Abstract 4688: Focused ultrasound for the treatment of osteosarcoma in a canine comparative oncology model: Findings from veterinary clinical trials

Abstract Osteosarcoma (OS) is the most common primary bone tumor in dogs and humans, and the similarities between human and canine OS make the dog a valuable comparative oncology model. Histotripsy, a non-invasive ablation modality using pulsed focused ultrasound to mechanically disintegrate tissue, shows promise for the treatment of bone tumors. Previous canine clinical trials have shown the safety and feasibility of ablating canine OS tumors, followed by limb amputation. The present study is the first use of histotripsy without standard-of-care tumor resection in OS, allowing for evaluation of long-term clinical outcomes. Pet dogs with spontaneous bone tumors were assessed at baseline and over time with MRI, gait analysis, pain & quality of life surveys, and lameness assessments. Histotripsy treatments were fractionated (separate treatments applied on different days) with a plan to ablate >50% of the tumor in 1-5 treatments. Additional treatments were applied if residual tumor was remaining or if untreated portions of tumor continued to grow on contrast-enhanced T1-weighted MRI. Histotripsy was delivered by a 700 kHz transducer designed for targeting musculoskeletal tumors, with coaxial ultrasound imaging to guide treatment planning and execution. 9 dogs with primary bone tumors were treated, and 6 dogs received long-term follow-up. Dogs generally tolerated histotripsy treatment well and were able to return home within 1-3 hours post-treatment. The maximum volume targeted in a single session was 29.2 cm3. The mean total ablation volume was 35.6 cm3, which equated to a mean percent ablation of 50.2% when compared to the pre-treatment tumor size on MRI. For each treatment, an area closely matching the targeted region was observed as a non-enhancing area on MRI. Whole tumor signal intensity as well as enhancing tumor volume decreased immediately after treatment but tended to return to baseline or increase by 6 weeks after the initial treatment. Considering clinical outcomes, 4/6 dogs with follow-up (all patients with >50% ablation coverage of their tumor) showed a clinically significant reduction in pain at the end of their follow-up period (mean 8 weeks) as compared to baseline. Across those 6 dogs, there was a significant increase in peak pressure on the tumor-bearing limb at the end of follow-up as compared to baseline. these results highlight the promise of histotripsy as a non-invasive limb salvage treatment for OS. This work also shows the potential of fractionated histotripsy treatments for the ablation of large tumors, which may expand the patient populations that can be treated with histotripsy. Ongoing studies are optimizing treatment strategies to achieve safe, rapid, and complete ablation of OS, including combination with immunotherapy. Citation Format: Elliana Vickers, Alayna Hay, Lauren Ruger, Ny Luong, Sheryl Coutermarsh-Ott, Gregory Daniel, Steven Soliman, Gunjan Malhotra, Timothy Ziemlewicz, Adam Maxwell, Eli Vlaisavljevich, Joanne Tuohy. Focused ultrasound for the treatment of osteosarcoma in a canine comparative oncology model: Findings from veterinary clinical trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4688.