Testing if High Dose Radiation Only to the Sites of Brain Cancer Compared to Whole Brain Radiation That Avoids the Hippocampus is Better at Preventing Loss of Memory and Thinking Ability
Start Date
6/8/2021
Completion Date
7/1/2030
Summary
This phase III trial compares the effect of stereotactic radiosurgery to standard of care memantine and whole brain radiation therapy that avoids the hippocampus (the memory zone of the brain) for the treatment of small cell lung cancer that has spread to the brain. Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue. Whole brain radiation therapy delivers a low dose of radiation to the entire brain including the normal brain tissue. Hippocampal avoidance during whole-brain radiation therapy (HA-WBRT) decreases the amount of radiation that is delivered to the hippocampus which is a brain structure that is important for memory. The drug, memantine, is also often given with whole brain radiotherapy because it may decrease the risk of side effects related to thinking and memory. Stereotactic radiosurgery may decrease side effects related to memory and thinking compared to standard of care HA-WBRT plus memantine.
Detailed Description
PRIMARY OBJECTIVE: I. Determine whether stereotactic radiosurgery (SRS) relative to whole brain radiotherapy with hippocampal avoidance (HA-WBRT) plus memantine hydrochloride (memantine) for brain metastases from small cell lung cancer (SCLC) prevents cognitive function failure as measured by cognitive decline on a battery of tests: the Hopkins Verbal Learning Test - Revised (HVLT-R), Controlled Oral Word Association (COWA) test, and the Trail Making Test (TMT). SECONDARY OBJECTIVES: I. Determine whether SRS relative to HA-WBRT plus memantine for brain metastases from SCLC preserves cognitive function as separately measured by the HVLT-R, COWA, TMT Parts A and B, and Clinical Trial Battery Composite (CTB COMP). II. Assess perceived difficulties in cognitive abilities using Patient Reported Outcomes Measurement Information System (PROMIS) after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC. III. Assess symptom burden using the MD Anderson Symptom Inventory for brain tumor (MDASI-BT) after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC. IV. Compare cumulative incidence of intracranial disease progression after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC. V. Compare overall survival after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC. VI. Compare cumulative incidence of neurologic death after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC. VII. Compare the number of salvage procedures used to manage recurrent intracranial disease following SRS relative to HA-WBRT plus memantine for SCLC brain metastases. VIII. Compare adverse events between the treatment arms according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 criteria. IX. Compare the risk of developing cerebral necrosis between SRS and HA-WBRT plus memantine in patients receiving concurrent immunotherapy. EXPLORATORY OBJECTIVES: I. Compare cumulative incidence of local brain recurrence, distant brain relapse, and leptomeningeal dissemination after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC. II. Compare the cost of brain-related therapies and quality-adjusted life years in patients who receive SRS relative to HA-WBRT plus memantine for brain metastases from SCLC. III. Evaluate the time delay to salvage WBRT or HA-WBRT in patients enrolled on the SRS arm. IV. Evaluate whether a time delay for chemotherapy has an effect on overall survival in patients receiving HA WBRT plus memantine relative to SRS for brain metastases from SCLC. V. Evaluate baseline magnetic resonance (MR) imaging biomarkers of white matter injury and hippocampal volumetry as potential predictors of cognitive decline and differential benefit from SRS relative to HA-WBRT plus memantine for brain metastases from SCLC. VI. Evaluate the correlation between neurocognitive functioning and patient-reported outcomes. VII. Collect serum, plasma and imaging studies for future translational research analyses. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo SRS over 1 day (in some cases several days). ARM II: Patients undergo HA-WBRT once daily (QD) for 2 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive memantine orally (PO) QD or twice daily (BID) for up to 24 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and magnetic resonance imaging (MRI) throughout the study. After completion of study treatment, patients are followed up every 2-3 months for 1 year, and then every 6 months thereafter.
