Circulating Tumor Cells Enumerated by a Centrifugal Microfluidic Device as a Predictive Marker for Monitoring Ovarian Cancer Treatment: A Pilot Study

Abstract

We investigated the size-based isolation and enumeration of circulating tumor cells (CTCs) using a centrifugal microfluidic device equipped with a fluid-assisted separation technology (FAST) disc. We further assessed the correlations among CTCs, cancer antigen-125 (CA125) levels, and clinical course of the disease in a prospective analysis of 47 serial blood samples collected at multiple time-points from 13 ovarian cancer patients. CTCs were isolated from whole blood using the FAST disc and were classified as epithelial cell adhesion molecule (EpCAM)/cytokeratin+, CD45−, and 4′,6-diamidino-2-phenylindole (DAPI)+. Mean CTC count at baseline was 20.2; 84.62% of patients had more than one CTC at baseline and had decreased CTCs counts after surgery and chemotherapy. The CTC counts in eight patients with complete responses were <3. CTC counts were correlated with CA125 levels in three patients without recurrence; they were elevated in three patients with recurrence and normal CA125 concentrations. CTC counts and CA125 levels showed high concordance with directional changes (increasing 71.4%; non-increasing 75.0%). CTC counts showed higher associations with clinical status, sensitivity (100.0% vs. 60.0%), positive predictive value (55.6% vs. 42.9%), and negative predictive value (100.0% vs. 87.5%) than CA125 levels. CTC counts were better associated with treatment response and recurrence than CA125 levels.

Comprehensive analysis of blood-based biomarkers for predicting immunotherapy benefits in patients with advanced non-small cell lung cancer

“…This system overcomes the limitations of inconsistency arising from CTC heterogeneity. The other advantages of CD-FAST TM solo (compared with the immunomagnetic separation method) include high-throughput isolation using centrifugal force, label-free isolation, high detection rate (22,23), and minimal loss of mesenchymal and stem celllike tumor cells with low EpCAM expression. CD-FAST TM also provided uniform, clog-free, ultrafast cell enrichment with pressure drops much less than conventional size-based filtration (24,25).…”

“…The CD-PRIME TM system (Clinomics Inc., Ulsan, Korea), comprising CD-FAST TM solo (disc) and CD-OPR-1000 TM (disc operating machine), was used for CTC enrichment (22)(23)(24)(25). CTCs were isolated on the membrane by rotating the disc using a programmed spin program.…”

Role of Circulating Tumor DNA in Hematological Malignancy

“…CTCs are thought to be part of cancer stem cells released into the bloodstream via the epithelial–mesenchymal transition and undergo hematogenous metastasis [ 15 ]. Therefore, analysis of the CTCs detected in the peripheral blood (PB) of cancer patients is useful for early cancer screening, elucidation of the metastatic process, prediction of prognosis, determination of therapeutic efficacy, and analysis of the mechanisms of therapeutic resistance [ 16 , 17 , 18 , 19 , 20 , 21 ]. There is a paucity of literature on CTCs in hematopoietic tumors, probably because, unlike solid tumors, the concept of metastasis is rarely used and because the detection of CTCs requires complex enrichment methods [ 22 , 23 ].…”

A Novel Liquid Biopsy Strategy to Detect Small Amounts of Cancer Cells Using Cancer-Specific Replication Adenoviruses

“…The CTC detection rate before and after operation was 77% and 57%, respectively. The presence of postoperative CTCs was associated with shorter PFS [ 45 ]. The technologies applied to the detection of CTCs in gynecological field are summarized in Table 1 .…”