Updated Japanese multicenter registry study evaluates the efficacy and safety of proton beam therapy for treating extrahepatic cholangiocarcinoma

This study aimed to analyze the efficacy and safety of a prospective, multicenter registry study of proton beam therapy (PBT) for extrahepatic cholangiocarcinoma (EHC) in Japan. Patients who underwent PBT for EHC between May 2016 and June 2021 were registered in the Particle Beam Therapy Committee and Subcommittee of the Japanese Society for Radiation Oncology. We updated the overall survival (OS), progression-free survival (PFS), local control rate (LC), and toxicity. Among 201 registered cases, 124 cases including elder population (median age 76 years old, range; 44-91) with initial definitive PBT were evaluated. The follow-up period for survivors was 18.3 months, the median OS time was 20.0 months (95% CI: 17.3-22.8 months), and the 2-year OS rate was 36.9% (27.3-46.4%). The 2-year LC and PFS were 65.2% and 23.0%. The OS was significantly higher for tumor size < 3 cm vs. ≥ 3 cm (p = 0.015); liver function Child-Pugh score normal/A vs. B/C (p < 0.001); and distance of the tumor from the gastrointestinal tract > 2 cm vs. ≤ 2 cm (p = 0.008) in multivariate analysis. Elderly patients age > 75 years underwent less chemotherapy and showed a 2-year OS of 41.3%, whereas young patients with age ≤ 75 years showed a 2-year OS of 32.0%. A higher prescribed dose (biologically effective dose: BED) > 89 Gy₁₀ was associated with better LC and PFS but not OS. PBT-related grade 3 acute and late adverse events occurred in 4.0 and 12.1% of the patients, respectively. These updated multicenter prospective registry data demonstrate that PBT is an effective treatment for unresectable EHC, including in elderly patients.