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Microbubble Therapy Offers Hope to Patients with Liver Cancer

A first-in-human clinical trial shows that microbubbles enhances the effectiveness of radiation, reducing tumor growth and improving patient survival.

After giving birth to a healthy baby boy and recovering in the hospital, Marilou Orgasan suddenly felt dizzy, almost falling on her way to the bathroom. A nurse for 51 years, Marilou suspected it must be her hemoglobin. Sure enough, when the doctors checked, it had fallen dangerously low and she was immediately given a blood transfusion. A month later, Marilou caught her reflection in the mirror, and noticed her eyes were yellow. It would take a number of doctors’ visits, tests, and 28 years for her to be diagnosed and receive treatment for Hepatitis C. But the damage had been done. In October 2017, she went to the hospital suffering from a gallbladder attack but during surgery, the doctors found cancer in her liver.

“It was a blessing in disguise,” says Marilou. “The doctors told me my liver enzymes were so high, my liver was on the brink of failing.”

Three years later, Marilou is not only cancer-free, she has a new liver. This was made possible by a new treatment Jefferson researchers offered to Marilou as part of a clinical trial, the very promising results of which published this week.

Marilou Orgasan, RN, pictured here with her granddaughter, while receiving treatment during the trial. She responded well, and went on to get a liver transplant last fall at Jefferson Health.

As part of the trial, funded in part by Sidney Kimmel Cancer – Jefferson Health (SKCC), Marilou received an infusion of microbubbles that were then popped using ultrasound directed at her liver. Microbubbles are gas-filled bubbles surrounded by a solid shell, and are used in ultrasound imaging. Scientists, including those at SKCC, began exploring their use in cancer treatment and found that when the microbubbles are hit with an ultrasound wave, they start to vibrate and if the wave is strong enough, they burst. The sheer energy of these tiny explosions causes physical and chemical damage to tumors, making them more sensitive to other treatments like radiation and chemotherapy. In fact, Jefferson researchers had previously found that bursting microbubbles made breast tumors three times more sensitive to radiation therapy.

“Our previous study and others like it were done using animal models to test this approach in treating solid tumors like bladder, prostate, and breast cancer,” says John Eisenbrey, PhD, associate professor of radiology and lead author of the study. “This is the first work to demonstrate this approach is safe and shows promise in humans with liver cancer, which is very exciting.”

Many patients with advanced liver cancer are recommended a treatment called trans-arterial radioembolization, whereby radioactive glass beads are placed in the blood vessels of the liver, and the radiation emitted destroys cancer cells. By combining microbubbles with radiation beads and targeting the ultrasound to exactly where the tumors are, the researchers can achieve sensitization exactly where it’s needed.

“Even at this early stage, we’ve been able to show a significant improvement in tumor outcomes with this synergistic therapy,” says Colette Shaw, MD, associate professor and interventional radiologist, and the lead clinical author of the study. “90% of tumors responded to this combined treatment, patients lived longer, and they were more likely to be eligible for a liver transplant, which offers the best chance for long term survival for patients with cirrhosis and liver cancer.”

Marilou is one of those patients who responded very well to this treatment and was a candidate for a new liver. Almost exactly two years after her diagnosis, she underwent a liver transplant in September 2019 at Jefferson Health with Adam S. Bodzin, MD.

For Marilou, the transplant, a major surgery, has come with its own set of challenges. “I lost a lot of weight over the course of my illness and the donor liver turned out to be a bit bigger for my body,” she describes. “I no longer have my Coca-cola bottle figure. Oh well!”

Ultimately, Marilou is grateful for this second lease on life. “I’m so happy I took part in the trial and that I responded well to the microbubbles,” she says. “I think this will give hope to other patients like me.”

“Our findings are really setting the stage for a whole range of studies to be done in humans,” says Dr. Eisenbrey. “This approach could be effective in treating metastatic liver tumors, but also other types of primary cancer. This is really the tip of the iceberg.”

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