Hippocampal-Avoiding Whole Brain Irradiation With Simultaneous Integrated Boost for Treatment of Brain Metastases

• Sponsor: University of Texas Southwestern Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01414738
• Collaborator: (none)
• Enrollment: 50
• Location: 1
• Arm: 1
• Actual Duration (Months): 97.9
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The investigators hypothesize that avoidance of the hippocampal region with WBRT (Whole-Brain Radiotherapy ) may delay or reduce the onset, frequency, and/or severity of NCF (neurocognitive function) decline, as measured with clinical neurocognitive tools.

Condition or Disease	Intervention/Treatment	Phase
Brain Neoplasms, Adult, Malignant	Radiation: Radiotherapy	Phase 2

Detailed Description

We propose to use conformal avoidance of the hippocampal region during whole brain radiotherapy to reduce the dose to the hippocampi, thereby putatively limiting the radiation-induced inflammation of the hippocampal region and subsequent alteration of the microenvironment of the neural progenitor cells

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Hippocampal-Avoiding Whole Brain Irradiation With Simultaneous Integrated Boost for Treatment of Brain Metastases
• Actual Study Start Date: Oct 18, 2011
• Actual Primary Completion Date: Dec 16, 2019
• Actual Study Completion Date: Dec 16, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Radiation Whole-Brain Radiotherapy	Radiation: Radiotherapy; Hippocampal-Avoiding Whole Brain Irradiation with Simultaneous Integrated Boost

Outcome Measures

Primary Outcome Measures

1. Mean Change in *Delayed* Recall Score by Hopkins Verbal Learning Test-Revised (HVLT-R DR) Score [Baseline, 3 months]

   The HVLT-R is a validated test to assess neurocognitive function and it incorporates 6 different forms, each including 12 nouns (targets) with 4 words drawn from 3 semantic categories. *Delayed*recall was measured by recalling the 12 targets after a 20-minute delay. 1 point is awarded for each successfully recalled target. There is no range- recalling more is more memory. Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline

Secondary Outcome Measures

1. Mean Change in *Immediate* Recall Score by Hopkins Verbal Learning Test-Revised (HVLT-R) [Baseline, at 3 months]

   The HVLT-R is a validated test to assess neurocognitive function and it incorporates 6 different forms, each including 12 nouns (targets) with 4 words drawn from 3 semantic categories. *Immediate* recall was measured by memorizing a list of 12 targets for 3 consecutive trials. 1 point is awarded for each successfully recalled target. There is no range- recalling more is more memory. Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline

2. Mean Change in *Delayed Recognition* Score by Hopkins Verbal Learning Test-Revised (HVLT-R) [Baseline, 3 months]

   The HVLT-R is a validated test to assess neurocognitive function and it incorporates 6 different forms, each including 12 nouns (targets) with 4 words drawn from 3 semantic categories. *Delayed recognition* was measured by using recognition discrimination index. 1 point is awarded for each successfully recalled target. There is no range- recalling more is more memory. Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline

3. Mean Change in Neurocognitive Function as Measured by Controlled Word Association Test [Baseline, at 3 months]

   Controlled Word Association Test (COWAT) is used to assess language and executive/frontal skills. The patient produces as many words as possible in 1 min. (each) for a specific letter (C, F, L or P, R, W). Requires about 5 min to complete. 1 point is awarded for each word produced. Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline

4. Mean Change in Trail Making Test (TMT- A) Score [Baseline, at 3 months]

   Trail Making Test (TMT) is a measure of visuospatial scanning, attention, sequencing, and speed and executive function. Patients must "connect the dots" either in a numbered sequence or alternating letters and numbers. The TMT has two parts that are referred to as the Trail Making Test Part A and the Trail Making Test Part B. In Part A, the circles are numbered 1 - 25, and the patient should draw lines to connect the numbers in ascending order. Possible score ranges from 0-3 minutes with higher score (more seconds/minutes) indicating significant cognitive impairment. Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline

5. Mean Change in Trail Making Test (TMT- B) Score [Baseline, at 3 months]

   Trail Making Test (TMT) is a measure of visuospatial scanning, attention, sequencing, and speed and executive function. Patients must "connect the dots" either in a numbered sequence or alternating letters and numbers. The TMT has two parts that are referred to as the Trail Making Test Part A and the Trail Making Test Part B. In Part B, the circles include both numbers (1 - 13) and letters (A - L). Possible score ranges from 0-5 minutes with higher score (more seconds/minutes) indicating significant cognitive impairment.

