Purpose

Treatment decisions for leptomeningeal disease (LMD) rely on patient risk stratification, since clinicians lack objective prognostic tools. The introduction of rare cell capture technology for identification of cerebrospinal fluid tumor cells (CSF-TCs), such as CNSide assay, improved the sensitivity of LMD diagnosis, but prognostic value is unknown. This study assesses the prognostic value of CSF-TC density in patients with LMD from solid tumors.

Methods

We conducted a retrospective cohort study of patients with newly diagnosed or previously treated LMD from a single institution who had CNSide assay testing for CSF-TCs from 2020 to 2023. Univariable and multivariable survival analyses were conducted with Cox proportional-hazards modeling. Maximally-selected rank statistics were used to determine an optimal cutpoint for CSF-TC density and survival.

Results

Of 31 patients, 29 had CSF-TCs detected on CNSide. Median (interquartile range [IQR]) CSF-TC density was 67.8 (4.7–639) TCs/mL. CSF cytology was positive in 16 of 29 patients with positive CNSide (CNSide diagnostic sensitivity = 93.5%, negative predictive value = 85.7%). Median (IQR) survival from time of CSF-TC detection was 176 (89–481) days. On univariable and multivariable analysis, CSF-TC density was significantly associated with survival. An optimal cutpoint for dichotomizing survival by CSF-TC density was 19.34 TCs/mL. The time-dependent sensitivity and specificity for survival using this stratification were 76% and 67% at 6 months and 65% and 67% at 1 year, respectively.

Conclusions

CSF-TC density may carry prognostic value in patients with LMD from solid tumors. Integrating CSF-TC density into LMD patient risk-stratification may help guide treatment decisions.

中文翻译：

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脑脊液肿瘤细胞计数对实体瘤软脑膜疾病的预后价值

目的

软脑膜疾病 (LMD) 的治疗决策依赖于患者风险分层，因为临床医生缺乏客观的预后工具。引入稀有细胞捕获技术来识别脑脊液肿瘤细胞（CSF-TC），例如 CNSide 检测，提高了 LMD 诊断的灵敏度，但预后价值尚不清楚。本研究评估了 CSF-TC 密度对实体瘤 LMD 患者的预后价值。

方法

我们对来自同一机构的新诊断或既往治疗过的 LMD 患者进行了一项回顾性队列研究，这些患者在 2020 年至 2023 年期间对 CSF-TC 进行了 CNSide 检测。使用 Cox 比例风险模型进行了单变量和多变量生存分析。使用最大选择的排名统计来确定 CSF-TC 密度和存活率的最佳切点。

结果

在 31 名患者中，29 名在 CNSide 上检测到了 CSF-TC。中位（四分位距 [IQR]）CSF-TC 密度为 67.8 (4.7–639) TC/mL。29 名 CNSide 阳性患者中，16 名脑脊液细胞学呈阳性（CNSide 诊断敏感性 = 93.5%，阴性预测值 = 85.7%）。从 CSF-TC 检测到的中位生存期 (IQR) 为 176 (89–481) 天。在单变量和多变量分析中，CSF-TC 密度与生存率显着相关。按 CSF-TC 密度二分生存的最佳切点是 19.34 TCs/mL。使用这种分层的生存时间依赖性敏感性和特异性在 6 个月时分别为 76% 和 67%，在 1 年时分别为 65% 和 67%。

结论

CSF-TC 密度可能对实体瘤 LMD 患者具有预后价值。将 CSF-TC 密度纳入 LMD 患者风险分层可能有助于指导治疗决策。