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Prognostic Value of Serum HE4 Levels and Risk of Ovarian Malignancy Algorithm Scores at the Time of Ovarian Cancer Diagnosis
  1. Jeroen Kaijser, MD, MSc*,,,
  2. Vanya Van Belle, PhD§,
  3. Toon Van Gorp, MD, PhD,,,#,
  4. Ahmad Sayasneh, MD, MRCOG**,
  5. Ignace Vergote, MD, PhD,,
  6. Tom Bourne, MD, PhD, FRCOG*,,,**,
  7. Ben Van Calster, PhD* and
  8. Dirk Timmerman, MD, PhD*,,
  1. *Departments of Department of Development and Regeneration, KU Leuven, Leuven, Belgium;
  2. Department of Obstetrics and Gynecology, and
  3. Leuven Cancer Institute, University Hospital KU Leuven, Leuven, Belgium;
  4. §Department of Electrical Engineering (ESAT) and
  5. iMinds Future Health Department, KU Leuven, Leuven, Belgium;
  6. Department of Obstetrics and Gynecology, Maastricht UMC+,
  7. #GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands; and
  8. **Department of Surgery and Cancer, Queen Charlotte’s & Chelsea Hospital, Imperial College, London, United Kingdom.
  1. Address correspondence and reprint requests to Dirk Timmerman, MD, PhD, Department of Development and Regeneration, Obstetrics and Gynecology, and Leuven Cancer Institute, University Hospital KU Leuven, Herestraat 49, 3000 Leuven, Belgium. E-mail:


Objectives 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.

  • Ovarian cancer
  • Biomarkers
  • Prognosis
  • Mortality
  • Survival analysis

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  • Funding: B.V.C. is a postdoctoral fellow from the Research Foundation–Flanders (FWO). D.T. and B.V.C. received a project grant from the FWO (grant G049312N) for the IOTA 5 project. T.B. is supported by the National Institute for Health Research Biomedical Research Centre based at the Imperial College Healthcare NHS Trust and Imperial College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research, or the Department of Health. T.V.G. is supported by the Academic Fund of the Maastricht University Medical Center. All study sponsors had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the study; and in the decision to submit the study for publication.

  • The authors declare no conflicts of interest.