Observation or Radiation Therapy in Treating Patients With Newly Diagnosed Grade II Meningioma That Has Been Completely Removed by Surgery
- Conditions
- Grade 2 MeningiomaIntracranial Meningioma
- Interventions
- Radiation: Radiation TherapyOther: Clinical Observation
- Registration Number
- NCT03180268
- Lead Sponsor
- NRG Oncology
- Brief Summary
This randomized phase III trial studies how well radiation therapy works compared with observation in treating patients with newly diagnosed grade II meningioma that has been completely removed by surgery. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors.
- Detailed Description
PRIMARY OBJECTIVE:
I. To determine the extent of clinical benefit of the addition of adjuvant radiotherapy (RT) to gross total resection (GTR) for patients with newly diagnosed World Health Organization (WHO) grade II meningioma.
SECONDARY OBJECTIVES:
I. Overall survival (OS). II. Disease-specific survival (DSS). III. Toxicity (grade 3+, exclusive of expected alopecia). IV. Neurocognitive function (NCF). V. Patient reported outcomes (PRO) measurements. VI. Adherence to protocol-specific target and normal tissue parameters. VII. Concordance measurements of central versus parent-institution pathology. VIII. Assessment of pHH3 mitotic index and its correlation with progression-free survival (PFS) and OS.
IX. Validation of the prognostic value of a 34-gene expression biomarker. X. Validation of the predictive value of a 34-gene expression biomarker in predicting the benefit of radiotherapy.
XI. Tissue and specimen collection for future translational research.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients undergo observation. Additionally, patients undergo magnetic resonance imaging (MRI) and blood collection throughout the study.
ARM II: Patients undergo intensity-modulated radiation therapy (IMRT) or proton beam radiation therapy 5 days a week over 6.5-7 weeks for a total of 33 fractions in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MRI and blood collection throughout the study.
After completion of study treatment, patients are followed up at 3, 6, and 12 months, every 6 months for year 2 and 3, then yearly for 10 years.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 163
- PRIOR TO STEP 1 REGISTRATION:
- The patient must have a newly diagnosed unifocal intracranial meningioma, gross totally resected, and histologically confirmed as WHO grade II based upon pathology findings at the enrolling institution. WHO grade will be assigned according to WHO 2016 criteria
- Gross total resection (GTR) will be interpreted as modified Simpson grade 1-3 without gross residual dural-based or extradural tumor. GTR must be confirmed both by modified Simpson grade and by post-operative magnetic resonance imaging (MRI) findings. The modified Simpson grade can be inferred from the operative report (surgeon does not need to explicitly describe the Simpson grade for the purposes of eligibility)
- Step 1 registration must occur within 180 days of the initial surgery; this will provide sufficient time for post-operative imaging confirmation of resection extent after resolution of operative changes. Moreover, it will permit additional surgery if needed to achieve a GTR. Within this 180 day interval, a second surgery is permitted in order to achieve GTR, but even with a second surgery, Step 1 registration must occur within 180 days of the initial resection
- GTR must be confirmed on post-operative imaging following the most recent surgery. For protocol enrollment, the assessment of GTR will be made at each site. However, submission of both pre-operative and post-operative MRIs is required for patients. If a second surgery is performed, submission of post-operative MRI is required and pre-operative MRI is required only if obtained. All sequences obtained in the pre- and post-operative MR imaging are to be submitted to National Radiology Group (NRG) Oncology for study registration. The post-operative MRI must be completed within sufficient time to permit step 1 registration within 180 days of the initial resection. These same conditions apply in the setting of a second surgical procedure, although if a second surgery is completed, step 1 registration must still occur with 180 days of initial surgery. Computed tomography (CT) imaging is not required, but may be obtained if desired clinically, for instance to assess calcifications or hyperostosis
- The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
- NOTE: Central pathology review must occur between steps 1 and 2 of registration. Once appropriate pathology specimens are received, central pathology review will occur within 10 business days, and must confirm WHO grade II meningioma before the patient can proceed to step 2 registration and randomization
- PRIOR TO STEP 2 REGISTRATION:
