Is the Concurrent Use of Sorafenib and External Radiotherapy Feasible for Advanced Hepatocellular Carcinoma? A Meta-Analysis

Abstract

We evaluate the feasibility of a concurrent application of sorafenib and external beam radiation therapy (EBRT) for advanced hepatocellular carcinoma (HCC). PubMed, Embase, Medline, and Cochrane Library were searched up to 9 April 2021. The primary endpoint was grade ≥3 complications, and the secondary endpoint was overall survival (OS). Subgroup analyses were performed for studies with the EBRT targets, intrahepatic vs. non-intrahepatic lesions (e.g., extrahepatic metastases or malignant vessel involvement only). Eleven studies involving 512 patients were included in this meta-analysis. Pooled rates of gastrointestinal, hepatologic, hematologic, and dermatologic grade ≥3 toxicities were 8.1% (95% confidence interval (CI): 4.8-13.5, I² = ~0%), 12.9% (95% CI: 7.1-22.1, I² = 22.4%), 9.1% (95% CI: 3.8-20.3, I² = 51.3%), and 6.8% (95% CI: 3.8-11.7, I² = ~0%), respectively. Pooled grade ≥3 hepatologic and hematologic toxicity rates were lower in studies targeting non-intrahepatic lesions than those targeting intrahepatic lesions (hepatologic: 3.3% vs. 17.1%, p = 0.041; hematologic: 3.3% vs. 16.0%, p = 0.078). Gastrointestinal and dermatologic grade ≥3 complications were not significantly different between the subgroups. Regarding OS, concurrent treatment was more beneficial than non-concurrent treatment (odds ratio: 3.3, 95% CI: 1.3-8.59, p = 0.015). One study reported a case of lethal toxicity due to tumor rupture and gastrointestinal bleeding. Concurrent treatment can be considered and applied to target metastatic lesions or local vessel involvement. Intrahepatic lesions should be treated cautiously by considering the target size and hepatic reserve.

Keywords: combined; concurrent; external beam radiation therapy; hepatocellular carcinoma; sorafenib; toxicity.

Figure 1

Study inclusion process.

Figure 2

Forest plots of pooled analyses of all included studies regarding (A) gastrointestinal, (B) hepatologic, (C) hematologic, (D) dermatologic grade ≥3 toxicities; subgroup analyses comparing studies with RT targets of intrahepatic and non-intrahepatic lesions, regarding (E) gastrointestinal, (F) hepatologic, (G) hematologic, (H) dermatologic grade ≥3 toxicities. (I) Overall survival comparing concurrent and non-concurrent arms.