Identifying leptomeningeal metastasis from breast cancer utilizing a novel immunocytochemical microfluidic device

摘要： 其目标是确定使用名为OncoCEE的微流控设备进行测试是否会有所改进 转移性乳腺癌患者软脑膜病诊断的敏感性 (MBC)与标准细胞病理学分析进行比较。诊断肌萎缩侧索硬化在临床上可能具有挑战性。 经常需要重复多部位和大容量的腰椎穿刺术，导致患者 并发症、治疗延误和病人不适。有一种未得到满足的提高能力的需求 为了通过改进的诊断测试来识别LM，提供者可以更早地干预符合以下条件的代理 已知可以跨越血脑屏障，包括全身化疗和/或鞘内治疗。在……里面 在这项研究中，我们将前瞻性地招募36名正在接受临床体检的MBC患者 怀疑路透社。具体目标1是评估OncoCEE细胞的浓缩和提取 提高对诊断明确或可疑的肺泡炎患者的敏感度 并与标准脑脊液分析(n=36例)进行比较。 具体目的#2是评估激素受体和HER2状态在 用肿瘤细胞浓缩和提取鉴定脊液细胞和转移组织 通过OncoCEE(n=32名患者，预计在36名参与者中的90%)患上肺泡炎。我们 假设肿瘤细胞的浓缩和提取将在LM中具有更高的敏感性 诊断与标准细胞学的比较。此外，我们预计OncoCEE细胞浓缩 提取液与细胞内激素受体和HER2状态有很大的一致性 在脊髓液和转移组织中发现，如果没有转移活检，则在原发组织中确定。 这一目标在临床上是相关的，因为雌激素受体/孕激素受体/HER2很重要。 预测治疗反应和最终选择治疗药物的因素。细胞学 Lm的测定仍然是金标准。用一个更可靠的系统来改善这一点 减少多次腰椎穿刺术的负担，包括重复尝试的风险，以及 潜在的成本，因为目前的临床实践需要磁共振成像。如果这个系统是 发现比标准细胞学更好，免疫表型与 对于转移的组织，下一步将是使用该设备进行更大规模的多中心试验，包括NEXT 脊髓液的世代测序。这将与专注于精度的目标保持一致 癌症治疗中的医学。

Abstract: The goal is to determine whether testing with a microfluidic device, known as OncoCEE, will improve the sensitivity in the diagnosis of leptomeningeal (LM) disease in patients with metastatic breast cancer (MBC) compared to standard cytopathologic analysis. Diagnosing LM can be clinically challenging. Repeat multi-site and high volume lumbar punctures are often required, leading to patient complications, treatment delays, and patient discomfort. There is an unmeet need to improve the ability to identify LM, With an improved diagnostic test, providers could intervene earlier with agents that are known to cross the blood brain barrier, including systemic chemotherapy and/or intrathecal therapy. In this study, we will prospectively enroll 36 patients with MBC who are undergoing workup for clinical suspicion of LM. Specific Aim #1 is to assess whether OncoCEE Cell Enrichment and Extraction improves the sensitivity in the diagnosis of LM in patients with unequivocal or suspicious findings for LM on magnetic resonance imaging compared to standard cerebrospinal fluid analysis (n=36 patients). Specific Aim #2 is to evaluate the concordance of hormone receptor and HER2 status between the spinal fluidic cells identified by OncoCEE Cell Enrichment and Extraction and metastatic tissue, in those with LM disease by OncoCEE (n=32 patients, anticipated in 90% of the 36 total participants). We hypothesize that OncoCEE Cell Enrichment and Extraction will have an improved sensitivity in LM diagnosis compared to standard cytology. In addition, we anticipate that OncoCEE Cell Enrichment and Extraction will have substantial concordance of the hormone receptor and HER2 status in cells identified in the spinal fluid and metastatic tissue, or primary tissue if metastatic biopsy not available. This aim is clinically relevant, as Estrogen Receptor/Progesterone Receptor/HER2 are important factors for prediction of treatment response and ultimate selection of therapeutic agents. Cytologic determination of LM remains the gold standard. Improving on this with a more reliable system would decrease the burden of multiple lumbar punctures, including the risks of repeated attempts, and potentially cost, as current clinical practice requires magnetic resonance imaging. If this system were found to be better than standard cytology, with substantial concordance in immunophenotype with metastatic tissue, the next step would be a larger, multi-center trial with this device, incorporating next generation sequencing of spinal fluid. This would be in line with the goal of focusing on precision medicine in cancer treatment.