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

Area of Science:

• Oncology
• Molecular Diagnostics
• Genetics

Background:

• Plasma-based tumor mutational profiling aids in treatment decisions by detecting resistance mutations.
• Accurate preanalytical assessment of cell-free DNA (cfDNA) is vital for reliable molecular profiling.

Purpose of the Study:

• To compare the performance of the Cobas® EGFR Mutation Test v2 and the UltraSEEK™ Lung Panel for detecting EGFR mutations.
• To evaluate the impact of preanalytical cfDNA quantification using the Liquid IQ® Panel on test concordance.

Main Methods:

• 137 plasma samples were analyzed using Cobas® and UltraSEEK™ tests.
• Liquid IQ® Panel was used for cfDNA input assessment and harmonization.
• Concordance analysis was performed on clinical (n=137) and harmonized (n=63) cohorts.

Main Results:

• Overall concordance between Cobas® and UltraSEEK™ was 86%.
• 100% concordance was achieved with >10 ng cfDNA input, as determined by Liquid IQ®.
• Cobas® detected more exon19 deletions and L858R mutations; UltraSEEK™ detected more T790M mutations.

Conclusions:

• Both tests demonstrate similar sensitivity for EGFR mutation detection with sufficient cfDNA.
• Accurate preanalytical cfDNA quantification is essential for reliable results and informed treatment decisions.