title: Application of a time-varying covariate model to the analysis of CA 19-9 as serum biomarker in patients with advanced pancreatic cancer.
abstract: OBJECTIVE
  The clinical relevance of CA 19-9 as surrogate biomarker in advanced pancreatic cancer is a matter of debate.
  
  
  METHODS
  This retrospective multicenter study included patients with histologically confirmed advanced pancreatic cancer treated with first-line therapy. Analysis of CA 19-9 was done using the Elecsys assay (Roche Diagnostics). For an analysis of CA 19-9 kinetics, at least three measurements during first-line chemotherapy had to be available. The effect of pretreatment CA 19-9 levels on time-to-progression (TTP) and overall survival (OS) was modeled by Cox proportional hazards regression. The effect of CA 19-9 kinetics was also modeled by Cox proportional hazards regression where CA 19-9 was treated as a time-varying covariate.
  
  
  RESULTS
  One hundred and fifteen patients from five German centers were included; 73% of them were treated within prospective clinical trials. Median TTP was 4.4 months and median OS was 9.4 months; univariate analysis indicated that pretreatment CA 19-9 [as continuous variable, log (CA 19-9)] was significantly associated with TTP [hazard ratio (HR), 1.24; P < 0.001] and OS (HR, 1.16; P = 0.002). These associations remained significant within multivariate analysis. For CA 19-9 kinetics during chemotherapy, data from 69 patients (TTP) and 84 patients (OS) were available, respectively; log (CA 19-9) kinetics after start of treatment were found to be a significant predictor for TTP in univariate (HR, 1.48; P < 0.001) and multivariate (HR, 1.45; P < 0.001) analyses, and also for OS (univariate: HR, 1.34; P < 0.001; multivariate: HR, 1.38; P < 0.001).
  
  
  CONCLUSIONS
  Pretreatment CA 19-9 and CA 19-9 kinetics may serve as a useful serum biomarker in advanced pancreatic cancer.
authors.affiliation: Department of Internal Medicine III, Ludwig-Maximilians-University of Munich, Munich, Germany. stefan.boeck@med.uni-muenchen.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Boeck
authors.forename: Michael
authors.initials: M
authors.lastname: Haas
authors.forename: Rüdiger P
authors.initials: RP
authors.lastname: Laubender
authors.forename: Frank
authors.initials: F
authors.lastname: Kullmann
authors.forename: Christina
authors.initials: C
authors.lastname: Klose
authors.forename: Christiane J
authors.initials: CJ
authors.lastname: Bruns
authors.forename: Ralf
authors.initials: R
authors.lastname: Wilkowski
authors.forename: Petra
authors.initials: P
authors.lastname: Stieber
authors.forename: Stefan
authors.initials: S
authors.lastname: Holdenrieder
authors.forename: Hannes
authors.initials: H
authors.lastname: Buchner
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mansmann
authors.forename: Volker
authors.initials: V
authors.lastname: Heinemann
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D018395:CA-19-9 Antigen / Q000097:blood*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000401:mortality; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen