Radiation Therapy With Concomitant and Adjuvant Temozolomide Versus Radiation Therapy With Adjuvant PCV Chemotherapy in Patients With Anaplastic Glioma or Low Grade Glioma
- Conditions
- Brain and Central Nervous System Tumors
- Interventions
- Registration Number
- NCT00887146
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief Summary
Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving radiation with concomitant and adjuvant temozolomide versus radiation with adjuvant PCV is more effective in treating anaplastic glioma or low grade glioma.
- Detailed Description
This study will be a randomized phase III for patients with newly diagnosed co-deleted 1p/19q anaplastic glioma or high risk low grade glioma. The trial will only enroll patients with 1p/19q co-deletion. This study includes two arms as described in the "Arms" section. A dynamic allocation procedure will be used to allocate an equal number of patients to different arms (Arms A:B = 1:1). This procedure will balance the marginal distributions of the stratification factors among arms. The stratification factors that will be used are cooperative groups (EORTC vs. all North American groups), age (≤ 50 vs. \> 50), performance score (ECOG 0-1 vs. 2), and tumor grade (anaplastic glioma vs. low grade glioma).
The primary goal is to determine whether patients who receive radiotherapy with concomitant temozolomide (TMZ) followed by adjuvant temozolomide (RT + TMZ --\> TMZ) (Arm B) have a marginally better progression free survival (PFS) as compared with patients who receive radiotherapy followed by PCV chemotherapy (RT --\> PCV)(Arm A).
Secondary Goals:
1. Time to Progression - To determine whether patients who receive (RT + TMZ --\> TMZ) have a significantly longer time to progression (clinical or radiographic progression) as compared with patients who receive radiotherapy followed by adjuvant PCV chemotherapy (RT --\> PCV).
2. Correlation between exploratory biomarkers and survival - To determine whether there is a difference in survival based on t(1;19)(q10, p10) translocation status and MGMT promoter hypermethylation status.
3. Descriptive Comparisons of Additional Secondary Endpoints - To perform descriptive comparisons of additional secondary outcome endpoints, including overall survival, objective tumor response, prognostic factor analysis and quality of life.
4. Toxicity - To determine the toxicity of the treatment in each arm and perform descriptive comparisons.
5. Neurocognitive and Quality of Life (QOL) Effects - To determine the neurocognitive and QOL effects in patients treated on this protocol and correlate these results with outcome endpoints.
6. Banking of Biospecimens and Neuroimaging Studies - To store blood products (i.e., plasma, DNA and buffy coat), tumor tissue and MRI/CT images for future scientific investigations.
After completion of study treatment, patients are followed every 12 weeks for 1 year, then every 4 months for 2 years and then every 6 months until progressive disease or until the end of study participation.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 305
-
United States (US) and Canadian sites:
* This review is mandatory prior to registration to confirm eligibility; patients must be willing to submit tissue samples for mandatory central pathology review submission; it should be initiated as soon after surgery as possible
-
Tissue must have been determined to have local 1p/9q co-deletion and IDH mutation prior to submission for central path review
- Tumor tissue must show co-deletion of chromosomes 1p and 19q; for eligibility, the 1p/19q analysis results will be accepted from the local site, as determined by either a locally available or reference laboratory (for US, must be Clinical Laboratory Improvement Act [CLIA] certified); acceptable methods for determination of 1p/19q loss include fluorescent in-situ hybridization (FISH), by genomic sequencing or methylomic analyses; US and Canadian sites must send a copy of the official report to the pathology coordinator and quality assurance specialist (QAS)
- Tumor must also show evidence of IDH mutation by immunohistochemistry or genomic analyses; this should be performed at the local site (US: performed in a CLIA certified laboratory); the site must send a copy of the official report to the pathology coordinator and QAS
Registration Inclusion Criteria:
-
Newly diagnosed and =< 3 months from surgical diagnosis; patients are also eligible if they have had a prior surgical procedure > 3 months earlier for low grade glioma, as long as the patient has not received prior radiation or prior chemotherapy
-
Histological evidence of World Health Organization (WHO) grade III anaplastic glioma or WHO grade II low grade glioma with locally diagnosed combined 1p/19q loss and the presence of an either IDH1 or IDH2, both as established by a local or referenced laboratory qualified for the study
