High-intensity focused ultrasound-based thermal ablation and histotripsy: potential for solid tumor therapy

High-intensity focused ultrasound (HIFU) offers a promising, non-invasive approach to treating solid tumors by employing thermal and histotripsy-based mechanical ablation. However, its effectiveness across different tumor types remains unclear. To explore its therapeutic potential and impact on the immune system, we conducted a comparative study of HIFU thermal ablation and histotripsy in dogs with spontaneous tumors. Additionally, we investigated whether non-ablative, HIFU-induced mild hyperthermia (40-45ºC) could enhance Doxorubicin delivery and immunomodulatory effects. Our findings revealed that HIFU thermal ablation led to tumor remission in most treated dogs within 60 days, whereas histotripsy resulted in partial responses or stable disease. Thermal ablation was associated with minor to moderate side effects, while histotripsy was generally well-tolerated. Notably, we identified a link between the therapeutic response to HIFU and the presence of serum anti-tumor cytokines and functionally active cytotoxic immune cells. Moreover, in Doxorubicin-treated dogs, HIFU-induced hyperthermia improved drug delivery, enhanced treatment efficacy, and stimulated anti-tumor immune responses. In summary, our study highlights that HIFU treatments, depending on the tumor type and specific parameters, can effectively control tumor growth, activate the immune system, and enhance chemotherapy outcomes in veterinary patients. These results underscore the potential of HIFU as a valuable cancer treatment strategy, with important clinical implications for veterinary oncology. (author)