Identification of early disease progression in ALK-rearranged lung cancer using circulating tumor DNA analysis (hipo K34R)

We utilized 343 longitudinal plasma DNA samples from 43 ALK+ NSCLC patients receiving targeted ALK therapy to evaluate ctDNA levels based on matched panel-based targeted next generation sequencing (tNGS) and untargeted shallow whole genome sequencing (sWGS). We measured the mean variant allele frequency (VAFmean) of genetic alterations called by tNGS and applied the t-MAD score as surrogate for the global copy number changes reflected by ctDNA. Both NGS metrics were assessed as indicators of disease progression, and more importantly, early molecular progression. Systematic establishment of thresholds in VAFmean and t-MAD changes indicating clinical progression was performed in our study cohort.EGA study EGAS00001005327