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dc.contributor.authorAllin, DM
dc.contributor.authorShaikh, R
dc.contributor.authorCarter, P
dc.contributor.authorThway, K
dc.contributor.authorSharabiani, MTA
dc.contributor.authorGonzales-de-Castro, D
dc.contributor.authorO'Leary, B
dc.contributor.authorGarcia-Murillas, I
dc.contributor.authorBhide, S
dc.contributor.authorHubank, M
dc.contributor.authorHarrington, K
dc.contributor.authorKim, D
dc.contributor.authorNewbold, K
dc.date.accessioned2019-03-26T14:54:17Z
dc.date.issued2018-11
dc.identifier.citationEuropean journal of cancer (Oxford, England : 1990), 2018, 103 pp. 165 - 175
dc.identifier.issn0959-8049
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3162
dc.identifier.eissn1879-0852en_US
dc.identifier.doi10.1016/j.ejca.2018.08.013en_US
dc.description.abstractBackground Conventional biomarkers in thyroid cancer are not disease specific and fluctuate in advanced disease, making interpretation difficult. Circulating tumour DNA (ctDNA) has been shown to be a useful biomarker in other solid tumours. This is a multimutational study of ctDNA over multiple timepoints, designed to test the hypothesis that ctDNA is a potential biomarker in patients with advanced thyroid cancer.Methods Mutational analysis of archival tumour tissue was performed using NGS with a targeted gene panel. Custom TaqMan assays were designed for plasma ctDNA testing using digital droplet polymerase chain reaction. Concentrations of detected ctDNA were correlated with the conventional biomarker concentration and axial imaging status defined by the Response Evaluation Criteria in Solid Tumours criteria.Results Tumour tissue from 51 patients was obtained, with the following histologies: 32 differentiated (differentiated thyroid cancer [DTC]), 15 medullary (medullary thyroid cancer [MTC]), three poorly differentiated and one anaplastic. NGS analysis detected variants in 42 (82%) of cases. Plasma was assayed for these patients in 190 samples, and ctDNA was detected in 67% of patients. Earlier detection of disease progression was noted in three patients with MTC. In two cases (PTC and ATC), where conventional biomarkers were not detectable, ctDNA was detected before disease progression. Changes in ctDNA concentration occurred earlier than conventional markers in response to disease progression in multiple patients with DTC receiving targeted therapies.Conclusion The majority of patients with advanced thyroid cancer had detectable ctDNA. ctDNA measurement may offer superiority over conventional markers in several scenarios: earlier detection of progression in MTC; as an alternative biomarker when conventional markers are not available; more rapid assessment of the disease status in response to targeted therapies, thereby potentially allowing prompter discontinuation of futile therapies. These early results support the hypothesis that ctDNA may be a clinically useful biomarker in thyroid cancer.
dc.formatPrint-Electronic
dc.format.extent165 - 175
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectHumans
dc.subjectThyroid Neoplasms
dc.subjectDisease Progression
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectBiomarkers, Tumor
dc.subjectPrecision Medicine
dc.subjectCirculating Tumor DNA
dc.titleCirculating tumour DNA is a potential biomarker for disease progression and response to targeted therapy in advanced thyroid cancer.
dc.typeJournal Article
dcterms.dateAccepted2018-08-19
rioxxterms.versionofrecord10.1016/j.ejca.2018.08.013
rioxxterms.licenseref.startdate2018-11en_US
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfEuropean journal of cancer (Oxford, England : 1990)
pubs.notesNo embargo
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Oncology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Genomics/Translational Genomics (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Oncology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Genomics/Translational Genomics (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy
pubs.publication-statusPublished
pubs.volume103en_US
pubs.embargo.termsNo embargo
icr.researchteamMolecular Oncologyen_US
icr.researchteamTranslational Genomicsen_US
icr.researchteamTargeted Therapyen_US
dc.contributor.icrauthorGarcia-Murillas, Isaacen
dc.contributor.icrauthorHubank, Michaelen
dc.contributor.icrauthorHarrington, Kevinen
dc.contributor.icrauthorO'Leary, Benjaminen


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