Testing if High Dose Radiation Only to the Sites of Brain Cancer Compared to Whole Brain Radiation That Avoids the Hippocampus is Better at Preventing Loss of Memory and Thinking Ability
- Conditions
- Metastatic Lung Small Cell CarcinomaMetastatic Malignant Neoplasm in the BrainRecurrent Lung Small Cell CarcinomaStage IV Lung Cancer AJCC v8
- Interventions
- Procedure: Biospecimen CollectionProcedure: Magnetic Resonance ImagingOther: Neurocognitive AssessmentRadiation: Stereotactic RadiosurgeryRadiation: Whole-Brain Radiotherapy
- Registration Number
- NCT04804644
- Lead Sponsor
- NRG Oncology
- Brief Summary
This phase III trial compares the effect of stereotactic radiosurgery to standard of care memantine and whole brain radiation therapy that avoids the hippocampus (the memory zone of the brain) for the treatment of small cell lung cancer that has spread to the brain. Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue. Whole brain radiation therapy delivers a low dose of radiation to the entire brain including the normal brain tissue. Hippocampal avoidance during whole-brain radiation therapy (HA-WBRT) decreases the amount of radiation that is delivered to the hippocampus which is a brain structure that is important for memory. The drug, memantine, is also often given with whole brain radiotherapy because it may decrease the risk of side effects related to thinking and memory. Stereotactic radiosurgery may decrease side effects related to memory and thinking compared to standard of care HA-WBRT plus memantine.
- Detailed Description
PRIMARY OBJECTIVE:
I. Determine whether stereotactic radiosurgery (SRS) relative to whole brain radiotherapy with hippocampal avoidance (HA-WBRT) plus memantine hydrochloride (memantine) for brain metastases from small cell lung cancer (SCLC) prevents cognitive function failure as measured by cognitive decline on a battery of tests: the Hopkins Verbal Learning Test - Revised (HVLT-R), Controlled Oral Word Association (COWA) test, and the Trail Making Test (TMT).
SECONDARY OBJECTIVES:
I. Determine whether SRS relative to HA-WBRT plus memantine for brain metastases from SCLC preserves cognitive function as separately measured by the HVLT-R, COWA, TMT Parts A and B, and Clinical Trial Battery Composite (CTB COMP).
II. Assess perceived difficulties in cognitive abilities using Patient Reported Outcomes Measurement Information System (PROMIS) after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC.
III. Assess symptom burden using the MD Anderson Symptom Inventory for brain tumor (MDASI-BT) after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC.
IV. Compare cumulative incidence of intracranial disease progression after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC.
V. Compare overall survival after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC.
VI. Compare cumulative incidence of neurologic death after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC.
VII. Compare the number of salvage procedures used to manage recurrent intracranial disease following SRS relative to HA-WBRT plus memantine for SCLC brain metastases.
VIII. Compare adverse events between the treatment arms according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 criteria.
IX. Compare the risk of developing cerebral necrosis between SRS and HA-WBRT plus memantine in patients receiving concurrent immunotherapy.
EXPLORATORY OBJECTIVES:
I. Compare cumulative incidence of local brain recurrence, distant brain relapse, and leptomeningeal dissemination after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC.
II. Compare the cost of brain-related therapies and quality-adjusted life years in patients who receive SRS relative to HA-WBRT plus memantine for brain metastases from SCLC.
III. Evaluate the time delay to salvage WBRT or HA-WBRT in patients enrolled on the SRS arm.
IV. Evaluate whether a time delay for chemotherapy has an effect on overall survival in patients receiving HA WBRT plus memantine relative to SRS for brain metastases from SCLC.
V. Evaluate baseline magnetic resonance (MR) imaging biomarkers of white matter injury and hippocampal volumetry as potential predictors of cognitive decline and differential benefit from SRS relative to HA-WBRT plus memantine for brain metastases from SCLC.
VI. Evaluate the correlation between neurocognitive functioning and patient-reported outcomes.
VII. Collect serum, plasma and imaging studies for future translational research analyses.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients undergo SRS over 1 day (in some cases several days).
