Whole-Brain Radiation Therapy or Stereotactic Radiosurgery With or Without Lapatinib Ditosylate in Treating Patients With Brain Metastasis From HER2-Positive Breast Cancer

Phase 2

Completed

Conditions: Metastatic Malignant Neoplasm in the Brain
Recurrent Breast Carcinoma
HER2-Positive Breast Carcinoma
Invasive Breast Carcinoma
Stage IV Breast Cancer AJCC v6 and v7

Interventions: Other: Laboratory Biomarker Analysis
Radiation: Stereotactic Radiosurgery
Drug: Lapatinib Ditosylate
Radiation: Whole-Brain Radiotherapy

Registration Number: NCT01622868

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This randomized phase II trial studies how well whole-brain radiation therapy or stereotactic radiosurgery with or without lapatinib ditosylate works in treating patients with breast cancer that has too many of a protein called human epidermal growth factor receptor 2 (HER2) on its cells and has spread to the brain. Radiation therapy uses high energy x rays to kill tumor cells and shrink tumors. Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may kill more tumor cells and cause less damage to normal tissue. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether whole-brain radiation therapy or stereotactic radiosurgery together with lapatinib ditosylate is an effective treatment for brain metastasis from breast cancer.

Detailed Description: PRIMARY OBJECTIVES:

I. To determine if there is a signal for an increase in complete response (CR) rate in the measurable brain metastases at 12 weeks post radiation therapy (RT) (whole brain or stereotactic radiosurgery \[SRS\]) as determined by magnetic-resonance imaging (MRI) scan of the brain, with the addition of lapatinib (lapatinib ditosylate) to whole-brain radiation therapy (WBRT)/SRS compared to WBRT/SRS alone.

SECONDARY OBJECTIVES:

I. To evaluate CR rate of the measurable brain metastases at 4 weeks post RT (WBRT/SRS) as determined by MRI scan of the brain, with the addition of lapatinib to WBRT/SRS compared to WBRT/SRS alone.

II. To evaluate objective response rate of measurable brain metastases at 4 and 12 weeks post RT (WBRT/SRS) as determined by MRI scan of the brain, with the addition of lapatinib to WBRT/SRS compared to WBRT/SRS alone.

III. To evaluate targeted lesion-specific objective response rate (CR + partial response \[PR\]) at 4 and 12 weeks post WBRT/SRS.

IV. To evaluate central nervous system (CNS) progressive disease outside the targeted measurable disease with addition of lapatinib to WBRT/SRS compared to WBRT/SRS alone.

V. To evaluate targeted lesion-specific progression at 4 and 12 weeks post WBRT/SRS.

VI. To evaluate treatment related adverse events when adding lapatinib to WBRT/SRS compared to WBRT/SRS alone.

VII. To evaluate overall CNS complete response: disappearance of all CNS target lesions sustained for at least 4 weeks; with no new lesions, no use of corticosteroids, and patient is stable or improved clinically, when adding lapatinib to WBRT/SRS compared to WBRT/SRS alone.

VIII. To evaluate overall CNS progressive disease (within or outside targeted measurable disease) with addition of lapatinib to WBRT/SRS compared to WBRT/SRS alone.

IX. To evaluate overall survival when adding lapatinib to WBRT/SRS compared to WBRT/SRS alone.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients undergo WBRT 5 days a week for 3 weeks for a total of 15 treatments or SRS for 1 treatment.

ARM B: Patients undergo WBRT or SRS as in Arm A. Patients also receive lapatinib ditosylate orally (PO) once daily (QD) for 6 weeks.

After completion of study treatment, patients are followed up at 4 and 12 weeks and then every 12 weeks thereafter.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 143

Inclusion Criteria

Pathologically (histologically or cytologically) proven diagnosis of invasive breast cancer
HER2-overexpressing breast cancer (3+ staining by immunohistochemistry or HER2 gene amplification by fluorescent in situ hybridization [FISH] or silver in situ hybridization [SISH] >= 2.0)
At least 1 measurable unirradiated parenchymal brain metastasis within 21 days prior to study entry; patients who are to undergo SRS must have no more than 10 brain metastases; there is no limit on number of brain metastases for WBRT; the minimum size as measured on T1-weighted gadolinium-enhanced MRI must be as follows according to the number of brain metastases:
- For a single solitary lesion the size must be >= 10 mm
- For 2 or more lesions, the size of at least 2 of the lesions must be >= 5 mm
- Patients may also have the following provided the size requirements above are met:
  - Progressive parenchymal brain metastasis following stereotactic radiosurgery for 1-3 brain metastases, with at least 1 new measurable brain lesion
  - Progressive parenchymal brain metastasis following surgical resection of 1-3 brain metastases, with at least 1 measurable brain lesion
History/physical examination within 21 days prior to study entry
Karnofsky performance status >= 60 within 21 days prior to study entry
Able to swallow and retain oral medication (note: for patients unable to swallow tablets, an oral suspension preparation is acceptable)
Absolute neutrophil count (ANC) >= 1,200 cells/mm^3 (within 21 days prior to study entry)
Platelets >= 70,000 cells/mm^3 (within 21 days prior to study entry)
Hemoglobin >= 8.0 g/dL (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dL is acceptable) (within 21 days prior to study entry)
Creatinine < 1.5 times institutional upper limit of normal (within 21 days prior to study entry)
Bilirubin < 1.5 times institutional upper limit of normal (within 21 days prior to study entry)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 times institutional upper limit of normal with or without liver metastasis (within 21 days prior to study entry)
Patient must provide study specific informed consent prior to study entry
Women of childbearing potential must have a negative serum pregnancy test within 21 days prior to study entry
Sexually active women of childbearing potential and sexually active men must practice adequate contraception during therapy and for 12 months after protocol treatment completion
Prior lapatinib is allowed as long as the last dose received was > 21 days prior to study entry and provided the patient has not received it at any time after the diagnosis of brain metastasis

