The goal of this phase II randomized trial is to determine if Stereotactic Radiosurgery (SRS) or Cognitive Sparing WBRT (CS-WBRT) better preserves neurocognitive function than standard Hippocampal Avoidance WBRT (HA-WBRT) in patients with multiple brain metastases ( $\\ge6$ lesions).
The main questions it aims to answer are:
* Which treatment best preserves cognitive function (memory and executive tasks) at 6 months post-intervention? * Can sparing the left hippocampus and corpus callosum (CS-WBRT) or using focal SRS reduce cognitive decline compared to bilateral sparing? Comparison Groups
Researchers will compare three arms to evaluate their impact on cognition and disease control:
* Arm A (SRS): Focal high-dose radiation (15-20 Gy in 1 fraction) to intracranial lesions. * Arm B (CS-WBRT): Whole-brain radiation (30 Gy in 10 fractions) sparing the left hippocampus and corpus callosum plus Memantine. * Arm C (HA-WBRT): Whole-brain radiation (30 Gy in 10 fractions) with bilateral hippocampal avoidance plus Memantine.
Participant Tasks
Participants will:
* Complete neurocognitive and neuropsychological tests (HVLT-R, TMT, COWAT, CANTAB) at baseline and follow-up. * Undergo contrast-enhanced brain MRI for planning and tracking tumor progression. * Take Memantine HCL daily for 24 weeks if assigned to the WBRT arms (B or C). * Provide blood samples for biomarker and genetic analysis (e.g., APOE, Tau). * Undergo olfactory function testing and complete quality-of-life questionnaires.
Patients with a histologic diagnosis of non-hematopoietic malignancy and radiographic evidence of brain metastases
Patients with brain metastasis outside a 5-mm margin around either hippocampus or corpus callosum on gadolinium contrast-enhanced MRI obtained within 30 days prior to registration
Patients with 6 or more active or progressive brain metastases that have not been treated by radiotherapy or radiosurgery
No evidence of diffuse leptomeningeal metastasis on gadolinium-enhanced MRI within 30 days prior registration
Prior radiotherapy to brain or radiosurgery to > 5 intracranial metastatic lesion(s)
Clinical diagnosis of symptomatic leptomeningeal metastsases
Contraindication to MR imaging such as implanted metal devices or foreign bodies, severe claustrophobia
Uncontrolled active infection requiring intravenous antibiotics at the time of registration