ARM II: Patients undergo HA-WBRT once daily (QD) for 2 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive memantine orally (PO) QD or twice daily (BID) for up to 24 weeks in the absence of disease progression or unacceptable toxicity.
Patients undergo blood sample collection and magnetic resonance imaging (MRI) throughout the study.
After completion of study treatment, patients are followed up every 2-3 months for 1 year, and then every 6 months thereafter.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 200
-
Pathologically (histologically or cytologically) proven diagnosis of small cell lung cancer within 5 years of registration. If the original histologic proof of malignancy is greater than 5 years, then pathological (i.e., more recent) confirmation is required (e.g., from a systemic or brain metastasis);
- Patients with de novo or recurrent small cell lung cancer are permitted.
-
Brain metastases =< 4 cm in largest diameter and outside a 5-mm margin around either hippocampus must be visible on contrast-enhanced magnetic resonance imaging (MRI) performed =< 21 days prior to study entry.
-
The total tumor volume must be 30 cm^3 or less. Lesion volume will be approximated by measuring the lesion's three perpendicular diameters on contrast enhanced, T1-weighted MRI and the product of those diameters will be divided by 2 to estimate the lesion volume (e.g. xyz/2). Alternatively, direct volumetric measurements via slice by slice contouring on a treatment planning software package can be used to calculate the total tumor volume.
-
Brain metastases can be diagnosed synchronous to the initial diagnosis of small cell lung cancer or metachronous to the initial diagnosis and management of small cell lung cancer.
-
Brain metastases must be diagnosed on MRI, which will include the following elements:
-
REQUIRED MRI ELEMENTS
- Post gadolinium contrast-enhanced T1-weighted three-dimensional (3D) spoiled gradient (SPGR). Acceptable 3D SPGR sequences include magnetization prepared 3D gradient recalled echo (GRE) rapid gradient echo (MP-RAGE), turbo field echo (TFE) MRI, BRAVO (Brain Volume Imaging) or 3D Fast FE (field echo). The T1-weighted 3D scan should use the smallest possible axial slice thickness, not to exceed 1.5 mm.
- Pre-contrast T1 weighted imaging (3D imaging sequence strongly encouraged).
- A minimum of one axial T2 FLAIR (preferred) or T2 sequence is required. This can be acquired as a two dimensional (2D) or 3D image. If 2D, the images should be obtained in the axial plane.
-
ADDITIONAL RECOMMENDATIONS
- Recommendation is that an axial T2 FLAIR (preferred) sequence be performed instead of a T2 sequence.
- Recommendation is that that pre-contrast 3D T1 be performed with the same parameters as the post-contrast 3D T1.
- Recommendation is that imaging be performed on a 3 Tesla (3T) MRI.
- Recommendation is that the study participants be scanned on the same MRI instrument at each time point.
- Recommendation is that if additional sequences are obtained, these should meet the criteria outlined in Kaufmann et al., 2020.
- If additional sequences are obtained, total imaging time should not exceed 60 minutes.
- If additional metastases not known at the time of registration/randomization or seen in the MRI used for eligibility are subsequently found on the radiation therapy (RT) planning MRI such that the total intacranial volume exceeds 30 cm^3, the patient is still considered eligible.
-
-
-
History/physical examination
-
Age >= 18
-
Karnofsky performance status of >= 70
-
Creatinine clearance >= 30 ml/min
-
Following the diagnosis of brain metastases, patients can initiate and treat with systemic (chemotherapy and/or immunotherapy) before enrollment only if their brain metastases are asymptomatic and not located in eloquent locations (e.g., brainstem, pre-/post-central gyrus, visual cortex). However, within 21 days prior to enrollment, brain MRI must be repeated to confirm eligibility.
- Patients with symptomatic brain metastases and/or brain metastases in eloquent locations (e.g., brainstem, pre-/post central gyrus, visual cortex) are eligible for enrollment on the trial; however, the specific treatment approach of starting with systemic therapy alone and delaying brain radiation is not recommended for these patients.
-
Concurrent immunotherapy with brain radiation (SRS or HA-WBRT) is permitted.
