Comparing the Addition of Radiation Either Before or After Surgery for Patients With Brain Metastases
- Conditions
- Metastatic Malignant Neoplasm in the Brain
- Interventions
- Procedure: Brain SurgeryOther: Quality-of-Life AssessmentOther: Questionnaire AdministrationRadiation: Stereotactic Radiosurgery
- Registration Number
- NCT05438212
- Lead Sponsor
- NRG Oncology
- Brief Summary
This phase III trial compares the usual treatment of surgery after stereotactic radiosurgery (SRS) to receiving SRS before surgery in treating patients with cancer that has spread to the brain (brain metastases). Stereotactic radiosurgery is a type of radiation therapy that delivers a high dose of radiation to target tumors and minimizes effect on normal surrounding brain tissue. The combination of surgery and radiation may stop the tumor from growing for a few months or longer and may reduce symptoms of brain metastases. This study investigates whether treating with SRS before surgery may be better than SRS after surgery in reducing the possibility of the tumor coming back, reducing or preventing the cancer from spreading to other areas of the brain and reducing the risk of scarring on the brain from radiation.
- Detailed Description
PRIMARY OBJECTIVE:
I. To determine if the time to composite adverse endpoint (CAE) (defined as: 1) local tumor progression within the surgical bed; and/or 2) adverse radiation effect \[ARE\], the imaging correlate of post-stereotactic radiosurgery \[SRS\] radiation necrosis; and/or 3) nodular meningeal disease \[nMD\]) is improved in patients treated with pre-resection SRS to the intact lesion versus those treated with post-resection SRS.
SECONDARY OBJECTIVES:
I. To assess the trajectory of symptom burden in patients treated with pre-resection SRS to the intact lesion versus those treated to the post-resection surgical cavity as measured by MD Anderson Symptom Inventory for brain tumor (MDASI-BT).
II. To determine whether there is improved overall survival (OS) in patients with resected brain metastases who undergo pre-resection SRS compared to patients who receive post-resection SRS.
III. To compare rates of ARE, the imaging correlate of radiation necrosis, in patients who receive pre-resection SRS to patients who receive post-resection SRS.
IV. To determine whether there is increased time to whole brain radiotherapy (WBRT) in patients who receive pre-resection SRS compared to patients who receive post-resection SRS.
V. To assess the trajectory of neuro-cognitive function in patients treated with pre-resection SRS to the intact lesion versus those treated to the post-resection surgical cavity as measured by the Montreal Cognitive Assessment (MoCA).
VI. To compare rates of nodular meningeal disease in patients who receive pre-resection SRS to patients who receive post-resection SRS.
VII. To compare rates of local recurrence in the resection cavity for patients who receive pre-resection SRS to patients who receive post-resection SRS.
VIII. To compare rates of local recurrence of intact, non-index metastases treated with SRS.
IX. To compare rates of distant brain failure in patients who receive pre-resection SRS to patients who receive post-resection SRS.
X. To assess toxicity in the two treatment arms.
EXPLORATORY OBJECTIVE:
I. To explore if the type of surgical resection (piece-meal versus \[vs.\] en-bloc) may be associated with the rate of nodular meningeal disease.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients undergo surgery per standard of care. Within 10-30 days after surgery, patients undergo stereotactic radiosurgery for 1 fraction.
ARM II: Within 7 days before surgery, patients undergo stereotactic radiosurgery for 1 fraction. Patients undergo surgery per standard of care.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for additional 2 years.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 236
-
Radiographic confirmation of 1-4 brain metastases, one of which requires resection, as defined by magnetic resonance imaging (MRI) with contrast obtained within 14 days prior to registration
- The maximum diameter of the lesion to be resected on the post-contrast MRI, as measured on any orthogonal plane (axial, sagittal, coronal), must measure >= 2.0 cm and =< 5.0 cm.
