A first-in-human clinical trial shows microbubbles augments radiation in liver cancer patients

December 15, 2020

PHILADELPHIA - Primary liver cancer is on the rise worldwide, largely due to an increase in hepatitis C infections and chronic liver disease. Liver cancer is also hard to treat - it kills 750,000 people a year worldwide, making it the second deadliest type of cancer behind lung cancer. Current treatments include a targeted radiation therapy delivered with the help of radiation-emitting glass beads. New research shows that this treatment can be augmented by infusing microbubbles - small gas bubbles surrounded by a lipid shell - into the liver, and popping those bubbles by ultrasound, in a first-in-human pilot clinical trial of the combination. The findings of this study were published in Radiology on December 8th.

"This approach has shown to be effective in preclinical studies using animal models of other 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."

About 15-25% of patients with advanced disease are recommended a treatment called trans-arterial radioembolization, whereby radioactive glass beads are inserted into blood vessels the liver, and the radiation emitted provides a therapeutic dose to the tumor, destroying it. However, the extent to which the radiation can penetrate liver tissue is limited, and tumor response is highly dependent on distance from the radioactive beads. By combining microbubbles with TARE, the synergistic approach reduces the dose of radiation needed to kill blood vessels in the tumor and increases the effectiveness of treatment.

"The microbubbles themselves are found in commercially available ultrasound contrast agents," says Colette Shaw, MD, associate professor and interventional radiologist, and the lead clinical author of the study. "The procedure to get the microbubbles into the tumor involves similar techniques used to access blood vessels."

When the microbubbles are hit with the 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 the blood vessels of the tumors, making them more sensitive to radiation. By targeting the ultrasound to exactly where the tumors are, the researchers can burst or destroy the bubbles right where the radiation beads are and achieve highly localized sensitization

The pilot study enrolled 28 patients who were randomly assigned to two treatment groups - trans-arterial radioembolization alone (TARE) or radioembolization and ultrasound-triggered destruction of microbubbles (TARE+UTMD). The team first evaluated the safety profile of the microbubbles - they observed no changes in vital signs like body temperature, blood pressure, and heart rate in patients receiving UTMD. Importantly, UTMD did not compromise liver function, and there were no additional side effects of the combined approach.

The researchers looked at 10 tumors in the TARE only group, and 15 tumors in the TARE+UTMD group, and evaluated tumor response to each treatment. 93% of tumors showed partial to complete response to the TARE+UTMD approach, while only 50% showed a response in the TARE alone group.

The team also found that patients receiving the combined therapy were also more likely to receive a liver transplant, which offers the best chance for long term survival for patients with cirrhosis and liver cancer. These patients also lived longer, and required fewer retreatments compared to those receiving TARE alone.

"Even at this early stage, we've been able to show a significant improvement in tumor outcomes with this combined therapy," says Dr. Shaw. "Looking ahead, we are enrolling more patients to demonstrate key benchmarks in the promise of this approach."

"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. The bubbles themselves can also be engineered to deliver chemotherapy or oxygen as they burst. This is really the tip of the iceberg."

This work was supported by NIH R01 CA238241. The ultrasound scanner used in this study was provided by Siemens Healthineers for research purposes. The authors report no conflict of interest.
By Karuna Meda

Article Reference: John R. Eisenbrey, Flemming Forsberg, Corinne E. Wessner, Lauren J. Delaney, Kristen Bradigan, Sriharsha Gummadi, Mohamed Tantawi, Andrej Lyshchik, Patrick O'Kane, Ji-Bin Liu, Charles Intenzo, Jesse Civan, Warren Maley, Scott W. Keith, Kevin Anton, Allison Tan, Amanda Smolock, Susan Shamimi-Noori Colette M. Shaw, "Ultrasound-Triggered Microbubble Destruction for Augmenting Hepatocellular Carcinoma Response to Transarterial Radioembolization: A Randomized Pilot Clinical Trial," Radiology, 2020

Media Contact:
Karuna Meda,

Thomas Jefferson University

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.