Exclusion Criteria

Prior WBRT
Prior radiation therapy (RT) (any site) with concurrent lapatinib defined as 1 or more days on which the patient received both radiation therapy and lapatinib on the same day
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Prior invasive malignancy (except non-melanomatous skin cancer, curatively resected thyroid papillary carcinoma, and invasive and non-invasive cancers related to the breast cancer) unless disease free for a minimum of 3 years
Leptomeningeal disease
Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields except patients who have progressed following stereotactic radiosurgery for 1-3 brain metastases, with at least one new lesion
Severe, active co-morbidity, defined as follows:
- Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
- Transmural myocardial infarction within the last 6 months
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of study entry
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of study entry
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; hepatic or biliary disease that is acute or currently active or that requires antiviral therapy (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease per investigator assessment)
- History of left ventricular ejection fraction (LVEF) below institutional normal unless repeated and within institutional normal range within 90 days of study entry
Grade 2 or greater rash of any cause at time of study entry
Grade 2 or greater diarrhea of any cause at time of study entry

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A (WBRT or SRS)	Laboratory Biomarker Analysis	Patients undergo WBRT 5 days a week for 3 weeks for a total of 15 treatments, or SRS for 1 treatment.
Arm A (WBRT or SRS)	Stereotactic Radiosurgery	Patients undergo WBRT 5 days a week for 3 weeks for a total of 15 treatments, or SRS for 1 treatment.
Arm A (WBRT or SRS)	Whole-Brain Radiotherapy	Patients undergo WBRT 5 days a week for 3 weeks for a total of 15 treatments, or SRS for 1 treatment.
Arm B (lapatinib ditosylate, WBRT or SRS)	Laboratory Biomarker Analysis	Patients undergo WBRT or SRS as in Arm A. Patients also receive lapatinib ditosylate PO QD for 6 weeks.
Arm B (lapatinib ditosylate, WBRT or SRS)	Lapatinib Ditosylate	Patients undergo WBRT or SRS as in Arm A. Patients also receive lapatinib ditosylate PO QD for 6 weeks.
Arm B (lapatinib ditosylate, WBRT or SRS)	Stereotactic Radiosurgery	Patients undergo WBRT or SRS as in Arm A. Patients also receive lapatinib ditosylate PO QD for 6 weeks.
Arm B (lapatinib ditosylate, WBRT or SRS)	Whole-Brain Radiotherapy	Patients undergo WBRT or SRS as in Arm A. Patients also receive lapatinib ditosylate PO QD for 6 weeks.

Primary Outcome Measures

Name	Time	Method
Complete Response (CR) Rate in the Brain at 12 Weeks Post-radiation Therapy (RT) Using the RECIST 1.1 Criteria Based on Brain Magnetic Resonance Imaging (MRI)	Baseline and 12 weeks post RT (approximately 12 weeks from start of treatment if SRS and 15 if WBRT)	The Response Evaluation Criteria in Solid Tumors (RECIST) criteria evaluates changes in the largest diameter (unidimensional measurement) of the tumor lesions. Complete response is defined as the complete disappearance of all enhancing disease and off all steroids. Rate is calculated by dividing the number of patients with complete response by the number of analyzable patients.

