Hackner Klaus, Buder Anna, Hochmair Maximilian J, Strieder Matthaeus, Grech Christina, Fabikan Hannah, Burghuber Otto C, Errhalt Peter, Filipits Martin
Department of Pneumology, University Hospital Krems, Karl Landsteiner University of Health Sciences, Krems, Austria.
Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria.
Clin Med Insights Oncol. 2021 Feb 17;15:1179554921993072. doi: 10.1177/1179554921993072. eCollection 2021.
Proof of the T790M resistance mutation is mandatory if patients with -mutated non-small cell lung cancer (NSCLC) progress under first- or second-generation tyrosine kinase inhibitor therapy. In addition to rebiopsy, analysis of plasma circulating tumor DNA is used to detect T790M resistance mutation. We studied whether sputum is another feasible specimen for detection of mutations.
Twenty-eight patients with advanced -mutated NSCLC were included during stable and/or progressive disease. The initial activating mutations (exon 19 deletions or L858R mutations) at stable disease and at progressive disease (together with T790M) were assessed in simultaneously collected plasma and sputum samples and detected by droplet digital polymerase chain reaction (ddPCR).
Activating mutations were detected in 47% of the plasma samples and 41% of sputum samples during stable disease, and in 57% of plasma samples and 64% of sputum samples during progressive disease. T790M was detected in 44% of the plasma samples and 66% of the sputum samples at progressive disease. In ddPCR T790M-negative results for both specimens (plasma and sputum), negativity was confirmed by rebiopsy in 5 samples. Concordance rate of plasma and sputum for T790M was 0.86, with a positive percent agreement of 1.0 and a negative percent agreement of 0.80.
We demonstrated that mutation analysis with ddPCR is feasible in sputum samples. Combination of plasma and sputum analyses for detection of T790M in NSCLC patients with progressive disease increases the diagnostic yield compared with molecular plasma analysis alone.
对于携带表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）患者，若在第一代或第二代酪氨酸激酶抑制剂治疗期间病情进展，则T790M耐药突变的检测证据是必不可少的。除了再次活检外，血浆循环肿瘤DNA分析也用于检测T790M耐药突变。我们研究了痰液是否是另一种检测EGFR突变的可行标本。
纳入28例处于病情稳定和/或进展期的晚期EGFR突变NSCLC患者。在同时采集的血浆和痰液样本中评估病情稳定期和进展期（连同T790M）的初始激活EGFR突变（外显子19缺失或L858R突变），并通过液滴数字聚合酶链反应（ddPCR）进行检测。
病情稳定期，47%的血浆样本和41%的痰液样本检测到激活EGFR突变；病情进展期，57%的血浆样本和64%的痰液样本检测到激活EGFR突变。病情进展期，44%的血浆样本和66%的痰液样本检测到T790M。在ddPCR检测中，若两个标本（血浆和痰液）的T790M结果均为阴性，则通过再次活检在5个样本中确认了阴性结果。血浆和痰液中T790M的一致性率为0.86，阳性一致率为1.0，阴性一致率为0.80。
我们证明了用ddPCR进行痰液样本中的EGFR突变分析是可行的。与单独的血浆分子分析相比，联合血浆和痰液分析来检测病情进展的NSCLC患者中的T790M可提高诊断率。