-
Negative urine or serum pregnancy test (in women of childbearing potential) within 14 days prior to registration. Women of childbearing potential and men who are sexually active must use contraception while on study.
-
Patients may have had prior intracranial surgical resection.
-
Because neurocognitive testing is the primary goal of this study, patients must be proficient in English or French Canadian.
-
The patient must provide study-specific informed consent prior to study entry.
- Patients with impaired decision-making capacity are not permitted on study.
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ELIGIBILITY CRITERIA PRIOR TO STEP 2 REGISTRATION
-
The following baseline neurocognitive tests must be completed within 21 days prior to Step 2 registration: HVLT-R, TMT, and COWA. The neurocognitive test will be uploaded into RAVE for evaluation by Dr. Wefel. Once the upload is complete, within 3 business days a notification will be sent via email to the RA to proceed to Step 2.
- NOTE: Completed baseline neurocognitive tests can be uploaded at the time of Step 1 registration.
-
PRIOR TO STEP 2 REGISTRATION: The following baseline neurocognitive tests must be completed within 21 days prior to Step 2 registration: HVLT-R, TMT, and COWA. The neurocognitive tests will be uploaded into RAVE for evaluation by Dr. Wefel. Once the upload is complete, within 3 business days a notification will be sent via email to the RA to proceed to Step 2.
NOTE: Completed baseline neurocognitive tests can be uploaded at the time of Step 1 registration.
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Planned infusion of cytotoxic chemotherapy on the same day as SRS or HA-WBRT treatment. Patients may have had prior chemotherapy. Concurrent immunotherapy is permitted.
- For patients receiving fractionated SRS on an every-other-day basis, planned infusion of cytotoxic chemotherapy is not permitted between SRS treatments.
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Brainstem metastasis > 10 cm^3
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Prior allergic reaction to memantine.
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Patients with definitive leptomeningeal metastases.
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Known history of demyelinating disease such as multiple sclerosis.
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Contraindication to MR imaging such as implanted metal devices that are MRI-incompatible, allergy to MRI contrast that cannot be adequately addressed with pre-contrast medications, or foreign bodies that preclude MRI imaging. (Questions regarding MRI compatibility of implanted objects should be reviewed with the Radiology Department performing the MRI).
-
Current use of (other N-methyl-D-aspartate [NMDA] antagonists) amantadine, ketamine, or dextromethorphan.
-
Radiographic evidence of hydrocephalus or other architectural change of the ventricular system resulting in significant anatomic distortion of the hippocampus, including placement of external ventricular drain or ventriculoperitoneal shunt.
- Mild cases of hydrocephalus not resulting in significant anatomic distortion of the hippocampus are permitted.
-
Prior radiotherapy to the brain, including SRS, WBRT, or prophylactic cranial irradiation (PCI).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I (SRS) Biospecimen Collection Patients undergo SRS over 1 day (in some cases several days). Patients undergo blood sample collection and MRI throughout the study. Arm I (SRS) Magnetic Resonance Imaging Patients undergo SRS over 1 day (in some cases several days). Patients undergo blood sample collection and MRI throughout the study. Arm I (SRS) Neurocognitive Assessment Patients undergo SRS over 1 day (in some cases several days). Patients undergo blood sample collection and MRI throughout the study. Arm I (SRS) Stereotactic Radiosurgery Patients undergo SRS over 1 day (in some cases several days). Patients undergo blood sample collection and MRI throughout the study. Arm II (HA-WBRT, memantine) Magnetic Resonance Imaging Patients also undergo HA-WBRT QD for 2 weeks in the absence of disease progression or unacceptable toxicity. Patients will also receive memantine PO QD or BID for up to 24 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and MRI throughout the study. Arm II (HA-WBRT, memantine) Memantine Hydrochloride Patients also undergo HA-WBRT QD for 2 weeks in the absence of disease progression or unacceptable toxicity. Patients will also receive memantine PO QD or BID for up to 24 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and MRI throughout the study. Arm II (HA-WBRT, memantine) Neurocognitive Assessment Patients also undergo HA-WBRT QD for 2 weeks in the absence of disease progression or unacceptable toxicity. Patients will also receive memantine PO QD or BID for up to 24 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and MRI throughout the study. Arm II (HA-WBRT, memantine) Whole-Brain Radiotherapy Patients also undergo HA-WBRT QD for 2 weeks in the absence of disease progression or unacceptable toxicity. Patients will also receive memantine PO QD or BID for up to 24 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and MRI throughout the study.
