Stereotactic Radiation Therapy With or Without Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases

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ClinicalTrials.gov Identifier: NCT00377156

Recruitment Status : Completed

First Posted : September 15, 2006

Results First Posted : August 24, 2017

Last Update Posted : February 12, 2020

Sponsor:

Collaborator:

National Cancer Institute (NCI)

Information provided by (Responsible Party):

Alliance for Clinical Trials in Oncology

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	Breast Cancer Cognitive/Functional Effects Lung Cancer Metastatic Cancer Prostate Cancer
Interventions	Radiation: radiation therapy Radiation: stereotactic radiosurgery
Enrollment	213

Participant Flow

Recruitment Details	At 34 institutions in North America, patients with 1 to 3 brain metastases were randomized to receive SRS or SRS plus WBRT between February 2002 and December 2013. 70 patients accrued by ACOSOG Z0300 were included in the power calculation and also included for this study.
Pre-assignment Details


Arm/Group Title	Arm I (SRS)	Arm II (SRS+WBRT)
Arm/Group Description	Patients undergo stereotactic radio...	Patients undergo stereotactic radio...
Arm/Group Description	Patients undergo stereotactic radiosurgery (SRS) received 24 Gy in a single fraction if lesions were less than 2.0cm or 20 Gy if lesions were 2 to 2.9 cm in maximum diameter.	Patients undergo stereotactic radiosurgery (SRS) plus whole-brain radiotherapy (WBRT) received 22 Gy in a single fraction if lesions were less than 2.0cm or 18 Gy if lesions were 2 to 2.9 cm in maximum diameter.> > Patients randomly assigned to SRS plus WBRT received 30 GY in 12 fractions of 2.5-Gy WBRT delivered 5 days a week. Whole brain radiotherapy began within 14 days of SRS.
Period Title: Overall Study
Started	111	102
Completed	63	48
Not Completed	48	54
Reason Not Completed
Death	23	19
Withdrawal by Subject	16	24
Had follow-up <90 d	3	6
Cancellation	1	0
Refused testing	0	1
Ineligible	0	1
Disability or language problem	0	1
Other	5	2

Baseline Characteristics

Arm/Group Title		Arm I (SRS)	Arm II (SRS+WBRT)	Total
Arm/Group Description		Patients undergo stereotactic radio...	Patients undergo stereotactic radio...	Total of all reporting groups
Arm/Group Description		Patients undergo stereotactic radiosurgery (SRS) received 24 Gy in a single fraction if lesions were less than 2.0cm or 20 Gy if lesions were 2 to 2.9 cm in maximum diameter.	Patients undergo stereotactic radiosurgery (SRS) plus whole-brain radiotherapy (WBRT) received 22 Gy in a single fraction if lesions were less than 2.0cm or 18 Gy if lesions were 2 to 2.9 cm in maximum diameter.> > Patients randomly assigned to SRS plus WBRT received 30 GY in 12 fractions of 2.5-Gy WBRT delivered 5 days a week. Whole brain radiotherapy began within 14 days of SRS.	Total of all reporting groups
Overall Number of Baseline Participants		111	102	213
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	111 participants	102 participants	213 participants
		59.8 (10.4)	61.4 (10.6)	60.6 (10.5)
Age, Customized Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	111 participants	102 participants	213 participants
18 to 59		53 47.7%	44 43.1%	97 45.5%
>= 60		58 52.3%	58 56.9%	116 54.5%
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	111 participants	102 participants	213 participants
	Female	57 51.4%	47 46.1%	104 48.8%
	Male	54 48.6%	55 53.9%	109 51.2%
Region of Enrollment Measure Type: Number Unit of measure: Participants	Number Analyzed	111 participants	102 participants	213 participants
Canada		23	22	45
United States		88	80	168

Outcome Measures

1.Primary Outcome


Title	Neurocognitive Progression as Measured by the Number of Participants With Cognitive Deterioration by 3 Months
Description	The primary endpoint was cognitive deterioration (progression), define...
Description	The primary endpoint was cognitive deterioration (progression), defined as a decline of greater than 1 SD from baseline on at least 1 of 7 cognitive tests (all tests are standardized based on published norms and transformed so that higher values represent improved cognition) at the 3-month post-SRS evaluation. The number of participants who experienced cognitive deterioration by 3 months is reported for each arm below. For primary analysis of the 3-month cognitive deterioration endpoint, the Fisher exact 2-group binomial test was used to compare the proportion of evaluable patients with 3-month cognitive deterioration between the 2 groups.
Time Frame	3 months post radiosurgery

Outcome Measure Data

Analysis Population Description

Patients who died prior to the 3-month evaluation, who did not return for the 3-month evaluation or a subsequent evaluation, or who did not complete the required baseline tests were excluded from the analysis population for the primary end point.


