Individualized Treatment in Treating Patients With Stage II-IVB Nasopharyngeal Cancer Based on EBV DNA
- Conditions
- Epstein-Barr Virus InfectionStage III Nasopharyngeal CarcinomaStage IVB Nasopharyngeal CarcinomaStage II Nasopharyngeal CarcinomaStage IVA Nasopharyngeal Carcinoma
- Interventions
- Other: Clinical ObservationRadiation: Intensity-Modulated Radiation TherapyOther: Laboratory Biomarker AnalysisOther: Quality-of-Life Assessment
- Registration Number
- NCT02135042
- Lead Sponsor
- NRG Oncology
- Brief Summary
There are two study questions we are asking in this randomized phase II/III trial based on a blood biomarker, Epstein Barr virus (EBV) deoxyribonucleic acid (DNA) for locoregionally advanced non-metastatic nasopharyngeal cancer. All patients will first undergo standard concurrent chemotherapy and radiation therapy. When this standard treatment is completed, if there is no detectable EBV DNA in their plasma, then patients are randomized to either standard adjuvant cisplatin and fluorouracil chemotherapy or observation. If there is still detectable levels of plasma EBV DNA, patients will be randomized to standard cisplatin and fluorouracil chemotherapy versus gemcitabine and paclitaxel. Radiation therapy uses high energy x rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, fluorouracil, gemcitabine hydrochloride, and paclitaxel work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving cisplatin and fluorouracil is more effective than gemcitabine hydrochloride and paclitaxel after radiation therapy in treating patients with nasopharyngeal cancer.
- Detailed Description
PRIMARY OBJECTIVES:
I. To determine whether substituting adjuvant concurrent high dose cisplatin (CDDP) and fluorouracil (5-FU) with gemcitabine (gemcitabine hydrochloride) and paclitaxel will result in superior progression-free survival. (Detectable Plasma Epstein Barr Virus \[EBV\] Deoxyribonucleic Acid \[DNA\] Cohort randomized Phase II) II. To determine whether omitting adjuvant CDDP and 5-FU (observation alone in the adjuvant setting) will result in non-inferior overall survival as compared with those patients receiving adjuvant CDDP and 5-FU chemotherapy. (Undetectable Plasma EBV DNA Cohort Phase III)
SECONDARY OBJECTIVES:
I. Time to distant metastasis. (Randomized Phase II and Phase III) II. Time to local progression. (Randomized Phase II and Phase III) III. Time to regional progression. (Randomized Phase II and Phase III) IV. Progression-free survival (Undetectable Cohort). V. Overall survival (Detectable Cohort). VI. Acute and late toxicity profiles based on clinician-reported Common Terminology Criteria for Adverse Events (CTCAE), version (v.) 4. (Randomized Phase II and Phase III) VII. Death during or within 30 days of end of protocol treatment. (Randomized Phase II and Phase III) VIII. Quality of life (general and physical well-being). (Randomized Phase II and Phase III) IX. Quality of life (hearing). (Randomized Phase II and Phase III) X. Quality of life (peripheral neuropathy). (Randomized Phase II and Phase III) XI. Cost effectiveness. (Randomized Phase II and Phase III)
OUTLINE:
Patients undergo intensity modulated radiation therapy (IMRT) once daily (QD) 5 days a week for 6.5 weeks and receive low-dose cisplatin intravenously (IV) over 30-60 minutes once weekly during IMRT. Beginning 1 week after chemoradiation, plasma samples are collected for EBV DNA analysis.
PHASE II: Patients with detectable EBV DNA from pre-treatment analysis are randomized to 1 of 2 treatment arms.
ARM I: Patients receive PF regimen comprising cisplatin IV over 60-120 minutes and fluorouracil IV over 96 hours continuously beginning at least 4 weeks after completion of IMRT. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive GT regimen comprising paclitaxel IV over 1 hour and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 at least 4 weeks after completion of IMRT. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
PHASE III:
Patients with undetectable EBV DNA from pre-treatment analysis are randomized to 1 of 2 treatment arms.
ARM III: Patients receive PF regimen as in Arm I.
ARM IV: Patients undergo clinical observation.
