Principal investigator Joanne Tuohy, assistant professor of surgical oncology in the Department of Small Animal Clinical Sciences (DSACS) and interim director of the Animal Cancer Care and Research Center, and co-investigators Eli Vlaisavljevich, assistant professor of biomedical engineering and mechanics in Virginia Tech's College of Engineering; Irving Coy Allen, associate professor of inflammatory disease in the Department of Biomedical Sciences and Pathobiology (DBSP); Sheryl Coutermarsh-Ott, assistant professor of anatomic pathology in DBSP; Nick Dervisis, associate professor of oncology in DSACS; Greg Daniel, professor of radiology in DSACS; and Shawna Klahn, associate professor of oncology in DSACS, have been awarded a three-year R21 grant from the National Institutes of Health's National Institute of Biomedical Imaging and Bioengineering (NIBIB) to non-surgically treat osteosarcoma with histotripsy.

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

FUNDING AGENCY
NIBIB

TOTAL AWARD
Direct:  $400,000
Indirect: $232,418

DURATION OF AWARD
3 years

KEY FACULTY PERSONNEL
PI/PD: Joanne Tuohy
CO-I: Eli Vlaisavljevich, Irving Coy Allen, Sheryl Coutermarsh-Ott, Nikolaos Dervisis, Greg Daniel, Shawna Klahn

SIGNFICANCE

Osteosarcoma (OS), a malignant primary tumor of bone, is the most common primary bone tumor in children and adolescents, as well as in the dog. Human and canine OS share many biologic similarities, and perhaps the most dismal is the lack of significant improvement in survival over the past three decades. Despite attempts with various permutations of adjunctive systemic 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 a 20-30% long-term survival in metastatic OS patients. Due to the similarities between human and canine OS, treatment advances investigated in canine patients have high potential of being translatable to humans. 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. Osteosarcoma treatment needs a new and innovative approach. A non-surgical limb salvage option for treating the primary tumor 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. This proposal aims to develop histotripsy as a novel method for the ablation of OS, providing a low morbidity limb salvage option and an immunotherapeutic to target metastatic disease.