Sound controls

Scientists eradicated liver cancer in rats using non-invasive sound waves

Rats with liver cancer have demonstrated the effectiveness of a fascinating, non-invasive treatment.

Using focused ultrasound, scientists managed to destroy up to 75% of the volume of a liver tumor. The treatment also seems to prompt the rats’ immune system to take over and clear out the rest.

In 80% of the animals, the cancer appeared to be destroyed, with no signs of metastasis or recurrence during the three months they were monitored, the researchers said.

The treatment, called histotripsy, is currently being tested in humans with liver cancer.

“Histotripsy is a promising option that can overcome the limitations of currently available ablation modalities and provide safe and effective noninvasive ablation of liver tumors,” said biomedical engineer Tejaswi Worlikar of the University of Michigan.

“We hope that our insights from this study will motivate future preclinical and clinical investigations of histotripsy toward the ultimate goal of clinical adoption of histotripsy therapy for patients with liver cancer.”

Developed and pioneered at the University of Michigan, histotripsy seems to offer new hope for patients with one of the deadliest forms of cancer: the five-year survival rate for liver cancer is currently lower 18% in the United States.

The technique uses an ultrasound transducer, not to bounce off internal structures for imaging purposes, but to physically disrupt cancerous tumors.

It works through ultrasonic cavitation – similar to the method used to non-invasively break down fat cells for weight loss treatments. The ultrasonic waves are directed towards the area to be treated; the vibrations generate tiny bubbles in the targeted tissue. When the bubbles collapse or burst, the tissue is disrupted, destroying that part of the tumor.

It is often not possible to target the whole tumor. The way the masses are positioned, their size, and their stage can all influence whether it is safe to use histotripsy on the whole tumor.

But even partial treatment resulted in complete regression in 81% of treated rats, the researchers found. In contrast, 100% of control rats showed tumor progression.

“Our transducer, designed and manufactured in [University of Michigan]delivers high-amplitude, microsecond ultrasound pulses – acoustic cavitation – to focus on the tumor specifically to break it up,” said biomedical engineer Zhen Xu of the University of Michigan.

“Even if we don’t target the whole tumor, we can still regress the tumor and also reduce the risk of future metastasis.”

For the purpose of this study, 22 laboratory rats were implanted with liver cancer. Half remained as a control group, while the other 11 were treated with histotripsy, targeting between 50 and 75% of the tumor volume.

Three other rats were treated to a lesser extent, with histotripsy targeting only 25% of the tumor volume.

After treatment, rats were euthanized and dissected to determine treatment success. The researchers looked for signs of progression, metastases and immune markers.

The prognosis for the control rats was dire. All 11 showed signs of progression and metastasis. Within three weeks, the tumors had reached the maximum size allowed by ethical protocols and the animals were euthanized.

But the treated rats fared much better. Not only was the treatment without complications or side effects, but the majority of rats – nine out of 11 – showed tumor regression and experienced tumor-free survival for the remainder of the study, approximately 10 weeks.

Previous histotripsy studies had demonstrated that the treatment is effective in reducing tumor volume. The new work shows that it also appears to significantly increase survival rates after treatment.

“This study demonstrated the potential of histotripsy for successful noninvasive tumor ablation and prevention of local tumor progression and metastasis. Even with partial ablation, complete local tumor regression was observed in 9 of 11 rats from treatment, with no recurrence or metastasis through the 12-week study endpoint, as evidenced by MRI and histology,” the researchers wrote in their paper.

“These results suggest that histotripsy may not increase the risk of developing metastases after ablation, compared to controls. Future studies will continue to investigate the safety, efficacy, and biological effects of histotripsy , for potential clinical translation.”

The research has been published in Cancer.