Safety and Efficacy of Liver-Directed Radiotherapy in Combination With Lenvatinib for Hepatocelluar Carcinoma With Macroscopic Tumor Thrombosis

Abstract

BackgroundThis study aimed to compare the clinical outcomes of patients with hepatocellular carcinoma (HCC) and macroscopic tumor thrombosis who were treated with lenvatinib with or without combined liver-directed radiotherapy (LRT).MethodsFrom the institutional registry, we enrolled 82 patients diagnosed with HCC involving macroscopic tumor thrombosis and treated with lenvatinib monotherapy (non-LRT group, n = 54, 65.9%) or lenvatinib in combination with LRT (LRT group, n = 28, 34.1%). Patients were classified into the LRT group if LRT was performed within 8 weeks of lenvatinib initiation.ResultsDuring the median follow-up period of 5.4 (range 1.4 to 17.5) months, there was no significant difference between the two groups in terms of overall adverse events. Although there was no statistical difference between the two groups in terms of overall response rate (32.1% vs. 20.4%, p = 0.15), a significantly higher treatment response was observed in the LRT group in terms of intrahepatic tumor response (67.9% vs. 20.4%, p < 0.001). In the LRT group, there was a slight difference in overall survival compared to the non-LRT group (64.1% in the LRT group vs. 37.7% in the non-LRT group at 12 months, hazard ratio [HR], 0.54; 95% confidence interval [CI] 0.28–1.03; p = .06), although it did not reach a statistically significant level. However, progression-free survival (PFS, 67.2% in the LRT group vs. 35.0% in the non-LRT group at 6 months, HR 0.47; 95% CI 0.27–0.82; p = 0.008) and intrahepatic progression-free survival (IHPFS, 74.3% in the LRT group vs. 43.3% in the non-LRT group at 6 months, HR 0.45; 95% CI 0.25–0.81; p = 0.008) were significantly superior in the LRT group. This result was also reproduced in the multivariate analysis adjusted for α-fetoprotein, another significant prognostic factor in this study, and the well-known prognostic factors, namely the presence of main portal vein tumor thrombosis and albumin-bilirubin grade.ConclusionsThe combination of lenvatinib and LRT is relatively safe and effective in increasing the intrahepatic tumor response and improving PFS and IHPFS in patients with HCC and macroscopic tumor thrombosis.

Stereotactic Body Radiotherapy versus Lenvatinib for Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis: A Propensity Score Analysis

“…To date, there are fewer studies on lenvatinib for the treatment of HCC with PVTT. In a study by Yu et al [32], lenvatinib treatment of HCC patients with macroscopic tumor thrombosis had a 1-year OS rate of 37.7%. In our study, the 1-year OS rate for lenvatinib treatment of HCC with PVTT was 39.5%, similar to the result of the study by Yu.…”

Lenvatinib with or without stereotactic body radiotherapy for hepatocellular carcinoma with portal vein tumor thrombosis: a retrospective study

“…To our knowledge, this is the first clinical study comparing SBRT in combination with lenvatinib and lenvatinib alone for the treatment of HCC with PVTT. Recently, Yu et al [ 38 ] conducted a retrospective clinical study of liver-directed radiotherapy (LRT) in combination with lenvatinib versus lenvatinib alone for the treatment of HCC with macroscopic tumor thrombosis and extrahepatic metastases. Their study showed that during a median follow-up period of 5.4 months (1.4–17.5 months), the combination treatment group had significantly better PFS (67.2% vs. 35.0% at 6 months, p = 0.008) and IHPFS (74.3% vs. 43.3% at 6 months, p = 0.008) were significantly better than in the monotherapy group, but there was no statistically significant difference in overall response rate (32.1% vs. 20.4%, p = 0.15) and OS rate (64.1% vs. 37.7% at 12 months, p = 0.06).…”

Lenvatinib with or without Stereotactic Body Radiotherapy for Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis: a retrospective study

“…To our knowledge, this is the rst clinical study comparing SBRT in combination with lenvatinib and lenvatinib alone for the treatment of HCC with PVTT. Recently, Yu et al [37] conducted a retrospective clinical study of liver-directed radiotherapy (LRT) in combination with lenvatinib versus lenvatinib alone for the treatment of HCC with macroscopic tumor thrombosis and extrahepatic metastases. Their study showed that during a median follow-up period of 5.4 months (1.4 to 17.5 months), the combination treatment group had signi cantly better PFS (67.2% vs. 35.0% at 6 months, p = 0.008) and IHPFS (74.3% vs. 43.3% at 6 months, p = 0.008) were signi cantly better than in the monotherapy group, but there was no statistically signi cant difference in overall response rate (32.1% vs. 20.4%, p = 0.15) and OS rate (64.1% vs. 37.7% at 12 months, p = 0.06).…”