* Note: mixed gliomas are eligible, regardless of the degree of astrocytic or oligodendrocytic predominance, as long as the tumor is also co-deleted for 1p and 19q
-
Patients with codeleted low grade gliomas must also be considered "high risk" by exhibiting one or more of the following characteristics:
- Age >= 40 and any surgical therapy
- Age < 40 with prior and subtotal resection or biopsy (i.e., anything less than gross total resection)
- Documented growth following prior surgery (NOTE: patients with prior surgery cannot have received prior radiation, chemotherapy or targeted therapy)
- Intractable seizures
-
Surgery (partial or gross total resection or biopsy) must be performed >= 2 weeks prior to registration; patient must have recovered adequately from the effects of surgery
-
Absolute neutrophil count (ANC) >= 1,500/mm^3 obtained =< 21 days prior to registration
-
Platelet (PLTs) count >= 100,000/mm^3 obtained =< 21 days prior to registration
-
Hemoglobin (Hgb) > 9.0 g/dL obtained =< 21 days prior to registration
-
Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) obtained =< 21 days prior to registration
-
Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3 x ULN obtained =< 21 days prior to registration
-
Creatinine =< 1.5 x ULN obtained =< 21 days prior to registration
-
Negative serum or urine pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
-
Willingness and ability to personally complete neurocognitive testing (without assistance) and willingness to complete the QOL testing, (either personally or with assistance)
-
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2
-
Written informed consent
-
Willingness to return to enrolling institution for follow-up during the active monitoring phase (that is, the active treatment and observation portion) of the study); patients who have been formally transferred to another active and approved site participating in this study would not need to return to the enrolling institution for this purpose
-
Willingness to allow the provision of tissue samples for correlative research, as long as adequate tissues are available; patients will not be excluded from participation in the study, if they are willing to allow provision of tissues for the correlative research, but there are insufficient quantities of tissue for the correlative analyses (e.g., a patient otherwise eligible and willing who had biopsy only) Willingness to allow the provision of blood samples for correlative research; patients are not excluded from participation in the study, if they are willing to provide the mandatory biospecimens for translational/correlative research, but for logistical reasons the specimens(s) were not obtainable or if the volume collected was insufficient
Registration
-
The following categories are ineligible:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception or contraceptive method during this study and 6 months following the completion of chemotherapy treatments
-
History of prior radiation therapy or chemotherapy for glioma; note: patients who have a history of prior low grade glioma (with or without a distant history of prior surgery for that glioma), but who have never received prior chemotherapy or radiation therapy for the glioma are eligible for the study
-
Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
-
Concomitant serious immunocompromised status (other than that related to concomitant steroids) that would compromise the safety of the patient on the study
-
Patients known to be human immunodeficiency virus (HIV) positive and currently receiving retroviral therapy are not eligible; note: patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for the study
-
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
-
Receiving any other investigational agent that would be considered as a treatment for the primary neoplasm
-
Other active malignancy within 5 years of registration; exceptions: non-melanotic skin cancer or carcinoma-in-situ of the cervix; note: if there is a history of prior malignancy, the patient is not eligible if they are receiving other specific treatment (with the exclusion of hormonal therapy or Her-2 inhibitors) for their cancer or if they have received prior total body irradiation which included the brain
-
History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
-
Recent history of hepatitis infection or if the treating physician determined that the patient would be at significant risk of reactivation of hepatitis
