title: Prognostic value of serum HE4 levels and risk of ovarian malignancy algorithm scores at the time of ovarian cancer diagnosis.
abstract: OBJECTIVE
  The aim of this study is to assess whether the pretreatment serum HE4 levels or the Risk of Ovarian Malignancy Algorithm (ROMA) scores at the time of initial diagnosis are associated with progression-free survival (PFS) and disease-specific survival (DSS) in patients with ovarian cancer receiving either primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery.
  
  
  METHODS
  A survival analysis of 101 cases of invasive ovarian cancer recruited in a previous diagnostic accuracy study was conducted from 2005 to 2009 at the University Hospital KU Leuven, Belgium. Serum HE4 levels (pM) and ROMA scores (%) were obtained before primary treatment. Dates of death were obtained by record linkage with patient hospital files. Progression was evaluated according to the Response Evaluation Criteria in Solid Tumors. Adjusted hazards ratios (HRs) were estimated using multivariable Cox regression.
  
  
  RESULTS
  Eighty patients (79%) with invasive ovarian cancer underwent primary debulking surgery, whereas 21 (21%) received neoadjuvant chemotherapy. The median DSS was 3.72 years (95% confidence interval [CI], 3.19-4.07). Fifty-two patients (51%) died of disease, and 74 patients (73%) had progressive disease during follow-up. On univariable analysis, elevated pretreatment HE4 levels and ROMA scores were related to worse prognosis. However, after the adjustment for classic prognostic variables, HE4 levels (log2-transformed) and ROMA scores were unrelated to DSS (log-2 HE4: adjusted HR, 1.01; 95% CI, 0.84-1.21 and ROMA: adjusted HR per 10% increase, 0.96; 95% CI, 0.84-1.12) and PFS (log-2 HE4: adjusted HR, 0.98; 95% CI, 0.84-1.13 and ROMA: adjusted HR per 10% increase, 0.98; 95% CI, 0.88-1.11).
  
  
  CONCLUSIONS
  Pretreatment HE4 levels and ROMA scores are not independent prognostic factors for DSS and PFS after multivariable adjustment in patients with ovarian cancer.
authors.affiliation: Departments of *Department of Development and Regeneration, KU Leuven, Leuven, Belgium; †Department of Obstetrics and Gynecology, and ‡Leuven Cancer Institute, University Hospital KU Leuven, Leuven, Belgium; §Department of Electrical Engineering (ESAT) and ∥iMinds Future Health Department, KU Leuven, Leuven, Belgium; ¶Department of Obstetrics and Gynecology, Maastricht UMC+, #GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands; and **Department of Surgery and Cancer, Queen Charlotte's & Chelsea Hospital, Imperial College, London, United Kingdom.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Kaijser
authors.forename: Vanya
authors.initials: V
authors.lastname: Van Belle
authors.forename: Toon
authors.initials: T
authors.lastname: Van Gorp
authors.forename: Ahmad
authors.initials: A
authors.lastname: Sayasneh
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.forename: Tom
authors.initials: T
authors.lastname: Bourne
authors.forename: Ben
authors.initials: B
authors.lastname: Van Calster
authors.forename: Dirk
authors.initials: D
authors.lastname: Timmerman
mesh_terms: D000368:Aged; D000465:Algorithms; D018284:Cystadenocarcinoma, Serous / Q000097:blood / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy; D011237:Predictive Value of Tests; D011379:Prognosis; D011506:Proteins / Q000032:analysis / Q000378:metabolism*; D012107:Research Design; D012307:Risk Factors; D013997:Time Factors; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human