Exploring the Feasibility of Cerebrospinal Fluid (CSF) and Blood Plasma Liquid Biopsy in Patients With Metastatic Solid Tumours and Primary Central Nervous System (CNS) Tumours: A Pilot Study

This is a prospective, single-centre feasibility study of CSF ctDNA conducted at the Sunnybrook Odette Cancer Centre (SOCC), Toronto, Canada, including multiple solid tumor, stratified into cohorts according to CNS disease involvement, including leptomeningeal disease (Cohort A), parenchymal brain metastases (Cohort B), and no evidence of CNS metastases (Cohort C).

Inclusion Criteria: * Diagnosed with a solid tumour in one of the following scenarios: 1. Patients in Cohort A will have previously untreated or progressing leptomeningeal metastatic disease (LMD) with or without parenchymal brain metastases (BrM). 2. Patients in Cohort B will have previously untreated or BrM but no evidence of LMD. 3. Patients in Cohort C will have progressing extra-cranial metastatic disease with no LMD or BrM. 4. Patients in Cohort D will have primary CNS tumours (such as, but not limited to, meningioma, glioblastoma, astrocytoma, ependymoma, and other rare histologies). * Patient is suitable for lumbar puncture and/or has an Ommaya reservoir that is accessible for CSF collection. * Patient is eligible at any time point in their treatment course, including whether or not they have already started treatment for LMD. Considering the poor prognosis associated with LMD, rapid clinical deterioration, and the fact that available local and systemic therapies have not been shown to completely eradicate LMD, there is a high likelihood of detecting CSF biomarkers regardless of the timing of assessment. This flexible enrollment strategy is particularly important to support feasibility and recruitment in this less common and clinically challenging population. However, efforts will be made to collect CSF samples prior to treatment initiation and/or at the time of disease progression whenever possible. * Patients with active brain metastases, defined as newly diagnosed and previously untreated lesions, or lesions that were previously treated and are now progressing. * Patients who were previously enrolled in the study and had negative CSF biomarkers may be re-enrolled at a later time point (e.g., upon progression of CNS disease). Exclusion Criteria: * Inability to understand or unwillingness to provide written informed consent (language barriers are not exclusionary; the use of a translator is permitted). * Patients with contraindications to lumbar puncture (e.g., infection at the LP site, uncontrolled bleeding diathesis \> 1.5\], severe thrombocytopenia \[platelet count \