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B (RT, temozolomide) adjuvant temozolomide (TMZ) Patients undergo RT as in arm I and receive temozolomide PO QD on days 1-5 for 5-7 weeks. Beginning 4 weeks after completion of concurrent chemoradiotherapy, patients receive adjuvant temozolomide PO QD days 1-5. Treatment with adjuvant temozolomide repeats every 4 weeks for 6-12 courses in the absence of disease progression and unacceptable toxicity. Arm A (RT, procarbazine, lomustine, vincristine) CCNU Patients undergo 3D-CRT or IMRT on days 1-5 for 5-7 weeks. Patients also receive procarbazine hydrochloride PO on days 8-21, lomustine PO on day 1 and vincristine sulfate IV on days 8 and 29 of courses 3-8. Treatment repeats every 6-7 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Arm A (RT, procarbazine, lomustine, vincristine) radiotherapy Patients undergo 3D-CRT or IMRT on days 1-5 for 5-7 weeks. Patients also receive procarbazine hydrochloride PO on days 8-21, lomustine PO on day 1 and vincristine sulfate IV on days 8 and 29 of courses 3-8. Treatment repeats every 6-7 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Arm B (RT, temozolomide) concomitant temozolomide (TMZ) Patients undergo RT as in arm I and receive temozolomide PO QD on days 1-5 for 5-7 weeks. Beginning 4 weeks after completion of concurrent chemoradiotherapy, patients receive adjuvant temozolomide PO QD days 1-5. Treatment with adjuvant temozolomide repeats every 4 weeks for 6-12 courses in the absence of disease progression and unacceptable toxicity. Arm B (RT, temozolomide) radiotherapy Patients undergo RT as in arm I and receive temozolomide PO QD on days 1-5 for 5-7 weeks. Beginning 4 weeks after completion of concurrent chemoradiotherapy, patients receive adjuvant temozolomide PO QD days 1-5. Treatment with adjuvant temozolomide repeats every 4 weeks for 6-12 courses in the absence of disease progression and unacceptable toxicity. Arm A (RT, procarbazine, lomustine, vincristine) procarbazine Patients undergo 3D-CRT or IMRT on days 1-5 for 5-7 weeks. Patients also receive procarbazine hydrochloride PO on days 8-21, lomustine PO on day 1 and vincristine sulfate IV on days 8 and 29 of courses 3-8. Treatment repeats every 6-7 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Arm A (RT, procarbazine, lomustine, vincristine) vincristine Patients undergo 3D-CRT or IMRT on days 1-5 for 5-7 weeks. Patients also receive procarbazine hydrochloride PO on days 8-21, lomustine PO on day 1 and vincristine sulfate IV on days 8 and 29 of courses 3-8. Treatment repeats every 6-7 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Progression-free survival Time from study registration to time of tumor progression or death due to any cause, whichever comes first, assessed up to 16 years The distribution of progression free survival for Arms A and B will be estimated using the Kaplan-Meier method. The hazard ratios and median progression free survival (PFS) will be estimated with their confidence intervals. The Cox proportional hazards model will be used to assess whether the distributions of progression survival times differ with respect to treatment regimen having adjusted for all stratification factors (cooperative groups, age, and performance score). Both non-inferiority and superiority will be tested in this trial for the primary goal and no multiple-comparison adjustment will be considered.
- Secondary Outcome Measures
Name Time Method Overall survival Time from study registration to time of death due to any cause, assessed up to 16 years The Cox proportional hazards model will be used to assess whether the distributions of overall survival times differ with respect to treatment regimen having adjusted for all stratification factors (cooperative groups, age, and Performance Score). The distribution of overall survival for Arm A and B will be estimated using the Kaplan-Meier method. The hazard ratios and median survivals will be estimated with their 95% confidence intervals.
Objective tumor response defined as a complete response or partial response Up to 16 years Summarized for each arm and compared between the arms using the Chi square test.
Time to progression Time from study registration to the earliest evidence of clinical progression, radiographic progression or neurocognitive progression, assessed up to 16 years Estimated by Kaplan-Meier method and analyzed by Cox regression model adjusting all stratification factors. Correlations among baseline neurocognitive test scores and progression free survival will be analyzed using Cox proportional hazards model.
Time to neurocognitive progression, assessed using the Hopkins Verbal Learning Test-Revised for Free Recall, Delayed Recall, and Delayed Recognition; the Controlled Oral Word Association test; and the Trail Making Test Part A or B Time from study registration to the first cognitive failure, assessed up to 16 years Estimated by Kaplan-Meier method and analyzed by Cox regression model adjusting all stratification factors. For each test in the battery, a standard error of measurement will be used to derive the Reliable Change Index (RCI) which will be used to represent the 90% confidence interval for the difference in raw scores from baseline to follow-up assessment will be coded as 1 (deterioration), 2 (no change), and 3 (improved) according to the RCI.
