Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, Palermo University Hospital, Palermo, Italy.
Phase I- Early Clinical Trials Unit, Oncology Department and Multidisciplinary Oncology Center Antwerp (MOCA), Antwerp University Hospital, Edegem, Belgium.
Curr Cancer Drug Targets. 2018;18(7):697-705. doi: 10.2174/1568009618666180308125110.
Recent studies evaluated the diagnostic accuracy of circulating tumor DNA (ctDNA) analysis in the detection of epidermal growth factor receptor (EGFR) mutations from plasma of NSCLC patients, overall showing a high concordance as compared to standard tissue genotyping. However it is less clear if the location of metastatic site may influence the ability to identify EGFR mutations.
This pooled analysis aims to evaluate the association between the metastatic site location and the sensitivity of ctDNA analysis in detecting EGFR mutations in NSCLC patients.
Data from all published studies, evaluating the sensitivity of plasma-based EGFRmutation testing, stratified by metastatic site location (extrathoracic (M1b) vs intrathoracic (M1a)) were collected by searching in PubMed, Cochrane Library, American Society of Clinical Oncology, and World Conference of Lung Cancer, meeting proceedings. Pooled Odds ratio (OR) and 95% confidence intervals (95% CIs) were calculated for the ctDNA analysis sensitivity, according to metastatic site location.
A total of ten studies, with 1425 patients, were eligible. Pooled analysis showed that the sensitivity of ctDNA-based EGFR-mutation testing is significantly higher in patients with M1b vs M1a disease (OR: 5.09; 95% CIs: 2.93 - 8.84). A significant association was observed for both EGFR-activating (OR: 4.30, 95% CI: 2.35-7.88) and resistant T790M mutations (OR: 11.89, 95% CI: 1.45-97.22), regardless of the use of digital-PCR (OR: 5.85, 95% CI: 3.56-9.60) or non-digital PCR technologies (OR: 2.96, 95% CI: 2.24-3.91).
These data suggest that the location of metastatic sites significantly influences the diagnostic accuracy of ctDNA analysis in detecting EGFR mutations in NSCLC patients.
最近的研究评估了循环肿瘤 DNA（ctDNA）分析在检测非小细胞肺癌（NSCLC）患者血浆中表皮生长因子受体（EGFR）突变的诊断准确性，总体上与标准组织基因分型相比具有较高的一致性。然而，转移部位的位置是否会影响识别 EGFR 突变的能力尚不清楚。
本汇总分析旨在评估转移性部位位置与 ctDNA 分析检测 NSCLC 患者 EGFR 突变的敏感性之间的关系。
通过在 PubMed、Cochrane 图书馆、美国临床肿瘤学会和世界肺癌大会会议记录中搜索，收集了所有评估基于血浆的 EGFR 突变检测敏感性的已发表研究数据，按转移部位位置（胸外（M1b）与胸内（M1a））进行分层。根据转移部位位置，计算 ctDNA 分析敏感性的合并优势比（OR）和 95%置信区间（95%CI）。
共有 10 项研究，共 1425 例患者符合条件。汇总分析显示，M1b 患者的 ctDNA 基于 EGFR 突变检测的敏感性明显高于 M1a 疾病患者（OR：5.09；95%CI：2.93-8.84）。观察到 EGFR 激活（OR：4.30，95%CI：2.35-7.88）和耐药 T790M 突变（OR：11.89，95%CI：1.45-97.22）均存在显著相关性，无论使用数字 PCR（OR：5.85，95%CI：3.56-9.60）还是非数字 PCR 技术（OR：2.96，95%CI：2.24-3.91）。
这些数据表明，转移部位的位置显著影响 ctDNA 分析检测 NSCLC 患者 EGFR 突变的诊断准确性。