6. Mean Change in Cognitive Function as Measured by Medical Outcomes Scale (MOS) [Baseline, at 3 months]

   Medical Outcomes Scale (MOS) assess cognitive function with possible score range from 0-100, with higher scores indicating better outcome. Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline

7. Mean Change in Cognitive Function as Measured by Mini-Mental Status Examination (MMSE) [Baseline, at 3 months]

   Mini-Mental Status Examination (MMSE) is a brief, standardized tool to grade patients' global cognitive function. Possible scores range from 0-30, with lower score indicating severe cognitive impairment. Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline

8. Mean Change in Relative Fatigue as Measured by Multidimensional Fatigue Inventory (MFI-20) Scores [Baseline, 3 months]

   The MFI-20 is a multidimensional, self-reporting instrument designed to measure fatigue. It covers the following dimensions: general fatigue, physical fatigue, mental fatigue, reduced motivation, and reduced activity. Possible subscore ranges from 4 to 20 is reported for each dimension, with 20 corresponding to maximal fatigue.

9. Cumulative Incidence of Local Failure [1 year]

   Cumulative incidence of local failure, defined as tumor recurrence . Percent local failure at 1 year. The Cox proportional hazards regression model will be used to evaluate Cumulative incidence of local failure. This is to evaluate local control of brain metastases treated with integrated boost.

10. Cumulative Incidence of Intracranial Failure [1 year]

    Cumulative incidence of intracranial failure was estimated by the Cox proportional hazards regression model. Intracranial failure is any failure in the brain.

11. Percentage of Participants With Local Failures Within the Region of Brain Within the CTV Receiving 20 Gy [1 year]

    Percentage of participants with local failures within the region of brain within the CTV (Clinical Target Volume ) receiving 20 Gy

12. Number of Participants With Recurrence in the Hippocampus [5 months]

    Recurrence in the hippocampus was noted after hippocampal-sparing whole brain irradiation with simultaneous integrated boost (HSIB-WBRT)

13. Median Progression Free Survival [39 months]

    Tumor progression is measured radiographically. The Kaplan-Meier estimator was used to determine the median time to death for this patient population.

14. Median Overall Survival. [39 months]

    Overall survival is measured by the Kaplan-Meier estimator used to determine the median overall survival for this patient population.

15. Number of Adverse Events Grade 3 or Higher Based on CTCAE (Common Terminology Criteria for Adverse Events) Criteria. [From start of treatment up to 39 months]

    The adverse event (AE) including any adverse event would be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

16. Health-related Quality of Life as Assessed by the Functional Assessment of Cancer Therapy With Brain Subscale (FACT-BR) [39 months]

    Quality of life will be assessed using the Functional Assessment of Cancer Therapy with Brain Subscale (FACT-BR). The FACT-BR is a multidimensional, self-report quality of life instrument specifically designed and validated for use with brain malignancy patients. It is written at the 4th grade reading level and can be completed in 5-10 minutes with little or no assistance in patients who are not neurologically incapacitated. It measures quality of life related to symptoms or problems across 5 scales: physical well-being (7 items); social/family well-being (7 items);emotional well-being (6 items); functional well-being (7 items); and concerns relevant to patients with brain tumors (23 items). Items are rated on a 5-point scale (0-5): 0-"not at all", 1- "a little bit", 2-"somewhat", 3-"quite a bit" and 4-"very much", with HIGHER scores indicating a better quality of life.

