Testing the Addition of Total Ablative Therapy to Usual Systemic Therapy Treatment for Limited Metastatic Colorectal Cancer, the ERASur Study
- Conditions
- Metastatic Colorectal AdenocarcinomaStage IV Colorectal Cancer AJCC V8
- Interventions
- Procedure: Stereotactic Ablative RadiotherapyProcedure: ResectionProcedure: Microwave AblationDrug: ChemotherapyProcedure: Computed TomographyProcedure: Magnetic Resonance ImagingProcedure: Positron Emission Tomography
- Registration Number
- NCT05673148
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief Summary
This phase III trial compares total ablative therapy and usual systemic therapy to usual systemic therapy alone in treating patients with colorectal cancer that has spread to up to 4 body sites (limited metastatic). The usual approach for patients who are not participating in a study is treatment with intravenous (IV) (through a vein) and/or oral medications (systemic therapy) to help stop the cancer sites from getting larger and the spread of the cancer to additional body sites. Ablative means that the intention of the local treatment is to eliminate the cancer at that metastatic site. The ablative local therapy will consist of very focused, intensive radiotherapy called stereotactic ablative radiotherapy (SABR) with or without surgical resection and/or microwave ablation, which is a procedure where a needle is temporarily inserted in the tumor and heat is used to destroy the cancer cells. SABR, surgical resection, and microwave ablation have been tested for safety, but it is not scientifically proven that the addition of these treatments are beneficial for your stage of cancer. The addition of ablative local therapy to all known metastatic sites to the usual approach of systemic therapy could shrink or remove the tumor(s) or prevent the tumor(s) from returning.
- Detailed Description
PRIMARY OBJECTIVE:
I. To evaluate and compare overall survival (OS) (measured from time of randomization) in patients with newly diagnosed oligometastatic colorectal cancer (oCRC) treated with total ablative therapy (TAT) in addition to standard of care (SOC) systemic therapy versus SOC systemic therapy.
SECONDARY OBJECTIVES:
I. To evaluate and compare event-free survival (EFS) (measured from time of randomization) between the two treatment arms.
II. To assess the adverse events (AE) profile within each of the two treatment arms.
III. To evaluate the time to local recurrence (TLR) (measured from completion of TAT) in patients with newly diagnosed oCRC treated with TAT + SOC systemic therapy.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM 1: Patients undergo TAT on study, consisting of SABR with or without surgical resection and/or microwave ablation. Patients also receive SOC chemotherapy on study. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) or positron emission tomography (PET)/CT scans throughout the trial.
ARM 2: Patients receive SOC chemotherapy on study. Patients also undergo Patients also undergo CT or MRI or PET/CT scans throughout the trial.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 364
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PRE-REGISTRATION (STEP 0): Histologically-confirmed metastatic colorectal adenocarcinoma
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PRE-REGISTRATION (STEP 0): No known microsatellite instable (MSI) tumor
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PRE-REGISTRATION (STEP 0): No known BRAF V600E mutation
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PRE-REGISTRATION (STEP 0): Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression. No known peritoneal and/or omental metastases. If radiologic studies suggest the presence of peritoneal disease, a diagnostic laparoscopy is recommended to verify the absence of peritoneal implants
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PRE-REGISTRATION (STEP 0): Primary tumor is already resected OR primary tumor is surgically amenable to resection, as determined by consultation and documentation with surgeon or documentation of discussion in the institutional multi-disciplinary tumor board where a surgeon confirms resectability. Patients with unresectable primary tumors are not eligible
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PRE-REGISTRATION (STEP 0): Four (4) or fewer apparent sites of metastatic disease based on review by local medical team of baseline radiographic imaging obtained prior to initiation of systemic therapy.
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Sites of metastatic disease must be radiographically evident, but pathologic confirmation is not required.
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Liver-only metastatic disease is NOT permitted. For patients with liver metastases, there must be at least one other site of metastasis in addition to the liver to be eligible for this study.
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Metastatic lesions must be amenable to any combination of surgical resection, microwave ablation, and/or stereotactic ablative body radiation therapy (SABR). SABR is required for at least one lesion. Therefore, the patient must be seen by a radiation oncologist in consultation to verify eligibility.
