Azpurua, Maria L Aguirre

Groen, Harry J.M.

Hiltermann, T. Jeroen N.

Irwin, Darryl

Janning, Melanie

Kropidlowski, Jolanthe

Lamy, Pierre-Jean

Loges, Sonja

Lozano, Nicolas

Pantel, Klaus

Rifaela, Naomi

Sartori, Alexander

Schuuring, Ed

van der Leest, Paul

van Kempen, L\ue9on

Wikman, Harriet

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\uae Lung Panel on the MassARRAY\uae 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\uae and ddPCR analyses revealed a 90% concordance. An 80% concordance between therapeutically targetable mutations detected in tumor tissue NGS and ccfDNA UltraSEEK\uae analysis at baseline was observed. Nine of 84 (11%) tumor tissue mutations were not covered by UltraSEEK\uae. A decrease in ctDNA levels at 4-6 weeks after treatment initiation detected with UltraSEEK\uae 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\uae 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

Institutional Repository Universiteit Antwerpen

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

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

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Institutional Repository Universiteit Antwerpen