Mass Spectrometry as a Highly Sensitive Method for Specific Circulating Tumor DNA Analysis in NSCLC: A Comparison Study

Abstract

Plasma-based tumor mutational profiling is arising as a reliable approach to detect primary and therapy-induced resistance mutations required for accurate treatment decision making. Here, we compared the FDA-approved Cobas^® EGFR Mutation Test v2 with the UltraSEEK™ Lung Panel on the MassARRAY^® System on detection of <i>EGFR</i> mutations, accompanied with preanalytical sample assessment using the novel Liquid IQ^® Panel. 137 cancer patient-derived cell-free plasma samples were analyzed with the Cobas^® and UltraSEEK™ tests. Liquid IQ^® analysis was initially validated (<i>n</i> = 84) and used to determine ccfDNA input for all samples. Subsequently, Liquid IQ^® results were applied to harmonize ccfDNA input for the Cobas^® and UltraSEEK™ tests for 63 NSCLC patients. The overall concordance between the Cobas^® and UltraSEEK™ tests was 86%. The Cobas^® test detected more <i>EGFR</i> exon19 deletions and L858R mutations, while the UltraSEEK™ test detected more T790M mutations. A 100% concordance in both the clinical (<i>n</i> = 137) and harmonized (<i>n</i> = 63) cohorts was observed when >10 ng of ccfDNA was used as determined by the Liquid IQ^® Panel. The Cobas^® and UltraSEEK™ tests showed similar sensitivity in <i>EGFR</i> mutation detection, particularly when ccfDNA input was sufficient. It is recommended to preanalytically determine the ccfDNA concentration accurately to ensure sufficient input for reliable interpretation and treatment decision making.