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Single sites include:
- Each hemiliver (right and left), each lobe of the lungs, each adrenal gland, lymph nodes amenable to a single resection or treatment in a single SABR field, bone metastases amenable to treatment in a single SABR field
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PRE-REGISTRATION (STEP 0): Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
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PRE-REGISTRATION (STEP 0): A maximum of 16 weeks (4 months) of systemic therapy may be administered prior to pre-registration
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REGISTRATION (STEP 1): Patients must have no overt evidence of disease progression during systemic therapy prior to registration
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REGISTRATION (STEP 1): Not eligible for hepatic artery infusion pump (HAIP) therapy or benefit of HAIP therapy is undefined
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REGISTRATION (STEP 1): Patients must have measurable disease per RECIST v1.1
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REGISTRATION (STEP 1): Patients must be receiving (or have received) first-line systemic therapy for metastatic disease for a minimum of 16 weeks (4 months) and a maximum of 24 weeks (6 months)
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REGISTRATION (STEP 1): Prior definitive therapy, including adjuvant chemotherapy, must have been completed at least 12 months prior to diagnosis of metastatic disease
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REGISTRATION (STEP 1): Not pregnant and not nursing, because this study involves an agent or treatment that has known genotoxic, mutagenic, and teratogenic effects.
* Therefore, for women of childbearing potential only, a negative pregnancy test done =< 14 days prior to registration is required
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REGISTRATION (STEP 1): Age >= 18 years
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REGISTRATION (STEP 1): Eastern Cooperative Oncology Group (ECOG) performance status: 0-2
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REGISTRATION (STEP 1): Absolute neutrophil count (ANC) >= 1,500/mm^3
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REGISTRATION (STEP 1): Platelet count >= 50,000/mm^3
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REGISTRATION (STEP 1): Creatinine =< 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance >= 30 mL/min
* Calculated using the Cockcroft-Gault equation
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REGISTRATION (STEP 1): Total bilirubin =< 1.5 x ULN
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REGISTRATION (STEP 1): Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT]) / alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x ULN
* In the event of metastatic liver disease, =< 5 x ULN
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REGISTRATION (STEP 1): Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Note: HIV testing is not required for eligibility
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REGISTRATION (STEP 1): No other planned concurrent investigational agents while on study
- N/A
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1 (TAT, SOC chemotherapy Stereotactic Ablative Radiotherapy Patients undergo TAT on study, consisting of SABR with or without surgical resection and/or microwave ablation. Patients also receive SOC chemotherapy on study. Patients also undergo CT or MRI or PET/CT scans throughout the trial. Arm 1 (TAT, SOC chemotherapy Resection Patients undergo TAT on study, consisting of SABR with or without surgical resection and/or microwave ablation. Patients also receive SOC chemotherapy on study. Patients also undergo CT or MRI or PET/CT scans throughout the trial. Arm 1 (TAT, SOC chemotherapy Microwave Ablation Patients undergo TAT on study, consisting of SABR with or without surgical resection and/or microwave ablation. Patients also receive SOC chemotherapy on study. Patients also undergo CT or MRI or PET/CT scans throughout the trial. Arm 1 (TAT, SOC chemotherapy Chemotherapy Patients undergo TAT on study, consisting of SABR with or without surgical resection and/or microwave ablation. Patients also receive SOC chemotherapy on study. Patients also undergo CT or MRI or PET/CT scans throughout the trial. Arm 1 (TAT, SOC chemotherapy Computed Tomography Patients undergo TAT on study, consisting of SABR with or without surgical resection and/or microwave ablation. Patients also receive SOC chemotherapy on study. Patients also undergo CT or MRI or PET/CT scans throughout the trial. Arm 1 (TAT, SOC chemotherapy Magnetic Resonance Imaging Patients undergo TAT on study, consisting of SABR with or without surgical resection and/or microwave ablation. Patients also receive SOC chemotherapy on study. Patients also undergo CT or MRI or PET/CT scans throughout the trial. Arm 1 (TAT, SOC chemotherapy Positron Emission Tomography Patients undergo TAT on study, consisting of SABR with or without surgical resection and/or microwave ablation. Patients also receive SOC chemotherapy on study. Patients also undergo CT or MRI or PET/CT scans throughout the trial. Arm 2 (SOC chemotherapy) Chemotherapy Patients receive SOC chemotherapy on study. Patients also undergo Patients also undergo CT or MRI or PET/CT scans throughout the trial. Arm 2 (SOC chemotherapy) Computed Tomography Patients receive SOC chemotherapy on study. Patients also undergo Patients also undergo CT or MRI or PET/CT scans throughout the trial. Arm 2 (SOC chemotherapy) Magnetic Resonance Imaging Patients receive SOC chemotherapy on study. Patients also undergo Patients also undergo CT or MRI or PET/CT scans throughout the trial. Arm 2 (SOC chemotherapy) Positron Emission Tomography Patients receive SOC chemotherapy on study. Patients also undergo Patients also undergo CT or MRI or PET/CT scans throughout the trial.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) From the date of randomization to the date of death due to all causes, assessed up to 5 years o Description: The hazard ratio (HR) for OS will be estimated using a stratified Cox proportional hazards model and the 95% confidence interval (CI) for the HR will be provided. The Kaplan-Meier methodology will be used to estimate the median OS for each treatment arm, and Kaplan-Meier curves will be produced. OS will also be compared between treatment arms using the log rank test
- Secondary Outcome Measures
Name Time Method Event Free Survival (EFS) From randomization to the date of first documented progression, recurrence, or death due to all causes, whichever occurs first, assessed up to 5 years The hazard ratio (HR) for EFS will be estimated using a stratified Cox proportional hazards model and the 95% confidence interval (CI) for the HR will be provided. The Kaplan-Meier methodology will be used to estimate the median EFS for each treatment arm, and Kaplan-Meier curves will be produced. EFS will also be compared between treatment arms using the log rank test.
