title: Decline in CA19-9 during chemotherapy predicts survival in four independent cohorts of patients with inoperable bile duct cancer.
abstract: BACKGROUND
  Carbohydrate associated antigen (CA19-9) has been approved by the FDA as a biomarker for monitoring treatment effect in pancreatic cancer. However, the value of serum CA19-9 as a biomarker of response to chemotherapy in bile duct cancer is unclear. The aim of this study was to determine if a decline in CA19-9 (CA19-9 response) during chemotherapy is predictive of survival in patients with inoperable bile duct cancer.
  
  
  METHODS
  Consecutive patients with inoperable bile duct cancer treated at a University Hospital were retrospectively included in an investigational cohort (n = 212). Three validation cohorts were established including patients 1) participating in phase I/II trials at a Danish Hospital (n = 71), 2) identified retrospectively in a Canadian cohort (n = 196) and 3) randomized in the ABC-02 trial (n = 410). Patients with a baseline CA19-9 and at least one CA19-9 value measured 10-12 weeks after the start of chemotherapy were included. Multivariate Cox regression analyses were performed.
  
  
  RESULTS
  Patients meeting the criteria to be included were 54 in the investigational cohort and 34, 68 and 148 in the three validation sets, respectively. Multivariate analysis included radiological response, performance status, bilirubin, gender, site of cancer, extend of disease, CA19-9 at baseline and age. A hazard ratio (HR) of 0.60 (95%CI: 0.44-0.80, p = 0.0005) for death in CA19-9 responders was reached in the investigational cohort. The predictive value of CA 19-9 response was confirmed in all three validation cohorts.
  
  
  CONCLUSIONS
  CA19-9 response is a robust predictor of survival in patients with inoperable bile duct cancer in four independent data sets.
authors.affiliation: Dept. of Oncology, Rigshospitalet, Blegdamsvej 9, DK2100 Copenhagen O, Denmark. Electronic address: mgrunnet@hotmail.com.
authors.forename: Mie
authors.initials: M
authors.lastname: Grunnet
authors.affiliation: The Finsen Laboratory, Rigshospitalet & Biotech Research and Innovation Centre, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
authors.forename: Ib J
authors.initials: IJ
authors.lastname: Christensen
authors.affiliation: Dept. of Oncology, Rigshospitalet, Blegdamsvej 9, DK2100 Copenhagen O, Denmark.
authors.forename: Ulrik
authors.initials: U
authors.lastname: Lassen
authors.affiliation: Dept. of Oncology, Lillebælt Hospital Vejle, DK-7100 Vejle, Denmark.
authors.forename: Lars H
authors.initials: LH
authors.lastname: Jensen
authors.affiliation: Dept. of Clinical Biochemistry and Immunology, National Institute for Health Data and Disease Control, DK-2300 Copenhagen S, Denmark.
authors.forename: Magnus
authors.initials: M
authors.lastname: Lydolph
authors.affiliation: Dept. of Medical Oncology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, ON M5G 2M9, Canada.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Knox
authors.affiliation: Dept. of Medical Oncology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, ON M5G 2M9, Canada; University of Manchester, Dept. Medical Oncology, The Christie Hospital, NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, United Kingdom.
authors.forename: Mairead G
authors.initials: MG
authors.lastname: McNamara
authors.affiliation: University College London Cancer Institute, Gower Street, London WC1E 6BT, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Jitlal
authors.affiliation: Hammersmith Hospital, Imperial College Health Care Trust, Du Cane Road, London, Greater London W12 0HS, United Kingdom.
authors.forename: Harpreet
authors.initials: H
authors.lastname: Wasan
authors.affiliation: University College London Cancer Institute, Gower Street, London WC1E 6BT, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Bridgewater
authors.affiliation: University of Manchester, Dept. Medical Oncology, The Christie Hospital, NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, United Kingdom.
authors.forename: Juan W
authors.initials: JW
authors.lastname: Valle
authors.affiliation: Dept. of Oncology, Rigshospitalet, Blegdamsvej 9, DK2100 Copenhagen O, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Mau-Sorensen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000097:blood* / Q000188:drug therapy*; D018395:CA-19-9 Antigen / Q000097:blood*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D018395:CA-19-9 Antigen
keywords: Bile duct cancer; Biomarkers; CA19-9; Response to therapy