From the Division of Pharmacology (M.T.J.v.B., D.P., B.M.K., J.H.B., J.H.M.S.), Clinical Pharmacology (M.T.J.v.B., B.M.K., J.H.B., J.H.M.S), Division of Pathology (M.B.), Department of Biometrics (K.S.), Department of Laboratory Medicine (D.T.C.L., D.v.d.B.), and Department of Neuro-oncology (D.B.), Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam; and Science Faculty (J.H.B., J.H.M.S), Pharmaceutical Sciences, Division of Pharmaco-epidemiology and Clinical Pharmacology, Utrecht University, the Netherlands.
Neurology. 2020 Feb 4;94(5):e521-e528. doi: 10.1212/WNL.0000000000008751. Epub 2020 Jan 6.
The primary objective was to determine the sensitivity and specificity of epithelial cell adhesion molecule (EpCAM) immunoflow cytometry circulating tumor cells (CTC) analysis in CSF in patients with suspected leptomeningeal metastases (LM). The secondary objective was to explore the distribution of driver mutations in the primary tumor, plasma, cell free CSF (cfCSF), and isolated CTC from CSF in non-small cell lung cancer (NSCLC).
We tested the performance of the CTC assay vs CSF cytology in a prospective study in 81 patients with a clinical suspicion of LM but a nonconfirmatory MRI. In an NSCLC subcohort, we analyzed circulating tumor (ct)DNA of the selected driver mutations by digital droplet PCR (ddPCR).
The sensitivity of the CTC assay was 94% (95% confidence interval [CI] 80-99) and the specificity was 100% (95% CI 91-100) at the optimal cutoff of 0.9 CTC/mL. The sensitivity of cytology was 76% (95% CI 58-89). Twelve of the 23 patients with NSCLC had mutated epidermal growth factor receptor (). All 5 tested patients with LM demonstrated the primary driver mutation in cfCSF. The driver mutation could also be detected in CTC isolated from CSF.
CTC in CSF are detected with a high sensitivity for the diagnosis of LM. ddPCR can determine mutations in both cfCSF and isolated CTC from CSF of patients with -mutated NSCLC and LM.
This study provides Class III evidence that EpCAM-based immunoflow cytometry analysis of CSF accurately identifies patients with LM.
主要目的是确定上皮细胞黏附分子（EpCAM）免疫荧光流式细胞术循环肿瘤细胞（CTC）分析在疑似脑膜转移（LM）患者脑脊液（CSF）中的敏感性和特异性。次要目的是探索非小细胞肺癌（NSCLC）中原发性肿瘤、血浆、无细胞 CSF（cfCSF）和 CSF 中分离的 CTC 中驱动突变的分布。
我们在一项前瞻性研究中测试了该 CTC 检测方法与 CSF 细胞学在 81 例临床怀疑 LM 但 MRI 不明确的患者中的表现。在 NSCLC 亚组中，我们通过数字液滴 PCR（ddPCR）分析了选定的驱动突变的循环肿瘤（ct）DNA。
CTC 检测方法的敏感性为 94%（95%置信区间 [CI] 80-99），特异性为 100%（95%CI 91-100），最佳截断值为 0.9 CTC/mL。细胞学的敏感性为 76%（95%CI 58-89）。23 例 NSCLC 患者中有 12 例存在突变表皮生长因子受体（）。所有 5 例 LM 测试患者的 cfCSF 中均存在原发性驱动突变。该驱动突变也可在 CSF 中分离的 CTC 中检测到。
CSF 中的 CTC 检测对 LM 的诊断具有高灵敏度。ddPCR 可确定 -突变 NSCLC 和 LM 患者 cfCSF 和 CSF 中分离的 CTC 中的突变。
本研究提供了 III 级证据，表明基于 EpCAM 的 CSF 免疫荧光流式细胞术分析准确识别 LM 患者。
