Circulating Tumor Cells and Cytology in Cerebrospinal Fluid of Patients Clinically Suspected for Leptomeningeal Metastases
Circulating Tumor Cells and Cytology in Cerebrospinal Fluid of Patients Clinically Suspected for Leptomeningeal Metastases
The purpose of this study is to determine whether the quantitative detection of circulating
 tumor cells (CTCs) in patients with Epcam expressing tumors can be used compared to standard
 qualitative method - cytology both in the cerebrospinal fluid of patients, clinically
 suspected for leptomeningeal metastases.
Leptomeningeal metastases (LM), is a diffuse dissemination of tumor cells into the
 cerebrospinal fluid (CSF) and leptomeninges.[1] 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). [6] 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.
Inclusion Criteria:

 -  Patients who are treated for advanced EpCam positive solid tumors (such as breast
 cancer, lung cancer, gastrointestinal cancer)

 -  Age >= 18 years;

 -  Able and willing to give written informed consent;

 -  WHO performance status (0, 1, 2, 3 or 4);

 -  Able and willing to undergo lumbar puncture and veni-puncture.

 Exclusion Criteria:

 -  Lumbar puncture not clinically / diagnostically indicated