The Long-Term Prognostic Significance of Circulating Tumor Cells in Ovarian Cancer—A Study of the OVCAD Consortium

Introduction: We previously reported the prognostic impact of circulating tumor cells (CTCs) in a multicenter study on minimal residual disease in primary ovarian cancer. With additional follow-up data, we evaluated the combined CTC approach (CTCs<sup>combo</sup>), in particular for the...

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Main Authors: Eva Obermayr, Angelika Reiner, Burkhard Brandt, Elena Ioana Braicu, Alexander Reinthaller, Liselore Loverix, Nicole Concin, Linn Woelber, Sven Mahner, Jalid Sehouli, Ignace Vergote, Robert Zeillinger
Format: Article
Language:English
Published: MDPI AG 2021-05-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/13/11/2613
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author Eva Obermayr
Angelika Reiner
Burkhard Brandt
Elena Ioana Braicu
Alexander Reinthaller
Liselore Loverix
Nicole Concin
Linn Woelber
Sven Mahner
Jalid Sehouli
Ignace Vergote
Robert Zeillinger
author_facet Eva Obermayr
Angelika Reiner
Burkhard Brandt
Elena Ioana Braicu
Alexander Reinthaller
Liselore Loverix
Nicole Concin
Linn Woelber
Sven Mahner
Jalid Sehouli
Ignace Vergote
Robert Zeillinger
author_sort Eva Obermayr
collection DOAJ
description Introduction: We previously reported the prognostic impact of circulating tumor cells (CTCs) in a multicenter study on minimal residual disease in primary ovarian cancer. With additional follow-up data, we evaluated the combined CTC approach (CTCs<sup>combo</sup>), in particular for the patients who had survived more than five years. Material and Methods: Blood samples taken at baseline and six months after adjuvant treatment (follow-up) were assessed by quantitative PCR (qPCR) measuring PPIC transcripts and immunofluorescent staining (IF). A positive result with either IF or qPCR was classified as CTC<sup>combo</sup>-positive. Further, PPIC was assessed in the primary tumor tissue. Results: The concordance of IF and qPCR was 65% at baseline and 83% after treatment. Results showed that 50.5% of the baseline and 29.5% of the follow-up samples were CTC<sup>combo</sup>-positive. CTCs<sup>combo</sup> after treatment were associated with increased mortality after adjusting for FIGO stage (HR 2.574, 95% CI: 1.227–5.398, <i>p</i> = 0.012), a higher risk of recurrence after adjusting for peritoneal carcinosis (HR 4.068, 95% CI: 1.948–8.498, <i>p</i> < 0.001), and increased mortality after five survived years. Discussion: The two-sided analytical approach revealed CTC subpopulations associated with ovarian cancer progression and may illuminate a potential treatment-related shift in molecular phenotypes. That approach can identify patients who have elevated risk of recurrence and death due to ovarian cancer and who may require risk-adapted treatment strategies.
