Background
Phase II trial. 50 enrolled, 47 evaluable patients with inoperable HCC and incomplete response after 1–5 TACE procedures. Eligibility: greatest tumor dimension sum <10 cm, Child-Pugh A (n=41) or B7 (n=6), inoperable, TACE-refractory/incomplete responders. SBRT prescribed up to 60 Gy in 3 fractions, with dose reduced to meet normal tissue constraints. Median SBRT dose 57 Gy (42–60 Gy); median tumor 29 mm.
Interventions and follow up
Arm A: SBRT as salvage after incomplete TACE — 42–60 Gy in 3 fractions (median 57 Gy)
Arm B: N/A — single-arm phase II
Primary endpoint: Local response and local control
mFollow up: 2 year
Arm B: N/A — single-arm phase II
Primary endpoint: Local response and local control
mFollow up: 2 year
Results
CR within 6 months: 38.3%
PR within 6 months: 38.3% (ORR 76.6%)
2-year local control rate: 94.6%
2-year OS: 68.7%
2-year PFS: 33.8%
PR within 6 months: 38.3% (ORR 76.6%)
2-year local control rate: 94.6%
2-year OS: 68.7%
2-year PFS: 33.8%
Adverse events
Main adverse events: Grade 3 GI toxicity: 6.4% (3 patients); grade 4 gastric ulcer perforation: 4.3% (2 patients). Highlights risk of bowel toxicity at 60 Gy/3 fx, particularly for tumors near stomach/duodenum. No radiation-induced liver failure.
Conclusions
SBRT as local salvage after incomplete TACE achieved 94.6% 2-year local control and 68.7% 2-year OS in inoperable HCC, with promising ORR of 76.6%. These results support the sequential TACE → SBRT strategy, though gastric ulcer perforation in 4.3% underscores the need for dose constraint refinement near upper GI structures.
Key Limitations
Key Limitations: Phase II single-arm, no comparator arm. Gastric ulcer perforation in 4.3% was clinically significant and prompted the recommendation for a modified multi-institutional phase II trial to reduce GI toxicity. Small tumor selection (<10 cm LD sum, median 29 mm) may not reflect typical TACE-refractory cohorts. CP-B patients included but outcomes not separately reported.
Clinical Context
Sequential TACE followed by SBRT for HCC is increasingly used at high-volume centers, particularly for patients who have residual tumor after TACE or who are not candidates for RFA due to tumor location or size. This trial established the proof-of-concept for TACE + SBRT combination and informed subsequent prospective studies (Yoon JAMA Oncol 2018). The strategy is particularly relevant as a bridge to liver transplantation or for patients with portal vein tumor thrombosis.
References