Prognostic analysis of invasive circulating tumor cells (iCTCs) in epithelial ovarian cancer

Abstract

Goals: Circulating tumor cells (CTCs) have been introduced as a biomarker in detecting advanced Epithelial Ovarian Cancer (EOC). The goals are to examine the prevalence of the invasive subpopulation of CTCs (iCTCs) in patients at high risk of EOC and to compare this biomarker to serum CA125. Methods: We used a unique Cell Adhesion Matrix (CAM)-based, functional cell enrichment and identification platform to isolate iCTCs from 129 preoperative patients. We confirmed the identity of iCTCs using positive epithelial (Epi+) markers and negative hematopoietic lineage (HL-) markers. Sensitivity and specificity of the assays were examined and iCTCs / CA125 were correlated with overall survival (OS), progression-free survival (PFS) and clinical parameters. Results: We found a 41.2% sensitivity, 95.1% specificity and 77.8% positive predictive value (PPV) of the iCTC assay in detecting patients with stage I and II EOC malignancy, and a 83% sensitivity and 97.3% PPV in detecting all stages of EOC malignancy. However, a positive CA125 test provided weak evidence to detect stage I and II malignancy (61.6% PPV) and all EOC (92.1% PPV), because of its 76.2% specificity. A significantly stronger concordance in OS and PFS of clinical factors (tumor stage, debulking and platinum sensitivity) was noted for elevated iCTCs than for serum CA125. Conclusion: The CAM-initiated CTC enrichment / identification method enabled the detection of early stage EOC. iCTCs were better correlated with worse OS and PFS, more specific and better PPV than CA125 in detecting EOC malignancy in patients at high risk of EOC.

Liquid biopsy in ovarian cancer: recent advances on circulating tumor cells and circulating tumor DNA

“…The same group also investigated the predictive value of CTC levels in a small group of 31 ovarian cancer patients that received standard taxol/carboplatin chemotherapy, where blood specimens were obtained at different time points, before and after surgery and up to 24 months after chemotherapy treatment. Using the same assay [27], they showed a statistically significant association between CTC levels and disease progression [26].…”

“…They reported that the CAM + CTCs were invasive and their presence significantly correlated with decreased progression-free survival(PFS) (p = 0.042) [34]. The same group evaluated the prognostic significance of CTCs in a group of 129 pre-surgery ovarian cancer patients using the same method for the detection and identification of CTCs and observed statistically significant association between the presence of CTCs and both OS (p = 0.0219) and PFS (p = 0.0024) [27]. The same group also investigated the predictive value of CTC levels in a small group of 31 ovarian cancer patients that received standard taxol/carboplatin chemotherapy, where blood specimens were obtained at different time points, before and after surgery and up to 24 months after chemotherapy treatment.…”

Circulating tumor cells as a new and additional approach to follow-up patients with serous low-grade ovarian adenocarcinoma – a case report and review of the literature

“…They also showed that in patients with high-grade adenocarcinoma there was a direct relationship between higher levels of CTCs, more aggressive disease, and higher levels of CA125. Poveda et al [28] also found a direct connection between elevated CTCs and shorter PFS and OS. The study conducted by Poveda was a multicentric phase III study, enrolling 672 patients.…”

Real-time RT-PCR systems for CTC detection from blood samples of breast cancer and gynaecological tumour patients (Review)

“…Just like in breast cancer studies, also in ovarian cancer a further characterization of CTCs by use of more marker genes, like PPIC, is pursued (178). A rather new topic in the CTC-field in ovarian cancer is the analysis of invasive CTCs (iCTCs), as it was shown that iCTCs are better correlated to progressionfree and overall survival and even more specific than the up to now widely used serum marker CA125 (179). The predictive value of CTC occurrence in ovarian cancer was reconfirmed in 2015 in a study of Zeng et al (180), who was able to demonstrate, that patients with CTCs in the peripheral blood had a shorter DFS and OAS than patients without CTCs in their blood.…”