A non-invasive sound technology that breaks down liver tumours in rats, killing cancer cells and spurring the immune system to prevent further spread (metastasis), has been developed by biomedical engineers at the University of Michigan (U-M) in the US.
The treatment, called histotripsy, focuses ultrasound waves to mechanically destroy target tissue with millimetre precision.
In a new study, the team has shown that by destroying only 50% to 75% of liver tumour volume with sound, the rats’ immune systems were able to clear away the rest, and there was no evidence of a recurrence or metastases in 81% of animals after 12 weeks.
“Even if we don’t target the entire tumour, we can still cause the tumour to regress and also reduce the risk of future metastasis,” says Zhen Xu, professor of Biomedical Engineering at U-M and senior author of the new research published in Cancers.
Liver cancer is one of the top 10 causes of cancer-related deaths worldwide, and although there are multiple treatment options available, prognosis continues to be poor. The five-year survival rates are less than 18% in the US.
Due to the high incidence of tumour recurrence and metastasis after initial treatment, there is great clinical need for improving these outcomes. Histotripsy, a relatively new technique pioneered by U-M engineers, is currently being trialed in a human liver cancer in the US and Europe.
It relies on a process known as acoustic cavitation, where microsecond-long, high-energy ultrasound pulses generate microbubbles within the targeted tissues that rapidly expand and collapse.
These violent but extremely localised mechanical stresses kill cancer cells and break up the tumour’s structure so that it can be cleared away by the body, without the harmful side effects associated with other currently available treatments (chemotherapy, radiotherapy, ablation).
“Our transducer, designed and built at U-M, delivers high amplitude microsecond-length ultrasound pulses – acoustic cavitation – to focus on the tumour specifically to break it up,” Xu explains. “Traditional ultrasound devices use lower amplitude pulses for imaging.”
The engineers were interested in investigating the effect of only partially destroying tumours with histotripsy because, in many clinical situations, the entirety of a cancerous tumour cannot be targeted directly due to the mass’ size, location, or stage of progression.
In rats, they targeted only a portion of each mass and left behind a viable intact tumour to show the approach’s effectiveness under less-than-optimal conditions.
The treatment stimulated the rats’ immune responses, indicated by increased immune cell infiltration of tumour tissue, which possibly contributed to the eventual regression of the untargeted portion of the tumour and prevented further spread of the cancer.
“Histotripsy is a promising option that can overcome the limitations of currently available ablation modalities and provide safe and effective non-invasive liver tumour ablation,” says Tejaswi Worlikar, a doctoral student in biomedical engineering at U-M.
“We hope that our learnings from this study will motivate future preclinical and clinical histotripsy investigations toward the ultimate goal of clinical adoption of histotripsy treatment for liver cancer patients.”