Memantine Hydrochloride and Whole-Brain Radiotherapy With or Without Hippocampal Avoidance in Reducing Neurocognitive Decline in Patients With Brain Metastases

Phase 3

Completed

Conditions: Cognitive Impairment
Solid Neoplasm
Metastatic Malignant Neoplasm in the Brain

Interventions: Radiation: Whole brain radiation therapy with hippocampal avoidance
Drug: Memantine
Radiation: Whole brain radiation therapy

Registration Number: NCT02360215

Lead Sponsor: NRG Oncology

Brief Summary: This randomized phase III trial compares memantine hydrochloride and whole-brain radiotherapy with or without hippocampal avoidance in reducing neurocognitive decline in patients with cancer that has spread from the primary site (place where it started) to the brain. Whole brain radiotherapy (WBRT) is the most common treatment for brain metastasis. Unfortunately, the majority of patients with brain metastases experience cognitive (such as learning and memory) deterioration after WBRT. Memantine hydrochloride may enhance cognitive function by binding to and inhibiting channels of receptors located in the central nervous system. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Using radiation techniques, such as intensity modulated radiotherapy to avoid the hippocampal region during WBRT, may reduce the radiation dose to the hippocampus and help limit the radiation-induced cognitive decline. It is not yet known whether giving memantine hydrochloride and WBRT with or without hippocampal avoidance works better in reducing neurocognitive decline in patients with brain metastases.

Detailed Description: PRIMARY OBJECTIVES:

I. Determine whether the addition of whole-brain radiotherapy with hippocampal avoidance (HA-WBRT) increases time to neurocognitive failure at months 2, 4, 6, and 12 as measured by neurocognitive decline on a battery of tests: the Hopkins Verbal Learning Test-Revised (HVLT-R) for Total Recall, Delayed Recall, and Delayed Recognition, Controlled Oral Word Association (COWA), and the Trail Making Test (TMT) Parts A and B.

SECONDARY OBJECTIVES:

I. Determine whether the addition of HA-WBRT preserves neurocognitive function at months 2, 4, 6, and 12 as separately measured by each test, the HVLT-R for Total Recall, Delayed Recall, and Delayed Recognition; COWA; and TMT Parts A and B.

II. Evaluate the potential benefit of HA-WBRT in symptom burden, as measured by the M. D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT).

III. Assessment of quality adjusted survival and cost analysis using the five-level version of the EuroQol five-dimensional (EQ-5D-5L).

IV. Compare cumulative incidence of progression and overall survival after WBRT versus HA-WBRT.

V. Compare adverse events between the treatment arms according to the Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0 criteria.

TERTIARY OBJECTIVES:

I. Collect serum, plasma, and imaging studies for future translational research analyses.

II. Evaluate magnetic resonance (MR) imaging biomarkers of white matter injury and hippocampal volumetry at baseline and 6 months as potential predictors of neurocognitive decline and differential benefit from HA-WBRT as compared to WBRT.

III. Association of symptom burden and anxiety/depression with neurocognitive function.

IV. Evaluate the potential correlation between the prognostic scoring systems Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) and the diagnosis-specific graded prognostic assessment (DS-GPA) and neurocognitive function at baseline and overtime.

After completion of study treatment, patients are followed up at 12 months.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 518

Inclusion Criteria

PRIOR TO STEP 1 REGISTRATION:
- Brain metastases outside a 5-mm margin around either hippocampus must be visible on contrast-enhanced magnetic resonance imaging (MRI) performed =< 21 days prior to Step 1 registration; an allowed exception, regarding ability to image brain metastases, would be that patients who had undergone radiosurgery or surgical resection and are planning adjuvant WBRT do not have to have visible disease but do need a pre-surgery MRI or computed tomography (CT) scan demonstrating brain metastases; however, the brain metastases could not have been within 5 mm of either hippocampus
- Patients must have a gadolinium contrast-enhanced three-dimensional spoiled gradient (SPGR), magnetization-prepared rapid gradient echo (MP-RAGE), or turbo field echo (TFE) axial MRI scan with standard axial and coronal gadolinium contrast-enhanced T1-weighted sequence and axial T2/FLAIR sequence acquisitions; to yield acceptable image quality, the gadolinium contrast-enhanced three-dimensional SPGR, MP-RAGE, or TFE axial MRI scan should use the smallest possible axial slice thickness not exceeding 1.5 mm; the associated coronal and sagittal contrast-enhanced T1 sequences can be up to 2.5 mm in slice thickness; this MRI must be obtained =< 21 days prior to step 1 registration; the vendor specific MRI protocols are available for download from the Alzheimer's Disease Neuroimaging Initiative (ADNI)
- Patients must provide study-specific informed consent prior to registration
PRIOR TO STEP 2 REGISTRATION:
- The following baseline neurocognitive assessments must be completed prior to Step 2 registration: HVLT-R, TMT, and COWA;
- Pathologically (histologically or cytologically) proven diagnosis of solid tumor malignancy within 5 years prior to Step 2 registration
- History and physical examination within 28 days prior to Step 2 registration
- Karnofsky performance status of >= 70 within 28 days prior to Step 2 registration
- Serum creatinine =< 3 mg/dL (265 umol/L) and creatinine clearance >= 30 ml/min
- Blood urea nitrogen (BUN) within institutional upper limit of normal (e.g. < 20 mg/dL)
- Total bilirubin =< 2.5 mg/dL (43 umol/L)
- Patients may have had prior therapy for brain metastasis, including radiosurgery and surgical resection; patients must have completed prior therapy by at least 14 days prior to Step 2 for surgical resection and 7 days for radiosurgery
- Negative serum pregnancy test (in women of childbearing potential) =< 14 days prior to Step 2; women of childbearing potential and men who are sexually active must practice adequate contraception while on study
- Patients who are primary English or French speakers are eligible

