Abstract
Osteosarcoma (OS) is a devastating primary bone cancer in dogs and humans. Histotripsy is a non-invasive ablation technique that mechanically destroys targeted tumor with focused ultrasound and has shown promise in treating small portions of canine OS followed by limb amputation. This study represents the first use of histotripsy to treat large volumes of canine OS, using fractionated treatments, without subsequent surgical resection. Our objective was to evaluate the safety and feasibility of treating large volumes of OS, following clinical outcomes after histotripsy. 9 dogs with suspected OS were treated with 1–5 histotripsy ablations, depending on tumor size, fractionated over 3 to 17 days. Pain, quality of life, and gait were followed over time, and MRI was used for pre-treatment planning and post-treatment monitoring. All dogs tolerated fractionated histotripsy treatments well, and the ablation zone was visible as a non-enhancing area on MRI matching the targeted location. There was a significant reduction in tumor contrast enhancement after completion of all histotripsy treatments and at the end of follow-up. Across all dogs with follow-up, there was a significant increase in pressure on the tumor-bearing limb during walking at the end of follow-up as compared to pre-treatment, indicating decreased pain. 4/6 dogs with follow-up showed a clinically significant decrease in pain. This study shows the promise of histotripsy as a non-invasive limb-sparing treatment for OS and advances the use of fractionated histotripsy treatments to ablate large and complicated tumors.
Data availability
The data presented in this study are available within the main manuscript and supplementary information files. Any additional data not explicitly detailed in the manuscript or supplementary files are available upon reasonable request by reaching out to the corresponding author.
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Acknowledgements
The authors would like to thank the following team members for their contributions to this clinical trial: Courtney Snead and Mindy Quigley, Clinical Research Office; Christy Barry, Clinical Business Office; Valerie Vaught, Radiology; and the Teaching and Research Animal Care Support Services at Virginia Tech. The authors would also thank Julianna Diodato, Triniti Antony Baskar, and Basem Huneidi from Virginia Tech for their contributions. The authors would especially like to thank all owners and dogs that participated in this trial.
Funding
This work was funded in part by grants from the National Institutes of Health (National Cancer Institute, 1R01CA289288-01; National Institute of Biomedical Imaging and Bioengineering, 1R21EB030182-01), the Focused Ultrasound Foundation, and the Veterinary Memorial Fund. Author E.R.V. was supported by a Ruth L. Kirschstein Predoctoral Individual National Research Service Award from the National Cancer Institute (1F31CA294976-01).
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E.R.V. and L.N.R. planned and executed treatment of canine patients. E.R.V. drafted the manuscript text and figures, with assistance from L.N.R. and A.N.H. E.R.V., J.S.K., and S.V.K. performed MRI quantitative segmentation analysis. G.B.D., T.J.Z., S.B.S., and G.B.M. performed MRI qualitative radiological analysis. E.V. and J.T. conceived the study. E.V., A.M., and L.N.R. provided engineering oversight and support. J.T. provided patient care as lead veterinarian. All authors reviewed, contributed to, and approved of the manuscript.
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Author L.N.R. has an ongoing consulting relationship with Theraclion. Author E.V. has an ongoing research partnership and financial relationship with HistoSonics and is a co-founder of Sound Blade Medical. Author T.J.Z. has ongoing consulting and financial relationships with Ethicon and HistoSonics, as well as a consulting relationship with Elephas. No other authors have a conflict of interest to report.
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All applicable international, national, and institutional protocols for the care and use of animals were followed. All animal experiments were performed according to IACUC and ARRIVE guidelines.
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Vickers, E.R., Ruger, L.N., Hay, A.N. et al. The first limb-sparing use of histotripsy for canine osteosarcoma. Sci Rep (2026). https://doi.org/10.1038/s41598-026-42319-z
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DOI: https://doi.org/10.1038/s41598-026-42319-z