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spelling doaj.art-bff0f2ea4a634a26986d7c7dca61077e2023-11-21T21:27:44ZengMDPI AGCancers2072-66942021-05-011311261310.3390/cancers13112613The Long-Term Prognostic Significance of Circulating Tumor Cells in Ovarian Cancer—A Study of the OVCAD ConsortiumEva Obermayr0Angelika Reiner1Burkhard Brandt2Elena Ioana Braicu3Alexander Reinthaller4Liselore Loverix5Nicole Concin6Linn Woelber7Sven Mahner8Jalid Sehouli9Ignace Vergote10Robert Zeillinger11Department of Obstetrics and Gynecology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Pathology, Klinikum Donaustadt, 1090 Vienna, AustriaInstitute of Tumor Biology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, GermanyDepartment of Gynecology, European Competence Center for Ovarian Cancer, Campus Virchow Klinikum, Charité, Universitätsmedizin Berlin, 13353 Berlin, GermanyDepartment of Obstetrics and Gynecology, Medical University of Vienna, 1090 Vienna, AustriaDivision of Gynecological Oncology, Department of Obstetrics and Gynecology, University Hospitals Leuven, Katholieke Universiteit Leuven, 3000 Leuven, BelgiumDepartment of Obstetrics and Gynecology, Innsbruck Medical University, 6020 Innsbruck, AustriaDepartment of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyDepartment of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyDepartment of Gynecology, European Competence Center for Ovarian Cancer, Campus Virchow Klinikum, Charité, Universitätsmedizin Berlin, 13353 Berlin, GermanyDivision of Gynecological Oncology, Department of Obstetrics and Gynecology, University Hospitals Leuven, Katholieke Universiteit Leuven, 3000 Leuven, BelgiumDepartment of Obstetrics and Gynecology, Medical University of Vienna, 1090 Vienna, AustriaIntroduction: We previously reported the prognostic impact of circulating tumor cells (CTCs) in a multicenter study on minimal residual disease in primary ovarian cancer. With additional follow-up data, we evaluated the combined CTC approach (CTCs<sup>combo</sup>), in particular for the patients who had survived more than five years. Material and Methods: Blood samples taken at baseline and six months after adjuvant treatment (follow-up) were assessed by quantitative PCR (qPCR) measuring PPIC transcripts and immunofluorescent staining (IF). A positive result with either IF or qPCR was classified as CTC<sup>combo</sup>-positive. Further, PPIC was assessed in the primary tumor tissue. Results: The concordance of IF and qPCR was 65% at baseline and 83% after treatment. Results showed that 50.5% of the baseline and 29.5% of the follow-up samples were CTC<sup>combo</sup>-positive. CTCs<sup>combo</sup> after treatment were associated with increased mortality after adjusting for FIGO stage (HR 2.574, 95% CI: 1.227–5.398, <i>p</i> = 0.012), a higher risk of recurrence after adjusting for peritoneal carcinosis (HR 4.068, 95% CI: 1.948–8.498, <i>p</i> < 0.001), and increased mortality after five survived years. Discussion: The two-sided analytical approach revealed CTC subpopulations associated with ovarian cancer progression and may illuminate a potential treatment-related shift in molecular phenotypes. That approach can identify patients who have elevated risk of recurrence and death due to ovarian cancer and who may require risk-adapted treatment strategies.https://www.mdpi.com/2072-6694/13/11/2613primary epithelial ovarian cancercirculating tumor cellslong-term survival
spellingShingle Eva Obermayr
Angelika Reiner
Burkhard Brandt
Elena Ioana Braicu
Alexander Reinthaller
Liselore Loverix
Nicole Concin
Linn Woelber
Sven Mahner
Jalid Sehouli
Ignace Vergote
Robert Zeillinger
The Long-Term Prognostic Significance of Circulating Tumor Cells in Ovarian Cancer—A Study of the OVCAD Consortium
Cancers
primary epithelial ovarian cancer
circulating tumor cells
long-term survival
title The Long-Term Prognostic Significance of Circulating Tumor Cells in Ovarian Cancer—A Study of the OVCAD Consortium
title_full The Long-Term Prognostic Significance of Circulating Tumor Cells in Ovarian Cancer—A Study of the OVCAD Consortium
title_fullStr The Long-Term Prognostic Significance of Circulating Tumor Cells in Ovarian Cancer—A Study of the OVCAD Consortium
title_full_unstemmed The Long-Term Prognostic Significance of Circulating Tumor Cells in Ovarian Cancer—A Study of the OVCAD Consortium
title_short The Long-Term Prognostic Significance of Circulating Tumor Cells in Ovarian Cancer—A Study of the OVCAD Consortium
title_sort long term prognostic significance of circulating tumor cells in ovarian cancer a study of the ovcad consortium
topic primary epithelial ovarian cancer
circulating tumor cells
long-term survival
url https://www.mdpi.com/2072-6694/13/11/2613
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