Secondary Outcome Measures

Name	Time	Method
Complete Response Rate in the Brain at 4 Weeks Post-RT Using the RECIST 1.1 Criteria Based on Brain MRI	Baseline and 4 weeks post RT (approximately 4 weeks from start of treatment if SRS and 7 if WBRT)	The RECIST criteria evaluates changes in the largest diameter (unidimensional measurement) of the tumor lesions. Complete response is defined as the complete disappearance of all enhancing disease and off all steroids. Rate is calculated by dividing the number of patients with complete response by the number of analyzable patients.
Targeted Lesion-specific Objective Response Rate Using the RECIST 1.1 Measurement Criteria Based on Brain MRI	Baseline, 4 and 12 weeks post RT (approximately 4 and 12 weeks from start of treatment if SRS, 7 and 15 if WBRT)	The RECIST criteria evaluates changes in the largest diameter (unidimensional measurement) of the tumor lesions. Objective response is defined as a complete or partial response. Complete response is defined as the complete disappearance of all enhancing disease and partial response is defined as ≥ 30% reduction in the diameter of the target lesion. Lesions were evaluated individually. Rate is calculated by dividing the number of lesions with objective response by the number of analyzable lesions.
Targeted Lesion-specific Progression Rate Using the RECIST 1.1 Measurement Criteria Based on Brain MRI	Baseline, 4 and 12 weeks post RT (approximately 4 and 12 weeks from start of treatment if SRS, 7 and 15 if WBRT)	The RECIST criteria evaluates changes in the largest diameter (unidimensional measurement) of the tumor lesions. Progression is defined as ≥ 20% increase in the diameter of the target lesion relative to nadir. Lesions were evaluated individually. Rate is calculated by dividing the number of lesions with progression by the number of analyzable lesions.
Complete Response Rate in the Brain Using the World Health Organization (WHO)/Modified McDonald Criteria Based on Brain MRI	Baseline, 4 and 12 weeks post RT (approximately 4 and 12 weeks from start of treatment if SRS, 7 and 15 if WBRT)	The WHO/modified McDonald Criteria evaluates changes in bidimensional tumor measurements. Complete response is defined as the complete disappearance of all enhancing disease and off all steroids. Rate is calculated by dividing the number of patients with complete response by the number of analyzable patients.
Percentage of Participants With Progression in the Brain Outside the Targeted Measurable Disease Using the RECIST 1.1 Criteria Based on Brain MRI	From randomization to last follow-up. MRIs occurred at baseline, 4 and 12 weeks post RT, then every 12 weeks thereafter until progression. Maximum follow-up at time of analysis was 71.6 months.	The RECIST criteria evaluates changes in the largest diameter (unidimensional measurement) of the tumor lesions. CNS progressive disease outside the targeted measureable disease was determined by a retrospective central review of MRI scans by the study neuroradiology co-chair and is defined as the first occurrence since baseline of new lesions or progression of non-target lesions. Time to CNS progressive disease is defined as time from randomization to the date of progressive disease, last known follow-up (censored), or death (competing risk). Progression rates are estimated using the cumulative incidence method. One-year rates are provided.
Overall Complete Response Rate in the Brain Using the RECIST 1.1 Criteria Based on Brain MRI	From randomization to last follow-up. MRIs occurred at baseline, 4 and 12 weeks post RT, then every 12 weeks thereafter until progression. Maximum follow-up at time of analysis was 71.6 months.	The RECIST criteria evaluates changes in the largest diameter (unidimensional measurement) of the tumor lesions. Overall complete response is defined as the complete disappearance of all CNS target lesions sustained for at least 4 weeks; with no new lesions, no use of corticosteroids, and patient is stable or improved clinically. All site-reported MRI data and all site-reporting of clinical progressive disease indicators were used in this analysis. Rate is calculated by dividing the number of participants with overall complete response by the number of analyzable participants.
Objective Response Rate in the Brain Using the RECIST 1.1 Criteria Based on Brain MRI	Baseline, 4 and 12 weeks post RT (approximately 4 and 12 weeks from start of treatment if SRS, 7 and 15 if WBRT)	The RECIST criteria evaluates changes in the largest diameter (unidimensional measurement) of the tumor lesions. Objective response is defined as a complete or partial response. Complete response is defined as the complete disappearance of all enhancing disease and off all steroids. Partial response is defined as ≥ 30% reduction in the sum of diameters of up to 2 of the largest target lesions. Rate is calculated by dividing the number of patients with objective response by the number of analyzable patients.
Overall Progression Rate in the Brain Using the RECIST 1.1 Criteria Based on Brain MRI	From randomization to last follow-up. MRIs occurred at baseline, 4 and 12 weeks post RT, then every 12 weeks thereafter until progression. Maximum follow-up at time of analysis was 71.6 months.	The RECIST criteria evaluates changes in the largest diameter (unidimensional measurement) of the tumor lesions. Overall progression is defined as unequivocal progression, new or worsening tumor-related neurological symptoms, tumor-related increase in steroid dose, new primary in brain, or progression in target lesions. All site-reported MRI data and all site-reporting of clinical progressive disease indicators were used in this analysis. Rate is calculated by dividing the number of participants with progression by the number of analyzable participants.
Frequency of Highest Treatment-related Adverse Event Per Participant	From randomization to last follow-up. Maximum follow-up at time of analysis was 71.6 months.	Adverse events reported as definitely, probably, or possibly related to protocol treatment. Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. Summary data provided in this outcome measure. See Adverse Events Module for specific Adverse Event data.
Overall Survival (OS)	From randomization to last follow-up. Maximum follow-up at time of analysis was 71.6 months.	An event for overall survival is death due to any cause. Survival time is defined as time from randomization to the date of death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. Analysis occurred after 101 deaths were reported.