- Primary Outcome Measures
Name Time Method Time to neurocognitive failure 1 year A failure is defined using the reliable change index (RCI) criteria, as measured by the Hopkins Verbal Learning Test - Revised (HVLT-R), Controlled Oral Word Association (COWA) test, and Trail Making Test (TMT) Parts A and B. The cumulative incidence approach will be used to estimate the median time to neurocognitive failure to account for the competing risk of death. Gray's test will be used to test for statistically significant difference in the distribution of neurocognitive failure times (Gray 1988). The cause-specific Cox proportional hazards regression model will be used to evaluate the effect of stratification variables (Disease-Specific Graded Prognostic Assessment \[DS-GPA\] and prior NCF testing exposure) and other baseline characteristics, such as age, number of brain metastases and its interaction with treatment arm, and Karnofsky performance status (KPS), on time to neurocognitive decline (Cox 1972).
- Secondary Outcome Measures
Name Time Method Preservation of neurocognitive function 1 year Measured separately by HVLT-R, COWA test, TMT Parts A and B, and Clinical Trial Battery Composite (CTB COMP) score. A mixed effects model will be used to assess changes of standardized neurocognitive scores across time using all available data while adjusting for stratification variables and other baseline characteristics. For discrete time point analyses, the change from baseline to each follow-up time point, will be calculated and compared between treatment arms using a t-test or Wilcoxon-Mann-Whitney test, depending on the normality of the data. Neurocognitive decline using the RCI for the HVLT-R, COWA, and TMT also will be compared between treatment arms at each follow-up time point using Fisher's exact test (Jacobson 1991; Chelune 1993).
Perceived difficulties in cognition 1 year Measured by Patient Reported Outcomes Measurement Information System (PROMIS). For discrete time point analyses, the change from baseline to each follow-up time point, will be calculated and compared between treatment arms using a t-test or Wilcoxon-Mann-Whitney test, depending on the normality of the data.
Symptom burden 1 year Measured by MD Anderson Symptom Inventory for brain tumor (MDASI-BT). Four subscales (symptom severity, symptom interference, neurologic factor, and cognitive factor score) as well as certain individual items (fatigue, neurologic factor items, and cognitive factor items) of the MDASI-BT will be analyzed. Mixed effects models will be used to assess changes of the four subscale scores (symptom severity, symptom interference, neurologic factor, and cognitive factor score) across time using all available data while adjusting for stratification variables and other baseline characteristics. For discrete time point analyses, the change from baseline to each follow-up time point, will be calculated and compared between treatment arms using a t-test or Wilcoxon-Mann-Whitney test, depending on the normality of the data.
Time to intracranial disease progression From the date of randomization to the date of intracranial disease progression, assessed up to 10 years Gray's test will be used to assess between treatment arm comparisons (Gray 1988). Cause-specific Cox proportional hazards models will be used to evaluate the effect of stratification variables (DS-GPA and prior NCF testing exposure) and other baseline characteristics, such as KPS, and number of brain metastases and its interaction with treatment arm. A two-sided significance level of 0.05 will be used.
Overall survival From the date of randomization to the date of death, or otherwise, the last follow-up date on which the patient was reported alive, assessed up to 10 years Will be estimated using the Kaplan-Meier method (Kaplan 1958), and differences between treatment arms will be tested using the log rank test (Mantel 1966). The Cox proportional hazard model (Cox 1972) will be performed with the stratification variables and other baseline characteristics as fixed variables to assess the treatment effect while adjusting for patient specific risk factors such as number of brain metastases and its interaction with treatment, KPS, and time to salvage chemotherapy as a time varying covariate. A two-sided significance level of 0.05 will be used.