Eligibility Criteria
Age Range: 18 years to No maximum
Interventions
Biospecimen Collection
Magnetic Resonance Imaging
Memantine Hydrochloride
Neurocognitive Assessment
Stereotactic Radiosurgery
Survey Administration
Whole-Brain Radiotherapy
Conditions
Locations
Mayo Clinic Hospital in Arizona
Phoenix, Arizona 85054
United States
Kaiser Permanente-Anaheim
Anaheim, California 92806
United States
Kaiser Permanente-Bellflower
Bellflower, California 90706
United States
Kaiser Permanente Los Angeles Medical Center
Los Angeles, California 90027
United States
Los Angeles General Medical Center
Los Angeles, California 90033
United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California 90033
United States
Kaiser Permanente-Ontario
Ontario, California 91761
United States
UCHealth University of Colorado Hospital
Aurora, Colorado 80045
United States
UCHealth Memorial Hospital Central
Colorado Springs, Colorado 80909
United States
Memorial Hospital North
Colorado Springs, Colorado 80920
United States
Smilow Cancer Hospital Care Center at Greenwich
Greenwich, Connecticut 06830
United States
Smilow Cancer Hospital Care Center - Guilford
Guilford, Connecticut 06437
United States
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut 06510
United States
Yale University
New Haven, Connecticut 06520
United States
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut 06611
United States
Smilow Cancer Hospital Care Center - Waterford
Waterford, Connecticut 06385
United States
Beebe Medical Center
Lewes, Delaware 19958
United States
Delaware Clinical and Laboratory Physicians PA
Newark, Delaware 19713
United States
Helen F Graham Cancer Center
Newark, Delaware 19713
United States
Medical Oncology Hematology Consultants PA
Newark, Delaware 19713
United States
Christiana Care Health System-Christiana Hospital
Newark, Delaware 19718
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Beebe Health Campus
Rehoboth Beach, Delaware 19971
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Christiana Care Health System-Wilmington Hospital
Wilmington, Delaware 19801
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UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida 33146
United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida 33442
United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida 32610
United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida 33136
United States
Moffitt Cancer Center-International Plaza
Tampa, Florida 33607
United States
Moffitt Cancer Center - McKinley Campus
Tampa, Florida 33612
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Moffitt Cancer Center
Tampa, Florida 33612
United States
Moffitt Cancer Center at Wesley Chapel
Wesley Chapel, Florida 33544
United States
Emory University Hospital Midtown
Atlanta, Georgia 30308
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Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia 30322
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Emory Saint Joseph's Hospital
Atlanta, Georgia 30342
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Northside Hospital
Atlanta, Georgia 30342
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Northside Hospital-Cherokee
Canton, Georgia 30115
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Northside Hospital-Forsyth
Cumming, Georgia 30041
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Memorial Health University Medical Center
Savannah, Georgia 31404
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Rush-Copley Medical Center
Aurora, Illinois 60504
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Centralia Oncology Clinic
Centralia, Illinois 62801
United States
Rush MD Anderson Cancer Center
Chicago, Illinois 60612
United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois 60637
United States
Carle at The Riverfront
Danville, Illinois 61832
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Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois 62526
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Decatur Memorial Hospital
Decatur, Illinois 62526
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Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois 60115
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Carle Physician Group-Effingham
Effingham, Illinois 62401
United States
Crossroads Cancer Center
Effingham, Illinois 62401
United States
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois 60134
United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois 61938
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UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois 60451
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Cancer Care Center of O'Fallon
O'Fallon, Illinois 62269
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HSHS Saint Elizabeth's Hospital
O'Fallon, Illinois 62269
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OSF Saint Francis Medical Center
Peoria, Illinois 61637
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Carle Cancer Center
Urbana, Illinois 61801
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The Carle Foundation Hospital
Urbana, Illinois 61801
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Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois 60555
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IU Health West Hospital
Avon, Indiana 46123
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IU Health North Hospital
Carmel, Indiana 46032
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Goshen Center for Cancer Care
Goshen, Indiana 46526
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Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana 46202
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IU Health Methodist Hospital
Indianapolis, Indiana 46202
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Mary Greeley Medical Center
