Cell-free DNA and neuromediators in detecting aggressive variant prostate cancer

• Verfasst von: Hardenberg, Jost von [VerfasserIn]
• Verfasst von: Worst, Thomas [VerfasserIn]
• Verfasst von: Westhoff, Niklas Christian [VerfasserIn]
• Verfasst von: Erben, Philipp [VerfasserIn]
• Verfasst von: Bolenz, Christian [VerfasserIn]
• Verfasst von: Weiß, Christel [VerfasserIn]
• Titel: Cell-free DNA and neuromediators in detecting aggressive variant prostate cancer
• Verf.angabe: Jost von Hardenberg, Thomas S. Worst, Niklas Westhoff, Philipp Erben, Stefan Fuxius, Markus Müller, Christian Bolenz, Christel Weiss, Elmar Heinrich
• E-Jahr: 2018
• Jahr: September 10, 2018
• Umfang: 7 S.
• Fussnoten: Gesehen am 05.04.2019
• Titel Quelle: Enthalten in: Oncology research and treatment
• Ort Quelle: Basel : Karger, 2014
• Jahr Quelle: 2018
• Band/Heft Quelle: 41(2018), 10, Seite 627-633
• ISSN Quelle: 2296-5262
• DOI: doi:10.1159/000490618
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Cabazitaxel
• Sach-SW: CGA
• Sach-SW: Liquid biopsy
• Sach-SW: Neuroendocrine
• Sach-SW: NSE
• K10plus-PPN: 1662892004

Abstract

BACKGROUND: Aggressive variant transformation in metastatic castration-resistant prostate cancer (mCRPC) represents an under-recognized phenomenon. There is an urgent need for non-invasive biomarkers to detect these variants and identify treatment alternatives. - METHODS: A prospective observational pilot study in mCRPC patients receiving treatment with cabazitaxel (CAB) was conducted. Neuromediators were sequentially evaluated and their impact on disease endpoints calculated. Targeted next-generation sequencing (NGS) of cell-free DNA (cfDNA) was also performed in a highly pretreated subset of patients. - RESULTS: 23 patients were included. Estimated effects indicate that neuron-specific enolase (NSE) levels at baseline may be correlated with overall survival (NSE unit 18.3 ng/ml: HR1.262 (95% confidence interval (CI) 0.985-1.616)) and that chromogranin A (CGA) may be correlated with progression-free survival (CGA unit 98.1 ng/ml: HR1.341 (95% CI 1.011-1.778)). cfDNA analysis revealed mutations annotated in prostate cancer (PCA) and small cell cancers (SCC). 1 patient showed elevated neuromediators along with annotated mutations in PCA and SCC, potentially indicating aggressive variant cancer. In 3 patients KIT mutations (e.g. pM541L, pV654A) known to be tissue-based biomarkers with level 1 evidence for the treatment with imatinib and sunitinib were found. - CONCLUSIONS: Sequential analysis of neuromediators and targeted NGS of cfDNA provide insight for the estimation of tumor heterogeneity under therapy with CAB.