Bevacizumab, Cisplatin, Radiation Therapy, and Fluorouracil in Treating Patients With Stage IIB, Stage III, Stage IVA, or Stage IVB Nasopharyngeal Cancer

Phase 2

Completed

• Conditions: Stage II Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage III Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage III Nasopharyngeal Undifferentiated Carcinoma AJCC v7; Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IV Nasopharyngeal Undifferentiated Carcinoma AJCC v7
• Interventions: Radiation: 3-Dimensional Conformal Radiation Therapy; Biological: Bevacizumab; Drug: Cisplatin; Drug: Fluorouracil; Radiation: Intensity-Modulated Radiation Therapy

• Registration Number: NCT00408694
• Lead Sponsor: National Cancer Institute (NCI)

Brief Summary

This phase II trial is studying how well giving bevacizumab together with cisplatin, radiation therapy, and fluorouracil works in treating patients with stage IIB, stage III, stage IVA, or stage IVB nasopharyngeal cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of nasopharyngeal cancer by blocking blood flow to the tumor. Drugs used in chemotherapy, such as cisplatin and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving bevacizumab together with chemotherapy and radiation therapy may kill more tumor cells.

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the safety and tolerability of bevacizumab and chemoradiotherapy comprising cisplatin and radiotherapy followed by adjuvant therapy comprising cisplatin, fluorouracil, and bevacizumab in patients with stage IIB-IVB nasopharyngeal cancer.

SECONDARY OBJECTIVES:

I. Determine the 1- and 2-year rates of locoregional progression-free in patients treated with this regimen.

II. Determine the 1- and 2-year rates of distant metastases-free in patients treated with this regimen.

III. Determine the 1- and 2-year rates of progression-free and overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

BEVACIZUMAB AND CHEMORADIOTHERAPY: Patients receive bevacizumab IV over 30-90 minutes and cisplatin IV over 20-30 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning in week 1, patients also undergo three-dimensional conformal radiotherapy or intensity-modulated radiotherapy once daily 5 days a week for a total of 33 fractions.

ADJUVANT THERAPY: Beginning in week 10, patients receive fluorouracil IV continuously over 96 hours on days 1-4, cisplatin IV over 20-30 minutes on day 1 OR days 1 and 2, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2006-12-06
• Study First Submitted QC: 2006-12-06
• Study First Posted: 2006-12-07
• Study Start: 2006-12-13
• Primary Completion: 2011-12-15
• Study Completion: 2011-12-15
• Results First Submitted: 2013-03-01
• Results First Submitted QC: 2013-03-01
• Results First Posted: 2013-04-18
• Status Verified: 2018-01
• Last Update Submitted: 2018-01-04
• Last Update Posted: 2018-01-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 46

Inclusion Criteria

• Histologically confirmed cancer of the nasopharynx based on biopsy of a primary lesion and/or lymph nodes

  • Histologic WHO types I-IIb/III

• Stage IIB-IVB disease

  • No T1-2, N1 disease in which node positivity is based on the presence of retropharyngeal lymph nodes

• No distant metastases

• Zubrod performance status 0-1

• WBC ? 4,000/mm?

• Hemoglobin ? 9.0 g/dL

• Platelet count ? 100,000/mm?

• Absolute neutrophil count ? 1,500/mm?

• INR ? 1.5

• aPTT ? 1.5 times upper limit of normal (ULN)

• Alkaline phosphatase ? 1.5 times ULN

• ALT and AST ? 1.5 times ULN

• Bilirubin ? 1.5 times ULN

• Creatinine ? 1.5 mg/dL OR creatinine clearance ? 55 mL/min

• Urine protein:creatinine (UPC) ratio < 1.0

  • If UPC > 0.5, 24-hour urine protein must be < 1,000 mg

• Hearing loss primarily sensorineural in nature and requiring a hearing aid or intervention that interferes in a clinically significant way with activities of daily living allowed

