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Introduction: Histotripsy is a non-invasive focused ultrasound therapy that uses controlled acoustic cavitation to mechanically disintegrate tissue. To date, there are no reports investigating histotripsy for the treatment of soft tissue sarcoma (STS). Objective: This study aimed to investigate the in vivo feasibility of ablating STS with histotripsy and to characterize the impact of partial histotripsy ablation on the acute immunologic response in canine patients with spontaneous STS. Methods: A custom 500 kHz histotripsy system was used to treat ten dogs with naturally occurring STS. Four to six days after histotripsy, tumors were surgically resected. Safety was determined by monitoring vital signs during treatment and posttreatment physical examinations, routine lab work, and owners' reports. Ablation was characterized using radiologic and histopathologic analyses. Systemic immunological impact was evaluated by measuring changes in cytokine concentrations, and tumor microenvironment changes were evaluated by characterizing changes in infiltration with tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs) using multiplex immunohistochemistry and differential gene expression. Results: Results showed histotripsy ablation was achievable and well-tolerated in all ten dogs. Immunological results showed histotripsy induced pro-inflammatory changes in the tumor microenvironment. Conclusion & Significance:

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CASE DESCRIPTION A 14-year-old 5.6-kg (12.3-lb) castrated male Toy Poodle was evaluated because of high serum activities of alkaline phosphatase and alanine amino-transferase and the presence of a hepatic mass. CLINICAL FINDINGS Abdominal CT revealed a large (approx 6.8 X 7.1 X 6.5-cm) soft tissue mass along the midline of the liver. The mass either originated from the papillary process of the caudate lobe or the left medial liver lobe. TREATMENT AND OUTCOME A partial liver lobectomy was performed, and approximately a third of the mass was successfully removed and submitted for histologic examination. Consultation with the oncology service was advised to determine whether radiation therapy could be used to treat the residual disease. On 5 consecutive days, the dog underwent imaging-guided intensity-modulated radiotherapy-stereotactic body radiation therapy (4 Gy/treatment) with a simultaneous integrated boost to the center of the tumor. The dog received a base dose of 20 Gy that was then boosted to 28 Gy. In the 10-month period after completion of radiation therapy, the hepatocellular mass continued to decrease in size, and overall improvements in the dog's serum liver enzyme abnormalities were evident. CLINICAL RELEVANCE There are few treatment options for dogs with incompletely excised hepatocellular carcinomas. On the basis of the positive outcome in this case, radiation therapy could be useful following incomplete surgical removal of hepatocellular carcinomas in dogs. (J Am Vet Med Assoc 2021;259:392–395)