ID #538 Harmonizing CSF collection schedule for circulating tumor DNA analysis in children with brain tumors – a Canadian Pediatric Brain Tumor Consortium (CPBTC) Consensus

Background Cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) offers a minimally invasive means into the genomic and epigenomic landscape of pediatric CNS tumors. It outperforms conventional cytology and can often detect recurrence prior to radiographic changes. However, interpretation is highly dependent on sampling context and timing. Disease-specific schedules for CSF collection have yet to be developed. Methods Members of the Canadian National Pediatric Brain Tumor Consortium (CPBTC) developed a consensus for CSF collection schedules across major pediatric CNS tumor entities. This was informed by Canadian multicenter CSF ctDNA experience (>550 specimens), and existing institutional practices for CSF liquid biopsy. Results The panel generated harmonized, disease-specific CSF sampling schedules encompassing diagnosis, post-operative and post-radiation, on-treatment, end-of-therapy MRD evaluation, and structured surveillance timepoints for medulloblastoma, CNS embryonal tumors, ependymoma, CNS germ cell tumors, and low- and high-grade glioma. Recommendations integrate feasibility constraints (age, access, volume), conventional protocol-specific evaluation timepoints, and procedural considerations (lumbar puncture vs Ommaya reservoir, use of stabilizing tubes when sample processing is delayed) to enable safe, reproducible sampling. Conclusion This consensus provides the first harmonized, pragmatic framework for CSF collection to support standardized ctDNA interpretation and MRD-informed decision-making in children with brain tumors. Implementation of these schedules across centers is expected to enhance comparability of results, facilitate multicenter trials, and accelerate evidence generation for liquid biopsy-guided precision therapy in pediatric neuro-oncology.