Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Mandel, P; Hoeh, B; Humke, C; Doering, C; Wenzel, M; Cano, Garcia, C; Fuhr, N; Koll, F; Fassl, A; Tilki, D; Steuber, T; Faull, I; Jeroch, J; Ebner, S; Schmitt, C; Reis, H; Köllermann, J; Kokkaliaris, KD; Demes, MC; Chun, FKH; Wild, PJ.
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.
Eur Urol Focus. 2024; 10(2): 339-345.
Doi: 10.1016/j.euf.2024.02.007
Web of Science
PubMed
FullText
FullText_MUG
- Co-authors Med Uni Graz
- Koll Florestan Johannes
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- Abstract:
- BACKGROUND 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Humans - administration & dosage
- Male - administration & dosage
- Liquid Biopsy - administration & dosage
- High-Throughput Nucleotide Sequencing - methods
- Circulating Tumor DNA - blood, genetics
- Feasibility Studies - administration & dosage
- Aged - administration & dosage
- Prostatic Neoplasms - genetics, pathology, blood, drug therapy
- Germany - administration & dosage
- Middle Aged - administration & dosage
- Neoplasm Metastasis - administration & dosage
- BRCA2 Protein - genetics
- Aged, 80 and over - administration & dosage
- Find related publications in this database (Keywords)
- Key findings and limitations
- TT NGS was successful in 44/50 patients (88%)
- with patho- genic 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