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MedStar Health Research Scholar Alexander Kim, MD recently presented his preliminary work on improving patient outcomes after liver directed therapies at the Research Scholars Capstone event. His two research studies were focused on the use of radioembolization and patient outcomes. Radioembolization is a type of intra-arterial therapy wherein radiation particles are infused from the hepatic artery to treat liver cancers. Previous research has demonstrated that radioembolization leads to high rates of local tumor response rates. However, randomized trials of radioembolization in various tumor types have not led to improve patient overall survival.
The objective for the first study was to identify a liver function test which could improve both patient selection criteria and define liver toxicity better than the current standard. A secondary goal was to identify methods to improve particle delivery to tumor and reduce particle delivery to normal liver which would improve disease response and reduce liver toxicity. The most commonly used parameter when assessing patients for radioembolization in clinical practice is the total bilirubin level. It is common for radiologists to use a total bilirubin level of 2 as the cutoff to determine treatment eligibility.
The study recruited 15 patients who were being considered for radioembolization. The patients underwent Quantitative Liver Spleen Scan (QLSS) and Perfused Hepatic Mass (PHM) values were correlated with the total bilirubin level and other indicators of liver function used in various clinical situations including Albumin, MELD, the ALBI score/grade, and Child Pugh Score (CPS). The study results found there was a poor correlation between PHM and all parameters except for the ALBI score, which was a moderate correlation. To conclude, even though total bilirubin level is often used to determine patient eligibility for radioembolization, it appears to be a poor measure of liver function in patients being considered for liver-directed therapy.
The objective of the second study was to identify a method which would allow for improved radiation targeting to tumor and sparing of the background liver. The goal was to improve treatment response rates but also reduce liver functional impairment.
The rationale for radioembolization and other intra-arterial therapies is dependent on the unique blood flow of the liver. However, for patient who develop liver cancers, studies have shown that over 90% of the tumor blood flow is arterial in origin. The standard method of performing radioembolization is to deliver radiation particles through a standard microcatheter. However, a newer type of catheter has recently been introduced in the market. These catheters have been demonstrated to alter the blood pressure in the hepatic artery.
To test Dr. Kim’s hypothesis, the research team used an animal model (woodchuck HCC) to perform a pathologic assessment of particle distribution. The woodchuck is large enough to allow for the performance of arterial catheterization. For this study, three woodchucks underwent embolization (two using the pressure altering catheter (PAC) and one with a standard microcatheter). After embolization, the woodchucks were sacrificed and pathologic assessment of the liver was performed where particles in tumor and background liver were manually counted.
The study results found that more particles appear to be delivered with the use of the pressure altering catheter compared to the standard catheters. The tumor to normal particle distribution ratio appears to overlap between the two catheter types. However, there appears to be a much greater particle density in tumors in the animals embolized with the pressure altering catheters. To conclude, when comparing particle distribution in the central half to the peripheral half of the tumor, there is a much greater ratio of particle deposition in the central half of the tumor, suggesting that the pressure altering catheter allows for deeper penetration of the infused particles.
For future research, the research team has a prospective study designed with partial funding secured in hopes to follow liver function prospectively, before and after treatment with radioembolization. The long-term goal is to identify a better measure of liver function and improved tumor delivery to perform a clinical study to test their overarching hypothesis.
This research was presented as part of the MedStar Health Teaching and Research Scholars Capstone event, which culminates both the two-year programs.