Ames, Iowa 50010
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McFarland Clinic - Ames
Ames, Iowa 50010
United States
Baptist Health Lexington
Lexington, Kentucky 40503
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The James Graham Brown Cancer Center at University of Louisville
Louisville, Kentucky 40202
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UofL Health Medical Center Northeast
Louisville, Kentucky 40245
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Mary Bird Perkins Cancer Center
Baton Rouge, Louisiana 70809
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Luminis Health Anne Arundel Medical Center
Annapolis, Maryland 21401
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University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland 21201
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MedStar Franklin Square Medical Center/Weinberg Cancer Institute
Baltimore, Maryland 21237
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UM Upper Chesapeake Medical Center
Bel Air, Maryland 21014
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Central Maryland Radiation Oncology in Howard County
Columbia, Maryland 21044
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University of Maryland Shore Medical Center at Easton
Easton, Maryland 21601
United States
UM Baltimore Washington Medical Center/Tate Cancer Center
Glen Burnie, Maryland 21061
United States
TidalHealth Richard A Henson Cancer Institute
Ocean Pines, Maryland 21811
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TidalHealth Peninsula Regional
Salisbury, Maryland 21801
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Boston Medical Center
Boston, Massachusetts 02118
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Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan 48106
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McLaren Cancer Institute-Bay City
Bay City, Michigan 48706
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Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan 48114
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Trinity Health Medical Center - Brighton
Brighton, Michigan 48114
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Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan 48188
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Trinity Health Medical Center - Canton
Canton, Michigan 48188
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Caro Cancer Center
Caro, Michigan 48723
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Chelsea Hospital
Chelsea, Michigan 48118
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Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan 48118
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Wayne State University/Karmanos Cancer Institute
Detroit, Michigan 48201
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Weisberg Cancer Treatment Center
Farmington Hills, Michigan 48334
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McLaren Cancer Institute-Flint
Flint, Michigan 48532
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Karmanos Cancer Institute at McLaren Greater Lansing
Lansing, Michigan 48910
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McLaren Cancer Institute-Lapeer Region
Lapeer, Michigan 48446
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Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan 48154
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Saint Mary's Oncology/Hematology Associates of Marlette
Marlette, Michigan 48453
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McLaren Cancer Institute-Macomb
Mount Clemens, Michigan 48043
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Mount Pleasant, Michigan 48858
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McLaren Cancer Institute-Northern Michigan
Petoskey, Michigan 49770
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McLaren-Port Huron
Port Huron, Michigan 48060
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MyMichigan Medical Center Saginaw
Saginaw, Michigan 48601
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Oncology Hematology Associates of Saginaw Valley PC
Saginaw, Michigan 48604
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MyMichigan Medical Center Tawas
Tawas City, Michigan 48764
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Saint Mary's Oncology/Hematology Associates of West Branch
West Branch, Michigan 48661
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Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan 48197
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Sanford Joe Lueken Cancer Center
Bemidji, Minnesota 56601
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Burnsville, Minnesota 55337
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Mercy Hospital
Coon Rapids, Minnesota 55433
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Coon Rapids, Minnesota 55433
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Fairview Southdale Hospital
Edina, Minnesota 55435
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Edina, Minnesota 55435
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Unity Hospital
Fridley, Minnesota 55432
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Fairview Clinics and Surgery Center Maple Grove
Maple Grove, Minnesota 55369
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Minnesota Oncology - Maple Grove
Maple Grove, Minnesota 55369
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Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota 55109
United States
Abbott-Northwestern Hospital
Minneapolis, Minnesota 55407
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Monticello Cancer Center
Monticello, Minnesota 55362
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Coborn Cancer Center at Saint Cloud Hospital
