ArticleNeuro-oncology2016
EpCAM-based flow cytometry in cerebrospinal fluid greatly improves diagnostic accuracy of leptomeningeal metastases from epithelial tumors.
Registry-linked trialOpen access · bronzeAbstract read
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Article in Neuro-oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01713699 (Determining the Sensitivity and Specificity of Circulating Tumor Cells and Cytology in Cerebrospinal Fluid of Patients Clinically Suspected for Leptomeningeal Metastases), which is not on this map. Cited by 34 papers.
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34citing papers in PubMed
3.8field-weighted citation impact, top 6% of its field
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Determining the Sensitivity and Specificity of Circulating Tumor Cells and Cytology in Cerebrospinal Fluid of Patients Clinically Suspected for Leptomeningeal Metastases
Who cites it
34 citing papers in PubMed, 73 citations in OpenAlex.
- Cerebral spinal fluid analyses and therapeutic implications for leptomeningeal metastatic disease.Journal of neuro-oncology · 2025Review
- Brain metastases from lung cancer: recent advances and novel therapeutic opportunities.Discover oncology · 2025Review
- Detection of circulating hybrid cells and circulating tumor cells in cerebrospinal fluid for leptomeningeal metastasis diagnosis and therapeutic prediction.Frontiers in cell and developmental biology · 2025Article
- Article
- Radiotherapy and Systemic Treatment for Leptomeningeal Disease.Biomedicines · 2024Review
- Quantification of cerebrospinal fluid tumor DNA in lung cancer patients with suspected leptomeningeal carcinomatosis.NPJ precision oncology · 2024Article
- Clinical applications of cerebrospinal fluid liquid biopsies in central nervous system tumors.Translational oncology · 2024Article
- Review
- Review
- Double-dose osimertinib combined with intrathecal injection of pemetrexed improves the efficacy of EGFR-mutant non-small cell lung cancer and leptomeningeal metastasis: case report and literature review.Frontiers in oncology · 2024Article
- A Novel Optical Fiber Terahertz Biosensor Based on Anti-Resonance for The Rapid and Nondestructive Detection of Tumor Cells.Biosensors · 2023Article
- Long-term response to sequential anti-HER2 therapies including trastuzumab-deruxtecan in a patient with HER2-positive metastatic breast cancer with leptomeningeal metastases: a case report and review of the literature.Frontiers in oncology · 2023Review
- Advances in Intraoperative Flow Cytometry.International journal of molecular sciences · 2022Review
- Single-Cell RNA Sequencing of Cerebrospinal Fluid as an Advanced Form of Liquid Biopsy for Neurological Disorders.Brain sciences · 2022Review
- Diagnosis of Leptomeningeal Metastasis in Women With Breast Cancer Through Identification of Tumor Cells in Cerebrospinal Fluid Using the CNSide™ Assay.Clinical breast cancer · 2022Article
- Evolving management of HER2+ breast cancer brain metastases and leptomeningeal disease.Journal of neuro-oncology · 2022Review
- Development of Two Diagnostic Prediction Models for Leptomeningeal Metastasis in Patients With Solid Tumors.Frontiers in neurology · 2022Article
- Solitary Leptomeningeal Metastasis from Lung Cancer: A Case Report.NMC case report journal · 2022Article
- Advances in the diagnosis, evaluation, and management of leptomeningeal disease.Neuro-oncology advances · 2021Article
- Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Bojana Milojkovic KerklaanDepartment of Molecular Pathology, Netherlands Cancer Institute-Antoni van Leeuwenhoek (NKI-AVL), Amsterdam, the Netherlands (B.M.K., D.P., I.H., J.H.M.S.); Department of Clinical Pharmacology, NKI-AVL, Amsterdam, the Netherlands (B.M.K., J.H.M.S.); Department of Pathology, NKI-AVL, Amsterdam, the Netherlands (M.B.), Core Facility Molecular Pathology & Biobanking (CFMPB), Department of Molecular Pathology, NKI-AVL, Amsterdam, the Netherlands (I.H.); Department of Pathology, Slotervaart Hospital, Amsterdam, the Netherlands (J.W.); Biometric Department, NKI-AVL, Amsterdam, the Netherlands (H.v.T.); Department of Pharmacy and Pharmacology, NKI-AVL, Amsterdam, the Netherlands (J.H.B.); Utrecht Institute of Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, the Netherlands (J.H.B., J.H.M.S.); Department of Neuro-oncology, NKI-AVL, Amsterdam, the Netherlands (W.B., D.B.).
