Temozolomide and Radiation Therapy With or Without Bevacizumab in Treating Patients With Newly Diagnosed Glioblastoma

Phase 3

Completed

Conditions: Glioblastoma
Supratentorial Glioblastoma
Gliosarcoma

Interventions: Radiation: 3-Dimensional Conformal Radiation Therapy
Radiation: Intensity-Modulated Radiation Therapy
Biological: Bevacizumab
Other: Placebo
Other: Laboratory Biomarker Analysis
Other: Quality-of-Life Assessment
Drug: Temozolomide

Registration Number: NCT00884741

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This randomized phase III trial studies temozolomide (TMZ) and radiation therapy (RT) to compare how well they work with or without bevacizumab in treating patients with newly diagnosed glioblastoma or gliosarcoma. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as bevacizumab, may find tumor cells and help kill them. It is not yet known whether temozolomide and radiation therapy are more effective when given together with or without bevacizumab in treating glioblastoma or gliosarcoma.

Detailed Description: PRIMARY OBJECTIVES:

I. To determine whether the addition of bevacizumab to temozolomide and radiation improves efficacy as measured by progression-free and/or overall survival.

II. To assess the association between overall survival and K\^trans change from T1 to T2. (ACRIN 6686) III. To assess the association between overall survival and spin echo cerebral blood volume (CBV) change from T1 to T2. (ACRIN 6686)

SECONDARY OBJECTIVES:

I. To determine whether the tumor molecular profile conferring a mesenchymal/angiogenic phenotype is associated with a selective increase in benefit, as measured by either overall survival or progression-free survival, from the addition of bevacizumab.

II. To compare and record the toxicities of the conventional and bevacizumab-containing regimens.

III. To assess the association between progression-free survival and K\^trans change from T1 to T2. (ACRIN 6686) IV. To assess the association between progression-free survival and spin echo CBV change from T1 to T2. (ACRIN 6686) V. To assess the association between values of K\^trans and spin echo CBV measured separately at T0 and at T1, and overall and progression-free survival. (ACRIN 6686) VI. To assess the association between overall survival and K\^trans changes from T0 to T1 and from T2 to T3. (ACRIN 6686) VII. To assess the association between overall survival and spin echo CBV changes from T0 to T1 and from T2 to T3. (ACRIN 6686) VIII. To assess the association between overall survival and apparent diffusion coefficient (ADC) change from T0 to T1. (ACRIN 6686) IX. To assess the association between overall survival and ADC change from T1 to T2. (ACRIN 6686) X. To assess the association between progression-free survival and ADC change from T0 to T1. (ACRIN 6686) XI. To assess the association between progression-free survival and ADC change from T1 to T2. (ACRIN 6686) XII. To assess the association between T1 values of ADC and overall and progression-free survival. (ACRIN 6686) XIII. To assess the association between change in lesion size between T1 and T3, as measured by advanced magnetic resonance imaging (MRI), and overall and progression-free survival. (ACRIN 6686)

TERTIARY OBJECTIVES:

I. To determine the differential acute effects associated with the addition of bevacizumab to temozolomide and radiation, as compared to the conventional arm, on measures of neurocognitive function, health-related quality of life, and symptoms during radiation and across the longitudinal progression-free interval.

II. To determine the relationship of neurocognitive function, health-related quality of life, and symptoms, with progression-free and overall survival.

III. To determine the association between tumor molecular profile (i.e., mesenchymal/angiogenic phenotype and proneural phenotype) and neurocognitive function, health-related quality of life, and symptoms.

IV. To describe the association between health-related quality of life as measured by the European Organization for Research and Treatment Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTC-QL30/BCM20) and mean symptom severity as measured by the M. D. Anderson Symptom Inventory Brain Tumor Module (MDASI-BT) in patients enrolled in this study.

V. To evaluate the relationship between self-reported neurocognitive function and objectively measured tests of neurocognitive function (NCF).

VI. To assess the association between measures of change in enhancing tumor size at week 22 and overall survival in participants with glioma receiving chemoradiotherapy with and without bevacizumab.

VII. To assess the association between measures of change in T2-based tumor size at week 22 and overall survival in participants with glioma receiving chemoradiotherapy with and without bevacizumab.

VIII. To assess the association between changes in ADC values and overall survival in participants with glioma receiving chemoradiotherapy with and without bevacizumab.

OUTLINE: Patients are randomized to 1 of 2 treatment arms (there are also two registration steps prior to randomization which are labeled as "arms" in ClinicalTrials.gov to facilitate entry of results into the website).

ARM I: Patients undergo intensity-modulated radiation therapy or 3-dimensional conformal radiation therapy 5 days a week for 6 weeks and receive temozolomide orally (PO) once daily (QD) for up to 7 weeks. Beginning 4 weeks after completion of chemotherapy and radiation therapy, patients receive temozolomide PO QD on days 1-5. Treatment with temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive placebo IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemotherapy and radiation therapy and continuing until the completion of temozolomide.