Exclusion Criteria

Prior external beam radiation therapy to the brain or whole brain radiation therapy
Planned cytotoxic chemotherapy during the WBRT only; patients may have had prior chemotherapy
Radiographic evidence of hydrocephalus or other architectural distortion of the ventricular system, including placement of external ventricular drain or ventriculoperitoneal shunt
Severe, active co-morbidity defined as follows:
- Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
- Transmural myocardial infarction within the last 6 months
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
- Chronic obstructive pulmonary disease exacerbation or other acute respiratory illness precluding study therapy at the time of registration
- Severe hepatic disease defined as a diagnosis of Child-Pugh class B or C hepatic disease
- Renal tubular acidosis or metabolic acidosis
- Human immunodeficiency virus (HIV) positive with cluster of differentiation (CD)4 count < 200 cells/microliter; note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to registration; Note also that HIV testing is not required for eligibility for this protocol
Pregnant or lactating women, or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
Prior allergic reaction to memantine (memantine hydrochloride)
Current alcohol or drug abuse (may exacerbate lethargy/dizziness with memantine)
Intractable seizures while on adequate anticonvulsant therapy-more than 1 seizure per month for the past 2 months
Patients with definitive leptomeningeal metastases
Patients with brain metastases from primary germ cell tumors, small cell carcinoma, unknown primary, or lymphoma
Contraindication to magnetic resonance (MR) imaging such as implanted metal devices or foreign bodies
Contraindication to gadolinium contrast administration during MR imaging, such as allergy or insufficient renal function
Current use of (other N-methyl D-aspartate [NMDA] antagonists) amantadine, ketamine, or dextromethorphan

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
WBRT + Memantine	Whole brain radiation therapy	Whole brain radiation therapy (WBRT) and memantine
HA-WBRT/IMRT+ Memantine	Whole brain radiation therapy with hippocampal avoidance	Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) using intensity modulated radiation therapy (IMRT) and memantine
WBRT + Memantine	Memantine	Whole brain radiation therapy (WBRT) and memantine
HA-WBRT/IMRT+ Memantine	Memantine	Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) using intensity modulated radiation therapy (IMRT) and memantine