- The maximum diameter of any lesions which will not be resected must be =< 4.0 cm in maximum diameter
-
Known active or history of invasive non-central nervous system (CNS) primary cancer based on documented pathologic diagnosis within the past 3 years
-
All brain metastases must be located >= 5 mm from the optic chiasm and outside the brainstem
-
Patient is able to medically tolerate surgery and SRS
-
Lesions chosen for surgical therapy must be deemed appropriate targets for safe, gross total resection by the treating surgeon
-
History/physical examination within 14 days prior to registration
-
Age >= 18
-
Karnofsky performance status (KPS) >= 60 within 14 days prior to registration
-
A negative urine or serum pregnancy test (in persons of childbearing potential) within =< 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
-
Participants who are sexually active must agree to use medically acceptable forms of contraception during treatment on this study to prevent pregnancy
-
The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
-
Prior cranial radiotherapy, including whole brain radiotherapy, or SRS to the resection site
- Note: The index lesion to be resected cannot have been previously treated with SRS (i.e. repeat radiosurgery to the same location/lesion is not allowed on this protocol). Previous SRS to other lesions is allowed
-
Evidence of leptomeningeal disease (LMD)
- Note: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive cerebrospinal fluid (CSF) cytology and/or unequivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion
-
Any medical conditions which would make this protocol unreasonably hazardous, including, but not limited to: contraindications to general endotracheal anesthesia; intracranial surgery; and stereotactic radiosurgery
-
Primary histology of germ cell tumor, small cell carcinoma or lymphoma
-
More than one brain metastasis planned for resection
-
Inability to undergo MRI with contrast
-
Planned administration of cytotoxic chemotherapy or tyrosine/multi-kinase inhibitors within the 3 days prior to, the day of, or within 3 days after the completion of SRS
- Note: chemotherapy and immunotherapy outside of this window are allowed
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I (surgery, stereotactic radiosurgery) Questionnaire Administration Patients undergo surgery per standard of care. Within 10-30 days after surgery, patients undergo stereotactic radiosurgery for 1 fraction. Arm II (stereotactic radiosurgery, surgery) Brain Surgery Within 7 days before surgery, patients undergo stereotactic radiosurgery for 1 fraction. Patients undergo surgery per standard of care. Arm I (surgery, stereotactic radiosurgery) Quality-of-Life Assessment Patients undergo surgery per standard of care. Within 10-30 days after surgery, patients undergo stereotactic radiosurgery for 1 fraction. Arm I (surgery, stereotactic radiosurgery) Stereotactic Radiosurgery Patients undergo surgery per standard of care. Within 10-30 days after surgery, patients undergo stereotactic radiosurgery for 1 fraction. Arm II (stereotactic radiosurgery, surgery) Quality-of-Life Assessment Within 7 days before surgery, patients undergo stereotactic radiosurgery for 1 fraction. Patients undergo surgery per standard of care. Arm II (stereotactic radiosurgery, surgery) Questionnaire Administration Within 7 days before surgery, patients undergo stereotactic radiosurgery for 1 fraction. Patients undergo surgery per standard of care. Arm I (surgery, stereotactic radiosurgery) Brain Surgery Patients undergo surgery per standard of care. Within 10-30 days after surgery, patients undergo stereotactic radiosurgery for 1 fraction. Arm II (stereotactic radiosurgery, surgery) Stereotactic Radiosurgery Within 7 days before surgery, patients undergo stereotactic radiosurgery for 1 fraction. Patients undergo surgery per standard of care.
- Primary Outcome Measures
Name Time Method Time to composite adverse endpoint (CAE) Time from surgery (with the post-operative MRI as the 'baseline' for purposes of disease assessment) to local tumor progression (within the surgical bed), nodular meningeal disease, or radiation necrosis, whichever occurs first, assessed up to 4 years Analysis for this endpoint will consist of testing the cause-specific hazard ratio in a Cox proportional hazards model.
- Secondary Outcome Measures
Name Time Method Overall survival (OS) Time from randomization to death due to any cause, assessed up to 4 years Analysis for this endpoint will consist of estimation of the OS distribution of each treatment arm via the Kaplan-Meier method and a stratified log-rank test.
Rate of local tumor progression Up to 4 years The time origin for these imaging-based endpoints will be time of surgery (with the post-operative magnetic resonance imaging \[MRI\] as the 'baseline' for purposes of disease assessment). These analyses will involve estimating the cumulative incidence function of local progression, radiation necrosis, nodular meningeal disease, and distant brain failures in the presence of competing event of deaths. The Gray's test will be used to evaluate the difference in the distribution of local progression between treatment arms.
