Hippocampal Sparing Whole Brain Radiation versus Stereotactic Radiation in Patients With 5-20 Brain Metastases: A Phase III, Randomized Trial

• MRI will be performed prior to radiation is administered
• A hippocampal sparing approach will be used when possible
• Dose will be 30 Gy in 10 fractions

Treatment of the whole brain with radiation. When possible the hippocampus will be spared from radiation.

• MRI will be performed prior to radiation is administered
• Radiation will be given in 1-5 fractions (dose depends on the size of the tumor that will be treated)

Focused radiation to each individual brain metastasis without treatment of the remainder of the brain.

Questionnaire - MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT). Results reflect patient-reported symptoms. Here they are presented as a mean change: the difference in the weighted mean of symptom severity and interference scores at baseline versus at 6 months. The difference between these scores is the mean change reported below. The MD Anderson Symptom Inventory has a scale of 0-10, 0 being not present and 10 being as bad as the patient could imagine. The calculated score change has a range of -10 to 10; -10 being the best. Change in score is calculated as the composite weighted means of symptom severity and interference at 6 months minus the composite weighted means of symptom severity and interference at baseline.

Clinical Parameter. Here we report the number of patients analyzed for the outcome as well as the number of deaths that occurred. We then report the 12 Month Cumulative Incidence with a 95% Confidence Interval.

Clinical parameter to be assessed via review of study visits and medical records indicating cause of death (neurologic versus systemic). Here we report the number of patients analyzed for the outcome as well as the number of events that occurred. We then report the 12 Month Cumulative Incidence with a 95% Confidence Interval.

Radiographic assessment of first appearance of new brain metastases. Here we report the number of patients analyzed for the outcome as well as the number of events that occurred. We then report the 12 Month Cumulative Incidence with a 95% Confidence Interval.

Radiographic assessment of first local recurrence in the 5-20 brain metastases that were initially treated with radiation. Here we report the number of patients analyzed for the outcome as well as the number of events that occurred. We then report the 12 Month Cumulative Incidence with a 95% Confidence Interval.

Radiographic assessment of first instance of progressive intracranial disease. Here we report the number of patients analyzed for the outcome as well as the number of events that occurred. We then report the 12 Month Cumulative Incidence with a 95% Confidence Interval.

Radiographic assessment of first appearance of radiation necrosis. Here we report the number of patients analyzed for the outcome as well as the number of events that occurred. We then report the 12 Month Cumulative Incidence with a 95% Confidence Interval.

Radiographic assessment of first appearance of leptomeningeal disease. Here we report the number of patients analyzed for the outcome as well as the number of events that occurred. We then report the 12 Month Cumulative Incidence with a 95% Confidence Interval.

Assessing time to dexamethasone initiation in patients who were not taking steroids at enrollment. Here we report the number of patients analyzed for the outcome as well as the number of events that occurred. We then report the 12 Month Cumulative Incidence with a 95% Confidence Interval.

Clinical assessment of first post-treatment seizure as assessed during routine study visits and via medical record review. Here we report the number of patients analyzed for the outcome as well as the number of events that occurred. We then report the 12 Month Cumulative Incidence with a 95% Confidence Interval.

Clinical assessment of first use of salvage stereotactic radiation. Here we report the number of patients analyzed for the outcome as well as the number of events that occurred. We then report the 12 Month Cumulative Incidence with a 95% Confidence Interval.

Clinical assessment of first use of salvage whole brain radiation with or without hippocampal avoidance. Here we report the number of patients analyzed for the outcome as well as the number of events that occurred. We then report the 12 Month Cumulative Incidence with a 95% Confidence Interval.

Clinical assessment of first use of neurosurgical resection as salvage therapy. Here we report the number of patients analyzed for the outcome as well as the number of events that occurred. We then report the 12 Month Cumulative Incidence with a 95% Confidence Interval.

Barthel Index ranges from 0 to 100 with higher scores indicating greater functional independence. A greater difference between the groups indicates greater functional independence in the stereotactic arm. Here we report the mean Barthel Index score at baseline for both arms.

Barthel Index ranges from 0 to 100 with higher scores indicating greater functional independence. A greater difference between the groups indicates greater functional independence in the stereotactic arm. Here we report the mean difference (95% Confidence Interval) at each timepoint.