Saint Cloud, Minnesota 56303
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Regions Hospital
Saint Paul, Minnesota 55101
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United Hospital
Saint Paul, Minnesota 55102
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Lakeview Hospital
Stillwater, Minnesota 55082
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Minnesota Oncology Hematology PA-Woodbury
Woodbury, Minnesota 55125
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Saint Francis Medical Center
Cape Girardeau, Missouri 63703
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Parkland Health Center - Farmington
Farmington, Missouri 63640
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Freeman Health System
Joplin, Missouri 64804
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Sainte Genevieve County Memorial Hospital
Sainte Genevieve, Missouri 63670
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Mercy Hospital Springfield
Springfield, Missouri 65804
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Missouri Baptist Medical Center
St Louis, Missouri 63131
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Missouri Baptist Sullivan Hospital
Sullivan, Missouri 63080
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BJC Outpatient Center at Sunset Hills
Sunset Hills, Missouri 63127
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Billings Clinic Cancer Center
Billings, Montana 59101
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Benefis Sletten Cancer Institute
Great Falls, Montana 59405
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Logan Health Medical Center
Kalispell, Montana 59901
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Cooper Hospital University Medical Center
Camden, New Jersey 08103
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Sands Cancer Center
Canandaigua, New York 14424
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Northwell Health/Center for Advanced Medicine
Lake Success, New York 11042
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Northern Westchester Hospital
Mount Kisco, New York 10549
United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York 10032
United States
Upstate Cancer Center Radiation Oncology at Oswego
Oswego, New York 13126
United States
Wilmot Cancer Institute Radiation Oncology at Greece
Rochester, New York 14606
United States
University of Rochester
Rochester, New York 14642
United States
State University of New York Upstate Medical University
Syracuse, New York 13210
United States
Upstate Cancer Center at Hill Radiation Oncology
Syracuse, New York 13210
United States
Montefiore Medical Center-Einstein Campus
The Bronx, New York 10461
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Montefiore Medical Center-Weiler Hospital
The Bronx, New York 10461
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Montefiore Medical Center - Moses Campus
The Bronx, New York 10467
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Upstate Cancer Center at Verona
Verona, New York 13478
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Wilmot Cancer Institute at Webster
Webster, New York 14580
United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina 27157
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Sanford Bismarck Medical Center
Bismarck, North Dakota 58501
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Sanford Broadway Medical Center
Fargo, North Dakota 58122
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Sanford Roger Maris Cancer Center
Fargo, North Dakota 58122
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UH Seidman Cancer Center at UH Avon Health Center
Avon, Ohio 44011
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University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio 45219
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Case Western Reserve University
Cleveland, Ohio 44106
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Ohio State University Comprehensive Cancer Center
Columbus, Ohio 43210
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Riverside Methodist Hospital
Columbus, Ohio 43214
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Grant Medical Center
Columbus, Ohio 43215
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Delaware Health Center-Grady Cancer Center
Delaware, Ohio 43015
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Grady Memorial Hospital
Delaware, Ohio 43015
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UH Seidman Cancer Center at Lake Health Mentor Campus
Mentor, Ohio 44060
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Mercy Health - Perrysburg Hospital
Perrysburg, Ohio 43551
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Mercy Health - Saint Anne Hospital
Toledo, Ohio 43623
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University of Cincinnati Cancer Center-West Chester
West Chester, Ohio 45069
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University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
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Saint Luke's Cancer Center - Allentown
Allentown, Pennsylvania 18104
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UPMC Altoona
Altoona, Pennsylvania 16601
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UPMC-Heritage Valley Health System Beaver
Beaver, Pennsylvania 15009
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Saint Luke's University Hospital-Bethlehem Campus
Bethlehem, Pennsylvania 18015
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Carlisle Regional Cancer Center
Carlisle, Pennsylvania 17015
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Christiana Care Health System-Concord Health Center
Chadds Ford, Pennsylvania 19317
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Chambersburg Hospital