- Histologically confirmed diagnosis of WHO grade II meningioma confirmed by central pathology review prior to step 2 registration
- Age >= 18
- History/physical examination, including neurologic examination within 60 days prior to step 2 registration
- Post-operative Zubrod performance status 0-1 within 60 days prior to step 2 registration
- If the patient is a woman is of childbearing potential, a serum pregnancy test, obtained within 14 days prior to step 2 registration, must be negative, and, if randomized to receive radiation therapy, the woman must agree to use contraception
-
Optic nerve sheath meningioma, spinal or other extracranial meningioma, multiple meningiomas, hemangiopericytoma
-
Definitive evidence of metastatic meningioma (metastasis, although rare, can occur and is exclusionary)
-
Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (carcinoma in situ of the breast, oral cavity, cervix, melanoma in situ, or other non-invasive malignancies are permissible)
-
Previous radiotherapy to the scalp, cranium, brain, or skull base and radiation-induced meningiomas
-
Major medical illnesses or psychiatric impairments, which in the investigators opinion, will prevent administration or completion of the protocol therapy and/or preclude informed consent; these include, but are not restricted to:
- Unstable angina and/or congestive heart failure requiring hospitalization at the time of step 2 registration
- Transmural myocardial infarction within the last 6 months prior to step 2 registration
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of step 2 registration
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of step 2 registration
- Type II neurofibromatosis (NF2)
- Ailments entailing substantial increases in sensitivity and side effect risk from radiation therapy (ataxia telangiectasia, Nijmegen breakage syndrome, and human immunodeficiency virus (HIV) with CD4 count < 200 cells/microliter); HIV testing is not required for eligibility for this protocol, and known HIV positive patients 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 step 2 registration
- Inability to undergo MRI with and without contrast (e.g. claustrophobia, non-MRI compatible implant or foreign body, gadolinium allergy or renal dysfunction preventing the patient from receiving gadolinium- institutional guidelines should be used to determine if patients are at risk for renal dysfunction). Note that patients with severe claustrophobia are permitted on this study if they are willing and able to undergo MRI with adequate sedation or anesthesia
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm II (Radiation Therapy) Radiation Therapy Patients undergo radiation therapy 5 days a week over 6.5-7 weeks for a total of 33 fractions after gross total resection. Arm I (Clinical Observation) Clinical Observation Patients undergo observation after gross total resection.
- Primary Outcome Measures
Name Time Method Progression free survival (PFS) From randomization to the first documented disease progression, or death due to any cause, whichever comes first, assessed up to 10 years Kaplan-Meier method will be used to calculate the PFS rates for each of the two arms. Hazard ratio (HR) on the treatment effect will be calculated using the Cox proportional hazard model. A one-sided log-rank test will be used to test the difference in PFS between the two arms.
- Secondary Outcome Measures
Name Time Method PFS From randomization to the first documented disease progression, or death due to any cause, whichever comes first, assessed up to 5 years Will be calculated based on the Kaplan-Meier curve. Cox proportional hazard model will be used to determine the adjusted treatment effect on PFS, with patient pretreatment characteristics as covariates.
Disease-specific survival (DSS) From randomization to disease-related death, assessed up to 10 years Will be calculated using the cumulative incidence function for each arm. The HR for the treatment effect on DSS will be calculated using Gray's method under the competing risk approach, with death due to non-disease related cause treated as the competing risk. Multivariate analysis on DSS will be performed using the Fine-Gray model, with patient pretreatment characteristics as covariates.
DSS rates At 5 years Will be calculated using the cumulative incidence function for each arm. The HR for the treatment effect on DSS will be calculated using Gray's method under the competing risk approach, with death due to non-disease related cause treated as the competing risk. Multivariate analysis on DSS will be performed using the Fine-Gray model, with patient pretreatment characteristics as covariates.
Overall survival (OS) From randomization to death due to any cause, assessed up to 10 years Cox proportional hazard model will be used to determine the adjusted treatment effect on OS, with patient pretreatment characteristics as covariates.
