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Oncotarget. 2016 Nov 8;8(48):83446-83456. doi: 10.18632/oncotarget.13225. eCollection 2017 Oct 13.

A pilot study evaluating concordance between blood-based and patient-matched tumor molecular testing within pancreatic cancer patients participating in the Know Your Tumor (KYT) initiative.

Author information

1
Perthera, Inc, McLean, VA, USA.
2
Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
3
The Pancreatic Cancer Action Network, Manhattan Beach, CA, USA.
4
Cedars-Sinai Medical Center, Los Angeles, CA, USA.
5
Ohio State University, Columbus, OH, USA.
6
City of Hope Cancer Center, Duarte, CA, USA.
7
Virginia Mason Medical Center, Seattle, WA, USA.
8
Jefferson Pancreatic, and Related Cancer Center, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
#
Contributed equally

Abstract

Recent improvements in next-generation sequencing (NGS) technology have enabled detection of biomarkers in cell-free DNA in blood and may ultimately replace invasive tissue biopsies. However, a better understanding of the performance of blood-based NGS assays is needed prior to routine clinical use. As part of an IRB-approved molecular profiling registry trial of pancreatic ductal adenocarcinoma (PDA) patients, we facilitated blood-based NGS testing of 34 patients from multiple community-based and high-volume academic oncology practices. 23 of these patients also underwent traditional tumor tissue-based NGS testing. cfDNA was not detected in 9/34 (26%) patients. Overall concordance between blood and tumor tissue NGS assays was low, with only 25% sensitivity of blood-based NGS for tumor tissue NGS. Mutations in KRAS, the major PDA oncogene, were only detected in 10/34 (29%) blood samples, compared to 20/23 (87%) tumor tissue biopsies. The presence of mutations in circulating DNA was associated with reduced overall survival (54% in mutation-positive versus 90% in mutation-negative). Our results suggest that in the setting of previously treated, advanced PDA, liquid biopsies are not yet an adequate substitute for tissue biopsies. Further refinement in defining the optimal patient population and timing of blood sampling may improve the value of a blood-based test.

KEYWORDS:

blood-based NGS; cfDNA; pancreatic cancer

Conflict of interest statement

CONFLICTS OF INTEREST Employment or Leadership Position: Michael J. Pishvaian, Perthera, Inc; R. Joseph Bender, Perthera, Inc; Lynn M. Matrisian, Pancreatic Cancer Action Network; Lola Rahib, Pancreatic Cancer Action Network; Anitra W. Engebretson, Pancreatic Cancer Action Network; Craig Heartwell, Perthera, Inc; Kimberly Mason, Perthera, Inc; Katelyn Varieur, Perthera, Inc; Metasebia Aberra, Perthera, Inc; Subha Madhavan, Perthera, Inc; Emanuel Petricoin III, Perthera, Inc; Jonathan R. Brody, Perthera, Inc. Consultant or Advisory Role: Andrew Hendifar, Perthera, Inc; Sam Mikhail, Perthera, Inc; Vincent Chung, Perthera, Inc; Vincent Picozzi, Perthera, Inc. Previously presented in part at the 2016 American Society of Clinical Oncology Gastrointestinal Cancers Symposium, San Francisco, CA, January 21-23, 2016.

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