This phase II clinical trial studies how well craniospinal irradiation (CSI) with hippocampal avoidance, using proton therapy or volumetric modulated arc therapy (VMAT), works in treating patients with breast cancer or non-small cell lung cancer (NSCLC) that has spread from the original (primary) tumor to the cerebrospinal fluid (CSF) and meninges (thin layers of tissue that cover and protect the brain and spinal cord) (leptomeningeal metastases). Radiation therapy is an effective treatment in relieving localized symptoms caused by leptomeningeal metastases. However, the type of radiation therapy typically used does not prevent the spread of leptomeningeal disease. CSI (radiation therapy directed at the brain and spinal cord to kill tumor cells) may be able to target all of the areas of possible leptomeningeal tumor spread. CSI may however result in significant neurological side effects due to radiation damage to a part of the brain called the hippocampus. Hippocampal avoidance (HA) reduces the amount of radiation to the hippocampus. Proton or VMAT CSI with HA may be an effective treatment while reducing neurological side effects for patients with leptomeningeal metastases from breast cancer and NSCLC.
Patients with breast cancer or NSCLC malignancies with leptomeningeal metastases established radiographically and/or through CSF cytology
Patients who are candidates for radiation therapy for the treatment of leptomeningeal metastases
Patients ≥ 18 years old
Karnofsky performance status (KPS) ≥ 60 or Eastern Cooperative Oncology Group (ECOG) ≥ 2
Patients with multiple, serious major neurologic deficits per physician/investigator assessment including encephalopathy
Patients with extensive systemic disease and without reasonable systemic treatment options
Patients who are unable to undergo MRI brain and spine with gadolinium contrast
Previous radiotherapy to the intended treatment site that precludes developing a treatment plan that respects normal tissue tolerances
Single group
Biospecimen Collection
Procedure/SurgeryUndergo CSF sample collection
Computed Tomography
Procedure/SurgeryUndergo PET/CT and/or CT
Electronic Health Record Review
Other interventionAncillary studies
Lumbar Puncture
Procedure/SurgeryUndergo lumbar puncture
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Positron Emission Tomography
Procedure/SurgeryUndergo PET/CT
Proton Beam Craniospinal Irradiation
RadiationUndergo proton CSI
Survey Administration
Other interventionAncillary studies
Volume Modulated Arc Therapy
RadiationUndergo photon VMAT CSI
Hippocampal-Avoidance Craniospinal Irradiation
Procedure/SurgeryUndergo HA
Central nervous system (CNS)-progression free survival (PFS)
PFS is defined as time from craniospinal irradiation (CSI) to CNS disease progression or death. CNS-PFS will be summarized using Kaplan-Meier methodology. Median, 95% confidence interval (CI) and Kaplan-Meier plot will be provided. One-sample log-rank test will be used to test if the median CNS PFS of hippocampal avoidance in CSI for leptomeningeal metastases from breast cancer or non-small cell lung cancer (NSCLC) is significantly larger than the expected median CNS PFS with involved-field radiation therapy (IFRT), i.e., 2.5 months. P-value will be provided.
Number of adverse events associated with hippocampal avoidance craniospinal irradiation (HA-CSI)
The analyses of the adverse events associated with HA-CSI will be descriptive in nature. Summary tables and listings will be provided for all reported adverse events (AEs).
Neurocognitive function assessment
Linear mixed models will be used to examine changes in neurocognitive domain (attention, executive functions, memory) performances from pre-RT baseline to 3, 6, and 12 months. Magnitude of change will be examined at each timepoint using standardized effect sizes (e.g., Cohen's d). For each timepoint, the study investigators will examine the proportion of individuals who demonstrate a reliable change in at least 2 (out of 10) test performances as compared to pre-RT baseline performances.
Overall survival (OS)
Comparison of OS between the study group and the historical cohort will be analyzed using stratified log-rank test. OS will be estimated and visualized using Kaplan-Meier methods.
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