Arm/Group Title	Arm I (SRS)	Arm II (SRS+WBRT)
Arm/Group Description:	Patients undergo stereotactic radio...	Patients undergo stereotactic radio...
Arm/Group Description:	Patients undergo stereotactic radiosurgery (SRS) received 24 Gy in a single fraction if lesions were less than 2.0cm or 20 Gy if lesions were 2 to 2.9 cm in maximum diameter.	Patients undergo stereotactic radiosurgery (SRS) plus whole-brain radiotherapy (WBRT) received 22 Gy in a single fraction if lesions were less than 2.0cm or 18 Gy if lesions were 2 to 2.9 cm in maximum diameter.> > Patients randomly assigned to SRS plus WBRT received 30 GY in 12 fractions of 2.5-Gy WBRT delivered 5 days a week. Whole brain radiotherapy began within 14 days of SRS.
Overall Number of Participants Analyzed	63	48
Measure Type: Count of Participants Unit of Measure: Participants
	40 63.5%	44 91.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (SRS), Arm II (SRS+WBRT)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	-28.2
	Confidence Interval	(2-Sided) 90% -41.9 to -14.4
	Estimation Comments	Cognitive deterioration, the primary end point in evaluable patients at 3 months, was less frequent after Arm I than Arm II (40/63 [63.5%] vs 44/48 [91.7%],> respectively. The percent difference was -28.2%; 90% CI, -41.9% to -14.4%; P < .001).

2.Secondary Outcome


Title	Number of Participants With Local and Distant Tumor Control up to 3 Months
Description	Number of Participants with Local and Distant Tumor Control up to 3 mo...
Description	Number of Participants with Local and Distant Tumor Control up to 3 months is defined as....
Time Frame	Up to 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Arm I (SRS)	Arm II (SRS+WBRT)
Arm/Group Description:	Patients undergo stereotactic radio...	Patients undergo stereotactic radio...
Arm/Group Description:	Patients undergo stereotactic radiosurgery (SRS) received 24 Gy in a single fraction if lesions were less than 2.0cm or 20 Gy if lesions were 2 to 2.9 cm in maximum diameter.	Patients undergo stereotactic radiosurgery (SRS) plus whole-brain radiotherapy (WBRT) received 22 Gy in a single fraction if lesions were less than 2.0cm or 18 Gy if lesions were 2 to 2.9 cm in maximum diameter.> > Patients randomly assigned to SRS plus WBRT received 30 GY in 12 fractions of 2.5-Gy WBRT delivered 5 days a week. Whole brain radiotherapy began within 14 days of SRS.
Overall Number of Participants Analyzed	105	95
Measure Type: Count of Participants Unit of Measure: Participants
	79 75.2%	89 93.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (SRS), Arm II (SRS+WBRT)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	-18.4
	Confidence Interval	(2-Sided) 95% -29.0 to -7.8
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Overall Quality of Life, as Measured by Mean Change From Baseline [3 Month]
Description	Quality of Life was assessed using the Functional Assessment of Cancer...
Description	Quality of Life was assessed using the Functional Assessment of Cancer Therapy-Brain, for which the range is from 0 to 200 and higher scores indicate better QOL. The Quality of Life (QOL) scores were transformed to a 0- to 100-point scale (with 100 being most favorable), in which a 10-point change was considered clinically significant. Intergroup changes in QOL scores were compared using a 2-sample t test.
Time Frame	From Baseline to 3-Month Evaluation

Outcome Measure Data

Analysis Population Description

All patients in the SRS and SRS+WBRT groups that had a baseline and 3-month QOL score were used in this analysis.


