Potential of sound waves to destroy liver tumors generates ‘good deal of excitement’
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A sound wave technique pioneered at University of Michigan has exhibited preliminary efficacy as a treatment for liver cancer.
The technique — called histotripsy — uses targeted ultrasound waves that create “microbubbles” within the tumor and ultimately break it down.
The approach, which the FDA approved for liver cancer treatment last year, has undergone evaluation in a human trial that launched in 2021. Preliminary efficacy and safety targets have been met.
“We’re always looking for new, less invasive treatment modalities, since many of the current treatments can be invasive or toxic,” Mishal Mendiratta-Lala, MD, professor of radiology at Michigan Medicine and principal investigator on the trial at University of Michigan’s Rogel Cancer Center, told Healio. “This gives us another tool in our arsenal in treating liver cancer.”
Healio spoke with Mendiratta-Lala about how histotripsy works, the results observed so far using this approach for liver tumors, and the potential for this technology to be used to treat other cancer types.
Healio: How did histotripsy for treatment of liver cancer come about?
Mendiratta-Lala: The research on histotripsy began just over 20 years ago. A PhD student, Zhen Xu, invented the technology. Initial investigation examined use of this technology for repair of fetal cardiac defects, but one night she discovered this cavitation mechanism of action in the lab. Fast forward to 2016, when we started using it for liver cancer applications.
Patients with liver cancer often have such advanced disease that they’re beyond the point of transplant. Also, the liver is one of the most common places for other types of tumors to metastasize.
Our traditional treatments for cancer, like chemotherapy and other systemic treatments, can be very toxic and don’t work for everybody. Surgery is invasive, and some therapies like radiofrequency ablation and cryoablation require a needle to be put in.
When our research on this started, I don’t think we imagined we would be where we are today, with the technology evolving into having an indication for liver cancer. It offers many advantages, even if it’s only in synergy with other available treatment options.
Healio: How does the approach work?
Mendiratta-Lala: Histotripsy is an ultrasound technology that uses cavitation to destroy cells. It’s noninvasive. It has a nonthermal and nonradiation mechanism of action. The patient gets an ultrasound, and an ultrasound probe is placed over the area of the liver. This probe is bigger than the usual ultrasound probe, and there are two ultrasound transducers. One probe is for diagnostic purposes, meaning we’re looking for the area that we want to treat. Once we find that, we use our therapy transducer to plan and program the target. Based on where the tumor is located, the size, and a few other procedure-related factors, we input coordinates into a computer system. Once we hit “start,” we can watch the treatment in real time under ultrasound as it scans through the target and irreversibly destroys cells.
We have follow-up at 1-year and 2-year time points. We’ve had 100% technical efficacy in creating the ablation zone and target zone size, and a complete destruction of the tumors that were properly targeted. These results were maintained in follow-up with no local recurrence.
Healio: Do you think histotripsy can be used to treat other cancer types?
Mendiratta-Lala: We are looking at future directions in various other cancers, such as renal cancer, pancreatic cancer, sarcoma and bone tumors. Work in many of those areas is still preclinical, but a clinical trial of humans with kidney cancer is now accruing patients.
Now that we have FDA approval of histotripsy and the delivery platform (Edison, HistoSonics) to treat liver tumors, there will be a need for much more research into the proper indication and role that this technology will play in treatment.
At University of Michigan, we are outlining our criteria for treatment eligibility. We think we have some great indications where we can add this to our toolbox of treatments. Our current indications are to treat patients with six or fewer tumors in their liver, usually in a staged approach — so over a few sessions. We also can treat patients with six or fewer liver tumors and three or fewer tumors outside of the liver, although we would only target the liver tumors and they would continue with systemic therapy. We do this in practice, where patients are on systemic therapy but have a few lesions in the liver. So, we’ll do ablation of the liver tumors while patients remain on systemic therapy. With histotripsy, we now have a noninvasive way of treating those tumors.
Healio: What is the next step in research?
Mendiratta-Lala: We hope to do further research into this “abscopal response” that has been demonstrated in histotripsy and is generating a good deal of excitement. It’s an immune-mediated response where you treat one tumor and it induces an immune response that fights tumors elsewhere in the body. We’ve seen this response in animal models, and we’ve seen it in some human patients we’ve treated. We want to evaluate it further to determine how real it is, and in which cancers we are seeing it. Eventually, I think we will develop a research protocol with certain cancer types that respond to immunotherapy, and we’ll add histotripsy with combination immunotherapy. That’s our goal. – by Jennifer Byrne
Reference:
- University of Michigan. Tumor-destroying sound waves receive FDA approval for liver treatment in humans (press release). Available at: https://news.umich.edu/tumor-destroying-sound-waves-receive-fda-approval-for-liver-treatment-in-humans/. Posted Oct. 9, 2023. Accessed Jan. 16, 2024.
For more information:
Mishal Mendiratta-Lala, MD, can be reached at University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-5030; email: mmendira@med.umich.edu.
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