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

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&reg
EGFR Mutation Test v2 with the UltraSEEK&trade
Lung Panel on the MassARRAY&reg
System on detection of EGFR mutations, accompanied with preanalytical sample assessment using the novel Liquid IQ&reg
Panel. 137 cancer patient-derived cell-free plasma samples were analyzed with the Cobas&reg
and UltraSEEK&trade
tests. Liquid IQ&reg
analysis was initially validated (n = 84) and used to determine ccfDNA input for all samples. Subsequently, Liquid IQ&reg
results were applied to harmonize ccfDNA input for the Cobas&reg
tests for 63 NSCLC patients. The overall concordance between the Cobas&reg
tests was 86%. The Cobas&reg
test detected more EGFR exon19 deletions and L858R mutations, while the UltraSEEK&trade
test detected more T790M mutations. A 100% concordance in both the clinical (n = 137) and harmonized (n = 63) cohorts was observed when &gt
10 ng of ccfDNA was used as determined by the Liquid IQ&reg
Panel. The Cobas&reg
tests showed similar sensitivity in EGFR 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.