Abstract
BackgroundThe diagnosis of leptomeningeal metastasis (LM) in patients with solid tumors remains difficult. The usual diagnostic methods of cytomorphological assessment of cerebro-spinal fluid (CSF) and gadolinium enhanced MRI of the entire neuraxis lack both specificity and sensitivity. The Veridex CellSearch® technology has been designed for the detection of circulating tumor cells (CTC) in blood from cancer patients and validated for the follow-up and prognosis of breast, prostate, colorectal, and lung cancer. Our aim was to adapt this technology for the detection and the enumeration of tumor cells in the CSF of breast cancer patients presenting with LM.MethodsOn the occasion of a randomized phase III study evaluating the role of the intrathecal treatment in LM from breast cancer (DEPOSEIN, EudraCT N°: 2010-023134-23), the CellSearch® technology was adapted to direct enrichment, enumeration and visualization of tumor cells in 5 mL CSF samples, collected on CellSave® Preservative Tubes and analyzed within 3 days after CSF sampling.ResultsSixteen CSF of 8 patients with primary breast cancer presenting with LM were studied. EpCAM+/cytokeratin + cells with typical morphology could be observed and enumerated sequentially with reproducible results in low or elevated numbers in 8 patients.ConclusionThis methodology, established on a limited volume of sample and allowing delayed processing, could prove of great interest in the diagnosis and follow-up of cancer patients with LM, especially to appreciate the efficacy of chemotherapy.
Highlights
The diagnosis of leptomeningeal metastasis (LM) in patients with solid tumors remains difficult
Malignant cells were observed at cytomorphological analysis in 12 samples, and in 14 samples with the CellSearchW technology, with tumor cells numbers ranging between 1 and 10500 /5 mL
We present here a simple modification of this technology allowing for a precise direct quantification of circulating tumor cells (CTC) in only 5 mL of cerebro-spinal fluid (CSF)
Summary
The diagnosis of leptomeningeal metastasis (LM) in patients with solid tumors remains difficult. Prognostic factors have been identified: age, performance status, neurological status, LM characteristics, cerebrospinal fluid (CSF) block, LM related encephalopathy, extension of systemic disease and its treatment options, interval between diagnosis of primary tumour and LM and type of primary tumour [1,9]. These factors remain heterogeneous among studies and are not very well validated. The sensitivity reaches 80% with a second CSF analysis, but little benefit is obtained from more than two repeated lumbar punctures [1]
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