Circulating Tumor Cells and Cytology in Cerebrospinal Fluid of Patients Clinically Suspected for Leptomeningeal Metastases
Recruitment status was Recruiting
|Study Design:||Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||Determining the Sensitivity and Specificity of Circulating Tumor Cells and Cytology in Cerebrospinal Fluid of Patients Clinically Suspected for Leptomeningeal Metastases|
- Determine the sensitivity and specificity of detection of circulating tumor cells (CTCs) in patients with Epcam expressing tumors compared to cytology in the cerebrospinal fluid of patients, clinically suspected for leptomeningeal metastases [ Time Frame: 3 months after end of study ] [ Designated as safety issue: No ]
- - To determine the relationship between the number of CTCs in CSF and the patient's neurological condition and WHO performance score [ Time Frame: 3 months after end of study ] [ Designated as safety issue: No ]
- - To determine the change in the CTC number between two sampling points and correlate this with the patient's neurological condition and therapy [ Time Frame: 3 months after end of study ] [ Designated as safety issue: No ]
- - To determine the relationships between demographics/tumor status and CTCs number in CSF. [ Time Frame: 3 months after end of study ] [ Designated as safety issue: No ]
- - To determine the relationship between the CTC cells in the CSF and the CTCs in the peripheral blood [ Time Frame: 3 months after end of study ] [ Designated as safety issue: No ]
- To confirm EPCAM positivity in archived primary tumor tissue and tumorcells in CSF. [ Time Frame: 3 months after end of study ] [ Designated as safety issue: No ]
- - To compare the predictive value of two CTC enumeration methods [ Time Frame: 3 months after end of study ] [ Designated as safety issue: No ]
|Study Start Date:||September 2012|
|Estimated Study Completion Date:||June 2014|
|Estimated Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
Using extra CSF material received by clinically indicated lumbar punctures to determine the sensitivity and specificity of CTCs in CSF (5ml CSF). Standard material of 5 ml CSF for cytology and 2 ml CSF for cell count and chemistry is being regularly used and processed.
|Procedure: lumbar puncture|
Leptomeningeal metastases (LM), is a diffuse dissemination of tumor cells into the cerebrospinal fluid (CSF) and leptomeninges. Up to 8% of all patients with cancer develop LM. Gadolinium enhanced MRI of the symptomatic location of the nervous system is the radiological method of choice when LM is clinically suspected. In patients with a metastasized tumor, based on clinical signs of LM and contrast enhancement of either the leptomeninges, pia mater/cortex or cranial or spinal nerves on MRI, the diagnosis LM can be made. The sensitivity of MRI with gadolineum for LM is 75% and the specificity 77%. If MRI does not show equivocal abnormalities, CSF cytology needs to be performed. In 55% of patients with LM from solid tumors, malignant cells are found during the first CSF examination. The sensitivity raises to 80-90% after the second CSF sampling, as determined in the pre-MRI era. The volume of sampled CSF determines partly the sensitivity of CSF cytology. If possible, 10 ml CSF needs to be taken and the material must be processed as quickly as possible.
Recently, Patel et al (2011) described the detection of breast cancer cells in the CSF using the Cell Search System (Veridex).  Using this method, the CSF is enriched immuno-magnetically for the epithelial cell adhesion molecule (EpCAM). Next nuclear staining with 4 ',6-diamidino-2-phenylindole (DAPI) and immunofluorescent detection with cytokeratin and CD45 is performed in 5 patients with leptomeningeal metastases from breast cancer and approximately 104 circulating tumor cells (CTCs)in 7,5 ml CSF were found, using this method. There seemed to be an association between the number of CTCs and response to intrathecal administered chemotherapy in this small group of patients.
In the future, the determination of CTCs in the CSF could be a new quantitative method for the anti-tumor response assessment of systemic or intrathecal therapy (as opposed to CSF cytology, which is subjective and not a quantitative method). If the method shows greater sensitivity than CSF cytology and can reliably measure single tumor cells, the sensitivity of CSF examination in patients with a clinical suspicion of LM will increase. Possibly, this method can also be used to detect micrometastases in the CSF in patients without neurological symptoms, but with a high risk of CNS metastases.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01713699
|Contact: D. Brandsma, MD, PhD||+31 (0)205122570|
|Contact: B. Milojkovic Kerklaan, MD|
|Dutch Cancer Institute - Antoni van Leeuwenhoek||Recruiting|
|Amsterdam, Netherlands, 1066CX|
|Contact: D. Brandsma, MD, PhD|
|Principal Investigator: D Brandsma, MD, PhD|
|Amsterdam, Netherlands, 1066EC|
|Contact: D. Brandsma, MD, PhD|
|Principal Investigator: D. Brandsma, MD, PhD|
|Principal Investigator:||D. Brandsma, MD, PhD||NKI-AvL|