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Utility of ctDNA to support patient selection for early phase clinical trials: the TARGET study
Utility of ctDNA to support patient selection for early phase clinical trials: the TARGET study
- Source :
- Rothwell, D, Ayub, M, Cook, N, Thistlethwaite, F, Carter, L, Dean, E, Smith, N, Villa, S, Dransfield, J, Clipson, A, White, D, Nessa, K, Ferdous, S, Howell, M, Gupta, A, Kilerci, B, Mohan, S, Frese, K, Gulati, S, Miller, C, Jordan, A, Eaton, H, Hickson, N, O'Brien, C, Graham, D, Kelly, C, Aruketty, S, Metcalf, R, Chiramel, J, Tinsley, N, Vickers, AJ, Kurup, R, Frost, H, Stevenson, J, Southam, S, Landers, D, Wallace, A, Marais, R, Hughes, AM, Brady, G, Dive, C & Krebs, M 2019, ' Utility of ctDNA to support patient selection for early phase clinical trials: The TARGET Study ', Nature Medicine, vol. 25, no. 5, pp. 738-743 . https://doi.org/10.1038/s41591-019-0380-z, https://doi.org/10.1038/s41591-019-0380-z
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) supports blood-based genomic profiling but is not yet routinely implemented in the setting of a phase I trials clinic. TARGET is a molecular profiling program with the primary aim to match patients with a broad range of advanced cancers to early phase clinical trials on the basis of analysis of both somatic mutations and copy number alterations (CNA) across a 641 cancer-associated-gene panel in a single ctDNA assay. For the first 100 TARGET patients, ctDNA data showed good concordance with matched tumor and results were turned round within a clinically acceptable timeframe for Molecular Tumor Board (MTB) review. When a 2.5% variant allele frequency (VAF) threshold was applied, actionable mutations were identified in 41 of 100 patients, and 11 of these patients received a matched therapy. These data support the application of ctDNA in this early phase trial setting where broad genomic profiling of contemporaneous tumor material enhances patient stratification to novel therapies and provides a practical template for bringing routinely applied blood-based analyses to the clinic.
- Subjects :
- 0301 basic medicine
Oncology
medicine.medical_specialty
Genomic profiling
DNA Copy Number Variations
Concordance
General Biochemistry, Genetics and Molecular Biology
Circulating Tumor DNA
03 medical and health sciences
0302 clinical medicine
Neoplasms
Internal medicine
Biomarkers, Tumor
medicine
Humans
Tumor board
Manchester Cancer Research Centre
Clinical Trials, Phase I as Topic
business.industry
ResearchInstitutes_Networks_Beacons/mcrc
Patient Selection
High-Throughput Nucleotide Sequencing
Phase i trials
Sequence Analysis, DNA
General Medicine
Variant allele
Clinical trial
030104 developmental biology
030220 oncology & carcinogenesis
Mutation
business
Early phase
Patient stratification
Subjects
Details
- ISSN :
- 1546170X and 10788956
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Nature Medicine
- Accession number :
- edsair.doi.dedup.....6ab8deb506ba3c33e67a2a24472d46ac
- Full Text :
- https://doi.org/10.1038/s41591-019-0380-z