Current Role and Future Potential of CSF ctDNA for the Diagnosis and Clinical Management of Pediatric Central Nervous System Tumors
Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.
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Most pediatric central nervous system (CNS) tumors are located in eloquent anatomic areas, making surgical resection and, in some cases, even biopsy risky or impossible. This diagnostic predicament coupled with the move toward molecular classification for diagnosis has exposed an urgent need to develop a minimally invasive means to obtain diagnostic information. In non-CNS solid tumors, the detection of circulating tumor DNA (ctDNA) in plasma and other bodily fluids has been incorporated into routine practice and clinical trial design for selection of molecular targeted therapy and longitudinal monitoring. For primary CNS tumors, however, detection of ctDNA in plasma has been challenging. This is likely related at least in part to anatomic factors such as the blood–brain barrier. Due to the proximity of primary CNS tumors to the cerebrospinal fluid (CSF) space, our group and others have turned to CSF as a rich alternative source of ctDNA. Although multiple studies at this time have demonstrated the feasibility of CSF ctDNA detection across multiple types of pediatric CNS tumors, the optimal role and utility of CSF ctDNA in the clinical setting has not been established. This review discusses the work-to-date on CSF ctDNA liquid biopsy in pediatric CNS tumors and the associated technical challenges, and reviews the promising opportunities that lie ahead for integration of CSF ctDNA liquid biopsy into clinical care and clinical trial design.
Submitted August 11, 2022; final revision received October 26, 2022; accepted for publication October 28, 2022.
Disclosures: Dr. Karajannis has disclosed receiving consulting and personal fees from AstraZeneca, Bayer, CereXis, QED Therapeutics, and Recursion Pharma. Dr. Miller has disclosed having no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.
Funding: Research reported in this publication was supported in part by the NCI of the NIH under Core Grant number P30 CA008748.
Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
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