SMART Trial: Cognitive Sparing Brain Radiotherapy for Multiple Brain Metastases

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.

NCT Number	NCT07505979
Lead Sponsor	National Taiwan University Hospital
Conditions	Brain Metastases From Solid Tumors
Enrollment	90 participants
Start Date	2026-04
Primary Completion	2029-04 (estimated)
Study Completion	2031-04 (estimated)
Updated on ClinicalTrials.gov	2026-04-13