Primary Outcome Measures

Name	Time	Method
Time to Neurocognitive Failure	From randomization to last follow-up. Maximum follow-up was 15.6 months.	Neurocognitive failure is defined as the first failure, defined as a neurocognitive decline using the reliable change index (RCI) on at least one of the following assessments or parts of : Hopkins Verbal Learning Test - Revised (HVLT-R), Trail Making Test (TMT), or Controlled Oral Word Association (COWA). The HVLT-R has 3 parts that were analyzed separately for decline: Total Recall, Delayed Recall, and Delayed Recognition. The TMT has 2 parts that were analyzed separately: Part A and Part B. Neurocognitive failure rate is estimated using the cumulative incidence method. Analysis was planned to occur after 233 events were reported. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Six-month rates are provided.Analysis was planned to occur after 233 events were reported.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in the Hopkins Verbal Learning Test -Revised (HVLT-R) Total Recall Score (Neurocognitive Decline)	Baseline, 2, 4, 6, and 12 months	The HVLT-R assesses verbal learning and memory. The test involves memorizing a list of 12 nouns for 3 consecutive trials (Total Recall), recalling the 12 targets after a 20-minute delay (Delayed Recall), and then identifying the 12 targets from a list of semantically related or unrelated items (delayed recognition). Raw scores are derived for total recall (sum of the number of targets correctly recalled), delayed recall (sum of the number of targets correctly recalled), and a delayed recognition discrimination index (sum of targets incorrectly identified subtracted from the sum of the number of targets correctly identified). The range of scores for total recall is 0 to 36, for delayed recall is 0 to 12, and -12 to 12 for recognition. A higher score indicates better functioning. Scores are standardized, adjusting for age, education, and gender as necessary, such that mean 0 and standard deviation is 1. Change is calculated as baseline score subtracted from post-baseline score.
Change From Baseline in the Hopkins Verbal Learning Test -Revised (HVLT-R) Delayed Recall Score (Neurocognitive Decline)	Baseline, 2, 4, 6, and 12 months	The HVLT-R assesses verbal learning and memory. The test involves memorizing a list of 12 nouns for 3 consecutive trials (Total Recall), recalling the 12 targets after a 20-minute delay (Delayed Recall), and then identifying the 12 targets from a list of semantically related or unrelated items (delayed recognition). Raw scores are derived for total recall (sum of the number of targets correctly recalled), delayed recall (sum of the number of targets correctly recalled), and a delayed recognition discrimination index (sum of targets incorrectly identified subtracted from the sum of the number of targets correctly identified). The range of scores for total recall is 0 to 36, for delayed recall is 0 to 12, and -12 to 12 for recognition. A higher score indicates better functioning. Scores are standardized, adjusting for age, education, and gender as necessary, such that mean 0 and standard deviation is 1. Change is calculated as baseline score subtracted from post-baseline score.
Change From Baseline in the Hopkins Verbal Learning Test -Revised (HVLT-R) Delayed Recognition (Neurocognitive Decline)	Baseline, 2, 4, 6, and 12 months	The HVLT-R assesses verbal learning and memory. The test involves memorizing a list of 12 nouns for 3 consecutive trials (Total Recall), recalling the 12 targets after a 20-minute delay (Delayed Recall), and then identifying the 12 targets from a list of semantically related or unrelated items (delayed recognition). Raw scores are derived for total recall (sum of the number of targets correctly recalled), delayed recall (sum of the number of targets correctly recalled), and a delayed recognition discrimination index (sum of targets incorrectly identified subtracted from the sum of the number of targets correctly identified). The range of scores for total recall is 0 to 36, for delayed recall is 0 to 12, and -12 to 12 for recognition. A higher score indicates better functioning. Scores are standardized by expressing the deviation from the mean score of the group in units of standard deviation. Change is calculated as baseline score subtracted from post-baseline score.
Change From Baseline in the Trail Making Test (TMT) Part A (Neurocognitive Decline)	Baseline, 2, 4, 6, and 12 months	The TMT is a neuropsychological test of visual attention and task switching that can provide information about visual search speed, scanning, speed of processing, mental flexibility, and executive functioning. Subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. There are two parts to the test: in the first (Part A), the targets are all numbers (1, 2, 3, etc.) and the test taker needs to connect them in sequential order; in the second part (Part B), the subject alternates between numbers and letters (1, A, 2, B, etc.). The score is the amount of time, in seconds, that it takes the patient to complete each maze. The range for Part A is 0 to 180 (3 minutes) and for Part B is 0 to 300 (5 minutes). Lower scores indicate better functioning. Scores are standardized, adjusting for age, education, gender as needed, so that mean is 0 and standard deviation is 1. Change is calculated as baseline score subtracted from post-baseline score.
Change From Baseline in the Trail Making Test (TMT) Part B (Neurocognitive Decline)	Baseline, 2, 4, 6, and 12 months	The TMT is a neuropsychological test of visual attention and task switching that can provide information about visual search speed, scanning, speed of processing, mental flexibility, and executive functioning. Subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. There are two parts to the test: in the first (Part A), the targets are all numbers (1, 2, 3, etc.) and the test taker needs to connect them in sequential order; in the second part (Part B), the subject alternates between numbers and letters (1, A, 2, B, etc.). The score is the amount of time, in seconds, that it takes the patient to complete each maze. The range for Part A is 0 to 180 (3 minutes) and for Part B is 0 to 300 (5 minutes). A lower score indicates better functioning. Scores are standardized by expressing the deviation from the mean score of the group in units of standard deviation. Change is calculated as baseline score subtracted from post-baseline score.
Change in M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Cognitive Factor Score	Baseline, 2, 4, 6, and 12 months	The MD Anderson Symptom Inventory for brain tumor (MDASI-BT) is a 28-item multi-symptom patient-reported outcome measure assessing the severity of symptoms experienced by cancer patients and the interference with daily living caused by these symptoms, with 9 items specific to brain tumors. Each item ranges from 0 (best condition) to 10 (worst condition). A subscale score (Cognitive Factor) is the average of the subscale items, given that a specified minimum numbers of items were completed.
Change in EQ-5D-5L Index Score at 2 Months	Baseline and 2 months	The EQ-5D-5L is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 5 problem levels (1-none to 5-extreme). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm scale ranging from 0 for the worst imaginable health state to 100 for best imaginable health state, marked at 10-point intervals. The index score is reported here.
