Defining Histotripsy's Role in Cancer Care
As public interest grows, radiologists are weighing where the emerging technology may fit among established therapies
Rising cancer incidence is driving interest in less invasive treatments. Histotripsy, a noninvasive, US-based ablation technique recently cleared by the U.S. Food and Drug Administration (FDA) for select liver tumors, is drawing growing attention as radiologists assess its role alongside current treatment modalities.
First described by investigators at the University of Michigan, Ann Arbor, in the early 2000s, histotripsy derives its name from the Greek words histo (soft tissue) and tripsy (breakdown). Unlike thermal ablation such microwave, radiofrequency and cryo-ablation, histotripsy relies on mechanical tissue destruction.
“Histotripsy utilizes high‑amplitude, very short (microsecond) focused‑ultrasound pulses to generate a cavitation bubble cloud whose rapid expansion and collapse mechanically destroys target tumor tissue,” said Mina Makary, MD, an interventional radiologist in the Department of Radiology at The Ohio State University Wexner Medical Center in Columbus, and an early adopter of histotripsy technology.
The rapid expansion and collapse of these microbubbles mechanically disrupt cells, leaving acellular debris that is typically reabsorbed over several months.
This mechanism has drawn interest in histotripsy for its potential to improve precision and limit injury to surrounding structures. It is also being explored for patients who are ineligible for surgical resection or other locoregional treatment options.
From FDA Clearance to Clinical Evidence
In 2023, the FDA cleared the first histotripsy system for the treatment of liver tumors based on data from the multicenter HOPE4LIVER trial.
“The FDA‑reviewed clinical evidence was structured around safety and short‑term ablation performance goals,” Dr. Makary said. “Clinicians should interpret this clearance as regulatory confirmation of an FDA‑cleared capability to noninvasively destroy liver tumor tissue with a short‑term safety and technical‑success profile that met predefined goals. Long‑term efficacy and outcomes have not been evaluated.”
While the early‑phase THERESA trial and the multicenter HOPE4LIVER study demonstrated favorable safety and very short technical efficacy for tumors measuring approximately 3–4 cm, questions remain regarding scalability for multifocal or diffuse hepatic disease and long‑term outcomes such as progression free and overall survival.
“Further research is necessary to understand ideal parameters for treatment with the device, long‑term outcomes after treatment, and randomized controlled trials comparing histotripsy to other ablation modalities and surgical resection,” said Nathan Loudon, MD, an interventional radiology fellow at the University of Michigan and co-author of a Radiology: Imaging Cancer review on histotripsy.
Selecting Patients for an Emerging Therapy
At present, patient selection remains closely tied to clinical trial criteria. In HOPE4LIVER, eligible patients were identified as adults able to undergo general anesthesia with preserved liver function, adequate performance status and tumors measuring 3 cm or less. Lesions also had to be visible through a suitable acoustic window for US guidance.
“Histotripsy currently offers is a unique potential treatment option for patients who are not candidates for standard‑of‑care therapies,” Dr. Makary said, noting that candidacy is driven as much by exclusion factors as by inclusion.
Dr. Loudon said early technical constraints limited treatment to tumors in the lower portions of the liver. Newer device iterations and refined techniques have expanded this range, but visualization remains a prerequisite.
“The general principle is: if you can see it with the device’s ultrasound, you can treat it,” Dr. Loudon said.
However, efficacy may decline for larger or deeper tumors, as increasing tissue depth results in acoustic attenuation and beam aberration, compromising cavitation efficiency and targeting precision.
Respiratory motion introduces additional challenges in maintaining treatment accuracy, as precise focal alignment is required during specific phases of respiration to avoid collateral injury to surrounding tissues. These constraints are particularly relevant in anatomically complex regions such as the pancreas, where proximity to critical vascular and biliary structures further narrows safe treatment windows.
In addition, the fate and clinical implications of acellular tissue debris left in situ are still under investigation.
“A lot of great work remains to be done to figure out which tumor biologies are best suited to treatment with the device and whether the immunogenic properties of the modality seen in animal studies can be replicated on a predictable basis in humans,” Dr. Loudon said.
Charting Histotripsy's Clinical Role
As awareness of histotripsy grows, so does patient interest. Clinicians may increasingly need to clarify what regulatory approval does—and does not—signify, while managing explanations.
“Histotripsy decisions, like other cancer therapy choices, are typically made within a multidisciplinary tumor board setting, where clinicians weigh benefits, risks and alternatives, and clarify goals of care and discuss how the technology fits within the broader treatment paradigm,” Dr. Makary said.
The technology’s next phase will likely depend on continued technical refinement and research comparing its efficacy to established modalities using the known levels of evidence and the known oncologic metrics.
Multidisciplinary evaluation, clear discussion of evidence limitations and appropriate follow-up imaging remain essential as histotripsy’s clinical role continues to take shape.
“If a physician is practicing in an institution that has access to the device already at this early stage, they are in a prime position to carry out this research and contribute to the body of knowledge around the modality,” Dr. Loudon said. “Data are evolving, and I anticipate that in the coming years we will have a much better sense of histotripsy’s ideal place in therapy.”
For More Information
Access the Radiology: Imaging Cancer review, “Development of Histotripsy as a Local-Regional Liver Cancer Therapy: Preclinical to Clinical Translation.”
Read the Cancers review, “Histotripsy: Recent Advances, Clinical Applications, and Future Prospects.”
Read previous RSNA News stories on interventional radiology:
- Thyroid Sparing Cancer Care Moves Into Mainstream
- Minimally Invasive Procedure Effectively Treats Small Kidney Cancers
- Addressing the Interventional Radiology Shortage