ARM II: Patients undergo radiation therapy and receive temozolomide as in Arm I. Patients also receive bevacizumab IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemoradiotherapy and continuing until the completion of adjuvant temozolomide.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, and then every 6 months thereafter.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 637

Inclusion Criteria

Histologically proven diagnosis of glioblastoma or gliosarcoma (World Health Organization [WHO] grade IV) confirmed by central review prior to step 2 registration
Tumor tissue that is determined by central pathology review prior to step 2 registration to be of sufficient size for analysis of O-6-methylguanine-DNA methyltransferase (MGMT) and determination of molecular profile
- Patients must have at least 1 block of tumor tissue; submission of 2 blocks is strongly encouraged to maximize the chances of eligibility; at least 1 cubic centimeter of tissue composed primarily of tumor must be present
- CUSA (Cavitron ultrasonic aspirator)-derived material is not allowed; fresh frozen tumor tissue acquisition is encouraged
- Diagnosis must be made by surgical excision, either partial or complete; stereotactic biopsy is not allowed because it will not provide sufficient tissue for MGMT analysis
- The tumor tissue should be sent as soon as possible to maximize the likelihood of eligibility; tumor tissue should be submitted by 4 weeks after the surgical procedure so that the study registration and treatment can commence by the mandatory 5 week post-surgery outer limit
- Sites must submit tissue fir central review in order to obtain the MGMT analysis; patients from sites not following protocol-specified process for obtaining MGMT results will be made ineligible
The tumor must have a supratentorial component
History/physical examination within 14 days prior to step 2 registration
The patient must have recovered from the effects of surgery, postoperative infection, and other complications before step 2 registration
A diagnostic contrast-enhanced MRI of the brain must be performed preoperatively and postoperatively prior to the initiation of radiotherapy; the postoperative scan must be performed within 28 days prior to step 1 registration
- An MRI or computed tomography (CT) scan (potentially in addition to the postoperative scan) must be obtained within 10 days prior to the start of radiation therapy and must not demonstrate significant postoperative hemorrhage defined as > 1 cm diameter of blood; if > 1 cm of acute blood is detected, the patient will be ineligible for this trial; the radiation planning MRI or CT scan may be used to determine presence of hemorrhage
- Patients unable to undergo MR imaging because of non-compatible devices can be enrolled, provided pre- and postoperative contrast-enhanced CT scans are obtained and are of sufficient quality; preoperative and postoperative scans must be the same type; such patients cannot be enrolled into the advanced imaging component
Documentation of steroid doses within 14 days prior to step 2 registration
Karnofsky performance status >= 70
Absolute neutrophil count (ANC) >= 1,800 cells/mm^3
Platelets >= 100,000 cells/mm^3
Hemoglobin >= 10.0 g/dL (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 10.0 g/dl is acceptable)
Blood urea nitrogen (BUN) =< 30 mg/dL within 14 days prior to step 2 registration
Creatinine =< 1.7 mg/dl within 14 days prior to step 2 registration
Urine protein screened by urine analysis for urine protein creatinine (UPC) ratio; for UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be < 1000 mg
Bilirubin =< 2.0 mg/dl within 14 days prior to step 2 registration
Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< 3 x normal range within 14 days prior to step 2 registration
Systolic blood pressure =< 160 mg Hg or diastolic pressure =< 90 mm Hg within 14 days prior to step 2 registration
Electrocardiogram without evidence of acute cardiac ischemia within 14 days prior to step 2 registration
Prothrombin time/international normalized ratio (PT INR) < 1.4 for patients not on warfarin confirmed by testing within 14 days prior to step 2 registration
Patients on full-dose anticoagulants (e.g., warfarin or low molecular weight [LMW] heparin) must meet both of the following criteria:
- No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
- In-range INR (between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of LMW heparin
Patient must provide study specific informed consent prior to study entry
Women of childbearing potential and male participants must practice adequate contraception
For females of child-bearing potential, negative serum pregnancy test within 14 days prior to step 2 registration