Rate of radiation necrosis Up to 4 years The time origin for these imaging-based endpoints will be time of surgery (with the post-operative MRI as the 'baseline' for purposes of disease assessment). These analyses will involve estimating the cumulative incidence function of local progression, radiation necrosis, nodular meningeal disease, and distant brain failures in the presence of competing event of deaths. The Gray's test will be used to evaluate the difference in the distribution of radiation necrosis between treatment arms.
Rate of nodular meningeal disease Up to 4 years The time origin for these imaging-based endpoints will be time of surgery (with the post-operative MRI as the 'baseline' for purposes of disease assessment). These analyses will involve estimating the cumulative incidence function of local progression, radiation necrosis, nodular meningeal disease, and distant brain failures in the presence of competing event of deaths. The Gray's test will be used to evaluate the difference in the distribution of nodular meningeal disease between treatment arms.
Rate of distant brain failures Up to 4 years The time origin for these imaging-based endpoints will be time of surgery (with the post-operative MRI as the 'baseline' for purposes of disease assessment). These analyses will involve estimating the cumulative incidence function of local progression, radiation necrosis, nodular meningeal disease, and distant brain failures in the presence of competing event of deaths. The Gray's test will be used to evaluate the difference in the distribution of distant brain failures between treatment arms.
Frequency of adverse events (AEs) Up to 4 years AEs will be graded according to Common Terminology Criteria for Adverse Events version 5.0. Comprehensive summaries of all AEs by treatment arm will be generated and examined. Counts and frequencies of worst (highest score) AE per patient will be presented overall and by AE type category, separately by assigned treatment group. The proportion of patients with at least one grade 3 or higher AE will be compared between treatment arms. Any frequencies to be tested will be evaluated using the chi-square or exact test as appropriate, with two-sided significance level 0.05.
Change in MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT) Baseline up to 2 years after surgery Will implement mixed effects models for repeated measures to evaluate the MDASI-BT scores longitudinally.
Change in cognitive function Baseline up to 2 years after surgery Measured by Montreal Cognitive Assessment (MoCA). Will implement mixed effects models for repeated measures to evaluate the MoCA scores longitudinally.
Trial Locations
- Locations (191)
Piedmont Hospital
🇺🇸Atlanta, Georgia, United States
Saint Joseph's Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
Banner University Medical Center - Tucson
🇺🇸Tucson, Arizona, United States
University of Arizona Cancer Center-North Campus
🇺🇸Tucson, Arizona, United States
Kaiser Permanente-Anaheim
🇺🇸Anaheim, California, United States
Sutter Auburn Faith Hospital
🇺🇸Auburn, California, United States
Sutter Cancer Centers Radiation Oncology Services-Auburn
🇺🇸Auburn, California, United States
Kaiser Permanente-Bellflower
🇺🇸Bellflower, California, United States
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
🇺🇸Irvine, California, United States
Kaiser Permanente Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
Memorial Medical Center
🇺🇸Modesto, California, United States
Kaiser Permanente-Ontario
🇺🇸Ontario, California, United States
Saint Joseph Hospital - Orange
🇺🇸Orange, California, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
🇺🇸Orange, California, United States
Stanford Cancer Institute Palo Alto
🇺🇸Palo Alto, California, United States
Sutter Cancer Centers Radiation Oncology Services-Roseville
🇺🇸Roseville, California, United States
