title: Clinical outcomes and toxicity of proton beam therapy for advanced cholangiocarcinoma.
abstract: BACKGROUND
  We examined the efficacy and toxicity of proton beam therapy (PBT) for treating advanced cholangiocarcinoma.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Radiation Oncology, Southern Tohoku Proton Therapy Center, 7-172, Yatsuyamada, 963-8052 Koriyama, Fukushima, Japan. chioko-makita@live.jp.
authors.forename: Chiyoko
authors.initials: C
authors.lastname: Makita
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Nakamura
authors.forename: Akinori
authors.initials: A
authors.lastname: Takada
authors.forename: Kanako
authors.initials: K
authors.lastname: Takayama
authors.forename: Motohisa
authors.initials: M
authors.lastname: Suzuki
authors.forename: Yojiro
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Azami
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kato
authors.forename: Iwao
authors.initials: I
authors.lastname: Tsukiyama
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kikuchi
authors.forename: Masato
authors.initials: M
authors.lastname: Hareyama
authors.forename: Masao
authors.initials: M
authors.lastname: Murakami
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Fuwa
authors.forename: Masaharu
authors.initials: M
authors.lastname: Hata
authors.forename: Tomio
authors.initials: T
authors.lastname: Inoue
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000532:radiotherapy*; D001653:Bile Ducts, Intrahepatic / Q000473:pathology; D018281:Cholangiocarcinoma / Q000175:diagnosis* / Q000473:pathology / Q000532:radiotherapy*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D061766:Proton Therapy / Q000009:adverse effects / Q000379:methods; D011832:Radiation Injuries / Q000453:epidemiology; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D016896:Treatment Outcome