After completion of study treatment, patients are followed up every 4 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 685
-
Biopsy proven (from primary lesion and/or lymph nodes) diagnosis of cancer of the nasopharynx
-
Sites are required to complete Step 1 registration before submitting specimens for EBV DNA analysis.
- Patients must have detectable pretreatment plasma EBV DNA, determined by the central lab prior to Step 2 registration (see Section 10.2 for details of specimen submission).
- For patients who have detectable plasma EBV DNA tested at one of the credentialed central labs (listed on the EBV DNA Testing Specimen Transmittal form) within 28 days prior to Step 1 registration: that test result can be used for eligibility without the need for re-testing. To use this test result for eligibility, the central lab must enter the test result through the pathology portal, and the site must follow the instructions in Section 5.4.
-
Stage II-IVB disease (AJCC, 7th ed.) with no evidence of distant metastasis, based upon the following minimum diagnostic workup:
- History/physical examination by a Medical Oncologist or Clinical Oncologist or Radiation Oncologist or ENT, which must include an endoscopic evaluation, a complete list of current medications, and assessment of weight and weight loss in the past 6 months within 21 days prior to registration;
- Evaluation of tumor extent required within 28 days prior to registration:
-
MRI of the nasopharynx and neck; or CT of the nasopharynx and neck with ≤ 3 mm contiguous slices with contrast and bone windows (to evaluate base of skull involvement).
Note: If a treatment planning CT scan is used, it must be with ≤ 3 mm contiguous slices with contrast and be read by a radiologist.
Please refer to section 6.3.2 for MRI requirement for target delineation.
-
To rule out distant metastasis, patients must undergo the following imaging within 28 days prior to registration:
- a CT scan with contrast of the chest and abdomen (required), and the pelvis (optional), or a total body PET/CT scan (non-contrast PET/CT is acceptable);
- a bone scan only when there is suspicion of bone metastases (a PET/CT scan can substitute for the bone scan).
-
Zubrod performance status 0-1 within 21 days prior to registration
-
Absolute neutrophil count (ANC) ≥ 1,500 cells/mm^3
-
Platelets ≥ 100,000 cells/mm^3
-
Hemoglobin ≥ 8.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] ≥ 8.0 g/dl is acceptable)
-
Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
-
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 x institutional ULN
-
Alkaline phosphatase ≤ 1.5 x institutional ULN
-
Serum creatinine ≤ 1.5 mg/dl or calculated creatinine clearance (CC) ≥ 50 ml/min determined by 24-hour urine collection or estimated by Cockcroft-Gault formula
-
Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential
-
Women of childbearing potential and male participants who are sexually active must agree to use a medically effective means of birth control throughout protocol treatment
-
Patient must provide study specific informed consent prior to study entry, including the mandatory pre-treatment plasma EBV DNA assay
-
Prior invasive malignancy (except node negative, non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years) (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
-
Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable; however, at least 6-weeks recovery is necessary if the last regimen included nitrosourea or mitomycin
-
Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
-
Patients with hearing loss assessed to be primarily sensorineural in nature, requiring a hearing aid, or intervention (i.e. interfering in a clinically significant way with activities of daily living); a conductive hearing loss that is tumor-related is allowed
-
≥ Grade 2 peripheral sensory neuropathy (CTCAE, v. 4.0)
-
Severe, active co-morbidity, defined as follows:
- Major medical or psychiatric illness, which in the investigator's opinion would interfere with the completion of therapy and follow up or with full understanding of the risks and potential complications of the therapy
- Unstable angina and/or uncontrolled congestive heart failure within the past 6 months
- Myocardial infarction within the last 6 months
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; note that patients switched from IV antibiotics and currently on oral antibiotics whose infection is assessed to be adequately treated or controlled are eligible
- Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days prior to registration
- Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that Human Immunodeficiency Virus (HIV) testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
-
Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
-
Prior allergic reaction to the study drug(s) involved in this protocol
-
Patients with undetectable pre-treatment plasma EBV DNA
