Circulating Tumor Cells as Potential Biomarkers in XXXX .

@entity1 @entity5 @entity900 @entity150 @entity3214
PURPOSE: We explored the diagnostic use of circulating @entity5 cells in @entity1 with neoadjuvant @entity150 using enumeration and next generation sequencing. MATERIALS AND METHODS: A total of 20 @entity1 with @entity150 who were eligible for @entity900 based neoadjuvant chemotherapy were enrolled in an institutional review board approved study. Subjects underwent blood draws at baseline and after 1 cycle of chemotherapy. A total of 11 @entity1 with metastatic @entity150 and 13 healthy donors were analyzed for comparison. Samples were enriched for circulating @entity5 cells using the novel IsoFlux    System microfluidic collection device. Circulating @entity5 cell counts were analyzed for repeatability and compared with Food and Drug Administration cleared circulating @entity5 cells. Circulating @entity5 cells were also analyzed for mutational status using next generation sequencing. RESULTS: Median circulating @entity5 cell counts were 13 at baseline and 5 at followup in the neoadjuvant group, 29 in the metastatic group and 2 in the healthy group. The concordance of circulating @entity5 cell levels, defined as low-fewer than 10, medium-11 to 30 and high-greater than 30, across replicate tubes was 100% in 15 preparations. In matched samples the IsoFlux test showed 10 or more circulating @entity5 cells in 4 of 9 samples (44%) while CellSearch   showed 0 of 9 (0%). At cystectomy 4 months after baseline all 3 @entity1 (100%) with medium/high circulating @entity5 cell levels at baseline and followup had unfavorable pathological stage disease ( @entity3214 or N+). Next generation sequencing analysis showed somatic variant detection in 4 of 8 @entity1 using a targeted @entity5 panel. All 8 cases (100%) had a medium/high circulating @entity5 cell level with a circulating @entity5 cell fraction of greater than 5% purity. CONCLUSIONS: This study demonstrates a potential role for circulating @entity5 cell assays in the management of @entity150 . The IsoFlux method of circulating @entity5 cell detection shows increased sensitivity compared with CellSearch. A next generation sequencing assay is presented with sufficient sensitivity to detect genomic alterations in circulating @entity5 cells.