Trial Locations

Locations (302): Greater Baltimore Medical Center
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Baltimore, Maryland, United States
Thomas Jefferson University Hospital
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Philadelphia, Pennsylvania, United States
UChicago Medicine Comprehensive Cancer Center - Saint Joseph Hospital
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Chicago, Illinois, United States
Case Western Reserve University
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Cleveland, Ohio, United States
Cleveland Clinic Foundation
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Cleveland, Ohio, United States
Ohio State University Comprehensive Cancer Center
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Columbus, Ohio, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
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Miami, Florida, United States
Miami Cancer Institute
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Miami, Florida, United States
Palo Alto Medical Foundation-Sunnyvale
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Sunnyvale, California, United States
Carle Cancer Center
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Urbana, Illinois, United States
United Hospital
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Saint Paul, Minnesota, United States
Bixby Medical Center
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Adrian, Michigan, United States
Memorial Medical Center - Las Cruces
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Las Cruces, New Mexico, United States
Centerpoint Medical Center LLC
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Independence, Missouri, United States
Central Care Cancer Center - Bolivar
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Bolivar, Missouri, United States
Regions Hospital
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Saint Paul, Minnesota, United States
Rice Memorial Hospital
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Willmar, Minnesota, United States
Siteman Cancer Center at West County Hospital
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Creve Coeur, Missouri, United States
Ridgeview Medical Center
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Waconia, Minnesota, United States
Saint Francis Medical Center
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Cape Girardeau, Missouri, United States
Mercy Hospital Joplin
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Joplin, Missouri, United States
Gibbs Cancer Center-Pelham
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Greer, South Carolina, United States
Wheeling Hospital/Schiffler Cancer Center
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Wheeling, West Virginia, United States
Green Bay Oncology at Saint Vincent Hospital
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Green Bay, Wisconsin, United States
Saint Vincent Hospital Cancer Center Green Bay
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Green Bay, Wisconsin, United States
Gangnam Severance Hospital
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Seoul, Korea, Republic of
UH Seidman Cancer Center at Salem Regional Medical Center
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Salem, Ohio, United States
Oncology Hematology Care Inc-Kenwood
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Cincinnati, Ohio, United States
Abbott-Northwestern Hospital
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Minneapolis, Minnesota, United States
Hennepin County Medical Center
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Minneapolis, Minnesota, United States
Health Partners Inc
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Minneapolis, Minnesota, United States
University of Texas Health Science Center at San Antonio
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San Antonio, Texas, United States
California Pacific Medical Center-Pacific Campus
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San Francisco, California, United States
Boston Medical Center
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Boston, Massachusetts, United States
University of Mississippi Medical Center
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Jackson, Mississippi, United States
University of Rochester
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Rochester, New York, United States
Saint Joseph's Hospital and Medical Center
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Phoenix, Arizona, United States
Henry Ford Hospital
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Detroit, Michigan, United States
The Kirklin Clinic at Acton Road
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Birmingham, Alabama, United States
Delbert Day Cancer Institute at PCRMC
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Rolla, Missouri, United States
Minnesota Oncology Hematology PA-Maplewood
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Maplewood, Minnesota, United States
Bronson Methodist Hospital
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Kalamazoo, Michigan, United States
Mercy Hospital Springfield
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Springfield, Missouri, United States
University of South Alabama Mitchell Cancer Institute
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Mobile, Alabama, United States
University of Alabama at Birmingham Cancer Center
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Birmingham, Alabama, United States
Banner University Medical Center - Tucson
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Tucson, Arizona, United States
Sutter Cancer Centers Radiation Oncology Services-Cameron Park
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Cameron Park, California, United States
Mills-Peninsula Medical Center
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Burlingame, California, United States