Change in EQ-5D-5L Index Score at 12 Months	Baseline and 12 months	The EQ-5D-5L is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 5 problem levels (1-none to 5-extreme). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm scale ranging from 0 for the worst imaginable health state to 100 for best imaginable health state, marked at 10-point intervals. The index score is reported here.
Change in EQ-5D-5L VAS Score at 4 Months	Baseline and 4 months	The EQ-5D-5L is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 5 problem levels (1-none to 5-extreme). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm scale ranging from 0 for the worst imaginable health state to 100 for best imaginable health state, marked at 10-point intervals. The VAS score is reported here.
Change From Baseline in the Controlled Oral Word Association (COWA) Test (Neurocognitive Decline)	Baseline, 2, 4, 6, and 12 months	The COWA is a verbal fluency test that measures spontaneous production of words belonging to the same category or beginning with some designated letter. Patients are given 1 minute to name as many words as possible beginning with the designated letter. The procedure is then repeated for the remaining two letters. Two alternate forms of the COWA are employed to minimize practice effects. The score is the sum of the correct responses with a range of 0 to infinity. A higher score indicates better functioning. Scores are standardized, adjusting for age, education, and gender as necessary, such that mean is 0 and standard deviation is 1. Change is calculated as baseline score subtracted from post-baseline score.
Change From Baseline in the Clinical Trial Battery Composite (CTB COMP) Score [Neurocognitive Decline]	Baseline, 2, 4, 6, and 12 months	Clinical Trial Battery Composite score is the arithmetic mean of the HVLT-R (Free Recall, Delayed Recall, Delayed Recognition), TMTA, TMTB, and COWA scores, all of which are standardized, adjusting for age, education, and gender as necessary, such that mean is 0 and standard deviation is 1. A participant must have at least 5 of the 6 scores. A higher composite score indicates better neurocognitive function.Change is calculated as baseline score subtracted from post-baseline score.
Change in M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score	Baseline, 2, 4, 6, and 12 months	The MD Anderson Symptom Inventory for brain tumor (MDASI-BT) is a 28-item multi-symptom patient-reported outcome measure assessing the severity of symptoms experienced by cancer patients and the interference with daily living caused by these symptoms, with 9 items specific to brain tumors. Each item ranges from 0 (best condition) to 10 (worst condition). A subscale score (Symptom Severity) is the average of the subscale items, given that a specified minimum numbers of items were completed.
Overall Survival	From randomization to last follow-up. Maximum follow-up was 15.6 months.	Overall survival time is defined as time from registration/randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. Analysis was planned to occur after 233 primary endpoint events (neurocognitive failure) were reported. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Six-month rates are provided.
Change in M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Interference Score	Baseline, 2, 4, 6, and 12 months	The MD Anderson Symptom Inventory for brain tumor (MDASI-BT) is a 28-item multi-symptom patient-reported outcome measure assessing the severity of symptoms experienced by cancer patients and the interference with daily living caused by these symptoms, with 9 items specific to brain tumors. Each item ranges from 0 (best condition) to 10 (worst condition). A subscale score (Interference) is the average of the subscale items, given that a specified minimum numbers of items were completed.
Change in M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Neurologic Factor Score	Baseline, 2, 4, 6, and 12 months	The MD Anderson Symptom Inventory for brain tumor (MDASI-BT) is a 28-item multi-symptom patient-reported outcome measure assessing the severity of symptoms experienced by cancer patients and the interference with daily living caused by these symptoms, with 9 items specific to brain tumors. Each item ranges from 0 (best condition) to 10 (worst condition). A subscale score (Neurologic Factor) is the average of the subscale items, given that a specified minimum numbers of items were completed.
Change in EQ-5D-5L Index Score at 4 Months	Baseline and 4 months	The EQ-5D-5L is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 5 problem levels (1-none to 5-extreme). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm scale ranging from 0 for the worst imaginable health state to 100 for best imaginable health state, marked at 10-point intervals. The index score is reported here.
Change in EQ-5D-5L Index Score at 6 Months	Baseline and 6 months	The EQ-5D-5L is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 5 problem levels (1-none to 5-extreme). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm scale ranging from 0 for the worst imaginable health state to 100 for best imaginable health state, marked at 10-point intervals. The index score is reported here.
Change in EQ-5D-5L VAS Score at 6 Months	Baseline and 6 months	The EQ-5D-5L is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 5 problem levels (1-none to 5-extreme). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm scale ranging from 0 for the worst imaginable health state to 100 for best imaginable health state, marked at 10-point intervals. The VAS score is reported here.
Number of Patients With a Grade 3+ Adverse Event (AE) Regardless of Relationship to Treatment	From randomization to last follow-up. Analysis was planned to occur after 233 events were reported. Maximum follow-up was 15.6 months.	. Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE.
Change in EQ-5D-5L VAS Score at 2 Months	Baseline and 2 months	The EQ-5D-5L is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 5 problem levels (1-none to 5-extreme). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm scale ranging from 0 for the worst imaginable health state to 100 for best imaginable health state, marked at 10-point intervals. The VAS score is reported here.
Change in EQ-5D-5L VAS Score at 12 Months	Baseline and 12 months	The EQ-5D-5L is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 5 problem levels (1-none to 5-extreme). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm scale ranging from 0 for the worst imaginable health state to 100 for best imaginable health state, marked at 10-point intervals. The VAS score is reported here.
Intracranial Progression-Free Survival	From randomization to last follow-up. Analysis was planned to occur after 233 events were reported. Maximum follow-up was 15.6 months.	Intracranial progression-free survival time is defined as time from registration/randomization to the date of progression in the brain or death from any cause. Intracranial progression-free survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. Analysis was planned to occur after 233 primary endpoint events (neurocognitive failure) were reported. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Six-month rates are provided.

