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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorSumanasuriya, Semini
dc.contributor.authorSeed, George
dc.contributor.authorParr, Harry
dc.contributor.authorChristova, Rossitza
dc.contributor.authorPope, Lorna
dc.contributor.authorBertan, Claudia
dc.contributor.authorMateo Valderrama, Joaquim
dc.date.accessioned2022-03-14T13:46:05Z
dc.date.available2022-03-14T13:46:05Z
dc.date.issued2021-08
dc.identifier.citationSumanasuriya S, Seed G, Parr H, Christova R, Pope L, Bertan C, et al. Elucidating Prostate Cancer Behaviour During Treatment via Low-pass Whole-genome Sequencing of Circulating Tumour DNA. Eur Urol. 2021 Aug;80(2):243–53.
dc.identifier.issn0302-2838
dc.identifier.urihttp://hdl.handle.net/11351/7175
dc.descriptionCabazitaxel; Cell-free DNA; Tumour fraction
dc.description.abstractBackground Better blood tests to elucidate the behaviour of metastatic castration-resistant prostate cancer (mCRPC) are urgently needed to drive therapeutic decisions. Plasma cell-free DNA (cfDNA) comprises normal and circulating tumour DNA (ctDNA). Low-pass whole-genome sequencing (lpWGS) of ctDNA can provide information on mCRPC behaviour. Objective To validate and clinically qualify plasma lpWGS for mCRPC. Design, setting, and participants Plasma lpWGS data were obtained for mCRPC patients consenting to optional substudies of two prospective phase 3 trials (FIRSTANA and PROSELICA). In FIRSTANA, chemotherapy-naïve patients were randomised to treatment with docetaxel (75 mg/m2) or cabazitaxel (20 or 25 mg/m2). In PROSELICA, patients previously treated with docetaxel were randomised to 20 or 25 mg/m2 cabazitaxel. lpWGS data were generated from 540 samples from 188 mCRPC patients acquired at four different time points (screening, cycle 1, cycle 4, and end of study). Outcome measurements and statistical analysis lpWGS data for ctDNA were evaluated for prognostic, response, and tumour genomic measures. Associations with response and survival data were determined for tumour fraction. Genomic biomarkers including large-scale transition (LST) scores were explored in the context of prior treatments. Results and limitations Plasma tumour fraction was prognostic for overall survival in univariable and stratified multivariable analyses (hazard ratio 1.75, 95% confidence interval 1.08–2.85; p = 0.024) and offered added value compared to existing biomarkers (C index 0.722 vs 0.709; p = 0.021). Longitudinal changes were associated with drug response. PROSELICA samples were enriched for LSTs (p = 0.029) indicating genomic instability, and this enrichment was associated with prior abiraterone and enzalutamide treatment but not taxane or radiation therapy. Higher LSTs were correlated with losses of RB1/RNASEH2B, independent of BRCA2 loss. Conclusions Plasma lpWGS of ctDNA describes CRPC behaviour, providing prognostic and response data of clinical relevance. The added prognostic value of the ctDNA fraction over established biomarkers should be studied further.
dc.language.isoeng
dc.publisherElsevier
dc.relation.ispartofseriesEuropean Urology;80(2)
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceScientia
dc.subjectPròstata - Càncer - Tractament
dc.subjectElements genètics mòbils
dc.subjectPròstata - Càncer - Aspectes genètics
dc.subject.meshProstatic Neoplasms, Castration-Resistant
dc.subject.mesh/drug therapy
dc.subject.meshCirculating Tumor DNA
dc.subject.mesh/genetics
dc.titleElucidating Prostate Cancer Behaviour During Treatment via Low-pass Whole-genome Sequencing of Circulating Tumour DNA
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1016/j.eururo.2021.05.030
dc.subject.decsneoplasias prostáticas resistentes a la castración
dc.subject.decs/farmacoterapia
dc.subject.decsADN tumoral circulante
dc.subject.decs/genética
dc.relation.publishversionhttps://doi.org/10.1016/j.eururo.2021.05.030
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Sumanasuriya S] The Institute of Cancer Research, University of London, London, UK. The Royal Marsden Hospital, London, UK. [Seed G, Parr H, Christova R, Pope L, Bertan C] The Institute of Cancer Research, University of London, London, UK. [Mateo J] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
dc.identifier.pmid34103179
dc.identifier.wos000673637600031
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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