Arm/Group Title	Arm I (SRS)	Arm II (SRS+WBRT)
Arm/Group Description:	Patients undergo stereotactic radio...	Patients undergo stereotactic radio...
Arm/Group Description:	Patients undergo stereotactic radiosurgery (SRS) received 24 Gy in a single fraction if lesions were less than 2.0cm or 20 Gy if lesions were 2 to 2.9 cm in maximum diameter.	Patients undergo stereotactic radiosurgery (SRS) plus whole-brain radiotherapy (WBRT) received 22 Gy in a single fraction if lesions were less than 2.0cm or 18 Gy if lesions were 2 to 2.9 cm in maximum diameter.> >> > >> Patients randomly assigned to SRS plus WBRT received 30 GY in 12 fractions of 2.5-Gy WBRT delivered 5 days a week. Whole brain radiotherapy began within 14 days of SRS.
Overall Number of Participants Analyzed	65	50
Mean (95% Confidence Interval) Unit of Measure: QOL score change from baseline points
	-0.1 (-4.8 to 4.5)	-12 (-17.5 to -6.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (SRS), Arm II (SRS+WBRT)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.001
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	11.9
	Confidence Interval	(2-Sided) 95% 4.8 to 19.0
	Estimation Comments	[Not Specified]

4.Secondary Outcome


Title	Long-Term Neurocognitive Status (Long-Term Cognitive Status), as Measured by Percentage of Long-term Survivors With Cognitive Deterioration at 12 Months
Description	Long-Term Neurocognitive Status > To ascertain in patients with one...
Description	Long-Term Neurocognitive Status > To ascertain in patients with one to three brain metastases whether there is better long-term neurocognitive status in patients who receive SRS alone (Arm A) compared to patients who receive SRS combined with WBRT (Arm B). Long-term survival status is defined as evaluable patients who survived for at least 12 months and had at least one cognitive assessment on or after 365 days.
Time Frame	From baseline to 12 months

Outcome Measure Data

Analysis Population Description

Patients who survived for at least 12 months and had at least one cognitive assessment on or after 365 days were included in this analysis.


Arm/Group Title	Arm I (SRS)	Arm II (SRS+WBRT)
Arm/Group Description:	Patients undergo stereotactic radio...	Patients undergo stereotactic radio...
Arm/Group Description:	Patients undergo stereotactic radiosurgery (SRS) received 24 Gy in a single fraction if lesions were less than 2.0cm or 20 Gy if lesions were 2 to 2.9 cm in maximum diameter.	Patients undergo stereotactic radiosurgery (SRS) plus whole-brain radiotherapy (WBRT) received 22 Gy in a single fraction if lesions were less than 2.0cm or 18 Gy if lesions were 2 to 2.9 cm in maximum diameter.> > Patients randomly assigned to SRS plus WBRT received 30 GY in 12 fractions of 2.5-Gy WBRT delivered 5 days a week. Whole brain radiotherapy began within 14 days of SRS.
Overall Number of Participants Analyzed	10	18
Measure Type: Number Unit of Measure: percentage of participants
	60	94.44

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (SRS), Arm II (SRS+WBRT)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.04
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-34.4
	Confidence Interval	(2-Sided) 95% -74.4 to 5.5
	Estimation Comments	The incidence of cognitive deterioration was less in Arm I than Arm II at 12 months (6/10 [60%] vs 17/18 [94.4%]. The percent difference was -34.4% (95% CI: -74.4% to 5.5%; P = .04)

5.Secondary Outcome


Title	Overall Survival
Description	Overall survival, defined as the time from randomization until death d...
Description	Overall survival, defined as the time from randomization until death due to any cause, was compared between the groups using stratified log-rank tests.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

A survival comparison was performed on an intention-to-treat basis using the entire study population.


