AUTHOR=Yu Jeong Il , Kang Wonseok , Yoo Gyu Sang , Goh Myung Ji , Sinn Dong Hyun , Gwak Geum-Youn , Paik Yong-Han , Choi Moon Seok , Lee Joon Hyeok , Koh Kwang Cheol , Paik Seung Woon , Hong Jung Yong , Lim Ho Yeong , Park Boram , Park Hee Chul TITLE=Safety and Efficacy of Liver-Directed Radiotherapy in Combination With Lenvatinib for Hepatocelluar Carcinoma With Macroscopic Tumor Thrombosis JOURNAL=Frontiers in Oncology VOLUME=12 YEAR=2022 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.888755 DOI=10.3389/fonc.2022.888755 ISSN=2234-943X ABSTRACT=Background

This 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).

Methods

From 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.

Results

During 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.

Conclusions

The 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.