Pender Alexandra, Hughesman Curtis, Law Elaine, Kristanti Amadea, McNeil Kelly, Wong Selina, Tucker Tracy, Bosdet Ian, Young Sean, Laskin Janessa, Karsan Aly, Yip Stephen, Ho Cheryl
Department of Medical Oncology, Royal Free London NHS Foundation Trust and North Middlesex University Hospital, London, UK.
Cancer Genetics & Genomics Laboratory, BC Cancer, Vancouver, Canada.
Transl Lung Cancer Res. 2020 Aug;9(4):1084-1092. doi: 10.21037/tlcr-19-581.
EGFR T790M testing is the standard of care for activating EGFR mutation (EGFRm) non-small cell lung cancer (NSCLC) progressing on 1st/2nd generation TKIs to select patients for osimertinib. Despite sensitive assays, detection of circulating tumour deoxyribonucleic acid (ctDNA) is variable and influenced by clinical factors. The number and location of sites of progressive disease at time of testing were reviewed to explore the effect on EGFR ctDNA detection. The prognostic value of EGFR ctDNA detection on survival outcomes was assessed.
Following extraction of cell-free DNA from plasma using the QIAamp Circulating Nucleic Acid Kit, custom droplet digital polymerase chair reaction (ddPCR) assays were used to assess EGFR ctDNA using the Bio-Rad QX200 system. The ddPCR assay has a limit of detection of ≤0.15% variant allele fraction. Baseline characteristics and imaging reports at time of EGFR ctDNA testing were reviewed retrospectively for a 1 year period.
The study included 177 patients who had an EGFR ctDNA test. Liver (aOR 3.13) or bone (aOR 2.76) progression or 3-5 sites of progression (aOR 2.22) were predictive of EGFR ctDNA detection. The median OS from first ctDNA test after multiple testing iterations was 12.3 m undetectable EGFR ctDNA, 7.6 m for original EGFR mutation only and 24.1 m with T790M (P=0.001).
Patients with liver or bone progression and 3-5 progressing sites are more likely to have informative EGFR ctDNA testing. Detection of EGFR ctDNA is a negative prognostic indicator in the absence of a T790M resistance mutation, potentially reflecting the disease burden in the absence of targeted therapy options.
表皮生长因子受体（EGFR）T790M检测是激活型EGFR突变（EGFRm）的非小细胞肺癌（NSCLC）患者在接受第一代/第二代酪氨酸激酶抑制剂（TKIs）治疗期间病情进展时的标准治疗手段，用于选择接受奥希替尼治疗的患者。尽管检测方法灵敏，但循环肿瘤脱氧核糖核酸（ctDNA）的检测结果存在差异，且受临床因素影响。本研究回顾了检测时疾病进展部位的数量和位置，以探讨其对EGFR ctDNA检测的影响，并评估EGFR ctDNA检测对生存结果的预后价值。
使用QIAamp循环核酸试剂盒从血浆中提取游离DNA后，采用定制的液滴数字聚合酶链反应（ddPCR）检测法，通过Bio-Rad QX200系统评估EGFR ctDNA。ddPCR检测法的检测限为变异等位基因分数≤0.15%。回顾性分析了1年期间EGFR ctDNA检测时的基线特征和影像学报告。
该研究纳入了177例接受EGFR ctDNA检测的患者。肝脏转移（调整后比值比[aOR] 3.13）或骨转移（aOR 2.76）或3 - 5个转移部位（aOR 2.22）可预测EGFR ctDNA检测结果。经过多次检测迭代后，首次ctDNA检测后，EGFR ctDNA未检出患者的中位总生存期（OS）为12.3个月，仅存在原始EGFR突变患者的中位OS为7.6个月，存在T790M突变患者的中位OS为24.1个月（P = 0.001）。
发生肝脏或骨转移以及有3 - 5个转移部位的患者更有可能获得有意义的EGFR ctDNA检测结果。在没有T790M耐药突变的情况下，EGFR ctDNA检测是一个负面的预后指标，可能反映了缺乏靶向治疗选择时的疾病负担。