Arm/Group Title	Arm I (SRS)	Arm II (SRS+WBRT)
Arm/Group Description:	Patients undergo stereotactic radio...	Patients undergo stereotactic radio...
Arm/Group Description:	Patients undergo stereotactic radiosurgery (SRS) received 24 Gy in a single fraction if lesions were less than 2.0cm or 20 Gy if lesions were 2 to 2.9 cm in maximum diameter.	Patients undergo stereotactic radiosurgery (SRS) plus whole-brain radiotherapy (WBRT) received 22 Gy in a single fraction if lesions were less than 2.0cm or 18 Gy if lesions were 2 to 2.9 cm in maximum diameter.>> >> Patients randomly assigned to SRS plus WBRT received 30 GY in 12 fractions of 2.5-Gy WBRT delivered 5 days a week. Whole brain radiotherapy began within 14 days of SRS.
Overall Number of Participants Analyzed	111	102
Median (Full Range) Unit of Measure: months
	10.4 (0 to 62.5)	7.4 (0 to 60.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (SRS), Arm II (SRS+WBRT)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.92
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95% 0.75 to 1.38
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Up to 60 months from the start of treatment
Adverse Event Reporting Description	All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.

Arm/Group Title	Arm I (SRS)		Arm II (SRS+WBRT)
Arm/Group Description	Patients undergo stereotactic radio...		Patients randomly assigned to SRS p...
Arm/Group Description	Patients undergo stereotactic radiosurgery (SRS) received 24 Gy in a single fraction if lesions were less than 2.0cm or 20 Gy if lesions were 2 to 2.9 cm in maximum diameter.		Patients randomly assigned to SRS plus WBRT received 30 GY in 12 fractions of 2.5-Gy WBRT delivered 5 days a week. Whole brain radiotherapy began within 14 days of SRS.
All-Cause Mortality
	Arm I (SRS)		Arm II (SRS+WBRT)
	Affected / at Risk (%)		Affected / at Risk (%)
Total	5/68 (7.35%)		7/64 (10.94%)
Serious Adverse Events Serious Adverse Events
	Arm I (SRS)		Arm II (SRS+WBRT)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/68 (11.76%)		11/64 (17.19%)
Ear and labyrinth disorders
Hearing loss ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Gastrointestinal disorders
Nausea ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Vomiting ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
General disorders
Death ^† 1	0/68 (0.00%)	0	3/64 (4.69%)	6
Disease progression ^† 1	3/68 (4.41%)	6	2/64 (3.13%)	3
Fatigue ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Infections and infestations
Bladder infection ^† 1	1/68 (1.47%)	1	0/64 (0.00%)	0
Bronchitis ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Encephalitis infection ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	1
Investigations
Alanine aminotransferase increased ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Alkaline phosphatase increased ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Aspartate aminotransferase increased ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Bilirubin increased ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Leukocyte count decreased ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Neutrophil count decreased ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Platelet count decreased ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Metabolism and nutrition disorders
Hyperglycemia ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Hyponatremia ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Nervous system disorders
Central nervous system necrosis ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Cognitive disturbance ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Encephalopathy ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Pleural effusion ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Pneumonitis ^† 1	1/68 (1.47%)	2	1/64 (1.56%)	2
Vascular disorders
Thrombosis ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
1 Term from vocabulary, MedDRA 9 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Arm I (SRS)		Arm II (SRS+WBRT)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	45/68 (66.18%)		53/64 (82.81%)
Blood and lymphatic system disorders
Hemoglobin decreased ^† 1	5/68 (7.35%)	12	3/64 (4.69%)	8
Cardiac disorders
Arrhythmia supraventricular ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Cardiopulmonary arrest ^† 1	1/68 (1.47%)	2	1/64 (1.56%)	2
Left ventricular dysfunction ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Pericardial effusion ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Sinus tachycardia ^† 1	1/68 (1.47%)	2	1/64 (1.56%)	2
Ear and labyrinth disorders
External ear inflammation ^† 1	2/68 (2.94%)	4	4/64 (6.25%)	8
Hearing loss ^† 1	1/68 (1.47%)	2	11/64 (17.19%)	28
Tinnitus ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Eye disorders
Diplopia ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Eye disorder ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Optic nerve disorder ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Retinopathy ^† 1	1/68 (1.47%)	2	2/64 (3.13%)	4
Gastrointestinal disorders
Abdominal distension ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Abdominal pain ^† 1	2/68 (2.94%)	6	1/64 (1.56%)	2
Colonic perforation ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Diarrhea ^† 1	2/68 (2.94%)	4	0/64 (0.00%)	0
Duodenal obstruction ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Dysphagia ^† 1	0/68 (0.00%)	0	2/64 (3.13%)	4
Esophageal ulcer ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Esophagitis ^† 1	1/68 (1.47%)	2	1/64 (1.56%)	2
Mucositis oral ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Nausea ^† 1	21/68 (30.88%)	62	26/64 (40.63%)	108
