Proton Beam Therapy for Intrahepatic and Perihilar Cholangiocarcinoma: A Multicenter Prospective Registry Study: Potential Candidates for High-Dose Proton Beam Therapy.

PURPOSE: Because dose escalation radiation therapy can improve local control (LC), stereotactic body radiation therapy has achieved better results than conventional radiation therapy in liver malignancies. This study aimed to investigate the role of dose escalation proton beam therapy (PT) in patients with intrahepatic cholangiocarcinoma (iCCA) and perihilar cholangiocarcinoma (pCCA).

METHODS AND MATERIALS: We analyzed data from a multi-institutional prospective registry that included all Japanese proton beam facilities between May 2016 and May 2021. Endpoints were LC, progression-free survival, overall survival (OS), and toxicity.

RESULTS

We included 236 patients with unresectable cholangiocarcinoma (133 iCCA and 103 pCCA) treated with PT with a median prescribed dose of 72.6 Gy (RBE) (range, 50-76 Gy Relative Biological Effectiveness (RBE)) in 25 fractions (range, 10-38 fractions). With a median follow-up of 20.0 months for surviving patients, the median OS was 19 months, and the 2-year OS was 44.8%. For iCCA and pCCA, the median OSs were 17 and 20 months, respectively. Two-year progression-free survival and LC rates were 20.6% and 66.5%, respectively. Multivariable analyses revealed that liver function and the distance between the tumor and the gastrointestinal tract were significantly associated with OS, whereas the overall treatment time was associated with LC. Furthermore, liver function and tumor diameter were associated with progression-free survival. The median OS for patients with gastrointestinal distance ≥2 cm and a higher prescribed dose (≥74 Gy in equivalent 2-Gy fractions) was 37 months (2-year OS 61.8%), compared with 18.0 months (33.1%) for other patients (P< .001). Twenty-one patients experienced adverse reactions of grade 3 or higher (8.9%).

CONCLUSIONS

PT showed good efficacy with acceptable toxicity for unresectable iCCA and pCCA without distant metastasis. Especially in patients with gastrointestinal distance ≥2 cm, high-dose PT was associated with improved OS.