Exclusion Criteria

Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for >= 3 years; (for example, carcinoma in situ of the breast, oral cavity, and cervix are all permissible)
Recurrent or multifocal malignant gliomas
Metastases detected below the tentorium or beyond the cranial vault
Prior chemotherapy or radiosensitizers for cancers of the head and neck region; note that prior chemotherapy for a different cancer is allowable, except prior temozolomide or bevacizumab; prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted
Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields
Severe, active co-morbidity, defined as follows:
- Unstable angina and/or congestive heart failure within the last 6 months
- Transmural myocardial infarction within the last 6 months
- Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of >= 2 mm using the analysis of an electrocardiogram (EKG) performed within 14 days of step 2 registration
- New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to step 2 registration
- History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months
- Serious and inadequately controlled cardiac arrhythmia
- Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease
- Evidence of bleeding diathesis or coagulopathy
- Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to step 2 registration, with the exception of the craniotomy for tumor resection
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of step 2 registration
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol
- Acquired immune deficiency syndrome (AIDS) based upon current Center for Disease Control (CDC) definition; note, however, that HIV testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive
- Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity
- Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy
Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
Pregnant or lactating women
Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study
For American College of Radiology Imaging Network (ACRIN) 6686 Advanced Imaging: inability to undergo MRI (e.g., due to safety reasons, such as presence of a pacemaker)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (radiation therapy, temozolomide, placebo)	Placebo	Patients undergo intensity-modulated radiation therapy or 3-dimensional conformal radiation therapy 5 days a week for 6 weeks and receive temozolomide PO QD for up to 7 weeks. Beginning 4 weeks after completion of chemotherapy and radiation therapy, patients receive temozolomide PO QD on days 1-5. Treatment with temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive placebo IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemotherapy and radiation therapy and continuing until the completion of temozolomide.
Arm II (radiation therapy, temozolomide, bevacizumab)	3-Dimensional Conformal Radiation Therapy	Patients undergo radiation therapy and receive temozolomide as in Arm I. Patients also receive bevacizumab IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemoradiotherapy and continuing until the completion of adjuvant temozolomide.
Arm I (radiation therapy, temozolomide, placebo)	3-Dimensional Conformal Radiation Therapy	Patients undergo intensity-modulated radiation therapy or 3-dimensional conformal radiation therapy 5 days a week for 6 weeks and receive temozolomide PO QD for up to 7 weeks. Beginning 4 weeks after completion of chemotherapy and radiation therapy, patients receive temozolomide PO QD on days 1-5. Treatment with temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive placebo IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemotherapy and radiation therapy and continuing until the completion of temozolomide.
Arm I (radiation therapy, temozolomide, placebo)	Intensity-Modulated Radiation Therapy	Patients undergo intensity-modulated radiation therapy or 3-dimensional conformal radiation therapy 5 days a week for 6 weeks and receive temozolomide PO QD for up to 7 weeks. Beginning 4 weeks after completion of chemotherapy and radiation therapy, patients receive temozolomide PO QD on days 1-5. Treatment with temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive placebo IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemotherapy and radiation therapy and continuing until the completion of temozolomide.
Arm II (radiation therapy, temozolomide, bevacizumab)	Bevacizumab	Patients undergo radiation therapy and receive temozolomide as in Arm I. Patients also receive bevacizumab IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemoradiotherapy and continuing until the completion of adjuvant temozolomide.
Arm II (radiation therapy, temozolomide, bevacizumab)	Intensity-Modulated Radiation Therapy	Patients undergo radiation therapy and receive temozolomide as in Arm I. Patients also receive bevacizumab IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemoradiotherapy and continuing until the completion of adjuvant temozolomide.
Arm II (radiation therapy, temozolomide, bevacizumab)	Laboratory Biomarker Analysis	Patients undergo radiation therapy and receive temozolomide as in Arm I. Patients also receive bevacizumab IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemoradiotherapy and continuing until the completion of adjuvant temozolomide.
Arm I (radiation therapy, temozolomide, placebo)	Laboratory Biomarker Analysis	Patients undergo intensity-modulated radiation therapy or 3-dimensional conformal radiation therapy 5 days a week for 6 weeks and receive temozolomide PO QD for up to 7 weeks. Beginning 4 weeks after completion of chemotherapy and radiation therapy, patients receive temozolomide PO QD on days 1-5. Treatment with temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive placebo IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemotherapy and radiation therapy and continuing until the completion of temozolomide.
Arm I (radiation therapy, temozolomide, placebo)	Quality-of-Life Assessment	Patients undergo intensity-modulated radiation therapy or 3-dimensional conformal radiation therapy 5 days a week for 6 weeks and receive temozolomide PO QD for up to 7 weeks. Beginning 4 weeks after completion of chemotherapy and radiation therapy, patients receive temozolomide PO QD on days 1-5. Treatment with temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive placebo IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemotherapy and radiation therapy and continuing until the completion of temozolomide.
Arm II (radiation therapy, temozolomide, bevacizumab)	Quality-of-Life Assessment	Patients undergo radiation therapy and receive temozolomide as in Arm I. Patients also receive bevacizumab IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemoradiotherapy and continuing until the completion of adjuvant temozolomide.
Arm I (radiation therapy, temozolomide, placebo)	Temozolomide	Patients undergo intensity-modulated radiation therapy or 3-dimensional conformal radiation therapy 5 days a week for 6 weeks and receive temozolomide PO QD for up to 7 weeks. Beginning 4 weeks after completion of chemotherapy and radiation therapy, patients receive temozolomide PO QD on days 1-5. Treatment with temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive placebo IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemotherapy and radiation therapy and continuing until the completion of temozolomide.
Arm II (radiation therapy, temozolomide, bevacizumab)	Temozolomide	Patients undergo radiation therapy and receive temozolomide as in Arm I. Patients also receive bevacizumab IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemoradiotherapy and continuing until the completion of adjuvant temozolomide.

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS)	From randomization to date of death or last follow-up. Analysis occurs after all 390 deaths have been reported.	Survival time was defined as time from randomization to date of death from any cause and was estimated by the Kaplan-Meier method. Patients last known to be alive were censored at the date of last contact. This analysis was planned to occur when 390 deaths had been reported.
Progression-free Survival (PFS)	From randomization to date of progression, death, or last follow-up for progression-free survival. Analysis occurs after all 390 deaths have been reported.	Progression-free survival was defined as time from randomization to date of progression, death, or last follow-up, and was estimated by the Kaplan-Meier method. Patients last known to be alive were censored at the date of last contact. This analysis was planned to occur when 390 deaths had been reported.

Secondary Outcome Measures

Name	Time	Method
Incidence of Grade 3 and Higher Treatment-related Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (AEs) Version 3.0	Up to 30 days	AEs are graded by using CTCAE 3.0. The difference between the two randomized arms in the percentage of patients with grade 3 or higher toxicities reported as possibly/probably/definitely related to protocol treatment will be tested using a chi square test.