Trial Locations

Locations (220): Los Angeles County-USC Medical Center
🇺🇸
Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center
🇺🇸
Los Angeles, California, United States
Marshfield Clinic Stevens Point Center
🇺🇸
Stevens Point, Wisconsin, United States
Allan Blair Cancer Centre
🇨🇦
Regina, Saskatchewan, Canada
University of Chicago Comprehensive Cancer Center
🇺🇸
Chicago, Illinois, United States
Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
Banner MD Anderson Cancer Center
🇺🇸
Gilbert, Arizona, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
🇺🇸
Coral Gables, Florida, United States
Kaiser Permanente Los Angeles Medical Center
🇺🇸
Los Angeles, California, United States
Lewis and Faye Manderson Cancer Center
🇺🇸
Tuscaloosa, Alabama, United States
Kaiser Permanente-Rancho Cordova Cancer Center
🇺🇸
Rancho Cordova, California, United States
Rohnert Park Cancer Center
🇺🇸
Rohnert Park, California, United States
University of Kentucky/Markey Cancer Center
🇺🇸
Lexington, Kentucky, United States
OSF Saint Francis Medical Center
🇺🇸
Peoria, Illinois, United States
McLaren Cancer Institute-Flint
🇺🇸
Flint, Michigan, United States
McLaren-Port Huron
🇺🇸
Port Huron, Michigan, United States
The Permanente Medical Group-Roseville Radiation Oncology
🇺🇸
Roseville, California, United States
Saint Luke's Mountain States Tumor Institute - Meridian
🇺🇸
Meridian, Idaho, United States
Cleveland Clinic-Weston
🇺🇸
Weston, Florida, United States
Penrose-Saint Francis Healthcare
🇺🇸
Colorado Springs, Colorado, United States
Mercy San Juan Medical Center
🇺🇸
Carmichael, California, United States
Sutter Solano Medical Center/Cancer Center
🇺🇸
Vallejo, California, United States
Rocky Mountain Cancer Centers-Boulder
🇺🇸
Boulder, Colorado, United States
Piedmont Hospital
🇺🇸
Atlanta, Georgia, United States
Helen F Graham Cancer Center
🇺🇸
Newark, Delaware, United States
Kaiser Permanente Medical Center - Santa Clara
🇺🇸
Santa Clara, California, United States
Saint Alphonsus Cancer Care Center-Boise
🇺🇸
Boise, Idaho, United States
Memorial Health University Medical Center
🇺🇸
Savannah, Georgia, United States
Christiana Care Health System-Christiana Hospital
🇺🇸
Newark, Delaware, United States
UC San Diego Moores Cancer Center
🇺🇸
La Jolla, California, United States
West Michigan Cancer Center
🇺🇸
Kalamazoo, Michigan, United States
City of Hope Comprehensive Cancer Center
🇺🇸
Duarte, California, United States
Saint Luke's Mountain States Tumor Institute
🇺🇸
Boise, Idaho, United States
Saint Joseph Mercy Oakland
🇺🇸
Pontiac, Michigan, United States
Kaiser Permanente Cancer Treatment Center
🇺🇸
South San Francisco, California, United States
Boca Raton Regional Hospital
🇺🇸
Boca Raton, Florida, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
🇺🇸
Deerfield Beach, Florida, United States
Grady Health System
🇺🇸
Atlanta, Georgia, United States
Wesley Medical Center
🇺🇸
Wichita, Kansas, United States
Crossroads Cancer Center
🇺🇸
Effingham, Illinois, United States
Swedish Medical Center
🇺🇸
Englewood, Colorado, United States
Emory University Hospital Midtown
🇺🇸
Atlanta, Georgia, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
Emory University Hospital/Winship Cancer Institute
🇺🇸
Atlanta, Georgia, United States
Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
🇺🇸
Savannah, Georgia, United States
Emory Saint Joseph's Hospital
🇺🇸
Atlanta, Georgia, United States
McLaren Cancer Institute-Lapeer Region
🇺🇸
Lapeer, Michigan, United States
Ascension Via Christi Hospitals Wichita
🇺🇸
Wichita, Kansas, United States
Saint Luke's Hospital
🇺🇸
Cedar Rapids, Iowa, United States
Lawrence Memorial Hospital
🇺🇸
Lawrence, Kansas, United States
Genesys Hurley Cancer Institute
🇺🇸
Flint, Michigan, United States
SIH Cancer Institute
🇺🇸
Carterville, Illinois, United States
Parkview Hospital Randallia
🇺🇸
Fort Wayne, Indiana, United States
Unity Hospital
🇺🇸
Fridley, Minnesota, United States
Northwestern Medicine Cancer Center Delnor
🇺🇸
Geneva, Illinois, United States
McLaren Cancer Institute-Macomb
🇺🇸
Mount Clemens, Michigan, United States
