Comparing Proton Therapy to Photon Radiation Therapy for Esophageal Cancer
- Conditions
- Clinical Stage I Esophageal Adenocarcinoma AJCC v8Clinical Stage I Esophageal Squamous Cell Carcinoma AJCC v8Clinical Stage I Gastroesophageal Junction Adenocarcinoma AJCC v8Clinical Stage II Esophageal Adenocarcinoma AJCC v8Clinical Stage II Esophageal Squamous Cell Carcinoma AJCC v8Clinical Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8Clinical Stage IIA Esophageal Adenocarcinoma AJCC v8Clinical Stage IIA Gastroesophageal Junction Adenocarcinoma AJCC v8Clinical Stage IIB Esophageal Adenocarcinoma AJCC v8Clinical Stage IIB Gastroesophageal Junction Adenocarcinoma AJCC v8
- Interventions
- Procedure: EsophagectomyRadiation: Intensity-Modulated Radiation TherapyRadiation: Proton Beam Radiation TherapyOther: Quality-of-Life AssessmentOther: Questionnaire AdministrationDrug: FOLFOX regimenDrug: CAPOX regimenDrug: 5FU
- Registration Number
- NCT03801876
- Lead Sponsor
- NRG Oncology
- Brief Summary
This trial studies how well proton beam radiation therapy compared with intensity modulated photon radiotherapy works in treating patients with stage I-IVA esophageal cancer. Proton beam radiation therapy uses a beam of protons (rather than x-rays) to send radiation inside the body to the tumor without damaging much of the healthy tissue around it. Intensity modulated photon radiotherapy uses high-energy x-rays to deliver radiation directly to the tumor without damaging much of the healthy tissue around it. It is not yet known whether proton beam therapy or intensity modulated photon radiotherapy will work better in treating patients with esophageal cancer.
- Detailed Description
PRIMARY OBJECTIVES:
I. To determine if overall survival (OS) is improved with proton beam radiation therapy (PBT) treatment as compared to intensity modulated photon radiation therapy (IMRT) as part of planned protocol treatment for patients with esophageal cancer.
II. To determine if OS with PBT is non-inferior to IMRT as part of planned protocol treatment and that there will be less grade 3+ cardiopulmonary toxicity with PBT than with IMRT.
SECONDARY OBJECTIVES:
I. To compare the symptom burden and impact on functioning of patients between treatment modalities based on Patient Reported Outcome (PRO) measures of symptoms using MD Anderson Symptom Inventory (MDASI) and Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue.
II. To compare the Quality-Adjusted Life Years (QALY) using EuroQol five-dimensional questionnaire (EQ5D) as a health outcome between PBT and IMRT, if the protocol primary endpoint is met.
III. To assess the pathologic response rate between PBT and IMRT. IV. To assess the cost-benefit economic analysis of treatment between radiation modalities.
V. To compare the length of hospitalization after protocol surgery between PBT and IMRT.
VI. To compare the incidence of grade 4 lymphopenia during chemoradiation between PBT and IMRT.
VII. To compare lymphocyte nadir at first follow-up visit after completion of chemoradiation between PBT \& IMRT.
VIII. To estimate the locoregional failure, distant metastatic free survival, and progression-free survival of patients treated with PBT versus IMRT.
IX. To compare incidence of both early (\< 90 days from treatment start) and late (≥ 90 days from treatment start) cardiovascular and pulmonary events between PBT versus IMRT.
X. To compare the Total Toxicity Burden (TTB) of IMRT versus PBT based on a composite index of 9 individual cardiopulmonary toxicities.
EXPLORATORY OBJECTIVES:
I. To collect biospecimens for future analyses, for example to assess cardiac and inflammatory biomarkers in association with treatment complications.
OUTLINE: Patients are randomized to 1 of 2 groups.
GROUP I: Patients undergo PBT over 28 fractions 5 days a week for 5.5 weeks. Patients also receive paclitaxel intravenously (IV) and carboplatin IV on days 1, 8, 15, 22, 29, and 36 while undergoing PBT.
GROUP II: Patients undergo IMRT over 28 fractions 5 days a week for 5.5 weeks. Patients also receive paclitaxel IV and carboplatin IV on days 1, 8, 15, 22, 29, and 36 while undergoing IMRT.
In both groups, within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion.
