Department of Neurology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
J Neurooncol. 2020 Jul;148(3):599-606. doi: 10.1007/s11060-020-03555-z. Epub 2020 Jun 6.
The CellSearch® system has been used to identify circulating tumor cells (CTCs) in cerebrospinal fluid (CSF) to diagnose leptomeningeal metastasis (LM) in patients with epithelial cancers. Using this system, we prospectively explored sequential CSF CTC enumeration in patients with LM from HER2+ cancers receiving intrathecal (IT) trastuzumab to capture dynamic changes in CSF CTC enumeration.
CSF from patients enrolled in an IRB-approved phase I/II dose escalation trial of IT trastuzumab for LM in HER2+ cancer (NCT01325207) was obtained on day 1 of each cycle and was evaluated by the CellSearch® platform for CTC enumeration. The results were correlated with CSF cytology from the same sample, along with clinical and radiographic response.
Fifteen out of 34 patients with HER2+ LM were enrolled in CSF CTC analysis; 14 were women. Radiographic LM was documented in 14 (93%) patients; CSF cytology was positive in 6 (40%) and CSF CTCs were identified in 13 (87%). Median CSF CTC was 22 CTCs (range 0-200 +) per 3 ml. HER2/neu expression analysis of CTCs was performed in 8 patients; 75% had confirmed expression of HER2/neu positivity in CSF and HER2/neu expression was absent in 25%. Four of 10 patients received 7 or more cycles of IT trastuzumab; in 3 of these patients, increase in CSF CTCs enumeration from baseline was detected 2-3 months prior to changes seen on MRI, and while CSF cytology remained negative.
Our study demonstrates that enumeration of CSF CTCs may provide dynamic, quantitative assessment of tumor burden in the central nervous system compartment during treatment for LM and prior to changes on MRI or CSF cytology.
Clinicaltrials.gov: NCT01325207; registered March 29th, 2011.
CellSearch®系统已被用于识别脑脊髓液（CSF）中的循环肿瘤细胞（CTC），以诊断上皮癌患者的脑膜转移（LM）。使用该系统，我们前瞻性地探索了接受鞘内（IT）曲妥珠单抗治疗 LM 的 HER2+癌症患者 CSF CTC 连续计数，以捕获 CSF CTC 计数的动态变化。
从接受 IT 曲妥珠单抗治疗 LM 的 HER2+癌症患者的 IRB 批准的 I/II 期剂量递增试验中获得每个周期第 1 天的 CSF，并通过 CellSearch®平台评估 CTC 计数。将结果与来自同一样本的 CSF 细胞学相关联，以及临床和放射学反应。
34 名 HER2+LM 患者中有 15 名被纳入 CSF CTC 分析；14 名女性。14 名患者有影像学 LM 记录；6 名患者的 CSF 细胞学阳性，13 名患者的 CSF CTC 阳性。中位数 CSF CTC 为 3 ml 中有 22 个 CTC（范围 0-200+）。对 8 名患者的 CTC 进行了 HER2/neu 表达分析；75%的患者 CSF 中 HER2/neu 表达阳性，25%的患者 HER2/neu 表达阴性。10 名患者中有 4 名接受了 7 个或更多周期的 IT 曲妥珠单抗治疗；在这 3 名患者中，CSF CTC 计数从基线增加的时间早于 MRI 上看到的变化，而 CSF 细胞学仍为阴性。
我们的研究表明，CSF CTC 计数可提供 LM 治疗期间中枢神经系统肿瘤负荷的动态、定量评估，并且早于 MRI 或 CSF 细胞学的变化。
Clinicaltrials.gov：NCT01325207；2011 年 3 月 29 日注册。
