Circulating Tumor Cells In The Peripheral Blood And Cerebrospinal Fluid Of Patients With Central Nervous System Metastases

The enumeration of circulating tumor cells in peripheral blood is a validated method of monitoring disease status in patients with epithelial malignancies involving the breast, colon, prostate, or lung. As cancer therapies improve and aim to decrease metastatic burden, the central nervous system (CNS) is emerging as an important sanctuary site for metastasis. Current surveillance and clinical markers of metastatic disease progression involving the CNS are lacking adequate sensitivity, reproducibility, and specificity. One of these clinical markers is cerebrospinal fluid (CSF) cytology, which lacks clarity, is insensitive, requires high sample volumes and is subject to interpretation bias by the pathologist. To overcome these limitations, we previously adapted the Cellsearch system (Veridex) to isolate and enumerate tumor cells in the CSF of breast or non-small cell lung cancer patients with CNS metastases. We recently reported that the number of cells in the CSF directly correlated with the subject9s clinical condition and Karnofsky performance status (KPS) in metastatic breast cancer. Furthermore, imaging of the neuroaxis in these patients revealed disease presence, however, was not indicative of disease burden. A sharp decline in the number of CSF tumor cells (CSFTCs) was universally noted after the onset and maintenance of such ventricular intrathecal chemotherapy. We have continued to follow these patients and have expanded our patient population to include non-small cell lung cancer. This includes a patient that we have followed from a baseline CSFTC count of >10,000 to zero over the course of intrathecal treatment, which as been accompanied by drastically reduced disease by and complete resolution of clinical symptoms. We have also begun to perform concomitant CTC enumeration from peripheral blood in conjunction with CSFTC analysis. Interestingly, while there appears to be no strong correlation between the two subpopulations, tumor cells seemed to be compartmentalized to either the blood or the CSF. Together, the current data indicates that CSFTCs may serve as viable markers for diagnosis and prognostication in the setting of CNS metastases. This novel method of isolating CSFTCs provides a semi-automated platform that greatly increases sensitivity, accuracy and reliability over the standard CSF cytology. Furthermore, this platform enables studies to elucidate the significance and biology of this unique subpopulation of tumor cells, including its relationship with CTCs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5565. doi:1538-7445.AM2012-5565