Correlation between progression-free survival, tumor burden, and circulating tumor DNA in the initial diagnosis of advanced-stage EGFR-mutated non-small cell lung cancer

Yunkyoung Lee, Sojung Park, Woo Sung Kim, Jae Cheol Lee, Se Jin Jang, Jene Choi, Chang Min Choi

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1104-1110
Number of pages7
JournalThoracic Cancer
Volume9
Issue number9
DOIs
StatePublished - Sep 2018

Keywords

  • Circulating tumor DNA
  • EGFR-tyrosine kinase inhibitor (TKI)
  • non-small cell lung cancer
  • progression-free survival
  • sensitivity

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