Author: Wesley S. Culberson, Aleksandra Ilina, Brian W Pogue, Matthew Reed, Connor Strainis, William Scott Thomas, Nathaniel Van Asselt, Albert van der Kogel π¨βπ¬
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 WisconsinβMadison, University of Wisconsin-Madison, University of Wisconsin - Madison π
Purpose: FLASH radiotherapy reduces skin damage in vivo from ultra-high dose rate (UHDR) irradiation relative to conventional dose rates (CDR), while preserving damage to tumor tissue. The FLASH effect has not been robustly reproduced in large animal models. The study designs tests FLASH skin sparing in radiotherapy of osteosarcoma in canine limbs, by directly comparing equivalent doses of UHDR and CDR. Osteosarcoma treatments are palliative but allow for assessment of skin sparing over a 4-week span, prior to surgical intervention.
Methods: This dose escalation study targeted limb osteosarcoma. An IntraOp Mobetron with 9 MeV electrons was used for all treatments. Doses escalate from single dose deliveries of 20 to 28 Gy in 2 Gy increments with 3 dogs per group. The two parallel arms are UHDR and CDR at 80 Gy/s and 0.2 Gy/s, respectively. Dosimetry employed includes two forms of passive dosimeters: TLD-400 and EBT-XD Gafchromic film, with online beam monitoring via beam current transformers for UHDR delivery. Dogs are monitored for changes in pain and skin damage defined by the veterinary VRTOGv2 grading scale for a month post-irradiation.
Results: The trial began in Fall 2024, following completion of murine studies to mimic this trial, and showing the need for a single dose treatment to preserve the FLASH effect. Two dogs have been successfully entered into randomized treatment to date, with post-irradiation monitoring of dose delivery for both arms. Skin damage has not been seen at the lowest dose levels of 20 Gy, and dose escalation to the next level is being planned.
Conclusion: This study planned to be the first definitive two-arm study evaluating efficacy of FLASH radiotherapy in a randomized veterinary trial of large animals. The results of this study will be a valuable resource for ongoing clinical and veterinary trials in FLASH RT.