• Conductive hearing loss from tumor-related otitis media is allowed

• No severe, active comorbidity, including any of the following:

  • Ongoing bleeding diathesis, hemorrhagic disorder, or coagulopathy within the past 6 months
  • Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
  • Esophageal varices, nonhealing wound, nonhealing ulcer, or bone fracture within the past 6 months
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within the past 30 days
  • Unstable angina and/or congestive heart failure or peripheral vascular disease requiring hospitalization within the past 12 months
  • Major medical or psychiatric illness that, in the opinion of the study investigator, would preclude study compliance
  • Active, untreated infection and/or acute bacterial or fungal infection requiring intravenous antibiotics
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
  • History of significant weight loss (> 15% from baseline)
  • History of arterial thromboembolic events
  • Acquired immune deficiency syndrome
  • Transmural myocardial infarction
  • Cerebrovascular accident
  • Transient ischemic attack
  • Any other cardiac condition that, in the opinion of the investigator, would preclude study compliance

• No gross hemoptysis or hematemesis, defined as bright red blood of ? 1 teaspoon per coughing episode, within the last 4 weeks (incidental blood mixed with phlegm allowed)

• No other invasive malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the breast, oral cavity, or cervix

• Nutritional and physical condition considered suitable for study treatment

• No significant traumatic injury within the past 4 weeks

• No history of allergic reaction to the study drugs

• No baseline blood pressure > 150/100 mm Hg

• No peripheral neuropathy ? grade 2

• Not pregnant or nursing

• Negative serum pregnancy test

• Fertile patients must use effective contraception during and for ? 6 months after completion of study treatment

• At least 10 days since prior and no concurrent dipyridamole, ticlopidine, clopidogrel bisulfate, cilostazol, warfarin, heparin, daily treatment with acetylsalicylic acid (> 325 mg/day), or nonsteroidal anti-inflammatory medications known to inhibit platelet function

• No prior head and neck surgery of the primary tumor or lymph nodes except for incisional or excisional biopsies

  • More than 15 days since prior biopsies

• More than 1 week since prior fine-needle aspirations or placement of percutaneous gastrostomy tube

• More than 4 weeks since prior major surgical procedures

• No prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields

• No prior bevacizumab or other vascular endothelial growth factor-targeting agents

• No prior systemic chemotherapy for the study cancer

  • Prior chemotherapy for a different cancer allowed

• No concurrent hematologic growth factors (e.g. filgrastim [G-CSF], darbepoetin alfa, epoetin alfa) during study chemoradiotherapy

• No concurrent prophylactic growth factors for neutropenia during study adjuvant therapy

