Regional chemotherapy for unresectable intrahepatic cholangiocarcinoma: a potential role for dynamic magnetic resonance imaging as an imaging biomarker and a survival update from two prospective clinical trials

Ann Surg Oncol. 2014 Aug;21(8):2675-83. doi: 10.1245/s10434-014-3649-y. Epub 2014 Mar 25.

Abstract

Background: For patients with unresectable intrahepatic cholangiocarcinoma (ICC), treatment options are limited and survival is poor. This study summarizes the long-term outcome of two previously reported clinical trials using hepatic arterial infusion (HAI) with floxuridine and dexamethasone (with or without bevacizumab) in advanced ICC.

Methods: Prospectively collected clinicopathologic and survival data were retrospectively reviewed. Response was based on Response Evaluation Criteria in Solid Tumors (RECIST). Pre-HAI dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) images were reviewed, and tumor perfusion data correlated with outcome.

Results: Forty-four patients were analyzed (floxuridine, 26; floxuridine/bevacizumab, 18). At a median follow-up of 29.3 months, 41 patients had died of disease. Partial response by RECIST was observed in 48 %, and 50 % had stable disease. Three patients underwent resection after response, and 82 % received additional HAI after removal from the trials. Median survival was similar in both trials (floxuridine 29.3 months vs. floxuridine/bevacizumab 28.5 months; p = 0.96). Ten (23 %) patients survived ≥3 years, including 5 (11 %) who survived ≥5 years. Tumor perfusion measured on pre-treatment DCE-MRI [area under the gadolinium concentration curve at 90 and 180 s (AUC90 and AUC180, respectively)] was significantly higher in ≥3-year survivors and was the only factor that distinguished this group from <3-year survivors (mean AUC90 22.6 vs. 15.9 mM s, p = 0.025, and mean AUC180 48.9 vs. 32.3 mM s, p = 0.003, respectively). Median hepatic progression-free survival was longer in ≥3-year survivors (12.9 vs. 9.3 months, respectively; p = 0.008).

Conclusions: HAI chemotherapy can result in prolonged survival in unresectable ICC. Pre-HAI DCE-MRI may predict treatment outcome.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Bile Duct Neoplasms / drug therapy
  • Bile Duct Neoplasms / mortality*
  • Bile Duct Neoplasms / pathology*
  • Bile Ducts, Intrahepatic / pathology*
  • Biomarkers, Tumor / analysis*
  • Cholangiocarcinoma / drug therapy
  • Cholangiocarcinoma / mortality*
  • Cholangiocarcinoma / pathology*
  • Dexamethasone / administration & dosage
  • Female
  • Floxuridine / administration & dosage
  • Follow-Up Studies
  • Humans
  • Infusions, Intra-Arterial*
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Prospective Studies
  • Retrospective Studies
  • Survival Rate

Substances

  • Antibodies, Monoclonal, Humanized
  • Biomarkers, Tumor
  • Floxuridine
  • Bevacizumab
  • Dexamethasone