EGFR and metastatic neoplasm: Since plasma detection of clinically important KRAS and Level 1 EGFR variants (such as Exon 19 deletions, L858R, and T790M) is primarily associated with advanced stages, finding these mutations in cfDNA from tissue biopsy-classified early-stage cases could signal that distant spread may have already occurred, with micro-metastatic disease undetectable by radiographic staging.