Title |
Improved EGFR mutation detection using combined exosomal RNA and circulating tumor DNA in NSCLC patient plasma
|
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Published in |
Annals of Oncology, December 2017
|
DOI | 10.1093/annonc/mdx765 |
Pubmed ID | |
Authors |
A.K. Krug, D. Enderle, C. Karlovich, T. Priewasser, S. Bentink, A. Spiel, K. Brinkmann, J. Emenegger, D.G. Grimm, E. Castellanos-Rizaldos, J.W. Goldman, L.V. Sequist, J.-C. Soria, D.R. Camidge, S.M. Gadgeel, H.A. Wakelee, M. Raponi, M. Noerholm, J. Skog |
Abstract |
A major limitation of circulating tumor DNA (ctDNA) for somatic mutation detection has been the low level of ctDNA found in a subset of cancer patients. We investigated whether using a combined isolation of exosomal RNA (exoRNA) and cell-free DNA (cfDNA) could improve blood-based liquid biopsy for EGFR mutation detection in NSCLC patients. Matched pretreatment tumor and plasma were collected from 84 patients enrolled in TIGER-X (NCT01526928), a Ph1/2 study of rociletinib in mutant EGFR NSCLC patients. The combined isolated exoRNA and cfDNA (exoNA) was analyzed for mutations using a targeted NGS panel (EXO1000), and compared to existing data from the same samples using analysis of ctDNA by BEAMing. For exoNA, the sensitivity was 98% for detection of activating EGFR mutations and 90% for EGFR T790M. The corresponding sensitivities for ctDNA by BEAMing were 82% for activating mutations and 84% for T790M. In a subgroup of patients with intrathoracic metastatic disease (M0/M1a; n = 21), the sensitivity increased from 26% to 74% for activating mutations (p = 0.003) and from 19% to 31% for T790M (p = 0.5) when using exoNA for detection. Combining exoRNA and ctDNA increased the sensitivity for EGFR mutation detection in plasma, with the largest improvement seen in the subgroup of M0/M1a disease patients known to have low levels of ctDNA which poses challenges for ctDNA-only based mutation detection. NCT01526928. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 7 | 14% |
Spain | 6 | 12% |
United Kingdom | 4 | 8% |
Greece | 2 | 4% |
Venezuela, Bolivarian Republic of | 2 | 4% |
France | 2 | 4% |
Saudi Arabia | 1 | 2% |
Argentina | 1 | 2% |
Australia | 1 | 2% |
Other | 6 | 12% |
Unknown | 17 | 35% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 23 | 47% |
Scientists | 14 | 29% |
Practitioners (doctors, other healthcare professionals) | 11 | 22% |
Science communicators (journalists, bloggers, editors) | 1 | 2% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 210 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 34 | 16% |
Researcher | 30 | 14% |
Other | 14 | 7% |
Student > Master | 12 | 6% |
Student > Bachelor | 10 | 5% |
Other | 28 | 13% |
Unknown | 82 | 39% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 50 | 24% |
Medicine and Dentistry | 31 | 15% |
Agricultural and Biological Sciences | 17 | 8% |
Engineering | 8 | 4% |
Chemistry | 5 | 2% |
Other | 14 | 7% |
Unknown | 85 | 40% |