Time to neurologic death From the date of randomization to the date of neurologic death, assessed up to 10 years Gray's test will be used to assess between treatment arm comparisons (Gray 1988). Cause-specific Cox proportional hazards models will be used to evaluate the effect of stratification variables (DS-GPA and prior NCF testing exposure) and other baseline characteristics, such as KPS, and number of brain metastases and its interaction with treatment arm. A two-sided significance level of 0.05 will be used.
Salvage procedures used to manage recurrent intracranial disease 10 years Will be collected and descriptively compared between arms using Chi-square tests.
Incidence of adverse events 10 years Graded by Common Terminology Criteria for Adverse Events version 5.0. Counts of all adverse events (AEs) by grade will be provided by treatment arm. Counts and frequencies will be provided for the worst grade AE experienced by the patient by treatment arm. The rate of grade 3+ AEs related to treatment and the rate of grade 3+ AEs regardless of relationship to treatment will be compared between treatment arms using a Chi-square test at a two-sided significance level of 0.05.
Development of cerebral necrosis 10 years
Trial Locations
- Locations (211)
Mayo Clinic Hospital in Arizona
🇺🇸Phoenix, Arizona, United States
Kaiser Permanente-Anaheim
🇺🇸Anaheim, California, United States
Kaiser Permanente-Bellflower
🇺🇸Bellflower, 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
Kaiser Permanente-Ontario
🇺🇸Ontario, California, United States
UCHealth University of Colorado Hospital
🇺🇸Aurora, Colorado, United States
UCHealth Memorial Hospital Central
🇺🇸Colorado Springs, Colorado, United States
Memorial Hospital North
🇺🇸Colorado Springs, Colorado, United States
Smilow Cancer Hospital Care Center at Greenwich
🇺🇸Greenwich, Connecticut, United States
Smilow Cancer Hospital Care Center - Guilford
🇺🇸Guilford, Connecticut, United States
Smilow Cancer Center/Yale-New Haven Hospital
🇺🇸New Haven, Connecticut, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Smilow Cancer Hospital Care Center-Trumbull
🇺🇸Trumbull, Connecticut, United States
Smilow Cancer Hospital Care Center - Waterford
🇺🇸Waterford, Connecticut, United States
Beebe Medical Center
🇺🇸Lewes, Delaware, United States
Delaware Clinical and Laboratory Physicians PA
🇺🇸Newark, Delaware, United States
Helen F Graham Cancer Center
🇺🇸Newark, Delaware, United States
Medical Oncology Hematology Consultants PA
🇺🇸Newark, Delaware, United States
Christiana Care Health System-Christiana Hospital
🇺🇸Newark, Delaware, United States
Beebe Health Campus
🇺🇸Rehoboth Beach, Delaware, United States
Christiana Care Health System-Wilmington Hospital
🇺🇸Wilmington, Delaware, 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
University of Florida Health Science Center - Gainesville
🇺🇸Gainesville, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Moffitt Cancer Center-International Plaza
🇺🇸Tampa, Florida, United States
Moffitt Cancer Center - McKinley Campus
🇺🇸Tampa, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Moffitt Cancer Center at Wesley Chapel
🇺🇸Wesley Chapel, Florida, United States
Emory University Hospital Midtown
🇺🇸Atlanta, Georgia, United States
Emory University Hospital/Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Emory Saint Joseph's Hospital
🇺🇸Atlanta, Georgia, United States
Unity Hospital
🇺🇸Fridley, Minnesota, United States
Northside Hospital
🇺🇸Atlanta, Georgia, United States
Northside Hospital-Cherokee
🇺🇸Canton, Georgia, United States
Northside Hospital-Forsyth
🇺🇸Cumming, Georgia, United States
Memorial Health University Medical Center
🇺🇸Savannah, Georgia, United States
Rush - Copley Medical Center
