Author: Xu Cao, Wesley S. Culberson, Aleksandra Ilina, Kendall Jarvis, Brian W Pogue, Matthew Reed, William Scott Thomas, Nathaniel Van Asselt, Albert van der Kogel 👨🔬
Affiliation: University of Wisconsin: Madison, University of Wisconsin: Madison School of Veterinary Medicine, Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin - Madison, Department of Human Oncology, University of Wisconsin–Madison, University of Wisconsin-Madison, University of Wisconsin - Madison, UW-Madison 🌍
Purpose: While FLASH radiotherapy is known to reduce skin damage in vivo from ultra-high dose rate (UHDR) irradiation relative to conventional dose rates (CDR). Currently it is not clear whether this sparing is preserved when delivered with daily fractionation. This study was designed to directly assess whether three daily fractions would maintain the sparing effects in the murine leg models and preserve the FLASH effect in murine skin sparing seen in single fraction treatments.
Methods: Eight-week-old C57Bl/6j female mice were irradiated with 9 MeV electrons under both UHDR (100 Gy/s) and CDR (0.17 Gy/s) conditions from a FLASH-capable Mobetron system. The delivered dose ranged from single doses of 22-30 Gy to three subsequent daily fractions of 10 - 16 Gy. The biological responses were quantified with a visual skin damage response rubric using 4-5 blind observers, and a leg contracture assay as a secondary measure of skin damage.
Results: The assay results showed a monotonic dose response in all treatment groups, with onset significant FLASH sparing at about 12 days for all single dose groups, showing dose modifying factor of ~1.3. Similarly in the single dose groups there were significant leg contracture differences between UHDR and CDR groups. In comparison, there was no significant skin damage sparing between UHDR and CDR at any of the three fraction doses for either assay.
Conclusion: The results of this study show no FLASH effect from three fractions, whereas there were substantial FLASH sparing effects noted for all single fraction studies at different dose levels. With ongoing translational work, it is paramount to investigate the optimal way to observe the benefit of the FLASH effect in radiotherapy. Under conditions used here fractionation of dose delivery did not benefit the overall efficacy of FLASH RT.