After completion of study treatment, patients are followed up every 3-6 months for 3 years and then annually thereafter.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 300
-
PRIOR TO STEP 1 REGISTRATION:
-
Histologically proven diagnosis of adenocarcinoma or squamous cell carcinoma of the thoracic esophagus or gastroesophageal junction (Siewert I-II)
-
Stage I-IVA, excluding T4b, according to the American Joint Committee on Cancer (AJCC) 8th edition based on the following diagnostic workup:
-
History/physical examination
-
Whole-body fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT) with or without (+/-) contrast (preferred) or chest/abdominal (include pelvic if clinically indicated) CT with contrast
-
For patients who DID NOT receive induction chemotherapy, scan must occur within 30 days prior to Step 1 registration
-
For patients who DID receive induction chemotherapy, scan must occur:
- Within 30 days after final induction chemotherapy dose; OR
- Within 30 days prior to Step 1 registration
-
Note: Patients who had prior endoscopic mucosal resection (EMR) with a diagnosis of AJCC stage I-IVA, excluding T4b, esophageal cancer are eligible
-
-
-
Surgical consultation to determine whether or not the patient is a candidate for resection after completion of chemoradiation
-
Induction chemotherapy for the current malignancy prior to concurrent chemoradiation allowed if last dose is no more than 90 days and no less than 10 days prior to Step 1 registration. Only FOLFOX will be allowed as the induction chemotherapy regimen.
-
Zubrod performance status 0, 1, or 2
-
Absolute neutrophil count (ANC) (within 30 days prior to Step 1 registration)
- For patients who DID NOT receive induction chemotherapy: ANC >= 1,500 cells/mm^3
- For patients who DID receive induction chemotherapy: ANC >= 1,000 cells/mm^3
-
Platelets (within 30 days prior to Step 1 registration)
- For patients who DID NOT receive induction chemotherapy: Platelets >= 100,000/uL
- For patients who DID receive induction chemotherapy: Platelets >= 75,000/uL
-
Hemoglobin >= 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb >= 8.0 g/dl is acceptable) (within 30 days prior to Step 1 registration)
-
Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or Creatinine clearance > 40 mL/min estimated by Cockcroft-Gault formula (within 30 days prior to Step 1 registration)
-
Total bilirubin =< 1.5 x upper limit of normal (ULN) (within 30 days prior to Step 1 registration)
-
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN (within 30 days prior to Step 1 registration)
-
Negative pregnancy test (serum or urine) within 14 days prior to Step 1 registration for women of child bearing potential
-
The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
-
Cervical esophageal cancers arisen from 15-18 cm from the incisors
-
Patients with T4b disease according to the AJCC 8th edition
-
Definitive clinical or radiologic evidence of metastatic disease
-
Any active malignancy within 2 years of study registration that may alter the course of esophageal cancer treatment
-
Prior thoracic radiotherapy that would result in overlap of radiation therapy fields
-
Severe, active co-morbidity defined as follows:
- Active uncontrolled infection requiring IV antibiotics at the time of Step 1 registration
- Uncontrolled symptomatic congestive heart failure, unstable angina, or cardiac arrhythmia not controlled by any device or medication at the time of Step 1 registration
- Myocardial infarction within 3 months prior to Step 1 registration
-
Pregnant and/or nursing females
-
Human immunodeficiency virus (HIV) positive with CD4 count < 200 cells/microliter. Note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to registration. Note also that HIV testing is not required for eligibility for this protocol. This exclusion criterion is necessary because the treatments involved in this protocol may be significantly immunosuppressive
-
PRIOR TO STEP 2 REGISTRATION:
-
Unable to obtain confirmation of payment coverage (insurance or other) for either possible radiation treatment
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group I (PBT, Chemotherapy, Esophagectomy) Esophagectomy Patients undergo PBT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU \[with capecitabine as an acceptable substitute for 5-FU\]) per institutional standards while undergoing PBT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion. Group I (PBT, Chemotherapy, Esophagectomy) Paclitaxel Patients undergo PBT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU \[with capecitabine as an acceptable substitute for 5-FU\]) per institutional standards while undergoing PBT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion. Group I (PBT, Chemotherapy, Esophagectomy) Proton Beam Radiation Therapy Patients undergo PBT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU \[with capecitabine as an acceptable substitute for 5-FU\]) per institutional standards while undergoing PBT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion. Group I (PBT, Chemotherapy, Esophagectomy) Quality-of-Life Assessment Patients undergo PBT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU \[with capecitabine as an acceptable substitute for 5-FU\]) per institutional standards while undergoing PBT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion. Group I (PBT, Chemotherapy, Esophagectomy) Questionnaire Administration Patients undergo PBT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU \[with capecitabine as an acceptable substitute for 5-FU\]) per institutional standards while undergoing PBT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion. Group I (PBT, Chemotherapy, Esophagectomy) FOLFOX regimen Patients undergo