Improved Risk Stratification by Circulating Tumor Cell Counts in Pancreatic Cancer

Abstract

Pancreatic cancer is one of the most devastating diseases with a 5-year survival rate of 3% to 5%. Here, we investigated whether circulating tumor cells (CTC) may predict metastatic spread and survival in pancreatic cancer patients. In a prospective study, we enrolled 69 pancreatic cancer patients. In peripheral blood, CTCs were identified by MACS enrichment (anti-cytokeratin/anti-EpCam) and subsequent automated analysis after combined anti-cytokeratin/anti-CD45/DAPI staining. CTC results were correlated to established clinicopathologic risk factors, detection of disseminated tumor cells (DTC) in bone marrow, and clinical outcome (follow-up time: 48 months). Median patient survival was 11 months (0-48 months). Thirty-eight patients were male and 31 were female, and the majority received gemcitabine (58/69). CTCs were present in 23 of 69 patients (33.3%) ranging from 1 to 19 cells (17 with >1 CTC). Although clinicopathologic parameters and DTC status did not correlate with CTC incidence, progression-free survival (PFS) and overall survival (OS) were significantly reduced in CTC-positive patients in univariate ( = 0.009, PFS; = 0.030, OS, both log rank) and multivariate analysis [HR = 4.543; confidence interval (CI), 1.549-13.329; = 0.006, PFS; HR = 2.093; CI, 1.081-4.050; = 0.028, OS, both Cox regression). Also within patients receiving chemotherapy, PFS was significantly reduced in CTC-positive patients in univariate ( = 0.013) and multivariate (HR = 4.203; CI, 1.416-12.471; = 0.010) analysis. CTCs affect the outcome of patients with pancreatic cancer independent from other risk factors, including patients receiving (adjuvant) cytotoxic therapy. CTC stratification may allow a better upfront identification of patients with a longer lifespan who might profit from new adjuvant therapies. .

Liquid biopsy in pancreatic ductal adenocarcinoma: current status of circulating tumor cells and circulating tumor DNA

“…CTC positivity in locally advanced pancreatic adenocarcinoma at any time point was an independent prognostic factor for overall survival (OS) in multivariable analysis but not for progression-free survival (PFS). A more recent study by Effenberger et al enrolled 69 patients with PDAC and identified CTCs using MACS enrichment: Here, CTC positivity was an independent risk factor of reduced PFS (HR = 4.543, P = 0.006) and OS (HR = 2.093, P = 0.028) (Effenberger et al, 2018). Studies using different platforms in PDAC patients exhibited Before the start of Tx: For a subset of cases, multiple time points after surgery The PFS of ctDNA (+) and ctDNA (À) patients (at baseline) were 7.9 and 15.2 months (P = 0.0151).…”

“…A more recent study by Effenberger et al . enrolled 69 patients with PDAC and identified CTCs using MACS enrichment: Here, CTC positivity was an independent risk factor of reduced PFS (HR = 4.543, P = 0.006) and OS (HR = 2.093, P = 0.028) (Effenberger et al ., ). Studies using different platforms in PDAC patients exhibited association of CTCs with survival rates.…”

Clinical Relevance of Circulating Tumor Cells in Esophageal Cancer Detected by a Combined MACS Enrichment Method

“…For CTC enumeration, red blood cells were lysed (RBC Lysis buffers; Thermo Fisher Scientific, Boston, MA, USA), followed by the blocking of unspecific binding sites, cell permeation, and fixation in a one-step procedure (Carcinoma Cell Enrichment and Detection Kit; Miltenyi Biotec, Bergisch Gladbach, Germany) [31,33]. After incubation, the cells were centrifuged, resuspended in 1 mL PBS solution and applied to an MS separation column attached to an OctoMACS separator (both Miltenyi Biotec, Bergisch Gladbach, Germany).…”

Current progress in the clinical use of circulating tumor cells as prognostic biomarkers

“…These include immunoaffinity analysis (for markers including EpCAM, CD15, CD45, and CD66b); techniques for the analysis of biophysical characteristics such as size, deformability, density, and surface charge; immunofluorescence for quantification; and molecular techniques including sequence analysis for genomics and transcriptomics, mass cytometry for proteomic analysis, and targeted bisulfite sequencing for epigenetic analysis . Table highlights the potential of CTCs as biomarkers for disease progression, prognosis, and outcomes for a wide range of cancers . Figure summarizes the potential prognostic role of CTCs at various stages of cancer.…”

“…4 Table 1 highlights the potential of CTCs as biomarkers for disease progression, prognosis, and outcomes for a wide range of cancers. [18][19][20][21][22][23][24][25][26][27][28][29][30][31] Figure 1 summarizes the potential prognostic role of CTCs at various stages of cancer.…”