The Karnofsky Performance Status (KPS) is a tool designed to assess a cancer patient's functional status. Scores range from 0 to 100 with higher scores indicating better function. Scores 90-100 indicate that the patient is independent and can perform daily activities with little to no effort. A score of 80 indicates that the patient can conduct their normal activities with some effort. A score of 70 indicates that a patient can care for themself but cannot carry on normal activities independently. Here we report the least squares mean Karnofsky Performance Score for each arm based on the Karnofsky Performance Status Scale at each timepoint from Baseline to 12 Months post-baseline.

Here we report the mean Hopkins Verbal Learning Test-Revised Total Recall (HVLT-R Total Recall) z-score in each arm at baseline. The HVLT-R Total Recall test measures rote verbal learning across 3 trials administered in one sitting. Scores were transformed into z scores. Z scores greater than 2.0 indicate exceptionally high function, between 1.36 and 2.0 indicate above average function, between 0.68 and 1.35 indicate high average function, between -0.67 and 0.67 indicate average function, between -0.68 and -1.35 indicate low average function, between -1.36 and -2.0 indicate below average function, and less than -2.0 indicate exceptionally low. The Z-Score central value is 0 and represents the population mean. Larger positive z scores indicate better neurocognitive function.

Here we report the mean Hopkins Verbal Learning Test-Revised Total Recall (HVLT-R Total Recall) z-score in each arm at the given timepoint. The HVLT-R Total Recall test measures rote verbal learning across 3 trials administered in one sitting. Scores were transformed into z scores. Z scores greater than 2.0 indicate exceptionally high function, between 1.36 and 2.0 indicate above average function, between 0.68 and 1.35 indicate high average function, between -0.67 and 0.67 indicate average function, between -0.68 and -1.35 indicate low average function, between -1.36 and -2.0 indicate below average function, and less than -2.0 indicate exceptionally low. The Z-Score central value is 0 and represents the population mean. Larger positive z scores indicate better neurocognitive function.

Here we report the mean Hopkins Verbal Learning Test-Revised Delayed Recall Z score at baseline. This test measures delayed memory function. Scores were transformed into z scores. Z scores greater than 2.0 indicate exceptionally high function, between 1.36 and 2.0 indicate above average function, between 0.68 and 1.35 indicate high average function, between -0.67 and 0.67 indicate average function, between -0.68 and -1.35 indicate low average function, between -1.36 and -2.0 indicate below average function, and less than -2.0 indicate exceptionally low. The Z score central value is 0 and represents the population mean. Larger positive z scores indicate better neurocognitive function.

Here we report the mean Hopkins Verbal Learning Test-Revised Delayed Recall Z score at the given timepoint. This test measures delayed memory function. Scores were transformed into z scores. Z scores greater than 2.0 indicate exceptionally high function, between 1.36 and 2.0 indicate above average function, between 0.68 and 1.35 indicate high average function, between -0.67 and 0.67 indicate average function, between -0.68 and -1.35 indicate low average function, between -1.36 and -2.0 indicate below average function, and less than -2.0 indicate exceptionally low. The Z score central value is 0 and represents the population mean. Larger positive z scores indicate better neurocognitive function.

Here we report the mean Hopkins Verbal Learning Test-Revised Recognition z scores in each arm at baseline. The Hopkins Verbal Learning Test - Revised Recognition measures memory storage and recognition. Scores were transformed into z scores. z Scores greater than 2.0 indicate exceptionally high function, between 1.36 and 2.0 indicate above average function, between 0.68 and 1.35 indicate high average function, between -0.67 and 0.67 indicate average function, between -0.68 and -1.35 indicate low average function, between -1.36 and -2.0 indicate below average function, and less than -2.0 indicate exceptionally low. The z score central value is 0 and represents the populaion mean. Larger, positive z scores indicate better neurocognitive function. Here we report the mean z score in each arm at baseline.

Here we report the mean Hopkins Verbal Learning Test-Revised Recognition z scores in each arm at the given timepoint. The Hopkins Verbal Learning Test - Revised Recognition measures memory storage and recognition. Scores were transformed into z scores. z Scores greater than 2.0 indicate exceptionally high function, between 1.36 and 2.0 indicate above average function, between 0.68 and 1.35 indicate high average function, between -0.67 and 0.67 indicate average function, between -0.68 and -1.35 indicate low average function, between -1.36 and -2.0 indicate below average function, and less than -2.0 indicate exceptionally low. The z score central value is 0 and represents the populaion mean. Larger, positive z scores indicate better neurocognitive function. Here we report the mean z score in each arm at the given timepoint.