🇺🇸Aurora, Illinois, United States
Centralia Oncology Clinic
🇺🇸Centralia, Illinois, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
Carle at The Riverfront
🇺🇸Danville, Illinois, United States
Cancer Care Specialists of Illinois - Decatur
🇺🇸Decatur, Illinois, United States
Decatur Memorial Hospital
🇺🇸Decatur, Illinois, United States
Northwestern Medicine Cancer Center Kishwaukee
🇺🇸DeKalb, Illinois, United States
Carle Physician Group-Effingham
🇺🇸Effingham, Illinois, United States
Crossroads Cancer Center
🇺🇸Effingham, Illinois, United States
Northwestern Medicine Cancer Center Delnor
🇺🇸Geneva, Illinois, United States
Carle Physician Group-Mattoon/Charleston
🇺🇸Mattoon, Illinois, United States
UC Comprehensive Cancer Center at Silver Cross
🇺🇸New Lenox, Illinois, United States
Cancer Care Center of O'Fallon
🇺🇸O'Fallon, Illinois, United States
HSHS Saint Elizabeth's Hospital
🇺🇸O'Fallon, Illinois, United States
OSF Saint Francis Medical Center
🇺🇸Peoria, Illinois, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
The Carle Foundation Hospital
🇺🇸Urbana, Illinois, United States
Northwestern Medicine Cancer Center Warrenville
🇺🇸Warrenville, Illinois, United States
IU Health West Hospital
🇺🇸Avon, Indiana, United States
IU Health North Hospital
🇺🇸Carmel, Indiana, United States
Goshen Center for Cancer Care
🇺🇸Goshen, Indiana, United States
Indiana University/Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
IU Health Methodist Hospital
🇺🇸Indianapolis, Indiana, United States
Mary Greeley Medical Center
🇺🇸Ames, Iowa, United States
McFarland Clinic - Ames
🇺🇸Ames, Iowa, United States
Baptist Health Lexington
🇺🇸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
Mary Bird Perkins Cancer Center
🇺🇸Baton Rouge, Louisiana, United States
Luminis Health Anne Arundel Medical Center
🇺🇸Annapolis, Maryland, United States
University of Maryland/Greenebaum Cancer Center
🇺🇸Baltimore, Maryland, United States
MedStar Franklin Square Medical Center/Weinberg Cancer Institute
🇺🇸Baltimore, Maryland, United States
UM Upper Chesapeake Medical Center
🇺🇸Bel Air, Maryland, United States
Central Maryland Radiation Oncology in Howard County
🇺🇸Columbia, Maryland, United States
University of Maryland Shore Medical Center at Easton
🇺🇸Easton, Maryland, United States
UM Baltimore Washington Medical Center/Tate Cancer Center
🇺🇸Glen Burnie, Maryland, United States
TidalHealth Richard A Henson Cancer Institute
🇺🇸Ocean Pines, Maryland, United States
TidalHealth Peninsula Regional
🇺🇸Salisbury, Maryland, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
🇺🇸Ann Arbor, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Brighton
🇺🇸Brighton, Michigan, United States
Trinity Health Medical Center - Brighton
🇺🇸Brighton, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Canton
🇺🇸Canton, Michigan, United States
Trinity Health Medical Center - Canton
🇺🇸Canton, Michigan, United States
Caro Cancer Center
🇺🇸Caro, Michigan, United States
Chelsea Hospital
🇺🇸Chelsea, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
🇺🇸Chelsea, Michigan, United States
Trinity Health Saint Mary Mercy Livonia Hospital
🇺🇸Livonia, Michigan, United States
Saint Mary's Oncology/Hematology Associates of Marlette
🇺🇸Marlette, Michigan, United States
MyMichigan Medical Center Saginaw
🇺🇸Saginaw, Michigan, United States
Oncology Hematology Associates of Saginaw Valley PC
🇺🇸Saginaw, Michigan, United States
MyMichigan Medical Center Tawas
🇺🇸Tawas City, Michigan, United States
Saint Mary's Oncology/Hematology Associates of West Branch
🇺🇸West Branch, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
🇺🇸Ypsilanti, Michigan, United States
Sanford Joe Lueken Cancer Center
🇺🇸Bemidji, Minnesota, United States
Minnesota Oncology - Burnsville
