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U-M HISTOTRIPSY RESEARCH CONTINUES TO IMPROVE OUTCOMES FOR PATIENTS WITH LIVER CANCER
Less than two years after its initial FDA approval, histotripsy is in high clinical demand and the subject of ongoing trials to advance its efficacy. As one of the co-inventors of histotripsy (2002) and co-founder of HistoSonics (2009), Zhen Xu, PhD, U-M Professor of Biomedical Engineering and Radiology, explains that creating a noninvasive therapy was always her lab’s overarching mission. Other co-inventors include Charles Cain, PhD, Timothy Hall, PhD, Brian Fowlkes, PhD, and William Roberts, MD.
Named a National Academy of Inventors Fellow and awarded the Li Ka Shing Endowed Professorship, Xu has dedicated her career to the development of the “the world’s first non-invasive autonomous robot.” She says that the high-precision therapy generates microbubbles to target tumors without any incisions. Using controlled cavitation (expansion/collapse of bubbles), histotripsy is also non-ionizing and non-thermal. This ultra high-intensity focused ultrasound (HIFU) technology was named using Greek words: “histo” meaning soft tissue and “tripsy” for mechanical breakdown.
Working with Xu on the clinical translation of the therapy, Mishal Mendiratta-Lala, MD, Professor of Radiology and interventionalist, says “while we know the use of histotripsy is good science, we’re further developing criteria to improve patient outcomes, such as setting treatment guidelines of ‘less than six lesions in the liver measuring no more than five centimeters in size’.”
Along with Xu (and other U-M researchers/authors), co-principal investigators and clinicians, Drs. Mendiratta-Lala and Neehar Parikh, MD, MS, Associate Professor of Internal Medicine in the Division of Gastroenterology, published the findings of their first histotripsy clinical trial in Radiology (Sept. 2024) entitled “#HOPE4LIVER Single-Arm Pivotal Trial for Histotripsy of Primary and Metastatic Liver Tumors” in which 40 patients with 44 tumors were treated.
“The goal of this initial trial was to “evaluate the safety and technical success of using this novel therapy specifically for the destruction of liver tumors,” says Dr. Parikh. “After each patient was treated with histotripsy, there was an immediate CT conducted, followed by a 30-day CT.
Dr. Mendiratta-Lala explained that these post-treatment endpoints were associated with no major adverse events, unlike other radiation and ablation modalities. “One of the benefits of utilizing histotripsy to target liver tumors is that the surrounding tissues and structures, including blood vessels and bile ducts, which are pervasive throughout the liver, are not damaged.” Generally, patients experience a relatively short recovery period with no pain associated with the procedure.
Sharing the story of his real-world experience with histotripsy is U-M patient, Matt Hendren, 51, a nurse and father of six children from Ypsilanti who was referred to the therapy by Grace Chen, MD, Professor, Division of Hematology & Oncology. “I experienced no significant complications from the procedure, just soreness for about 3-4 days post-op, mild throat discomfort from the double lumen ET tube, and a little bit of a fever,” says Mr. Hendren, who underwent therapy for his stage 4 colon cancer with liver metastases on May 28, 2024.
“I had four tumors, three in my right liver segments and one in my left. Prior to treatment, my circulating tumor DNA (ctDNA) was 307 ng/mL. Six weeks post-histotripsy treatment, it dropped to 0.13, and after completing nine rounds of FOLFOX chemotherapy, paired with localized hyperthermia, I received my first zero ctDNA result. I have now had two consecutive months of zero ctDNA, and my first PET scan in October 2024 showed no activity in my previous liver lesions. My recent MRI and CT scans taken in January of this year confirmed that I remain NED (No Evidence of Disease). I feel really great,” he says, “and I give high praise to what they’re doing at Michigan.”
More data including long term patient follow-up will be needed to fully understand the therapeutic potential of histotripsy for hepatic malignancy. Upcoming publications will include a safety assessment of the initial 230 treatments and a one-year update of clinical outcomes based on the #HOPE4LIVER study. In addition to its utility for primary and metastatic cancers of the liver, histotripsy is being investigated to treat other cancers (prostate cancer, melanoma, neuroblastoma, cholangiocarcinoma, renal cell carcinoma, pancreatic adenocarcinoma, osteosarcoma, and glioma), along with non-oncologic cardiovascular and neurological applications in the pre-clinical setting. U-M will continue to lead the way in exploring the many potential uses of this promising new therapeutic technology.
by Nikolas Charles
