A recent study published in Nature has demonstrated that 5-Fluorouracil drug-eluting beads transarterial chemoembolization (5-Fu-DEB-TACE) using CalliSpheres microspheres improves tumor response and progression-free survival (PFS) compared to conventional TACE (5-Fu-cTACE) in patients with unresectable hepatocellular carcinoma (HCC). The research highlights the potential of DEB-TACE with CalliSpheres to enhance local tumor control and reduce recurrence risk.
The study compared the efficacy and safety of 5-Fu-DEB-TACE and 5-Fu-cTACE in treating unresectable HCC. Key findings included a better tumor response and longer PFS in the 5-Fu-DEB-TACE group. Specifically, the objective response rate (ORR) and disease control rate (DCR) at 1, 3, and 6 months post-treatment were significantly higher in the 5-Fu-DEB-TACE group compared to the 5-Fu-cTACE group. The study also identified the Barcelona Clinic Liver Cancer (BCLC) stage, Model for End-Stage Liver Disease (MELD) score, and ascites as independent predictive factors for PFS.
Efficacy of 5-Fu-DEB-TACE
The improved outcomes with 5-Fu-DEB-TACE are attributed to the sustained drug release and enhanced embolization achieved by CalliSpheres. These microspheres, with a diameter of 100–300 μm, can deliver chemotherapeutic drugs directly to the tumor site, ensuring a more uniform and sustained drug release. This property allows for a longer duration of drug action, improving local tumor control and reducing the risk of recurrence. The ability of CalliSpheres to embolize to the periphery of tumor blood vessels also leads to more extensive tumor necrosis.
The study revealed that the efficacy of both treatment methods was superior to that of previous methods, potentially due to increasing detection rates of HCC and the inclusion of fewer patients in the terminal stage. The infusion of 5-fluorouracil into the hepatic artery before embolization may also contribute to the improved outcomes.
Progression-Free Survival Analysis
The study addressed the controversy regarding the superiority of DEB-TACE over cTACE in improving PFS for HCC patients. The results demonstrated that the 5-Fu-DEB-TACE group had a longer median PFS compared to the 5-Fu-cTACE group. Multivariate Cox proportional hazards regression model further supported this finding, indicating that 5-Fu-DEB-TACE was an independent predictor of longer PFS.
Subgroup Analysis and Personalized Treatment
The researchers conducted a subgroup analysis based on liver function and tumor burden, revealing that 5-Fu-DEB-TACE treatment demonstrated superior PFS, ORR, and DCR compared to 5-Fu-cTACE in cases with lower tumor burden and better liver function. However, when tumor burden was higher and liver function poorer, the efficacy of TACE was reduced, underscoring the importance of personalized treatment plans.
Safety Profile
The safety of 5-Fu-DEB-TACE using CalliSpheres was found to be comparable to that of 5-Fu-cTACE. Postoperative complications mainly manifested as embolism syndrome, primarily at grades I-II. While the 5-Fu-DEB-TACE group had a higher incidence of abdominal pain, no significant differences were observed in other symptoms. The 5-Fu-DEB-TACE group also had relatively lower transaminase levels, possibly due to the different drug release mechanisms of CalliSpheres, causing less damage to the surrounding normal liver tissue during embolization.
Microsphere Size Considerations
The study used microspheres with a size range of 100–300 μm, considering factors such as drug loading, release efficiency, and embolization capabilities. While smaller microspheres may lead to a larger area of tumor necrosis, excessively small microspheres can result in incomplete or ectopic embolization and impact drug loading and release.
Study Limitations
The authors noted several limitations, including an insufficient follow-up period, challenges in accurately assessing tumor response due to iodized oil deposition and irregular necrosis, and a limited sample size from a single center. Future studies with larger cohorts and longer follow-up periods are needed to validate these findings.
