CellSearch® technology applied to the detection and quantification of tumor cells in CSF of patients with lung cancer leptomeningeal metastasis

Tu, Qian; Wu, Xianglei; Rhun, Émilie Le; Blonski, Marie; Wittwer, B.; Taillandier, Luc; Bittencourt, Marcelo De Carvalho; Fauré, G

doi:10.1016/j.lungcan.2015.09.008

Cited by 48 publications

(31 citation statements)

References 32 publications

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“…[11][12][13][14]. This technology has also been applied to diagnose leptomeningeal metastases by capturing malignant cells in the CSF of patients with solid tumors (15)(16)(17)(18). However, the potential role of CSFCTCs for the molecular testing of leptomeningeal metastases remains uncertain.…”

Section: Introductionmentioning

confidence: 99%

Detection of Driver and Resistance Mutations in Leptomeningeal Metastases of NSCLC by Next-Generation Sequencing of Cerebrospinal Fluid Circulating Tumor Cells

Jiang

Guo

et al. 2017

Clinical Cancer Research

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Leptomeningeal metastases are more common in non-small cell lung cancer (NSCLC) with mutations. The diagnosis is difficult by traditional imaging only, and leads to poor understanding of resistance mechanisms of leptomeningeal metastases. We compared the CellSearch Assay, the Thinprep cytologic test (TCT), and brain magnetic resonance imaging (MRI) in 21 NSCLC patients with suspected leptomeningeal metastases. Next-generation sequencing that included 416 cancer-associated genes was also performed on cerebrospinal fluid circulating tumor cells (CSFCTC) of 19 patients. Twenty-one patients were diagnosed with leptomeningeal metastases, and CSFCTCs were captured by CellSearch in 20 patients (median, 969 CSFCTCs/7.5 mL; range, 27-14,888). CellSearch had a sensitivity of 95.2% for leptomeningeal metastases diagnosis, which was higher than that of TCT (12/21, 57.1%), MRI (10/21, 47.6%), and MRI plus TCT (19/21, 90.5%), respectively. CTCs were found only in 5 of 14 patients (median, 2 CTCs/7.5 mL; range, 2-4), which was a much lower ratio than CSFCTCs. Genetic profiles of CSFCTCs were highly concordant with molecular mutations identified in the primary tumor (17/19, 89.5%). The resistance gene T790M was detected in 7 of 9 patients with extracranial lesions, but was detected in only 1 of 14 CSFCTC samples. Other potential resistant mutations, such as amplification and mutation, were also identified in CSFCTCs. CSFCTCs captured by CellSearch may be a more sensitive and effective way to diagnose leptomeningeal metastases, and may serve as a liquid biopsy medium for gene profiles in NSCLC patients with leptomeningeal metastases. .

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Section: Introductionmentioning

confidence: 99%

Detection of Driver and Resistance Mutations in Leptomeningeal Metastases of NSCLC by Next-Generation Sequencing of Cerebrospinal Fluid Circulating Tumor Cells

Jiang

Guo

et al. 2017

Clinical Cancer Research

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“…108 It is worth mentioning that new technologies to collect CSF circulating cancer cells are being evaluated because they have been shown to perform better than cytology in detecting neoplastic meningitis in patients with lung cancer. 109 Lin et al 110 presented the validation of CSF circulating tumor cells (CTCs) to diagnose neoplastic meningitis from epithelial tumors in patients suspected of having the disease. MRI and CSF analyses were performed using conventional cytology and enumeration of CSF CTCs for all study participants.…”

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confidence: 99%

Clinical Presentation, Diagnosis, and Radiological Findings of Neoplastic Meningitis

Rigakos¹,

Liakou²,

Felipe

et al. 2017

Cancer Control

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“…The adhesion between CTCs and endothelial cells is essential in tumor metastasis (101), by facilitating the circulation and invasion of the metastatic cells (102). The up-regulation of adhesion-related genes in CSF-CTCs are also important for CTCs clusters formation, which have been detected by CellSearch technology previously (12). Blood-CTC cluster termed "circulating tumor microemboli" (CTM), or CTC-WBC cluster have been described with higher malignancy and have a better change to survive in bloodstream (103,104).…”

Section: Ctcsmentioning

confidence: 96%

“…Tumor cells in CSF were considered as circulating tumor cells (CTCs) as CTCs in blood (11). The CellSearch technique (12), which utilizes immunomagnetic selection, identification and quantification of CTCs in the CSF, is more sensitive than the conventional cytology and MRI for the diagnosis of LM. Moreover, evaluation of CSF circulating free DNA (cfDNA) has the potential to facilitate and supplement LM diagnosis and the detection of genomic alterations can also inform targeted therapy (13).…”

Section: Introductionmentioning

confidence: 99%

Circulating tumor cell characterization of lung cancer brain metastasis in the cerebrospinal fluid through single-cell transcriptome analysis

Ruan

Zhou

Shen

et al. 2020

Preprint

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Brain metastases explain the majority of lung cancer associated mortality, which is the leading cause of cancer death. Cytological analysis in the cerebrospinal fluid (CSF) remains the diagnostic gold standard, and the circulating tumor cells (CTCs) in CSF is not well defined at molecular and transcriptome level. We established an effective CSF-CTC collection procedure and isolated individual CSF cells from lung adenocarcinoma leptomeningeal metastases (LUAD-LM) patients and controls. 3,744 single-cell transcriptomes were sequenced and analyzed to perform a comprehensive characterization of CSF cells. Through clustering and expression analysis, we defined CSF-CTCs at the transcriptome level based on epithelial markers, proliferative markers and genes with lung origin. 290 genes are upregulated by 2-fold in LUAD-LM patients. These metastatic-CTC signature genes are enriched for metabolic pathway and cell-adhesion molecule categories, indicating their roles in tumor cell survival and metastases. We discovered substantial heterogeneity in patient CSF-CTCs, in sharp contrast to the lack of heterogeneity in cancer cell lines or xenograft models. We quantified the degree of heterogeneity and found significantly greater among-patient heterogeneity compared to among-cell heterogeneity within-patient. This observation could be explained by spacial heterogeneity of metastatic sites, cell-cycle gene expression profiles as well as the proportion of CTCs displaying mesenchymal and cancer stem-cell properties. In addition, our CSF-CTC transcriptome profiling allowed us to determine the biomarkers during the progression of an LM patient with cancer of unknown primary site (CUP). Our results will shed light on the mechanism of LUAD-LM and provide new directions of diagnostics and therapeutics of LM.

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CellSearch® technology applied to the detection and quantification of tumor cells in CSF of patients with lung cancer leptomeningeal metastasis

Cited by 48 publications

References 32 publications

Detection of Driver and Resistance Mutations in Leptomeningeal Metastases of NSCLC by Next-Generation Sequencing of Cerebrospinal Fluid Circulating Tumor Cells

Detection of Driver and Resistance Mutations in Leptomeningeal Metastases of NSCLC by Next-Generation Sequencing of Cerebrospinal Fluid Circulating Tumor Cells

Clinical Presentation, Diagnosis, and Radiological Findings of Neoplastic Meningitis

Circulating tumor cell characterization of lung cancer brain metastasis in the cerebrospinal fluid through single-cell transcriptome analysis

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