• No concurrent prophylactic amifostine or pilocarpine

• No other concurrent experimental therapeutic cancer treatments

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (bevacizumab, cisplatin, fluorouracil, IMRT, 3D-CRT)	3-Dimensional Conformal Radiation Therapy	BEVACIZUMAB AND CHEMORADIOTHERAPY: Patients receive bevacizumab IV over 30-90 minutes and cisplatin IV over 20-30 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning in week 1, patients also undergo three-dimensional conformal radiotherapy or intensity-modulated radiotherapy once daily 5 days a week for a total of 33 fractions. ADJUVANT THERAPY: Beginning in week 10, patients receive fluorouracil IV continuously over 96 hours on days 1-4, cisplatin IV over 20-30 minutes on day 1 OR days 1 and 2, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Treatment (bevacizumab, cisplatin, fluorouracil, IMRT, 3D-CRT)	Fluorouracil	BEVACIZUMAB AND CHEMORADIOTHERAPY: Patients receive bevacizumab IV over 30-90 minutes and cisplatin IV over 20-30 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning in week 1, patients also undergo three-dimensional conformal radiotherapy or intensity-modulated radiotherapy once daily 5 days a week for a total of 33 fractions. ADJUVANT THERAPY: Beginning in week 10, patients receive fluorouracil IV continuously over 96 hours on days 1-4, cisplatin IV over 20-30 minutes on day 1 OR days 1 and 2, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Treatment (bevacizumab, cisplatin, fluorouracil, IMRT, 3D-CRT)	Intensity-Modulated Radiation Therapy	BEVACIZUMAB AND CHEMORADIOTHERAPY: Patients receive bevacizumab IV over 30-90 minutes and cisplatin IV over 20-30 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning in week 1, patients also undergo three-dimensional conformal radiotherapy or intensity-modulated radiotherapy once daily 5 days a week for a total of 33 fractions. ADJUVANT THERAPY: Beginning in week 10, patients receive fluorouracil IV continuously over 96 hours on days 1-4, cisplatin IV over 20-30 minutes on day 1 OR days 1 and 2, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Treatment (bevacizumab, cisplatin, fluorouracil, IMRT, 3D-CRT)	Bevacizumab	BEVACIZUMAB AND CHEMORADIOTHERAPY: Patients receive bevacizumab IV over 30-90 minutes and cisplatin IV over 20-30 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning in week 1, patients also undergo three-dimensional conformal radiotherapy or intensity-modulated radiotherapy once daily 5 days a week for a total of 33 fractions. ADJUVANT THERAPY: Beginning in week 10, patients receive fluorouracil IV continuously over 96 hours on days 1-4, cisplatin IV over 20-30 minutes on day 1 OR days 1 and 2, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Treatment (bevacizumab, cisplatin, fluorouracil, IMRT, 3D-CRT)	Cisplatin	BEVACIZUMAB AND CHEMORADIOTHERAPY: Patients receive bevacizumab IV over 30-90 minutes and cisplatin IV over 20-30 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning in week 1, patients also undergo three-dimensional conformal radiotherapy or intensity-modulated radiotherapy once daily 5 days a week for a total of 33 fractions. ADJUVANT THERAPY: Beginning in week 10, patients receive fluorouracil IV continuously over 96 hours on days 1-4, cisplatin IV over 20-30 minutes on day 1 OR days 1 and 2, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Percentage of Patients With a Grade 4 Hemorrhage or Any Grade 5 Adverse Event Assessed to be Definitely, Probably, or Possibly Related to Protocol Treatment During the First Year.	From start of treatment to one year.	Estimated using a binomial distribution along with the 95% confidence interval. Adverse events (AE) are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.

