Open Access Research

Clinical outcomes and toxicity of proton beam therapy for advanced cholangiocarcinoma

Chiyoko Makita1*, Tatsuya Nakamura2, Akinori Takada1, Kanako Takayama1, Motohisa Suzuki1, Yojiro Ishikawa1, Yusuke Azami1, Takahiro Kato1, Iwao Tsukiyama1, Yasuhiro Kikuchi1, Masato Hareyama1, Masao Murakami2, Nobukazu Fuwa3, Masaharu Hata4 and Tomio Inoue4

Author Affiliations

1 Department of Radiation Oncology, Southern Tohoku Proton Therapy Center, 7-172, Yatsuyamada, 963-8052 Koriyama, Fukushima, Japan

2 Department of Radiology, Graduate School of Medicine, Dokkyo Medical University, 880 Kitakobayashi, Mibu-machi, 321-0293 Shimotsuga, Tochigi, Japan

3 Hyogo ion beam Medical Center, 1-2-1 Koto, Shingu, 679-5165 Tatsuno, Hyogo, Japan

4 Department of Radiology, Graduate School of Medicine, Yokohama City University, 3-9 Fukuura, 236-0004 Kanazawa-ku, Yokohama, Japan

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Radiation Oncology 2014, 9:26  doi:10.1186/1748-717X-9-26

Published: 14 January 2014



We examined the efficacy and toxicity of proton beam therapy (PBT) for treating advanced cholangiocarcinoma.


The clinical data and outcomes of 28 cholangiocarcinoma patients treated with PBT between January 2009 and August 2011 were retrospectively examined. The Kaplan–Meier method was used to estimate overall survival (OS), progression-free survival (PFS), and local control (LC) rates, and the log-rank test to analyze the effects of different clinical and treatment variables on survival. Acute and late toxicities were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.


The median age of the 17 male and 11 female patients was 71 years (range, 41 to 84 years; intrahepatic/peripheral cholangiocarcinoma, n = 6; hilar cholangiocarcinoma/Klatskin tumor, n = 6; distal extrahepatic cholangiocarcinoma, n = 3; gallbladder cancer, n = 3; local or lymph node recurrence, n = 10; size, 20–175 mm; median 52 mm). The median radiation dose was 68.2 Gy (relative biological effectiveness [RBE]) (range, 50.6 to 80 Gy (RBE)), with delivery of fractions of 2.0 to 3.2 Gy (RBE) daily. The median follow-up duration was 12 months (range, 3 to 29 months). Fifteen patients underwent chemotherapy and 8 patients, palliative biliary stent placement prior to PBT. OS, PFS, and LC rates at 1 year were 49.0%, 29.5%, and 67.7%, respectively. LC was achieved in 6 patients, and was better in patients administered a biologically equivalent dose of 10 (BED10) > 70 Gy compared to those administered < 70 Gy (83.1% vs. 22.2%, respectively, at 1 year). The variables of tumor size and performance status were associated with survival. Late gastrointestinal toxicities grade 2 or greater were observed in 7 patients <12 months after PBT. Cholangitis was observed in 11 patients and 3 patients required stent replacement.


Relatively high LC rates after PBT for advanced cholangiocarcinoma can be achieved by delivery of a BED10 > 70 Gy. Gastrointestinal toxicities, especially those of the duodenum, are dose-limiting toxicities associated with PBT, and early metastatic progression remains a treatment obstacle.

Cholangiocarcinoma; Proton beam therapy; Chemoradiotherapy; Cholangitis; Gastrointestinal toxicity