Department of Pulmonary Diseases, AZ Delta General Hospital, Roeselare, Belgium.
Department of Laboratory Medicine, AZ Delta General Hospital, Roeselare, Belgium.
Sci Rep. 2024 Aug 6;14(1):18191. doi: 10.1038/s41598-024-68350-6.
Cobas EGFR mutation Test v2 was FDA-approved as qualitative liquid biopsy for actionable EGFR variants in non-small cell lung cancer (NSCLC). It generates semiquantitative index (SQI) values that correlate with mutant allele levels, but decision thresholds for clinical use in NSCLC surveillance are lacking. We conducted long-term ctDNA monitoring in 20 subjects with EGFR-mutated NSCLC; resulting in a 155 on-treatment samples. We defined optimal SQI intervals to predict/rule-out progression within 12 weeks from sampling and performed orthogonal calibration versus deep-sequencing and digital PCR. SQI showed significant diagnostic power (AUC 0.848, 95% CI 0.782-0.901). SQI below 5 (63% of samples) had 93% (95% CI 87-96%) NPV, while SQI above 10 (25% of samples) had 69% (95% CI 56-80%) PPV. Cobas EGFR showed perfect agreement with sequencing (Kappa 0.860; 95% CI 0.674-1.00) and digital PCR. SQI values strongly (r: 0.910, 95% 0.821-0.956) correlated to mutant allele concentrations with SQI of 5 and 10 corresponding to 6-9 (0.2-0.3%) and 64-105 (1.1-1.6%) mutant allele copies/mL (VAF) respectively. Our dual-threshold classifier of SQI 0/5/10 yielded informative results in 88% of blood draws with high NPV and good overall clinical utility for patient-centric surveillance of metastatic NSCLC.
Cobas EGFR mutation Test v2 获得美国食品药品监督管理局（FDA）批准，作为非小细胞肺癌（NSCLC）中可操作的 EGFR 变异的定性液体活检方法。它生成与突变等位基因水平相关的半定量指数（SQI）值，但缺乏 NSCLC 监测中用于临床的决策阈值。我们对 20 名 EGFR 突变 NSCLC 患者进行了长期 ctDNA 监测；共获得 155 个治疗期间的样本。我们定义了最佳 SQI 区间，以预测/排除从采样开始 12 周内的进展，并与深度测序和数字 PCR 进行正交校准。SQI 显示出显著的诊断能力（AUC 0.848，95%CI 0.782-0.901）。SQI 低于 5（63%的样本）时，NPV 为 93%（95%CI 87-96%），而 SQI 高于 10（25%的样本）时，PPV 为 69%（95%CI 56-80%）。Cobas EGFR 与测序（Kappa 0.860；95%CI 0.674-1.00）和数字 PCR 具有完美的一致性。SQI 值与突变等位基因浓度具有很强的相关性（r：0.910，95%置信区间为 0.821-0.956），当 SQI 为 5 和 10 时，分别对应 6-9%（0.2-0.3%）和 64-105%（1.1-1.6%）的突变等位基因拷贝/ml（VAF）。我们的 SQI 0/5/10 双阈值分类器在 88%的血液采集样本中产生了有意义的结果，具有高 NPV 和良好的总体临床实用性，可用于转移性 NSCLC 以患者为中心的监测。
