Immunological and Clinical Outcomes Associated with Histotripsy Ablation in Spontaneously Occurring Canine Osteosarcoma; Veterinary Clinical Trial Results.

BACKGROUND: Osteosarcoma (OS) is a devasting bone cancer that occurs primarily in pediatric patients, and pet dogs, and treatment options have not advanced in decades. There is a profound need for advancement of treatment options to improve patient prognosis given the grim 70% 5-year survival rate for human patients, and 10-12-month median survival for canine patients. A major hurdle in advancing treatment options is overcoming the immunosuppressive tumor microenvironment to mitigate metastatic disease progression-the leading cause of mortality in OS patients. METHODS: We investigated the ability of a mechanical focused ultrasound ablation modality, histotripsy, to induce acute immunomodulation in canine patients with spontaneously occurring OS. RESULTS: Immunomodulation was evident locally and systemically. Tumor gene signatures indicated upregulation of pro-inflammatory signaling pathways and T-cell receptor signaling, and B-cell activation, and systemically, increased monocyte activation was observed within 5 days post-histotripsy ablation. A subset of patients who received histotripsy prior to definitive standard-of-care exceeded the reported expected median survival time of 10-12 months for canine OS patients that received definitive standard-of-care only. CONCLUSIONS: Our results demonstrate the promising potential of histotripsy to overcome the immunosuppressive tumor microenvironment.