🇺🇸Burnsville, Minnesota, United States
Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
Fairview Clinics and Surgery Center Maple Grove
🇺🇸Maple Grove, Minnesota, United States
Minnesota Oncology Hematology PA-Maplewood
🇺🇸Maplewood, Minnesota, United States
Abbott-Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Monticello Cancer Center
🇺🇸Monticello, Minnesota, United States
Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
Lakeview Hospital
🇺🇸Stillwater, Minnesota, United States
Minnesota Oncology Hematology PA-Woodbury
🇺🇸Woodbury, Minnesota, United States
Saint Francis Medical Center
🇺🇸Cape Girardeau, Missouri, United States
Parkland Health Center - Farmington
🇺🇸Farmington, Missouri, United States
Freeman Health System
🇺🇸Joplin, Missouri, United States
Missouri Baptist Medical Center
🇺🇸Saint Louis, Missouri, United States
Sainte Genevieve County Memorial Hospital
🇺🇸Sainte Genevieve, Missouri, United States
Mercy Hospital Springfield
🇺🇸Springfield, Missouri, United States
Missouri Baptist Sullivan Hospital
🇺🇸Sullivan, Missouri, United States
BJC Outpatient Center at Sunset Hills
🇺🇸Sunset Hills, Missouri, United States
Billings Clinic Cancer Center
🇺🇸Billings, Montana, United States
Benefis Sletten Cancer Institute
🇺🇸Great Falls, Montana, United States
Logan Health Medical Center
🇺🇸Kalispell, Montana, United States
Cooper Hospital University Medical Center
🇺🇸Camden, New Jersey, United States
Montefiore Medical Center-Einstein Campus
🇺🇸Bronx, New York, United States
Montefiore Medical Center-Weiler Hospital
🇺🇸Bronx, New York, United States
Montefiore Medical Center - Moses Campus
🇺🇸Bronx, New York, United States
Sands Cancer Center
🇺🇸Canandaigua, New York, United States
Northwell Health/Center for Advanced Medicine
🇺🇸Lake Success, New York, United States
Northern Westchester Hospital
🇺🇸Mount Kisco, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
🇺🇸New York, New York, United States
Wilmot Cancer Institute Radiation Oncology at Greece
🇺🇸Rochester, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
Upstate Cancer Center at Verona
🇺🇸Verona, New York, United States
Wilmot Cancer Institute at Webster
🇺🇸Webster, New York, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Sanford Bismarck Medical Center
🇺🇸Bismarck, North Dakota, United States
Sanford Broadway Medical Center
🇺🇸Fargo, North Dakota, United States
Sanford Roger Maris Cancer Center
🇺🇸Fargo, North Dakota, United States
University of Cincinnati Cancer Center-UC Medical Center
🇺🇸Cincinnati, Ohio, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Riverside Methodist Hospital
🇺🇸Columbus, Ohio, United States
Grant Medical Center
🇺🇸Columbus, Ohio, United States
Delaware Health Center-Grady Cancer Center
🇺🇸Delaware, Ohio, United States
Grady Memorial Hospital
🇺🇸Delaware, Ohio, United States
UH Seidman Cancer Center at Lake Health Mentor Campus
🇺🇸Mentor, Ohio, United States
Mercy Health - Perrysburg Hospital
🇺🇸Perrysburg, Ohio, United States
Mercy Health - Saint Anne Hospital
🇺🇸Toledo, Ohio, United States
University of Cincinnati Cancer Center-West Chester
🇺🇸West Chester, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Saint Luke's Cancer Center - Allentown
🇺🇸Allentown, Pennsylvania, United States
UPMC Altoona
🇺🇸Altoona, Pennsylvania, United States
Saint Luke's University Hospital-Bethlehem Campus
🇺🇸Bethlehem, Pennsylvania, United States
Carlisle Regional Cancer Center
🇺🇸Carlisle, Pennsylvania, United States
Christiana Care Health System-Concord Health Center
🇺🇸Chadds Ford, Pennsylvania, United States
Chambersburg Hospital
🇺🇸Chambersburg, Pennsylvania, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Saint Luke's Hospital-Anderson Campus
🇺🇸Easton, Pennsylvania, United States
