title: The prognostic and predictive value of combined HE4 and CA-125 in ovarian cancer patients.
abstract: OBJECTIVE
  A risk-of-ovarian-malignancy algorithm (ROMA) based on human epididymis protein 4 (HE4) and CA-125 has been reported to categorize women with a pelvic mass into high or low risk of ovarian malignancy. Originally, the ROMA score was developed for diagnostic purposes and the clinical application of HE4 for other purposes such as a predictor of survival or platinum resistance has not been extensively investigated. The objective of the present study was to evaluate the prognostic importance of prechemotherapy combined levels of HE4 and CA-125 and prediction of platinum resistance. Furthermore, we wanted to investigate the dynamics of the markers during treatment.
  
  
  METHODS
  Serum from 137 patients with newly diagnosed serous ovarian cancer was analyzed for CA-125 and HE4 using ELISAs in a training data set. Patients with high levels (upper third percentiles) of both HE4 and CA-125 were classified as high-risk patients. Data were validated in an independent data set of an additional 94 patients. HE4 and CA-125 were also analyzed at all cycles of subsequent chemotherapy.
  
  
  RESULTS
  The combined score of HE4 and CA-125 was highly predictive of both progression-free and overall survival in univariate as well as multivariate survival analysis. Values in the upper third percentiles (66th) were significantly associated with decreased progression-free and overall survival in both the training and in the validation set (P < 0.05 in all analyses).The positive predictive value in relation to platinum resistance was higher for the combination of markers than for the markers individually. The positive predictive values were 64.3% and 60.7% for combined CA-125/HE4 in the training and validation sets, respectively.
  
  
  CONCLUSIONS
  The combination of HE4 and CA-125 levels at baseline just before initiation of chemotherapy was significantly associated with decreased progression-free and overall survival and to some extent with platinum resistance.
authors.affiliation: Department of Oncology, Vejle Hospital, Kabbeltoft 25, Vejle, Denmark. Karina.Dahl.Steffensen@slb.regionsyddanmark.dk
authors.forename: Karina Dahl
authors.initials: KD
authors.lastname: Steffensen
authors.forename: Marianne
authors.initials: M
authors.lastname: Waldstrøm
authors.forename: Ivan
authors.initials: I
authors.lastname: Brandslund
authors.forename: Max
authors.initials: M
authors.lastname: Petzold
authors.forename: Anders
authors.initials: A
authors.lastname: Jakobsen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood; D018394:CA-125 Antigen / Q000032:analysis / Q000097:blood* / Q000378:metabolism; D000077216:Carcinoma, Ovarian Epithelial; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000097:blood* / Q000378:metabolism; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D011506:Proteins / Q000032:analysis*; D016019:Survival Analysis; D016896:Treatment Outcome; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; C451759:MUC16 protein, human; D008565:Membrane Proteins; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human