Publication:
Feasibility of next-generation sequencing of liquid biopsy (circulating tumor DNA) samples and tumor tissue from patients with metastatic prostate cancer in a real-world clinical setting in germany

dc.contributor.coauthorMandel, Philipp
dc.contributor.coauthorHoeh, Benedikt
dc.contributor.coauthorHumke, Clara
dc.contributor.coauthorDoering, Claudia
dc.contributor.coauthorWenzel, Mike
dc.contributor.coauthorCano Garcia, Cristina
dc.contributor.coauthorFuhr, Nina
dc.contributor.coauthorKoll, Florestan
dc.contributor.coauthorFassl, Anne
dc.contributor.coauthorSteuber, Thomas
dc.contributor.coauthorFaull, Iris
dc.contributor.coauthorJeroch, Jan
dc.contributor.coauthorEbner, Silvana
dc.contributor.coauthorSchmitt, Christina
dc.contributor.coauthorReis, Henning
dc.contributor.coauthorKöllermann, Jens
dc.contributor.coauthorKokkaliaris, Konstantinos D.
dc.contributor.coauthorDemes, Melanie C.
dc.contributor.coauthorChun, Felix K.H.
dc.contributor.coauthorWild, Peter J.
dc.contributor.kuauthorTilki, Derya
dc.contributor.schoolcollegeinstituteSchool of Medicine
dc.date.accessioned2024-12-29T09:41:27Z
dc.date.issued2024
dc.description.abstractBackground and objective: With European Medicines Agency approval of PARP inhibitors in metastatic castration-resistant prostate cancer and ongoing trials in metastatic hormone-sensitive prostate cancer, detection of genetic alterations in BRCA1/2 and other homologous recombination repair genes has gained an important role. Our aim was to investigate the feasibility and comparability of comprehensive next-generation sequencing (NGS) of liquid biopsy (LB; circulating tumor DNA) and tumor tissue (TT) samples in a real-world clinical setting. Methods: The study cohort consisted of 50 patients with metastatic prostate cancer (mPC) who had TT NGS performed for BRCA1/2 alterations and consent for additional LB NGS. The Oncomine Comprehensive Assay v3 (Thermo Fisher Scientific, Waltham, MA, USA) was used for TT NGS. The Guardant360 83-gene assay (Guardant Health, Palo Alto, CA, USA) was used for LB NGS, including all types of somatic alterations, microsatellite instability, and blood tumor mutational burden. We calculated BRCA1/2 alteration rates and the negative percentage agreement (NPA) and positive percentage agreement (PPA) between TT and LB results. Key findings and limitations: TT NGS was successful in 44/50 patients (88%), with pathogenic BRCA1/2 alterations detected in four (9%). LB NGS was successful in all 50 patients (100%), with BRCA1/2 alterations detected in ten (20%). In a subgroup analysis for the 44 patients with successful TT NGS, NPA was 85% and PPA was 50%. The median time between TT sample collection and blood sampling for NGS was 132 wk (IQR 94–186). The limited sample size and differences in the time of NGS assessment are limitations. Conclusions and clinical implications: LB NGS resulted in a higher detection rate for BRCA1/2 alterations in comparison to conventional TT NGS (20% vs 9%). Ideally, BRCA1/2 testing should be based on both approaches to identify all patients with mPC eligible for PARP inhibitor therapy. Patient summary: Our study shows that genetic tests for both tumor tissue and blood samples results in higher rates of detection of BRCA1/2 gene alterations in patients with metastatic prostate cancer.
dc.description.indexedbyWoS
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.issue2
dc.description.openaccessHybrid Gold Open Access
dc.description.publisherscopeInternational
dc.description.sponsorsThis study was sponsored by Guardant Health, who provided 50 Guardant360 liquid biopsy tests and shipment to their central laboratory (Redwood City, CA, USA), and was supported in part by funding from the German Federal Ministry of Education and Research to Peter J. Wild (PROSurvival, grant number 01KD2213C). The sponsor played a role in data collection.
dc.description.volume10
dc.identifier.doi10.1016/j.euf.2024.02.007
dc.identifier.eissn2405-4569
dc.identifier.quartileQ1
dc.identifier.scopus2-s2.0-85187999604
dc.identifier.urihttps://doi.org/10.1016/j.euf.2024.02.007
dc.identifier.urihttps://hdl.handle.net/20.500.14288/23650
dc.identifier.wos1273515800001
dc.keywordsN/A
dc.languageen
dc.publisherElsevier B.V.
dc.relation.grantnoGuardant Health
dc.relation.grantnoBundesministerium für Bildung und Forschung, BMBF, (01KD2213C)
dc.sourceEuropean Urology Focus
dc.subjectMedicine
dc.titleFeasibility of next-generation sequencing of liquid biopsy (circulating tumor DNA) samples and tumor tissue from patients with metastatic prostate cancer in a real-world clinical setting in germany
dc.typeJournal article
dspace.entity.typePublication
local.contributor.kuauthorTilki, Derya

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