PBT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU \[with capecitabine as an acceptable substitute for 5-FU\]) per institutional standards while undergoing PBT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion. Group I (PBT, Chemotherapy, Esophagectomy) CAPOX regimen Patients undergo PBT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU \[with capecitabine as an acceptable substitute for 5-FU\]) per institutional standards while undergoing PBT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion. Group I (PBT, Chemotherapy, Esophagectomy) Docetaxel Patients undergo PBT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU \[with capecitabine as an acceptable substitute for 5-FU\]) per institutional standards while undergoing PBT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion. Group I (PBT, Chemotherapy, Esophagectomy) 5FU Patients undergo PBT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU \[with capecitabine as an acceptable substitute for 5-FU\]) per institutional standards while undergoing PBT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion. Group II (IMRT, Chemotherapy, Esophagectomy) Esophagectomy Patients undergo IMRT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU \[with capecitabine as an acceptable substitute for 5-FU\]) per institutional standards while undergoing IMRT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion. Group II (IMRT, Chemotherapy, Esophagectomy) Intensity-Modulated Radiation Therapy Patients undergo IMRT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU \[with capecitabine as an acceptable substitute for 5-FU\]) per institutional standards while undergoing IMRT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion. Group II (IMRT, Chemotherapy, Esophagectomy) Quality-of-Life Assessment Patients undergo IMRT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU \[with capecitabine as an acceptable substitute for 5-FU\]) per institutional standards while undergoing IMRT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion. Group II (IMRT, Chemotherapy, Esophagectomy) Questionnaire Administration Patients undergo IMRT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU \[with capecitabine as an acceptable substitute for 5-FU\]) per institutional standards while undergoing IMRT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion. Group II (IMRT, Chemotherapy, Esophagectomy) FOLFOX regimen Patients undergo IMRT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU \[with capecitabine as an acceptable substitute for 5-FU\]) per institutional standards while undergoing IMRT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion. Group II (IMRT, Chemotherapy, Esophagectomy) CAPOX regimen Patients undergo IMRT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU \[with capecitabine as an acceptable substitute for 5-FU\]) per institutional standards while undergoing IMRT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion. Group II (IMRT, Chemotherapy, Esophagectomy) 5FU Patients undergo IMRT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU \[with capecitabine as an acceptable substitute for 5-FU\]) per institutional standards while undergoing IMRT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion. Group I (PBT, Chemotherapy, Esophagectomy) Carboplatin Patients undergo PBT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU \[with capecitabine as an acceptable substitute for 5-FU\]) per institutional standards while undergoing PBT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion. Group II (IMRT, Chemotherapy, Esophagectomy) Carboplatin Patients undergo IMRT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU \[with capecitabine as an acceptable substitute for 5-FU\]) per institutional standards while undergoing IMRT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion. Group II (IMRT, Chemotherapy, Esophagectomy) Paclitaxel Patients undergo IMRT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU \[with capecitabine as an acceptable substitute for 5-FU\]) per institutional standards while undergoing IMRT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion. Group II (IMRT, Chemotherapy, Esophagectomy) Docetaxel Patients undergo IMRT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU \[with capecitabine as an acceptable substitute for 5-FU\]) per institutional standards while undergoing IMRT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion.
- Primary Outcome Measures
Name Time Method Overall survival (OS) From the date of randomization to the date of death due to any cause or date of last follow-up for patients without an OS event reported. This analysis occurs after 173 deaths; estimated to occur 4 years after accrual completion Will be estimated by the Kaplan-Meier method. The distributions of OS between treatment arms will be compared using the log rank test.
Incidence of specific grade 3+ cardiopulmonary adverse events (AEs) that are definitely, probably, or possibly related to protocol treatment From baseline up to 8 years Will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Difference in proportion of defined cardiopulmonary AEs will be analyzed with a chi-squared test.
- Secondary Outcome Measures
Name Time Method Pathologic response rate At time of surgery A Chi-square test will be used to compare the pathologic response rates between the treatment arms.
Grade 4 lymphopenia during chemoradiation From the start of chemoradiation to the end of chemoradiation treatment assessed up to 31 days Will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. The proportion of patients experiencing grade 4 lymphopenia during chemoradiation will be compared between treatment arms using a chi-squared test.
