Sound technology helps to destroy tumours


Tuesday, 26 April, 2022

Sound technology helps to destroy tumours

Non-invasive sound technology developed at the University of Michigan (U-M) has been shown in rats to break down liver tumours, kill cancer cells and spur the immune system to prevent further spread — an advance that could lead to improved cancer outcomes in humans, according to a new study published in the journal Cancers.

Liver cancer ranks among the top 10 causes of cancer-related deaths worldwide and in the US. Even with multiple treatment options the prognosis remains poor, with five-year survival rates less than 18% in the US. Furthermore, in many clinical situations the entirety of a cancerous tumour cannot be targeted directly in treatments for reasons that include the mass’s size, location or stage. The high prevalence of tumour recurrence and metastasis after initial treatment highlights the clinical need for improving outcomes of liver cancer.

Where a typical ultrasound uses soundwaves to produce images of the body’s interior, U-M engineers have pioneered the use of those waves for treatment — without the harmful side effects of current approaches such as radiation and chemotherapy. The treatment, called histotripsy, non-invasively focuses ultrasound waves to mechanically destroy target tissue with millimetre precision.

“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,” said Professor Zhen Xu, corresponding author on the study. “Traditional ultrasound devices use lower amplitude pulses for imaging.”

The microsecond-long pulses from the transducer generate microbubbles within the targeted tissues — bubbles that rapidly expand and collapse. These violent but extremely localised mechanical stresses kill cancer cells and break up the tumour’s structure.

To investigate the effects of partially destroying tumours with sound, the U-M team’s study in rats targeted only a portion of each mass, leaving behind a viable intact tumour. This also allowed the team, including researchers at Michigan Medicine and the Ann Arbor VA Hospital, to show the approach’s effectiveness under less-than-optimal conditions.

By destroying only 50–75% of liver tumour volume, the rats’ immune systems were able to clear away the rest, with no evidence of recurrence or metastases in more than 80% of animals. Results also showed the treatment stimulated the rats’ immune responses, possibly contributing to the eventual regression of the untargeted portion of the tumour and preventing further spread of the cancer.

“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,” Xu said.

Since 2001, Xu’s laboratory at U-M has pioneered the use of histotripsy in the fight against cancer, leading to the human liver cancer trial ‘#HOPE4LIVER’ in the US and Europe. More recently, the group’s research has produced promising results on histotripsy treatment of brain therapy and immunotherapy.

“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,” said U-M doctoral student Tejaswi Worlikar. “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.”

Image caption: Zhen Xu and Tejaswi Worlikar with the 700 kHz, 260-element histotripsy ultrasound array transducer used in Xu’s lab. Image credit: Marcin Szczepanski, Michigan Engineering.

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