17. Health-related Quality of Life as Assessed by Euroqol EQ-5D [39 months]

    The EQ (Euroqol)-5D (5 Dimension) health related quality of life questionnaire is a standardized instrument for use as a measure of health outcome. Applicable to a wide range of health conditions and treatments, it provides a simple descriptive profile and a single index value for health status. . The US version of the EQ-5D will be used, to enable mapping of general HR-QoL (Health-related quality of life) scores from EQ-5D scores into health state utility scores (ranging from 0 to 1) for the US population. Possible scores range from 0 to 1, with HIGHER scores indicating a better quality of life.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Pathologically (histologically or cytologically) proven diagnosis of a non-hematopoietic malignancy other than small cell lung cancer and germ cell malignancy.. Direct biopsy of CNS (central nervous system) lesions is not necessarily required although could constitute an allowed site of tissue confirmation as medically prudent. Patients who have been disease free for more than 5 years prior to the appearance of CNS metastases should undergo repeat biopsy of either a systemic metastasis or the CNS metastases to confirm the recurrent malignancy.

2. Patients with measurable brain metastasis outside a 5-mm margin around either hippocampus

3. Patients with measurable brain metastasis who have not been or will not be treated with SRS (stereotactic radiosurgery ) or surgical resection (Note: These treatment options are only permitted at relapse)

4. History/physical examination within 28 days prior to registration

5. Patients must fall into RTOG (Radiation Therapy Oncology Group) recursive partitioning analysis (RPA) class I or II

6. Patients must have a life expectancy of at least 4 months.

7. Age ≥ 18 years

8. Karnofsky performance status ≥ 70

9. Patients must provide study-specific informed consent prior to study entry

10. Women of childbearing potential and male participants must practice adequate contraception

11. Women of childbearing potential must have a negative, qualitative serum pregnancy test ≤2 weeks prior to study entry

Exclusion Criteria:

1. Patients with greater than 9 discrete metastases on MRI.

2. Patients with leptomeningeal metastases

3. Patients with measurable brain metastasis not resulting from small cell lung cancer and germ cell malignancy

4. Plan for chemotherapy or targeted therapies during WBRT or over the subsequent 7 days

5. Contraindication to MR (Magnetic resonance) imaging such as implanted metal devices or foreign bodies, severe claustrophobia AND patients unable to receive gadolinium contrast agents

6. Serum creatinine > 1.4 mg/dl ≤ 28 days prior to study entry

7. Prior radiation therapy to the brain

8. Patients planning to undergo radiosurgery to any CNS lesion OR patients planning to have surgical resection of ALL of their CNS lesions

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390

Sponsors and Collaborators

• University of Texas Southwestern Medical Center

Investigators

• Principal Investigator: Robert Timmerman, MD, UT Southwestern Medical Center Dallas

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 30, 2014

More Information

Publications

None provided.

• Responsible Party: Robert Timmerman, PROFESSOR, University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT01414738
• Other Study ID Numbers: STU 042011-050
• First Posted: Aug 11, 2011
• Last Update Posted: Jan 26, 2021
• Last Verified: Mar 1, 2020

• Additional relevant MeSH terms: Brain Neoplasms

Study Results

Participant Flow

Arm/Group Title	Radiation
Arm/Group Description	Whole-Brain Radiotherapy Radiotherapy: Hippocampal-Avoiding Whole Brain Irradiation with Simultaneous Integrated Boost
Period Title: Overall Study
STARTED	49
Follow-up (3 Months)	18
Follow-up (6 Months)	8
Follow-up (9 Months)	5
COMPLETED	5
NOT COMPLETED	44

Baseline Characteristics

Arm/Group Title	Radiation
Arm/Group Description	Whole-Brain Radiotherapy Radiotherapy: Hippocampal-Avoiding Whole Brain Irradiation with Simultaneous Integrated Boost
Overall Participants	49
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	60
Sex: Female, Male (Count of Participants)
Female	25 51%
Male	24 49%
Race/Ethnicity, Customized (Count of Participants)
White	31 63.3%
African American	11 22.4%
Other	7 14.3%

