Improving TARE of Liver Cancers Using Ultrasound-Triggered Microbubble Destruction
Tuesday, October 24, 2023
1:00 PM-3:00 PM
BIOMED PhD Research Proposal
Title:
Improving Transarterial Radioembolization (TARE) of Liver Cancers Using Ultrasound-Triggered Microbubble Destruction
Speaker:
Corinne Wessner, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University
Advisors:
Margaret Wheatley, PhD
John M. Reid Professor
School of Biomedical Engineering, Science and Health Systems
Drexel University
John R. Eisenbrey, PhD
Associate Professor
Department of Radiology
Thomas Jefferson University
Details:
Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) account for roughly 80% and 20% of all primary liver cancers, respectively. Additionally, liver metastasis is more common than primary liver cancers, with cancer originating elsewhere in the body and traveling to the liver. The preferred curative treatment for these tumors is surgical resection or liver transplantation. Unfortunately, most patients are not eligible for these treatment options due to tumor burden, extrahepatic disease, or poor medical conditions. Locoregional therapies such as transarterial radioembolization (TARE) are essential in managing disease in patients with liver tumors. TARE is performed in patients with unresectable tumors and preserved liver function. TARE is comprised of small glass beads encapsulating the radioisotope yttrium-90 (Y90). These glass beads are delivered to the liver tumor. Although Y90-TARE has been proven effective for downstaging disease, the treatment response after Y90-TARE is between 25-70% using modified response evaluation criteria in solid tumors (mRECIST), highlighting the need for improvements in treatment response.
Traditionally, treatment efficacy for Y90-TARE is determined by a CT or MRI scan 2-6 months post-treatment. Patients often have to wait 4-6 months to conclusively determine if the treatment is effective. An imaging technique that could be performed earlier than a CT or MRI is contrast-enhanced ultrasound (CEUS). CEUS uses small gas filled ultrasound contrast agents (UCA) (1-8 µm in diameter) and has improved temporal resolution with the capability to image in real time without ionizing radiation.
A unique characteristic of a UCA is its ability to generate nonlinear responses at sufficient pressures. UCAs undergo oscillations, and at higher pressures produce bioeffects via inertial or stable cavitation. Cavitation-related bioeffects have been shown to produce endothelial cell apoptosis via a ceramide-mediated pathway. Endothelial cells are susceptible to stress, and when activated by ultrasound-triggered microbubble destructions (UTMD), this destruction can mechanically perturb cell membranes of the tumor endothelial cells. This stress within the tumor vasculature leads to the upregulation of ceramide, leading to endothelial cell apoptosis up to 8 Gy. Consequently, one way to improve the therapeutic response in patients that receive Y90-TARE is to perform UTMD to increase the ceramide-induced endothelial cell apoptosis.
We hypothesize that incorporating UTMD in patients receiving Y90-TARE may act as both a radiosensitizer to enhance treatment efficacy and an imaging method for identifying treatment response. This will be evaluated in two prospective clinical trials. In Specific Aim 1, I plan to characterize the ability of localized UTMD to improve HCC response to Y90-TARE. In Specific Aim 2, I plan to determine if dynamic CEUS parametric imaging predicts treatment response earlier than the standard-of-care (2-6 month CT/MRI) by evaluating tumor vascularity parameters. Finally, in specific aim 3, I will be incorporating Y90-TARE in non-HCC liver tumors to characterize the safety and preliminary efficacy of localized quantitative volumetric UTMD to improve response to Y90-TARE. Our scientific hypothesis is that UTMD is a safe technology that will sensitize liver tumors to Y90-TARE radiation treatment.
Contact Information
Natalia Broz
njb33@drexel.edu