OS rates At 5 years Will be calculated based on the Kaplan-Meier curve. Cox proportional hazard model will be used to determine the adjusted treatment effect on OS, with patient pretreatment characteristics as covariates.
Incidence of adverse events (exclusive of alopecia) Up to 3 years Will be measured by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4 (version 5 beginning April 5, 2018).
Adherence rate to protocol-specific target and normal tissue parameters Up to 10 years Concordance rate of central versus parent-institution pathology Up to 10 years Prognostic value of 34-gene expression biomarker Up to 5 years Will generate Kaplan-Meier curves for different risk subgroups defined by the risk scores, separately for post-operative observation and post-operative radiotherapy arms. The log-rank test will be used to test the difference in clinical outcomes (PFS and OS) between molecular risk subgroups (separately for the post-operative observation arm and post-operative radiotherapy arm). Cox proportional hazard model will be used to estimate the prognostic effect of the gene expression defined risk groups on clinical outcomes adjusting for pre-treatment patient characteristics as well as treatment arm.
Predictive value of 34-gene expression biomarker Up to 5 years Will be evaluated formally through the test of a statistical interaction between molecular risk group (low/intermediate versus high) and treatment (observation versus radiotherapy). The Kaplan-Meier curves of PFS and OS between treatment arms will be displayed separately among low/intermediate risk and high-risk groups. A Cox proportional hazards model will be built including treatment group, gene expression risk group, an interaction term between treatment and gene expression risk group, as well as other pre-treatment patient characteristics. The interaction test will be based on a two-sided 0.05 level Wald test in the Cox proportional hazards model. The treatment difference between radiation therapy and observation will also be tested within each gene expression risk subgroup in a multivariable Cox proportional hazards model, adjusting for other patient characteristics.
Change in neurocognitive function (NCF) assessed by MD Anderson Symptom Inventory with Brain Tumor (MDASI-BT) Baseline up to 60 months Will use a 2-sample t-test with a one-sided significance level of 0.05, with a Bonferroni adjustment to account for the neurocognitive function and symptom assessments resulting in an overall type I error of 0.1, there will be 72% statistical power to detect a medium effect size of 0.5 standard deviation (SD) for a comparison of the change from baseline to 6 months after randomization between the experimental and the control arm. Will compare NCF outcomes between IMRT to proton therapy.
Change in patient reported outcomes (PRO) as assessed by MDASI-BT Baseline up to 60 months Will use a 2-sample t-test with a one-sided significance level of 0.05, with a Bonferroni adjustment to account for the neurocognitive function and symptom assessments resulting in an overall type I error of 0.1, there will be 72% statistical power to detect a medium effect size of 0.5 standard deviation for a comparison of the change from baseline to 6 months after randomization between the experimental and the control arm. Will compare PRO outcomes between IMRT to proton therapy.
Trial Locations
- Locations (208)
University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States
Saint Joseph's Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
Mayo Clinic Hospital in Arizona
🇺🇸Phoenix, Arizona, United States
Mayo Clinic in Arizona
🇺🇸Scottsdale, Arizona, United States
University of Arizona Cancer Center-Orange Grove Campus
🇺🇸Tucson, 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 Cancer Centers Radiation Oncology Services-Auburn
🇺🇸Auburn, California, United States
Kaiser Permanente-Bellflower
🇺🇸Bellflower, California, United States
Kaiser Permanente Dublin