Summa Akron City Hospital/Cooper Cancer Center
🇺🇸
Akron, Ohio, United States
University of Kansas Cancer Center-Overland Park
🇺🇸
Overland Park, Kansas, United States
21st Century Oncology MHP - Farmington
🇺🇸
Farmington Hills, Michigan, United States
Spectrum Health at Butterworth Campus
🇺🇸
Grand Rapids, Michigan, United States
McLaren Cancer Institute-Bay City
🇺🇸
Bay City, Michigan, United States
New York-Presbyterian/Brooklyn Methodist Hospital
🇺🇸
Brooklyn, New York, United States
Henry Ford Cancer Institute-Downriver
🇺🇸
Brownstown, Michigan, United States
University of Rochester
🇺🇸
Rochester, New York, United States
West Virginia University Healthcare
🇺🇸
Morgantown, West Virginia, United States
Lakeland Medical Center Saint Joseph
🇺🇸
Saint Joseph, Michigan, United States
Saint Francis Medical Center
🇺🇸
Cape Girardeau, Missouri, United States
Mayo Clinic Radiation Therapy-Northfield
🇺🇸
Northfield, Minnesota, United States
UHHS-Westlake Medical Center
🇺🇸
Westlake, Ohio, United States
Sanford Bismarck Medical Center
🇺🇸
Bismarck, North Dakota, United States
Ogden Regional Medical Center
🇺🇸
Ogden, Utah, United States
Case Western Reserve University
🇺🇸
Cleveland, Ohio, United States
Norris Cotton Cancer Center-North
🇺🇸
Saint Johnsbury, Vermont, United States
NHRMC Radiation Oncology - 16th Street
🇺🇸
Wilmington, North Carolina, United States
Legacy Mount Hood Medical Center
🇺🇸
Gresham, Oregon, United States
Northeast Radiation Oncology Center
🇺🇸
Dunmore, Pennsylvania, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Christiana Care Health System-Concord Health Center
🇺🇸
Chadds Ford, Pennsylvania, United States
Cleveland Clinic Cancer Center/Fairview Hospital
🇺🇸
Cleveland, Ohio, United States
Aurora Cancer Care-Grafton
🇺🇸
Grafton, Wisconsin, United States
Billings Clinic Cancer Center
🇺🇸
Billings, Montana, United States
Renown Regional Medical Center
🇺🇸
Reno, Nevada, United States
Sanford Roger Maris Cancer Center
🇺🇸
Fargo, North Dakota, United States
Riddle Memorial Hospital
🇺🇸
Media, Pennsylvania, United States
Langlade Hospital and Cancer Center
🇺🇸
Antigo, Wisconsin, United States
Cleveland Clinic Akron General
🇺🇸
Akron, Ohio, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
🇺🇸
New York, New York, United States
Geisinger Wyoming Valley/Henry Cancer Center
🇺🇸
Wilkes-Barre, Pennsylvania, United States
Cleveland Clinic Cancer Center Independence
🇺🇸
Independence, Ohio, United States
Self Regional Healthcare
🇺🇸
Greenwood, South Carolina, United States
Mayo Clinic Health System-Franciscan Healthcare
🇺🇸
La Crosse, Wisconsin, United States
Vince Lombardi Cancer Clinic - Oshkosh
🇺🇸
Oshkosh, Wisconsin, United States
CHUM - Hopital Notre-Dame
🇨🇦
Montreal, Quebec, Canada
Vince Lombardi Cancer Clinic-Two Rivers
🇺🇸
Two Rivers, Wisconsin, United States
Aspirus UW Cancer Center
🇺🇸
Wisconsin Rapids, Wisconsin, United States
Aurora West Allis Medical Center
🇺🇸
West Allis, Wisconsin, United States
Tufts Medical Center
🇺🇸
Boston, Massachusetts, United States
Virginia Mason Medical Center
🇺🇸
Seattle, Washington, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸
Miami, Florida, United States
Community Cancer Center South
🇺🇸
Indianapolis, Indiana, United States
Community Cancer Center North
🇺🇸
Indianapolis, Indiana, United States
UM Upper Chesapeake Medical Center
🇺🇸
Bel Air, Maryland, United States
Central Maryland Radiation Oncology in Howard County
🇺🇸
Columbia, Maryland, United States
University of California San Diego
🇺🇸
San Diego, California, United States
North Kansas City Hospital
🇺🇸
Kansas City, Missouri, United States
California Pacific Medical Center-Pacific Campus
🇺🇸
San Francisco, California, United States
Huntsman Cancer Institute/University of Utah
🇺🇸
Salt Lake City, Utah, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States
CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)
🇨🇦
Quebec City, Quebec, Canada
Wayne State University/Karmanos Cancer Institute
🇺🇸
Detroit, Michigan, United States
Henry Ford Hospital
🇺🇸
Detroit, Michigan, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Legacy Good Samaritan Hospital and Medical Center