Treatment-related adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 Up to 16 years The maximum grade for each type of treatment-related adverse event will be recorded for each patient, and frequency tables for each arm will be reviewed to determine patterns. In addition, will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. Adverse events and treatment-related adverse events will be evaluated using all patients. Treatment-related adverse events will be tabulated for each arm.
Trial Locations
- Locations (290)
Mount Carmel Health Center West
🇺🇸Columbus, Ohio, United States
Emory University Hospital/Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
Radiation Oncology Centers of Nevada Southeast
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada - Central Valley
🇺🇸Las Vegas, Nevada, United States
Mills-Peninsula Medical Center
🇺🇸Burlingame, California, United States
Providence Hospital
🇺🇸Mobile, Alabama, United States
Sutter Cancer Centers Radiation Oncology Services-Auburn
🇺🇸Auburn, California, United States
Arizona Oncology Services Foundation
🇺🇸Scottsdale, Arizona, United States
Kaiser Permanente Medical Center - Santa Clara
🇺🇸Santa Clara, California, United States
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States
Katmai Oncology Group
🇺🇸Anchorage, Alaska, United States
UC San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
Community Cancer Institute
🇺🇸Clovis, California, United States
Maine Medical Partners - South Portland
🇺🇸South Portland, Maine, United States
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
🇺🇸Grand Rapids, Michigan, United States
Cancer Trials Support Unit
🇺🇸Rockville, Maryland, United States
Corewell Health William Beaumont University Hospital
🇺🇸Royal Oak, 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
Maine Medical Center- Scarborough Campus
🇺🇸Scarborough, Maine, United States
Corewell Health Beaumont Troy Hospital
🇺🇸Troy, Michigan, United States
West Jefferson Medical Center
🇺🇸Marrero, Louisiana, United States
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
Maine Medical Center-Bramhall Campus
🇺🇸Portland, Maine, United States
Maine Medical Partners Neurology
🇺🇸Scarborough, Maine, United States
Bixby Medical Center
🇺🇸Adrian, Michigan, United States
Billings Clinic Cancer Center
🇺🇸Billings, Montana, United States
Saint Vincent Healthcare
🇺🇸Billings, Montana, United States
Munson Medical Center
🇺🇸Traverse City, Michigan, United States
Rice Memorial Hospital
🇺🇸Willmar, Minnesota, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
The Mark H Zangmeister Center
🇺🇸Columbus, Ohio, United States
GenesisCare USA - Las Vegas
🇺🇸Las Vegas, Nevada, United States
Unity Hospital
🇺🇸Fridley, Minnesota, United States
CHI Health Good Samaritan
🇺🇸Kearney, Nebraska, United States
Hillcrest Hospital Cancer Center
🇺🇸Mayfield Heights, Ohio, United States
Cancer Partners of Nebraska
🇺🇸Lincoln, Nebraska, United States
Great Falls Clinic
🇺🇸Great Falls, Montana, United States
Radiation Oncology Associates
🇺🇸Reno, Nevada, United States
University of Kansas Cancer Center at North Kansas City Hospital
🇺🇸North Kansas City, Missouri, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
MU Health - University Hospital/Ellis Fischel Cancer Center
🇺🇸Columbia, Missouri, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Ridgeview Medical Center
🇺🇸Waconia, Minnesota, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
🇺🇸New Brunswick, New Jersey, United States
University of Kansas Cancer Center - Lee's Summit
🇺🇸Lee's Summit, Missouri, United States
Saint Luke's Hospital-Anderson Campus
🇺🇸Easton, Pennsylvania, United States
Saint Mary's Regional Medical Center
🇺🇸Reno, Nevada, United States
Minnesota Oncology Hematology PA-Woodbury
🇺🇸Woodbury, Minnesota, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Jersey Shore Medical Center