Outcome Measures

1. Primary Outcome

Title	Mean Change in *Delayed* Recall Score by Hopkins Verbal Learning Test-Revised (HVLT-R DR) Score
Description	The HVLT-R is a validated test to assess neurocognitive function and it incorporates 6 different forms, each including 12 nouns (targets) with 4 words drawn from 3 semantic categories. *Delayed*recall was measured by recalling the 12 targets after a 20-minute delay. 1 point is awarded for each successfully recalled target. There is no range- recalling more is more memory. Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline
Time Frame	Baseline, 3 months

Outcome Measure Data

Analysis Population Description

Complete case analysis was done for this and 1 participant who missed the test was excluded from the analysis.

Arm/Group Title	Radiation
Arm/Group Description	Whole-Brain Radiotherapy Radiotherapy: Hippocampal-Avoiding Whole Brain Irradiation with Simultaneous Integrated Boost
Measure Participants	17
Mean (Standard Deviation) [percentage difference]	-10.6 (50.4)

2. Secondary Outcome

Title	Mean Change in *Immediate* Recall Score by Hopkins Verbal Learning Test-Revised (HVLT-R)
Description	The HVLT-R is a validated test to assess neurocognitive function and it incorporates 6 different forms, each including 12 nouns (targets) with 4 words drawn from 3 semantic categories. *Immediate* recall was measured by memorizing a list of 12 targets for 3 consecutive trials. 1 point is awarded for each successfully recalled target. There is no range- recalling more is more memory. Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline
Time Frame	Baseline, at 3 months

Outcome Measure Data

Analysis Population Description

Complete case analysis was done for this and 1 participant who missed the test was excluded from the analysis.

Arm/Group Title	Radiation
Arm/Group Description	Whole-Brain Radiotherapy Radiotherapy: Hippocampal-Avoiding Whole Brain Irradiation with Simultaneous Integrated Boost
Measure Participants	17
Mean (Standard Deviation) [percentage difference]	39.6 (129.4)

3. Secondary Outcome

Title	Mean Change in *Delayed Recognition* Score by Hopkins Verbal Learning Test-Revised (HVLT-R)
Description	The HVLT-R is a validated test to assess neurocognitive function and it incorporates 6 different forms, each including 12 nouns (targets) with 4 words drawn from 3 semantic categories. *Delayed recognition* was measured by using recognition discrimination index. 1 point is awarded for each successfully recalled target. There is no range- recalling more is more memory. Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline
Time Frame	Baseline, 3 months

Outcome Measure Data

Analysis Population Description

Complete case analysis was done for this and 1 participant who missed the test was excluded from the analysis.

Arm/Group Title	Radiation
Arm/Group Description	Whole-Brain Radiotherapy Radiotherapy: Hippocampal-Avoiding Whole Brain Irradiation with Simultaneous Integrated Boost
Measure Participants	17
Mean (Standard Deviation) [percentage difference]	-0.4 (19.9)

4. Secondary Outcome

Title	Mean Change in Neurocognitive Function as Measured by Controlled Word Association Test
Description	Controlled Word Association Test (COWAT) is used to assess language and executive/frontal skills. The patient produces as many words as possible in 1 min. (each) for a specific letter (C, F, L or P, R, W). Requires about 5 min to complete. 1 point is awarded for each word produced. Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline
Time Frame	Baseline, at 3 months

Outcome Measure Data

Analysis Population Description

Complete case analysis was done for this and 1 participant who missed the test was excluded from the analysis.

