Mechanical High-Intensity Focused Ultrasound (Histotripsy) in Dogs With Spontaneously Occurring Soft Tissue Sarcomas

Area of Science:

• Oncology
• Medical Physics
• Immunology

Background:

• Histotripsy is a non-invasive focused ultrasound therapy utilizing acoustic cavitation for tissue ablation.
• Soft tissue sarcoma (STS) is a group of cancers with limited non-invasive treatment options.
• No prior studies have investigated histotripsy for STS treatment.

Purpose of the Study:

• To assess the feasibility of using histotripsy to ablate STS in vivo.
• To characterize the immunologic response following partial histotripsy ablation of STS.
• To evaluate safety and efficacy of histotripsy in canine patients with spontaneous STS.

Main Methods:

• A custom 500 kHz histotripsy system was employed on ten dogs with naturally occurring STS.
• Tumors were surgically resected 4-6 days post-treatment for analysis.
• Safety was monitored via vital signs, physical exams, and lab work; ablation was assessed radiologically and histopathologically.
• Immunologic impact was evaluated by cytokine analysis and characterization of tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs) via multiplex immunohistochemistry and gene expression.

Main Results:

• Histotripsy ablation was successfully achieved and well-tolerated in all ten canine subjects.
• Histotripsy treatment induced pro-inflammatory changes within the tumor microenvironment.
• Radiologic and histopathologic analyses confirmed successful ablation.
• No significant adverse events were reported during monitoring.

Conclusions:

• Histotripsy is a feasible and safe non-invasive treatment modality for soft tissue sarcoma.
• The therapy elicits a favorable immunologic response within the tumor microenvironment.
• Histotripsy shows significant potential as a precise, non-invasive therapeutic option for STS.