Phase 2 Study of Adjuvant Radiotherapy Following Narrow-Margin Hepatectomy in Patients With HCC

Bo Chen, Jian-Xiong Wu, Shu-Hui Cheng, Li-Ming Wang, Wei-Qi Rong, Fan Wu, Shu-Lian Wang, Jing Jin, Yue-Ping Liu, Yong-Wen Song, Hua Ren, Hui Fang, Yuan Tang, Ning Li, Ye-Xiong Li, Wei-Hu Wang, Bo Chen, Jian-Xiong Wu, Shu-Hui Cheng, Li-Ming Wang, Wei-Qi Rong, Fan Wu, Shu-Lian Wang, Jing Jin, Yue-Ping Liu, Yong-Wen Song, Hua Ren, Hui Fang, Yuan Tang, Ning Li, Ye-Xiong Li, Wei-Hu Wang

Abstract

Background and aims: Surgical resection is the primary treatment for HCC; however, it is associated with a high rate of recurrence and death. We conducted this phase 2 study to investigate the efficacy and safety of postoperative intensity-modulated radiotherapy (IMRT) for HCC after narrow-margin hepatectomy.

Approach and results: We designed a single-arm, prospective phase 2 trial to evaluate overall survival (OS), disease-free survival (DFS), recurrence patterns, and toxicity in patients receiving adjuvant radiotherapy. The eligibility criteria included the following: pathological diagnosis of HCC after hepatectomy, with narrow pathological margins (< 1 cm); age > 18 years; and Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients received IMRT within 4-6 weeks after surgical resection. This trial was registered at ClinicalTrials.gov (NCT01456156). Between 2008 and 2016, a total of 76 eligible patients who underwent narrow-margin resection were enrolled. The median follow-up duration was 70 months; the 3-year OS and DFS rates were 88.2% and 68.1%, respectively; and the 5-year OS and DFS rates were 72.2% and 51.6%, respectively. Intrahepatic recurrence was the primary recurrence pattern. No marginal recurrence was found. Intrahepatic, extrahepatic, and combined recurrences at the first relapse were found in 33, 5, and 1 patient, respectively. The most common radiation-related grade-3 toxicities were leukopenia (7.9%), elevated alanine aminotransferase (3.9%) and aspartate aminotransferase (2.6%) levels, and thrombocytopenia (1.3%). Classical or nonclassical radiation-induced liver disease was not noted.

Conclusions: Adjuvant radiotherapy is an effective, well-tolerated, and promising adjuvant regimen in patients with HCC who have undergone narrow-margin hepatectomy. Our trial provides evidence and a rationale for planning a future phase 3 trial.

© 2021 by the American Association for the Study of Liver Diseases.

Figures

FIG. 1
FIG. 1
OS and DFS of patients with HCC receiving adjuvant radiotherapy after narrow‐margin hepatectomy. (A) OS and DFS of all patients; (B) OS and (C) DFS of patients with HCC stratified into stage 1 and stages 2‐3; (D) DFS of patients with HCC stratified into MVI‐positive and MVI‐negative.
FIG. 2
FIG. 2
Cumulative recurrence rate in patients with HCC with adjuvant radiotherapy after narrow‐margin hepatectomy. (A) Total, intrahepatic, and extrahepatic recurrence rates in all patients; (B) intrahepatic recurrence rate; and (C) extrahepatic recurrence rate in patients with HCC stratified according to stage 1 and stage 2‐3 disease.

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