Hepatocellular Carcinoma · Radiation · Salvage / Recurrent

Proton Beam Therapy vs RFA (Kim et al.)

Clinical question: What are the efficacy and safety outcomes of recurrent/residual hcc ≤2 lesions, <3 cm?

Registry: NCT01963429 · Phase III randomized non-inferiority trial; n=144 ITT. Evidence cut-off: 13 November 2026.

Design, eligibility and treatment

Population

Recurrent/residual HCC <3 cm, ≤2 lesions; crossover allowed for technical infeasibility.

Intervention / comparator

Proton beam therapy versus RFA.

Design

Phase III randomized non-inferiority trial; n=144 ITT.

Primary endpoint

2-y local PFS; non-inferiority margin 15%.

Key efficacy outcomes

2-y LPFS ITT 92.8% vs 83.2%; difference 9.6 percentage points (90% CI 0.7–18.4), meeting non-inferiority. Per-protocol 94.8% vs 83.9%.

Safety

PBT pneumonitis 32.5%, leukopenia 23.8%; RFA ALT rise 96.4%, abdominal pain 30.4%; no grade 4 AEs or mortality.

Interpretation and limitations

Met non-inferiority, not superiority; crossover and ITT/PP distinctions are important.

Median survival differences and hazard ratios must not be converted into NNT. A patient pictogram is omitted unless a defensible fixed-time absolute event difference is reported.

Primary and supporting sources

Primary publication

Registry / supporting source

Primary-source data reviewed; the page explicitly identifies unavailable full-text toxicity details rather than imputing them.

Current-practice context · 13 November 2026

Historical trial results are distinct from current treatment recommendations. Check current jurisdiction-specific guidance, liver function, biomarker requirements, local expertise and regulatory availability before applying these findings. Comprehensive guideline reconciliation and browser-rendered QA remain pending.