Ultrasound-Guided Histotripsy for Non-Invasive Treatment of Ex Vivo Soft Tissue Tumors: Preclinical Feasibility Study

Abstract Background Soft tissue sarcoma (STS) is a rare and heterogeneous malignancy with more than 100 histologic subtypes that can arise in virtually any part of the body. Although surgical resection is the standard of care, complete surgical resection is often limited by involvement of critical anatomy, and most subtypes are resistant to systemic therapies. Histotripsy uses microsecond length, high-pressure ultrasound (US) pulses delivered externally to generate cavitation inside the target tumor to mechanically liquefy tissue to acellular homogenate. This study tested the effect of histotripsy in a variety of soft tissue tumors (STTs) including benign tumors and sarcomas. Methods Histotripsy was delivered to 45 surgically excised ex vivo human samples with a custom 1 MHz 8-element US transducer guided by US imaging. Results Histotripsy was successful in creating an identifiable treatment effect across all subtypes including adipocytic tumors, benign myxoid and nerve sheath tumors, aggressive fibrous sarcomas, and high-grade sarcomas. Immediately after histotripsy, B -mode and shear-wave elastography US imaging was shown to effectively evaluate the treatment. Tissue structure heterogeneity among the tumor subtypes dictated the variation in histologic treatment effects. Conclusions The data demonstrate effective US-guided histotripsy ablation on a robust cohort of ex vivo STTs. The variable treatment effects observed across tumor subtypes highlight the need for histotripsy parameter optimization, with support for its potential as a promising non-invasive treatment modality for sarcoma patients who currently have limited therapeutic options.