BRain-AVOidant Proton Craniospinal Irradiation for Leptomeningeal Metastases From Solid Tumor Malignancies

The purpose of this study is to determine the efficacy of BRain-AVOidant proton craniospinal irradiation (BRAVO pCSI) in adult participants with leptomeningeal metastases from solid tumors.

Inclusion Criteria: 1. Participants with leptomeningeal metastases established radiographically and/or through Cerebrospinal Fluid (CSF) cytology or circulating tumor cells (CTCs). Participants may have newly diagnosed or recurrent LM. 2. Pathologically confirmed breast or non-small cell lung cancer (NSCLC) primary (group 1 and). Pathologically confirmed solid tumor malignancy (group 2). 3. Participants with adequate bone marrow function. 4. Participants with a Karnofsky Performance Status (KPS) ≥ 60. 5. Male and female participants ages ≥ 18 years. 6. Female participants must be of either non-childbearing potential OR must agree to practice an effective contraceptive method. 7. Male participants must be of either non-childbearing potential OR must agree to practice an effective contraceptive method. Exclusion Criteria: 1. Participants with metastases within the memory-avoidance structures (hippocampus, corpus callosum, fornix, amygdala) that preclude developing a treatment plan that respects dosimetric constraints for these structures. 2. Participants with multiple, serious major neurologic deficits per physician/investigator assessment including encephalopathy. 3. Participants with extensive systemic disease and without reasonable systemic treatment options. 4. Participants unable to undergo MRI brain and spine with gadolinium contrast. 5. Participants who have had radiation therapy to the spinal cord with equivalent dose in 2Gy fractions (EQD2) more than 40Gy or cauda equina with EQD2 more than 50Gy using α/β of 3. 6. Female participants who are pregnant or lactating. 7. Participants with impaired decision-making capacity.