Combined transarterial chemoembolization and radiotherapy as a first-line treatment for hepatocellular carcinoma with macroscopic vascular invasion: Necessity to subclassify Barcelona Clinic Liver Cancer stage C

Abstract

Background and purpose: Systemic therapy such as sorafenib is the standard for Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC); however, the survival benefits are modest especially for HCC with macroscopic vascular invasion (MVI). Transarterial chemoembolization (TACE) plus external beam radiotherapy (RT) is an alternative treatment to sorafenib, with favorable clinical results. We evaluated the outcomes of respiratory-gated RT and TACE in treatment-naïve BCLC stage C HCC patients with MVI and proposed a subclassification model.

Methods: In this study, 639 patients received TACE plus RT for HCC with MVI as a first-line treatment between January 2010 and December 2015.

Results: Main/bilateral portal vein and/or inferior vena cava tumor thrombus was observed in 353 (55.2%) patients. The median radiation dose was 39 Gy (range 24-50) with a 2.5-Gy (2-5) median fraction size. The median overall survival was 10.7 months, with 1- and 2-year survival rates of 46.5% and 23.9%, respectively. In the multivariate analysis, Child-Pugh classification B, tumor size >10 cm, infiltrative/diffuse type, presence of extrahepatic metastasis, alpha-fetoprotein >150,000 ng/mL, and radiation dose ≤40 Gy were significant predictors for poor overall survival. Subclassification of patients into very low, low, intermediate, and high-risk groups showed median survivals of 84.8, 14.7, 10.3, and 5.7 months, respectively (p < 0.001).

Conclusion: TACE plus RT is an effective and safe treatment for HCC with MVI and could be considered a first-line treatment option. The subclassification scheme accurately predicted the prognosis of these patients and may be useful for tailored treatment.

Keywords: Hepatocellular carcinoma; Radiotherapy; Subclassification; Transarterial chemoembolization; Vascular invasion.