Abstract
BACKGROUND: Osteosarcoma (OS) is a devastating primary bone tumor. Histotripsy, a non-invasive ablation modality that mechanically destroys tissue with focused ultrasound, has shown promise for the treatment of OS. The goal of this study is to characterize the ablative effects after histotripsy treatment in an orthotopic mouse model of OS. METHODS: Mice (n=53) were grouped based on tumor volume on the day of histotripsy treatment: treated-small (<200 mm(3), 143 ± 35 mm(3)) and treated-large (>200 mm(3), 268 ± 44 mm(3)). Histotripsy outcomes were evaluated and compared on MRI and histopathology at different acute (1 and 3) and sub-acute (7 and 14) days post-treatment (DPT). 5 mice were survived up to 30 DPT, and factors correlating with survival were evaluated. RESULTS: At 1 DPT, treated tumors show significant hemorrhage (p < 0.0001), loss of contrast enhancement (34% decrease, p = 0.0480), and reduction in tumor volume (treated-small: 74% decrease from untreated, p = 0.0002; treated-large, 47% decrease from untreated, p = 0.0002). There was no significant change in treated-small tumor volume from 7 to 14 DPT (p = 0.7302), and treatment zones showed significant involution by 14 DPT (75% decrease, p = 0.0055). Only treated-small mice survived beyond 14 DPT, and survival was significantly extended by histotripsy treatment (p < 0.0001) by a median of 15 days compared to untreated OS mice. CONCLUSIONS: Histotripsy treatment significantly reduced tumor burden and extended survival compared to untreated controls. These results highlight histotripsy's promise as a safe and effective non-invasive treatment for OS.