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Histotripsy and immunotherapy: first results of iFOCUS

Cancer Infection & Immunity

Researchers at UMC Utrecht have presented the first results of the iFOCUS study: the world’s first clinical trial combining histotripsy, the mechanical destruction of tumors using powerful sound waves, with immunotherapy in patients with metastatic cancer. The early findings are promising, though the researchers emphasize that this involves a small group of patients at an early stage of research.

Why this combination?

Immunotherapy with so-called checkpoint inhibitors are drugs that enable the body’s own immune system to attack cancer cells. In some patients with metastatic cancer, this treatment has shown promising results, keeping the disease under control for extended periods — or sometimes even achieving a cure. However, many types of cancer still do not respond to these drugs. These cancers are immunologically “cold”: they are not adequately recognized by the immune system, allowing them to evade immunotherapy.

Histotripsy may offer a key. In this technique, focused ultrasound waves mechanically destroy part of a tumor by vibrating the tissue apart. In doing so, tumor-specific proteins are released that can activate the immune system. Laboratory research and animal studies have shown that histotripsy can convert a “cold” tumor into a “warm,” immune-responsive tumor, resulting in enhanced effectiveness of immunotherapy. The iFOCUS study investigates for the first time whether the combination of immunotherapy and histotripsy also works in humans.

The study

The iFOCUS study is a phase 1 trial focused primarily on the safety, tolerability, and feasibility of the combined treatment. Patients with various forms of metastatic or inoperable cancer that are no longer responding to standard treatments receive up to four cycles of immunotherapy with ipilimumab and nivolumab, followed by nivolumab alone. Seven days after the first immunotherapy cycle, patients undergo a single histotripsy treatment session. The study is structured in two phases: a first group of six patients to assess safety, followed by a second group of eighteen patients. The study is registered in the Dutch trial registry (NL-OMON56837 / NCT06524570).

Portrait of Emma van Dijk

Emma van Dijk

First findings: safe and promising

The six patients in the first group have been treated and evaluated. Physician-researcher Emma van Dijk presented the results in April 2026 at the European Conference on Interventional Oncology (ECIO) in Basel.

The researchers emphasize that these are early, not yet published findings from a small group of patients, and that caution is warranted when drawing conclusions. The results are nonetheless encouraging: in all six patients, the histotripsy procedure was technically successful. No serious adverse events occurred that could be directly attributed to the histotripsy or to the combination of histotripsy with immunotherapy. The immune-related adverse events that did occur are comparable to what is known from immunotherapy alone, and none of the patients had to discontinue treatment early. In addition, the researchers observed signs of treatment response in multiple patients — a notable finding for a phase 1 safety study, in which the likelihood of treatment response is generally low.

“These are early results from a small group of patients, but they strengthen our confidence that we are on the right track. For the first time, we can show that this combination treatment is safe and that in some patients, a treatment effect is visible. That is promising — though we must remain cautious until we have more data.”

Portrait of Karijn Suijkerbuijk
Karijn Suijkerbuijk
Principal investigator iFOCUS study

Who is conducting this research?

The study is led by Karijn Suijkerbuijk, internist-oncologist and Professor of Immunotherapy of Solid Tumors at UMC Utrecht and Utrecht University. Her research group plays an internationally leading role in immuno-oncology: from mapping the side effects of immunotherapy to developing algorithms that predict which patients will respond to treatment. The iFOCUS study fits within her broader mission: making immunotherapy effective for a larger group of cancer patients.

Emma van Dijk is a physician-researcher, internist-oncologist in training, and doctoral candidate on this project. The other researchers involved — Manon Braat, Roel Deckers, Clemens Bos, and Chrit Moonen — are also affiliated with the Division of Imaging and Oncology at UMC Utrecht.

Funding

The iFOCUS study was made possible by donations from the Focused Ultrasound Foundation and the Schumacher-Kramer Foundation through the UMC Utrecht & Wilhelmina Children’s Hospital Foundation.

About the UMC Utrecht Cancer Center

The UMC Utrecht Cancer Center provides specialized care for patients with complex and rare forms of cancer, combining this with active scientific research. Immunotherapy has been part of clinical practice at UMC Utrecht for over ten years, both as a treatment and as a central research focus.

Support the iFOCUS research

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Frequently Asked Questions (FAQ)

No. The iFOCUS study is an early-phase clinical trial (phase 1). The primary goal is to determine whether the treatment is safe and feasible. Whether and when this combination treatment may become routinely available cannot be determined at this time. The second phase of the study, in which eighteen additional patients will be treated, is currently ongoing. Enrollment is still open for patients who have no other adequate treatment options and who have a tumor or metastasis located less than 3 cm beneath the skin. Physicians are welcome to contact the research team.

Histotripsy is a technique in which a highly focused beam of ultrasound waves is directed at a tumor. The sound waves generate tiny air bubbles within the tumor tissue. As these bubbles rapidly alternate between expanding and collapsing, the cancer cells are disrupted from within. Because the treatment is guided in real time by MRI-imaging, the surrounding healthy tissue can be spared. No surgery is required; the treatment can be performed as a day procedure.

Histotripsy mechanically destroys part of the tumor, releasing tumor-specific proteins that the immune system can recognize as alarm signals. Combined with checkpoint inhibitors, this may trigger a stronger immune response, including against metastases elsewhere in the body that were not directly treated. This so-called “abscopal effect” has been demonstrated in animal models and is one of the expectations being investigated in the iFOCUS study in humans.

HIFU (High Intensity Focused Ultrasound) is an umbrella term for treatments using focused ultrasound. The most common application destroys tissue through heating. Histotripsy works differently: it destroys tissue mechanically through the force of sound waves, while minimizing heat generation. This distinction is critical for the iFOCUS study: excessive heat can damage the structure of proteins released from the tumor, whereas those proteins must remain intact to activate the immune system.

Checkpoint inhibitors are immunotherapy drugs that remove a natural “brake” on the immune system. Cancer cells can exploit this braking mechanism to evade immune detection. By blocking this brake, immune cells can once again recognize and attack cancer cells. The iFOCUS study uses nivolumab and ipilimumab, both approved drugs already used as standard treatment for several types of cancer.

Immunotherapy works best in tumors where the immune system is already active, so-called “hot” tumors. In “cold” tumors, few immune cells are present around the tumor, meaning checkpoint inhibitors have little to no effect. Many common cancer types, including colorectal cancer, pancreatic cancer, breast cancer, and prostate cancer, are predominantly “cold.”

The study is being conducted exclusively at UMC Utrecht, which is the first and only hospital in the world to investigate this combination of treatment in humans.

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