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.
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-naïve patients (21% vs. 69%; P<0.001). ctDNA levels dropped significantly after tumor resection. Persistence of ctDNA in the immediate post-operative period was associated with a high rate of recurrence and poor median RFS (5 months). ctDNA detected during follow-up predicted clinical recurrence (sensitivity 90% (95% CI 74-98%), specificity 88% (95% CI 62-98%)) with a median lead time of 84 days (IQR 25-146). Detection of ctDNA during post-pancreatectomy follow-up was associated with a median OS of 17 months, while median OS was not yet reached at 30 months for patients without ctDNA (P=0.011).
Measurement of KRAS ctDNA in a CLIA laboratory setting can be used to predict recurrence and survival in PDAC patients.
https://clincancerres.aacrjournals.org/content/early/2019/05/29/1078-0432.CCR-19-0197
