dc.contributor
Institut Català de la Salut
dc.contributor
[Chi KN] BC Cancer Agency, Vancouver, Canada. [Barnicle A] Translational Medicine, AstraZeneca, Cambridge, United Kingdom. [Sibilla C, Corcoran C] Precision Medicine and Biosamples, AstraZeneca, Cambridge, United Kingdom. [Lai Z, Barrett JC] Translational Medicine, AstraZeneca, Waltham, Massachusetts. [Mateo J] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Chi, Kim
dc.contributor.author
Barnicle, Alan
dc.contributor.author
sibilla, caroline
dc.contributor.author
Lai, Zhongwu
dc.contributor.author
Corcoran, Claire
dc.contributor.author
Barrett, Carl
dc.contributor.author
Mateo, Joaquin
dc.date.issued
2023-05-11T07:14:03Z
dc.date.issued
2023-05-11T07:14:03Z
dc.date.issued
2023-01-04
dc.identifier
Chi KN, Barnicle A, Sibilla C, Lai Z, Corcoran C, Barrett JC, et al. Detection of BRCA1, BRCA2, and ATM Alterations in Matched Tumor Tissue and Circulating Tumor DNA in Patients with Prostate Cancer Screened in PROfound. Clin Cancer Res. 2023 Jan 4;29(1):81–91.
dc.identifier
https://hdl.handle.net/11351/9507
dc.identifier
10.1158/1078-0432.CCR-22-0931
dc.identifier
000907928500001
dc.description.abstract
Circulating tumor DNA; Prostate cancer
dc.description.abstract
ADN tumoral circulante; Cáncer de próstata
dc.description.abstract
ADN tumoral circulant; Càncer de pròstata
dc.description.abstract
Purpose:
Not all patients with metastatic castration-resistant prostate cancer (mCRPC) have sufficient tumor tissue available for multigene molecular testing. Furthermore, samples may fail because of difficulties within the testing procedure. Optimization of screening techniques may reduce failure rates; however, a need remains for additional testing methods to detect cancers with alterations in homologous recombination repair genes. We evaluated the utility of plasma-derived circulating tumor DNA (ctDNA) in identifying deleterious BRCA1, BRCA2 (BRCA), and ATM alterations in screened patients with mCRPC from the phase III PROfound study.
Patients and Methods:
Tumor tissue samples were sequenced prospectively at Foundation Medicine, Inc. (FMI) using an investigational next-generation sequencing (NGS) assay based on FoundationOne®CDx to inform trial eligibility. Matched ctDNA samples were retrospectively sequenced at FMI, using an investigational assay based on FoundationOne®Liquid CDx.
Results:
81% (503/619) of ctDNA samples yielded an NGS result, of which 491 had a tumor tissue result. BRCA and ATM status in tissue compared with ctDNA showed 81% positive percentage agreement and 92% negative percentage agreement, using tissue as reference. At variant-subtype level, using tissue as reference, concordance was high for nonsense (93%), splice (87%), and frameshift (86%) alterations but lower for large rearrangements (63%) and homozygous deletions (27%), with low ctDNA fraction being a limiting factor.
Conclusions:
We demonstrate that ctDNA can greatly complement tissue testing in identifying patients with mCRPC and BRCA or ATM alterations who are potentially suitable for receiving targeted PARP inhibitor treatments, particularly patients with no or insufficient tissue for genomic analyses.
dc.description.abstract
This study was funded by AstraZeneca and is part of an alliance between AstraZeneca and Merck Sharp & Dohme Corp.
dc.format
application/pdf
dc.publisher
American Association for Cancer Research
dc.relation
Clinical Cancer Research;29(1)
dc.relation
https://doi.org/10.1158/1078-0432.CCR-22-0931
dc.rights
Attribution-NonCommercial-NoDerivatives 4.0 International
dc.rights
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Cèl·lules canceroses
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Medicaments antineoplàstics
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Pròstata - Càncer
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DISEASES::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms::Prostatic Neoplasms, Castration-Resistant
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CHEMICALS AND DRUGS::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::Cell-Free Nucleic Acids::Circulating Tumor DNA
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CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents
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ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales masculinos::neoplasias de la próstata::neoplasias prostáticas resistentes a la castración
dc.subject
COMPUESTOS QUÍMICOS Y DROGAS::nucleótidos y nucleósidos de ácidos nucleicos::ácidos nucleicos::ácidos nucleicos libres de células::ADN tumoral circulante
dc.subject
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos
dc.title
Detection of BRCA1, BRCA2, and ATM Alterations in Matched Tumor Tissue and Circulating Tumor DNA in Patients with Prostate Cancer Screened in PROfound
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
