Research And Grants

CSF Cell-free Tumor DNA (CSF cfDNA) Liquid Biopsies for Pediatric, Adolescent, and Young Adult Patients with Primary Brain Tumors

Pediatric brain tumors are the leading cause of cancer-related death in children and adolescents [1]. Recent advances in molecular analysis have led to major improvements in diagnostic accuracy and prognostication for pediatric patients with brain tumors, allowing physicians to adapt available therapies to specific patient’s needs[2-4]. However, access to tumor tissue for molecular testing in these patients requires an invasive procedure, which can be high-risk and/or unfeasible depending on the anatomical location of the tumor. Furthermore, repeated tissue sampling to monitor therapy response or resistance is often not clinically advisable or risky. We have successfully developed a minimally invasive “liquid biopsy” clinical assay to detect circulating tumor DNA (ctDNA) in cerebrospinal fluid (CSF) of pediatric brain tumor patients[5]. We have previously shown that CSF ctDNA genomics captures the genomic and clonal architecture of brain tumors, which recently led to the securing of a CLIA certification for this assay[5, 6]. To enhance tumor diagnosis through molecular subclassification and guide therapeutic decision making for pediatric brain tumor patients using this minimally invasive approach, we established a Pediatric Brain Tumor Consortium (PBTC)-sponsored trial, with the goal of integrating CSF ctDNA liquid biopsies into the clinical care of pediatric brain tumor patients across the PBTC sites.

The PBTC consortium is composed of 17 of the leading pediatric cancer centers across North America. Our non-therapeutic protocol entitled “CSF Cell-free Tumor DNA (CSF ctDNA) Liquid Biopsies for Pediatric, Adolescent, and Young Adult Patients with Primary Brain Tumors” has been approved by the scientific review committee of the PBTC, the NIH’s Cancer Therapy Evaluation Program (CTEP) and the NIH’s Central Institutional Review Board (CIRB) and is expected to open at the first sites during summer 2023. This protocol is investigator-initiated, and hence we are requesting funding to cover the costs associated with CSF ctDNA sequencing to enable full execution of this pre-approved PBTC-sponsored study.