Denis Marc G, Lafourcade Marie-Pierre, Le Garff Gwenaëlle, Dayen Charles, Falchero Lionel, Thomas Pascal, Locher Chrystèle, Oliviero Gérard, Licour Muriel, Reck Martin, Normanno Nicola, Molinier Olivier
Department of Biochemistry and INSERM U1232, Nantes University Hospital, 9 quai Moncousu, F-44093 Nantes Cedex, France.
Centre Hospitalier D'Angoulême, rond-point Girac, 16470 Saint Michel, France.
J Thorac Dis. 2019 Apr;11(4):1370-1378. doi: 10.21037/jtd.2019.03.95.
The non-interventional ASSESS study (NCT01785888) evaluated the utility of circulating free tumor-derived DNA (ctDNA) from plasma for epidermal growth factor receptor () mutation testing in patients with advanced non-small-cell lung cancer (NSCLC), in a real-world setting across 56 centers in Europe and Japan. The high mutation status concordance between 1162 matched tissue/cytology and plasma samples (89%, sensitivity =46%, specificity =97%) suggested that ctDNA is a feasible sample for mutation analysis. We report data for the French subset of patients (pre-planned analysis).
Eligible patients (stage IIIA/B/IV locally advanced/metastatic treatment-naive advanced NSCLC) provided diagnostic tissue/cytology and plasma samples. DNA extracted from tissue/cytology samples was subjected to mutation testing as per local practice; a designated laboratory performed ctDNA extraction/mutation testing of plasma samples. The primary outcome was mutation status concordance between matched tumor and plasma samples.
Of the 1,311 patients enrolled in the ASSESS trial, 145 were recruited from 9 centers in France. Tumor samples from 130 patients were collected and 126 were evaluable for mutation analysis. Activating mutations were identified in 13 of the 126 patient tumor samples ( mutation frequency 10.3%). For plasma testing, 10 of the 145 samples tested were positive for mutations ( mutation frequency 6.9%). mutation rate was significantly higher in never- versus ever-smokers (stepwise logistic regression: tumor, P<0.0001; plasma, P=0.0008). Mutation status concordance between 126 matched patient samples was 96.0% [121/126; 95% confidence intervals (CI), 91.0-98.7]. Of the 113 mutation-negative patient tissue samples, one tested plasma-positive; reanalysis of plasma via two different techniques confirmed the presence of a L858R mutation, indicating a tissue false-negative result. Based on these data, sensitivity of plasma testing was 64.3% (9/14; 95% CI, 35.1-87.2%) and its specificity was 100.0% (112/112; 95% CI, 96.8-100.0%).
Data confirm ctDNA as an alternative sample for mutation analysis in patients with advanced NSCLC.
非干预性ASSESS研究（NCT01785888）在欧洲和日本的56个中心的实际临床环境中，评估了血浆中循环游离肿瘤来源DNA（ctDNA）用于晚期非小细胞肺癌（NSCLC）患者表皮生长因子受体（EGFR）突变检测的效用。1162对匹配的组织/细胞学和血浆样本之间的高突变状态一致性（89%，敏感性=46%，特异性=97%）表明，ctDNA是进行EGFR突变分析的可行样本。我们报告法国患者亚组的数据（预先计划的分析）。
符合条件的患者（IIIA/B/IV期局部晚期/转移性未经治疗的晚期NSCLC）提供诊断性组织/细胞学和血浆样本。从组织/细胞学样本中提取的DNA按照当地实践进行EGFR突变检测；指定实验室进行血浆样本的ctDNA提取/突变检测。主要结局是匹配的肿瘤和血浆样本之间的EGFR突变状态一致性。
在ASSESS试验纳入的1311例患者中，145例来自法国的9个中心。收集了130例患者的肿瘤样本，其中126例可用于EGFR突变分析。在126例患者肿瘤样本中的13例中检测到激活型EGFR突变（突变频率10.3%）。对于血浆检测，145份检测样本中有10份EGFR突变呈阳性（突变频率6.9%）。从不吸烟者与曾经吸烟者相比，EGFR突变率显著更高（逐步逻辑回归：肿瘤，P<0.0001；血浆，P=0.0008）。126对匹配患者样本之间的突变状态一致性为96.0%[121/126；95%置信区间（CI），91.0 - 98.7]。在113例EGFR突变阴性的患者组织样本中，有1例血浆检测呈阳性；通过两种不同技术对血浆进行重新分析证实存在L858R突变，表明组织检测结果为假阴性。基于这些数据，血浆检测的敏感性为64.3%（9/14；95%CI，35.1 - 87.2%），特异性为100.0%（112/112；95%CI，96.8 - 100.0%）。
数据证实ctDNA可作为晚期NSCLC患者EGFR突变分析的替代样本。
