title: 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.
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.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, gian7ni@hotmail.com.
authors.forename: Ioannis T
authors.initials: IT
authors.lastname: Konstantinidis
authors.forename: Richard K G
authors.initials: RK
authors.lastname: Do
authors.forename: David H
authors.initials: DH
authors.lastname: Gultekin
authors.forename: Mithat
authors.initials: M
authors.lastname: Gönen
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Schwartz
authors.forename: Yuman
authors.initials: Y
authors.lastname: Fong
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Allen
authors.forename: Michael I
authors.initials: MI
authors.lastname: D'Angelica
authors.forename: Ronald P
authors.initials: RP
authors.lastname: DeMatteo
authors.forename: David S
authors.initials: DS
authors.lastname: Klimstra
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Kemeny
authors.forename: William R
authors.initials: WR
authors.lastname: Jarnagin
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D001650:Bile Duct Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D018281:Cholangiocarcinoma / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D007261:Infusions, Intra-Arterial; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D005467:Floxuridine; D000068258:Bevacizumab; D003907:Dexamethasone