Secondary Outcome Measures

Name	Time	Method
Percentage of Patients With Grade 4 Hemorrhage or Any Grade 5 Adverse Event Assessed to be Definitely, Probably, or Possibly Related to Protocol Treatment After the First Year.	Analysis occurs after all patients have been on study for at least 2 years. Patients are followed from day 366 to death or study termination whichever occurs first, up to 3.6 years.	Estimated using a binomial distribution along with the 95% confidence interval. Adverse events (AE) are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.
Patient Tolerability to Each Component (Concurrent and Adjuvant) of the Protocol Treatment Regimen	From start of treatment to end of treatment (approximately day 109).	Evaluated in terms of protocol treatment delivery. For concurrent treatment, measured by the percentage of patients who received 2 or more cycles of cisplatin (CDDP) and bevacizumab (BV) during concurrent treatment with radiation therapy(RT) and who had RT scored by the study chair as no variation or minor variation. For adjuvant treatment, measured by the percentage of patients who received 2 or more cycles of CDDP and 5-FU and BV during the adjuvant treatment phase. Estimated using a binomial distribution along with their associated 95% confidence intervals.
Death During or Within 30 Days of Discontinuation of Protocol Treatment.	From start of treatment to 30 days after end of treatment (treatment ends approximately day 109).	The percentage of patients dying during protocol treatment or within 30 days after the end of treatment. Estimated using a binomial distribution along with associated 95% confidence interval.
One- and Two-year Distant Metastases-free Rates	From registration to two years	Distant metastasis is defined as clear evidence of distant metastases (lung, bone, brain, etc.); biopsy is recommended where possible. Distant metastasis-free rate estimated by cumulative incidence method with death considered a competing risk.
One- and Two-year Loco-regional Progression-free Rates	Analysis occurs after all patients have been on study for at least 2 years. Patients are followed from study registration to death or study termination whichever occurs first, up to 3.6 years.	Loco-regional progression is defined as an estimated increase in the size of the tumor (product of the perpendicular diameters of the two largest dimensions) of greater than 25%, taking as reference the smallest value of all previous measurements or appearance of new areas of malignant disease. Local-regional progression-free rate estimated by cumulative incidence with death considered a competing risk.
One- and Two-year Progression-free Survival Rates	Analysis occurs after all patients have been on study for at least 2 years. Patients are followed from study registration to death or study termination whichever occurs first, up to 3.6 years.	Progression-free survival rate estimated by Kaplan-Meier method along with 95% confidence interval. An event is loco-regional or distant progression, or death due to any cause. Loco-regional progression is defined as an estimated increase in the size of the tumor (product of the perpendicular diameters of the two largest dimensions) of greater than 25%, taking as reference the smallest value of all previous measurements or appearance of new areas of malignant disease. Distant progression is defined as distant metastases.
One- and Two-year Overall Survival Rates	Analysis occurs after all patients have been on study for at least 2 years. Patients are followed from study registration to death or study termination whichever occurs first, up to 3.6 years.	Overall survival rate estimated by Kaplan-Meier method along with 95% confidence interval. An event is death due to any cause.
Percentage of Patients With Other Grade 3-5 Adverse Events Assessed to be Definitely, Probably, or Possibly Related to Protocol Treatment	Analysis occurs after all patients have been on study for at least 2 years. Patients are followed from start of treatment to death or study termination whichever occurs first, up to 3.6 years.	Estimated using a binomial distribution along with the 95% confidence interval. Adverse events (AE) are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.

Trial Locations

Locations (108)

AnMed Health Hospital; 🇺🇸 Anderson, South Carolina, United States

Rutgers New Jersey Medical School; 🇺🇸 Newark, New Jersey, United States

UPMC-Presbyterian Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

UPMC-Shadyside Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

UPMC Jefferson Regional Radiation Oncology; 🇺🇸 Pittsburgh, Pennsylvania, United States

University Medical Center of Southern Nevada; 🇺🇸 Las Vegas, Nevada, United States

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

University of Alabama at Birmingham Cancer Center; 🇺🇸 Birmingham, Alabama, United States

Siteman Cancer Center at Saint Peters Hospital; 🇺🇸 Saint Peters, Missouri, United States

Thomas Jefferson University Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States

UPMC Cancer Center-Natrona Heights; 🇺🇸 Natrona Heights, Pennsylvania, United States

Spartanburg Medical Center; 🇺🇸 Spartanburg, South Carolina, United States

Upper Delaware Valley Cancer Center; 🇺🇸 Milford, Pennsylvania, United States

Brooke Army Medical Center; 🇺🇸 Fort Sam Houston, Texas, United States

UPMC-Coraopolis/Heritage Valley Radiation Oncology; 🇺🇸 Moon, Pennsylvania, United States

UPMC-Saint Margaret; 🇺🇸 Pittsburgh, Pennsylvania, United States

UPMC Uniontown Hospital Radiation Oncology; 🇺🇸 Uniontown, Pennsylvania, United States

UPMC Jameson; 🇺🇸 New Castle, Pennsylvania, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

UPMC-Saint Clair Hospital Cancer Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