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I (chemoradiation, cisplatin, fluorouracil) Quality-of-Life Assessment Patients receive PF regimen comprising cisplatin IV over 60-120 minutes and fluorouracil IV over 96 hours continuously beginning at least 4 weeks after completion of IMRT. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. Arm I (chemoradiation, cisplatin, fluorouracil) Intensity-Modulated Radiation Therapy Patients receive PF regimen comprising cisplatin IV over 60-120 minutes and fluorouracil IV over 96 hours continuously beginning at least 4 weeks after completion of IMRT. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. Arm I (chemoradiation, cisplatin, fluorouracil) Laboratory Biomarker Analysis Patients receive PF regimen comprising cisplatin IV over 60-120 minutes and fluorouracil IV over 96 hours continuously beginning at least 4 weeks after completion of IMRT. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. Arm II (chemoradiation, gemcitabine hydrochloride, paclitaxel) Quality-of-Life Assessment Patients receive GT regimen comprising paclitaxel IV over 1 hour and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 at least 4 weeks after completion of IMRT. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Arm IV (chemoradiation, observation) Clinical Observation Patients undergo clinical observation. Arm IV (chemoradiation, observation) Quality-of-Life Assessment Patients undergo clinical observation. Arm II (chemoradiation, gemcitabine hydrochloride, paclitaxel) Gemcitabine Hydrochloride Patients receive GT regimen comprising paclitaxel IV over 1 hour and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 at least 4 weeks after completion of IMRT. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Arm II (chemoradiation, gemcitabine hydrochloride, paclitaxel) Laboratory Biomarker Analysis Patients receive GT regimen comprising paclitaxel IV over 1 hour and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 at least 4 weeks after completion of IMRT. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Arm II (chemoradiation, gemcitabine hydrochloride, paclitaxel) Intensity-Modulated Radiation Therapy Patients receive GT regimen comprising paclitaxel IV over 1 hour and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 at least 4 weeks after completion of IMRT. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Arm III (chemoradiation, cisplatin, fluorouracil) Intensity-Modulated Radiation Therapy Patients receive PF regimen as in Arm I of Phase II. Arm IV (chemoradiation, observation) Laboratory Biomarker Analysis Patients undergo clinical observation. Arm II (chemoradiation, gemcitabine hydrochloride, paclitaxel) Paclitaxel Patients receive GT regimen comprising paclitaxel IV over 1 hour and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 at least 4 weeks after completion of IMRT. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Arm III (chemoradiation, cisplatin, fluorouracil) Laboratory Biomarker Analysis Patients receive PF regimen as in Arm I of Phase II. Arm III (chemoradiation, cisplatin, fluorouracil) Quality-of-Life Assessment Patients receive PF regimen as in Arm I of Phase II. Arm IV (chemoradiation, observation) Intensity-Modulated Radiation Therapy Patients undergo clinical observation. Arm I (chemoradiation, cisplatin, fluorouracil) Cisplatin Patients receive PF regimen comprising cisplatin IV over 60-120 minutes and fluorouracil IV over 96 hours continuously beginning at least 4 weeks after completion of IMRT. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. Arm I (chemoradiation, cisplatin, fluorouracil) Fluorouracil Patients receive PF regimen comprising cisplatin IV over 60-120 minutes and fluorouracil IV over 96 hours continuously beginning at least 4 weeks after completion of IMRT. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. Arm II (chemoradiation, gemcitabine hydrochloride, paclitaxel) Cisplatin Patients receive GT regimen comprising paclitaxel IV over 1 hour and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 at least 4 weeks after completion of IMRT. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Arm III (chemoradiation, cisplatin, fluorouracil) Cisplatin Patients receive PF regimen as in Arm I of Phase II. Arm III (chemoradiation, cisplatin, fluorouracil) Fluorouracil Patients receive PF regimen as in Arm I of Phase II. Arm IV (chemoradiation, observation) Cisplatin Patients undergo clinical observation.
- Primary Outcome Measures
Name Time Method Progression-free survival (PFS) (Detectable Plasma EBV DNA Cohort Phase II) Up to 7 years Estimated using the Kaplan-Meier method for each arm. Their distributions will be compared between treatment arms with a 1-sided log rank test. A one-sided log rank test will be used to compare the PFS at a significance level of 0.1379.
Overall survival (OS) (Undetectable Plasma EBV DNA Cohort Phase III) Up to 7 years Estimated using the Kaplan-Meier method for each arm. Their distributions will be compared between treatment arms with a 1-sided log rank test. The confidence interval approach will be used for the final analysis of OS.
