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Published on: October 28, 2021
Histotripsy treatment reduces tumor burden and extends survival in an orthotopic mouse model of osteosarcoma
Elliana R Vickers1,2, Alayna N Hay1, Victor A Lopez2
1Virginia Tech Animal Cancer Care and Research Center, Virginia-Maryland College of Veterinary Medicine, Roanoke, VA, United States.
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 mm3, 143 ± 35 mm3) and treated-large (>200 mm3, 268 ± 44 mm3). 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.
Insights
Histotripsy, a non-invasive ultrasound treatment, significantly reduced osteosarcoma tumor size and extended survival in mice. This study highlights its potential as a safe and effective therapy for this bone cancer.
Area of Science:
- Oncology
- Biomedical Engineering
- Medical Physics
Background:
- Osteosarcoma (OS) is a primary bone tumor with limited treatment options.
- Histotripsy, a non-invasive focused ultrasound ablation technique, offers a novel therapeutic approach.
- Characterizing histotripsy's effects in an orthotopic OS mouse model is crucial for clinical translation.
Purpose of the Study:
- To evaluate the ablative effects of histotripsy in an orthotopic osteosarcoma mouse model.
- To assess tumor response, including volume reduction and hemorrhage, post-histotripsy treatment.
- To determine the impact of histotripsy on animal survival rates.
Main Methods:
- 53 mice with orthotopic osteosarcoma were divided into treated-small and treated-large tumor volume groups.
- Histotripsy treatment was administered, and outcomes were assessed using MRI and histopathology at 1, 3, 7, and 14 days post-treatment (DPT).
- Survival analysis was performed, with 5 mice monitored up to 30 DPT.
Main Results:
- Histotripsy induced significant hemorrhage and reduced contrast enhancement in treated tumors at 1 DPT.
- Tumor volume decreased significantly post-treatment (74% in small, 47% in large tumors).
- Treated mice showed extended survival, with a median increase of 15 days compared to controls.
Conclusions:
- Histotripsy effectively reduced tumor burden and improved survival in an osteosarcoma mouse model.
- The findings support histotripsy as a promising non-invasive therapeutic option for osteosarcoma.
- Further research is warranted to explore histotripsy's full potential in treating primary bone tumors.
