By destroying 50-75% of a liver tumor, the researchers enabled the rats’ immune system to clear out the rest. In 80% of rats treated thusly, tumors don’t come back.

Using sound like a scalpel

Cancer has developed quite an arsenal to attack the human body — but researchers are also working on new ways to fight it. Among the relatively new weapons humans deploy against cancer is something called histotripsy.

Histotripsy is an ultrasound-based approach that uses high-frequency ultrasound to target tumors specifically, without damaging the tissues next to the tumor. The sound generates nano-sized “bubbles” of gasses in targeted areas inside the human body. These bubbles form and collapse within microseconds, creating a cavitation effect and producing enough pressure to break the cells in targeted tissues. It’s very precise.

“The result is very precise ablation, occurring at a focal point of about 1 millimeter,” says Amanda Smolock, who was not involved in this study but is carrying out a trial to study the effects of histotripsy on humans. “That’s why it might be a tool to use in areas that have conventionally been off limits or unsafe with other tools, where we worry about damaging structures nearby.”

The method has received plenty of attention in recent years because the treatment is cheap and could be used to treat tumors that cannot be targeted with conventional methods (either due to their mass, their location, or their stage). In the new study, researchers wanted to see if the method works even when the tumor can’t be targeted completely, which is the case in many real-life situations. This also allowed the team to test the method’s effectiveness under less than optimal conditions.

So in this study on 11 rats, they only targeted 50-75% of the tumor. They found that in 9 out of the 11 rats treated in this way, the tumors were destroyed by the immune systems and didn’t return.

“Even if we don’t target the entire tumor, we can still cause the tumor to regress and also reduce the risk of future metastasis,” said Zhen Xu, professor of biomedical engineering at U-M and corresponding author of the study.

Since 2001, Xu’s lab has been a pioneer in the use of histotripsy against cancer, producing remarkable results not just against liver tumors but also in the treatment of brain therapy and immunotherapy. Traditional ultrasound devices don’t work for this type of application, so instead, they used a device built by Xu’s lab. The device is essentially a transducer, which is a fancy way of saying you convert one form of energy to another — but in this case, you need the output to be a very specific type of sound energy.

“Our transducer, designed and built at U-M, delivers high amplitude microsecond-length ultrasound pulses—acoustic cavitation—to focus on the tumor specifically to break it up,” Xu said. “Traditional ultrasound devices use lower amplitude pulses for imaging.”

Liver cancer is one of the most dangerous types of cancer worldwide, and even with multiple treatment options, the prognosis remains generally poor, and there is a high prevalence of tumor recurrence after the initial treatment. The new technique offers new hope for long-lasting treatments, researchers say.

“Histotripsy is a promising option that can overcome the limitations of currently available ablation modalities and provide safe and effective noninvasive liver tumor ablation,” said Tejaswi Worlikar, a doctoral student in biomedical engineering. “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.”

From rats to humans

Of course, this was just a study in rats — there’s no guarantee that the same results will carry out for humans. However, a human trial is already underway. A separate team is carrying out a human trial on liver tumors. The trial at the Froedtert & the Medical College of Wisconsin Cancer Network will assess how well this innovative treatment works against primary and metastatic liver tumors. Usually, treating this type of health problem is invasive and painful.

“Histotripsy is completely different,” said Amanda Smolock, a subinvestigator of the trial. “This technology is noninvasive and doesn’t use heat the way other ablation therapies do. It is a new method of ablation that uses focused ultrasound to mechanically destroy tissues.”

“It’s exciting to study this groundbreaking technology for treating liver cancer — no punctures, no thermal energy, no radiation,” Dr. Smolock said. “We’re hopeful of its potential for use with other cancers.”

Within the trial, physicians will target one or several tumors in the liver. They’re using a different device that features an articulating arm with a curved ultrasound transmitter that is placed over the skin. With this, the team can target tumors from any angle, and they can also control the geometry of the targeted area.

“During the procedure, the device moves around under robotic control to cover the ablation field, which can be anything we want — sphere, egg-shaped, whatever we program,” Dr. Smolock said. “Ultrasound imaging allows us to watch the ablation zone in real-time. We can see the bubble cloud form precisely at the targeted area and watch tissue being destroyed.”

Patients in the human trial will be followed for five years after the treatment. The jury is still out on how successful the approach will prove to be, but for now, at least, the results look encouraging.