Sutter Auburn Faith Hospital
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Auburn, California, United States
Sutter Cancer Centers Radiation Oncology Services-Auburn
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Auburn, California, United States
Alta Bates Summit Medical Center-Herrick Campus
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Berkeley, California, United States
Mercy San Juan Medical Center
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Carmichael, California, United States
Bay Area Breast Surgeons Inc
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Emeryville, California, United States
Epic Care-Dublin
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Dublin, California, United States
Sutter Davis Hospital
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Davis, California, United States
Memorial Medical Center
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Modesto, California, United States
Contra Costa Regional Medical Center
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Martinez, California, United States
Epic Care Partners in Cancer Care
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Emeryville, California, United States
Palo Alto Medical Foundation-Camino Division
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Mountain View, California, United States
Alta Bates Summit Medical Center - Summit Campus
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Oakland, California, United States
Palo Alto Medical Foundation-Gynecologic Oncology
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Mountain View, California, United States
Sutter Cancer Research Consortium
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Novato, California, United States
Palo Alto Medical Foundation Health Care
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Palo Alto, California, United States
Bay Area Tumor Institute
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Oakland, California, United States
Stanford Cancer Institute Palo Alto
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Palo Alto, California, United States
Sutter Cancer Centers Radiation Oncology Services-Roseville
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Roseville, California, United States
Sutter Roseville Medical Center
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Roseville, California, United States
Palo Alto Medical Foundation-Santa Cruz
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Santa Cruz, California, United States
Sutter Pacific Medical Foundation
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Santa Rosa, California, United States
Sutter Cancer Centers Radiation Oncology Services-Vacaville
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Vacaville, California, United States
Sutter Solano Medical Center/Cancer Center
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Vallejo, California, United States
Smilow Cancer Hospital Care Center at Saint Francis
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Hartford, Connecticut, United States
Epic Care Cyberknife Center
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Walnut Creek, California, United States
Beebe Medical Center
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Lewes, Delaware, United States
The Hospital of Central Connecticut
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New Britain, Connecticut, United States
Christiana Gynecologic Oncology LLC
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Newark, Delaware, United States
Delaware Clinical and Laboratory Physicians PA
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Newark, Delaware, United States
Christiana Care Health System-Christiana Hospital
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Newark, Delaware, United States
Helen F Graham Cancer Center
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Newark, Delaware, United States
Beebe Health Campus
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Rehoboth Beach, Delaware, United States
TidalHealth Nanticoke / Allen Cancer Center
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Seaford, Delaware, United States
Medical Oncology Hematology Consultants PA
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Newark, Delaware, United States
Christiana Care Health System-Wilmington Hospital
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Wilmington, Delaware, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
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Deerfield Beach, Florida, United States
Piedmont Hospital
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Atlanta, Georgia, United States
Northside Hospital
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Atlanta, Georgia, United States
Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
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Savannah, Georgia, United States
Northside Hospital-Forsyth
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Cumming, Georgia, United States
Saint Alphonsus Cancer Care Center-Boise
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Boise, Idaho, United States
Piedmont Fayette Hospital
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Fayetteville, Georgia, United States
Saint Alphonsus Cancer Care Center-Caldwell
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Caldwell, Idaho, United States
Idaho Urologic Institute-Meridian
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Meridian, Idaho, United States
John H Stroger Jr Hospital of Cook County
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Chicago, Illinois, United States
Rush - Copley Medical Center
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Aurora, Illinois, United States
Carle Physician Group-Effingham
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Effingham, Illinois, United States
Carle on Vermilion