🇺🇸Neptune, New Jersey, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
🇺🇸New York, New York, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
🇺🇸Lebanon, New Hampshire, United States
Riverside Methodist Hospital
🇺🇸Columbus, Ohio, United States
Prisma Health Cancer Institute - Greer
🇺🇸Greer, South Carolina, United States
New York-Presbyterian/Brooklyn Methodist Hospital
🇺🇸Brooklyn, New York, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
ProMedica Flower Hospital
🇺🇸Sylvania, Ohio, United States
Prisma Health Cancer Institute - Seneca
🇺🇸Seneca, South Carolina, United States
Jefferson Abington Hospital
🇺🇸Abington, Pennsylvania, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Legacy Mount Hood Medical Center
🇺🇸Gresham, Oregon, United States
Spartanburg Medical Center
🇺🇸Spartanburg, South Carolina, United States
University of Texas Medical Branch
🇺🇸Galveston, Texas, United States
Prisma Health Cancer Institute - Faris
🇺🇸Greenville, South Carolina, United States
Skagit Regional Health Cancer Care Center
🇺🇸Mount Vernon, Washington, United States
VCU Community Memorial Health Center
🇺🇸South Hill, Virginia, United States
Prisma Health Cancer Institute - Eastside
🇺🇸Greenville, South Carolina, United States
Ottawa Hospital and Cancer Center-General Campus
🇨🇦Ottawa, Ontario, Canada
University Health Network-Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
ProHealth D N Greenwald Center
🇺🇸Mukwonago, Wisconsin, United States
Centre Antoine Lacassagne
🇫🇷Nice, France
Allan Blair Cancer Centre
🇨🇦Regina, Saskatchewan, Canada
Gustave Roussy
🇫🇷Villejuif, France
CHUM - Hopital Notre-Dame
🇨🇦Montreal, Quebec, Canada
UW Cancer Center at ProHealth Care
🇺🇸Waukesha, Wisconsin, United States
Odette Cancer Centre- Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Centre Leon Berard
🇫🇷Lyon, France
ProHealth Waukesha Memorial Hospital
🇺🇸Waukesha, Wisconsin, United States
Alegemeen Ziekenhuis Middelheim
🇧🇪Antwerpen, Belgium
Erasmus University Medical Center
🇳🇱Rotterdam, Netherlands
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Vanderbilt University/Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Huntsman Cancer Institute/University of Utah
🇺🇸Salt Lake City, Utah, United States
LDS Hospital
🇺🇸Salt Lake City, Utah, United States
University of Kansas Hospital-Westwood Cancer Center
🇺🇸Westwood, Kansas, United States
University of Kansas Cancer Center
🇺🇸Kansas City, Kansas, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Saint Joseph's Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
Arizona Oncology-Deer Valley Center
🇺🇸Phoenix, Arizona, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States
Legacy Good Samaritan Hospital and Medical Center
🇺🇸Portland, Oregon, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Providence Saint Vincent Medical Center
🇺🇸Portland, Oregon, United States
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
London Regional Cancer Program
🇨🇦London, Ontario, Canada
CHUM - Centre Hospitalier de l'Universite de Montreal
🇨🇦Montreal, Quebec, Canada
Mercy Hospital Saint Louis
🇺🇸Saint Louis, Missouri, United States
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States
Missouri Valley Cancer Consortium
🇺🇸Omaha, Nebraska, United States
Alegent Health Bergan Mercy Medical Center
🇺🇸Omaha, Nebraska, United States
Alegent Health Immanuel Medical Center
🇺🇸Omaha, Nebraska, United States
Nebraska Cancer Specialists - Omaha
🇺🇸Omaha, Nebraska, United States
Alegent Health Lakeside Hospital
🇺🇸Omaha, Nebraska, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Aurora Saint Luke's Medical Center
🇺🇸Milwaukee, Wisconsin, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
Abbott-Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
North Memorial Medical Health Center