Trial Locations

Locations (328): Riverside Methodist Hospital
🇺🇸
Columbus, Ohio, United States
Grant Medical Center
🇺🇸
Columbus, Ohio, United States
The Mark H Zangmeister Center
🇺🇸
Columbus, Ohio, United States
John Muir Medical Center-Concord Campus
🇺🇸
Concord, California, United States
FirstHealth of the Carolinas-Moore Regional Hosiptal
🇺🇸
Pinehurst, North Carolina, United States
Mercy San Juan Medical Center
🇺🇸
Carmichael, California, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸
Dallas, Texas, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸
Chicago, Illinois, United States
Allegheny General Hospital
🇺🇸
Pittsburgh, Pennsylvania, United States
UPMC-Passavant Hospital
🇺🇸
Pittsburgh, Pennsylvania, United States
Minnesota Oncology Hematology PA-Maplewood
🇺🇸
Maplewood, Minnesota, United States
Siteman Cancer Center at Saint Peters Hospital
🇺🇸
Saint Peters, Missouri, United States
Concord Hospital
🇺🇸
Concord, New Hampshire, United States
Cleveland Clinic Cancer Center/Fairview Hospital
🇺🇸
Cleveland, Ohio, United States
Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
M D Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Virginia Mason Medical Center
🇺🇸
Seattle, Washington, United States
Swedish Medical Center-First Hill
🇺🇸
Seattle, Washington, United States
IU Health Methodist Hospital
🇺🇸
Indianapolis, Indiana, United States
Community Cancer Center East
🇺🇸
Indianapolis, Indiana, United States
IU Health Central Indiana Cancer Centers-East
🇺🇸
Indianapolis, Indiana, United States
Community Cancer Center North
🇺🇸
Indianapolis, Indiana, United States
Saint Vincent Hospital and Health Care Center
🇺🇸
Indianapolis, Indiana, United States
University of California San Diego
🇺🇸
San Diego, California, United States
University of Cincinnati/Barrett Cancer Center
🇺🇸
Cincinnati, Ohio, United States
Abbott-Northwestern Hospital
🇺🇸
Minneapolis, Minnesota, United States
University of Texas Health Science Center at San Antonio
🇺🇸
San Antonio, Texas, United States
Sanford Broadway Medical Center
🇺🇸
Fargo, North Dakota, United States
Saint Barnabas Medical Center
🇺🇸
Livingston, New Jersey, United States
Kansas City NCI Community Oncology Research Program
🇺🇸
Prairie Village, Kansas, United States
Abington Memorial Hospital
🇺🇸
Abington, Pennsylvania, United States
California Pacific Medical Center-Pacific Campus
🇺🇸
San Francisco, California, United States
Huntsman Cancer Institute/University of Utah
🇺🇸
Salt Lake City, Utah, United States
LDS Hospital
🇺🇸
Salt Lake City, Utah, United States
Saint John Hospital and Medical Center
🇺🇸
Detroit, Michigan, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Providence Portland Medical Center
🇺🇸
Portland, Oregon, United States
Froedtert and the Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
Nebraska Methodist Hospital
🇺🇸
Omaha, Nebraska, United States
Alegent Health Immanuel Medical Center
🇺🇸
Omaha, Nebraska, United States
Alegent Health Bergan Mercy Medical Center
🇺🇸
Omaha, Nebraska, United States
University of Nebraska Medical Center
🇺🇸
Omaha, Nebraska, United States
Rocky Mountain Cancer Centers-Aurora
🇺🇸
Aurora, Colorado, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Southeast Clinical Oncology Research (SCOR) Consortium NCORP
🇺🇸
Winston-Salem, North Carolina, United States
Sutter Medical Center Sacramento
🇺🇸
Sacramento, California, United States
Mercy General Hospital Radiation Oncology Center
🇺🇸
Sacramento, California, United States
South Sacramento Cancer Center
🇺🇸
Sacramento, California, United States
Saint Joseph Mercy Hospital
🇺🇸
Ann Arbor, Michigan, United States
Novant Health Forsyth Medical Center
🇺🇸
Winston-Salem, North Carolina, United States
The James Graham Brown Cancer Center at University of Louisville
🇺🇸
Louisville, Kentucky, United States
Florida Hospital Orlando
🇺🇸
Orlando, Florida, United States
Providence Hospital
🇺🇸
Mobile, Alabama, United States
Arizona Oncology Associates-West Orange Grove
🇺🇸
Tucson, Arizona, United States
Mayo Clinic in Arizona
🇺🇸
Scottsdale, Arizona, United States
Arizona Oncology Services Foundation
🇺🇸
Scottsdale, Arizona, United States
Sutter Cancer Centers Radiation Oncology Services-Auburn
🇺🇸
Auburn, California, United States
Alta Bates Summit Medical Center-Herrick Campus
🇺🇸
Berkeley, California, United States
Sutter Cancer Centers Radiation Oncology Services-Cameron Park
🇺🇸
Cameron Park, California, United States
California Cancer Center - North Fresno
🇺🇸
Fresno, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸
Duarte, California, United States
USC / Norris Comprehensive Cancer Center
🇺🇸
Los Angeles, California, United States
UC San Diego Moores Cancer Center
🇺🇸
La Jolla, California, United States
