Background: This study was conducted to identify whether the presence of circulating tumor DNA (ctDNA) in plasma before treatment with EGFR-tyrosine kinase inhibitors (TKIs) is associated with clinical outcomes. Methods: Fifty-seven pairs of tissues and plasma samples were obtained from patients with NSCLC adenocarcinoma harboring activating EGFR mutations before the administration of EGFR-TKI treatment. ctDNA mutation was identified using the PANAMutyper EGFR mutation kit. Both qualitative and quantitative analyzes of the data were performed. Results: Concordance rates with tissue biopsy were 40.4% and 59.6% for the qualitative and quantitative methods, respectively. Bone metastasis showed a statistically significant correlation with ctDNA detection (odds ratio 3.985, 95% confidence interval [CI] 1.027–15.457; P = 0.046). Progression-free survival (PFS) was significantly shorter in the group detected with ctDNA than in the undetected ctDNA group (median PFS 9.8 vs. 20.7 months; hazard ratio [HR] 2.30, 95% CI 1.202–4.385; P = 0.012). Detection of ctDNA before treatment with EGFR-TKIs (HR 2.388, 95% CI 1.138–5.014; P = 0.021) and extra-thoracic lymph node metastasis (HR 13.533, 95% CI 2.474–68.747; P = 0.002) were independently associated with PFS. Six of 11 patients (45.5%) monitored by serial sampling showed a dynamic change in ctDNA prior to disease progression. Conclusion: Quantitative testing can increase the sensitivity of the ctDNA detection test. Patients with detectable ctDNA had significantly shorter PFS after receiving EGFR-TKIs than those with undetectable ctDNA. Tumor burden may be associated with plasma ctDNA detection. A shorter PFS was associated with detection of ctDNA and extra-thoracic lymph node metastasis. Dynamic changes in the ctDNA level may help predict clinical outcomes.
- Circulating tumor DNA
- EGFR-tyrosine kinase inhibitor (TKI)
- non-small cell lung cancer
- progression-free survival