- Secondary Outcome Measures
Name Time Method Incidence of death (Phase II and III) Up to 30 days of end of protocol treatment Incidence of late grade 3-5 adverse events (Phase II and III) Up to 7 years Rates of specific acute toxicity profiles and late toxicity profiles will be estimated using a binomial distribution along with their associated 95% confidence intervals and will be compared using Fisher's exact test between the 2 treatment arms.
Time to local progression (Phase II and III) Up to 7 years The cumulative incidence method will be used to estimate local, regional, and distant failure rates. The failure rates for the experimental treatment will be compared against the control using a failure-specific log-rank test. Multivariate analysis will be performed using the Cox proportional hazards model.
Time to regional progression (Phase II and III) Up to 7 years 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. The cumulative incidence method will be used to estimate local, regional, and distant failure rates. The failure rates for the experimental treatment will be compared against the control using a failure-specific log-rank test. Multivariate analysis will be performed using the Cox proportional hazards model.
Changes in quality of life (QOL) (general and physical well-being) assessed using the Functional Assessment of Cancer Therapy (FACT)-Nasopharyngeal (NP) (Phase II and III) Baseline to up to 24 months Changes in patient reported outcome (PRO) scores will be correlated to clearance or non-clearance of EBV titers. Descriptive statistics derived from FACT-NP will be used to enrich the understanding of QOL as it pertains to the 2 phase III arms of observation versus additional adjuvant chemotherapy. Univariable and multivariable analysis will be performed using the Cox proportional hazards model for OS and distant metastasis. Pearson correlation will be estimated between general and physical well-being. QOL measures and change from baseline will be correlated to EBV DNA.
Incidence of acute grade 3-5 adverse events (Phase II and III) Up to 7 years Rates of specific acute toxicity profiles and late toxicity profiles will be estimated using a binomial distribution along with their associated 95% confidence intervals and will be compared using Fisher's exact test between the 2 treatment arms.
OS (Detectable Plasma EBV DNA Cohort Phase II) Up to 7 years Estimated using the Kaplan-Meier method for each arm. Their distributions will be compared between treatment arms with a 1-sided log rank test.
Changes in pure tone audiometry (Phase II and III) Baseline to up to 1 year Correlation between categorical measures will be summarized by odds ratios, chi-square tests, and associated measures. Adjusted correlation may be derived from analysis of covariance (ANCOVA) models or derived directly using nonparametric analysis of variance (ANOVA) models if normality assumption is violated. Correlations between HHIE-S PRO scores and PTA and FACT-NP hearing, and PTA will be compared as dependent statistics
PFS (Undetectable Plasma EBV DNA Cohort Phase III) Up to 7 years Estimated using the Kaplan-Meier method for each arm. Their distributions will be compared between treatment arms with a 1-sided log rank test.
Changes in QOL (peripheral neuropathy) as assessed by the FACT-Taxane (Phase II and III) Baseline to up to 24 months Time to distant metastasis (DM) (Phase II and III) Up to 7 years The cumulative incidence method will be used to estimate local, regional, and distant failure rates. The failure rates for the experimental treatment will be compared against the control using a failure-specific log-rank test. Multivariate analysis will be performed using the Cox proportional hazards model.
Changes in QOL (hearing) as assessed by the Hearing Handicap Inventory for the Elderly-Screening version (HHIE-S) (Phase II and III) Baseline to up to 24 months QOL analysis including overall score and change from baseline will be summarized using mean and standard deviation at each time point for each arm. Overall and nasopharyngeal-specific QOL, hearing QOL (FACT-NP hearing domain, HHIE-S scores), peripheral neuropathy QOL over the short and long term and pure-tone audiometry (PTA) scores will be compared using a two sample independent t test and paired t test if the comparison is within the experimental arm between different time points.
Cost effectiveness as assessed by the health-related QOL (HRQOL) from the EuroQol (EQ-5D) instrument (Phase II and III) Up to 24 months Incremental cost effectiveness ratios will be compared to determine the probability of cost effectiveness of various interventions, with sensitivity analyses to identify model weaknesses. The expected value of perfect information will be determined to delimit the upper boundary for cost-effective future investment in this area of research.
