States and one in Europe. They are multicenter, open-label, single-arm trials with eight sites in the United States and six in Europe. The principal investigators in the two trials plan to enroll up to 45 patients each. Dr. Lee expects the data to be submitted to the U.S. Food and Drug Administration within the next year.


In the initial study in Spain, two of the eight patients experienced off-target immune response after histotripsy. Although the treatment targeted a liver tumor, at 8 weeks, imaging showed that nontarget tumors were stable or had decreased.


“If we can eliminate some of the barriers to local regional therapy, some of those stumbling blocks that exist right now, it would expand the reach of interventional radiology,” Dr. Lee says. “I see that in my own mind as the floor for histotripsy, and then the ceiling would be if we’re able to prove out some of the immune effects that we’re seeing in animal models right now. Then the ceiling becomes very high, and we’re going to be very busy.”


Dr. Lee sees an opportunity for IRs to be an even more integral part of a patient’s oncology team, combining histotripsy with immunotherapies, radiation therapy or conventional ablation therapy.


Another benefit for IRs is that, because histotripsy is noninvasive, it doesn’t have to be done in a particular surgical suite. Patients currently undergo general anesthesia, but conscious sedation could potentially be used, Dr. Lee says. The technology hasn’t been used on conscious patients with liver or kidney tumors, but in early studies on prostate cancer some patients were awake and reported only a mild tingling feeling.


Researchers are also considering histotripsy’s potential in treating oligometastatic sites of disease. Physicians have traditionally considered it futile to treat patients with a small number of metastatic tumors, such as pancreatic tumors, lung cancers and melanomas. But combining histotripsy with other therapies could allow physicians to treat tumors in difficult locations, such as in the bowel, retroperitoneum or next to the ureter, Dr. Lee says.


Emily Knott Fred T. Lee Jr., MD


Biomedical engineer Emily Knott has been involved in histotripsy research since 2017 as an undergraduate student of Fred T. Lee Jr., MD, at the University of Wisconsin. The potential of ultrasound to destroy tumors noninvasively has so fascinated Knott that she is considering becoming an interventional radiologist. She is now a first-year medical student at the Cleveland Clinic Lerner College of Medicine.


“I’ve been really excited about this project since I started,” Ms. Knott says. “As a sophomore in biomedical engineering, when I first got brought down to the lab, I didn’t know much about medical devices or anything.”


She was tasked with assisting a researcher on an early histotripsy liver study in a swine model. Later, she was able to visit one of the first trial sites in Spain. “I was amazed by the technology, and it has been incredible to see the progress.”


Ms. Knott is particularly enthusiastic about histotripsy’s potential for renal therapy. “The current clinical trial is for the liver, but I did a project with the kidney and we saw some cool findings that are challenges with thermal ablation right now, such as ablation in the central kidney where thermal ablation is limited. We saw [where the] cells around the collecting system were completely destroyed in this pig model and the collecting system itself was spared.”


Although she had already planned to go to medical school, Ms. Knott didn’t know anything about interventional radiology, ultrasound or ablation until she joined Dr. Lee’s lab. Now, she’s seriously considering specializing in IR.


“The combination of using things less invasively and using image guidance has been fascinating to me,” she says. “I’m kind of a nerd for medical devices and imaging. That’s leading me toward IR.”


Histotripsy inspires med student to consider IR


“My personal belief is that histotripsy is best delivered by people who have a very deep knowledge about the imaging of various anatomical parts,” Dr. Lee says. “To me, that’s radiologists. I think it’s going to be really important that IRs understand this technology and get involved early.”


To learn more about histotripsy, read


“Breaking down histotripsy” by the technique’s creators: bit.ly/2XLRLiT or listen to the article via IRQ audio: bit.ly/irqa-2


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