Saint Jude Medical Center
🇺🇸
Fullerton, California, United States
Bay Area Tumor Institute
🇺🇸
Oakland, California, United States
Memorial Medical Center
🇺🇸
Springfield, Illinois, United States
Kaiser Permanente Oakland-Broadway
🇺🇸
Oakland, California, United States
Saint Joseph Hospital - Orange
🇺🇸
Orange, California, United States
Pomona Valley Hospital Medical Center
🇺🇸
Pomona, California, United States
Kaiser Permanente-Rancho Cordova Cancer Center
🇺🇸
Rancho Cordova, California, United States
The Permanente Medical Group-Roseville Radiation Oncology
🇺🇸
Roseville, California, United States
Rohnert Park Cancer Center
🇺🇸
Rohnert Park, California, United States
Sutter Cancer Centers Radiation Oncology Services-Roseville
🇺🇸
Roseville, California, United States
John Muir Medical Center-Walnut Creek
🇺🇸
Walnut Creek, 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 Cancer Centers Radiation Oncology Services-Vacaville
🇺🇸
Vacaville, California, United States
Boulder Community Hospital
🇺🇸
Boulder, Colorado, United States
Swedish Medical Center
🇺🇸
Englewood, Colorado, United States
Porter Adventist Hospital
🇺🇸
Denver, Colorado, United States
Poudre Valley Hospital
🇺🇸
Fort Collins, Colorado, United States
Rocky Mountain Cancer Centers-Littleton
🇺🇸
Littleton, Colorado, United States
North Suburban Medical Center
🇺🇸
Thornton, Colorado, United States
SCL Health Lutheran Medical Center
🇺🇸
Wheat Ridge, Colorado, United States
The Hospital of Central Connecticut
🇺🇸
New Britain, Connecticut, United States
Hartford Hospital
🇺🇸
Hartford, Connecticut, United States
Saint Vincent's Medical Center
🇺🇸
Bridgeport, Connecticut, United States
Broward Health Medical Center
🇺🇸
Fort Lauderdale, Florida, United States
William Backus Hospital
🇺🇸
Norwich, Connecticut, United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
🇺🇸
Hollywood, Florida, United States
Baptist MD Anderson Cancer Center
🇺🇸
Jacksonville, Florida, United States
Integrated Community Oncology Network-Southside Cancer Center
🇺🇸
Jacksonville, Florida, United States
Integrated Community Oncology Network-Florida Cancer Center Beaches
🇺🇸
Jacksonville Beach, Florida, United States
Mayo Clinic in Florida
🇺🇸
Jacksonville, Florida, United States
Mount Sinai Medical Center
🇺🇸
Miami Beach, Florida, United States
Baptist Hospital of Miami
🇺🇸
Miami, Florida, United States
Baptist Medical Center South
🇺🇸
Jacksonville, Florida, United States
UF Cancer Center at Orlando Health
🇺🇸
Orlando, Florida, United States
21st Century Oncology-Orange Park
🇺🇸
Orange Park, Florida, United States
21st Century Oncology-Palatka
🇺🇸
Palatka, Florida, United States
Emory University Hospital/Winship Cancer Institute
🇺🇸
Atlanta, Georgia, United States
Sacred Heart Hospital
🇺🇸
Eau Claire, Wisconsin, United States
Integrated Community Oncology Network-Flager Cancer Center
🇺🇸
Saint Augustine, Florida, United States
Robert and Carol Weissman Cancer Center at Martin Health
🇺🇸
Stuart, Florida, United States
Piedmont Hospital
🇺🇸
Atlanta, Georgia, United States
Northeast Georgia Medical Center-Gainesville
🇺🇸
Gainesville, Georgia, United States
Dekalb Medical Center
🇺🇸
Decatur, Georgia, United States
John B Amos Cancer Center
🇺🇸
Columbus, Georgia, United States
Memorial University Medical Center
🇺🇸
Savannah, Georgia, United States
Southern Regional Medical Center
🇺🇸
Riverdale, Georgia, United States
Northwest Community Hospital
🇺🇸
Arlington Heights, Illinois, United States
John H Stroger Jr Hospital of Cook County
🇺🇸
Chicago, Illinois, United States
Ingalls Memorial Hospital
🇺🇸
Harvey, Illinois, United States
Trinity Medical Center
🇺🇸
Moline, Illinois, United States
Decatur Memorial Hospital
🇺🇸
Decatur, Illinois, United States
Loyola University Medical Center
🇺🇸
Maywood, Illinois, United States
Edward Hospital/Cancer Center
🇺🇸
Naperville, Illinois, United States
Methodist Medical Center of Illinois
🇺🇸
Peoria, Illinois, United States
IU Health Bloomington
🇺🇸
Bloomington, Indiana, United States
Radiation Oncology Associates PC
🇺🇸
Fort Wayne, Indiana, United States
IU Health Ball Memorial Hospital
🇺🇸
Muncie, Indiana, United States
McFarland Clinic PC-William R Bliss Cancer Center
🇺🇸
Ames, Iowa, United States
Physicians' Clinic of Iowa PC
🇺🇸
Cedar Rapids, Iowa, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸
Iowa City, Iowa, United States
Mercy Medical Center - North Iowa
🇺🇸
Mason City, Iowa, United States
University of Kansas Cancer Center-Overland Park
🇺🇸
Overland Park, Kansas, United States
University of Kansas Cancer Center
🇺🇸
Kansas City, Kansas, United States
Mary Bird Perkins Cancer Center
🇺🇸
Baton Rouge, Louisiana, United States
Central Maine Medical Center
🇺🇸
