Stereotactic Body Radiation Therapy as A Radical or Salvage Treatment for Early-stage Hepatocellular Carcinoma: A Prospective Phase II Study

Abstract

Preliminary retrospective studies have shown that stereotactic body radiation therapy (SBRT) was an alternative to the local treatment of early stage hepatocellular carcinoma (HCC) with encouraging long-term efficacy and low side effects. The aim of this study was to prospectively validate the efficacy of SBRT as radical or salvage ablative treatment for early stage HCC who were not considered for surgery or local radiofrequency ablative therapy. This single-center prospective phase 2 trial enrolled patients with HCC including 1-3 tumor lesions with total diameter less than 10 cm and Child-Pugh A and B disease, without major vascular invasion or extrahepatic metastasis. Most of patients received SBRT with 45Gy in 3 fractions (36-50Gy/2-6 fraction). The endpoints were the 1-, 4-year overall survival (OS), and progression-free survival (PFS), local control (LC), and intrahepatic control (IC) rate defined by Response Evaluation Criteria in Solid Tumors. From January 2014 to December 2016, 126 eligible patients were analyzed, including 87 patients with primary HCC underwent SBRT as radical treatment and 39 with residual/recurrent HCC after TACE as salvage treatment. 97 (77.0%) patients were Child–Pugh grade A5 and 16 (13.0%) grade A6 and 13 (10.0%) grade B7-9. The median follow-up time was 50.0 months (range, 2-70 months). The median OS and PFS were 57.0 and 18.0 months, respectively. The 1-, 4-year OS, PFS, LC and IC rate were 82.0% and 51.8%, 66.9% and 20.6%, 86.7% and 63.8%, 75.2% and 29.5%, respectively. There was no significant difference in outcome between primary and residual/recurrent groups. After SBRT, one old patient with Child-Pugh B7 died at 4 months after SBRT duo to classic radiation-induced liver disease. Treatment-related GI-bleed occurred in 1 patient who died at 9 months. 21 patients (16.6%) experienced +1 score decline in Child–Pugh, and 12 (9.5%) experienced ≥2 scores decline in Child–Pugh. SBRT as a radical or salvage treatment for patients with inoperable early stage HCC was an effective and well tolerated modality. Decline in Child–Pugh score was a most common SBRT-induced hepatic toxicity.