Dick PluimDepartment of Molecular Pathology, Netherlands Cancer Institute-Antoni van Leeuwenhoek (NKI-AVL), Amsterdam, the Netherlands (B.M.K., D.P., I.H., J.H.M.S.); Department of Clinical Pharmacology, NKI-AVL, Amsterdam, the Netherlands (B.M.K., J.H.M.S.); Department of Pathology, NKI-AVL, Amsterdam, the Netherlands (M.B.), Core Facility Molecular Pathology & Biobanking (CFMPB), Department of Molecular Pathology, NKI-AVL, Amsterdam, the Netherlands (I.H.); Department of Pathology, Slotervaart Hospital, Amsterdam, the Netherlands (J.W.); Biometric Department, NKI-AVL, Amsterdam, the Netherlands (H.v.T.); Department of Pharmacy and Pharmacology, NKI-AVL, Amsterdam, the Netherlands (J.H.B.); Utrecht Institute of Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, the Netherlands (J.H.B., J.H.M.S.); Department of Neuro-oncology, NKI-AVL, Amsterdam, the Netherlands (W.B., D.B.).
Mijke BolDepartment of Molecular Pathology, Netherlands Cancer Institute-Antoni van Leeuwenhoek (NKI-AVL), Amsterdam, the Netherlands (B.M.K., D.P., I.H., J.H.M.S.); Department of Clinical Pharmacology, NKI-AVL, Amsterdam, the Netherlands (B.M.K., J.H.M.S.); Department of Pathology, NKI-AVL, Amsterdam, the Netherlands (M.B.), Core Facility Molecular Pathology & Biobanking (CFMPB), Department of Molecular Pathology, NKI-AVL, Amsterdam, the Netherlands (I.H.); Department of Pathology, Slotervaart Hospital, Amsterdam, the Netherlands (J.W.); Biometric Department, NKI-AVL, Amsterdam, the Netherlands (H.v.T.); Department of Pharmacy and Pharmacology, NKI-AVL, Amsterdam, the Netherlands (J.H.B.); Utrecht Institute of Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, the Netherlands (J.H.B., J.H.M.S.); Department of Neuro-oncology, NKI-AVL, Amsterdam, the Netherlands (W.B., D.B.).
Ingrid HoflandDepartment of Molecular Pathology, Netherlands Cancer Institute-Antoni van Leeuwenhoek (NKI-AVL), Amsterdam, the Netherlands (B.M.K., D.P., I.H., J.H.M.S.); Department of Clinical Pharmacology, NKI-AVL, Amsterdam, the Netherlands (B.M.K., J.H.M.S.); Department of Pathology, NKI-AVL, Amsterdam, the Netherlands (M.B.), Core Facility Molecular Pathology & Biobanking (CFMPB), Department of Molecular Pathology, NKI-AVL, Amsterdam, the Netherlands (I.H.); Department of Pathology, Slotervaart Hospital, Amsterdam, the Netherlands (J.W.); Biometric Department, NKI-AVL, Amsterdam, the Netherlands (H.v.T.); Department of Pharmacy and Pharmacology, NKI-AVL, Amsterdam, the Netherlands (J.H.B.); Utrecht Institute of Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, the Netherlands (J.H.B., J.H.M.S.); Department of Neuro-oncology, NKI-AVL, Amsterdam, the Netherlands (W.B., D.B.).
