Ultrasensitive plasma ctDNA KRAS assay for detection, prognosis, and assessment of therapeutic response in patients with unresectable pancreatic ductal adenocarcinoma.

摘要: Precision oncology requires sensitive and specific clinical biomarkers. Carbohydrate Antigen 19-9 (CA19-9) is widely used in pancreatic ductal adenocarcinoma (PDA) but lacks sensitivity specificity. Nearly all PDAs harbor somatic KRAS mutations, nominating circulating tumor DNA (ctDNA) as an alternative disease biomarker, however, variable performance has limited its utility. We applied ultrasensitive, PCR mutation enrichment, next generation sequencing ctDNA assay a large cohort of patients with unresectable PDA (N = 189) recruited to the BIOPAC study between 2008-2015. Baseline longitudinal serum CA19-9 plasma were correlated time progression (TTP) overall survival (OS). detection rate was 93.7% (86.4% non-elevated CA19-9). positively yet independently associated TTP OS (ctDNA p 0.0018 0.0014; 0.0294 0.0007, respectively). A generated model quantitating correctly assessed greater than 80% patient responses. Quantitative informative prognostic complementary PDA. Longitudinal may inform therapeutic decision making provides kinetically dynamic quantitative metric response.