🇺🇸Robbinsdale, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸Saint Louis Park, Minnesota, United States
Lakeview Hospital
🇺🇸Stillwater, Minnesota, United States
The Medical Center of Aurora
🇺🇸Aurora, Colorado, United States
UCHealth University of Colorado Hospital
🇺🇸Aurora, Colorado, United States
Walter Reed National Military Medical Center
🇺🇸Bethesda, Maryland, United States
Kaiser Permanente-South San Francisco
🇺🇸South San Francisco, California, United States
Alaska Oncology and Hematology LLC
🇺🇸Anchorage, Alaska, United States
Alaska Women's Cancer Care
🇺🇸Anchorage, Alaska, United States
Providence Alaska Medical Center
🇺🇸Anchorage, Alaska, United States
Anchorage Associates in Radiation Medicine
🇺🇸Anchorage, Alaska, United States
Anchorage Oncology Centre
🇺🇸Anchorage, Alaska, United States
Kaiser Permanente-Anaheim
🇺🇸Anaheim, California, United States
Kaiser Permanente Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
Memorial Medical Center
🇺🇸Springfield, Illinois, United States
University Oncology Associates
🇺🇸Clovis, California, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
🇺🇸Orange, California, United States
Sutter Cancer Centers Radiation Oncology Services-Roseville
🇺🇸Roseville, California, United States
Kaiser Permanente-Ontario
🇺🇸Ontario, California, United States
Kaiser Permanente Oakland-Broadway
🇺🇸Oakland, California, United States
Sutter Roseville Medical Center
🇺🇸Roseville, California, United States
Sutter Cancer Centers Radiation Oncology Services-Vacaville
🇺🇸Vacaville, California, United States
Sutter Solano Medical Center/Cancer Center
🇺🇸Vallejo, California, United States
Rocky Mountain Cancer Centers-Penrose
🇺🇸Colorado Springs, Colorado, United States
Penrose-Saint Francis Healthcare
🇺🇸Colorado Springs, Colorado, United States
Saint Francis Cancer Center
🇺🇸Colorado Springs, Colorado, United States
Porter Adventist Hospital
🇺🇸Denver, Colorado, United States
Littleton Adventist Hospital
🇺🇸Littleton, Colorado, United States
Saint Anthony Hospital
🇺🇸Lakewood, Colorado, United States
Banner McKee Medical Center
🇺🇸Loveland, Colorado, United States
Longmont United Hospital
🇺🇸Longmont, Colorado, United States
Parker Adventist Hospital
🇺🇸Parker, Colorado, United States
Saint Mary Corwin Medical Center
🇺🇸Pueblo, Colorado, United States
Smilow Cancer Hospital Care Center-Trumbull
🇺🇸Trumbull, Connecticut, United States
Boca Raton Regional Hospital
🇺🇸Boca Raton, Florida, United States
Sibley Memorial Hospital
🇺🇸Washington, District of Columbia, United States
Baptist MD Anderson Cancer Center
🇺🇸Jacksonville, Florida, United States
Mayo Clinic in Florida
🇺🇸Jacksonville, Florida, United States
Emory Proton Therapy Center
🇺🇸Atlanta, Georgia, United States
Emory University Hospital Midtown
🇺🇸Atlanta, Georgia, United States
Saint Alphonsus Cancer Care Center-Caldwell
🇺🇸Caldwell, Idaho, United States
Piedmont Hospital
🇺🇸Atlanta, Georgia, United States
Kootenai Clinic Cancer Services - Post Falls
🇺🇸Post Falls, Idaho, United States
Saint Alphonsus Cancer Care Center-Nampa
🇺🇸Nampa, Idaho, United States
Illinois CancerCare-Bloomington
🇺🇸Bloomington, Illinois, United States
Centralia Oncology Clinic
🇺🇸Centralia, Illinois, United States
Illinois CancerCare-Canton
🇺🇸Canton, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
Cancer Care Specialists of Illinois - Decatur
🇺🇸Decatur, Illinois, United States
Decatur Memorial Hospital
🇺🇸Decatur, Illinois, United States
Crossroads Cancer Center
🇺🇸Effingham, Illinois, United States
Illinois CancerCare-Kewanee Clinic
🇺🇸Kewanee, Illinois, United States
Western Illinois Cancer Treatment Center
🇺🇸Galesburg, Illinois, United States
AMITA Health Adventist Medical Center
🇺🇸La Grange, Illinois, United States
Illinois CancerCare-Macomb
🇺🇸Macomb, Illinois, United States
