Background
Randomized phase II trial (Asan Medical Center, Korea). 90 patients with HCC and portal vein tumor thrombosis (PVTT) randomized 1:1 to TACE + SBRT vs sorafenib. Portal vein tumor thrombosis (main branch or first-order branch) was present in all patients. Enrolled 2012–2015.
Interventions and follow up
Arm A: TACE (conventional or DEB-TACE) × 1–5 cycles + SBRT 21–54 Gy in 3–6 fractions to the PVTT
Arm B: Sorafenib 400 mg BID continuously
Primary endpoint: Time to progression (TTP)
mFollow up: ~11 month
Arm B: Sorafenib 400 mg BID continuously
Primary endpoint: Time to progression (TTP)
mFollow up: ~11 month
Results
TTP: 31.0 weeks (TACE+SBRT) vs 11.7 weeks (sorafenib), HR 0.35, P<.001
OS: 55 weeks (TACE+SBRT) vs 43 weeks (sorafenib), HR 0.58, P=.04
ORR: 68.9% (TACE+SBRT) vs 28.9% (sorafenib), P<.001
PVTT response: 59.6% (TACE+SBRT) vs 2.2% (sorafenib)
OS: 55 weeks (TACE+SBRT) vs 43 weeks (sorafenib), HR 0.58, P=.04
ORR: 68.9% (TACE+SBRT) vs 28.9% (sorafenib), P<.001
PVTT response: 59.6% (TACE+SBRT) vs 2.2% (sorafenib)
Adverse events
Main adverse events: Grade 3/4 AEs: 43.5% (TACE+SBRT) vs 54.5% (sorafenib). Most common grade 3/4 with TACE+SBRT: AST elevation (25%) and thrombocytopenia (9%). With sorafenib: hand-foot skin reaction (17%) and AST elevation (20%). No treatment-related deaths.
Conclusions
TACE + SBRT significantly improved TTP (31.0 vs 11.7 weeks) and OS (55 vs 43 weeks) vs sorafenib in HCC with portal vein tumor thrombosis, with superior tumor response rates and comparable toxicity, establishing TACE+SBRT as the preferred locoregional approach for HCC with PVTT in experienced centers.
Key Limitations
Key Limitations: Phase II trial — underpowered for definitive OS comparison; confirmatory phase III evidence needed. Single Korean center, high proportion of HBV-related HCC (92%) and Child-Pugh A (82%) — may not reflect Western HCC with alcohol/NASH cirrhosis and more impaired liver function. Sorafenib as the comparator is now being challenged by atezolizumab + bevacizumab (IMbrave150) as first-line standard. Crossover not permitted but did not affect interpretation given short OS.
Clinical Context
HCC with PVTT is BCLC stage C and carries poor prognosis. This trial established TACE+SBRT as superior to sorafenib in this population, with 55-week median OS representing a meaningful improvement over the historical 6–10 month median with sorafenib alone in PVTT-HCC. Practice has shifted at high-volume centers to offer TACE+SBRT to carefully selected patients with PVTT. First-line systemic immunotherapy (atezo+bev, durvalumab+tremelimumab) remains standard per current guidelines but TACE+SBRT may be preferred for selected resection candidates.
References