🇺🇸
Portland, Oregon, United States
Siteman Cancer Center-South County
🇺🇸
Saint Louis, Missouri, United States
Siteman Cancer Center at Saint Peters Hospital
🇺🇸
Saint Peters, Missouri, United States
Abbott-Northwestern Hospital
🇺🇸
Minneapolis, Minnesota, United States
McLaren Cancer Institute-Central Michigan
🇺🇸
Mount Pleasant, Michigan, United States
Saint Mary Mercy Hospital
🇺🇸
Livonia, Michigan, United States
Abington Memorial Hospital
🇺🇸
Abington, Pennsylvania, United States
Providence Saint Joseph Medical Center/Disney Family Cancer Center
🇺🇸
Burbank, California, United States
Kaiser Permanente Oakland-Broadway
🇺🇸
Oakland, California, United States
Stanford Cancer Institute Palo Alto
🇺🇸
Palo Alto, California, United States
Sutter Cancer Centers Radiation Oncology Services-Roseville
🇺🇸
Roseville, California, United States
Stanford Cancer Center South Bay
🇺🇸
San Jose, California, United States
Saint Vincent's Medical Center
🇺🇸
Bridgeport, Connecticut, United States
UCHealth Memorial Hospital Central
🇺🇸
Colorado Springs, Colorado, United States
John H Stroger Jr Hospital of Cook County
🇺🇸
Chicago, Illinois, United States
Decatur Memorial Hospital
🇺🇸
Decatur, Illinois, United States
Saint Luke's Mountain States Tumor Institute - Nampa
🇺🇸
Nampa, Idaho, United States
Saint Luke's Mountain States Tumor Institute-Twin Falls
🇺🇸
Twin Falls, Idaho, United States
Methodist Medical Center of Illinois
🇺🇸
Peoria, Illinois, United States
Loyola University Medical Center
🇺🇸
Maywood, Illinois, United States
Edward Hines Jr VA Hospital
🇺🇸
Hines, Illinois, United States
Northwestern Medicine Cancer Center Warrenville
🇺🇸
Warrenville, Illinois, United States
Condell Memorial Hospital
🇺🇸
Libertyville, Illinois, United States
Carle Cancer Center
🇺🇸
Urbana, Illinois, United States
Memorial Medical Center
🇺🇸
Springfield, Illinois, United States
Community Cancer Center East
🇺🇸
Indianapolis, Indiana, United States
University of Kansas Cancer Center
🇺🇸
Kansas City, Kansas, United States
Lahey Hospital and Medical Center
🇺🇸
Burlington, Massachusetts, United States
UM Saint Joseph Medical Center
🇺🇸
Towson, Maryland, United States
MedStar Union Memorial Hospital
🇺🇸
Baltimore, Maryland, United States
UM Baltimore Washington Medical Center/Tate Cancer Center
🇺🇸
Glen Burnie, Maryland, United States
University of Maryland/Greenebaum Cancer Center
🇺🇸
Baltimore, Maryland, United States
Lowell General Hospital
🇺🇸
Lowell, Massachusetts, United States
Saint Joseph Mercy Chelsea
🇺🇸
Chelsea, Michigan, United States
Henry Ford Macomb Hospital-Clinton Township
🇺🇸
Clinton Township, Michigan, United States
21st Century Oncology MHP - Clarkston
🇺🇸
Clarkston, Michigan, United States
McLaren Cancer Institute-Clarkston
🇺🇸
Clarkston, Michigan, United States
Henry Ford West Bloomfield Hospital
🇺🇸
West Bloomfield, Michigan, United States
21st Century Oncology MHP - Troy
🇺🇸
Troy, Michigan, United States
Mayo Clinic Health System in Albert Lea
🇺🇸
Albert Lea, Minnesota, United States
Mayo Clinic Health Systems-Mankato
🇺🇸
Mankato, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸
Saint Louis Park, Minnesota, United States
Siteman Cancer Center at West County Hospital
🇺🇸
Creve Coeur, Missouri, United States
Missouri Baptist Medical Center
🇺🇸
Saint Louis, Missouri, United States
CoxHealth South Hospital
🇺🇸
Springfield, Missouri, United States
Community Medical Hospital
🇺🇸
Missoula, Montana, United States
Wentworth-Douglass Hospital
🇺🇸
Dover, New Hampshire, United States
Benefis Healthcare- Sletten Cancer Institute
🇺🇸
Great Falls, Montana, United States
Dartmouth Hitchcock Medical Center
🇺🇸
Lebanon, New Hampshire, United States
Ohio State University Comprehensive Cancer Center
🇺🇸
Columbus, Ohio, United States
Cleveland Clinic Cancer Center Strongsville
🇺🇸
Strongsville, Ohio, United States
McLaren Cancer Institute-Owosso
🇺🇸
Owosso, Michigan, United States
McLaren Cancer Institute-Northern Michigan
🇺🇸
Petoskey, Michigan, United States
Mercy Hospital Saint Louis
🇺🇸
