Radiotherapy prior to or after transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma with portal vein tumor thrombus: a randomized controlled trial

Abstract

Introduction: To compare survival outcomes of radiotherapy (RT) prior to transcatheter arterial chemoembolization (TACE) (RT + TACE) with TACE followed with RT (TACE + RT) in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT).

Methods: A randomized controlled study was conducted from August 2016 to December 2019 on patients with unresectable HCC and PVTT. The patients were randomly assigned to RT + TACE group or TACE + RT group in a 1:1 ratio. Evaluation of therapeutic effects on the primary tumor was based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST), while that on PVTT was based on the changing of Cheng's PVTT classification. The primary end-point was overall survival (OS).

Results: The 120 patients who entered this study were evenly assigned to two groups. In the intention-to-treat (ITT) population, the OS rates for RT + TACE group at 1, 2 and 3 years were 61.7%, 27.4% and 15.6%, compared with 45.0%, 16.1% and 4.7% in TACE + RT group. The median OS was increased in patients with RT + TACE compared with those who had TACE + RT with a marginally significance (15.4 versus 11.5 months, HR = 0.68, 95% CI 0.46-1.01, p = 0.054). The median progression-free survival (PFS) in RT + TACE group was 6.6 months versus 4.2 months in TACE + RT group (HR = 0.66, 95% CI 0.46-0.96, p = 0.030). The corresponding disease control rate (DCR) at 3 months was 86.7% versus 66.7% (p = 0.017) and 61.7% versus 46.7% (p = 0.099) at 6 months. In subgroup analyses, RT + TACE was associated with better OS (HR, 0.48; 95% CI 0.33-0.99, p = 0.048) and PFS (HR, 0.55; 95% CI 0.33-0.93, p = 0.026) versus TACE + RT among patients with type III/IV PVTT. There were 3 patients in RT + TACE group and 2 in TACE + RT group had adverse events ≥ grade 3.

Conclusion: Applying RT prior to TACE provided better survival outcomes than TACE followed by RT for patients with HCC and PVTT, which may act as an optimized regional modality to further improve local control rates (Trial registration: ChiCTR ChiCTR2000033573.).

Keywords: Hepatocellular carcinoma; Portal vein tumor thrombus; Radiotherapy; Sequential treatment; Transcatheter arterial chemoembolization.