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Danville, Illinois, United States
Good Samaritan Regional Health Center
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Mount Vernon, Illinois, United States
Carle Physician Group-Mattoon/Charleston
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Mattoon, Illinois, United States
Elkhart General Hospital
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Elkhart, Indiana, United States
Elkhart Clinic
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Elkhart, Indiana, United States
Parkview Hospital Randallia
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Fort Wayne, Indiana, United States
Michiana Hematology Oncology PC-Elkhart
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Elkhart, Indiana, United States
Radiation Oncology Associates PC
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Fort Wayne, Indiana, United States
IU Health La Porte Hospital
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La Porte, Indiana, United States
Parkview Regional Medical Center
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Fort Wayne, Indiana, United States
Community Howard Regional Health
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Kokomo, Indiana, United States
Saint Joseph Regional Medical Center-Mishawaka
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Mishawaka, Indiana, United States
Michiana Hematology Oncology PC-Mishawaka
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Mishawaka, Indiana, United States
Memorial Regional Cancer Center Day Road
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Mishawaka, Indiana, United States
Reid Health
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Richmond, Indiana, United States
South Bend Clinic
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South Bend, Indiana, United States
Michiana Hematology Oncology PC-Plymouth
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Plymouth, Indiana, United States
Memorial Hospital of South Bend
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South Bend, Indiana, United States
Michiana Hematology Oncology PC-South Bend
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South Bend, Indiana, United States
Michiana Hematology Oncology PC-Westville
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Westville, Indiana, United States
Saint Luke's Hospital
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Cedar Rapids, Iowa, United States
Central Care Cancer Center - Great Bend
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Great Bend, Kansas, United States
Central Care Cancer Center - Garden City
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Garden City, Kansas, United States
Kansas Institute of Medicine Cancer and Blood Center
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Lenexa, Kansas, United States
Menorah Medical Center
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Overland Park, Kansas, United States
Saint Luke's South Hospital
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Overland Park, Kansas, United States
Minimally Invasive Surgery Hospital
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Lenexa, Kansas, United States
Bronson Battle Creek
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Battle Creek, Michigan, United States
Hickman Cancer Center
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Adrian, Michigan, United States
Spectrum Health Big Rapids Hospital
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Big Rapids, Michigan, United States
Saint Joseph Mercy Brighton
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Brighton, Michigan, United States
Henry Ford Cancer Institute-Downriver
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Brownstown, Michigan, United States
Saint Joseph Mercy Canton
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Canton, Michigan, United States
Saint Joseph Mercy Chelsea
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Chelsea, Michigan, United States
Beaumont Hospital - Dearborn
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Dearborn, Michigan, United States
Henry Ford Macomb Hospital-Clinton Township
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Clinton Township, Michigan, United States
Ascension Saint John Hospital
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Detroit, Michigan, United States
Green Bay Oncology - Escanaba
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Escanaba, Michigan, United States
Genesys Hurley Cancer Institute
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Flint, Michigan, United States
Mercy Health Saint Mary's
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Grand Rapids, Michigan, United States
Spectrum Health at Butterworth Campus
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Grand Rapids, Michigan, United States
Green Bay Oncology - Iron Mountain
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Iron Mountain, Michigan, United States
Hurley Medical Center
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Flint, Michigan, United States
Allegiance Health
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Jackson, Michigan, United States
Borgess Medical Center
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Kalamazoo, Michigan, United States
West Michigan Cancer Center
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Kalamazoo, Michigan, United States
Trinity Health Saint Mary Mercy Livonia Hospital
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Livonia, Michigan, United States
Sparrow Hospital
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Lansing, Michigan, United States
Mercy Memorial Hospital
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Monroe, Michigan, United States
Mercy Health Mercy Campus
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Muskegon, Michigan, United States
