Detection and monitoring of tumor-derived mutations in circulating tumor DNA using the UltraSEEK lung panel on the MassARRAY system in metastatic non-small cell lung cancer patients

• Verfasst von: Van der Leest, Paul [VerfasserIn]
• Verfasst von: Janning, Melanie [VerfasserIn]
• Verfasst von: Rifaela, Naomi [VerfasserIn]
• Verfasst von: Azpurua, Maria L. Aguirre [VerfasserIn]
• Verfasst von: Kropidlowski, Jolanthe [VerfasserIn]
• Verfasst von: Loges, Sonja [VerfasserIn]
• Verfasst von: Lozano, Nicolas [VerfasserIn]
• Verfasst von: Sartori, Alexander [VerfasserIn]
• Verfasst von: Irwin, Darryl [VerfasserIn]
• Verfasst von: Lamy, Pierre-Jean [VerfasserIn]
• Verfasst von: Hiltermann, T. Jeroen N. [VerfasserIn]
• Verfasst von: Groen, Harry J. M. [VerfasserIn]
• Verfasst von: Pantel, Klaus [VerfasserIn]
• Verfasst von: Kempen, Léon C. van [VerfasserIn]
• Verfasst von: Wikman, Harriet [VerfasserIn]
• Verfasst von: Schuuring, Ed [VerfasserIn]
• Titel: Detection and monitoring of tumor-derived mutations in circulating tumor DNA using the UltraSEEK lung panel on the MassARRAY system in metastatic non-small cell lung cancer patients
• Verf.angabe: Paul van der Leest, Melanie Janning, Naomi Rifaela, Maria L. Aguirre Azpurua, Jolanthe Kropidlowski, Sonja Loges, Nicolas Lozano, Alexander Sartori, Darryl Irwin, Pierre-Jean Lamy, T. Jeroen N. Hiltermann, Harry J. M. Groen, Klaus Pantel, Léon C. van Kempen, Harriet Wikman and Ed Schuuring
• Jahr: 2023
• Umfang: 14 S.
• Illustrationen: Illustrationen
• Fussnoten: Veröffentlicht: 29. August 2023 ; Gesehen am 19.10.2023
• Titel Quelle: Enthalten in: International journal of molecular sciences
• Ort Quelle: Basel : Molecular Diversity Preservation International, 2000
• Jahr Quelle: 2023
• Band/Heft Quelle: 24(2023), 17, Artikel-ID 13390, Seite 1-14
• ISSN Quelle: 1422-0067
• ISSN Quelle: 1661-6596
• DOI: doi:10.3390/ijms241713390
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: circulating tumor DNA
• Sach-SW: liquid biopsy
• Sach-SW: metastatic non-small cell lung cancer
• Sach-SW: progressive disease
• Sach-SW: resistance mutations
• K10plus-PPN: 186638886X

Abstract

Analysis of circulating tumor DNA (ctDNA) is a potential minimally invasive molecular tool to guide treatment decision-making and disease monitoring. A suitable diagnostic-grade platform is required for the detection of tumor-specific mutations with high sensitivity in the circulating cell-free DNA (ccfDNA) of cancer patients. In this multicenter study, the ccfDNA of 72 patients treated for advanced-stage non-small cell lung cancer (NSCLC) was evaluated using the UltraSEEK® Lung Panel on the MassARRAY® System, covering 73 hotspot mutations in EGFR, KRAS, BRAF, ERBB2, and PIK3CA against mutation-specific droplet digital PCR (ddPCR) and routine tumor tissue NGS. Variant detection accuracy at primary diagnosis and during disease progression, and ctDNA dynamics as a marker of treatment efficacy, were analyzed. A multicenter evaluation using reference material demonstrated an overall detection rate of over 90% for variant allele frequencies (VAFs) > 0.5%, irrespective of ccfDNA input. A comparison of UltraSEEK® and ddPCR analyses revealed a 90% concordance. An 80% concordance between therapeutically targetable mutations detected in tumor tissue NGS and ccfDNA UltraSEEK® analysis at baseline was observed. Nine of 84 (11%) tumor tissue mutations were not covered by UltraSEEK®. A decrease in ctDNA levels at 4-6 weeks after treatment initiation detected with UltraSEEK® correlated with prolonged median PFS (46 vs. 6 weeks; p < 0.05) and OS (145 vs. 30 weeks; p < 0.01). Using plasma-derived ccfDNA, the UltraSEEK® Lung Panel with a mid-density set of the most common predictive markers for NSCLC is an alternative tool to detect mutations both at diagnosis and during disease progression and to monitor treatment response.