Hypofractionated Radiation Therapy for Unresectable/Locally Recurrent Intrahepatic Cholangiocarcinoma

Ann Surg Oncol. 2020 Apr;27(4):1122-1129. doi: 10.1245/s10434-019-08142-9. Epub 2019 Dec 23.


Objective: The aim of this study was to evaluate outcomes for patients with unresectable intrahepatic cholangiocarcinoma (ICC) treated with hypofractionated proton or photon radiation therapy (HF-RT).

Methods: We retrospectively identified 66 patients with ICC who were treated with HF-RT from 2008 to 2018. Median age at RT was 76 years (range 30-92), including 27 patients (41%) aged ≥ 80 years. Median RT dose was 58.05 Gy (range 37.5-67.5), all delivered in 15 daily fractions. Thirty-two patients received proton RT and 34 patients received photon RT.

Results: Median follow-up times from diagnosis and RT start were 21 months and 14 months, respectively. In total, five patients (7.6%) developed local failure. The 2-year outcomes were 84% local control (LC) and 58% OS. Among the 51 patients treated with definitive intent, the 2-year LC rate was 93% and the OS rate was 62%. On multivariate analysis for LC, older age was associated with a lower risk of local failure [hazard ratio (HR) 0.91; p = 0.02], while prior surgery (HR 16.5; p = 0.04) and macrovascular invasion (HR 123.93; p = 0.02) were independently associated with an increased risk of local failure. On multivariate analysis for OS, female sex (HR 0.33; p = 0.001) and prior chemotherapy (HR 0.38; p = 0.003) remained significantly associated with OS. On multivariate analysis for OS, compared with photon RT, there was a trend towards improved survival with proton RT (HR 0.50; p = 0.05). The rate of overall grade 3 + toxicity was 11%. One patient developed radiation-induced liver disease and was treated with corticosteroids.

Conclusions: HF-RT yields high rates of local control and is an effective modality to optimize biliary control for unresectable/locally recurrent ICC.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bile Duct Neoplasms / pathology
  • Bile Duct Neoplasms / radiotherapy*
  • Cholangiocarcinoma / pathology
  • Cholangiocarcinoma / radiotherapy*
  • Combined Modality Therapy
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Proton Therapy / adverse effects
  • Proton Therapy / methods*
  • Radiation Dose Hypofractionation*
  • Radiation Injuries
  • Retrospective Studies
  • Treatment Failure


  • Fluorouracil