Phase One Randomized Two-Arm Dose Escalation of Flash RT In Veterinary Canine Osteosarcoma: Status Update In Year 2
Abstract
Purpose
FLASH radiotherapy reduces skin damage in vivo from ultra-high dose rate (UHDR) irradiation relative to conventional dose rates (CDR), while preserving tumor tissue damage. The macroscopic FLASH tissue sparing effect has not yet been robustly reproduced in large animal models nor humans. This study tests FLASH skin sparing in canines with osteosarcoma by directly comparing equivalent doses delivered at UHDR and CDR. Careful attention has been paid to the verification dosimetry, both to determine dose rates ahead of time, as well as during treatments.
Methods
An IntraOp Mobetron with 9 MeV electrons delivered all treatments of recruited client owned dogs presenting osteosarcoma. Doses are planned to escalate from single-fraction deliveries of 20 to 28 Gy, with three dogs per group. The two parallel arms are UHDR and CDR at 80 Gy/s and 0.2 Gy/s, respectively. In-vivo dosimetry includes two forms of passive dosimeters, both TLD-400s 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 one-month post-irradiation.
Results
The trial began in Fall 2024 and since then ten dogs have been successfully enrolled into randomized treatment to date, with post-irradiation monitoring confirming dose delivery within 5% for both arms.
Conclusion
This trial has shown success via accurate delivery dosimetry in a veterinary setting. Grade 2 skin damage was observed at the lowest dose level of 20 Gy in only CDR. Overall no dose limiting toxicities have been observed. This study is planned to be the first definitive two-arm trial evaluating the efficacy of FLASH radiotherapy in a randomized veterinary model of large animals. The results of this study will provide a valuable resource for ongoing clinical and veterinary trials in FLASH RT.