Illinois CancerCare-Ottawa Clinic
🇺🇸Ottawa, Illinois, United States
Cancer Care Center of O'Fallon
🇺🇸O'Fallon, Illinois, United States
Advocate Lutheran General Hospital
🇺🇸Park Ridge, Illinois, United States
Illinois CancerCare-Peoria
🇺🇸Peoria, Illinois, United States
OSF Saint Francis Radiation Oncology at Peoria Cancer Center
🇺🇸Peoria, Illinois, United States
Methodist Medical Center of Illinois
🇺🇸Peoria, Illinois, United States
OSF Saint Francis Medical Center
🇺🇸Peoria, Illinois, United States
Illinois CancerCare-Peru
🇺🇸Peru, Illinois, United States
Illinois CancerCare-Princeton
🇺🇸Princeton, Illinois, United States
Valley Radiation Oncology
🇺🇸Peru, Illinois, United States
Parkview Hospital Randallia
🇺🇸Fort Wayne, Indiana, United States
Parkview Regional Medical Center
🇺🇸Fort Wayne, Indiana, United States
Memorial Regional Cancer Center Day Road
🇺🇸Mishawaka, Indiana, United States
Memorial Hospital of South Bend
🇺🇸South Bend, Indiana, United States
McFarland Clinic - Ames
🇺🇸Ames, Iowa, United States
Mercy Cancer Center-West Lakes
🇺🇸Clive, Iowa, United States
Mission Cancer and Blood - West Des Moines
🇺🇸Clive, Iowa, United States
Methodist West Hospital
🇺🇸West Des Moines, Iowa, United States
University of Kansas Cancer Center-Overland Park
🇺🇸Overland Park, Kansas, United States
University of Kansas Hospital-Indian Creek Campus
🇺🇸Overland Park, Kansas, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸Baltimore, Maryland, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Fairview Ridges Hospital
🇺🇸Burnsville, Minnesota, United States
Minnesota Oncology Hematology PA-Maplewood
🇺🇸Maplewood, Minnesota, United States
Saint Francis Regional Medical Center
🇺🇸Shakopee, Minnesota, United States
Coborn Cancer Center at Saint Cloud Hospital
🇺🇸Saint Cloud, Minnesota, United States
Saint Francis Medical Center
🇺🇸Cape Girardeau, Missouri, United States
Nebraska Cancer Specialists/Oncology Hematology West PC
🇺🇸Grand Island, Nebraska, United States
Benefis Sletten Cancer Institute
🇺🇸Great Falls, Montana, United States
Midlands Community Hospital
🇺🇸Papillion, Nebraska, United States
Radiation Oncology Centers of Nevada Central
🇺🇸Las Vegas, Nevada, United States
Regional West Medical Center Cancer Center
🇺🇸Scottsbluff, Nebraska, United States
Renown Regional Medical Center
🇺🇸Reno, Nevada, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Saint Ann's Hospital
🇺🇸Westerville, Ohio, United States
Oklahoma Cancer Specialists and Research Institute-Tulsa
🇺🇸Tulsa, Oklahoma, United States
Clackamas Radiation Oncology Center
🇺🇸Clackamas, Oregon, United States
Lehigh Valley Hospital-Cedar Crest
🇺🇸Allentown, Pennsylvania, United States
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Saint Luke's University Hospital-Bethlehem Campus
🇺🇸Bethlehem, Pennsylvania, United States
Reading Hospital
🇺🇸West Reading, Pennsylvania, United States
Geisinger Wyoming Valley/Henry Cancer Center
🇺🇸Wilkes-Barre, Pennsylvania, United States
University of Pittsburgh Cancer Institute (UPCI)
🇺🇸Pittsburgh, Pennsylvania, United States
Greenville Health System Cancer Institute-Andrews
🇺🇸Greenville, South Carolina, United States
Prisma Health Cancer Institute - Butternut
🇺🇸Greenville, South Carolina, United States
Rapid City Regional Hospital
🇺🇸Rapid City, South Dakota, United States
Parkland Memorial Hospital
🇺🇸Dallas, Texas, United States
UTMB Cancer Center at Victory Lakes
🇺🇸League City, Texas, United States
Sandra L Maxwell Cancer Center
🇺🇸Cedar City, Utah, United States
Saint George Regional Medical Center
🇺🇸Saint George, Utah, United States
Utah Valley Regional Medical Center
🇺🇸Provo, Utah, United States
Dartmouth Cancer Center - North
🇺🇸Saint Johnsbury, Vermont, United States
Illinois CancerCare-Pekin
🇺🇸Pekin, Illinois, United States
OSF Saint Francis Radiation Oncology at Pekin
