A review of the development of histotripsy for extremity tumor ablation with a canine comparative oncology model to inform human treatments

Abstract

Cancer is a devasting disease resulting in millions of deaths worldwide in both humans and companion animals, including dogs. Treatment of cancer is complex and challenging and therefore often multifaceted, as in the case of osteosarcoma (OS) and soft tissue sarcoma (STS). OS predominantly involves the appendicular skeleton and STS commonly develops in the extremities, resulting in treatment challenges due to the need to balance wide-margin resections to achieve local oncological control against the functional outcomes for the patient. To achieve wide tumor resection, invasive limb salvage surgery is often required, and the patient is at risk for numerous complications which can ultimately lead to impaired limb function and mobility. The advent of tumor ablation techniques offers the exciting potential of developing noninvasive or minimally invasive treatment options for extremity tumors. One promising innovative tumor ablation technique with strong potential to serve as a noninvasive limb salvage treatment for extremity tumor patients is histotripsy. Histotripsy is a novel, noninvasive, non-thermal, and non-ionizing focused ultrasound technique which uses controlled acoustic cavitation to mechanically disintegrate tissue with high precision. In this review, we present the ongoing development of histotripsy as a non-surgical alternative for extremity tumors and highlight the value of spontaneously occurring OS and STS in the pet dog as a comparative oncology research model to advance this field of histotripsy research.

Keywords:

• Histotripsy
• soft tissue sarcoma
• extremity tumors
• osteosarcoma
• canine comparative oncology model

Authors’ contributions

A.N.H. and L.R.- Contributed equally to the composition manuscript and are the primary contributors.

A.H.- Contributed to the composition of this manuscript.

E.R.V- Contributed to the composition of this manuscript.

S.K.- Contributed to the composition of this manuscript and is the principal investigator on the canine histotripsy STS study reported in this review.

E.V.- Oversaw the engineering work involved in the canine histotripsy STS and OS studies reported in this review, contributed to manuscript composition and revision.

J.T.- Contributed to the composition and revision of this manuscript, is corresponding author, and is the principal investigator of the canine histotripsy OS studies reported in this review.

Disclosure statement

Eli Vlaisavljevich has an ongoing research partnership and financial relationship with HistoSonics, Inc. Lauren Ruger has an ongoing consulting relationship with Theraclion. No other authors have a conflict of interest to report.

Data availability statement

Not applicable.

Additional information

Funding

The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. NIH funding (Project ID 1R21EB030182-01)(J.T.), American Kennel Club (Canine Health Foundation No. 02773)(J.T.) and Focused Ultrasound Foundation (FUSF-RAP-823R1)(J.T.) and (Grant #453047) (S.K) helped support the canine OS and STS studies reported in this review.