely restore [O2] to their pre-radiation baseline before the next round of radiation pulse arrives. Combining the knowledge of the radiolysis and oxygen diffusion, we establish [O2] as a function of time. Using the parametrization of the Oxygen Enhancement Ratio (OER) formula, we studied the RIOD effect on cell survival fraction (SF) following each radiation pulse. Combining the SF per radiation pulse for all pulses, we calculated the RIOD effect on overall SF for the entire irradiation.
Results: We mathematically derived the SF for cells irradiated by ultra-short radiation pulses at high repetition rates. When both radiation dose per pulse and pulse repetition rate are high, [O2] continually decreases pulse after pulse, resulting in a much lower effective OER over the entire irradiation. The OER reduction depends on the pre-irradiation [O2], i.e., [O2]-rich cells will see a much more significant OER reduction than hypoxic cells, particularly with initial [O2] in high gradient region of OER curve. This may explain the observations of the FLASH RT effect.
Conclusion: We conducted a theoretical study on the impact of RIOD on cell SF in ultra-short pulsed cell irradiation at high repetition rates. Our result may provide insights into the FLASH RT effect and facilitate future experimental designs.