Toledo Clinic Cancer Centers-Monroe
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Monroe, Michigan, United States
21st Century Oncology-Pontiac
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Pontiac, Michigan, United States
Lakeland Hospital Niles
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Niles, Michigan, United States
Saint Joseph Mercy Oakland
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Pontiac, Michigan, United States
Lakeland Medical Center Saint Joseph
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Saint Joseph, Michigan, United States
Lake Huron Medical Center
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Port Huron, Michigan, United States
Ascension Saint Mary's Hospital
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Saginaw, Michigan, United States
Marie Yeager Cancer Center
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Saint Joseph, Michigan, United States
Henry Ford West Bloomfield Hospital
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West Bloomfield, Michigan, United States
Saint John Macomb-Oakland Hospital
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Warren, Michigan, United States
Munson Medical Center
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Traverse City, Michigan, United States
Mercy Hospital
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Coon Rapids, Minnesota, United States
Metro Health Hospital
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Wyoming, Michigan, United States
Fairview Ridges Hospital
🇺🇸
Burnsville, Minnesota, United States
Unity Hospital
🇺🇸
Fridley, Minnesota, United States
Fairview Southdale Hospital
🇺🇸
Edina, Minnesota, United States
Fairview Clinics and Surgery Center Maple Grove
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Maple Grove, Minnesota, United States
Saint John's Hospital - Healtheast
🇺🇸
Maplewood, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸
Saint Louis Park, Minnesota, United States
North Memorial Medical Health Center
🇺🇸
Robbinsdale, Minnesota, United States
Singing River Hospital
🇺🇸
Pascagoula, Mississippi, United States
Saint Luke's East - Lee's Summit
🇺🇸
Lee's Summit, Missouri, United States
Liberty Radiation Oncology Center
🇺🇸
Liberty, Missouri, United States
Mercy Clinic-Rolla-Cancer and Hematology
🇺🇸
Rolla, Missouri, United States
Heartland Regional Medical Center
🇺🇸
Saint Joseph, Missouri, United States
Saint Joseph Oncology Inc
🇺🇸
Saint Joseph, Missouri, United States
Saint Louis Cancer and Breast Institute-South City
🇺🇸
Saint Louis, Missouri, United States
Mercy Hospital Saint Louis
🇺🇸
Saint Louis, Missouri, United States
Siteman Cancer Center at Saint Peters Hospital
🇺🇸
Saint Peters, Missouri, United States
Siteman Cancer Center-South County
🇺🇸
Saint Louis, Missouri, United States
Saint Louis-Cape Girardeau CCOP
🇺🇸
Saint Louis, Missouri, United States
Renown Regional Medical Center
🇺🇸
Reno, Nevada, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Elliot Hospital
🇺🇸
Manchester, New Hampshire, United States
CoxHealth South Hospital
🇺🇸
Springfield, Missouri, United States
Virtua Voorhees
🇺🇸
Voorhees, New Jersey, United States
Saint Barnabas Medical Center
🇺🇸
Livingston, New Jersey, United States
Virtua Memorial
🇺🇸
Mount Holly, New Jersey, United States
New York-Presbyterian/Brooklyn Methodist Hospital
🇺🇸
Brooklyn, New York, United States
Roswell Park Cancer Institute
🇺🇸
Buffalo, New York, United States
Hematology Oncology Associates of Central New York-East Syracuse
🇺🇸
East Syracuse, New York, United States
Highland Hospital
🇺🇸
Rochester, New York, United States
Mount Sinai Hospital
🇺🇸
New York, New York, United States
AdventHealth Hendersonville
🇺🇸
Hendersonville, North Carolina, United States
Iredell Memorial Hospital
🇺🇸
Statesville, North Carolina, United States
Radiation Oncology Center
🇺🇸
Alliance, Ohio, United States
Cleveland Clinic Akron General
🇺🇸
Akron, Ohio, United States
Summa Health System - Akron Campus
🇺🇸
Akron, Ohio, United States
Toledo Clinic Cancer Centers-Bowling Green
🇺🇸
Bowling Green, Ohio, United States
UHHS-Chagrin Highlands Medical Center
🇺🇸
Beachwood, Ohio, United States
Cleveland Clinic Mercy Hospital
🇺🇸
Canton, Ohio, United States
Summa Health System - Barberton Campus
🇺🇸
Barberton, Ohio, United States
Cleveland Clinic Cancer Center Beachwood
🇺🇸
Beachwood, Ohio, United States
Dayton Physicians LLC-Miami Valley South
🇺🇸
Centerville, Ohio, United States
Geauga Hospital
🇺🇸
Chardon, Ohio, United States
Miami Valley Hospital South
🇺🇸
Centerville, Ohio, United States
Cleveland Clinic Cancer Center/Fairview Hospital
🇺🇸
Cleveland, Ohio, United States
Good Samaritan Hospital - Dayton
🇺🇸
Dayton, Ohio, United States
Miami Valley Hospital
🇺🇸
Dayton, Ohio, United States
Miami Valley Hospital North
🇺🇸
Dayton, Ohio, United States
Dayton Physician LLC-Miami Valley Hospital North
🇺🇸
Dayton, Ohio, United States
Armes Family Cancer Center
🇺🇸
Findlay, Ohio, United States
Mercy Cancer Center-Elyria
🇺🇸
Elyria, Ohio, United States
Blanchard Valley Hospital
🇺🇸
Findlay, Ohio, United States
Orion Cancer Care
🇺🇸
Findlay, Ohio, United States
Atrium Medical Center-Middletown Regional Hospital
🇺🇸
Franklin, Ohio, United States
Dayton Physicians LLC-Wayne
🇺🇸
Greenville, Ohio, United States
Dayton Physicians LLC-Atrium
🇺🇸
Franklin, Ohio, United States
Cleveland Clinic Cancer Center Independence
🇺🇸
Independence, Ohio, United States
Wayne Hospital
🇺🇸
Greenville, Ohio, United States
Lima Memorial Hospital
🇺🇸
Lima, Ohio, United States
Kettering Medical Center
🇺🇸
Kettering, Ohio, United States
Summa Health Medina Medical Center
🇺🇸
Medina, Ohio, United States
UH Seidman Cancer Center at Southwest General Hospital
🇺🇸
Middleburg Heights, Ohio, United States
Toledo Clinic Cancer Centers-Maumee
🇺🇸
Maumee, Ohio, United States
Cleveland Clinic Cancer Center Mansfield
🇺🇸
Mansfield, Ohio, United States
Toledo Radiation Oncology at Northwest Ohio Onocolgy Center
