Histotripsy: Current and Future Applications

Histotripsy and the #HOPE4LIVER Trial

Osman Ahmed, MD, University of Chicago Medicine, Illinois, shares insights about the use of histotripsy for treatment of patients with liver cancer. Dr Ahmed gives an overview of what histotripsy is and how the mechanism of action is different from other techniques within interventional oncology.

The #HOPE4LIVER trial is a first-in-human trial evaluating the safety and efficacy of histotripsy for primary or metastatic liver tumors. Dr Ahmed describes this trial and some future trials to be aware of as the data around histotripsy continues to develop.

Transcript:

Osman Ahmed, MD: Hi. My name is Osman or Oz Ahmed. I'm an interventional radiologist at the University of Chicago.

What is histotripsy?

Dr Ahmed: Histotripsy is a very new, exciting technology. We are currently using it to treat liver tumors. It's a way to use ultrasound, the way we normally use ultrasound to visualize parts of the body just like a pregnancy, a woman goes to get ultrasound. It's the same technology using ultrasound. However, it relies on ultrasound energy to create what's called cavitation, or bubbles, to help essentially eviscerate tumor or liquefy the tumor.

What are the practical methods for performing histotripsy?

Dr Ahmed: Probably the closest concept would be HIFU, or high intensity focus ultrasound. It's a type of focus ultrasound technology, but fundamentally it's very different in terms of the mechanism of action. It's relying more on the mechanical effect of ultrasound energy to create cavitation, or microbubbles, that essentially liquefy the tumor and eviscerate the tumor that way.

What are the pros and cons of this method?

Dr Ahmed: The pros are pretty great in terms of the fact that the technology is actually completely non-invasive. Nothing enters the skin, nothing breaks the skin. It's actually not even a sterile procedure for that reason.

It's non-thermal in its mechanism, so it doesn't rely on heat or cold energy to treat the tumor, which allows us to potentially treat tumors that are abutting critical structures like blood vessels and/or bile ducts. And it also doesn't involve the use of radiation, so it keeps the procedure safer in that sense.

The drawbacks of the technology are the drawbacks of any new technology that emerges in that we still don't really understand its role currently with respect to how it fits in the algorithm of treatment of tumors.

It is right now fairly limited in the types of tumors that it can treat. Primarily, that’s lesions that are subcostal in nature, in addition to tumors that are less than 3 cm. That is similar to other percutaneous ablation methods. And then going back to efficacy, it's unclear yet how well it works compared to more well-established technologies.

Are there any factors about a patient that would make them more suited for histotripsy?

Dr Ahmed: There's some technical limitations to the device at present. Obviously, this is rapidly evolving and probably will continue to improve. But for the most part, if you're trying to get a complete tumor treatment, we focus on lesions that are 3 cm or less. We talked about subcostal, so we have to be able to visualize the tumor from a subcostal approach because we don't want to get the bone from the ribs in the way to potentially obscure the ultrasound energy. And then the tumor has to be a certain depth from the abdominal wall as well. There’s sort of a sweet spot for the tumor.

But with that said if you can visualize the tumor with the ultrasound, from a subcostal approach, typically, then you can treat it.

Please describe the background and methods for the #HOPE4LIVER trial.

Dr Ahmed: The Hope for Liver trial was a trial to basically evaluate the use of histotripsy for the first time in humans within the United States, and also brought in data from Europe. The trial was sort of cancer-agnostic, meaning you could do primary liver cancer, or you could do metastatic liver cancer.

It was designed to sort of just evaluate the safety and efficacy of histotripsy because this is the first time it was being done in humans, and particularly in the United States. That data was generated and used to submit to the FDA for approval, which now the device does have FDA approval for use in America. And then the manuscript for the actual study is under review.

The readouts have started, I believe the data was presented at SPECTRUM as well as CIRSE. Hopefully the manuscript presentation will be published sooner than later. I would anticipate this year, hopefully.

Are there any other studies or trials evaluating histotripsy?

Dr Ahmed: The company has started Hope for Kidney, that is a very similar study to evaluate the safety and efficacy of histotripsy for renal cell carcinoma.

This is a platform technology, so I do think that the technology can and has already been applied to other tumor types, for example, and also other disease states. For example, even in my own lab that I work with our basic science team we've used it for treating blood clots or DVT [deep vein thrombosis].

What should practitioners know about histotripsy or this platform?

Dr Ahmed: The technology is very different than percutaneous ablation. With that said, I think right now it's current application is to lesions that we can conventionally think of for percutaneous ablation.

Typically for patients who would have oligometastatic disease and/or primary liver cancer, so anywhere between 1 and 3 lesions, less than 3 cm, there is a lot of excitement and enthusiasm around the concept of the abscopal effect. That’s obviously not scientifically proven, and its understanding in terms of safety and efficacy has not really borne out yet with clinical data. That’s probably a future application, right now, of this technology.

Is there anything else you’d like to add?

Dr Ahmed: Now that it's FDA approved, we'll probably start seeing a lot more data hopefully coming out, whether it's through investigator-initiated trials and/or just retrospective data, in terms of experience that people have.

As far as the technology goes, I think it's an evolving technology and its application and use, is still sort of yet to be determined. And I believe, over the next few months to years, we'll understand really where we can use this technology, both for liver cancer, but also outside of it as well.