Small intestinal obstruction ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Vomiting ^† 1	11/68 (16.18%)	28	14/64 (21.88%)	52
General disorders
Chest pain ^† 1	2/68 (2.94%)	4	0/64 (0.00%)	0
Edema limbs ^† 1	4/68 (5.88%)	10	0/64 (0.00%)	0
Fatigue ^† 1	8/68 (11.76%)	22	9/64 (14.06%)	30
Gait abnormal ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Localized edema ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Pain ^† 1	0/68 (0.00%)	0	4/64 (6.25%)	10
Hepatobiliary disorders
Hepatic failure ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Immune system disorders
Hypersensitivity ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Infections and infestations
Gingival infection ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Infection ^† 1	1/68 (1.47%)	2	1/64 (1.56%)	2
Pancreas infection ^† 1	1/68 (1.47%)	4	0/64 (0.00%)	0
Pneumonia ^† 1	3/68 (4.41%)	6	1/64 (1.56%)	4
Skin infection ^† 1	2/68 (2.94%)	4	0/64 (0.00%)	0
Injury, poisoning and procedural complications
Dermatitis radiation ^† 1	5/68 (7.35%)	12	11/64 (17.19%)	26
Vascular access complication ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Investigations
Alanine aminotransferase increased ^† 1	0/68 (0.00%)	0	2/64 (3.13%)	4
Alkaline phosphatase increased ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Amylase increased ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Aspartate aminotransferase increased ^† 1	2/68 (2.94%)	4	2/64 (3.13%)	4
Bilirubin increased ^† 1	1/68 (1.47%)	2	1/64 (1.56%)	2
Coagulopathy ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Creatinine increased ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
INR increased ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Leukocyte count decreased ^† 1	0/68 (0.00%)	0	2/64 (3.13%)	8
Lipase increased ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Lymphocyte count decreased ^† 1	2/68 (2.94%)	8	2/64 (3.13%)	8
Neutrophil count decreased ^† 1	1/68 (1.47%)	2	2/64 (3.13%)	8
Platelet count decreased ^† 1	2/68 (2.94%)	4	3/64 (4.69%)	8
Weight gain ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Weight loss ^† 1	2/68 (2.94%)	4	1/64 (1.56%)	2
Metabolism and nutrition disorders
Acidosis ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Anorexia ^† 1	2/68 (2.94%)	4	5/64 (7.81%)	12
Blood bicarbonate decreased ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Dehydration ^† 1	0/68 (0.00%)	0	5/64 (7.81%)	12
Hyperglycemia ^† 1	2/68 (2.94%)	6	0/64 (0.00%)	0
Hypermagnesemia ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Hypoalbuminemia ^† 1	1/68 (1.47%)	2	1/64 (1.56%)	2
Hypocalcemia ^† 1	1/68 (1.47%)	4	1/64 (1.56%)	2
Hypokalemia ^† 1	1/68 (1.47%)	2	1/64 (1.56%)	2
Hypomagnesemia ^† 1	1/68 (1.47%)	2	1/64 (1.56%)	2
Hyponatremia ^† 1	1/68 (1.47%)	2	1/64 (1.56%)	2
Hypophosphatemia ^† 1	1/68 (1.47%)	2	1/64 (1.56%)	2
Musculoskeletal and connective tissue disorders
Back pain ^† 1	3/68 (4.41%)	10	1/64 (1.56%)	2
Bone pain ^† 1	2/68 (2.94%)	4	0/64 (0.00%)	0
Chest wall pain ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Muscle weakness ^† 1	0/68 (0.00%)	0	2/64 (3.13%)	8
Muscle weakness left-sided ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	4
Muscle weakness lower limb ^† 1	3/68 (4.41%)	5	0/64 (0.00%)	0
Muscle weakness upper limb ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Myalgia ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Pain in extremity ^† 1	1/68 (1.47%)	2	1/64 (1.56%)	2
Nervous system disorders
Central nervous system necrosis ^† 1	4/68 (5.88%)	12	3/64 (4.69%)	10
Cognitive disturbance ^† 1	14/68 (20.59%)	36	13/64 (20.31%)	42
Depressed level of consciousness ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Dizziness ^† 1	1/68 (1.47%)	2	3/64 (4.69%)	6
Encephalopathy ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Headache ^† 1	5/68 (7.35%)	12	4/64 (6.25%)	12
Neurological disorder NOS ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Peripheral motor neuropathy ^† 1	16/68 (23.53%)	51	13/64 (20.31%)	40
Peripheral sensory neuropathy ^† 1	1/68 (1.47%)	2	1/64 (1.56%)	2
Seizure ^† 1	4/68 (5.88%)	10	1/64 (1.56%)	2
Syncope ^† 1	0/68 (0.00%)	0	2/64 (3.13%)	4
Tremor ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Psychiatric disorders
Agitation ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Confusion ^† 1	1/68 (1.47%)	2	2/64 (3.13%)	4
Insomnia ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Renal and urinary disorders
Renal failure ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Dyspnea ^† 1	8/68 (11.76%)	17	6/64 (9.38%)	20
Hiccough ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Hypoxia ^† 1	2/68 (2.94%)	4	2/64 (3.13%)	4
Pleural effusion ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Pleural hemorrhage ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Pneumonitis ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	4
Pneumothorax ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Respiratory disorder ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Skin and subcutaneous tissue disorders
Alopecia ^† 1	23/68 (33.82%)	105	40/64 (62.50%)	162
Hand-and-foot syndrome ^† 1	0/68 (0.00%)	0	1/64 (1.56%)	2
Pain of skin ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Pruritus ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Rash desquamating ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Skin disorder ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Vascular disorders
Hematoma ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
Hypertension ^† 1	1/68 (1.47%)	4	0/64 (0.00%)	0
Hypotension ^† 1	0/68 (0.00%)	0	3/64 (4.69%)	6
Thrombosis ^† 1	4/68 (5.88%)	8	1/64 (1.56%)	2
Vascular disorder ^† 1	1/68 (1.47%)	2	0/64 (0.00%)	0
1 Term from vocabulary, MedDRA 9 † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