Arm/Group Title	Radiation
Arm/Group Description	Whole-Brain Radiotherapy Radiotherapy: Hippocampal-Avoiding Whole Brain Irradiation with Simultaneous Integrated Boost
Measure Participants	17
Mean (Standard Deviation) [percentage difference]	3.7 (40.0)

5. Secondary Outcome

Title	Mean Change in Trail Making Test (TMT- A) Score
Description	Trail Making Test (TMT) is a measure of visuospatial scanning, attention, sequencing, and speed and executive function. Patients must "connect the dots" either in a numbered sequence or alternating letters and numbers. The TMT has two parts that are referred to as the Trail Making Test Part A and the Trail Making Test Part B. In Part A, the circles are numbered 1 - 25, and the patient should draw lines to connect the numbers in ascending order. Possible score ranges from 0-3 minutes with higher score (more seconds/minutes) indicating significant cognitive impairment. Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline
Time Frame	Baseline, at 3 months

Outcome Measure Data

Analysis Population Description

Complete case analysis was done for this and 2 participants who missed the test were excluded from the analysis.

Arm/Group Title	Radiation
Arm/Group Description	Whole-Brain Radiotherapy Radiotherapy: Hippocampal-Avoiding Whole Brain Irradiation with Simultaneous Integrated Boost
Measure Participants	16
Mean (Standard Deviation) [percentage difference]	17.7 (86.6)

6. Secondary Outcome

Title	Mean Change in Trail Making Test (TMT- B) Score
Description	Trail Making Test (TMT) is a measure of visuospatial scanning, attention, sequencing, and speed and executive function. Patients must "connect the dots" either in a numbered sequence or alternating letters and numbers. The TMT has two parts that are referred to as the Trail Making Test Part A and the Trail Making Test Part B. In Part B, the circles include both numbers (1 - 13) and letters (A - L). Possible score ranges from 0-5 minutes with higher score (more seconds/minutes) indicating significant cognitive impairment.
Time Frame	Baseline, at 3 months

Outcome Measure Data

Analysis Population Description

Complete case analysis was done for this and 4 participants who missed the test were excluded from the analysis.

Arm/Group Title	Radiation
Arm/Group Description	Whole-Brain Radiotherapy Radiotherapy: Hippocampal-Avoiding Whole Brain Irradiation with Simultaneous Integrated Boost
Measure Participants	14
Mean (Standard Deviation) [percentage difference]	12.0 (34.9)

7. Secondary Outcome

Title	Mean Change in Cognitive Function as Measured by Medical Outcomes Scale (MOS)
Description	Medical Outcomes Scale (MOS) assess cognitive function with possible score range from 0-100, with higher scores indicating better outcome. Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline
Time Frame	Baseline, at 3 months

Outcome Measure Data

Analysis Population Description

Complete case analysis was done for this and 1 participant who missed the test was excluded from the analysis.

Arm/Group Title	Radiation
Arm/Group Description	Whole-Brain Radiotherapy Radiotherapy: Hippocampal-Avoiding Whole Brain Irradiation with Simultaneous Integrated Boost
Measure Participants	17
Mean (Standard Deviation) [percentage difference]	3.2 (18.2)

8. Secondary Outcome

Title	Mean Change in Cognitive Function as Measured by Mini-Mental Status Examination (MMSE)
Description	Mini-Mental Status Examination (MMSE) is a brief, standardized tool to grade patients' global cognitive function. Possible scores range from 0-30, with lower score indicating severe cognitive impairment. Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline
Time Frame	Baseline, at 3 months

Outcome Measure Data

Analysis Population Description

Complete case analysis was done for this and 1 participant who missed the test was excluded from the analysis.

Arm/Group Title	Radiation
Arm/Group Description	Whole-Brain Radiotherapy Radiotherapy: Hippocampal-Avoiding Whole Brain Irradiation with Simultaneous Integrated Boost
Measure Participants	17
Mean (Standard Deviation) [percentage difference]	-0.1 (7.0)

9. Secondary Outcome

Title	Mean Change in Relative Fatigue as Measured by Multidimensional Fatigue Inventory (MFI-20) Scores
Description	The MFI-20 is a multidimensional, self-reporting instrument designed to measure fatigue. It covers the following dimensions: general fatigue, physical fatigue, mental fatigue, reduced motivation, and reduced activity. Possible subscore ranges from 4 to 20 is reported for each dimension, with 20 corresponding to maximal fatigue.
Time Frame	Baseline, 3 months

Outcome Measure Data

Analysis Population Description

Complete case analysis was done for this and 2 participants who missed the test were excluded from the analysis.

