A non-invasive method to counter liver cancer shows great promise

Researchers have developed non-invasive sound technology that breaks down liver tumours in rats, obliterates cancer cells and boosts the immune system. This could, according to a news release, lead to improved cancer outcomes in humans.

The researchers used the non-invasive sound technology to break down 50 to 75 percent of liver tumour volume, leaving the rest to the rats’ immune systems. The results were impressive: 80 percent of the rats were cancer-free, with no recurrence or metastases.

"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 the University of Michigan and corresponding author of the study published in Cancers.

The non-invasive sound technology also stimulated the rats’ immune responses, which is probably why the untargeted portion of the tumour eventually regressed and the cancer stopped spreading.

The treatment is called histotripsy: the authors write that it is “a novel technique that mechanically disrupts tumours, through precisely controlled acoustic cavitation.” 

“Histotripsy was pioneered by researchers at the University of Michigan in the US and relies on a process called cavitation — creating an empty space inside something solid — to eradicate cancer.” It is a relatively new technique that is currently undergoing human liver cancer trials in the US and Europe.

In most cases of cancer, the entirety of the tumour cannot be targeted because it may be too big, too advanced or too hard to reach. This recent study decided to leave behind a viable intact tumour while targeting and partially destroying only a portion of each mass with sound. That way the team at Michigan Medicine and the Ann Arbor VA Hospital could check the approach’s effectiveness under less than ideal conditions.

"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 the University of Michigan.

"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."

Worldwide, liver cancer is the third leading cause of cancer death. In 2020, an estimated 830,180 people around the world died from the disease.

The authors note that “Symptoms associated with liver cancer may not show at early stages, placing the patients at an increased risk for nodal and distant metastases, which further lowers their 5-year survival rate to an estimated 3–11 percent. Even after treatment, the high prevalence of tumour recurrence and metastasis highlights the clinical need for improving outcomes of liver cancer.

“In fact, metastasis accounts for [more than] 90 percent of all cancer-associated deaths, and metastatic progression is predominantly regulated by the complex signalling pathways between the primary tumour and stromal cells, especially the immune cells.”

University of Michigan (UM) engineers have managed to arrange sound waves used by a typical ultrasound into a machine for cancer treatment. A big plus of histotripsy is that it doesn’t have harmful side effects such as radiation and chemotherapy, the current popular approaches used to treat cancer.

"Our transducer, designed and built at UM, delivers high amplitude microsecond-length ultrasound pulses — acoustic cavitation — to focus on the tumour specifically to break it up," Xu says. "Traditional ultrasound devices use lower amplitude pulses for imaging."

The UM transducer sends out microsecond long pulses which then generate microbubbles within the targeted tissues. Bubbles that, according to a news release, rapidly expand and collapse. The news release calls the mechanical stresses that kill cancer cells “violent but extremely localised” bursts that break up the tumour’s structure.

Xu’s laboratory at the University of Michigan has been working on cancer treatments with histotripsy since 2001, which resulted in the clinical trial #HOPE4LIVER sponsored by HistoSonics, a University of Michigan spinoff company. As of late, the group’s research has produced “promising results” on histotripsy treatment on brain therapy and immunotherapy.