Ephrata Cancer Center
🇺🇸Ephrata, Pennsylvania, United States
Saint Vincent Hospital
🇺🇸Erie, Pennsylvania, United States
Adams Cancer Center
🇺🇸Gettysburg, Pennsylvania, United States
UPMC Cancer Centers - Arnold Palmer Pavilion
🇺🇸Greensburg, Pennsylvania, United States
UPMC Pinnacle Cancer Center/Community Osteopathic Campus
🇺🇸Harrisburg, Pennsylvania, United States
Sechler Family Cancer Center
🇺🇸Lebanon, Pennsylvania, United States
Geisinger Medical Oncology-Lewisburg
🇺🇸Lewisburg, Pennsylvania, United States
UPMC Cancer Center - Monroeville
🇺🇸Monroeville, Pennsylvania, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Jefferson Torresdale Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC-Magee Womens Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC-Presbyterian Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC-Saint Margaret
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC-Shadyside Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC-Passavant Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC-Saint Clair Hospital Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Saint Luke's Hospital - Upper Bucks Campus
🇺🇸Quakertown, Pennsylvania, United States
Saint Luke's Hospital-Quakertown Campus
🇺🇸Quakertown, Pennsylvania, United States
Saint Luke's Hospital - Monroe Campus
🇺🇸Stroudsburg, Pennsylvania, United States
Geisinger Wyoming Valley/Henry Cancer Center
🇺🇸Wilkes-Barre, Pennsylvania, United States
Divine Providence Hospital
🇺🇸Williamsport, Pennsylvania, United States
WellSpan Health-York Cancer Center
🇺🇸York, Pennsylvania, United States
WellSpan Health-York Hospital
🇺🇸York, Pennsylvania, United States
UPMC Memorial
🇺🇸York, Pennsylvania, United States
McLeod Regional Medical Center
🇺🇸Florence, South Carolina, United States
Gibbs Cancer Center-Gaffney
🇺🇸Gaffney, South Carolina, United States
Self Regional Healthcare
🇺🇸Greenwood, South Carolina, United States
Gibbs Cancer Center-Pelham
🇺🇸Greer, South Carolina, United States
Spartanburg Medical Center
🇺🇸Spartanburg, South Carolina, United States
SMC Center for Hematology Oncology Union
🇺🇸Union, South Carolina, United States
Sanford Cancer Center Oncology Clinic
🇺🇸Sioux Falls, South Dakota, United States
Avera Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸Sioux Falls, South Dakota, United States
MD Anderson in The Woodlands
🇺🇸Conroe, Texas, United States
M D Anderson Cancer Center
🇺🇸Houston, Texas, United States
MD Anderson West Houston
🇺🇸Houston, Texas, United States
MD Anderson League City
🇺🇸League City, Texas, United States
MD Anderson in Sugar Land
🇺🇸Sugar Land, Texas, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Langlade Hospital and Cancer Center
🇺🇸Antigo, Wisconsin, United States
ThedaCare Regional Cancer Center
🇺🇸Appleton, Wisconsin, United States
Gundersen Lutheran Medical Center
🇺🇸La Crosse, 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
Froedtert Menomonee Falls Hospital
🇺🇸Menomonee Falls, Wisconsin, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Cancer Center of Western Wisconsin
🇺🇸New Richmond, Wisconsin, United States
Drexel Town Square Health Center
🇺🇸Oak Creek, Wisconsin, United States
Aspirus Cancer Care - James Beck Cancer Center
🇺🇸Rhinelander, Wisconsin, United States
Aspirus Cancer Care - Stevens Point
🇺🇸Stevens Point, Wisconsin, United States
Aspirus Regional Cancer Center
🇺🇸Wausau, Wisconsin, United States
Froedtert West Bend Hospital/Kraemer Cancer Center
🇺🇸West Bend, Wisconsin, United States
University Health Network-Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)
🇨🇦Quebec City, Quebec, Canada
Allan Blair Cancer Centre
🇨🇦Regina, Saskatchewan, Canada
Saskatoon Cancer Centre
🇨🇦Saskatoon, Saskatchewan, Canada