Automated Capture and Analysis of Circulating Tumor Cells in Pediatric, Adolescent and Young Adult Patients with Central Nervous System Tumors

SIMPLE SUMMARY: Central nervous system (CNS) tumors are the most common solid malignancy in pediatrics and prognosis remains poor for patients with relapsed or refractory disease. Currently, for most of these tumors, there are no biomarkers available to monitor treatment response or detect early recurrent disease. Patients are therefore subjected to serial imaging which provides limited information. There is an urgent need to develop minimally invasive, easily accessible biomarkers that can be used to monitor disease and help guide future treatment. Circulating tumor cells (CTCs) are cells that are shed from the primary tumor and can be detected from peripheral blood. In this first pediatric study, we show that the detection of CTCs is feasible and highly sensitive in patients with CNS tumors. Large-scale studies using our novel method of CTC detection will further help validate these findings and encourage large-scale implementation in future clinical trials. ABSTRACT: Tumors of the central nervous system (CNS) are the most common and lethal childhood malignancy. Detection of residual disease and longitudinal monitoring of treatment response in patients are challenging and rely on serial imaging. This current standard of care fails to detect microscopic disease or provide molecular characteristics of residual tumors. As such, there is dire need for minimally invasive liquid biopsy techniques. We have previously shown the high specificity of using cell surface vimentin (CSV) to identify circulating tumor cells (CTCs) from patients bearing various types of cancers. Here, we describe the first report of CTCs captured from peripheral blood samples in 58 pediatric CNS tumor patients. In this study, we used a CSV-coated cell capture chip, the Abnova CytoQuest automated CTC isolation system, to boost the CTC capture from pediatric patients with CNS tumors. We successfully isolated CTCs in six glioma patients using immunostaining of histone H3 lysine27-to-methionine (H3K27M) mutations which are highly expressed by this tumor. We show that CSV is a viable marker for CNS CTC isolation and that this is a feasible method for detecting microscopic disease. Larger-scale studies focusing on CTCs in pediatric CNS tumors to explore their diagnostic and prognostic value are warranted.