A Phase 2 Study of Image-Guided Proton Therapy for Operable or Ablation-Treatable Primary Hepatocellular Carcinoma.

Purpose: Because most previous data on proton therapy for hepatocellular carcinoma (HCC) were retrospectively collected from inoperable or previously treated cases, our aim was to evaluate the outcome of image-guided proton therapy (IGPT) for operable or radiofrequency ablation-treatable primary HCC.
Methods and Materials: This phase 2 study prospectively investigated the efficacy and safety of IGPT and quality of life (QoL) after IGPT for operable/ablatable HCC. The primary endpoint was overall survival, and the secondary endpoints were local control, incidence of grade ≥3 adverse events, and changes in QoL. Toxicities were evaluated with Common Terminology Criteria for Adverse Events, version 4.0. QoL scores were assessed with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, version 3.0, and Quality of Life Questionnaire-Hepatocellular Carcinoma/Primary Liver Cancer Module. IGPT was performed using respiratory-gated techniques.
Results: Forty-five patients (median age: 68 years; range, 36-80 years) were enrolled between June 2013 and February 2016; 38 were considered operable and 14 were indicated for radiofrequency ablation. The major underlying liver diseases were hepatitis B (n = 16), hepatitis C (n = 13), alcoholic hepatitis (n = 3), and nonalcoholic fatty liver disease (n = 13). The Child-Pugh score was A5 in 32 patients, A6 in 9 patients, and B7 in 4 patients. Thirty-seven patients with a peripherally located tumor were given 66 Gy relative biological effectiveness in 10 fractions, and 8 patients with a centrally located tumor received 72.6 Gy relative biological effectiveness in 22 fractions. The median follow-up period of surviving patients was 60 months (range, 42-75 months). Two- and 5-year overall survival rates were 84% (95% confidence interval [CI], 74%-95%) and 70% (95% CI, 56%-84%), respectively, and local control rates were 95% (95% CI, 89%-100%) and 92% (95% CI, 84%-100%), respectively. Grade 3 radiation-induced liver disease was observed in 1 patient. No significant changes were noted in QoL scores 1 year after treatment, except for body image.
Conclusions: Although the primary endpoint did not meet statistical significance as planned in the study design, IGPT is a safe and effective treatment for solitary primary HCC and may become a treatment option.
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