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

摘要： 其目标是确定使用微流体设备（称为OncoCEE）进行的测试是否会改善 转移性乳腺癌患者软脑膜（LM）疾病诊断的敏感性 (MBC)与标准细胞病理学分析相比。诊断LM在临床上可能具有挑战性。 经常需要重复多部位和高容量腰椎穿刺，导致患者 并发症、治疗延迟和患者不适。对提高这一能力有着迫切的需求 为了识别LM，通过改进的诊断测试，提供者可以更早地对 已知可穿过血脑屏障，包括全身化疗和/或鞘内治疗。在 在这项研究中，我们将前瞻性地招募36名正在接受临床检查的MBC患者， 怀疑LM。具体目标#1是评估OncoCEE细胞富集和提取是否 提高了明确或可疑LM结果患者诊断LM的灵敏度 磁共振成像与标准脑脊液分析（n = 36例患者）。 具体目标#2是评价激素受体和HER2状态之间的一致性， 通过OncoCEE细胞富集和提取鉴定的脊髓流体细胞和转移组织， OncoCEE评估的LM疾病患者（n = 32例患者，预计在36例参与者中占90%）。我们 假设OncoCEE细胞富集和提取将在LM中具有提高的灵敏度 与标准细胞学诊断相比。此外，我们预计OncoCEE细胞富集 和浸提将具有细胞中激素受体和HER2状态的实质一致性 在脊髓液和转移性组织中识别，或在转移性活检不可用的情况下在原发性组织中识别。 这一目标具有临床意义，因为雌激素受体/孕激素受体/HER2很重要 用于预测治疗反应和最终选择治疗剂的因素。细胞学 LM的测定仍然是金标准。通过更可靠的系统改进这一点， 减少多次腰椎穿刺的负担，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 发现比标准细胞学更好，免疫表型与 转移组织，下一步将是一个更大的，多中心试验与此设备，结合下一个 脊髓液的生成顺序。这将符合注重精确度的目标 治疗癌症的药物。

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.