title: Predictive value of modeled AUC(AFP-hCG), a dynamic kinetic parameter characterizing serum tumor marker decline in patients with nonseminomatous germ cell tumor.
abstract: OBJECTIVE
  The early decline profile of alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) in patients with nonseminomatous germ cell tumors (NSGCT) treated with chemotherapy may be related to the risk of relapse. We assessed the predictive values of areas under the curve of hCG (AUC(hCG)) and AFP (AUC(AFP)) of modeled concentration-time equations on progression-free survival (PFS).
  
  
  METHODS
  Single-center retrospective analysis of hCG and AFP time-points from 65 patients with IGCCCG intermediate-poor risk NSGCT treated with 4 cycles of bleomycin-etoposide-cisplatin (BEP). To determine AUC(hCG) and AUC(AFP) for D0-D42, AUCs for D0-D7 were calculated using the trapezoid rule and AUCs for D7-D42 were calculated using the mathematic integrals of equations modeled with NONMEM. Combining AUC(AFP) and AUC(hCG) enabled us to define 2 predictive groups: namely, patients with favorable and unfavorable AUC(AFP-hCG). Survival analyses and ROC curves assessed the predictive values of AUC(AFP-hCG) groups regarding progression-free survival (PFS) and compared them with those of half-life (HL) and time-to-normalization (TTN).
  
  
  RESULTS
  Mono-exponential models best fit the patterns of marker decreases. Patients with a favorable AUC(AFP-hCG) had a significantly better PFS (100% vs 71.5%, P = .014). ROC curves confirmed the encouraging predictive accuracy of AUC(AFP-hCG) against HL or TTN regarding progression risk (ROC AUCs = 79.6 vs 71.9 and 70.2 respectively). Because of the large number of patients with missing data, multivariate analysis could not be performed.
  
  
  CONCLUSIONS
  AUC(AFP-hCG) is a dynamic parameter characterizing tumor marker decline in patients with NSGCT during BEP treatment. Its value as a promising predictive factor should be validated.
authors.affiliation: Université de Lyon, Lyon, France. benoit.you@chu-lyon.fr
authors.forename: Benoit
authors.initials: B
authors.lastname: You
authors.forename: Ludivine
authors.initials: L
authors.lastname: Fronton
authors.forename: Helen
authors.initials: H
authors.lastname: Boyle
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Droz
authors.forename: Pascal
authors.initials: P
authors.lastname: Girard
authors.forename: Brigitte
authors.initials: B
authors.lastname: Tranchand
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ribba
authors.forename: Michel
authors.initials: M
authors.lastname: Tod
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chabaud
authors.forename: Henri
authors.initials: H
authors.lastname: Coquelin
authors.forename: Aude
authors.initials: A
authors.lastname: Fléchon
mesh_terms: D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D006063:Chorionic Gonadotropin / Q000097:blood*; D006801:Humans; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000097:blood*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D013736:Testicular Neoplasms / Q000097:blood*; D013997:Time Factors; D000509:alpha-Fetoproteins / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D006063:Chorionic Gonadotropin; D000509:alpha-Fetoproteins