Peripheral Blood for Epidermal Growth Factor Receptor Mutation Detection in Non-Small Cell Lung Cancer Patients

Abstract

OBJECTIVE: It is important to analyze and track Epidermal Growth Factor Receptor (EGFR) mutation status for predicting efficacy and monitoring resistance throughout EGFR-tyrosine kinase inhibitors (TKIs) treatment in non-small cell lung cancer (NSCLC) patients. The objective of this study was to determine the feasibility and predictive utility of EGFR mutation detection in peripheral blood. METHODS: Plasma, serum and tumor tissue samples from 164 NSCLC patients were assessed for EGFR mutations using Amplification Refractory Mutation System (ARMS). RESULTS: Compared with matched tumor tissue, the concordance rate of EGFR mutation status in plasma and serum was 73.6% and 66.3%, respectively. ARMS for EGFR mutation detection in blood showed low sensitivity (plasma, 48.2%; serum, 39.6%) but high specificity (plasma, 95.4%; serum, 95.5%). Treated with EGFR-TKIs, patients with EGFR mutations in blood had significantly higher objective response rate (ORR) and insignificantly longer progression-free survival (PFS) than those without mutations (ORR: plasma, 68.4% versus 38.9%, P = 0.037; serum, 75.0% versus 39.5%, P = 0.017; PFS: plasma, 7.9 months versus 6.1 months, P = 0.953; serum, 7.9 months versus 5.7 months, P = 0.889). In patients with mutant tumors, those without EGFR mutations in blood tended to have prolonged PFS than patients with mutations (19.7 months versus 11.0 months, P = 0.102). CONCLUSIONS: EGFR mutations detected in blood may be highly predictive of identical mutations in corresponding tumor, as well as showing correlations with tumor response and survival benefit from EGFR-TKIs. Therefore, blood for EGFR mutation detection may allow NSCLC patients with unavailable or insufficient tumor tissue the opportunity to benefit from personalized treatment. However, due to the high false negative rate in blood samples, analysis for EGFR mutations in tumor tissue remains the gold standard.

Circulating Tumor DNA Is Effective for the Detection of EGFR Mutation in Non–Small Cell Lung Cancer: A Meta-analysis

“…1). In the study reported by Li and colleagues (49), EGFR mutation was detected in both plasma and serum, and the data of plasma and serum were analyzed as two independently studies. Thus, 27 eligible studies were included in meta-analysis.…”

Circulating cell-free DNA as a prognostic and predictive biomarker in non-small cell lung cancer

“…30 articles were reviewed in detail after the article titles and abstracts were checked [9, 16, 19–46]. Eight studies were excluded from the meta-analysis [39–46], leaving 22 studies that fulfilled the eligibility criteria [9, 16, 19–38] (Table 1). Among the 8 excluded studies, 7 did not provide sufficient data for extracting odds ratio (OR) or hazard ratio (HR) [39–45], and other 1 study was excluded because the same cohort of patients was used in other selected study [46].…”

“…4 studies reported the prognostic role of KRAS genotype detected in cfDNA for NSCLC [20, 23, 25, 34]]. Another 7 studies dealt with the predictive role of EGFR genotype presented in cfDNA for NSCLC patients who were treated with tyrosine kinase inhibitors of EGFR (EGFR-TKIs) [16, 24, 26, 35–38]. …”

Total DNA input is a crucial determinant of the sensitivity of plasma cell-free DNA EGFR mutation detection using droplet digital PCR

“…Li et al [30] found that EGFR-TKI treatment of tumor-tissue EGFR M+ patients prolonged the PFS of plasma EGFR M- patients compared with plasma EGFR M+ patients, though the result was not statistically significant (19.7 months vs. 11.0 months, P = 0.102). Furthermore, Lam et al [31] found that both the PFS and the OS of plasma EGFR M+ patients were shorter than those of plasma EGFR M- patients.…”