Lewiston, Maine, United States
Anne Arundel Medical Center
🇺🇸
Annapolis, Maryland, United States
Maine Medical Center- Scarborough Campus
🇺🇸
Scarborough, Maine, United States
Saint Anne's Hospital
🇺🇸
Fall River, Massachusetts, United States
Cape Cod Hospital
🇺🇸
Hyannis, Massachusetts, United States
University of Maryland/Greenebaum Cancer Center
🇺🇸
Baltimore, Maryland, United States
Saint Agnes Hospital
🇺🇸
Baltimore, Maryland, United States
Massachusetts General Hospital Cancer Center
🇺🇸
Boston, Massachusetts, United States
Lowell General Hospital
🇺🇸
Lowell, Massachusetts, United States
D'Amour Center for Cancer Care
🇺🇸
Springfield, Massachusetts, United States
Beaumont Hospital-Dearborn
🇺🇸
Dearborn, Michigan, United States
Genesys Regional Medical Center-West Flint Campus
🇺🇸
Flint, Michigan, United States
West Michigan Cancer Center
🇺🇸
Kalamazoo, Michigan, United States
William Beaumont Hospital-Royal Oak
🇺🇸
Royal Oak, Michigan, United States
Saint John Macomb-Oakland Hospital
🇺🇸
Warren, Michigan, United States
Saint Mary's of Michigan
🇺🇸
Saginaw, Michigan, United States
Sanford Clinic North-Bemidgi
🇺🇸
Bemidji, Minnesota, United States
Fairview Ridges Hospital
🇺🇸
Burnsville, Minnesota, United States
Saint Luke's Hospital of Duluth
🇺🇸
Duluth, Minnesota, United States
Coborn Cancer Center at Saint Cloud Hospital
🇺🇸
Saint Cloud, Minnesota, United States
Ridgeview Medical Center
🇺🇸
Waconia, Minnesota, United States
Regions Hospital
🇺🇸
Saint Paul, Minnesota, United States
Cape Radiation Oncology
🇺🇸
Cape Girardeau, Missouri, United States
United Hospital
🇺🇸
Saint Paul, Minnesota, United States
Siteman Cancer Center at West County Hospital
🇺🇸
Creve Coeur, Missouri, United States
Singing River Hospital
🇺🇸
Pascagoula, Mississippi, United States
Billings Clinic Cancer Center
🇺🇸
Billings, Montana, United States
CHI Health Good Samaritan
🇺🇸
Kearney, Nebraska, United States
Saint Elizabeth Regional Medical Center
🇺🇸
Lincoln, Nebraska, United States
Renown Regional Medical Center
🇺🇸
Reno, Nevada, United States
Nevada Cancer Research Foundation CCOP
🇺🇸
Las Vegas, Nevada, United States
Elliot Hospital
🇺🇸
Manchester, New Hampshire, United States
Monmouth Medical Center
🇺🇸
Long Branch, New Jersey, United States
Riverview Medical Center/Booker Cancer Center
🇺🇸
Red Bank, New Jersey, United States
Sparta Cancer Treatment Center
🇺🇸
Sparta, New Jersey, United States
New York Oncology Hematology PC - Albany
🇺🇸
Albany, New York, United States
Sands Cancer Center
🇺🇸
Canandaigua, New York, United States
South Nassau Communities
🇺🇸
Oceanside, New York, United States
State University of New York Upstate Medical University
🇺🇸
Syracuse, New York, United States
Hudson Valley Oncology Associates
🇺🇸
Poughkeepsie, New York, United States
Stony Brook University Medical Center
🇺🇸
Stony Brook, New York, United States
Novant Health Presbyterian Medical Center
🇺🇸
Charlotte, North Carolina, United States
Carolinas Medical Center/Levine Cancer Institute
🇺🇸
Charlotte, North Carolina, United States
Margaret R Pardee Memorial Hospital
🇺🇸
Hendersonville, North Carolina, United States
Duke Women's Cancer Care Raleigh
🇺🇸
Raleigh, North Carolina, United States
Akron General Medical Center
🇺🇸
Akron, Ohio, United States
Mercy Medical Center
🇺🇸
Canton, Ohio, United States
Summa Barberton Hospital
🇺🇸
Barberton, Ohio, United States
UHHS-Chagrin Highlands Medical Center
🇺🇸
Beachwood, Ohio, United States
MetroHealth Medical Center
🇺🇸
Cleveland, Ohio, United States
Aultman Health Foundation
🇺🇸
Canton, Ohio, United States
Ohio State University Comprehensive Cancer Center
🇺🇸
Columbus, Ohio, United States
Hillcrest Hospital Cancer Center
🇺🇸
Mayfield Heights, Ohio, United States
Lake University Ireland Cancer Center
🇺🇸
Mentor, Ohio, United States
Cancer Care Center, Incorporated
🇺🇸
Salem, Ohio, United States
Saint Charles Hospital
🇺🇸
Oregon, Ohio, United States
Southwest General Health Center Ireland Cancer Center
🇺🇸
Middleburg Heights, Ohio, United States
North Coast Cancer Care
🇺🇸
Sandusky, Ohio, United States
Trinity's Tony Teramana Cancer Center
🇺🇸
Steubenville, Ohio, United States
Flower Hospital
🇺🇸
Sylvania, Ohio, United States
Mercy Saint Anne Hospital
🇺🇸
Toledo, Ohio, United States
UHHS-Westlake Medical Center
🇺🇸
Westlake, Ohio, United States
University Pointe
🇺🇸
West Chester, Ohio, United States
Legacy Good Samaritan Hospital and Medical Center
🇺🇸
Portland, Oregon, United States
Natalie Warren Bryant Cancer Center at Saint Francis
🇺🇸
Tulsa, Oklahoma, United States
Willamette Valley Cancer Center
🇺🇸
Eugene, Oregon, United States
Providence Saint Vincent Medical Center
🇺🇸
Portland, Oregon, United States
Salem Hospital
🇺🇸
Salem, Oregon, United States