Here we report the mean Trail Making Test A z score in each arm at baseline. The Trail Making Test A measures visuomotor processing speed. Scores were transformed into z scores. z Scores greater than 2.0 indicate exceptionally high function, between 1.36 and 2.0 indicate above average function, between 0.68 and 1.35 indicate high average function, between -0.67 and 0.67 indicate average function, between -0.68 and -1.35 indicate low average function, between -1.36 and -2.0 indicate below average function, and less than -2.0 indicate exceptionally low. The z score central value is 0 and represents the population mean. Larger, positive z scores inicate better visuomotor processing speed.

Here we report the mean Trail Making Test A z score in each arm at the given timepoint. The Trail Making Test A measures visuomotor processing speed. Scores were transformed into z scores. z Scores greater than 2.0 indicate exceptionally high function, between 1.36 and 2.0 indicate above average function, between 0.68 and 1.35 indicate high average function, between -0.67 and 0.67 indicate average function, between -0.68 and -1.35 indicate low average function, between -1.36 and -2.0 indicate below average function, and less than -2.0 indicate exceptionally low. The z score central value is 0 and represents the population mean. Larger, positive z scores inicate better visuomotor processing speed.

Here we report the mean Trail Making Test B z score in each arm at baseline. The Trail Making Test B measures visuomotor processing speed. Scores were transformed into z scores. z Scores greater than 2.0 indicate exceptionally high function, between 1.36 and 2.0 indicate above average function, between 0.68 and 1.35 indicate high average function, between -0.67 and 0.67 indicate average function, between -0.68 and -1.35 indicate low average function, between -1.36 and -2.0 indicate below average function, and less than -2.0 indicate exceptionally low. The z score central value is 0 and represents the population mean. Larger, positive z scores inicate better visuomotor processing speed.

Here we report the mean Trail Making Test B z score in each arm at the given timepoint. The Trail Making Test B measures visuomotor processing speed. Scores were transformed into z scores. z Scores greater than 2.0 indicate exceptionally high function, between 1.36 and 2.0 indicate above average function, between 0.68 and 1.35 indicate high average function, between -0.67 and 0.67 indicate average function, between -0.68 and -1.35 indicate low average function, between -1.36 and -2.0 indicate below average function, and less than -2.0 indicate exceptionally low. The z score central value is 0 and represents the population mean. Larger, positive z scores inicate better visuomotor processing speed.

Here we report the mean controlled oral word test z score in each arm at baseline. The controlled oral word test (COWAT) measures verbal fluency. Scores were transformed into z scores. z Scores greater than 2.0 indicate exceptionally high function, between 1.36 and 2.0 indicate above average function, between 0.68 and 1.35 indicate high average function, between -0.67 and 0.67 indicate average function, between -0.68 and -1.35 indicate low average function, between -1.36 and -2.0 indicate below average function, and less than -2.0 indicate exceptionally low. The z score central value is 0 and represents the population mean. A larger positive z score indicates better performance.

Here we report the change in mean controlled oral word test z score in each arm at the given timepoints from baseline. The controlled oral word test (COWAT) measures verbal fluency. Scores were transformed into z scores. z Scores greater than 2.0 indicate exceptionally high function, between 1.36 and 2.0 indicate above average function, between 0.68 and 1.35 indicate high average function, between -0.67 and 0.67 indicate average function, between -0.68 and -1.35 indicate low average function, between -1.36 and -2.0 indicate below average function, and less than -2.0 indicate exceptionally low. The z score central value is 0 and represents the population mean. A larger positive z score indicates better performance.

Here we report the Mini-Mental State Examination mean in each arm at baseline. The Mini-Mental State Examination measures global cognition on a scale from 0 to 30. Higher scores indicate better perfromance.

Here we report the change in the mean Mini-Mental State Examination z score in each arm at the given timepoints. The Mini-Mental State Examination Scores measures global cognition on a scale from 0 to 30. Test scores were transformed into z scores Larger positive scores indicate better performance. Z scores greater than 2.0 indicate exceptionally high function, between 1.36 and 2.0 indicate above average function, between 0.68 and 1.35 indicate high average function, between -0.67 and 0.67 indicate average function, between -0.68 and -1.35 indicate low average function, between -1.36 and -2.0 indicate below average function, and less than -2.0 indicate exceptionally low. The Z-Score central value is 0 and represents the population mean. Larger, positive differences indicate better global cognition.

Scores global cognition on a scale from 0 to 100. Higher scores indicate better cognitive function. Scores were transformed into normative scores ranging from 7.51 to 58.61. Larger scores indicate better function.

Scores global cognition on a scale from 0 to 100. Higher scores indicate better cognitive function. Scores were transformed into normative scores ranging from 7.51 to 58.61. Larger positive differences indicate better function.