Chambersburg, Pennsylvania 17201
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Geisinger Medical Center
Danville, Pennsylvania 17822
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Saint Luke's Hospital-Anderson Campus
Easton, Pennsylvania 18045
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Ephrata Cancer Center
Ephrata, Pennsylvania 17522
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UPMC Hillman Cancer Center Erie
Erie, Pennsylvania 16505
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Saint Vincent Hospital
Erie, Pennsylvania 16544
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UPMC Cancer Center at UPMC Horizon
Farrell, Pennsylvania 16121
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Adams Cancer Center
Gettysburg, Pennsylvania 17325
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UPMC Cancer Centers - Arnold Palmer Pavilion
Greensburg, Pennsylvania 15601
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UPMC Pinnacle Cancer Center/Community Osteopathic Campus
Harrisburg, Pennsylvania 17109
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Sechler Family Cancer Center
Lebanon, Pennsylvania 17042
United States
Geisinger Medical Oncology-Lewisburg
Lewisburg, Pennsylvania 17837
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UPMC Cancer Center - Monroeville
Monroeville, Pennsylvania 15146
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Thomas Jefferson University Hospital
Philadelphia, Pennsylvania 19107
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Jefferson Torresdale Hospital
Philadelphia, Pennsylvania 19114
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Allegheny General Hospital
Pittsburgh, Pennsylvania 15212
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UPMC-Magee Womens Hospital
Pittsburgh, Pennsylvania 15213
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UPMC-Presbyterian Hospital
Pittsburgh, Pennsylvania 15213
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UPMC-Saint Margaret
Pittsburgh, Pennsylvania 15215
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UPMC-Shadyside Hospital
Pittsburgh, Pennsylvania 15232
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UPMC-Passavant Hospital
Pittsburgh, Pennsylvania 15237
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UPMC-Saint Clair Hospital Cancer Center
Pittsburgh, Pennsylvania 15243
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Saint Luke's Hospital - Upper Bucks Campus
Quakertown, Pennsylvania 18951
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Saint Luke's Hospital-Quakertown Campus
Quakertown, Pennsylvania 18951
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Saint Luke's Hospital - Monroe Campus
Stroudsburg, Pennsylvania 18360
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Geisinger Wyoming Valley/Henry Cancer Center
Wilkes-Barre, Pennsylvania 18711
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Divine Providence Hospital
Williamsport, Pennsylvania 17754
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WellSpan Health-York Cancer Center
York, Pennsylvania 17403
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WellSpan Health-York Hospital
York, Pennsylvania 17403
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UPMC Memorial
York, Pennsylvania 17408
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McLeod Regional Medical Center
Florence, South Carolina 29506
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Gibbs Cancer Center-Gaffney
Gaffney, South Carolina 29341
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Self Regional Healthcare
Greenwood, South Carolina 29646
United States
Gibbs Cancer Center-Pelham
Greer, South Carolina 29651
United States
Spartanburg Medical Center
Spartanburg, South Carolina 29303
United States
SMC Center for Hematology Oncology Union
Union, South Carolina 29379
United States
Sanford Cancer Center Oncology Clinic
Sioux Falls, South Dakota 57104
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Avera Cancer Institute
Sioux Falls, South Dakota 57105
United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota 57117-5134
United States
MD Anderson in The Woodlands
Conroe, Texas 77384
United States
UT MD Anderson Cancer Center
Houston, Texas 77030
United States
MD Anderson West Houston
Houston, Texas 77079
United States
UT MD Anderson - League City
League City, Texas 77573
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MD Anderson in Sugar Land
Sugar Land, Texas 77478
United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia 23298
United States
Langlade Hospital and Cancer Center
Antigo, Wisconsin 54409
United States
ThedaCare Regional Cancer Center
Appleton, Wisconsin 54911
United States
Gundersen Lutheran Medical Center
La Crosse, Wisconsin 54601
United States
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin 53718
United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin 53792
United States
Froedtert Menomonee Falls Hospital
Menomonee Falls, Wisconsin 53051
United States
Medical College of Wisconsin
Milwaukee, Wisconsin 53226
United States
Cancer Center of Western Wisconsin
New Richmond, Wisconsin 54017
United States
Drexel Town Square Health Center
Oak Creek, Wisconsin 53154
United States
Aspirus Cancer Care - James Beck Cancer Center
Rhinelander, Wisconsin 54501
United States
Aspirus Cancer Care - Stevens Point
Stevens Point, Wisconsin 54481
United States
Aspirus Regional Cancer Center
Wausau, Wisconsin 54401
United States
Froedtert West Bend Hospital/Kraemer Cancer Center
West Bend, Wisconsin 53095
United States
University Health Network-Princess Margaret Hospital
Toronto, Ontario M5G 2M9
Canada
CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)
Québec, Quebec G1R 2J6
Canada
Allan Blair Cancer Centre
Regina, Saskatchewan S4T 7T1
Canada
Saskatoon Cancer Centre
Saskatoon, Saskatchewan S7N 4H4
Canada