Abstract

PurposePresence of circulating tumor cells (CTCs) is associated with impaired clinical outcome in several solid cancers. Limited data are available on the significance of CTCs in gynaecological malignancies. The aims of the present study were to evaluate the dynamics of CTCs in patients with ovarian, fallopian tube and peritoneal cancer during chemotherapy and to assess their clinical relevance.Methods43 patients with ovarian, fallopian tube and peritoneal cancer were included into this prospective study. Patients received chemotherapy according to national guidelines. CTC analysis was performed using the CellSearch system prior to chemotherapy, after three and six cycles.ResultsIn 26% of the patients, ≥ 1CTC per 7.5 ml of blood was detected at baseline (17% of patients with de novo disease, compared to 35% in recurrent patients). Presence of CTCs did not correlate with other factors. After three cycles of therapy, CTC positivity rate declined to 4.8%. After six cycles, no patient showed persistent CTCs. Patients with ≥ 1 CTC at baseline had significantly shorter overall survival and progression-free survival compared to CTC-negative patients (OS: median 3.1 months vs. not reached, p = 0.006, PFS: median 3.1 vs. 23.1 months, p = 0.005). When only the subgroup with newly diagnosed cancer was considered, the association between CTC status and survival was not significant (OS: mean 17.4 vs. 29.0 months, p = 0.192, PFS: 14.3 vs. 26.9 months, p = 0.085). Presence of ≥ 1 CTC after three cycles predicted shorter OS in the entire patient cohort (p < 0.001).ConclusionsHematogenous tumor cell dissemination is a common phenomenon in ovarian, fallopian tube and peritoneal cancer. CTC status before start of systemic therapy correlates with clinical outcome. Chemotherapy leads to a rapid decline in CTC counts; further research is needed to evaluate the clinical value of CTC monitoring after therapy.

Highlights

  • Ovarian cancer is the second most common gynaecological cancer and accounts for more deaths than any other cancer of the female reproductive system [1]

  • In a large pooled analysis of 495 patients with primary ovarian cancer disseminated tumor cells in bone marrow were detected in 27% of patients and predicted significantly shorter overall survival (OS) [6]

  • 43 patients from two certified Gynaecological Cancer Centers were enrolled in this prospective, open-label, nonrandomized study. 34 patients were diagnosed with ovarian cancer, five with fallopian tube cancer and four with primary peritoneal cancer

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Summary

Introduction

Ovarian cancer is the second most common gynaecological cancer and accounts for more deaths than any other cancer of the female reproductive system [1]. Improved strategies to identify patients at risk for recurrence are urgently needed. In this context, blood-based biomarkers such as circulating tumor cells (CTCs) have emerged as a promising candidate. Based on clinical studies, isolated tumor cells can be detected in blood and bone marrow samples of patients with ovarian cancer with similar positivity rates as in breast cancer [5,6,7]. In a large pooled analysis of 495 patients with primary ovarian cancer disseminated tumor cells in bone marrow were detected in 27% of patients and predicted significantly shorter overall survival (OS) [6]. Presence of two or more CTCs have already been shown to be associated with an unfavourable prognosis in relapsed ovarian cancer [7]

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