Background: Leptomeningeal disease (LMD) is challenging to diagnose and monitor given the poor sensitivity of current gold-standard diagnostics. Cerebrospinal fluid tumor cells (CSF-TCs) have been studied as a biomarker for disease management because oncogene amplification of the primary, metastatic, and CNS metastatic tumors can be heterogeneous. The CNSide platform enumerates CSF-TCs and analyzes oncogene expression via immunocytochemistry (ICC), fluorescent in situ hybridization (FISH), and next-generation sequencing (NGS). We report the utility of this combined enumerative and mutational testing for LMD diagnosis and disease monitoring. Methods: A multicenter, retrospective analysis of commercially ordered assays from two health systems between January 2020 and July 2023 included 613 tests on 218 individual patients with suspected or confirmed LMD. To date, this is the largest cohort of patients in LMD literature evaluated using CSF-TCs. Results: CSF-TCs were detected in 67% (412/613) of samples. The most analyzed cancer types were breast (n= 105) and lung (n= 65). In lung cancer, anaplastic lymphoma kinase (ALK) was detected in 14% (17/118), and c-MET was detected in 61% (78/128). In breast cancer, HER2 was detected in 39% (65/168), and estrogen receptor (ER) was detected in 26% (44/168). Sixty-six patients underwent 2+ longitudinal CSF draws; among these, there were 58 flips in oncogene detection over time, and 30% (20/66) of patients had at least one biomarker change in the CSF. Conclusions: Longitudinal combined ICC/FISH/NGS CSF testing demonstrates a wide range in CSF-TC enumeration, which may be correlated with clinical course, and furthermore identifies actionable tumor markers that frequently fluctuate over time. Utilization of this platform would enable timely, personalized LMD-specific chemotherapy.
背景：鉴于当前金标准诊断方法的敏感性较低，软脑膜疾病（LMD）的诊断和监测具有挑战性。由于原发性、转移性和中枢神经系统转移性肿瘤的癌基因扩增可能存在异质性，脑脊液肿瘤细胞（CSF-TCs）已被研究作为疾病管理的生物标志物。CNSide平台通过免疫细胞化学（ICC）、荧光原位杂交（FISH）和下一代测序（NGS）对CSF-TCs进行计数并分析癌基因表达。我们报告了这种结合计数与突变检测的方法在LMD诊断和疾病监测中的应用价值。 方法：本研究对2020年1月至2023年7月期间来自两个医疗系统的商业检测订单进行了多中心回顾性分析，共纳入218例疑似或确诊LMD患者的613次检测。迄今为止，这是LMD文献中使用CSF-TCs评估的最大患者队列。 结果：在67%（412/613）的样本中检测到CSF-TCs。分析最多的癌症类型是乳腺癌（n=105）和肺癌（n=65）。在肺癌中，间变性淋巴瘤激酶（ALK）的检出率为14%（17/118），c-MET的检出率为61%（78/128）。在乳腺癌中，HER2的检出率为39%（65/168），雌激素受体（ER）的检出率为26%（44/168）。66例患者接受了2次及以上纵向脑脊液取样；其中，随时间推移出现58次癌基因检测结果的转变，30%（20/66）的患者脑脊液中至少有一种生物标志物发生变化。 结论：纵向联合ICC/FISH/NGS脑脊液检测显示CSF-TCs计数范围广泛，这可能与临床病程相关，并且进一步识别出随时间频繁波动的可干预肿瘤标志物。应用该平台可实现及时、个性化的LMD特异性化疗。
肿瘤(癌症)患者之家