ctDNA-Guided Intraventricular Therapy for CNS Malignancies

Inclusion Criteria: * Age ≥ 18 years. * Diagnosis of histologically or cytologically confirmed HER2+ breast cancer, or triple negative breast cancer, or Stage IV non-small cell lung cancer, or recurrent high-grade glioma). * Undergoing clinically indicated cerebrospinal fluid (CSF) collection as part of routine clinical care: CSF may be obtained via lumbar puncture or existing CSF access device. Decision for CSF collection must be made independently by the treating clinical team and not solely for research purposes. * Detectable CSF ctDNA and/or positive CSF cytology, with consideration for CNS-directed management by the treating neuro-oncology team. * Ability to provide informed consent, or availability of a legally authorized representative (LAR). Exclusion Criteria: * Age \<18 years. * Inability to provide informed consent and no legally authorized representative (LAR) available. * Not undergoing clinically indicated CSF collection as part of standard clinical care. * Absence of detectable CSF ctDNA and absence of positive CSF cytology. * Not being considered for CNS-directed management by the treating neuro-oncology team. * Clinical contraindications to CSF collection, including but not limited to: Significant intracranial mass effect; (e.g., midline shift \>5 mm or effacement of basal cisterns); Obstructive hydrocephalus or posterior fossa mass effect; Coagulopathy or bleeding risk precluding lumbar puncture or CSF access; Inability to safely obtain CSF access.