News | Radiation Therapy | December 16, 2020

A First-in-human Clinical Trial Shows Microbubbles Augments Radiation in Liver Cancer Patients

Bursting gas-filled microbubbles using ultrasound waves sensitizes tumors to targeted radiation, reducing tumor growth and improving overall survival after treatment

Primary liver cancer is on the rise worldwide, largely due to an increase in hepatitis C infections and chronic liver disease

Getty Images

December 16, 2020 — 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," said John Eisenbrey, Ph.D., 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," said Colette Shaw, M.D., 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," said 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," said 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.

For more information: www.jefferson.edu

Related Content

The key trends Clinicians reviewing a COVID-19 patient's lung CT that reveals the severity of COVID-caused pneumonia. The impact of COVID on radiology was a major, over arching trend at  the 2020 Radiological Society of North America (RSNA) meeting. Getty Imagesbserved at 2020 Radiological Society of North America (RSNA) meeting all focused around COVID-19 (SARS-CoV-2) and the impact it has had on radiology. #RSNA #RSNA20 #RSNA2020

Clinicians reviewing a COVID-19 patient's lung CT that reveals the severity of COVID-caused pneumonia. The impact of COVID on radiology was a major, over arching trend at  the 2020 Radiological Society of North America (RSNA) meeting. Getty Images

Feature | RSNA | January 20, 2021 | By Melinda Taschetta-Millane and Dave Fornell
Radiologists have recently taken on the role of activists and are tackling pressing issues in healthcare, including breast density

Getty Images

Feature | Women's Health | January 20, 2021 | By Fazila Seker, Ph.D.
Radiologists — who have long been professionals in the metaphorical and literal back-rooms of healthcare — have recen
MRI Targeted biopsy is performed using cognitive fusion more easily with anatomical guidance based on the radiology report. MRI targets can be identified quickly in real-time along with micro-ultrasound targets, which may have been missed on MRI.

MRI Targeted biopsy is performed using cognitive fusion more easily with anatomical guidance based on the radiology report. MRI targets can be identified quickly in real-time along with micro-ultrasound targets, which may have been missed on MRI. Image courtesy of Exact Imaging

Feature | Prostate Cancer | January 20, 2021 | By Brian Wodlinger, Ph.D.
Historically when a patient had an elevated PSA (prostate specific antigen) test their urologist would take the next
An interview with Eric Liederman, M.D., MPH, Director of Medical Informatics for The Permanente Medical Group, in Kaiser Permanente’s Northern California Region, on the explosion of telemedicine in the COVID-19 era

Getty Images

Feature | Radiology Business | January 20, 2021 | By Melinda Taschetta-Millane
Vendor neutral archives enable a single, central location to store large volumes of radiology data, but now need to be able to house data from dozens of other departments with a wide array of data formats. This article originally ran as an introduction to the Vendor Neutral Archives comparison chart.
Feature | Vendor Neutral Archive (VNA) | January 20, 2021 | By Dave Fornell
Most radiologists and clinicians are not trained as...
According to a new research report1 on the contrast media injectors published by MarketsandMarkets, the market was estimated to be $1.3 billion in 2020 and projected to reach $1.9 billion by 2025, at a compound annual growth rate (CAGR) of 7.4 percent over 2020-2025.

The ulrich CTmotion

Feature | Contrast Media Injectors | January 20, 2021 | By Melinda Taschetta-Millane
According to a new...
The exceptionally high dose rate of the FLASH Beam is 3,000 times higher than normal therapy treatment (300 Gray per second vs. 0.1 Gray per second, Gray being a standard unit measuring absorbed radiation). Instead of treatment over 20 seconds, an entire treatment is completed in 6 milliseconds, giving the therapy its nickname, "FLASH." Image courtesy of Brian Pogue, PhD

The exceptionally high dose rate of the FLASH Beam is 3,000 times higher than normal therapy treatment (300 Gray per second vs. 0.1 Gray per second, Gray being a standard unit measuring absorbed radiation). Instead of treatment over 20 seconds, an entire treatment is completed in 6 milliseconds, giving the therapy its nickname, "FLASH." Image courtesy of Brian Pogue, PhD

News | Linear Accelerators | January 20, 2021
January 20, 2021 — A joint team of researchers from Radiation Oncology at Dartmouth's and...
Previously approved by FDA in the USA, MyLab X8 expands the reach of the MyLab Ultrasound Product Line with a fully featured premium imaging solution, integrating the latest technologies and delivering superior image quality without compromising workflow or efficiency.
News | Ultrasound Imaging | January 20, 2021
January 20, 2021 — Esaote North America announces that the...