Sutter Roseville Medical Center
🇺🇸Roseville, California, United States
Sutter Medical Center Sacramento
🇺🇸Sacramento, California, United States
University of California Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
California Pacific Medical Center-Pacific Campus
🇺🇸San Francisco, California, United States
UCSF Medical Center-Parnassus
🇺🇸San Francisco, California, United States
Sutter Pacific Medical Foundation
🇺🇸Santa Rosa, California, United States
Sutter Solano Medical Center/Cancer Center
🇺🇸Vallejo, California, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
🇺🇸Coral Gables, Florida, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
🇺🇸Deerfield Beach, Florida, United States
Mayo Clinic in Florida
🇺🇸Jacksonville, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Miami Cancer Institute
🇺🇸Miami, Florida, United States
Moffitt Cancer Center-International Plaza
🇺🇸Tampa, Florida, United States
Moffitt Cancer Center - McKinley Campus
🇺🇸Tampa, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Moffitt Cancer Center at Wesley Chapel
🇺🇸Wesley Chapel, Florida, United States
Grady Health System
🇺🇸Atlanta, Georgia, United States
Emory University Hospital Midtown
🇺🇸Atlanta, Georgia, United States
Emory University Hospital/Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Emory Saint Joseph's Hospital
🇺🇸Atlanta, Georgia, United States
Advocate Outpatient Center - Aurora
🇺🇸Aurora, Illinois, United States
Advocate Good Shepherd Hospital
🇺🇸Barrington, Illinois, United States
Centralia Oncology Clinic
🇺🇸Centralia, Illinois, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
AMG Crystal Lake - Oncology
🇺🇸Crystal Lake, Illinois, United States
Carle at The Riverfront
🇺🇸Danville, Illinois, United States
Cancer Care Specialists of Illinois - Decatur
🇺🇸Decatur, Illinois, United States
Decatur Memorial Hospital
🇺🇸Decatur, Illinois, United States
Advocate Good Samaritan Hospital
🇺🇸Downers Grove, Illinois, United States
Carle Physician Group-Effingham
🇺🇸Effingham, Illinois, United States
Crossroads Cancer Center
🇺🇸Effingham, Illinois, United States
Elmhurst Memorial Hospital
🇺🇸Elmhurst, Illinois, United States
Advocate South Suburban Hospital
🇺🇸Hazel Crest, Illinois, United States
AMG Libertyville - Oncology
🇺🇸Libertyville, Illinois, United States
Carle Physician Group-Mattoon/Charleston
🇺🇸Mattoon, Illinois, United States
Edward Hospital/Cancer Center
🇺🇸Naperville, Illinois, United States
UC Comprehensive Cancer Center at Silver Cross
🇺🇸New Lenox, Illinois, United States
Cancer Care Center of O'Fallon
🇺🇸O'Fallon, Illinois, United States
Advocate Christ Medical Center
🇺🇸Oak Lawn, Illinois, United States
Advocate Lutheran General Hospital
🇺🇸Park Ridge, Illinois, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
Springfield Clinic
🇺🇸Springfield, Illinois, United States
Springfield Memorial Hospital
🇺🇸Springfield, Illinois, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Northwestern Medicine Cancer Center Warrenville
🇺🇸Warrenville, Illinois, United States
Ascension Saint Vincent Indianapolis Hospital
🇺🇸Indianapolis, Indiana, United States
UI Health Care Mission Cancer and Blood - Ankeny Clinic
🇺🇸Ankeny, Iowa, United States
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
🇺🇸Clive, Iowa, United States
Iowa Methodist Medical Center
🇺🇸Des Moines, Iowa, United States
UI Health Care Mission Cancer and Blood - Des Moines Clinic
🇺🇸Des Moines, Iowa, United States
UI Health Care Mission Cancer and Blood - Laurel Clinic
🇺🇸Des Moines, Iowa, United States
UI Health Care Mission Cancer and Blood - Waukee Clinic
🇺🇸Waukee, Iowa, United States
University of Maryland/Greenebaum Cancer Center
🇺🇸Baltimore, Maryland, United States
UM Baltimore Washington Medical Center/Tate Cancer Center
🇺🇸Glen Burnie, Maryland, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Weisberg Cancer Treatment Center
🇺🇸Farmington Hills, Michigan, United States
