van Kessel Emma, Woerdman Noor, Pluim Dick, Kerklaan Bojana Milojkovic, van den Broek Daan, Huitema Alwin D R, Brandsma Dieta
Department of Neurology & Neurosurgery, University Medical Center Utrecht/UMC Utrecht Brain Center, Utrecht University, the Netherlands; Department of Neuro-Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam, the Netherlands.
Department of Neuro-Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam, the Netherlands.
Eur J Cancer. 2025 May 2;220:115377. doi: 10.1016/j.ejca.2025.115377. Epub 2025 Mar 28.
Leptomeningeal metastases (LM) from solid tumors are described in up to 10 % of patients, and median survival rates are low. Advanced techniques for circulating tumor cell enumeration in cerebrospinal fluid (CSF) can help in diagnosing patients with LM but also could have value in prognostication. Our aim was to investigate whether the number of circulating tumor cells (CTCs) in CSF are of added value in survival prediction in LM patients.
We performed a single-center retrospective study in a cohort of consecutive patients with LM from epithelial tumors. Circulating tumor cells in CSF were measured by an Epithelial Cell Adhesion Molecule (EpCAM)-based immunoflow cytometry method at LM diagnosing. The added prognostic value of the number of CTCs in CSF on top of known clinical prognostic factors for LM was assessed. We compared Cox proportional hazards regression models with and without CTCs by discriminative performance measures.
We included 103 eligible patients with epithelial tumors (60 % NSCLC, 29 % breast cancer), who were diagnosed with either possible, probable, or confirmed LM according to EANO-ESMO criteria. Median survival was 129 days. CTC numbers in CSF were of significant added prognostic value in a multivariable prognostic model (HR = 1.86, 95 % CI = 1.26-2.76, likelihood ratio test p-value=0.003 for models with CTCs versus without CTCs).
Our findings indicate that the number of CTCs in CSF, as measured by EpCAM immunoflow cytometry, are of additional prognostic value to other well-known clinical predictors of survival in LM. The number of CTCs in CSF should be taken in account when assessing the prognosis of patients with LM.
实体瘤的软脑膜转移(LM)在高达10%的患者中被描述,且中位生存率较低。脑脊液(CSF)中循环肿瘤细胞计数的先进技术有助于诊断LM患者,也可能具有预后价值。我们的目的是研究CSF中循环肿瘤细胞(CTC)的数量在LM患者生存预测中是否具有附加价值。
我们对一组连续的上皮性肿瘤LM患者进行了单中心回顾性研究。在诊断LM时,通过基于上皮细胞粘附分子(EpCAM)的免疫流式细胞术方法测量CSF中的循环肿瘤细胞。评估了CSF中CTC数量在已知LM临床预后因素基础上的附加预后价值。我们通过判别性能指标比较了有和没有CTC的Cox比例风险回归模型。
我们纳入了103例符合条件的上皮性肿瘤患者(60%为非小细胞肺癌,29%为乳腺癌),这些患者根据EANO-ESMO标准被诊断为可能、很可能或确诊的LM。中位生存期为129天。在多变量预后模型中,CSF中的CTC数量具有显著的附加预后价值(HR = 1.86,95%CI = 1.26 - 2.76,有CTC与无CTC的模型似然比检验p值 = 0.003)。
我们的研究结果表明,通过EpCAM免疫流式细胞术测量的CSF中CTC数量,对LM生存的其他知名临床预测指标具有额外的预后价值。在评估LM患者的预后时应考虑CSF中CTC的数量。