Johan WestergaDepartment of Molecular Pathology, Netherlands Cancer Institute-Antoni van Leeuwenhoek (NKI-AVL), Amsterdam, the Netherlands (B.M.K., D.P., I.H., J.H.M.S.); Department of Clinical Pharmacology, NKI-AVL, Amsterdam, the Netherlands (B.M.K., J.H.M.S.); Department of Pathology, NKI-AVL, Amsterdam, the Netherlands (M.B.), Core Facility Molecular Pathology & Biobanking (CFMPB), Department of Molecular Pathology, NKI-AVL, Amsterdam, the Netherlands (I.H.); Department of Pathology, Slotervaart Hospital, Amsterdam, the Netherlands (J.W.); Biometric Department, NKI-AVL, Amsterdam, the Netherlands (H.v.T.); Department of Pharmacy and Pharmacology, NKI-AVL, Amsterdam, the Netherlands (J.H.B.); Utrecht Institute of Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, the Netherlands (J.H.B., J.H.M.S.); Department of Neuro-oncology, NKI-AVL, Amsterdam, the Netherlands (W.B., D.B.).
Harm van TinterenDepartment of Molecular Pathology, Netherlands Cancer Institute-Antoni van Leeuwenhoek (NKI-AVL), Amsterdam, the Netherlands (B.M.K., D.P., I.H., J.H.M.S.); Department of Clinical Pharmacology, NKI-AVL, Amsterdam, the Netherlands (B.M.K., J.H.M.S.); Department of Pathology, NKI-AVL, Amsterdam, the Netherlands (M.B.), Core Facility Molecular Pathology & Biobanking (CFMPB), Department of Molecular Pathology, NKI-AVL, Amsterdam, the Netherlands (I.H.); Department of Pathology, Slotervaart Hospital, Amsterdam, the Netherlands (J.W.); Biometric Department, NKI-AVL, Amsterdam, the Netherlands (H.v.T.); Department of Pharmacy and Pharmacology, NKI-AVL, Amsterdam, the Netherlands (J.H.B.); Utrecht Institute of Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, the Netherlands (J.H.B., J.H.M.S.); Department of Neuro-oncology, NKI-AVL, Amsterdam, the Netherlands (W.B., D.B.).
Jos H BeijnenDepartment of Molecular Pathology, Netherlands Cancer Institute-Antoni van Leeuwenhoek (NKI-AVL), Amsterdam, the Netherlands (B.M.K., D.P., I.H., J.H.M.S.); Department of Clinical Pharmacology, NKI-AVL, Amsterdam, the Netherlands (B.M.K., J.H.M.S.); Department of Pathology, NKI-AVL, Amsterdam, the Netherlands (M.B.), Core Facility Molecular Pathology & Biobanking (CFMPB), Department of Molecular Pathology, NKI-AVL, Amsterdam, the Netherlands (I.H.); Department of Pathology, Slotervaart Hospital, Amsterdam, the Netherlands (J.W.); Biometric Department, NKI-AVL, Amsterdam, the Netherlands (H.v.T.); Department of Pharmacy and Pharmacology, NKI-AVL, Amsterdam, the Netherlands (J.H.B.); Utrecht Institute of Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, the Netherlands (J.H.B., J.H.M.S.); Department of Neuro-oncology, NKI-AVL, Amsterdam, the Netherlands (W.B., D.B.).
Willem BoogerdDepartment of Molecular Pathology, Netherlands Cancer Institute-Antoni van Leeuwenhoek (NKI-AVL), Amsterdam, the Netherlands (B.M.K., D.P., I.H., J.H.M.S.); Department of Clinical Pharmacology, NKI-AVL, Amsterdam, the Netherlands (B.M.K., J.H.M.S.); Department of Pathology, NKI-AVL, Amsterdam, the Netherlands (M.B.), Core Facility Molecular Pathology & Biobanking (CFMPB), Department of Molecular Pathology, NKI-AVL, Amsterdam, the Netherlands (I.H.); Department of Pathology, Slotervaart Hospital, Amsterdam, the Netherlands (J.W.); Biometric Department, NKI-AVL, Amsterdam, the Netherlands (H.v.T.); Department of Pharmacy and Pharmacology, NKI-AVL, Amsterdam, the Netherlands (J.H.B.); Utrecht Institute of Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, the Netherlands (J.H.B., J.H.M.S.); Department of Neuro-oncology, NKI-AVL, Amsterdam, the Netherlands (W.B., D.B.).
