Catharina Hospital Eindhoven, Clinical Laboratory, Eindhoven, Netherlands; Eindhoven University of Technology, Institute for Complex Molecular Systems and Department of Biomedical Engineering, Laboratory of Chemical Biology, Eindhoven, Netherlands; Expert Center Clinical Chemistry Eindhoven, Eindhoven, Netherlands.
Catharina Hospital Eindhoven, Department of Respiratory Medicine, Eindhoven, Netherlands.
Cancer Treat Res Commun. 2021;29:100449. doi: 10.1016/j.ctarc.2021.100449. Epub 2021 Aug 25.
Supernatant pleural effusions (PE) have shown to be a valuable source for the detection of driver mutations in circulating tumor DNA (ctDNA). In this prospective study, the clinical value of ctDNA analysis in supernatant PE to support therapy selection and disease monitoring in lung cancer patients is assessed. Paired PE and plasma samples were collected from lung cancer patients before initiation of therapy (N = 2) and from EGFR positive patients during therapy (N = 3). Supernatant PE and plasma were tested for mutations in EGFR, KRAS and BRAF by droplet digital PCR. In PE of two patients with suspected lung cancer, a KRAS mutation was detected with a 5- and 8-fold higher fractional abundance (FA) compared to plasma. For three patients with progressive disease during therapy, both the EGFR L858R and T790M mutations were detected in PE. However, in plasma only for two of these patients the L858R mutation was detected with a 46- and 14- fold lower FA, and only for one patient the T790M mutation was detected with a 8-fold lower FA. For one patient, longitudinal ctDNA analysis in PE revealed the T790M and L858R mutations already two months prior to detection of progressive disease by CT-scan. In this study, a higher ctDNA concentration and FA was obtained from PE compared to the corresponding blood samples, which enables more sensitive mutation analysis. Thus, PE is a valuable liquid biopsy, complementing plasma, for ctDNA analysis to support therapy selection and disease monitoring in lung cancer patients.
胸腔积液上清液（PE）已被证明是检测循环肿瘤 DNA（ctDNA）中驱动突变的有价值的来源。在这项前瞻性研究中，评估了 ctDNA 分析在胸腔积液上清液中对支持肺癌患者治疗选择和疾病监测的临床价值。在开始治疗前（N=2）和 EGFR 阳性患者治疗期间（N=3），从肺癌患者中采集配对的 PE 和血浆样本。通过液滴数字 PCR 检测 EGFR、KRAS 和 BRAF 中的突变。在两名疑似肺癌患者的 PE 中，检测到 KRAS 突变，与血浆相比，其分数丰度（FA）高 5 倍和 8 倍。对于治疗期间疾病进展的 3 名患者，均在 PE 中检测到 EGFR L858R 和 T790M 突变。然而，在这些患者中，只有 2 名患者的血浆中检测到 L858R 突变，FA 分别低 46 倍和 14 倍，只有 1 名患者检测到 T790M 突变，FA 低 8 倍。对于一名患者，PE 中的纵向 ctDNA 分析在 CT 扫描检测到疾病进展前两个月就已经揭示了 T790M 和 L858R 突变。在这项研究中，与相应的血液样本相比，PE 中获得了更高的 ctDNA 浓度和 FA，这使得突变分析更敏感。因此，PE 是一种有价值的液体活检，可与血浆互补，用于 ctDNA 分析，以支持肺癌患者的治疗选择和疾病监测。
