NewYork-Presbyterian and Weill Cornell Medicine is now offering histotripsy, a promising noninvasive technology that uses sound waves to obliterate cancerous liver tumors. Approved by the U.S. Food & Drug Administration last November, this technology provides significant benefits over other methods of removing or eliminating tumors in the liver, such as surgery, ablation, and embolization.
“This is a disruptive technology that is significantly different from the standard of care today,” says Juan P. Rocca, MD, MHA, surgical director for the NewYork-Presbyterian and Weill Cornell Medicine Liver Cancer Program, which is one of just a few centers around the country to now offer histotripsy. “There are multiple potential advantages to this technology, and we’re very excited to have it.”
Histotripsy uses a wand outside the body to deliver focused ultrasound pulses, precisely targeting and destroying liver tissue containing tumors without the need for incisions. The sound waves generate controlled acoustic cavitation in a millimetric space, creating micro-bubbles that rapidly expand and collapse, producing mechanical forces that break down the tissue at the cellular level, leading to its destruction. Unlike heat or radiation, the mechanical forces from cavitation destroy the cells within the tissue, preserving surrounding scaffolding structures (predominant in collagen), like blood vessels, lymphatics or bile ducts. The acellular liquid residue is eventually reabsorbed by the lymphatic system, potentially improving the ability of the immune system to recognize tumoral antigens.
A multicenter international study involving 44 patients led to the technology’s approval by the FDA to treat liver tumors in the clinical setting. “The overall efficacy in terms of targeting and destroying tumors at 30 days follow-up was 95%,” says Dr. Rocca. “Serious adverse events occurred only in three of the patients.”
This is a disruptive technology that is significantly different from the standard of care today. There are multiple potential advantages to this technology, and we’re very excited to have it.
— Dr. Juan Rocca
Significant Advantages
According to Dr. Rocca, there are several significant advantages to this tumor-targeting technology. As a noninvasive tool for destroying liver tumors, histotripsy may expand access to treatment to frailer cancer patients, such as those unable to withstand harsher treatments like surgery or other invasive interventions to the liver.
Histotripsy has also been shown to facilitate an immune reaction, which may magnify the response to treatment, says Dr. Rocca. Research with other local treatment modalities including radiation shows that by breaking down cell walls, expose otherwise hidden tumor antigens that activate the body’s defense system against tumors elsewhere that were not the direct target of local therapy, leading to their shrinkage—called the abscopal effect. The treated tumor can become a kind of vaccine against the other tumors, and even synergize with other medications like chemotherapy and/or immunotherapy.
“By only destroying tissue cells, histotripsy allows for the regeneration of the tissue there, which is an important goal in liver surgery,” says Dr. Rocca. “We like to preserve as much liver tissue as we can because it allows us to leave enough liver tissue to treat again if the cancer comes back.”
Multidisciplinary Approach to the Implementation of Histotripsy
At NewYork-Presbyterian and Weill Cornell Medicine, comprehensive liver cancer care results from close multi-disciplinary collaboration. The Chief of Liver Transplantation and Hepatobiliary Surgery is Benjamin Samstein, MD. Additional providers of histotripsy include Adam Talenfeld, MD, MS; Benjamin May, MD; and Brian Currie, MD from the division of interventional radiology. Alana Nguyen, MD, PhD, and Anthony Choi, MD, champion the histotripsy program in medical oncology and hepatology, respectively.
The implementation of histotripsy for clinical use and research follows the same philosophy. A core multidisciplinary team is tasked with the creation of a clinical protocol for the indications of histotripsy in a context of comprehensive cancer care as well as research studies to generate evidence to support current and expanded indications.
The Research Agenda
Although histotripsy has the potential to be a game changer for treating malignant tumors in the liver, much work needs to be done to fulfill its promise. “Now that this is in clinical use, we can start collecting data about how it compares to the other interventions that currently make the standard of care in cancer affecting the liver,” says Dr. Rocca. “We’re trying to create enough research around it to validate its application in what we do every day.”
NewYork-Presbyterian and Weill Cornell Medicine are participating in a study to collect data on all patients that receive histotripsy around the country to compare their results to other treatments. These patients will be followed for five years. So far, about 200 patients have been treated nationally with histotripsy.
“We're also crafting our own studies addressing different benefits of the technology,” says Dr. Rocca. In one Weill Cornell Medicine study, researchers will compare tumors treated with histotripsy with those not treated.
“If patients have two tumors in the liver, we're going to treat one with histotripsy and not treat the other one,” Dr. Rocca says. “Then we're going to remove both tumors and look at the differences. In the tumor treated with histotripsy, we’ll analyze the lysate for tumor viability. And we’ll also see if there's any immunologic response around in the non-treated tumor.”
Another study will investigate whether histotripsy has a synergistic effect with immunotherapy in the treatment of colorectal cancer patients with metastases in the liver, compared to radiation or other treatments. “This is a trial to specifically investigate the abscopal effect, or immunologic synergy, in patients who are receiving immunotherapy for colorectal cancer,” says Dr. Rocca.
A third trial will explore the use of histotripsy as a bridge-to-transplant technique. “Patients with liver cancer who are on the organ transplant wait list typically receive local regional treatments to keep the tumor at bay, like ablation, chemoembolization, radioembolization, or even radiation, while they are waiting for the transplant,” says Dr. Rocca. “We want to investigate the effect of histotripsy for this purpose.”
Treatment Protocols
Not every patient with liver tumors is currently eligible for histotripsy and the long-term outcomes as part of a comprehensive plan of cancer care are yet to be determined. An important message to prospective patients seeking this treatment is that they should not dismiss or abandon treatments within the current standard of care. “If treating liver lesions with histotripsy can potentially benefit the patient without interfering with the overall oncologic treatment plan, that's the patient we would like to consider ideal to treat during this initial phase,” says Dr. Rocca.
We are incorporating this tool as part of the whole spectrum of treatment options for liver cancer. We can offer everything from the least invasive approach to liver transplant to treat a patients’ cancer.
— Dr. Juan Rocca
A wide range of minimally invasive, ambulatory procedures exist ranging from ablation (using a needle to deliver energy to destroy tumors) or embolization (using catheters and wires to block blood flow or deliver therapy to tumors) that could also be offered by NewYork-Presbyterian’s multidisciplinary team should the patient not be eligible for histotripsy.
Patient selection may also depend on whether the sound waves can be safely delivered without damaging adjacent tissues or other organs. The size, number and location of the lesions are also factored into the feasibility. This is determined with help from simulation software and a specially-tailored screening ultrasound exam.
“The simulator will move the beam like it does in real life and give us the right angle to hit the target,” says Dr. Rocca. “We can see if the ribs or the stomach or some other organ, for example, is getting in the way. Those structures may decrease the energy that is being delivered by the beam or, depending on where the conversion point is, may cause an injury to the other organs.”
Performed by either hepatobiliary surgeons or interventional radiologists, these procedures are done in a specialized area that harnesses advanced confirmation imaging to further ensure that the novel therapy is delivered safely and effectively.
A Suite of Cancer Services
The technology adds to a growing repertoire of multidisciplinary therapies offered by the Liver Cancer Program. According to Dr. Rocca, the breadth of services sets NewYork-Presbyterian apart from other local and regional institutions.
“We are incorporating this tool as part of the whole spectrum of treatment options for liver cancer,” says Dr. Rocca. “We can offer everything from the least invasive approach to liver transplant to treat a patients’ cancer. That makes a difference to patients because we are not boxing them in to any one treatment. We can offer them what is right for them.”