🇺🇸Pekin, Illinois, United States
UCHealth Memorial Hospital Central
🇺🇸Colorado Springs, Colorado, United States
Illinois CancerCare-Galesburg
🇺🇸Galesburg, Illinois, United States
Nebraska Hematology and Oncology
🇺🇸Lincoln, Nebraska, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Greater Regional Medical Center
🇺🇸Creston, Iowa, United States
Mercy Medical Center-West Lakes
🇺🇸West Des Moines, Iowa, United States
Prisma Health Cancer Institute - Spartanburg
🇺🇸Boiling Springs, South Carolina, United States
Intermountain Medical Center
🇺🇸Murray, Utah, United States
Cleveland Clinic Wooster Family Health and Surgery Center
🇺🇸Wooster, Ohio, United States
PeaceHealth Saint Joseph Medical Center
🇺🇸Bellingham, Washington, United States
Kadlec Clinic Hematology and Oncology
🇺🇸Kennewick, Washington, United States
Tri-Cities Cancer Center
🇺🇸Kennewick, Washington, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
FHCC South Lake Union
🇺🇸Seattle, Washington, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
University of Washington Medical Center - Montlake
🇺🇸Seattle, Washington, United States
PeaceHealth Southwest Medical Center
🇺🇸Vancouver, Washington, United States
Northwest Wisconsin Cancer Center
🇺🇸Ashland, Wisconsin, United States
West Virginia University Healthcare
🇺🇸Morgantown, West Virginia, United States
Gundersen Lutheran Medical Center
🇺🇸La Crosse, Wisconsin, United States
Medical University Vienna
🇦🇹Vienna, Austria
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
ProHealth Oconomowoc Memorial Hospital
🇺🇸Oconomowoc, Wisconsin, United States
BCCA-Vancouver Cancer Centre
🇨🇦Vancouver, British Columbia, Canada
Academ Zienkenhuis Bij De University
🇳🇱Amsterdam, Netherlands
Maastro Clinic-Maastricht Radiation Oncology
🇳🇱Maastricht, Netherlands
Sutter Medical Center Sacramento
🇺🇸Sacramento, California, United States
University of California Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
Sutter Cancer Centers Radiation Oncology Services-Cameron Park
🇺🇸Cameron Park, California, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Illinois CancerCare-Carthage
🇺🇸Carthage, Illinois, United States
Saint John's Hospital - Healtheast
🇺🇸Maplewood, Minnesota, United States
Illinois CancerCare-Eureka
🇺🇸Eureka, Illinois, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸Dallas, Texas, United States
Overlook Hospital
🇺🇸Summit, New Jersey, United States
Skagit Valley Hospital
🇺🇸Mount Vernon, Washington, United States
Altru Cancer Center
🇺🇸Grand Forks, North Dakota, United States
Utah Cancer Specialists-Salt Lake City
🇺🇸Salt Lake City, Utah, United States
AdventHealth Orlando
🇺🇸Orlando, Florida, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Orlando Health Cancer Institute
🇺🇸Orlando, Florida, United States
Norton Hospital Pavilion and Medical Campus
🇺🇸Louisville, Kentucky, United States
Norton Brownsboro Hospital and Medical Campus
🇺🇸Louisville, Kentucky, United States
University of Kansas Cancer Center - North
🇺🇸Kansas City, Missouri, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
University of Florida Health Science Center - Gainesville
🇺🇸Gainesville, Florida, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Iowa Methodist Medical Center
🇺🇸Des Moines, Iowa, United States
Mission Cancer and Blood - Des Moines
🇺🇸Des Moines, Iowa, United States
Broadlawns Medical Center
🇺🇸Des Moines, Iowa, United States
Mercy Medical Center - Des Moines
🇺🇸Des Moines, Iowa, United States
Mission Cancer and Blood - Laurel
🇺🇸Des Moines, Iowa, United States
Iowa Lutheran Hospital
🇺🇸Des Moines, Iowa, United States
University of Kentucky/Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Highland Hospital
🇺🇸Rochester, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Trinity Health Grand Rapids Hospital
🇺🇸Grand Rapids, Michigan, United States