Trial Locations
- Locations (214)
Emory University Hospital/Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Emory Saint Joseph's Hospital
🇺🇸Atlanta, Georgia, United States
Rutgers New Jersey Medical School
🇺🇸Newark, New Jersey, United States
Memorial Sloan Kettering Bergen
🇺🇸Montvale, New Jersey, United States
Aspirus Regional Cancer Center
🇺🇸Wausau, Wisconsin, United States
Diagnostic and Treatment Center
🇺🇸Weston, Wisconsin, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
John H Stroger Jr Hospital of Cook County
🇺🇸Chicago, Illinois, United States
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
Fresno Cancer Center
🇺🇸Fresno, California, United States
Sutter Cancer Centers Radiation Oncology Services-Roseville
🇺🇸Roseville, California, United States
Decatur Memorial Hospital
🇺🇸Decatur, Illinois, United States
Emory University Hospital Midtown
🇺🇸Atlanta, Georgia, United States
UC San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
Sutter Cancer Centers Radiation Oncology Services-Auburn
🇺🇸Auburn, California, United States
Greater Baltimore Medical Center
🇺🇸Baltimore, Maryland, United States
Banner University Medical Center - Tucson
🇺🇸Tucson, Arizona, United States
Sutter Cancer Centers Radiation Oncology Services-Cameron Park
🇺🇸Cameron Park, California, United States
Kaiser Permanente-Rancho Cordova Cancer Center
🇺🇸Rancho Cordova, California, United States
Alta Bates Summit Medical Center-Herrick Campus
🇺🇸Berkeley, California, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸Iowa City, Iowa, United States
Geauga Hospital
🇺🇸Chardon, Ohio, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸Baltimore, Maryland, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Mercy Cancer Center-Elyria
🇺🇸Elyria, Ohio, United States
Riverton Hospital
🇺🇸Riverton, Utah, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
University of Cincinnati Cancer Center-West Chester
🇺🇸West Chester, Ohio, United States
Cleveland Clinic Akron General
🇺🇸Akron, Ohio, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
🇺🇸New York, New York, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Minnesota Oncology - Burnsville
🇺🇸Burnsville, Minnesota, United States
UHHS-Westlake Medical Center
🇺🇸Westlake, Ohio, United States
Cleveland Clinic Cancer Center/Fairview Hospital
🇺🇸Cleveland, Ohio, United States
Memorial Sloan Kettering Commack
🇺🇸Commack, New York, United States
New York Proton Center
🇺🇸New York, New York, United States
Fairview Ridges Hospital
🇺🇸Burnsville, Minnesota, United States
Cleveland Clinic Cancer Center Mansfield
🇺🇸Mansfield, Ohio, United States
Siteman Cancer Center at Saint Peters Hospital
🇺🇸Saint Peters, Missouri, United States
Inova Schar Cancer Institute
🇺🇸Fairfax, Virginia, United States
New York-Presbyterian/Brooklyn Methodist Hospital
🇺🇸Brooklyn, New York, United States
Lewistown Hospital
🇺🇸Lewistown, Pennsylvania, United States
CoxHealth South Hospital
🇺🇸Springfield, Missouri, United States
Saint Francis Cancer Center
🇺🇸Greenville, South Carolina, United States
Intermountain Medical Center
🇺🇸Murray, Utah, United States
Inova Fairfax Hospital
🇺🇸Falls Church, Virginia, United States
Geisinger Wyoming Valley/Henry Cancer Center
🇺🇸Wilkes-Barre, Pennsylvania, United States
Cleveland Clinic Cancer Center Strongsville
🇺🇸Strongsville, Ohio, United States
Legacy Mount Hood Medical Center
🇺🇸Gresham, Oregon, United States
Logan Regional Hospital
🇺🇸Logan, Utah, United States
Utah Valley Regional Medical Center
🇺🇸Provo, Utah, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
London Regional Cancer Program
🇨🇦London, Ontario, Canada
Saint George Regional Medical Center
🇺🇸Saint George, Utah, United States
Spartanburg Medical Center
🇺🇸Spartanburg, South Carolina, United States
Cleveland Clinic Wooster Family Health and Surgery Center
🇺🇸Wooster, Ohio, United States
