Participants in this research study have cancer that has spread to their brain, called brain metastases. One treatment for this type of cancer is called whole brain radiotherapy that stays away from a specific neurocognitive substructure, called the hippocampus, combined with medication to preserve cognitive function. This study compares that approach to another approach of whole brain radiotherapy that stays away from additional structures that are thought to have a role in cognitive function. Researchers want to see if there is a difference in the preservation of cognitive function between these two approaches.
Participants must have histologically, cytologically, or radiographically confirmed diagnosis of solid tumor with brain metastases
Age >18 years
Performance status: Karnofsky Performance Status (KPS) ≥ 70
Estimated life expectancy of at least 3 months
Prior whole brain radiation
Participant has Multiple Sclerosis, Alzheimer's, dementia, or mental disability
Pregnant or breastfeeding women are excluded from this study.
Participant is not able to receive an MRI
Parallel
MA-WBRT (Memory Avoidance Whole Brain Radiation Therapy (MA-WBRT))
RadiationParticipants will receive 10 daily fractions of WBRT per standard of care. Participants receiving MA-WBRT will receive WBRT that avoids the hippocampus, the amygdala, corpus callosum, fornix, hypothalamus, and pituitary.
HA-WBRT (Hippocampal Avoidance Whole Brain Radiation Therapy (HA-WBRT))
RadiationParticipants will receive 10 daily fractions of WBRT per standard of care. Participants receiving HA-WBRT will receive WBRT that avoids the hippocampus.
Memantine
DrugMemantine is prescribed per standard of care. Participants will continue on memantine for 24 weeks. The target dose for memantine is 20 mg (10 mg divided twice daily). Dose is escalated by 5 mg per week to target of 10 mg twice daily (i.e., 5 mg a day for week 1, then 5 mg twice daily for week 2, then 10 mg in the morning and 5 mg in the evening for week 3, then 10 mg in the morning and 10 mg in the evening by week 4). Participants will also be prescribed extended release memantine. The target dose for extended release memantine is 28 mg. Dose is escalated by 7 mg per week to target of 28 mg daily (i.e., 7 mg a day for week 1, then 14 mg a day for week 2, then 21 mg a day for week 3, then 28 mg a day for by week 4).
Time to neurocognitive failure (NCF)
Time to NCF is defined as cognitive decline on the reliable change index (RCI) on at least one of the following tests: HVLT-R, TMT A/B, COWAT, BVMT-R. Tests are defined below.
Hopkins Verbal Learning Test-Revised (HVLT-R)
The HVLT-R involves three learning trials: Total Recall, Delayed Recall, and Delayed Recognition. The HVLT-R is administered by the examiner reading a 12-item list of words and asking the participant to recall as many as possible (Total Recall). After a 20-25 minutes interval of unrelated tasks, the examiner asks the participant to recall as many words as possible from the original list (Delayed Recall). Then, the examiner reads a 24-item list of words, where 12 words were on the original list and 12 were not (Delayed Recognition). The examiner asks the participant to respond "yes" if the word was on the original list or "no" if it was not. The HVLT-R is scored by summing the number of correctly recalled words across the three trials. Higher scores indicate greater recall.
Hopkins Verbal Learning Test-Revised (HVLT-R)
The HVLT-R involves three learning trials: Total Recall, Delayed Recall, and Delayed Recognition. The HVLT-R is administered by the examiner reading a 12-item list of words and asking the participant to recall as many as possible (Total Recall). After a 20-25 minutes interval of unrelated tasks, the examiner asks the participant to recall as many words as possible from the original list (Delayed Recall). Then, the examiner reads a 24-item list of words, where 12 words were on the original list and 12 were not (Delayed Recognition). The examiner asks the participant to respond "yes" if the word was on the original list or "no" if it was not. The HVLT-R is scored by summing the number of correctly recalled words across the three trials. Higher scores indicate greater recall.
Hopkins Verbal Learning Test-Revised (HVLT-R)
The HVLT-R involves three learning trials: Total Recall, Delayed Recall, and Delayed Recognition. The HVLT-R is administered by the examiner reading a 12-item list of words and asking the participant to recall as many as possible (Total Recall). After a 20-25 minutes interval of unrelated tasks, the examiner asks the participant to recall as many words as possible from the original list (Delayed Recall). Then, the examiner reads a 24-item list of words, where 12 words were on the original list and 12 were not (Delayed Recognition). The examiner asks the participant to respond "yes" if the word was on the original list or "no" if it was not. The HVLT-R is scored by summing the number of correctly recalled words across the three trials. Higher scores indicate greater recall.
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