🇺🇸Dublin, California, United States
Kaiser Permanente Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
Los Angeles General Medical Center
🇺🇸Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Memorial Medical Center
🇺🇸Modesto, California, United States
Kaiser Permanente Oakland-Broadway
🇺🇸Oakland, California, United States
Kaiser Permanente-Ontario
🇺🇸Ontario, 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
Kaiser Permanente-Rancho Cordova Cancer Center
🇺🇸Rancho Cordova, California, United States
Rohnert Park Cancer Center
🇺🇸Rohnert Park, California, United States
Sutter Cancer Centers Radiation Oncology Services-Roseville
🇺🇸Roseville, California, United States
The Permanente Medical Group-Roseville Radiation Oncology
🇺🇸Roseville, California, United States
Sutter Medical Center Sacramento
🇺🇸Sacramento, California, United States
South Sacramento Cancer Center
🇺🇸Sacramento, California, United States
California Pacific Medical Center-Pacific Campus
🇺🇸San Francisco, California, United States
Kaiser Permanente Medical Center - Santa Clara
🇺🇸Santa Clara, California, United States
Kaiser Permanente Cancer Treatment Center
🇺🇸South San Francisco, California, United States
Sutter Solano Medical Center/Cancer Center
🇺🇸Vallejo, California, United States
Hartford Hospital
🇺🇸Hartford, Connecticut, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Helen F Graham Cancer Center
🇺🇸Newark, Delaware, United States
Christiana Care Health System-Christiana Hospital
🇺🇸Newark, Delaware, United States
Beebe Health Campus
🇺🇸Rehoboth Beach, Delaware, United States
TidalHealth Nanticoke / Allen Cancer Center
🇺🇸Seaford, Delaware, United States
Boca Raton Regional Hospital
🇺🇸Boca Raton, Florida, 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
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
🇺🇸Hollywood, Florida, United States
Baptist MD Anderson Cancer Center
🇺🇸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
AdventHealth Orlando
🇺🇸Orlando, Florida, United States
AdventHealth East Orlando
🇺🇸Orlando, Florida, United States
Memorial Hospital West
🇺🇸Pembroke Pines, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Grady Health System
🇺🇸Atlanta, Georgia, United States
Emory Proton Therapy Center
🇺🇸Atlanta, Georgia, United States
Piedmont Hospital
🇺🇸Atlanta, Georgia, United States
Emory University Hospital/Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Emory Saint Joseph's Hospital
🇺🇸Atlanta, Georgia, United States
Northside Hospital
🇺🇸Atlanta, Georgia, United States
Northside Hospital-Forsyth
🇺🇸Cumming, Georgia, United States
Piedmont Fayette Hospital
🇺🇸Fayetteville, Georgia, United States
Piedmont Newnan Hospital
🇺🇸Newnan, Georgia, United States
Piedmont Henry Hospital
🇺🇸Stockbridge, Georgia, United States
Queen's Medical Center
🇺🇸Honolulu, Hawaii, United States
The Cancer Center of Hawaii-Liliha
🇺🇸Honolulu, Hawaii, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
Maryland Proton Treatment Center
🇺🇸Baltimore, Maryland, United States
Decatur Memorial Hospital
🇺🇸Decatur, Illinois, United States
NorthShore University HealthSystem-Evanston Hospital
🇺🇸Evanston, Illinois, United States
Northwestern Medicine Cancer Center Delnor
🇺🇸Geneva, Illinois, United States
NorthShore University HealthSystem-Glenbrook Hospital
🇺🇸Glenview, Illinois, United States
NorthShore University HealthSystem-Highland Park Hospital
🇺🇸Highland Park, Illinois, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Northwestern Medicine Cancer Center Warrenville
🇺🇸Warrenville, Illinois, United States
Indiana University/Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
IU Health Methodist Hospital
🇺🇸Indianapolis, Indiana, United States
Iowa Methodist Medical Center
🇺🇸Des Moines, Iowa, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸Iowa City, Iowa, United States
University of Kansas Cancer Center
🇺🇸Kansas City, Kansas, United States
University of Kansas Cancer Center-Overland Park
🇺🇸Overland Park, Kansas, United States
