Introduction

High Intensity Focused Ultrasound (HIFU) is a non-invasive tissue ablative technique approved for specific benign tumors in humans. Preclinical modeling suggests that HIFU may induce systemic antineoplastic immune responses. We designed, executed, and report the results of a pilot trial of HIFU for dogs diagnosed with subcutaneous solid tumors. Our primary objective was to evaluate the safety and feasibility of delivering HIFU to canine cancer patients. Our secondary objectives were to characterize the immediate adverse events, the pathologic changes in the treated tumor tissue, and the changes to the treated tumor microenvironment.

Methods

Dogs with subcutaneous solid tumors were recruited. Pretreatment biopsies were obtained and a single HIFU treatment for partial tumor ablation was delivered. Tumors were excised 4–6 days post HIFU and submitted for histopathology and immunohistochemistry. Gene expression analysis using a custom superarray was used to evaluate immunologic changes in the intratumoral microenvironment.

Results

Twenty dogs were recruited and treated. Tumors histologies included 15 soft tissue sarcomas, 3 mast cell tumors, 1 osteosarcoma, and 1 thyroid carcinoma. Complications secondary to HIFU were generally self-limiting and included various degrees of cutaneous thermal injury. Immunohistochemistry revealed an increase in the number of T-cells within the periphery of the ablation zone. Quantitative RT-PCR revealed a >2-fold increase in genes associated with pro-inflammatory cytokine signaling in post treatment samples.

Conclusion

HIFU appears to be feasible, safe, and results in predictable tumor ablation characterized by discrete regions of coagulative necrosis. HIFU resulted in tentative immunostimulatory alterations to the tumor microenvironment.

Funding Information

Focused Ultrasound Foundation and Theraclion