Fragment size and dynamics of EGFR-mutated tumor-derived DNA provide prognostic information regarding EGFR-TKI efficacy in patients with EGFR-mutated NSCLC

Circulating tumor DNA (ctDNA)-based next-generation sequencing (NGS) is a complementary and alternative test to tissue-based NGS. e performed NGS analysis of ctDNA samples collected from patients with EGFR -mutated non-small cell lung cancer (NSCLC) who received osimertinib; the samples were collected after second-line treatment, before osimertinib treatment, one week and one month after osimertinib treatment, and at the time of resistance formation, and the correlation with osimertinib efficacy was examined. From January to December 2018, 34 patients with EGFR -mutated NSCLC harboring EGFR T790M mutations were enrolled, and a total of 132 peripheral blood samples were collected. The fragment sizes of EGFR -mutated ctDNAs were significantly shorter than those of their corresponding normal fragments. Osimertinib treatment of EGFR -mutated patients with shorter EGFR -mutated ctDNA fragments resulted in shorter progression-free survival (PFS). Disappearance timing of EGFR -mutated fragment fractions and clonal evolution patterns (new driver mutation group, additional mutation group vs. attenuation group) were each associated with osimertinib PFS, although multivariate analysis revealed that only shorter EGFR -mutated ctDNA fragments were associated with osimertinib PFS. EGFR -mutated ctDNA fragment size, disappearance timing, and clonal evolution pattern were related to the effects of osimertinib. In particular, short EGFR -mutated ctDNA fragmentation may be closely related to osimertinib efficacy prediction.