Time to local recurrence (TLR) from the end of TAT to the date of first documented recurrence at any disease site treated with TAT, assessed up to 5 years after randomization TLR will be measured only for patients who receive treatment with TAT and is defined as the time from the end of TAT until the date of first documented recurrence at any disease site treated with TAT. The Kaplan-Meier methodology will be used to estimate the median TLR for patients treated with TAT , and a Kaplan-Meier curve will be produced.
• Incidence of Adverse Events (AEs), assessed using National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) version 5.0 (v5.0) Up to 5 years Defined as the proportion of patients experienced at least one Grade 3, Grade 4, or Grade 5 of each type of AE. The maximum grade for each type of adverse events that are possibly, probably, or definitely related to study treatments will be recorded for each patient. The frequency tables will be reviewed to determine the patterns. The overall adverse event rates for grade 3 or higher adverse events will be compared between two treatment groups using Chi-square test (or Fisher's exact test if the data in the contingency table is sparse).
Related Research Topics
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Trial Locations
- Locations (130)
Kingman Regional Medical Center
🇺🇸Kingman, Arizona, United States
Mayo Clinic Hospital in Arizona
🇺🇸Phoenix, Arizona, United States
Tower Cancer Research Foundation
🇺🇸Beverly Hills, California, United States
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
🇺🇸Irvine, California, United States
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
🇺🇸Orange, California, United States
University of California Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
Beebe Medical Center
🇺🇸Lewes, Delaware, United States
Beebe South Coastal Health Campus
🇺🇸Millville, 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
Sibley Memorial Hospital
🇺🇸Washington, District of Columbia, United States
University of Florida Health Science Center - Gainesville
🇺🇸Gainesville, Florida, United States
Miami Cancer Institute
🇺🇸Miami, Florida, United States
Grady Health System
🇺🇸Atlanta, Georgia, United States
Emory Proton Therapy Center
🇺🇸Atlanta, Georgia, United States
Emory University Hospital Midtown
🇺🇸Atlanta, Georgia, United States
Emory University Hospital/Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Emory Saint Joseph's Hospital
🇺🇸Atlanta, Georgia, United States
Saint Luke's Cancer Institute - Boise
🇺🇸Boise, Idaho, United States
Saint Luke's Cancer Institute - Fruitland
🇺🇸Fruitland, Idaho, United States
Saint Luke's Cancer Institute - Meridian
🇺🇸Meridian, Idaho, United States
Saint Luke's Cancer Institute - Nampa
🇺🇸Nampa, Idaho, United States
Saint Luke's Cancer Institute - Twin Falls
🇺🇸Twin Falls, Idaho, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
Mission Cancer and Blood - Ankeny
🇺🇸Ankeny, Iowa, United States
Mercy Cancer Center-West Lakes
🇺🇸Clive, Iowa, United States
Mission Cancer and Blood - West Des Moines
🇺🇸Clive, Iowa, United States
Greater Regional Medical Center
🇺🇸Creston, Iowa, United States
Iowa Methodist 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
Mission Cancer and Blood - Des Moines
🇺🇸Des Moines, Iowa, United States
Mercy Medical Center-West Lakes
🇺🇸West Des Moines, Iowa, United States
University of Kentucky/Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸Baltimore, Maryland, 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
Chelsea Hospital
🇺🇸Chelsea, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
🇺🇸Chelsea, Michigan, United States
Corewell Health Dearborn Hospital
🇺🇸Dearborn, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Corewell Health Farmington Hills Hospital
🇺🇸Farmington Hills, Michigan, United States
Genesys Hurley Cancer Institute
🇺🇸Flint, Michigan, United States
Hurley Medical Center
🇺🇸Flint, Michigan, United States
University of Michigan Health - Sparrow Lansing
🇺🇸Lansing, Michigan, United States
Trinity Health Saint Mary Mercy Livonia Hospital
🇺🇸Livonia, Michigan, United States
Henry Ford Health Providence Novi Hospital
🇺🇸Novi, Michigan, United States
Corewell Health William Beaumont University Hospital
🇺🇸Royal Oak, Michigan, United States
Henry Ford Health Providence Southfield Hospital
🇺🇸Southfield, Michigan, United States
Corewell Health Beaumont Troy Hospital
🇺🇸Troy, 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
