A phenomenological model of proton FLASH oxygen depletion effects depending on tissue vasculature and oxygen supply.
Autor: | Zou W; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Kim H; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Diffenderfer ES; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Carlson DJ; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Koch CJ; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Xiao Y; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Teo BK; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Kim MM; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Metz JM; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Fan Y; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Maity A; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Koumenis C; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Busch TM; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Wiersma R; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Cengel KA; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Dong L; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States. |
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Jazyk: | angličtina |
Zdroj: | Frontiers in oncology [Front Oncol] 2022 Nov 28; Vol. 12, pp. 1004121. Date of Electronic Publication: 2022 Nov 28 (Print Publication: 2022). |
DOI: | 10.3389/fonc.2022.1004121 |
Abstrakt: | Introduction: Radiation-induced oxygen depletion in tissue is assumed as a contributor to the FLASH sparing effects. In this study, we simulated the heterogeneous oxygen depletion in the tissue surrounding the vessels and calculated the proton FLASH effective-dose-modifying factor (FEDMF), which could be used for biology-based treatment planning. Methods: The dose and dose-weighted linear energy transfer (LET) of a small animal proton irradiator was simulated with Monte Carlo simulation. We deployed a parabolic partial differential equation to account for the generalized radiation oxygen depletion, tissue oxygen diffusion, and metabolic processes to investigate oxygen distribution in 1D, 2D, and 3D solution space. Dose and dose rates, particle LET, vasculature spacing, and blood oxygen supplies were considered. Using a similar framework for the hypoxic reduction factor (HRF) developed previously, the FEDMF was derived as the ratio of the cumulative normoxic-equivalent dose (CNED) between CONV and UHDR deliveries. Results: Dynamic equilibrium between oxygen diffusion and tissue metabolism can result in tissue hypoxia. The hypoxic region displayed enhanced radio-resistance and resulted in lower CNED under UHDR deliveries. In 1D solution, comparing 15 Gy proton dose delivered at CONV 0.5 and UHDR 125 Gy/s, 61.5% of the tissue exhibited ≥20% FEDMF at 175 μm vasculature spacing and 18.9 μM boundary condition. This percentage reduced to 34.5% and 0% for 8 and 2 Gy deliveries, respectively. Similar trends were observed in the 3D solution space. The FLASH versus CONV differential effect remained at larger vasculature spacings. A higher FLASH dose rate showed an increased region with ≥20% FEDMF. A higher LET near the proton Bragg peak region did not appear to alter the FLASH effect. Conclusion: We developed 1D, 2D, and 3D oxygen depletion simulation process to obtain the dynamic HRF and derive the proton FEDMF related to the dose delivery parameters and the local tissue vasculature information. The phenomenological model can be used to simulate or predict FLASH effects based on tissue vasculature and oxygen concentration data obtained from other experiments. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Zou, Kim, Diffenderfer, Carlson, Koch, Xiao, Teo, Kim, Metz, Fan, Maity, Koumenis, Busch, Wiersma, Cengel and Dong.) |
Databáze: | MEDLINE |
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