The role of external beam radiotherapy for hepatocellular carcinoma patients with lymph node metastasis: a meta-analysis of observational studies

Abstract

Purpose: Lymph node metastasis of hepatocellular carcinoma is categorized as advanced in Barcelona Clinic of Liver Cancer staging, and sorafenib is a sole treatment recommended. However, appliance of local treatment including external beam radiotherapy (EBRT) has not been uncommon. We performed a meta-analysis and systemically reviewed current literature to evaluate the efficacy and safety of EBRT.

Methods: PubMed, Medline, Cochrane library, and Embase were systemically searched until December 17, 2017. The primary endpoint of analyses was response rate (RR), and 1-year overall survival and complication rates of grade ≥3 were secondary endpoints. Complications were primarily assessed descriptively.

Results: A total of 8 studies comprising 521 patients were included. The pooled RR was 73.1% (95% confidence interval [CI]: 63.6-80.9), and high-dose EBRT groups had better RR than the low-dose group (82.2% [95% CI: 74.4-88.1] vs 51.1% [95% CI: 40.3-61.7]; P=0.001]. The pooled 1-year overall survival rate was 41.0% (95% CI: 32.9-49.6). Six studies assessed the survival benefit according to RR, and 5 (83.3%) of these 6 studies reported statistically significant survival benefit. The most common grade ≥3 toxicities were thrombocytopenia and gastrointestinal complication, with pooled rates of 3.4% (95% CI: 1.2-9.5) and 3.5% (95% CI:1.7-7.2), respectively.

Conclusion: EBRT showed a pooled RR of 73.1% and was safely performed. EBRT might palliate symptoms through tumor reductions and improve survival. Use of sorafenib combined or sequentially with EBRT can be recommended rather than monotherapy.

Keywords: hepatocellular carcinoma; lymph node metastasis; meta-analysis; radiation therapy.

Figure 1

The study inclusion process.

Figure 2

(A) Forest plots of the RRs and 1-year OS rates. The P-values from the Cochran Q test and I² statistics are described below the figures. Significant heterogeneity among the studies was found in regard to RRs, but not in 1-year OS rates. (B) Forest plots of RRs comparing high- and low-dose groups. The P-value was derived from a Q-test, based on an analysis of the variance and a random-effects model, where P (total between) <0.001 suggests a significant difference of RRs between high-dose and low-dose subgroups. Abbreviations: OS, overall survival; RR, response rate.

Figure 3

(A) Forest plot of GI toxicities of grade 3 or higher, (B) forest plot of thrombocytopenia of grade 3 or higher. Abbreviations: CI, confidence interval; GI, gastrointestinal.

Figure 4

Funnel plots assessing RRs and OS rates. Abbreviations: OS, overall survival; RR, response rate.