Abstract
BackgroundTo characterize prognostic and risk factors of central nervous system (CNS) metastases in patients with epithelial ovarian cancer (EOC).MethodsA retrospective analysis of Xijing Hospital electronic medical records was conducted to identify patients with pathologically confirmed EOC and CNS metastases. In addition to patient demographics, tumor pathology, treatment regimens, and clinical outcomes, we compared putative cancer stem cell marker CD133 expression patterns in primary and metastatic lesions as well as in recurrent EOC with and without CNS metastases.ResultsAmong 1366 patients with EOC, metastatic CNS lesions were present in 29 (2.1%) cases. CD133 expression in primary tumor was the only independent risk factor for CNS metastases; whilst the extent of surgical resection of primary EOC and platinum resistance were two independent factors significantly associated with time to CNS metastases. Absence of CD133 expression in primary tumors was significantly associated with high platinum sensitivity in both patient groups with and without CNS metastases. Platinum resistance and CD133 cluster formation in CNS metastases were associated with decreased survival, while multimodal therapy including stereotactic radiosurgery (SRS) for CNS metastases was associated with increased survival following the diagnosis of CNS metastases.ConclusionsThese data suggest that there exist a positive association between CD133 expression in primary EOC, platinum resistance and the increased risk of CNS metastases, as well as a less favorable prognosis of EOC. The absence of CD133 clusters and use of multimodal therapy including SRS could improve the outcome of metastatic lesions. Further investigation is warranted to elucidate the true nature of the association between platinum sensitivity, CD133 expression, and the risk and prognosis of CNS metastases from EOC.
Highlights
To characterize prognostic and risk factors of central nervous system (CNS) metastases in patients with epithelial ovarian cancer (EOC)
There was no correlation between the percentage of CD133+ cells in the metastases and the corresponding primary EOC; but there was a correlation between the CD133+ category in the metastases and primary EOC (Spearman’s rank correlation coefficient, r = 0.706; P = 0.001)
We found that CD133 expression was a risk factor for the development of CNS metastases and that non-optimal cytoreduction and platinum resistance were risk factors for shorter time to the diagnosis of CNS metastases, Figure 3 Kaplan–Meier curves of cumulative overall survival after the diagnosis of central nervous system (CNS) metastases in 29 patients with CNS metastases from ovarian cancer. (A) Platinum-resistant vs. platinum-sensitive disease
Summary
To characterize prognostic and risk factors of central nervous system (CNS) metastases in patients with epithelial ovarian cancer (EOC). The estimated incidence of central nervous system (CNS) metastases in patients with epithelial ovarian cancer (EOC) is 1.01% (range from 0.49% - 2.2%) [1]. An increased incidence of CNS metastases in EOC has been reported [2,3,4], possibly due to a result of better control of the primary cancer, advances in CNS imaging techniques, and use of platinum-based chemotherapies [4]. It has been shown that prognostic factors for EOC patients with CNS metastases vary. CD133 expression was shown to be an unfavorable prognostic factor for overall and disease-free survival in patients with ovarian cancer, which is associated with poor response to platinumbased chemotherapy [17]. As a marker for “stemness”, CD133 is shown to be associated with brain tumor stem cells that play key roles in both brain tumor initiation and recurrence because of their capacity for self-renewal and inherent chemo- and radio-resistance [18]; but limited data are available on its role in tumor metastasis
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