title: The role of HE4 for prediction of recurrence in epithelial ovarian cancer patients-results from the OVCAD study.
abstract: Patients with epithelial ovarian cancer (EOC) are at high risk of tumor recurrence. Human epididymis protein 4 (HE4) has been shown to be overexpressed in EOC. The primary aim of our study was to evaluate the role of HE4 in predicting recurrence in EOC patients. Furthermore, we assessed the role of HE4 in predicting recurrence after second-line chemotherapy. We retrospectively analyzed data of 92 out of 275 primary EOC patients of the multicenter project "Ovarian Cancer: Diagnosis of a silent killer" (OVCAD). The concentrations of HE4 and CA125 were determined preoperatively and 6 months after the end of platinum-based first-line chemotherapy (FU) using ELISA and Luminex technique, respectively. The role of HE4 and CA125 for prediction of recurrence was determined using receiver operating characteristics (ROC) curves. Out of 92 patients included, 70 (76 %) were responders and 22 (23 %) non-responders in terms of response to platinum-based first-line chemotherapy. Median HE4 concentrations at follow-up (FU) differed between responders and non-responders (60.5 vs. 237.25 pM, p = 0.0001), respectively. The combined use of HE4 and CA125 at FU with cut-off values of 49.5 pM and 25 U/ml for HE4 and CA125, respectively, for predicting recurrence within 12 months after first-line chemotherapy performed better than HE4 or CA125 alone (area under the curve (AUC) 0.928, 95 % confidence intervals (CI) 0.838-1, p < 0.001). HE4 at FU could predict recurrence within 6 months after second-line chemotherapy (AUC 0.719, 95 % CI 0.553-0.885, p = 0.024). The combination of both elevated biomarkers revealed significantly worse estimated median progression-free survival (PFS; hazard ratio (HR) 8.14, 95 % CI 3.75-17.68, p < 0.001) and slightly worse PFS in those in whom only one biomarker was elevated (HR 1.46, 95 % CI 0.72-2.96, p = 0.292) compared to those patients in whom no biomarker was elevated. For the estimated median overall survival (OS), our analysis revealed similar results. HE4 in combination with CA125 performed better than CA125 and HE4 alone in predicting recurrence within 12 months after first-line chemotherapy.
authors.affiliation: Department of Gynecology, Tumor Bank Ovarian Cancer (TOC), European Competence Center for Ovarian Cancer, Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. mani.nassir@charite.de.|Center for Clinical Research and Management Education, Division of Health Care Sciences, Dresden International University, Dresden, Germany. mani.nassir@charite.de.
authors.forename: Mani
authors.initials: M
authors.lastname: Nassir
authors.affiliation: Department of Gynecology, Tumor Bank Ovarian Cancer (TOC), European Competence Center for Ovarian Cancer, Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Jun
authors.initials: J
authors.lastname: Guan
authors.affiliation: Department of Gynecology, Tumor Bank Ovarian Cancer (TOC), European Competence Center for Ovarian Cancer, Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Luketina
authors.affiliation: Center for Clinical Research and Management Education, Division of Health Care Sciences, Dresden International University, Dresden, Germany.|Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Siepmann
authors.affiliation: Department of Gynecology, Tumor Bank Ovarian Cancer (TOC), European Competence Center for Ovarian Cancer, Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Irena
authors.initials: I
authors.lastname: Rohr
authors.affiliation: Department of Gynecology, Tumor Bank Ovarian Cancer (TOC), European Competence Center for Ovarian Cancer, Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Richter
authors.affiliation: Molecular Oncology Group, Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria.
authors.forename: Dan Cacsire
authors.initials: DC
authors.lastname: Castillo-Tong
authors.affiliation: Molecular Oncology Group, Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria.|Ludwig Boltzmann Cluster Translational Oncology, General Hospital of Vienna, Vienna, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Zeillinger
authors.affiliation: Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, Leuven Cancer Institute, University Hospitals Leuven, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.affiliation: Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, Leuven Cancer Institute, University Hospitals Leuven, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Els
authors.initials: E
authors.lastname: Van Nieuwenhuysen
authors.affiliation: Department of Obstetrics and Gynecology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Nicole
authors.initials: N
authors.lastname: Concin
authors.affiliation: Department of Obstetrics and Gynecology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Marth
authors.affiliation: Fujirebio Diagnostics AB, Gothenburg, Sweden.
authors.forename: Christina
authors.initials: C
authors.lastname: Hall
authors.affiliation: Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Mahner
authors.affiliation: Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Linn
authors.initials: L
authors.lastname: Woelber
authors.affiliation: Department of Gynecology, Tumor Bank Ovarian Cancer (TOC), European Competence Center for Ovarian Cancer, Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
authors.affiliation: Department of Gynecology, Tumor Bank Ovarian Cancer (TOC), European Competence Center for Ovarian Cancer, Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Elena Ioana
authors.initials: EI
authors.lastname: Braicu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018394:CA-125 Antigen / Q000097:blood; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D011506:Proteins / Q000032:analysis*; D012189:Retrospective Studies; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: D018394:CA-125 Antigen; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human
keywords: CA125; Epithelial ovarian cancer; HE4; Prediction; Recurrence