McKay-Dee Hospital Center
🇺🇸Ogden, Utah, United States
Legacy Salmon Creek Hospital
🇺🇸Vancouver, Washington, United States
Prisma Health Cancer Institute - Faris
🇺🇸Greenville, South Carolina, United States
Geisinger Medical Oncology-Lewisburg
🇺🇸Lewisburg, Pennsylvania, United States
Reading Hospital
🇺🇸West Reading, Pennsylvania, United States
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
National Cancer Centre Singapore
🇸🇬Singapore, Singapore
Chang Gung Hospital-Lin Kou Medical Center
🇨🇳Taoyuan, Taiwan
Zhongshan Hospital Fudan University
🇨🇳Guangdong Province, Shanghai, China
M D Anderson Cancer Center
🇺🇸Houston, Texas, United States
Radiation Oncology Centers of Nevada Central
🇺🇸Las Vegas, Nevada, United States
Radiation Oncology Centers of Nevada Southeast
🇺🇸Las Vegas, Nevada, United States
University of Cincinnati Cancer Center-UC Medical Center
🇺🇸Cincinnati, Ohio, United States
Chinese University of Hong Kong-Prince of Wales Hospital
🇨🇳Shatin, Hong Kong, China
Sun Yat-sen University Cancer Center
🇨🇳Guangzhou, China
Abbott-Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
California Pacific Medical Center-Pacific Campus
🇺🇸San Francisco, California, United States
UCSF Medical Center-Mission Bay
🇺🇸San Francisco, California, United States
Utah Cancer Specialists-Salt Lake City
🇺🇸Salt Lake City, Utah, United States
Queen's Medical Center
🇺🇸Honolulu, Hawaii, United States
The Cancer Center of Hawaii-Liliha
🇺🇸Honolulu, Hawaii, United States
Iowa Methodist Medical Center
🇺🇸Des Moines, Iowa, United States
Parker Adventist Hospital
🇺🇸Parker, Colorado, United States
Ascension Via Christi Hospitals Wichita
🇺🇸Wichita, Kansas, United States
The Cancer Center of Hawaii-Pali Momi
🇺🇸'Aiea, Hawaii, United States
McKee Medical Center
🇺🇸Loveland, Colorado, United States
SCL Health Cancer Centers of Colorado - Lutheran Medical Center
🇺🇸Golden, Colorado, United States
Wesley Medical Center
🇺🇸Wichita, Kansas, United States
Kaiser Permanente Oakland-Broadway
🇺🇸Oakland, California, United States
Memorial Medical Center
🇺🇸Springfield, Illinois, United States
Palo Alto Medical Foundation Health Care
🇺🇸Palo Alto, California, United States
Kaiser Permanente Dublin
🇺🇸Dublin, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Kaiser Permanente Cancer Treatment Center
🇺🇸South San Francisco, California, United States
Kaiser Permanente Medical Center - Santa Clara
🇺🇸Santa Clara, California, United States
North Colorado Medical Center
🇺🇸Greeley, Colorado, United States
Palo Alto Medical Foundation-Sunnyvale
🇺🇸Sunnyvale, California, United States
SCL Health Lutheran Medical Center
🇺🇸Wheat Ridge, Colorado, United States
Baptist MD Anderson Cancer Center
🇺🇸Jacksonville, Florida, United States
Emory Proton Therapy Center
🇺🇸Atlanta, Georgia, United States
Crossroads Cancer Center
🇺🇸Effingham, Illinois, United States
Memorial Hospital of South Bend
🇺🇸South Bend, Indiana, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
McLaren Cancer Institute-Bay City
🇺🇸Bay City, Michigan, United States
Henry Ford Cancer Institute-Downriver
🇺🇸Brownstown, Michigan, United States
McLaren Cancer Institute-Clarkston
🇺🇸Clarkston, Michigan, United States
McLaren Cancer Institute-Flint
🇺🇸Flint, Michigan, United States
Sparrow Hospital
🇺🇸Lansing, Michigan, United States
McLaren Cancer Institute-Macomb
🇺🇸Mount Clemens, Michigan, United States
Ascension Saint Mary's Hospital
🇺🇸Saginaw, Michigan, United States
Unity Hospital
🇺🇸Fridley, Minnesota, United States
Minnesota Oncology Hematology PA-Maplewood
🇺🇸Maplewood, Minnesota, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
North Memorial Medical Health Center
🇺🇸Robbinsdale, Minnesota, United States
Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
Rice Memorial Hospital
🇺🇸Willmar, Minnesota, United States
Delbert Day Cancer Institute at PCRMC
🇺🇸Rolla, Missouri, United States
