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
| Autor: | Lynn M. Matrisian, Kimberly Mason, William Arthur Hoos, Michael J. Pishvaian, Andrew Eugene Hendifar, R Joseph Bender, Jonathan R. Brody, Sam Mikhail, Subha Madhavan, Lola Rahib, Emanuel F. Petricoin, Vincent J. Picozzi, Katelyn Varieur, Vincent Chung, Metasebia Aberra, Craig Heartwell |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty Pathology Pancreatic ductal adenocarcinoma Concordance pancreatic cancer Oncology and Carcinogenesis medicine.disease_cause 03 medical and health sciences 0302 clinical medicine Rare Diseases Clinical Research Internal medicine Pancreatic cancer medicine Overall survival Genetics University medical cfDNA Cancer blood-based NGS screening and diagnosis business.industry medicine.disease 4.1 Discovery and preclinical testing of markers and technologies Detection 030104 developmental biology 030220 oncology & carcinogenesis KRAS Previously treated business Digestive Diseases Blood sampling Research Paper 4.2 Evaluation of markers and technologies |
| Zdroj: | Oncotarget, vol 8, iss 48 Oncotarget |
| Popis: | // Michael J. Pishvaian 1,2,* , R. Joseph Bender 1,* , Lynn M. Matrisian 3 , Lola Rahib 3 , Andrew Hendifar 4 , William A. Hoos 3 , Sam Mikhail 5 , Vincent Chung 6 , Vincent Picozzi 7 , Craig Heartwell 1 , Kimberly Mason 1 , Katelyn Varieur 1 , Metasebia Aberra 1 , Subha Madhavan 1,2 , Emanuel Petricoin III 1 and Jonathan R. Brody 1,8 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 * These authors have contributed equally to this work Correspondence to: Jonathan R. Brody, email: // Keywords : cfDNA, pancreatic cancer, blood-based NGS Received : June 15, 2016 Accepted : September 25, 2016 Published : November 08, 2016 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. |
| Databáze: | OpenAIRE |
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