Lymphocyte counts From the last date of chemoradiation up to 8 weeks post chemoradiation Mean lymphocyte counts at first post chemoradiation follow-up will be compared between treatment arms using a t-test. If the data do not satisfy the normality assumption, a Wilcoxin test may be used instead.
Locoregional failure (LRF) From the date of randomization to the date of first LRF or date of last follow-up for patients without an LRF event reported, assessed up to 8 years Will be defined as local/regional recurrence or progression. Will be estimated by the cumulative incidence method, with death as a competing risk. The distribution of LRF estimates between the two arms will be compared using Gray?s test. The Fine-Gray regression model will be used to analyze the effects of factors, in addition to treatment, which may be associated with LRF.
Distant metastatic-free survival (DMFS) From the date of randomization to the date of first DMFS failure or last follow-up for patients without a reported DMFS event, assessed up to 8 years Will be defined as appearance of distant metastasis or death due to any cause. Will be estimated by the Kaplan-Meier method and estimates between the two treatment arms will be compared using the log rank test. The Cox proportional hazard regression model will be used to analyze the effects of factors, in addition to treatment, which may be associated with DMFS.
Progression-free survival From the date of randomization to the date of first PFS failure or last follow-up for patients without a reported PFS event, assessed up to 8 years Will be defined as appearance of local/regional/distant failure or death due to any cause. Will be estimated by the Kaplan-Meier method and estimates between the two treatment arms will be compared using the log rank test. The Cox proportional hazard regression model will be used to analyze the effects of factors, in addition to treatment, which may be associated with PFS.
Quality-adjusted life years (QALY) Assessed up to 8 years Will be evaluated and compared using EuroQol five-dimensional questionnaire (EQ-5D) only if the primary endpoint is met.
Cost-benefit economic analysis of treatment Assessed up to 8 years Will be calculated by the visual analog scale (VAS) and index scores form the EQ-5D-5L only be done if primary endpoint is met. Will be compared between treatment arms using a t-test with a 2-sided significance level of 0.05. If there are significant differences, then a cost analysis will be conducted.
Trial Locations
- Locations (90)
Mayo Clinic Hospital in Arizona
🇺🇸Phoenix, Arizona, United States
Miami Cancer Institute
🇺🇸Miami, Florida, United States
Northwestern Medicine Cancer Center Delnor
🇺🇸Geneva, Illinois, United States
University of Maryland/Greenebaum Cancer Center
🇺🇸Baltimore, Maryland, United States
UM Upper Chesapeake Medical Center
🇺🇸Bel Air, Maryland, United States
Mayo Clinic in Arizona
🇺🇸Scottsdale, Arizona, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
🇺🇸Deerfield Beach, Florida, United States
Northwestern Medicine Cancer Center Kishwaukee
🇺🇸DeKalb, Illinois, United States
Maryland Proton Treatment Center
🇺🇸Baltimore, Maryland, United States
McLaren Cancer Institute-Bay City
🇺🇸Bay City, Michigan, United States
Corewell Health Dearborn Hospital
🇺🇸Dearborn, Michigan, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
McLaren Cancer Institute-Lapeer Region
🇺🇸Lapeer, Michigan, United States
Corewell Health Beaumont Troy Hospital
🇺🇸Troy, Michigan, United States
Memorial Sloan Kettering Westchester
🇺🇸Harrison, New York, United States
UH Seidman Cancer Center at UH Avon Health Center
🇺🇸Avon, Ohio, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
🇺🇸Coral Gables, Florida, United States
Emory University Hospital/Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Emory Saint Joseph's Hospital
🇺🇸Atlanta, Georgia, United States
Memorial Hospital East
🇺🇸Shiloh, Illinois, United States
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
Karmanos Cancer Institute at McLaren Greater Lansing
🇺🇸Lansing, Michigan, United States
Corewell Health William Beaumont University Hospital
🇺🇸Royal Oak, Michigan, United States
Mayo Clinic Health System in Albert Lea
🇺🇸Albert Lea, Minnesota, United States
Minnesota Oncology Hematology PA-Maplewood
🇺🇸Maplewood, Minnesota, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
