Characterizing the Ablative Effects of Histotripsy for Osteosarcoma: In Vivo Study in Dogs

SIMPLE SUMMARY: Histotripsy is a non-invasive focused ultrasound therapy, in development, for treating osteosarcoma (OS). Small pilot studies describing ex vivo and in vivo histotripsy ablation of OS have demonstrated the feasibility and safety of the technique. The current study builds on the initial pilot studies to expand the characterization of the in vivo histotripsy ablation of OS. Ten canine patients with spontaneously occurring primary bone tumors received a single histotripsy treatment within their tumor before surgical removal of the mass via limb amputation one day after histotripsy. The results of this study echoed the finding that histotripsy ablation of OS is achievable while showing (1) more extensive tissue destruction relative to past in vivo ablations due to the increased treatment dose and (2) distinguishable changes in the radiographic characteristics of the tumor post-treatment. ABSTRACT: Osteosarcoma (OS) is a malignant bone tumor treated by limb amputation or limb salvage surgeries and chemotherapy. Histotripsy is a non-thermal, non-invasive focused ultrasound therapy using controlled acoustic cavitation to mechanically disintegrate tissue. Recent ex vivo and in vivo pilot studies have demonstrated the ability of histotripsy for ablating OS but were limited in scope. This study expands on these initial findings to more fully characterize the effects of histotripsy for bone tumors, particularly in tumors with different compositions. A prototype 500 kHz histotripsy system was used to treat ten dogs with suspected OS at an intermediate treatment dose of 1000 pulses per location. One day after histotripsy, treated tumors were resected via limb amputation, and radiologic and histopathologic analyses were conducted to determine the effects of histotripsy for each patient. The results of this study demonstrated that histotripsy ablation is safe and feasible in canine patients with spontaneous OS, while offering new insights into the characteristics of the achieved ablation zone. More extensive tissue destruction was observed after histotripsy compared to that in previous reports, and radiographic changes in tumor size and contrast uptake following histotripsy were reported for the first time. Overall, this study significantly expands our understanding of histotripsy bone tumor ablation and informs future studies for this application.