1. Circulating Tumor Cells Predict Occult Metastatic Disease and Prognosis in Pancreatic Cancer.
- Author
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Court CM, Ankeny JS, Sho S, Winograd P, Hou S, Song M, Wainberg ZA, Girgis MD, Graeber TG, Agopian VG, Tseng HR, and Tomlinson JS
- Subjects
- Aged, Carcinoma, Pancreatic Ductal blood, Carcinoma, Pancreatic Ductal surgery, Female, Follow-Up Studies, Humans, Liver Neoplasms blood, Liver Neoplasms surgery, Lymphatic Metastasis, Male, Middle Aged, Neoplasm Invasiveness, Neoplasm Recurrence, Local blood, Neoplasm Recurrence, Local surgery, Pancreatectomy, Pancreatic Neoplasms blood, Pancreatic Neoplasms surgery, Peritoneal Neoplasms blood, Peritoneal Neoplasms surgery, Prognosis, Prospective Studies, Survival Rate, Biomarkers, Tumor blood, Carcinoma, Pancreatic Ductal secondary, Liver Neoplasms secondary, Neoplasm Recurrence, Local pathology, Neoplastic Cells, Circulating pathology, Pancreatic Neoplasms pathology, Peritoneal Neoplasms secondary
- Abstract
Background: Occult metastatic tumors, below imaging thresholds, are a limitation of staging systems that rely on cross-sectional imaging alone and are a cause of the routine understaging of pancreatic ductal adenocarcinomas (PDACs). We investigated circulating tumor cells (CTCs) as a preoperative predictor of occult metastatic disease and as a prognostic biomarker for PDAC patients., Experimental Design: A total of 126 patients (100 with cancer, 26 with benign disease) were enrolled in our study and CTCs were identified and enumerated from 4 mL of venous blood using the microfluidic NanoVelcro assay. CTC enumeration was correlated with clinicopathologic variables and outcomes following both surgical and systemic therapies., Results: CTCs were identified in 78% of PDAC patients and CTC counts correlated with increasing stage (ρ = 0.42, p < 0.001). Of the 53 patients taken for potentially curative surgery, 13 (24.5%) had occult metastatic disease intraoperatively. Patients with occult disease had significantly more CTCs than patients with local disease only (median 7 vs. 1 CTC, p < 0.0001). At a cut-off of three or more CTCs/4 mL, CTCs correctly identified patients with occult metastatic disease preoperatively (area under the receiver operating characteristic curve 0.82, 95% confidence interval (CI) 0.76-0.98, p < 0.0001). CTCs were a univariate predictor of recurrence-free survival following surgery [hazard ratio (HR) 2.36, 95% CI 1.17-4.78, p = 0.017], as well as an independent predictor of overall survival on multivariate analysis (HR 1.38, 95% CI 1.01-1.88, p = 0.040)., Conclusions: CTCs show promise as a prognostic biomarker for PDAC patients at all stages of disease being treated both medically and surgically. Furthermore, CTCs demonstrate potential as a preoperative biomarker for identifying patients at high risk of occult metastatic disease.
- Published
- 2018
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