Research Papers:
Ultrasensitive plasma ctDNA KRAS assay for detection, prognosis, and assessment of therapeutic response in patients with unresectable pancreatic ductal adenocarcinoma
Metrics: PDF 1852 views | HTML 3453 views | ?
Abstract
Inna Chen1, Victoria M. Raymond2, Jennifer A. Geis2, Eric A. Collisson3, Benny V. Jensen1, Kirstine L. Hermann4, Mark G. Erlander2, Margaret Tempero3 and Julia S. Johansen1,5,6
1Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark
2Trovagene, Inc., San Diego, California, USA
3Department of Medicine, University of California San Francisco, San Francisco, California, USA
4Department of Radiology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark
5Department of Medicine, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark
6Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Correspondence to:
Inna Chen, email: [email protected]
Victoria M. Raymond, email: [email protected]
Keywords: ctDNA; KRAS; pancreatic ductal adenocarcinoma; CA19-9; prognostic biomarker
Received: January 17, 2017 Accepted: October 11, 2017 Published: October 26, 2017
ABSTRACT
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 and specificity. Nearly all PDAs harbor somatic KRAS mutations, nominating circulating tumor DNA (ctDNA) KRAS as an alternative disease biomarker, however, variable clinical performance has limited its clinical utility. We applied an ultrasensitive, PCR mutation enrichment, next generation sequencing ctDNA KRAS assay in a large cohort of patients with unresectable PDA (N = 189) recruited to the BIOPAC study between 2008–2015. Baseline and longitudinal serum CA19-9 and plasma ctDNA KRAS were correlated with time to progression (TTP) and overall survival (OS). Baseline ctDNA KRAS detection rate was 93.7% (86.4% in patients with non-elevated CA19-9). ctDNA KRAS and CA19-9 were positively correlated yet independently associated with TTP and OS (ctDNA KRAS p = 0.0018 and 0.0014; CA19-9 p = 0.0294 and 0.0007, respectively). A generated model quantitating longitudinal ctDNA KRAS correctly assessed greater than 80% of patient responses. Quantitative detection of KRAS ctDNA is an informative prognostic biomarker, complementary to CA19-9 in patients with unresectable PDA. Longitudinal ctDNA KRAS may inform therapeutic decision making and provides a kinetically dynamic and quantitative metric of patient response.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 22080