Saint Louis, Missouri, United States
University Hospitals Parma Medical Center
🇺🇸
Parma, Ohio, United States
Crozer Regional Cancer Center at Brinton Lake
🇺🇸
Glen Mills, Pennsylvania, United States
Bryn Mawr Hospital
🇺🇸
Bryn Mawr, Pennsylvania, United States
Geisinger Medical Center
🇺🇸
Danville, Pennsylvania, United States
Thomas Jefferson University Hospital
🇺🇸
Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States
Aria Health-Torresdale Campus
🇺🇸
Philadelphia, Pennsylvania, United States
Temple University Hospital
🇺🇸
Philadelphia, Pennsylvania, United States
Reading Hospital
🇺🇸
West Reading, Pennsylvania, United States
Lankenau Medical Center
🇺🇸
Wynnewood, Pennsylvania, United States
Greenville Health System Cancer Institute-Faris
🇺🇸
Greenville, South Carolina, United States
Greenville Health System Cancer Institute-Eastside
🇺🇸
Greenville, South Carolina, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸
Sioux Falls, South Dakota, United States
The Radiation Oncology Center-Hilton Head/Bluffton
🇺🇸
Hilton Head Island, South Carolina, United States
Greenville Health System Cancer Institute-Spartanburg
🇺🇸
Spartanburg, South Carolina, United States
UTMB Cancer Center at Victory Lakes
🇺🇸
League City, Texas, United States
University of Texas Medical Branch
🇺🇸
Galveston, Texas, United States
M D Anderson Cancer Center
🇺🇸
Houston, Texas, United States
North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
🇺🇸
Yakima, Washington, United States
Wheeling Hospital/Schiffler Cancer Center
🇺🇸
Wheeling, West Virginia, United States
Mayo Clinic Health System-Eau Claire Clinic
🇺🇸
Eau Claire, Wisconsin, United States
Aurora BayCare Medical Center
🇺🇸
Green Bay, Wisconsin, United States
Aurora Cancer Care-Kenosha South
🇺🇸
Kenosha, Wisconsin, United States
UW Cancer Center Johnson Creek
🇺🇸
Johnson Creek, Wisconsin, United States
Gundersen Lutheran Medical Center
🇺🇸
La Crosse, Wisconsin, United States
Community Memorial Hospital
🇺🇸
Menomonee Falls, Wisconsin, United States
University of Wisconsin Hospital and Clinics
🇺🇸
Madison, Wisconsin, United States
Aurora Medical Center in Summit
🇺🇸
Summit, Wisconsin, United States
Aspirus Regional Cancer Center
🇺🇸
Wausau, Wisconsin, United States
Diagnostic and Treatment Center
🇺🇸
Weston, Wisconsin, United States
McGill University Department of Oncology
🇨🇦
Montreal, Quebec, Canada
CHUM - Centre Hospitalier de l'Universite de Montreal
🇨🇦
Montreal, Quebec, Canada
The Research Institute of the McGill University Health Centre (MUHC)
🇨🇦
Montreal, Quebec, Canada
Saskatoon Cancer Centre
🇨🇦
Saskatoon, Saskatchewan, Canada
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
🇨🇦
Sherbrooke, Quebec, Canada
Mercy Cancer Center - Sacramento
🇺🇸
Sacramento, California, United States
Sutter Medical Center Sacramento
🇺🇸
Sacramento, California, United States
Saint Joseph Mercy Hospital
🇺🇸
Ann Arbor, Michigan, United States
University of Nebraska Medical Center
🇺🇸
Omaha, Nebraska, United States
Ascension Columbia Saint Mary's Water Tower Medical Commons
🇺🇸
Milwaukee, Wisconsin, United States
Aurora Saint Luke's Medical Center
🇺🇸
Milwaukee, Wisconsin, United States
Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Aurora Sinai Medical Center
🇺🇸
Milwaukee, Wisconsin, United States
Zablocki Veterans Administration Medical Center
🇺🇸
Milwaukee, Wisconsin, United States
UF Cancer Center at Orlando Health
🇺🇸
Orlando, Florida, United States
Tulane University Health Sciences Center
🇺🇸
New Orleans, Louisiana, United States
Montefiore Medical Center - Moses Campus
🇺🇸
Bronx, New York, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸
Chapel Hill, North Carolina, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸
Richmond, Virginia, United States
Banner University Medical Center - Tucson
🇺🇸
Tucson, Arizona, United States
Mercy Health Mercy Campus
🇺🇸
Muskegon, Michigan, United States
UH Seidman Cancer Center at Southwest General Hospital
🇺🇸
Middleburg Heights, Ohio, United States
Crozer-Keystone Regional Cancer Center at Broomall
🇺🇸
Broomall, Pennsylvania, United States