(P 341) THE EFFECTS OF ULTRASOUND-GUIDED HISTOTRIPSY ON SOFT TISSUE SARCOMA

Objective: With a 5-year survival rate [SR] of 65% that drastically declines to 15% when the disease has distantly metastasized, soft tissue sarcomas [STS] comprise a subset of cancers where novel therapies are desperately needed. Currently, the most effective therapy is surgical resection however, patients have a high risk of recurrence and derive limited benefits from current systemic treatments like chemotherapy or immunotherapy highlighting a critical need for novel therapeutics. Additionally, some benign soft tissue tumors pose a challenging management problem when difficult to remove due to size or location to critical structures. Our objective is to determine the pathological effects of ultrasound [US]-guided histotripsy treatment as a potential neoadjuvant therapy for malignant STS and treatment strategy for unresectable benign soft tissue tumors.

Methods: Soft tissue tumors including both benign and malignant histologies were collected from surgical specimens (n=46). Histotripsy was delivered to fresh samples including adipocytic (lipoma, well-differentiated liposarcoma, dedifferentiated liposarcoma), fibrous (desmoid, dermatofibrosarcoma protuberans, myxofibrosarcoma), and poorly differentiated (undifferentiated pleomorphic sarcoma, ganglioneuroma) with a custom 1 MHz 8-element histotripsy US transducer using 1-cycle pulses at 100 Hz pulse-repetition frequency for 50 pulses per focal location and 0.5 mm spacings with peak negative pressure > 30 MPa. Histotripsy treatments were guided by B-mode US. Shear Wave Elastography [SWE] and B-mode were both collected pre-treatment and post-treatment to evaluate the lesion. Following treatment, histology was confirmed, and treatment effect was determined by a soft tissue sarcoma pathologist using H&E staining.

Results: Most tumors were adipocytic [56.5%], followed by various poorly differentiated sarcomas [23.9%] and fibrous aggressive sarcomas [19.6%]. Histotripsy resulted in effective treatment across all histologies, including both benign and malignant. This included well-defined areas of liquefactive necrosis with no viable cells in liposarcomas and near-complete dissolution of cells confined within the treatment zone in fibrous STS as compared to the tissue outside the treatment zone [Figure 1]. Intermediate-high grade sarcomas showed necrosis, however, in those previously treated with radiation, it was challenging histologically to determine whether this observed necrosis was caused by histotripsy or radiation. B-mode imaging showed hypoechoic regions where treatment occurred. Histotripsy definitively created necrosis in highly mitotic tumors that have not responded well to neoadjuvant treatment such as dedifferentiated liposarcoma. SWE measurement showed a ~30-90% decrease in shear modulus of non-lipomatous tumors post-treatment, however, the shear modulus did not significantly change for lipomatous tumors.

Conclusion: US-guided histotripsy was efficacious in inducing necrosis within the treatment zone across multiple different benign and malignant soft tissue tumors including notoriously difficult to treat tumors such as DDLPS and desmoid fibromatosis. Based on these preliminary preclinical results, histotripsy seems to be a viable novel neoadjuvant treatment strategy for STS patients and potential treatment for symptomatic unresectable benign tumors. Thus, histotripsy is a promising FDA-approved treatment for tumors of the liver which should be validated for sarcoma in clinical trials.