Researchers at Duke University (Durham, North Carolina) have used high-intensity focused ultrasound (HIFU) in a study indicating that not only did HIFU cause a reduction in the growth of primary tumors, it also generated an anti-tumor immune response in the body that could be a challenge to metastatic cancer. This potentially could lead the way to a less toxic, noninvasive cancer treatment.

The research appears in the Aug. 3 issue of the Journal of Translational Medicine.

“This potential for HIFU-elicited anti-tumor immunity clearly warrants a thorough investigation for the further development of effective cancer treatment with focused ultrasound,” the researchers wrote of their study in mouse models.

According to Duke’s Pratt School of Engineering, where study researcher Pei Zhong is an associate professor in the mechanical engineering and materials science department.

This intense form of ultrasound “shakes a tumor until its cells start to leak,” which then triggers an “alarm” that enlists immune defenses against the cancerous invasion.

“Based on Matzinger’s danger theory, the maturation of DC [dendritic cells] can be induced by endogenous danger signals released from distressed or injured cells, such as those exposed to pathogens, toxins or mechanical damage,” the researchers wrote.

Speaking to Medical Device Daily, Zhong said that HIFU has been used in Europe and Asia and has been proven in treating primary tumors, but the thing that most cancer patients fear is a recurrence of the tumor or metastasis.

“Cancer is a pretty tough disease to treat, and a fundamental challenge for cancer treatment for a certain group of patients, especially patients with metastatic disease,” is that getting rid of the primary tumor is not the end of the treatment, Zhong said.

“The motivation of our study is ... since HIFU has such a unique advantage [in] being noninvasive, so you can actually perform multiple treatments in contrast to surgery or radiation therapy, which are often limited due to patient tolerance,” he said.

Zhong suggests envisioning a “new treatment strategy” whereby physicians can alternate HIFU treatment methods ...”first, to induce antitumor immune response, which would be effective against metastatic cancer cells.”

That initial treatment, which theoretically would injure the cells causing an immune response in the cells, would be followed by a second procedure to use the HIFU to attack the primary tumor.

In the study, mice with cancerous tumors in the colon were treated with thermal and mechanical HIFU exposure settings “in order to independently observe HIFU-induced effects on the host’s immunological response.”

The HIFU treatment resulted in tumor volume reduction by 85% with thermal HIFU and 43% with mechanical HIFU, which “shakes” the cells.

But the researchers said it also “provided protection against subcutaneous tumor re-challenge.”

While mechanical HIFU was not as effective in killing tumor cells directly, it has the potential to induce a stronger anti-tumor immune response — and that is what is “intriguing” about this study, Zhong said.

Improvements would have to be made to current ultrasound systems, which, although working nicely for current uses, may not be the most ideal in this new way of targeting cells.

For the study, the researchers used an experimental system from Sonic Concepts (Seattle).

Since the study was published, two medical device companies have contacted the researchers to express an interest in working with them, Zhong said, adding that the study is based on very preliminary research in animal models.

The researchers are continuing their studies, with new results expected in about a year, Zhong said, by focusing on the way HIFU works in different tumor models in mice in models of breast cancer, prostate cancer and melanoma to determine the “best HIFU treatment.”

“In this paper, we really didn’t have the opportunity to optimize the HIFU exposure, so that’s something we need to do in the next set of experiments,” Zhong said.

That flows hand-in-hand with what are perhaps needed improvements in the ultrasound devices, since Zhong said that the specific kinds of improvements needed will have to be known “before [they] can attack that issue.”

Commenting on the research, Michael McManus, president/CEO of Misonix, maker of the Sonablate 500 for HIFU treatment of prostate cancer, said in a statement that the company has maintained all along its belief that Misonix possesses the most advanced HIFU platform.

“Our investments and efforts to advance the development of unique products for effective and patient-friendly eradication of cancerous tissue in the prostate, kidney, liver and breast has, with the findings of the Duke University study, the potential to significantly alter the treatment of cancer,” he said.

He called the implications of the study for HIFU “astounding” and said that “the entire industry should be taking note” of its potential.

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