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

机械高强度聚焦超声(组织碎裂术)治疗自发性软组织肉瘤的狗

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作者:Lauren Ruger, Ester Yang, Jessica Gannon, Hannah Sheppard, Sheryl Coutermarsh-Ott, Timothy J Ziemlewicz, Nikolaos Dervisis, Irving C Allen, Gregory B Daniel, Joanne Tuohy, Eli Vlaisavljevich, Shawna Klahn

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 post-treatment 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.

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.

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.

Significance

Overall, this study demonstrates histotripsy's potential as a precise, non-invasive treatment for STS.

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