Abstract
Detection of an epidermal growth factor receptor (EGFR) mutation in circulating cell-free DNA (cfDNA) is a noninvasive method to collect genetic information to guide treatment of lung cancer with tyrosine-kinase inhibitors (TKIs). However, the association between cfDNA and detection of EGFR mutations in tumor tissue remains unclear. Here, a meta-analysis was performed to determine whether cfDNA could serve as a substitute for tissue specimens for the detection of EGFR mutations. The pooled sensitivity, specificity, and areas under the curve of cfDNA were 0.60, 0.94, and 0.9208 for the detection of EGFR mutations, 0.64, 0.99, and 0.9583 for detection of the exon 19 deletion, and 0.57, 0.99, and 0.9605 for the detection of the L858R mutation, respectively. Our results showed that cfDNA has a high degree of specificity to detect exon 19 deletions and L858R mutation. Due to its high specificity and noninvasive characteristics, cfDNA analysis presents a promising method to screen for mutations in NSCLC and predict patient response to EGFR-TKI treatment, dynamically assess treatment outcome, and facilitate early detection of resistance mutations.
Highlights
Lung cancer is the leading cause of cancer-related death, accounting for more than 27% of all cancer deaths worldwide [1]
Due to its high specificity and noninvasive characteristics, cell-free DNA (cfDNA) analysis presents a promising method to screen for mutations in non-small cell lung cancer (NSCLC) and predict patient response to epidermal growth factor receptor (EGFR)-tyrosine-kinase inhibitors (TKIs) treatment, dynamically assess treatment outcome, and facilitate early detection of resistance mutations
Tumor tissue is the gold standard for detection of EGFR mutation status, major barriers exist in terms of acquisition and utility
Summary
Lung cancer is the leading cause of cancer-related death, accounting for more than 27% of all cancer deaths worldwide [1]. The most commonly found mutations are in-frame deletions of amino acids 747–750 in exon 19 (exon 19 deletion), accounting for 45% of mutations, and exon 21 mutations resulting in the single-point substitution mutation L858R, which accounts for 40%–45% of such mutations [4] Both exon 19 deletions and the L858R point mutation result in activation of the TK domain, and both are correlated with sensitivity to small molecule TK inhibitors (TKIs), such as erlotinib, gefitinib, and afatinib. Treatment with TKIs is correlated with a statistically significant and clinically meaningful response rate and prognosis [5]. Among wildtype EGFR patients, survival was superior in those who received first-line chemotherapy than those who received erlotinib first followed by subsequent chemotherapy www.impactjournals.com/oncotarget (11.6 vs 8.7 months, respectively), while the point mutation T790M in exon 20 is associated with poorer response and shorter survival [6, 7]. Detection of EGFR mutation type is important to predict the effect of TKI treatment
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