Jan H M SchellensDepartment of Molecular Pathology, Netherlands Cancer Institute-Antoni van Leeuwenhoek (NKI-AVL), Amsterdam, the Netherlands (B.M.K., D.P., I.H., J.H.M.S.); Department of Clinical Pharmacology, NKI-AVL, Amsterdam, the Netherlands (B.M.K., J.H.M.S.); Department of Pathology, NKI-AVL, Amsterdam, the Netherlands (M.B.), Core Facility Molecular Pathology & Biobanking (CFMPB), Department of Molecular Pathology, NKI-AVL, Amsterdam, the Netherlands (I.H.); Department of Pathology, Slotervaart Hospital, Amsterdam, the Netherlands (J.W.); Biometric Department, NKI-AVL, Amsterdam, the Netherlands (H.v.T.); Department of Pharmacy and Pharmacology, NKI-AVL, Amsterdam, the Netherlands (J.H.B.); Utrecht Institute of Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, the Netherlands (J.H.B., J.H.M.S.); Department of Neuro-oncology, NKI-AVL, Amsterdam, the Netherlands (W.B., D.B.).
Dieta BrandsmaDepartment of Molecular Pathology, Netherlands Cancer Institute-Antoni van Leeuwenhoek (NKI-AVL), Amsterdam, the Netherlands (B.M.K., D.P., I.H., J.H.M.S.); Department of Clinical Pharmacology, NKI-AVL, Amsterdam, the Netherlands (B.M.K., J.H.M.S.); Department of Pathology, NKI-AVL, Amsterdam, the Netherlands (M.B.), Core Facility Molecular Pathology & Biobanking (CFMPB), Department of Molecular Pathology, NKI-AVL, Amsterdam, the Netherlands (I.H.); Department of Pathology, Slotervaart Hospital, Amsterdam, the Netherlands (J.W.); Biometric Department, NKI-AVL, Amsterdam, the Netherlands (H.v.T.); Department of Pharmacy and Pharmacology, NKI-AVL, Amsterdam, the Netherlands (J.H.B.); Utrecht Institute of Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, the Netherlands (J.H.B., J.H.M.S.); Department of Neuro-oncology, NKI-AVL, Amsterdam, the Netherlands (W.B., D.B.).
Utrecht University · NLSlotervaartziekenhuis · NLThe Netherlands Cancer Institute · NL
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundModerate diagnostic accuracy of MRI and initial cerebrospinal fluid (CSF) cytology analysis results in at least 10%-15% false negative diagnoses of leptomeningeal metastases (LM) of solid tumors, thus postponing start of therapy. The aim of this prospective clinical study was to determine the diagnostic value of epithelial cell adhesion molecule (EpCAM)-based flow cytometry versus cytology in CSF for the diagnosis of LM in patients with epithelial tumors.
methodsPatients with a clinical suspicion of LM but a negative or inconclusive MRI in whom a diagnostic lumbar puncture has to be performed were included. At least 5 mL of CSF for cytology, 5 mL for flow cytometry, 2 mL for cell count and biochemistry, and 8 mL whole blood samples for circulating tumor cells measurements and biochemistry were drawn. Tumor cells in CSF and whole blood were detected by multiparameter flow cytometry using EpCAM antibody.
resultsIn total 29 eligible patients were enrolled in the study. Thirteen patients were ultimately diagnosed with LM. The flow cytometry assay showed 100% sensitivity and 100% specificity for diagnosing LM, while sensitivity of CSF cytology was only 61.5%. Cell count or biochemical parameters in CSF were abnormal in 100% of patients with LM.
conclusionsOur results suggest that the EpCAM-based flow cytometry assay is superior to CSF cytology for the diagnosis of LM in patients with an epithelial tumor, a clinical suspicion of LM, and a nonconclusive MRI. Confirmation of these data is needed in a larger dataset to recommend dual CSF diagnostics for LM. CLINICALTRIALSGOV IDENTIFIER: NCT01713699.
Indexed as
AdultAgedAged, 80 and overEpithelial Cell Adhesion MoleculeEpithelial CellsFemaleFlow CytometryHumansMagnetic Resonance ImagingMaleMeningeal NeoplasmsMiddle AgedProspective StudiesYoung AdultEpithelial Cell Adhesion Moleculecarcinomatous meningitiscerebrospinal fluid (CSF)circulating tumor cells (CTC)epithelial cell adhesion molecule (EpCAM)leptomeningeal metastases (LM)
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NCT01713699ClinicalTrials.gov
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