Siteman Cancer Center at West County Hospital
🇺🇸Creve Coeur, Missouri, United States
Memorial Sloan Kettering Commack
🇺🇸Commack, New York, United States
New York Proton Center
🇺🇸New York, New York, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Orlando Health Cancer Institute
🇺🇸Orlando, Florida, United States
Emory Proton Therapy Center
🇺🇸Atlanta, Georgia, United States
Emory University Hospital Midtown
🇺🇸Atlanta, Georgia, United States
Alton Memorial Hospital
🇺🇸Alton, Illinois, United States
Weisberg Cancer Treatment Center
🇺🇸Farmington Hills, Michigan, United States
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States
Ridgeview Medical Center
🇺🇸Waconia, Minnesota, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center-South County
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center at Christian Hospital
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center at Saint Peters Hospital
🇺🇸Saint Peters, Missouri, United States
Northwestern Medicine Cancer Center Warrenville
🇺🇸Warrenville, Illinois, United States
McLaren Cancer Institute-Flint
🇺🇸Flint, Michigan, United States
McLaren Cancer Institute-Owosso
🇺🇸Owosso, Michigan, United States
Unity Hospital
🇺🇸Fridley, Minnesota, United States
Mayo Clinic Health Systems-Mankato
🇺🇸Mankato, Minnesota, United States
Mercy Hospital Springfield
🇺🇸Springfield, Missouri, United States
Memorial Sloan Kettering Basking Ridge
🇺🇸Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Bergen
🇺🇸Montvale, New Jersey, United States
University of Cincinnati Cancer Center-UC Medical Center
🇺🇸Cincinnati, Ohio, United States
Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Mayo Clinic Radiation Therapy-Northfield
🇺🇸Northfield, Minnesota, United States
Mercy Hospital Saint Louis
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan Kettering Monmouth
🇺🇸Middletown, New Jersey, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Geauga Hospital
🇺🇸Chardon, Ohio, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Memorial Sloan Kettering Nassau
🇺🇸Uniondale, New York, United States
UHHS-Chagrin Highlands Medical Center
🇺🇸Beachwood, Ohio, United States
Mercy Cancer Center-Elyria
🇺🇸Elyria, Ohio, United States
UH Seidman Cancer Center at Landerbrook Health Center
🇺🇸Mayfield Heights, Ohio, United States
UH Seidman Cancer Center at Lake Health Mentor Campus
🇺🇸Mentor, Ohio, United States
UH Seidman Cancer Center at Southwest General Hospital
🇺🇸Middleburg Heights, Ohio, United States
University Hospitals Parma Medical Center
🇺🇸Parma, Ohio, United States
University Hospitals Portage Medical Center
🇺🇸Ravenna, Ohio, United States
UH Seidman Cancer Center at Firelands Regional Medical Center
🇺🇸Sandusky, Ohio, United States
University Hospitals Sharon Health Center
🇺🇸Wadsworth, Ohio, United States
University of Cincinnati Cancer Center-West Chester
🇺🇸West Chester, Ohio, United States
UH Seidman Cancer Center at Saint John Medical Center
🇺🇸Westlake, Ohio, United States
UHHS-Westlake Medical Center
🇺🇸Westlake, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
University of Pennsylvania/Abramson Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Thompson Proton Center
🇺🇸Knoxville, Tennessee, United States
Thompson Cancer Survival Center
🇺🇸Knoxville, Tennessee, United States
Thompson Cancer Survival Center - West
🇺🇸Knoxville, Tennessee, United States
Thompson Oncology Group-Maryville
🇺🇸Maryville, Tennessee, United States
Thompson Oncology Group-Oak Ridge
🇺🇸Oak Ridge, Tennessee, United States
MD Anderson in The Woodlands
🇺🇸Conroe, Texas, United States
MD Anderson West Houston
🇺🇸Houston, Texas, United States
Inova Schar Cancer Institute
🇺🇸Fairfax, Virginia, United States
M D Anderson Cancer Center
🇺🇸Houston, Texas, United States
MD Anderson League City
🇺🇸League City, Texas, United States
MD Anderson in Sugar Land
🇺🇸Sugar Land, Texas, United States
Huntsman Cancer Institute/University of Utah
🇺🇸Salt Lake City, Utah, United States
Inova Loudoun Hospital
🇺🇸Leesburg, Virginia, United States
University of Washington Medical Center - Montlake
🇺🇸Seattle, Washington, United States
Inova Alexandria Hospital
🇺🇸Alexandria, Virginia, United States
Inova Fair Oaks Hospital
🇺🇸Fairfax, Virginia, United States
Mayo Clinic Health System-Eau Claire Clinic
🇺🇸Eau Claire, Wisconsin, United States