Lehigh Valley Hospital-Cedar Crest
🇺🇸
Allentown, Pennsylvania, United States
UPMC-Heritage Valley Health System Beaver
🇺🇸
Beaver, Pennsylvania, United States
Saint Luke's University Hospital-Bethlehem Campus
🇺🇸
Bethlehem, Pennsylvania, United States
Bryn Mawr Hospital
🇺🇸
Bryn Mawr, Pennsylvania, United States
Geisinger Medical Center
🇺🇸
Danville, Pennsylvania, United States
Northeast Radiation Oncology Center
🇺🇸
Dunmore, Pennsylvania, United States
Fox Chase Cancer Center Buckingham
🇺🇸
Furlong, Pennsylvania, United States
Pocono Medical Center
🇺🇸
East Stroudsburg, Pennsylvania, United States
The Regional Cancer Center
🇺🇸
Erie, Pennsylvania, United States
Adams Cancer Center
🇺🇸
Gettysburg, Pennsylvania, United States
Cherry Tree Cancer Center
🇺🇸
Hanover, Pennsylvania, United States
Penn State Milton S Hershey Medical Center
🇺🇸
Hershey, Pennsylvania, United States
UPMC Cancer Centers - Arnold Palmer Pavilion
🇺🇸
Greensburg, Pennsylvania, United States
Armstrong Center for Medicine and Health
🇺🇸
Kittanning, Pennsylvania, United States
Lancaster General Hospital
🇺🇸
Lancaster, Pennsylvania, United States
UPMC Cancer Center at UPMC McKeesport
🇺🇸
McKeesport, Pennsylvania, United States
Allegheny Valley Hospital
🇺🇸
Natrona Heights, Pennsylvania, United States
Paoli Memorial Hospital
🇺🇸
Paoli, Pennsylvania, United States
Intercommunity Cancer Center
🇺🇸
Monroeville, Pennsylvania, United States
UPMC Jameson
🇺🇸
New Castle, Pennsylvania, United States
Aria Health-Torresdale Campus
🇺🇸
Philadelphia, Pennsylvania, United States
UPMC-Shadyside Hospital
🇺🇸
Pittsburgh, Pennsylvania, United States
UPMC Jefferson Regional Radiation Oncology
🇺🇸
Pittsburgh, Pennsylvania, United States
Reading Hospital
🇺🇸
West Reading, Pennsylvania, United States
UPMC Cancer Center at UPMC Northwest
🇺🇸
Seneca, Pennsylvania, United States
UPMC Washington Hospital Radiation Oncology
🇺🇸
Washington, Pennsylvania, United States
Lankenau Medical Center
🇺🇸
Wynnewood, Pennsylvania, United States
WellSpan Health-York Hospital
🇺🇸
York, Pennsylvania, United States
Spartanburg Medical Center
🇺🇸
Spartanburg, South Carolina, United States
Sanford Cancer Center-Oncology Clinic
🇺🇸
Sioux Falls, South Dakota, United States
Rapid City Regional Hospital
🇺🇸
Rapid City, South Dakota, United States
Erlanger Medical Center
🇺🇸
Chattanooga, Tennessee, United States
Jackson-Madison County General Hospital
🇺🇸
Jackson, Tennessee, United States
Thompson Cancer Survival Center
🇺🇸
Knoxville, Tennessee, United States
Texas Oncology Bedford
🇺🇸
Bedford, Texas, United States
Texas Oncology-Arlington South
🇺🇸
Arlington, Texas, United States
Saint Joseph Regional Cancer Center
🇺🇸
Bryan, Texas, United States
Texas Oncology Methodist Charlton Cancer Center
🇺🇸
Dallas, Texas, United States
Texas Oncology-Denton South
🇺🇸
Denton, Texas, United States
University of Texas Medical Branch
🇺🇸
Galveston, Texas, United States
Texas Oncology-Longview Cancer Center
🇺🇸
Longview, Texas, United States
West Texas Cancer Center
🇺🇸
Odessa, Texas, United States
Covenant Medical Center-Lakeside
🇺🇸
Lubbock, Texas, United States
Texas Cancer Center-Sherman
🇺🇸
Sherman, Texas, United States
Texas Oncology Cancer Center Sugar Land
🇺🇸
Sugar Land, Texas, United States
McKay-Dee Hospital Center
🇺🇸
Ogden, Utah, United States
Tyler Cancer Center
🇺🇸
Tyler, Texas, United States
Dixie Medical Center Regional Cancer Center
🇺🇸
Saint George, Utah, United States
Utah Valley Regional Medical Center
🇺🇸
Provo, Utah, United States
Intermountain Medical Center
🇺🇸
Murray, Utah, United States
Utah Cancer Specialists-Salt Lake City
🇺🇸
Salt Lake City, Utah, United States
Harrison Medical Center
🇺🇸
Bremerton, Washington, United States
Inova Alexandria Hospital
🇺🇸
Alexandria, Virginia, United States
Sentara Norfolk General Hospital
🇺🇸
Norfolk, Virginia, United States
Naval Medical Center - Portsmouth
🇺🇸
Portsmouth, Virginia, United States
PeaceHealth Saint Joseph Medical Center
🇺🇸
Bellingham, Washington, United States
Cancer Care Northwest - Spokane South
🇺🇸
Spokane, Washington, United States
PeaceHealth Southwest Medical Center
🇺🇸
Vancouver, Washington, United States
Compass Oncology Vancouver
🇺🇸
Vancouver, Washington, United States
North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
🇺🇸
Yakima, Washington, United States
Wheeling Hospital/Schiffler Cancer Center
🇺🇸
Wheeling, West Virginia, United States
Langlade Hospital and Cancer Center
🇺🇸
Antigo, Wisconsin, United States
Radiology Associates of Appleton/ThedaCare Regional Medical Center
🇺🇸
Appleton, Wisconsin, United States
Saint Vincent Hospital Cancer Center Green Bay
🇺🇸
Green Bay, Wisconsin, United States
Bellin Memorial Hospital
🇺🇸
