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

doi:10.1111/1759-7714.12793

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

Thorac Cancer. 2018 Sep;9(9):1104-1110. doi: 10.1111/1759-7714.12793. Epub 2018 Jul 10.

Authors

Yunkyoung Lee¹, Sojung Park², Woo Sung Kim³, Jae Cheol Lee⁴, Se Jin Jang⁵, Jene Choi⁵, Chang-Min Choi^{3

4}

Affiliations

¹ Department of Pulmonary and Critical Care Medicine, Chungnam National University Hospital, Daejeon, South Korea.
² Department of Pulmonary and Critical Care Medicine, Hallym University Medical Center, University of Hallym College of Medicine, Kangwon, Korea.
³ Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea.
⁴ Department of Oncology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea.
⁵ Department of Pathology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea.

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.

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

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Biomarkers, Tumor
Carcinoma, Non-Small-Cell Lung / diagnosis*
Carcinoma, Non-Small-Cell Lung / drug therapy
Carcinoma, Non-Small-Cell Lung / genetics*
Carcinoma, Non-Small-Cell Lung / mortality
Circulating Tumor DNA*
ErbB Receptors / genetics*
Female
Humans
Kaplan-Meier Estimate
Lung Neoplasms / diagnosis*
Lung Neoplasms / genetics*
Lung Neoplasms / mortality
Male
Middle Aged
Mutation*
Neoplasm Staging
Odds Ratio
Prognosis
Protein Kinase Inhibitors / pharmacology
Protein Kinase Inhibitors / therapeutic use
Tumor Burden

Substances

Biomarkers, Tumor
Circulating Tumor DNA
Protein Kinase Inhibitors
ErbB Receptors