Circulating Tumor DNA as a Clinical Test in Resected Pancreatic Cancer

Purpose: In research settings, circulating tumor DNA (ctDNA) shows promise as a tumor-specific biomarker for pancreatic ductal adenocarcinoma (PDAC). This study aims to perform analytical and clinical validation of a KRAS ctDNA assay in a Clinical Laboratory Improvement Amendments (CLIA) and College of American Pathology (CAP) certified clinical laboratory. Experimental Design: Digital-droplet PCR (ddPCR) was used to detect the major PDAC-associated somatic KRAS mutations (G12D, G12V, G12R and Q61H) in liquid biopsies. For clinical validation, 290 pre-operative and longitudinal post-operative plasma samples were collected from 59 PDAC patients. The utility of ctDNA status to predict PDAC recurrence during follow-up was assessed. Results: ctDNA was detected pre-operatively in 29 (49%) patients and was an independent predictor of decreased recurrence-free (RFS) and overall survival (OS). Patients who had neoadjuvant chemotherapy were less likely to have pre-operative ctDNA than were chemo-naive patients (21% vs. 69%; P P =0.011). Conclusions: Measurement of KRAS ctDNA in a CLIA laboratory setting can be used to predict recurrence and survival in PDAC patients.