Pancreatic circulating tumor cells as a diagnostic adjunct in pancreatic cancer.

Abstract

175 Background: Current diagnosis of pancreatic ductal adenocarcinoma (PDAC) relies upon image guided tissue sampling, which is expensive, inconvenient, and not without patient risk. Circulating tumor cells (CTCs) may improve our ability to diagnose PDAC, obtain pure molecular information uncontaminated by stromal cells, and potentially improve our ability to accurately stage patients at the time of diagnosis. Therefore, we evaluated CTCs as an adjunctive diagnostic biomarker of PDAC at the time of presentation. Methods: We performed a prospective analysis on 50 consecutive pre-treatment patients with either suspicion for, or recent diagnosis of PDAC who were referred to our UCLA Center for Pancreatic Diseases. 2 mL venous blood was evaluated for the presence and number of CTCs. Capture and enumeration was carried out with a novel microfluidic NanoVelcro technology enhanced by anti-EpCAM enrichment. CTCs were defined by size > 10 um and IHC staining pattern (DAPI+, CK+, and CD45-). Of note, KRAS mutational status was assessed in CTCs from 3 patients to confirm PDAC origin of CTCs. Diagnostic performance was then assessed via analysis of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristic (ROC) curves. Results: Of the 50 patients, 32 patients had PDAC and 18 had non-malignant pathology on tissue biopsy. CTCs were detected in 62.5% of PDAC patients, and in 5.5% of patients with non-malignant pathology. Specificity of CTCs for the diagnosis of PDAC was 94.4%, PPV 95.2%, and NPV 58.6%. ROC curve analysis determined optimal ability for CTCs to distinguish between benign and malignant disease with detection of ≥ 1 CTC. Additionally, in patients with a diagnosis of PDAC, CTC number correlated with stage and the presence of ≥ 2 CTCs distinguished local from systemic disease. Conclusions: In this study, CTCs were a useful adjunct for diagnosis of PDAC. Additionally, CTCs were capable of identifying patients with metastases. Addition of outcomes data may allow CTCs to be established as a biomarker for improved staging at the time of diagnosis, with subsequent improvement in delivery of stage-specific treatments.