Steendam Christi M J, Atmodimedjo Peggy, de Jonge Evert, Paats Marthe S, van der Leest Cor, Oomen-de Hoop Esther, Jansen Maurice P H M, Del Re Marzia, von der Thüsen Jan H, Dinjens Winand N M, van Schaik Ron H N, Aerts Joachim G J V, Dubbink Hendrikus Jan
Erasmus MC Rotterdam, Rotterdam, the Netherlands.
Amphia Hospital, Breda, the Netherlands.
JCO Precis Oncol. 2019 Dec;3:1-9. doi: 10.1200/PO.18.00401.
To compare the results of plasma cell-free DNA (cfDNA) droplet digital PCR (ddPCR) and next-generation sequencing (NGS) on detection of epidermal growth factor receptor () primary activating mutations and p.T790M with results of tissue analysis in patients with mutated non-small-cell lung cancer.
All patients with EGFR mutated non-small cell lung cancer for which a pathology and a plasma specimen were available upon progression between November 2016 and July 2018 were selected. Concordance, Cohen's κ, and intraclass correlation coefficients were calculated.
Plasma cfDNA and pathology specimens of 36 patients were analyzed. Agreement between ddPCR and NGS was 86% (κ = 0.63) for the primary activating mutation and 94% (κ = 0.89) for the p.T790M detection. Allele ratios were comparable, with an intraclass correlation coefficient of 0.992 and 0.997, respectively. Discrepancies of some degree were found in 15 patients (41.7%). In six patients (16.7%), no mutations were detected in cfDNA. In three patients (8.3%), p.T790M was detected in plasma but not in the pathology specimen, whereas in three other patients (8.3%), p.T790M was demonstrated in the pathology specimen but not in plasma. Concordance of cfDNA and pathology for the primary activating mutation was 69% for ddPCR and 83% for NGS. For the detection of p.T790M, this was 75% (κ = 0.49) for ddPCR as well as for NGS.
Mutual agreement is high between NGS and ddPCR in cfDNA on the level of a specific mutation, with comparable ratio results. Plasma testing of primary activating mutations and p.T790M shows high concordance with pathology results, for NGS as well as for ddPCR, depending on the extent of the panel used. In NGS, more genetic aberrations can be investigated at once.
比较血浆游离DNA（cfDNA）液滴数字PCR（ddPCR）和下一代测序（NGS）检测表皮生长因子受体（EGFR）原发性激活突变及p.T790M的结果与EGFR突变的非小细胞肺癌患者组织分析结果。
选取2016年11月至2018年7月疾病进展时可获得病理和血浆标本的所有EGFR突变的非小细胞肺癌患者。计算一致性、科恩kappa系数和组内相关系数。
分析了36例患者的血浆cfDNA和病理标本。ddPCR和NGS检测原发性激活突变的一致性为86%（κ = 0.63），检测p.T790M的一致性为94%（κ = 0.89）。等位基因比率具有可比性，组内相关系数分别为0.992和0.997。15例患者（41.7%）存在一定程度的差异。6例患者（16.7%）的cfDNA未检测到突变。3例患者（8.3%）血浆中检测到p.T790M，但病理标本中未检测到；另外3例患者（8.3%）病理标本中检测到p.T790M，但血浆中未检测到。ddPCR检测原发性激活突变时cfDNA与病理结果的一致性为69%，NGS为83%。对于p.T790M的检测，ddPCR和NGS均为75%（κ = 0.49）。
在cfDNA中，NGS和ddPCR在特定突变水平上的相互一致性较高，比率结果具有可比性。EGFR原发性激活突变和p.T790M的血浆检测与病理结果具有高度一致性，对于NGS和ddPCR均如此，这取决于所使用检测组合的范围。在NGS中，可以同时研究更多的基因畸变。