Corewell Health William Beaumont University Hospital
🇺🇸Royal Oak, Michigan, United States
Corewell Health Beaumont Troy Hospital
🇺🇸Troy, Michigan, United States
Essentia Health Saint Joseph's Medical Center
🇺🇸Brainerd, Minnesota, United States
Essentia Health - Deer River Clinic
🇺🇸Deer River, Minnesota, United States
Essentia Health Cancer Center
🇺🇸Duluth, Minnesota, United States
Essentia Health Saint Mary's Medical Center
🇺🇸Duluth, Minnesota, United States
Miller-Dwan Hospital
🇺🇸Duluth, Minnesota, United States
Essentia Health Hibbing Clinic
🇺🇸Hibbing, Minnesota, United States
Coborn Cancer Center at Saint Cloud Hospital
🇺🇸Saint Cloud, Minnesota, United States
Essentia Health Sandstone
🇺🇸Sandstone, Minnesota, United States
Essentia Health Virginia Clinic
🇺🇸Virginia, Minnesota, United States
Parkland Health Center - Farmington
🇺🇸Farmington, Missouri, United States
Saint Luke's Hospital of Kansas City
🇺🇸Kansas City, Missouri, United States
Missouri Baptist Medical Center
🇺🇸Saint Louis, Missouri, United States
Sainte Genevieve County Memorial Hospital
🇺🇸Sainte Genevieve, Missouri, United States
Mercy Hospital Springfield
🇺🇸Springfield, Missouri, United States
Missouri Baptist Sullivan Hospital
🇺🇸Sullivan, Missouri, United States
BJC Outpatient Center at Sunset Hills
🇺🇸Sunset Hills, Missouri, United States
Billings Clinic Cancer Center
🇺🇸Billings, Montana, United States
Benefis Sletten Cancer Institute
🇺🇸Great Falls, Montana, United States
Renown Regional Medical Center
🇺🇸Reno, Nevada, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
🇺🇸Lebanon, New Hampshire, United States
Cooper Hospital University Medical Center
🇺🇸Camden, New Jersey, United States
Saint Barnabas Medical Center
🇺🇸Livingston, New Jersey, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Newark Beth Israel Medical Center
🇺🇸Newark, New Jersey, United States
The Valley Hospital - Luckow Pavilion
🇺🇸Paramus, New Jersey, United States
Capital Health Medical Center-Hopewell
🇺🇸Pennington, New Jersey, United States
Valley Health System Ridgewood Campus
🇺🇸Ridgewood, New Jersey, United States
Community Medical Center
🇺🇸Toms River, New Jersey, United States
Valley Health System-Hematology/Oncology
🇺🇸Westwood, New Jersey, United States
Montefiore Medical Center-Einstein Campus
🇺🇸Bronx, New York, United States
Montefiore Medical Center-Weiler Hospital
🇺🇸Bronx, New York, United States
Montefiore Medical Center - Moses Campus
🇺🇸Bronx, New York, United States
New York-Presbyterian/Brooklyn Methodist Hospital
🇺🇸Brooklyn, New York, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
The New York Hospital Medical Center of Queens
🇺🇸Flushing, New York, United States
Northern Westchester Hospital
🇺🇸Mount Kisco, New York, United States
Mount Sinai Chelsea
🇺🇸New York, New York, United States
Mount Sinai West
🇺🇸New York, New York, United States
Mount Sinai Hospital
🇺🇸New York, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
🇺🇸New York, New York, United States
Manhattan Eye Ear and Throat Hospital
🇺🇸New York, New York, United States
NYP/Weill Cornell Medical Center
🇺🇸New York, New York, United States
Lenox Hill Hospital
🇺🇸New York, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
Stony Brook University Medical Center
🇺🇸Stony Brook, New York, United States
Good Samaritan University Hospital
🇺🇸West Islip, New York, United States
Carolinas Medical Center/Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Atrium Health Cabarrus/LCI-Concord
🇺🇸Concord, North Carolina, United States
CaroMont Regional Medical Center
🇺🇸Gastonia, North Carolina, United States
Novant Health Cancer Institute Radiation Oncology - Wilmington
🇺🇸Wilmington, North Carolina, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Sanford Broadway Medical Center
🇺🇸Fargo, North Dakota, United States
Sanford Roger Maris Cancer Center
🇺🇸Fargo, North Dakota, United States
Indu and Raj Soin Medical Center
