title: Efficacy of neoadjuvant chemoradiation, followed by liver transplantation, for perihilar cholangiocarcinoma at 12 US centers.
abstract: OBJECTIVE
  Excellent single-center outcomes of neoadjuvant chemoradiation and liver transplantation for unresectable perihilar cholangiocarcinoma caused the United Network of Organ Sharing to offer a standardized model of end-stage liver disease (MELD) exception for this disease. We analyzed data from multiple centers to determine the effectiveness of this treatment and the appropriateness of the MELD exception.
  
  
  METHODS
  We collected and analyzed data from 12 large-volume transplant centers in the United States. These centers met the inclusion criteria of treating 3 or more patients with perihilar cholangiocarcinoma using neoadjuvant therapy, followed by liver transplantation, from 1993 to 2010 (n = 287 total patients). Center-specific protocols and medical charts were reviewed on-site.
  
  
  RESULTS
  The patients completed external radiation (99%), brachytherapy (75%), radiosensitizing therapy (98%), and/or maintenance chemotherapy (65%). Seventy-one patients dropped out before liver transplantation (rate, 11.5% in 3 months). Intent-to-treat survival rates were 68% and 53%, 2 and 5 years after therapy, respectively; post-transplant, recurrence-free survival rates were 78% and 65%, respectively. Patients outside the United Network of Organ Sharing criteria (those with tumor mass >3 cm, transperitoneal tumor biopsy, or metastatic disease) or with a prior malignancy had significantly shorter survival times (P < .001). There were no differences in outcomes among patients based on differences in surgical staging or brachytherapy. Although most patients came from 1 center (n = 193), the other 11 centers had similar survival times after therapy.
  
  
  CONCLUSIONS
  Patients with perihilar cholangiocarcinoma who were treated with neoadjuvant therapy followed up by liver transplantation at 12 US centers had a 65% rate of recurrence-free survival after 5 years, showing this therapy to be highly effective. An 11.5% drop-out rate after 3.5 months of therapy indicates the appropriateness of the MELD exception. Rigorous selection is important for the continued success of this treatment.
authors.affiliation: William J. von Liebig Transplant Center, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Sarwa
authors.initials: S
authors.lastname: Darwish Murad
authors.forename: W Ray
authors.initials: WR
authors.lastname: Kim
authors.forename: Denise M
authors.initials: DM
authors.lastname: Harnois
authors.forename: David D
authors.initials: DD
authors.lastname: Douglas
authors.forename: James
authors.initials: J
authors.lastname: Burton
authors.forename: Laura M
authors.initials: LM
authors.lastname: Kulik
authors.forename: Jean F
authors.initials: JF
authors.lastname: Botha
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Mezrich
authors.forename: William C
authors.initials: WC
authors.lastname: Chapman
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Schwartz
authors.forename: Johnny C
authors.initials: JC
authors.lastname: Hong
authors.forename: Jean C
authors.initials: JC
authors.lastname: Emond
authors.forename: Hoonbae
authors.initials: H
authors.lastname: Jeon
authors.forename: Charles B
authors.initials: CB
authors.lastname: Rosen
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Gores
authors.forename: Julie K
authors.initials: JK
authors.lastname: Heimbach
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000628:therapy*; D001653:Bile Ducts, Intrahepatic; D059248:Chemoradiotherapy; D018281:Cholangiocarcinoma / Q000628:therapy*; D005260:Female; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D012189:Retrospective Studies; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult