Illustration of a DNA-Damage Induction Model for FLASH Proton Irradiation
F Van den Heuvel1*, F Fiorini2, (1) Zuidwest Radiotherapeutisch Instituut, Vlissingen, Zeeland, NL, (2) Rutherford Cancer Centre Thames Valley, UK
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PO-GePV-T-11 (Sunday, 7/10/2022) [Eastern Time (GMT-4)]
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Purpose: To illustrate the impact of using a model-based approach in analyzing experiments by applying a DNA-damage induction model to an experiment with laser-driven proton high-intensity beams irradiating single layer cell cultures. The experiment showed no FLASH-effect despite reaching dose rates up to 10⁹Gy/s.
Methods: A methodology based on oxygen dose histograms (ODH) is used to calculate the FLASH effect taking into account the dose, oxygenation level and proton spectra. The FLASH effect is defined as the ratio between conventional dose rates, where no oxygenation changes (temporal or spatial) takes place and an ODH which was shown to predict experiments using electrons on cell cultures, well. The calculations were repeated for oxygenation conditions of 20 Torr (2.6% pO₂).
Results: For the dose levels, oxygenation levels (20% pO₂) and energy spetra FLASH protective effects were between 0.2 and 0.5%. In the lower oxygenation regimen values of op to 40% reduction of DNA-damage induction are calculated. The FLASH effect shows a weak dependence on the energy spectra, diminishing as the proton energy diminishes. An increase in dose also shows a higher effect.
Conclusion: Using a model as proposed here informs the experimenters about which choices to take. If the goal was to generate a FLASH effect they could have chosen to vary the dose to higher levels or to introduce some hypoxia in the cell cultures. An added observation in that there is a weak dependency on proton energy spectra, leads to the prediction that experiments in different parts of a clinical beam there will be no significant differences in the FLASH effect, not even at the distal end of the Bragg peak
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