Baptist Memorial Hospital and Cancer Center-Golden Triangle
🇺🇸Columbus, Mississippi, United States
Baptist Cancer Center-Grenada
🇺🇸Grenada, Mississippi, United States
Baptist Memorial Hospital and Cancer Center-Union County
🇺🇸New Albany, Mississippi, United States
Baptist Memorial Hospital and Cancer Center-Oxford
🇺🇸Oxford, Mississippi, United States
Baptist Memorial Hospital and Cancer Center-Desoto
🇺🇸Southhaven, Mississippi, United States
Mercy Hospital Saint Louis
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital Springfield
🇺🇸Springfield, Missouri, United States
Billings Clinic Cancer Center
🇺🇸Billings, Montana, United States
Benefis Sletten Cancer Institute
🇺🇸Great Falls, Montana, United States
Nebraska Medicine-Bellevue
🇺🇸Bellevue, Nebraska, United States
Nebraska Medicine-Village Pointe
🇺🇸Omaha, Nebraska, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Renown Regional Medical Center
🇺🇸Reno, Nevada, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
🇺🇸Lebanon, New Hampshire, United States
Memorial Sloan Kettering Basking Ridge
🇺🇸Basking Ridge, New Jersey, United States
Northern Westchester Hospital
🇺🇸Mount Kisco, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Lenox Hill Hospital
🇺🇸New York, New York, 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
Dayton Physicians LLC-Miami Valley South
🇺🇸Centerville, Ohio, United States
Memorial Sloan Kettering Monmouth
🇺🇸Middletown, New Jersey, United States
Northwell Health/Center for Advanced Medicine
🇺🇸Lake Success, New York, United States
Mount Sinai West
🇺🇸New York, New York, United States
Mount Sinai Hospital
🇺🇸New York, New York, United States
Memorial Sloan Kettering Bergen
🇺🇸Montvale, New Jersey, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
New York-Presbyterian/Brooklyn Methodist Hospital
🇺🇸Brooklyn, New York, United States
Memorial Sloan Kettering Commack
🇺🇸Commack, New York, United States
The New York Hospital Medical Center of Queens
🇺🇸Flushing, New York, United States
Northwell Health Physicians Partners Radiation Medicine at Queens
🇺🇸Forest Hills, New York, United States
Northwell Health Cancer Institute at Huntington
🇺🇸Greenlawn, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
🇺🇸New York, New York, United States
Westchester Medical Center
🇺🇸Valhalla, New York, United States
Wilmot Cancer Institute at Webster
🇺🇸Webster, New York, United States
Memorial Sloan Kettering Westchester
🇺🇸West Harrison, New York, United States
Manhattan Eye Ear and Throat Hospital
🇺🇸New York, New York, United States
NYP/Weill Cornell Medical Center
🇺🇸New York, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
Queens Cancer Center
🇺🇸Rego Park, New York, United States
Memorial Sloan Kettering Nassau
🇺🇸Uniondale, New York, United States
Miami Valley Hospital South
🇺🇸Centerville, Ohio, United States
MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Miami Valley Hospital
🇺🇸Dayton, Ohio, United States
Premier Blood and Cancer Center
🇺🇸Dayton, Ohio, United States
Dayton Physician LLC - Englewood
🇺🇸Dayton, Ohio, United States
Miami Valley Hospital North
🇺🇸Dayton, Ohio, United States
Atrium Medical Center-Middletown Regional Hospital
🇺🇸Franklin, Ohio, United States
Dayton Physicians LLC-Atrium
🇺🇸Franklin, Ohio, United States
Miami Valley Cancer Care and Infusion
🇺🇸Greenville, Ohio, United States
Upper Valley Medical Center
🇺🇸Troy, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Christiana Care Health System-Concord Health Center
🇺🇸Chadds Ford, Pennsylvania, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Geisinger Medical Oncology-Lewisburg
🇺🇸Lewisburg, Pennsylvania, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
West Penn Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Geisinger Wyoming Valley/Henry Cancer Center
🇺🇸Wilkes-Barre, Pennsylvania, United States
Sanford Cancer Center Oncology Clinic
🇺🇸Sioux Falls, South Dakota, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸Sioux Falls, South Dakota, United States
Baptist Memorial Hospital and Cancer Center-Memphis
🇺🇸Memphis, Tennessee, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Huntsman Cancer Institute/University of Utah
🇺🇸Salt Lake City, Utah, United States
Valley Medical Center
🇺🇸Renton, Washington, United States
Langlade Hospital and Cancer Center
🇺🇸Antigo, Wisconsin, United States
Medical College of Wisconsin
🇺🇸Milwaukee, 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 Cancer Care - Wisconsin Rapids
🇺🇸Wisconsin Rapids, Wisconsin, United States