High rate of complete histopathological response in hepatocellular carcinoma patients after combined transarterial chemoembolization and stereotactic body radiation therapy

Abstract

BACKGROUND Liver transplantation (LT) presents a curative treatment option in patients with early stage hepatocellular carcinoma (HCC) who are not eligible for resection or ablation therapy. Due to a risk of up 30% for waitlist drop-out upon tumor progression, bridging therapies are used to halt tumor growth. Transarterial chemoembolization (TACE) and less commonly stereotactic body radiation therapy (SBRT) or a combination of TACE and SBRT, are used as bridging therapies in LT. However, it remains unclear if one of those treatment options is superior. The analysis of explant livers after transplantation provides the unique opportunity to investigate treatment response by histopathology. AIM To analyze histopathological response to a combination of TACE and SBRT in HCC in comparison to TACE or SBRT alone. METHODS In this multicenter retrospective study, 27 patients who received liver transplantation for HCC were analyzed. Patients received either TACE or SBRT alone, or a combination of TACE and SBRT as bridging therapy to liver transplantation. Liver explants of all patients who received at least one TACE and/or SBRT were analyzed for the presence of residual vital tumor tissue by histopathology to assess differences in treatment response to bridging therapies. Statistical analysis was performed using Fisher-Freeman-Halton exact test, Kruskal-Wallis and Mann-Whitney- U tests. RESULTS Fourteen patients received TACE only, four patients SBRT only, and nine patients a combination therapy of TACE and SBRT. There were no significant differences between groups regarding age, sex, etiology of underlying liver disease or number and size of tumor lesions. Strikingly, analysis of liver explants revealed that almost all patients in the TACE and SBRT combination group (8/9, 89%) showed no residual vital tumor tissue by histopathology, whereas TACE or SBRT alone resulted in significantly lower rates of complete histopathological response (0/14, 0% and 1/4, 25%, respectively, P value < 0.001). CONCLUSION Our data suggests that a combination of TACE and SBRT increases the rate of complete histopathological response compared to TACE or SBRT alone in bridging to liver transplantation.

Locoregional Treatments for Bridging and Downstaging HCC to Liver Transplantation

“…The safety and effectiveness of the combination of TACE and SBRT has also been evaluated in the bridging scenario. The rate of complete necrosis in liver specimens was higher in the combination therapy group (8 out of 9 patients, 89%) with respect to the TACE (0 of 14 patients, 0%) and SBRT (1 of 4 patients, 25%) groups [ 89 ]. The low sample size and retrospective nature of the study do not allow definitive conclusions to be drawn about the role of this combination therapy, which needs to be investigated in further studies.…”

Comparison of the Treatment Response of Drug-Eluting Bead Transarterial Chemoembolization and Conventional Transarterial Chemoembolization in Patients With Hepatocellular Carcinoma

“…TACE is the most widely used method. In SIRT, yttrium-90 microspheres are infused intra-arterially for radioembolization [ 13 , 14 ].…”

Bridge Therapy before Liver Transplant for Advanced Hepatocellular Carcinoma

“…Then, it was concluded that SBRT is a good option as an alternative to conventional therapies [ 60 ]. Bauer et al published a multi-center study in 2021 [ 61 ]. They analyzed the microscopic response to TACE and SBRT combined therapy in comparison to TACE or SBRT alone for the treatment of HCC.…”

“…Nevertheless, TACE or SBRT as a single approach presented lower rates of histopathologic CR (0% and 25%, respectively; p < 0.001). These data revealed that combined TACE and SBRT improve the outcomes in bridging to OLT [ 61 ].…”