Green Bay, Wisconsin, United States
Marshfield Clinic Cancer Center at Sacred Heart
🇺🇸
Eau Claire, Wisconsin, United States
UW Cancer Center Johnson Creek
🇺🇸
Johnson Creek, Wisconsin, United States
Saint Vincent Hospital Cancer Center at Saint Mary's
🇺🇸
Green Bay, Wisconsin, United States
Marshfield Clinic
🇺🇸
Marshfield, Wisconsin, United States
Bay Area Medical Center
🇺🇸
Marinette, Wisconsin, United States
Gundersen Lutheran Medical Center
🇺🇸
La Crosse, Wisconsin, United States
Marshfield Clinic-Minocqua Center
🇺🇸
Minocqua, Wisconsin, United States
Saint Michael's Hospital
🇺🇸
Stevens Point, Wisconsin, United States
Diagnostic and Treatment Center
🇺🇸
Weston, Wisconsin, United States
Aspirus Regional Cancer Center
🇺🇸
Wausau, Wisconsin, United States
ProHealth Waukesha Memorial Hospital
🇺🇸
Waukesha, Wisconsin, United States
Health Sciences North
🇨🇦
Sudbury, Ontario, Canada
Aspirus UW Cancer Center
🇺🇸
Wisconsin Rapids, Wisconsin, United States
Doctor H. Bliss Murphy Cancer Centre
🇨🇦
St. John's, Newfoundland and Labrador, Canada
CHUM - Hopital Notre-Dame
🇨🇦
Montreal, Quebec, Canada
McGill University Department of Oncology
🇨🇦
Montreal, Quebec, Canada
Allan Blair Cancer Centre
🇨🇦
Regina, Saskatchewan, Canada
Tel Aviv Sourasky Medical Center
🇮🇱
Tel Aviv, Israel
Northern Indiana Cancer Research Consortium
🇺🇸
South Bend, Indiana, United States
University of Vermont Medical Center
🇺🇸
Burlington, Vermont, United States
Summa Akron City Hospital/Cooper Cancer Center
🇺🇸
Akron, Ohio, United States
Cancer Care Associates of Fresno Medical Group Inc
🇺🇸
Fresno, California, United States
Saint Alphonsus Cancer Care Center-Boise
🇺🇸
Boise, Idaho, United States
Thomas Jefferson University Hospital
🇺🇸
Philadelphia, Pennsylvania, United States
Parkview Hospital Randallia
🇺🇸
Fort Wayne, Indiana, United States
Sparrow Hospital
🇺🇸
Lansing, Michigan, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸
Saint Louis Park, Minnesota, United States
Mission Hospital-Memorial Campus
🇺🇸
Asheville, North Carolina, United States
The Klabzuba Cancer Center
🇺🇸
Fort Worth, Texas, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸
New York, New York, United States
Maimonides Medical Center
🇺🇸
Brooklyn, New York, United States
North Memorial Medical Health Center
🇺🇸
Robbinsdale, Minnesota, United States
Marshfield Medical Center
🇺🇸
Marshfield, Wisconsin, United States
Mercy Hospital
🇺🇸
Coon Rapids, Minnesota, United States
Advocate Lutheran General Hospital
🇺🇸
Park Ridge, Illinois, United States
Providence Alaska Medical Center
🇺🇸
Anchorage, Alaska, United States
Penrose-Saint Francis Healthcare
🇺🇸
Colorado Springs, Colorado, United States
Dartmouth Hitchcock Medical Center
🇺🇸
Lebanon, New Hampshire, United States
Fox Chase Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States
Marshfield Clinic - Weston Center
🇺🇸
Weston, Wisconsin, United States
Toledo Clinic Cancer Centers-Maumee
🇺🇸
Maumee, Ohio, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
🇺🇸
New Brunswick, New Jersey, United States
Case Western Reserve University
🇺🇸
Cleveland, Ohio, United States
Yale University
🇺🇸
New Haven, Connecticut, United States
Louisiana State University Health Sciences Center Shreveport
🇺🇸
Shreveport, Louisiana, United States
Truman Medical Center
🇺🇸
Kansas City, Missouri, United States
The University of Kansas Cancer Center-South
🇺🇸
Kansas City, Missouri, United States
The University of Kansas Cancer Center-North
🇺🇸
Kansas City, Missouri, United States
University of Hawaii Cancer Center
🇺🇸
Honolulu, Hawaii, United States
Iowa Methodist Medical Center
🇺🇸
Des Moines, Iowa, United States
Mercy Medical Center - Des Moines
🇺🇸
Des Moines, Iowa, United States
Ochsner Medical Center Jefferson
🇺🇸
New Orleans, Louisiana, United States
Montefiore Medical Center - Moses Campus
🇺🇸
Bronx, New York, United States
Dean Hematology and Oncology Clinic
🇺🇸
Madison, Wisconsin, United States
University of Wisconsin Hospital and Clinics
🇺🇸
Madison, Wisconsin, United States
Via Christi Regional Medical Center
🇺🇸
Wichita, Kansas, United States
Wesley Medical Center
🇺🇸
Wichita, Kansas, United States
Lovelace Medical Center-Downtown
🇺🇸
Albuquerque, New Mexico, United States
New Mexico Oncology Hematology Consultants
🇺🇸
Albuquerque, New Mexico, United States
University of Rochester
🇺🇸
Rochester, New York, United States
University of New Mexico Cancer Center
🇺🇸
Albuquerque, New Mexico, United States
Highland Hospital
🇺🇸
Rochester, New York, United States
University Radiation Oncology
🇺🇸
Rochester, New York, United States
UPMC-Johnstown/John P. Murtha Regional Cancer Center
🇺🇸
Johnstown, Pennsylvania, United States
Rhode Island Hospital
🇺🇸
Providence, Rhode Island, United States