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

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, Ed Schuuring*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)
33 Downloads (Pure)

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.

Original languageEnglish
Article number13390
Number of pages14
JournalInternational Journal of Molecular Sciences
Volume24
Issue number17
DOIs
Publication statusPublished - 29-Aug-2023

Keywords

  • Humans
  • Circulating Tumor DNA/genetics
  • Carcinoma, Non-Small-Cell Lung/diagnosis
  • Lung Neoplasms/diagnosis
  • Cell-Free Nucleic Acids
  • Mutation
  • Disease Progression
  • Lung

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