Arm/Group Title	Radiation
Arm/Group Description	Whole-Brain Radiotherapy Radiotherapy: Hippocampal-Avoiding Whole Brain Irradiation with Simultaneous Integrated Boost
Measure Participants	16
Mean (Standard Deviation) [percentage difference]	6.6 (32.2)

10. Secondary Outcome

Title	Cumulative Incidence of Local Failure
Description	Cumulative incidence of local failure, defined as tumor recurrence . Percent local failure at 1 year. The Cox proportional hazards regression model will be used to evaluate Cumulative incidence of local failure. This is to evaluate local control of brain metastases treated with integrated boost.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Radiation
Arm/Group Description	Whole-Brain Radiotherapy Radiotherapy: Hippocampal-Avoiding Whole Brain Irradiation with Simultaneous Integrated Boost
Measure Participants	49
Median (95% Confidence Interval) [hazard (probability) of tumor recurrence]	8.8

11. Secondary Outcome

Title	Cumulative Incidence of Intracranial Failure
Description	Cumulative incidence of intracranial failure was estimated by the Cox proportional hazards regression model. Intracranial failure is any failure in the brain.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Radiation
Arm/Group Description	Whole-Brain Radiotherapy Radiotherapy: Hippocampal-Avoiding Whole Brain Irradiation with Simultaneous Integrated Boost
Measure Participants	49
Number (95% Confidence Interval) [hazard (probability) of tumor recurrence]	21.3

12. Secondary Outcome

Title	Percentage of Participants With Local Failures Within the Region of Brain Within the CTV Receiving 20 Gy
Description	Percentage of participants with local failures within the region of brain within the CTV (Clinical Target Volume ) receiving 20 Gy
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Radiation
Arm/Group Description	Whole-Brain Radiotherapy Radiotherapy: Hippocampal-Avoiding Whole Brain Irradiation with Simultaneous Integrated Boost
Measure Participants	49
Number [percentage of participants]	10.5 21.4%

13. Secondary Outcome

Title	Number of Participants With Recurrence in the Hippocampus
Description	Recurrence in the hippocampus was noted after hippocampal-sparing whole brain irradiation with simultaneous integrated boost (HSIB-WBRT)
Time Frame	5 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Radiation
Arm/Group Description	Whole-Brain Radiotherapy Radiotherapy: Hippocampal-Avoiding Whole Brain Irradiation with Simultaneous Integrated Boost
Measure Participants	49
Count of Participants [Participants]	1 2%

14. Secondary Outcome

Title	Median Progression Free Survival
Description	Tumor progression is measured radiographically. The Kaplan-Meier estimator was used to determine the median time to death for this patient population.
Time Frame	39 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Radiation
Arm/Group Description	Whole-Brain Radiotherapy Radiotherapy: Hippocampal-Avoiding Whole Brain Irradiation with Simultaneous Integrated Boost
Measure Participants	49
Median (95% Confidence Interval) [months]	2.9

15. Secondary Outcome

Title	Median Overall Survival.
Description	Overall survival is measured by the Kaplan-Meier estimator used to determine the median overall survival for this patient population.
Time Frame	39 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Radiation
Arm/Group Description	Whole-Brain Radiotherapy Radiotherapy: Hippocampal-Avoiding Whole Brain Irradiation with Simultaneous Integrated Boost
Measure Participants	49
Median (95% Confidence Interval) [months]	9

16. Secondary Outcome

Title	Number of Adverse Events Grade 3 or Higher Based on CTCAE (Common Terminology Criteria for Adverse Events) Criteria.
Description	The adverse event (AE) including any adverse event would be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time Frame	From start of treatment up to 39 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Radiation
Arm/Group Description	Whole-Brain Radiotherapy Radiotherapy: Hippocampal-Avoiding Whole Brain Irradiation with Simultaneous Integrated Boost
Measure Participants	49
Number [events]	3

