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Normal Tissue Sparing by FLASH as a Function of Single-Fraction Dose: A Quantitative Analysis.
Till Tobias Böhlen1, Jean-François Germond1, Jean Bourhis2
1Institute of Radiation Physics, Lausanne University Hospital and Lausanne University, Lausanne, Switzerland.
Summary
The FLASH effect spares normal tissues during ultra-high dose rate (UHDR) radiation therapy, with sparing increasing with dose. This effect is organ-specific and can be modeled using a piecewise linear function for optimized clinical translation.
Area of Science:
- Radiation Oncology
- Medical Physics
- Radiobiology
Background:
- Ultra-high dose rate (UHDR) radiation, known as the FLASH effect, offers potential for normal tissue sparing without compromising tumor control.
- Quantifying the magnitude of normal tissue sparing and its dose dependency is crucial for clinical implementation of FLASH radiation therapy.
Purpose of the Study:
- To evaluate the magnitude of normal tissue sparing provided by the FLASH effect as a function of radiation dose.
- To develop a data-driven phenomenological parameterization for the FLASH effect's dose dependency.
Main Methods:
- Gathered in vivo data on normal tissue sparing comparing conventional (CONV) and UHDR single-fraction doses.
- Calculated FLASH-modifying factors (FMF) using isoeffect dose ratios (FMF = (DCONV/DUHDR)|isoeffect).
- Assessed the suitability of a piecewise linear function to parameterize FMF as a function of UHDR dose.
Main Results:
- Normal tissue sparing generally increased with higher single-fraction doses, indicated by a decreasing FMF.
- The FLASH effect magnitude is organ-specific, with consistent dose-dependent trends observed in pooled skin-reaction data.
- Average FMF values varied by dose and tissue: <10 Gy (0.95 ± 0.11), mouse gut 10-25 Gy (0.92 ± 0.06), mammalian skin 10-25 Gy (0.96 ± 0.07), and >25 Gy (0.71 ± 0.06).
Conclusions:
- Normal tissue sparing by the FLASH effect escalates with increasing dose and is influenced by the specific tissue irradiated.
- A piecewise linear function effectively parameterizes the dose-response relationship of the FLASH effect based on current experimental data.