🇺🇸
Maumee, Ohio, United States
Hillcrest Hospital Cancer Center
🇺🇸
Mayfield Heights, Ohio, United States
UH Seidman Cancer Center at Lake Health Mentor Campus
🇺🇸
Mentor, Ohio, United States
Saint Charles Hospital
🇺🇸
Oregon, Ohio, United States
Toledo Clinic Cancer Centers-Oregon
🇺🇸
Oregon, Ohio, United States
University Hospitals Portage Medical Center
🇺🇸
Ravenna, Ohio, United States
University Hospitals Parma Medical Center
🇺🇸
Parma, Ohio, United States
North Coast Cancer Care
🇺🇸
Sandusky, Ohio, United States
Springfield Regional Cancer Center
🇺🇸
Springfield, Ohio, United States
Springfield Regional Medical Center
🇺🇸
Springfield, Ohio, United States
Mercy Hospital of Tiffin
🇺🇸
Tiffin, Ohio, United States
Mercy Health - Saint Anne Hospital
🇺🇸
Toledo, Ohio, United States
University of Toledo
🇺🇸
Toledo, Ohio, United States
ProMedica Flower Hospital
🇺🇸
Sylvania, Ohio, United States
Cleveland Clinic Cancer Center Strongsville
🇺🇸
Strongsville, Ohio, United States
Saint Vincent Mercy Medical Center
🇺🇸
Toledo, Ohio, United States
Toledo Community Hospital Oncology Program CCOP
🇺🇸
Toledo, Ohio, United States
Toledo Clinic Cancer Centers-Toledo
🇺🇸
Toledo, Ohio, United States
Dayton Physicians LLC-Upper Valley
🇺🇸
Troy, Ohio, United States
UHHS-Westlake Medical Center
🇺🇸
Westlake, Ohio, United States
Upper Valley Medical Center
🇺🇸
Troy, Ohio, United States
Fulton County Health Center
🇺🇸
Wauseon, Ohio, United States
Cancer Treatment Center
🇺🇸
Wooster, Ohio, United States
Cleveland Clinic Wooster Family Health and Surgery Center
🇺🇸
Wooster, Ohio, United States
Warren Clinic Oncology-Tulsa
🇺🇸
Tulsa, Oklahoma, United States
Natalie Warren Bryant Cancer Center at Saint Francis
🇺🇸
Tulsa, Oklahoma, United States
Legacy Mount Hood Medical Center
🇺🇸
Gresham, Oregon, United States
Legacy Good Samaritan Hospital and Medical Center
🇺🇸
Portland, Oregon, United States
Lehigh Valley Hospital - Muhlenberg
🇺🇸
Bethlehem, Pennsylvania, United States
Pocono Medical Center
🇺🇸
East Stroudsburg, Pennsylvania, United States
Lehigh Valley Hospital-Cedar Crest
🇺🇸
Allentown, Pennsylvania, United States
Jefferson Abington Hospital
🇺🇸
Abington, Pennsylvania, United States
Reading Hospital
🇺🇸
West Reading, Pennsylvania, United States
AnMed Health Cancer Center
🇺🇸
Anderson, South Carolina, United States
Gibbs Cancer Center-Gaffney
🇺🇸
Gaffney, South Carolina, United States
Covenant Medical Center-Lakeside
🇺🇸
Lubbock, Texas, United States
Spartanburg Medical Center
🇺🇸
Spartanburg, South Carolina, United States
Central Vermont Medical Center/National Life Cancer Treatment
🇺🇸
Berlin, Vermont, United States
University of Vermont Medical Center
🇺🇸
Burlington, Vermont, United States
University of Vermont and State Agricultural College
🇺🇸
Burlington, Vermont, United States
Fredericksburg Oncology Inc
🇺🇸
Fredericksburg, Virginia, United States
Legacy Salmon Creek Hospital
🇺🇸
Vancouver, Washington, United States
Green Bay Oncology Limited at Saint Mary's Hospital
🇺🇸
Green Bay, Wisconsin, United States
Saint Vincent Hospital Cancer Center at Saint Mary's
🇺🇸
Green Bay, Wisconsin, United States
UW Cancer Center Johnson Creek
🇺🇸
Johnson Creek, Wisconsin, United States
Holy Family Memorial Hospital
🇺🇸
Manitowoc, Wisconsin, United States
Ascension Columbia Saint Mary's Hospital Ozaukee
🇺🇸
Mequon, Wisconsin, United States
Bay Area Medical Center
🇺🇸
Marinette, Wisconsin, United States
Cancer Center of Western Wisconsin
🇺🇸
New Richmond, Wisconsin, United States
Saint Vincent Hospital Cancer Center at Sturgeon Bay
🇺🇸
Sturgeon Bay, Wisconsin, United States
Saint Vincent Hospital Cancer Center at Oconto Falls
🇺🇸
Oconto Falls, Wisconsin, United States
National Cancer Center-Korea
🇰🇷
Goyang-si, Gyeonggi-do, Korea, Republic of
Jewish General Hospital
🇨🇦
Montreal, Quebec, Canada
Green Bay Oncology - Sturgeon Bay
🇺🇸
Sturgeon Bay, Wisconsin, United States
Keimyung University-Dongsan Medical Center
🇰🇷
Dalseo-gu, Daegu, Korea, Republic of
Juravinski Cancer Centre at Hamilton Health Sciences
🇨🇦
Hamilton, Ontario, Canada
Samsung Medical Center
🇰🇷
Seoul, Korea, Korea, Republic of
Yonsei University Health System-Severance Hospital
🇰🇷
Seoul, Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷
Hwasun-gun, Jeollanam-do, Korea, Republic of
Seoul National University Hospital
🇰🇷
Seoul, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷
Seongnam City, Kyeonggi-do, Korea, Republic of
Sutter Medical Center Sacramento
🇺🇸
Sacramento, California, United States
Saint Joseph Mercy Hospital
🇺🇸
Ann Arbor, Michigan, United States
University of Michigan Comprehensive Cancer Center
🇺🇸
Ann Arbor, Michigan, United States
Ascension Columbia Saint Mary's Hospital - Milwaukee
🇺🇸
Milwaukee, Wisconsin, United States
Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Mercy General Hospital Radiation Oncology Center
🇺🇸
Sacramento, California, United States
Norton Hospital Pavilion and Medical Campus
🇺🇸
Louisville, Kentucky, United States
Norton Suburban Hospital and Medical Campus
🇺🇸
Louisville, Kentucky, United States
Ochsner Medical Center Jefferson
🇺🇸
New Orleans, Louisiana, United States
Saint Luke's Hospital of Kansas City
🇺🇸
Kansas City, Missouri, United States
North Kansas City Hospital
🇺🇸
Kansas City, Missouri, United States
Heartland Hematology and Oncology Associates Incorporated
🇺🇸
Kansas City, Missouri, United States
Research Medical Center
🇺🇸
Kansas City, Missouri, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸
Richmond, Virginia, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸
Chapel Hill, North Carolina, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
University of New Mexico Cancer Center
🇺🇸
Albuquerque, New Mexico, United States
Montefiore Medical Center - Moses Campus
🇺🇸
Bronx, New York, United States
University of Wisconsin Carbone Cancer Center
🇺🇸
Madison, Wisconsin, United States
Northeast Georgia Medical Center-Gainesville
🇺🇸
Gainesville, Georgia, United States