Adjuvant Sorafenib Following Radiofrequency Ablation for Early-Stage Recurrent Hepatocellular Carcinoma With Microvascular Invasion at the Initial Hepatectomy

Meng-Chao Wei; Yao-Jun Zhang; Min-Shan Chen; Yong Chen; Wan-Yee Lau; Zhen-Wei Peng

doi:10.3389/fonc.2022.868429

Adjuvant Sorafenib Following Radiofrequency Ablation for Early-Stage Recurrent Hepatocellular Carcinoma With Microvascular Invasion at the Initial Hepatectomy

Front Oncol. 2022 Jun 23:12:868429. doi: 10.3389/fonc.2022.868429. eCollection 2022.

Authors

Meng-Chao Wei^{1

2}, Yao-Jun Zhang¹, Min-Shan Chen^{1

3}, Yong Chen⁴, Wan-Yee Lau⁵, Zhen-Wei Peng^{4

6}

Affiliations

¹ Department of Liver Surgery, Cancer Center, Sun Yat-sen University, Guangzhou, China.
² Department of Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
³ State Key Laboratory of Oncology in South China, Guangzhou, China.
⁴ Department of Radiation Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
⁵ Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, Hong Kong SAR, China.
⁶ The Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Abstract

Background: The efficacy of radiofrequency ablation (RFA) for patients with early-stage recurrent hepatocellular carcinoma (HCC) with microvascular invasion (MVI) at the initial hepatectomy is limited. Our study aimed to explore whether adjuvant sorafenib following RFA could improve the situation.

Methods: We retrospectively included 211 patients with early-stage (tumor number of ≤3 and tumor size of 2-5 cm) recurrent HCC with MVI at the initial hepatectomy who underwent adjuvant sorafenib following RFA or RFA alone in 13 centers from June 2013 to June 2020. In the combination group, sorafenib of 400 mg twice daily was administered within 7 days after RFA. Overall survival (OS) and recurrence-free survival (RFS) were compared. Subgroup analysis based on MVI grade was performed. MVI grade was based on the practice guidelines for the pathological diagnosis of HCC and included M1 (≤5 MVI sites, all located within adjacent peritumoral liver tissues 0-1 cm away from the tumor margin) and M2 (>5 MVI sites, or any MVI site located within adjacent peritumoral liver tissues > 1 cm away from the tumor margin).

Results: A total of 103 patients received the combination therapy and 108 patients received RFA alone. The combination therapy provided better survival than RFA alone (median RFS: 17.7 vs. 13.1 months, P < 0.001; median OS: 32.0 vs. 25.0 months, P = 0.002). Multivariable analysis revealed that treatment allocation was an independent prognostic factor. On subgroup analysis, the combination therapy provided better survival than RFA alone in patients with M1 along with either a tumor size of 3-5 cm, tumor number of two to three, or alpha-fetoprotein (AFP) > 400 μg/L, and in those with M2 along with either a tumor size of 2-3 cm, one recurrent tumor, or AFP ≤ 400 μg/L.

Conclusions: Adjuvant sorafenib following RFA was associated with better survival than RFA alone in patients with early-stage recurrent HCC with MVI at the initial hepatectomy. Moreover, MVI grade could guide the application of adjuvant sorafenib.

Keywords: adjuvant therapy; microvascular invasion; radiofrequency ablation; recurrent hepatocellular carcinoma; sorafenib.