🇺🇸Beavercreek, Ohio, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Riverside Methodist Hospital
🇺🇸Columbus, Ohio, United States
Grant Medical Center
🇺🇸Columbus, Ohio, United States
Delaware Health Center-Grady Cancer Center
🇺🇸Delaware, Ohio, United States
Grady Memorial Hospital
🇺🇸Delaware, Ohio, United States
Kettering Medical Center
🇺🇸Kettering, Ohio, United States
Mercy Health - Perrysburg Hospital
🇺🇸Perrysburg, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Northeast Radiation Oncology Center
🇺🇸Dunmore, Pennsylvania, United States
Penn State Milton S Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
UPMC-Presbyterian Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC-Shadyside Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Gibbs Cancer Center-Gaffney
🇺🇸Gaffney, South Carolina, United States
Gibbs Cancer Center-Pelham
🇺🇸Greer, South Carolina, United States
Spartanburg Medical Center
🇺🇸Spartanburg, South Carolina, United States
SMC Center for Hematology Oncology Union
🇺🇸Union, South Carolina, United States
Sanford Cancer Center Oncology Clinic
🇺🇸Sioux Falls, South Dakota, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸Sioux Falls, South Dakota, United States
The Children's Hospital at TriStar Centennial
🇺🇸Nashville, Tennessee, United States
Covenant Medical Center-Lakeside
🇺🇸Lubbock, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Huntsman Cancer Institute/University of Utah
🇺🇸Salt Lake City, Utah, United States
Inova Schar Cancer Institute
🇺🇸Fairfax, Virginia, United States
Henrico Doctor's Hospital
🇺🇸Richmond, Virginia, United States
CJW Medical Center - Johnston-Willis Campus
🇺🇸Richmond, Virginia, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Carilion Roanoke Memorial Hospital
🇺🇸Roanoke, Virginia, United States
ThedaCare Regional Cancer Center
🇺🇸Appleton, Wisconsin, United States
Duluth Clinic Ashland
🇺🇸Ashland, Wisconsin, United States
Northwest Wisconsin Cancer Center
🇺🇸Ashland, Wisconsin, United States
Aurora Cancer Care-Southern Lakes VLCC
🇺🇸Burlington, Wisconsin, United States
Aurora Health Care Germantown Health Center
🇺🇸Germantown, Wisconsin, United States
Aurora Cancer Care-Grafton
🇺🇸Grafton, Wisconsin, United States
Aurora BayCare Medical Center
🇺🇸Green Bay, Wisconsin, United States
Essentia Health-Hayward Clinic
🇺🇸Hayward, Wisconsin, United States
Aurora Cancer Care-Kenosha South
🇺🇸Kenosha, Wisconsin, United States
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
🇺🇸Madison, Wisconsin, United States
University of Wisconsin Carbone Cancer Center - University Hospital
🇺🇸Madison, Wisconsin, United States
Aurora Cancer Care-Milwaukee
🇺🇸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
Vince Lombardi Cancer Clinic - Oshkosh
🇺🇸Oshkosh, Wisconsin, United States
Aurora Cancer Care-Racine
🇺🇸Racine, Wisconsin, United States
Aspirus Cancer Care - James Beck Cancer Center
🇺🇸Rhinelander, Wisconsin, United States
Vince Lombardi Cancer Clinic-Sheboygan
🇺🇸Sheboygan, Wisconsin, United States
Essentia Health-Spooner Clinic
🇺🇸Spooner, Wisconsin, United States
Aspirus Cancer Care - Stevens Point
🇺🇸Stevens Point, Wisconsin, United States
Aurora Medical Center in Summit
🇺🇸Summit, Wisconsin, United States
Essentia Health Saint Mary's Hospital - Superior
🇺🇸Superior, Wisconsin, United States
UW Cancer Center at ProHealth Care
🇺🇸Waukesha, Wisconsin, United States
Aspirus Regional Cancer Center
🇺🇸Wausau, Wisconsin, United States
Aurora Cancer Care-Milwaukee West
🇺🇸Wauwatosa, Wisconsin, United States
Aurora West Allis Medical Center
🇺🇸West Allis, Wisconsin, United States
Aspirus Cancer Care - Wisconsin Rapids
🇺🇸Wisconsin Rapids, Wisconsin, United States
CHUM - Centre Hospitalier de l'Universite de Montreal
🇨🇦Montreal, Quebec, Canada
The Research Institute of the McGill University Health Centre (MUHC)
🇨🇦Montreal, Quebec, Canada
CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)
🇨🇦Quebec City, Quebec, Canada