University of Kentucky/Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
The James Graham Brown Cancer Center at University of Louisville
🇺🇸Louisville, Kentucky, United States
UofL Health Medical Center Northeast
🇺🇸Louisville, Kentucky, United States
LSU Health Sciences Center at Shreveport
🇺🇸Shreveport, Louisiana, United States
MaineHealth Coastal Cancer Treatment Center
🇺🇸Bath, Maine, United States
MaineHealth Maine Medical Center - Portland
🇺🇸Portland, Maine, United States
MaineHealth Cancer Care Center of York County
🇺🇸Sanford, Maine, United States
MaineHealth Maine Medical Center- Scarborough
🇺🇸Scarborough, Maine, United States
University of Maryland/Greenebaum Cancer Center
🇺🇸Baltimore, Maryland, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
🇺🇸Ann Arbor, Michigan, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Chelsea Hospital
🇺🇸Chelsea, Michigan, United States
Henry Ford Macomb Hospital-Clinton Township
🇺🇸Clinton Township, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Henry Ford Health Saint John Hospital
🇺🇸Detroit, Michigan, United States
Trinity Health Saint Mary Mercy Livonia Hospital
🇺🇸Livonia, Michigan, United States
MyMichigan Medical Center Saginaw
🇺🇸Saginaw, Michigan, United States
Henry Ford Health Warren Hospital
🇺🇸Warren, Michigan, United States
Henry Ford West Bloomfield Hospital
🇺🇸West Bloomfield, Michigan, United States
University of Michigan Health - West
🇺🇸Wyoming, Michigan, United States
Essentia Health Cancer Center
🇺🇸Duluth, Minnesota, United States
Miller-Dwan Hospital
🇺🇸Duluth, Minnesota, United States
Abbott-Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸Saint Louis Park, Minnesota, United States
Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
MU Health - University Hospital/Ellis Fischel Cancer Center
🇺🇸Columbia, Missouri, United States
Siteman Cancer Center at West County Hospital
🇺🇸Creve Coeur, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center-South County
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center at Saint Peters Hospital
🇺🇸Saint Peters, Missouri, United States
Benefis Sletten Cancer Institute
🇺🇸Great Falls, Montana, United States
Logan Health Medical Center
🇺🇸Kalispell, Montana, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
🇺🇸Lebanon, New Hampshire, United States
Memorial Sloan Kettering Basking Ridge
🇺🇸Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Monmouth
🇺🇸Middletown, New Jersey, United States
Memorial Sloan Kettering Bergen
🇺🇸Montvale, New Jersey, United States
Jersey Shore Medical Center
🇺🇸Neptune, New Jersey, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Rutgers New Jersey Medical School
🇺🇸Newark, New Jersey, United States
Capital Health Medical Center-Hopewell
🇺🇸Pennington, New Jersey, United States
ProCure Proton Therapy Center-Somerset
🇺🇸Somerset, New Jersey, United States
Robert Wood Johnson University Hospital Somerset
🇺🇸Somerville, New Jersey, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
New York-Presbyterian/Brooklyn Methodist Hospital
🇺🇸Brooklyn, New York, United States
Memorial Sloan Kettering Commack
🇺🇸Commack, New York, United States
The New York Hospital Medical Center of Queens
🇺🇸Flushing, New York, United States
Memorial Sloan Kettering Westchester
🇺🇸Harrison, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
NYP/Weill Cornell Medical Center
🇺🇸New York, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
Memorial Sloan Kettering Nassau
🇺🇸Uniondale, New York, United States
Westchester Medical Center
🇺🇸Valhalla, New York, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Mercy Cancer Center-Elyria
🇺🇸Elyria, Ohio, United States
Kettering Medical Center
🇺🇸Kettering, Ohio, United States
UH Seidman Cancer Center at Lake Health Mentor Campus
🇺🇸Mentor, Ohio, United States
ProMedica Flower Hospital
🇺🇸Sylvania, Ohio, United States
UHHS-Westlake Medical Center
🇺🇸Westlake, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Legacy Mount Hood Medical Center
🇺🇸Gresham, Oregon, United States
