The Absolute Effect / Evidence
Phase II hypofractionated proton beam therapy for hepatocellular carcinoma
Clinical question: What local control and survival outcomes can be achieved with hypofractionated proton beam therapy in carefully selected patients with HCC?
Registry: NCT02395523 · Prospective, single-institution, single-arm phase II study · n=45. Evidence cut-off: 14 November 2026.
Design, population and eligibility
Prospective, single-arm phase II study; 45 patients enrolled and analysed at the National Cancer Center, Korea.
Primary or recurrent/residual HCC after failure of, difficulty with, or refusal of other local treatments; no extrahepatic metastasis.
Target lesion(s) ≤7 cm, ≤2 lesions, and ≥2 cm from gastrointestinal organs; Child–Pugh score ≤7; ECOG performance status ≤1; age ≥18 years; no prior RT to target lesion(s).
Hypofractionated proton beam therapy, 70 Gy equivalent (GyE) in 10 fractions.
Primary endpoint: 3-year local progression-free survival (LPFS). Secondary outcomes included PFS, OS, response and toxicity. This was not a randomized comparison.
Source-reported efficacy outcomes
At median follow-up of 35.1 months (range 11.2–56.3), the estimated 3-year LPFS was 95.2% (95% CI 89.1–100%), 3-year PFS was 45.2% (95% CI 29.9–60.5%), and 3-year OS was 86.4% (95% CI 72.9–99.9%).
All treated lesions eventually achieved complete response; median time to complete response was 5.1 months (95% CI 4.3–6.3). Local progression was reported in two patients. Disease progression of any site occurred in 23 patients; intrahepatic progression predominated.
Safety and treatment delivery
All 45 patients completed the planned treatment without interruption. No grade ≥3 acute toxicity occurred. The report states that no patient experienced late gastrointestinal toxicity; comprehensive late-toxicity detail is limited in the publication and should not be interpreted as absence of all late adverse effects.
Quality-of-life outcomes were not reported as a formal endpoint.
Absolute effect and interpretation
Although local control was high in this selected cohort, PFS was substantially lower, reflecting intrahepatic and distant progression beyond the treated target. The small, single-institution cohort and selection criteria limit generalisability, particularly to patients with poorer liver function, larger/multiple lesions, lesions close to gastrointestinal organs or extrahepatic disease.
NCCN citation provenance and current-practice context · 14 November 2026
The NCCN Guidelines Insights for Hepatocellular Carcinoma, Version 2.2026 (October 2026), explicitly cites this phase II study in its radiation-therapy update as reference 42. The article reports the same 45-patient cohort and 3-year LPFS and OS estimates. The Insights discussion states that proton beam therapy may be appropriate in selected settings; this citation does not make this single-arm study randomized evidence or establish superiority over other local therapies.
NCCN Guidelines Insights are a focused discussion of selected updates and do not represent the complete NCCN guideline. Apply current full guideline recommendations, liver function, tumour location, dose constraints, local expertise and multidisciplinary judgement.
Primary publication and registry
Kim TH et al. Frontiers in Oncology. 2020;10:542. PMID 32411594; DOI 10.3389/fonc.2020.00542.
Full open-access primary publication
ClinicalTrials.gov record NCT02395523
Primary-source review completed. The page distinguishes reported estimates from comparative effects and identifies limitations in late-toxicity and QoL reporting.