Eva Obermayr1, Angelika Reiner2, Burkhard Brandt3,4, Elena Ioana Braicu5, Alexander Reinthaller1, Liselore Loverix6, Nicole Concin7, Linn Woelber8, Sven Mahner8,9, Jalid Sehouli5, Ignace Vergote6, Robert Zeillinger1. 1. Department of Obstetrics and Gynecology, Medical University of Vienna, 1090 Vienna, Austria. 2. Department of Pathology, Klinikum Donaustadt, 1090 Vienna, Austria. 3. Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany. 4. Institute of Clinical Chemistry, University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany. 5. Department of Gynecology, European Competence Center for Ovarian Cancer, Campus Virchow Klinikum, Charité, Universitätsmedizin Berlin, 13353 Berlin, Germany. 6. Division of Gynecological Oncology, Department of Obstetrics and Gynecology, University Hospitals Leuven, Katholieke Universiteit Leuven, 3000 Leuven, Belgium. 7. Department of Obstetrics and Gynecology, Innsbruck Medical University, 6020 Innsbruck, Austria. 8. Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. 9. Department of Obstetrics and Gynecology, University Hospital, LMU Munich, 81377 Munich, Germany.
Abstract
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 (CTCscombo), 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 CTCcombo-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 CTCcombo-positive. CTCscombo after treatment were associated with increased mortality after adjusting for FIGO stage (HR 2.574, 95% CI: 1.227-5.398, p = 0.012), a higher risk of recurrence after adjusting for peritoneal carcinosis (HR 4.068, 95% CI: 1.948-8.498, p < 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.
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 (CTCscombo), 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 CTCcombo-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 CTCcombo-positive. CTCscombo after treatment were associated with increased mortality after adjusting for FIGO stage (HR 2.574, 95% CI: 1.227-5.398, p = 0.012), a higher risk of recurrence after adjusting for peritoneal carcinosis (HR 4.068, 95% CI: 1.948-8.498, p < 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.
Entities:
Keywords:
circulating tumor cells; long-term survival; primary epithelial ovarian cancer
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