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FLASH: Flash Leverages A Sudden Hypoxia

F Van den Heuvel*, A Vella, K Petersson, M Brooke, M Hill, B Vojnovic, A Giaccia, CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford

Presentations

(Sunday, 7/12/2020)   [Eastern Time (GMT-4)]

Room: AAPM ePoster Library

Purpose:
To outline and verify a methodology to include FLASH-effects in treatment planning software. FLASH effects occur when subjects are irradiated at ultra-high dose rates ~40Gy/s. The effect reduces the biological effects of the irradiation with between 20 and 50%.

Methods:
One of the possible mechanisms for FLASH-effects is oxygen depletion during the dose deposition generating a transient hypoxic environment. We developed a frame work to quantify the effect of oxygen concentration on the generation of clustered DNA-damage and combined this with an
oxygen depletion model. The work in this paper is limited to single pulse treatments, where we assume no re-oxygenation during the dose pulse occurs. We extended the model to include different modalities: electrons (and by extension photons), protons, alpha-particles, and carbon ions.

Results:
The applied model predicts the FLASH-effect to be dependent on a combination of factors: The total dose delivered during the radiation pulse, the initial oxygenation of the tissue, and the energy (or LET) of the charged particles. The model is verified in historical cell data (Town 1967, Brenner 1970) and more current mouse models. All showing good agreement. The application to a carbon beam shows that the FLASH--effect in this case also shows a dependency on the energy. More specifically the contribution of high-LET carbon-ions diminishes the effect.

Conclusion:
We have shown that taking into account oxygen effects alone provides a good model to quantify a major factor in effects of FLASH--therapy in different modalities. The model also provides a guideline helping in the design of FLASH experiments, helping to distinguish between oxygen related effects and possible other mechanisms. Because the model we apply is analytical it is easily incorporated in a treatment planning system.

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Funding Support, Disclosures, and Conflict of Interest: FVdH: is supported by a Cancer Centre grant CRUK C2195/A25014 and CRUK OIRO Number C5255/A23755. AV: is supported by a Cancer Research UK Grant: ArtNET: Number C309/A21993 MB: is supported by Cancer Research UK Grant No. C2195/A25197, through a CRUK Oxford Centre DPhil Prize Studentship

Keywords

Dose Response, Hypoxia, Modeling

Taxonomy

TH- Radiobiology(RBio)/Biology(Bio): RBio- general

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