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Circulating epithelial tumor cell analysis in CSF in patients with leptomeningeal metastases.

软脑膜转移患者脑脊液循环上皮肿瘤细胞分析。

  • 影响因子:3.85
  • DOI:10.1212/WNL.0000000000008751
  • 作者列表:"van Bussel MTJ","Pluim D","Milojkovic Kerklaan B","Bol M","Sikorska K","Linders DTC","van den Broek D","Beijnen JH","Schellens JHM","Brandsma D
  • 发表时间:2020-02-04
Abstract

OBJECTIVE: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). METHODS: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). RESULTS: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 (EGFR). All 5 tested patients with LM demonstrated the primary EGFR driver mutation in cfCSF. The driver mutation could also be detected in CTC isolated from CSF. CONCLUSION:CTC in CSF are detected with a high sensitivity for the diagnosis of LM. ddPCR can determine EGFR mutations in both cfCSF and isolated CTC from CSF of patients with EGFR-mutated NSCLC and LM. CLASSIFICATION OF EVIDENCE:This study provides Class III evidence that EpCAM-based immunoflow cytometry analysis of CSF accurately identifies patients with LM.

摘要

目的: 主要目的是确定上皮细胞粘附分子 (EpCAM) 免疫流式细胞术循环肿瘤细胞 (CTC) 的敏感性和特异性。疑似软脑膜转移 (LM) 患者的CSF分析。次要目的是探讨驱动突变在原发肿瘤、血浆、无细胞CSF (cfCSF) 、并从非小细胞肺癌 (NSCLC) 的CSF中分离出CTC。 方法: 我们在一项前瞻性研究中,对 81 例临床怀疑LM但有非验证性MRI的患者进行了CTC检测与CSF细胞学比较。在NSCLC亚组中,我们通过数字液滴PCR (ddPCR) 分析了所选驱动突变的循环肿瘤 (ct)DNA。 结果: CTC试验的敏感性为 94% (95% 置信区间 [CI] 80-99),特异性为 100% (95% CI 91-100) 在 0.9 CTC/mL的最佳截止值。细胞学检查的敏感性为 76% (95% CI 58-89)。23 例NSCLC患者中 12 例表皮生长因子受体 (EGFR) 突变。所有 5 名经测试的LM患者均证明了cfCSF中的原发性EGFR驱动突变。也可以在从CSF分离的CTC中检测到驱动突变。 结论: 检测CSF中CTC对LM的诊断具有较高的敏感性,ddPCR可同时检测EGFR突变的NSCLC和LM患者CSF中分离的CTC和cfCSF中的EGFR突变。 证据分类: 本研究提供了基于EpCAM的CSF免疫流式细胞术分析准确鉴定LM患者的III类证据。

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影响因子:6.93
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DOI:10.1002/ijc.32530
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肺肿瘤方向

肺肿瘤,又叫支气管肺癌,是常见的恶性肿瘤之一。肺肿瘤的治疗为包括手术、中药、放疗、化疗及免疫等多学科的综合治疗。

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