# Histotripsy as a novel limb salvage treatment and immunotherapy for osteosarcoma

> **NIH NIH R21** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2022 · $157,398

## Abstract

PROJECT SUMMARY
Osteosarcoma (OS) survival has not improved substantially for humans and dogs in the past 30 years. OS is the
3rd most commonly diagnosed tumor in adolescents 12-18 years of age, and is the most common primary bone
tumor in the dog. Current standard-of-care treatment for OS includes surgical resection of the primary tumor via
limb amputation or limb salvage surgery, and chemotherapy for treatment of metastatic disease. Limb salvage
surgery is associated with a high complication rate, and metastasis remains the primary cause of death despite
chemotherapeutics. Despite attempts with various permutations of adjunctive therapies, the median survival for
dogs with OS remains at 10-12 months. Similarly, the 5-year survival rate in humans with non-metastatic OS
remains around 70%, with no better than 20-30% long-term survival in OS patients with metastatic disease. The
problems with limb salvage surgery and with metastatic disease in OS need a new and innovative approach. A
non-surgical option for treating the primary tumor and controlling local disease in OS will help canine and human
patients preserve their limb and avoid the complications of surgical limb-salvage. A therapy that stimulates an
anti-tumor immune response can increase OS survival. Histotripsy is a precision non-thermal focused ultrasound
method that mechanically disintegrates tissues through the precise control of acoustic cavitation generated by
high-pressure pulses. Histotripsy does not have the limitations of thermal ablation and can produce consistent
ablation, even when delivered near vessels. Histotripsy can treat large tumor volumes and potentially induce
activation towards an anti-tumor immune response. Thus histotripsy, as a novel ablation treatment for OS, has
the potential to fulfill the dual role of being a non-surgical limb salvage option and an immunotherapeutic for OS.
However, it has not been evaluated for treatment of bone tumors. This study aims to demonstrate the
feasibility of treating canine OS with histotripsy, optimize the histotripsy treatment strategies for
targeting OS, and evaluate the effect of histotripsy on tumor cells, the OS immune microenvironment,
as well as the immune profile and clinical outcome of canine OS patients. Aim 1 proposes to develop the
optimal histotripsy parameters for treating OS. Aim 2 proposes to evaluate the oncological and immunological
effects of histotripsy treatment for OS. Since canine OS shares many biologic similarities to human OS, treatment
advances investigated in canine patients have high potential of being translatable to human OS patients. The
results of this study will advance the development of histotripsy as a novel limb salvage treatment option for
primary OS and an immunotherapeutic against metastatic disease for OS, thereby improving the standard of
care and outcomes for OS patients.

## Key facts

- **NIH application ID:** 10459533
- **Project number:** 5R21EB030182-03
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Joanne Tuohy
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $157,398
- **Award type:** 5
- **Project period:** 2020-09-02 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10459533

## Citation

> US National Institutes of Health, RePORTER application 10459533, Histotripsy as a novel limb salvage treatment and immunotherapy for osteosarcoma (5R21EB030182-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10459533. Licensed CC0.

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