Legacy Good Samaritan Hospital and Medical Center
🇺🇸Portland, Oregon, United States
Saint Luke's University Hospital-Bethlehem Campus
🇺🇸Bethlehem, Pennsylvania, United States
Christiana Care Health System-Concord Health Center
🇺🇸Chadds Ford, Pennsylvania, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Geisinger Medical Oncology-Lewisburg
🇺🇸Lewisburg, Pennsylvania, United States
Lewistown Hospital
🇺🇸Lewistown, Pennsylvania, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Geisinger Cancer Services-Pottsville
🇺🇸Pottsville, Pennsylvania, United States
Geisinger Wyoming Valley/Henry Cancer Center
🇺🇸Wilkes-Barre, Pennsylvania, United States
Lankenau Medical Center
🇺🇸Wynnewood, Pennsylvania, United States
Prisma Health Cancer Institute - Spartanburg
🇺🇸Boiling Springs, South Carolina, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Prisma Health Cancer Institute - Faris
🇺🇸Greenville, South Carolina, United States
Prisma Health Cancer Institute - Eastside
🇺🇸Greenville, South Carolina, United States
Prisma Health Cancer Institute - Greer
🇺🇸Greer, South Carolina, United States
Prisma Health Cancer Institute - Seneca
🇺🇸Seneca, South Carolina, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸Dallas, Texas, United States
M D Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
American Fork Hospital / Huntsman Intermountain Cancer Center
🇺🇸American Fork, Utah, United States
Logan Regional Hospital
🇺🇸Logan, Utah, United States
Intermountain Medical Center
🇺🇸Murray, Utah, United States
McKay-Dee Hospital Center
🇺🇸Ogden, Utah, United States
Utah Valley Regional Medical Center
🇺🇸Provo, Utah, United States
Riverton Hospital
🇺🇸Riverton, Utah, United States
LDS Hospital
🇺🇸Salt Lake City, Utah, United States
Dartmouth Cancer Center - North
🇺🇸Saint Johnsbury, Vermont, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸Richmond, Virginia, United States
University of Washington Medical Center - Montlake
🇺🇸Seattle, Washington, United States
Legacy Salmon Creek Hospital
🇺🇸Vancouver, Washington, United States
Langlade Hospital and Cancer Center
🇺🇸Antigo, Wisconsin, United States
Marshfield Medical Center-EC Cancer Center
🇺🇸Eau Claire, 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
Marshfield Medical Center-Marshfield
🇺🇸Marshfield, Wisconsin, United States
Froedtert Menomonee Falls Hospital
🇺🇸Menomonee Falls, Wisconsin, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Marshfield Medical Center - Minocqua
🇺🇸Minocqua, Wisconsin, United States
Drexel Town Square Health Center
🇺🇸Oak Creek, Wisconsin, United States
Marshfield Medical Center-Rice Lake
🇺🇸Rice Lake, Wisconsin, United States
Aspirus Cancer Care - Stevens Point
🇺🇸Stevens Point, Wisconsin, United States
Marshfield Medical Center-River Region at Stevens Point
🇺🇸Stevens Point, Wisconsin, United States
Aspirus Regional Cancer Center
🇺🇸Wausau, Wisconsin, United States
Diagnostic and Treatment Center
🇺🇸Weston, Wisconsin, United States
Aspirus Cancer Care - Wisconsin Rapids
🇺🇸Wisconsin Rapids, Wisconsin, United States
Arthur J E Child Comprehensive Cancer Centre
🇨🇦Calgary, Alberta, Canada
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Juravinski Cancer Centre at Hamilton Health Sciences
🇨🇦Hamilton, Ontario, Canada
London Regional Cancer Program
🇨🇦London, Ontario, Canada
University Health Network-Princess Margaret Hospital
🇨🇦Toronto, Ontario, 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
Allan Blair Cancer Centre
🇨🇦Regina, Saskatchewan, Canada
Tata Memorial Hospital
🇮🇳Mumbai, India
Hokkaido University Hospital
🇯🇵Sapporo, Hokkaido, Japan
Iwate Medical University Hospital
🇯🇵Shiwa-gun, Iwate, Japan
Kyorin University Hospital
🇯🇵Mitaka-shi, Tokyo, Japan
Keio University
🇯🇵Shinjuku-ku, Tokyo, Japan
Hiroshima University Hospital
🇯🇵Hiroshima City, Japan
Saitama Medical University International Medical Center
🇯🇵Saitama, Japan
National Cancer Center Hospital
🇯🇵Tokyo, Japan
King Faisal Specialist Hospital and Research Centre
🇸🇦Riyadh, Saudi Arabia