UPMC Cancer Center at UPMC Northwest; 🇺🇸 Seneca, Pennsylvania, United States

McGill University Department of Oncology; 🇨🇦 Montreal, Quebec, Canada

Metro Health Hospital; 🇺🇸 Wyoming, Michigan, United States

UF Cancer Center at Orlando Health; 🇺🇸 Orlando, Florida, United States

Radiation Therapy Oncology Group; 🇺🇸 Philadelphia, Pennsylvania, United States

Sutter Cancer Centers Radiation Oncology Services-Auburn; 🇺🇸 Auburn, California, United States

Providence Saint Joseph Medical Center/Disney Family Cancer Center; 🇺🇸 Burbank, California, United States

Mercy San Juan Medical Center; 🇺🇸 Carmichael, California, United States

East Bay Radiation Oncology Center; 🇺🇸 Castro Valley, California, United States

Eden Hospital Medical Center; 🇺🇸 Castro Valley, California, United States

Valley Medical Oncology Consultants-Castro Valley; 🇺🇸 Castro Valley, California, United States

City of Hope Comprehensive Cancer Center; 🇺🇸 Duarte, California, United States

Bay Area Breast Surgeons Inc; 🇺🇸 Emeryville, California, United States

Contra Costa Regional Medical Center; 🇺🇸 Martinez, California, United States

Highland General Hospital; 🇺🇸 Oakland, California, United States

Valley Medical Oncology Consultants-Fremont; 🇺🇸 Fremont, California, United States

Bay Area Tumor Institute; 🇺🇸 Oakland, California, United States

Tom K Lee Inc; 🇺🇸 Oakland, California, United States

Alta Bates Summit Medical Center - Summit Campus; 🇺🇸 Oakland, California, United States

Hematology and Oncology Associates-Oakland; 🇺🇸 Oakland, California, United States

Stanford Cancer Institute Palo Alto; 🇺🇸 Palo Alto, California, United States

Valley Medical Oncology Consultants; 🇺🇸 Pleasanton, California, United States

Valley Care Health System - Pleasanton; 🇺🇸 Pleasanton, California, United States

Sutter Medical Center Sacramento; 🇺🇸 Sacramento, California, United States

Sutter Cancer Centers Radiation Oncology Services-Roseville; 🇺🇸 Roseville, California, United States

Mercy General Hospital Radiation Oncology Center; 🇺🇸 Sacramento, California, United States

Doctors Medical Center- JC Robinson Regional Cancer Center; 🇺🇸 San Pablo, California, United States

Sutter Cancer Centers Radiation Oncology Services-Vacaville; 🇺🇸 Vacaville, California, United States

Beebe Medical Center; 🇺🇸 Lewes, Delaware, United States

Christiana Care Health System-Christiana Hospital; 🇺🇸 Newark, Delaware, United States

Baptist MD Anderson Cancer Center; 🇺🇸 Jacksonville, Florida, United States

Boca Raton Regional Hospital; 🇺🇸 Boca Raton, Florida, United States

Integrated Community Oncology Network-Florida Cancer Center Beaches; 🇺🇸 Jacksonville Beach, Florida, United States

Integrated Community Oncology Network-Southside Cancer Center; 🇺🇸 Jacksonville, Florida, United States

21st Century Oncology-Orange Park; 🇺🇸 Orange Park, Florida, United States

Baptist Hospital of Miami; 🇺🇸 Miami, Florida, United States

21st Century Oncology-Palatka; 🇺🇸 Palatka, Florida, United States

Memorial University Medical Center; 🇺🇸 Savannah, Georgia, United States

John H Stroger Jr Hospital of Cook County; 🇺🇸 Chicago, Illinois, United States

Saint Vincent Anderson Regional Hospital/Cancer Center; 🇺🇸 Anderson, Indiana, United States

Union Hospital of Cecil County; 🇺🇸 Elkton, Maryland, United States

Spectrum Health Big Rapids Hospital; 🇺🇸 Big Rapids, Michigan, United States

Cancer Research Consortium of West Michigan NCORP; 🇺🇸 Grand Rapids, Michigan, United States