17. Secondary Outcome

Title	Health-related Quality of Life as Assessed by the Functional Assessment of Cancer Therapy With Brain Subscale (FACT-BR)
Description	Quality of life will be assessed using the Functional Assessment of Cancer Therapy with Brain Subscale (FACT-BR). The FACT-BR is a multidimensional, self-report quality of life instrument specifically designed and validated for use with brain malignancy patients. It is written at the 4th grade reading level and can be completed in 5-10 minutes with little or no assistance in patients who are not neurologically incapacitated. It measures quality of life related to symptoms or problems across 5 scales: physical well-being (7 items); social/family well-being (7 items);emotional well-being (6 items); functional well-being (7 items); and concerns relevant to patients with brain tumors (23 items). Items are rated on a 5-point scale (0-5): 0-"not at all", 1- "a little bit", 2-"somewhat", 3-"quite a bit" and 4-"very much", with HIGHER scores indicating a better quality of life.
Time Frame	39 months

Outcome Measure Data

Analysis Population Description

This data was not collected as we were no longer interested in collecting this.

Arm/Group Title	Radiation
Arm/Group Description	Whole-Brain Radiotherapy Radiotherapy: Hippocampal-Avoiding Whole Brain Irradiation with Simultaneous Integrated Boost
Measure Participants	0

18. Secondary Outcome

Title	Health-related Quality of Life as Assessed by Euroqol EQ-5D
Description	The EQ (Euroqol)-5D (5 Dimension) health related quality of life questionnaire is a standardized instrument for use as a measure of health outcome. Applicable to a wide range of health conditions and treatments, it provides a simple descriptive profile and a single index value for health status. . The US version of the EQ-5D will be used, to enable mapping of general HR-QoL (Health-related quality of life) scores from EQ-5D scores into health state utility scores (ranging from 0 to 1) for the US population. Possible scores range from 0 to 1, with HIGHER scores indicating a better quality of life.
Time Frame	39 months

Outcome Measure Data

Analysis Population Description

This data was not collected as we were no longer interested in collecting this.

Arm/Group Title	Radiation
Arm/Group Description	Whole-Brain Radiotherapy Radiotherapy: Hippocampal-Avoiding Whole Brain Irradiation with Simultaneous Integrated Boost
Measure Participants	0

Adverse Events

Time Frame	39 months
Arm/Group Title	Radiation
Arm/Group Description	Whole-Brain Radiotherapy Radiotherapy: Hippocampal-Avoiding Whole Brain Irradiation with Simultaneous Integrated Boost
All Cause Mortality
	Radiation
	Affected / at Risk (%)	# Events
Total	26/49 (53.1%)
Serious Adverse Events
	Radiation
	Affected / at Risk (%)	# Events
Total	0/49 (0%)
Other (Not Including Serious) Adverse Events
	Radiation
	Affected / at Risk (%)	# Events
Total	13/49 (26.5%)
Blood and lymphatic system disorders
Edema face	1/49 (2%)
Ear and labyrinth disorders
Hearing loss	1/49 (2%)
Gastrointestinal disorders
Constipation	1/49 (2%)
Vomiting	2/49 (4.1%)
General disorders
Aphasia	1/49 (2%)
Dizziness	2/49 (4.1%)
Headache	10/49 (20.4%)
Insomnia	1/49 (2%)
Nausea	10/49 (20.4%)
Metabolism and nutrition disorders
Anorexia	2/49 (4.1%)
Nervous system disorders
Fatigue	13/49 (26.5%)
Dysarthria	1/49 (2%)
Gait disturbance	1/49 (2%)
Seizures	1/49 (2%)
Skin and subcutaneous tissue disorders
Alopecia	4/49 (8.2%)

Limitations/Caveats

SAE (Serious Adverse Events) were not analyzed on a per patient basis and hence reported as '0' within the AE module.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.