Results Point of Contact

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Name/Title:	Paul Brown, M.D.
Organization:	Mayo Clinic
Phone:	507-538-0948
EMail:	Brown.Paul@mayo.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Churilla TM, Ballman KV, Brown PD, Twohy EL, Jaeckle K, Farace E, Cerhan JH, Anderson SK, Carrero XW, Garces YI, Barker FG 2nd, Deming R, Dixon JG, Burri SH, Chung C, Ménard C, Stieber VW, Pollock BE, Galanis E, Buckner JC, Asher AL. Stereotactic Radiosurgery With or Without Whole-Brain Radiation Therapy for Limited Brain Metastases: A Secondary Analysis of the North Central Cancer Treatment Group N0574 (Alliance) Randomized Controlled Trial. Int J Radiat Oncol Biol Phys. 2017 Dec 1;99(5):1173-1178. doi: 10.1016/j.ijrobp.2017.07.045. Epub 2017 Aug 5.

Brown PD, Jaeckle K, Ballman KV, Farace E, Cerhan JH, Anderson SK, Carrero XW, Barker FG 2nd, Deming R, Burri SH, Ménard C, Chung C, Stieber VW, Pollock BE, Galanis E, Buckner JC, Asher AL. Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial. JAMA. 2016 Jul 26;316(4):401-409. doi: 10.1001/jama.2016.9839. Erratum in: JAMA. 2018 Aug 7;320(5):510.

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Responsible Party:	Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:	NCT00377156
Other Study ID Numbers:	N0574 NCCTG-N0574 ACOSOG-N0574 CDR0000499633 ( Registry Identifier: PDQ (Physician Data Query) ) NCI-2009-00653 ( Registry Identifier: CTRP (Clinical Trials Reporting System) )
First Submitted:	September 13, 2006
First Posted:	September 15, 2006
Results First Submitted:	February 27, 2017
Results First Posted:	August 24, 2017
Last Update Posted:	February 12, 2020

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