Spectrum Health at Butterworth Campus; 🇺🇸 Grand Rapids, Michigan, United States

Bronson Battle Creek; 🇺🇸 Battle Creek, Michigan, United States

Holland Community Hospital; 🇺🇸 Holland, Michigan, United States

Mercy Health Saint Mary's; 🇺🇸 Grand Rapids, Michigan, United States

Borgess Medical Center; 🇺🇸 Kalamazoo, Michigan, United States

Bronson Methodist Hospital; 🇺🇸 Kalamazoo, Michigan, United States

West Michigan Cancer Center; 🇺🇸 Kalamazoo, Michigan, United States

Munson Medical Center; 🇺🇸 Traverse City, Michigan, United States

Singing River Hospital; 🇺🇸 Pascagoula, Mississippi, United States

Mercy Health Partners-Hackley Campus; 🇺🇸 Muskegon, Michigan, United States

Saint Louis Children's Hospital; 🇺🇸 Saint Louis, Missouri, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Mercy Hospital Springfield; 🇺🇸 Springfield, Missouri, United States

CoxHealth South Hospital; 🇺🇸 Springfield, Missouri, United States

Virtua Memorial; 🇺🇸 Mount Holly, New Jersey, United States

Cooper Hospital University Medical Center; 🇺🇸 Camden, New Jersey, United States

Saint Peter's University Hospital; 🇺🇸 New Brunswick, New Jersey, United States

Community Medical Center; 🇺🇸 Toms River, New Jersey, United States

Roswell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States

Saint Luke's Roosevelt Hospital Center - Saint Luke's Division; 🇺🇸 New York, New York, United States

Summa Akron City Hospital/Cooper Cancer Center; 🇺🇸 Akron, Ohio, United States

Rutherford Hospital; 🇺🇸 Rutherfordton, North Carolina, United States

Beth Israel Medical Center; 🇺🇸 New York, New York, United States

UPMC-Heritage Valley Health System Beaver; 🇺🇸 Beaver, Pennsylvania, United States

University of Oklahoma Health Sciences Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

UPMC Cancer Center at Clarion Hospital; 🇺🇸 Clarion, Pennsylvania, United States

Pocono Medical Center; 🇺🇸 East Stroudsburg, Pennsylvania, United States

UPMC Cancer Centers - Arnold Palmer Pavilion; 🇺🇸 Greensburg, Pennsylvania, United States

UPMC Cancer Center at UPMC McKeesport; 🇺🇸 McKeesport, Pennsylvania, United States

UPMC-Johnstown/John P. Murtha Regional Cancer Center; 🇺🇸 Johnstown, Pennsylvania, United States

UPMC-Magee Womens Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

UPMC-Passavant Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

UPMC Washington Hospital Radiation Oncology; 🇺🇸 Washington, Pennsylvania, United States

Wilford Hall Medical Center; 🇺🇸 Lackland Air Force Base, Texas, United States

Froedtert and the Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

Wheeling Hospital/Schiffler Cancer Center; 🇺🇸 Wheeling, West Virginia, United States

Aspirus UW Cancer Center; 🇺🇸 Wisconsin Rapids, Wisconsin, United States

Tom Baker Cancer Centre; 🇨🇦 Calgary, Alberta, Canada

London Regional Cancer Program; 🇨🇦 London, Ontario, Canada

University Health Network-Princess Margaret Hospital; 🇨🇦 Toronto, Ontario, Canada

Sutter Cancer Centers Radiation Oncology Services-Cameron Park; 🇺🇸 Cameron Park, California, United States

Baptist Medical Center South; 🇺🇸 Jacksonville, Florida, United States

Northeast Radiation Oncology Center; 🇺🇸 Dunmore, Pennsylvania, United States

Integrated Community Oncology Network-Flager Cancer Center; 🇺🇸 Saint Augustine, Florida, United States