Siteman Cancer Center at West County Hospital
🇺🇸Creve Coeur, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center-South County
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital Saint Louis
🇺🇸Saint Louis, Missouri, United States
Maimonides Medical Center
🇺🇸Brooklyn, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
Memorial Sloan Kettering Sleepy Hollow
🇺🇸Sleepy Hollow, New York, United States
North Coast Cancer Care
🇺🇸Sandusky, Ohio, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
ProMedica Flower Hospital
🇺🇸Sylvania, Ohio, United States
Geisinger Cancer Services-Pottsville
🇺🇸Pottsville, Pennsylvania, United States
Prisma Health Cancer Institute - Spartanburg
🇺🇸Boiling Springs, South Carolina, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸Dallas, Texas, United States
American Fork Hospital / Huntsman Intermountain Cancer Center
🇺🇸American Fork, Utah, United States
Langlade Hospital and Cancer Center
🇺🇸Antigo, Wisconsin, United States
Gundersen Lutheran Medical Center
🇺🇸La Crosse, Wisconsin, United States
Marshfield Medical Center
🇺🇸Marshfield, Wisconsin, United States
Marshfield Medical Center - Weston
🇺🇸Weston, Wisconsin, United States
University Health Network-Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
Wayne State University/Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States
The Kirklin Clinic at Acton Road
🇺🇸Birmingham, Alabama, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Mercy Hospital Oklahoma City
🇺🇸Oklahoma City, Oklahoma, United States
Legacy Good Samaritan Hospital and Medical Center
🇺🇸Portland, Oregon, United States
Saint Francis Medical Center
🇺🇸Cape Girardeau, Missouri, United States
Mercy Hospital Springfield
🇺🇸Springfield, Missouri, United States
Rohnert Park Cancer Center
🇺🇸Rohnert Park, California, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
🇺🇸Orange, California, United States
Stanford Cancer Institute Palo Alto
🇺🇸Palo Alto, California, United States
The Permanente Medical Group-Roseville Radiation Oncology
🇺🇸Roseville, California, United States
City of Hope South Pasadena
🇺🇸South Pasadena, California, United States
Sutter Cancer Centers Radiation Oncology Services-Vacaville
🇺🇸Vacaville, California, United States
Rush - Copley Medical Center
🇺🇸Aurora, Illinois, United States
Cancer Care Specialists of Illinois - Decatur
🇺🇸Decatur, Illinois, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Christiana Care Health System-Concord Health Center
🇺🇸Chadds Ford, Pennsylvania, United States
Naval Medical Center - Portsmouth
🇺🇸Portsmouth, Virginia, United States
Memorial Sloan Kettering Westchester
🇺🇸Harrison, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Nassau
🇺🇸Uniondale, New York, United States
UCSF Medical Center-Mount Zion
🇺🇸San Francisco, California, United States
Sutter Medical Center Sacramento
🇺🇸Sacramento, California, United States
University of California Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
South Sacramento Cancer Center
🇺🇸Sacramento, California, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States
Saint Joseph Mercy Hospital
🇺🇸Ann Arbor, Michigan, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Nebraska Methodist Hospital
🇺🇸Omaha, Nebraska, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Saint Alphonsus Cancer Care Center-Boise
🇺🇸Boise, Idaho, United States
Christiana Care Health System-Christiana Hospital
🇺🇸Newark, Delaware, United States
Mid-Michigan Physicians-Lansing
🇺🇸Lansing, Michigan, United States
Saint Mary's Regional Medical Center
🇺🇸Reno, Nevada, United States
Gibbs Cancer Center-Pelham
🇺🇸Greer, South Carolina, United States
Trinity Health Saint Mary Mercy Livonia Hospital
🇺🇸Livonia, Michigan, United States
Prisma Health Cancer Institute - Seneca
🇺🇸Seneca, South Carolina, United States
Karmanos Cancer Institute at McLaren Greater Lansing
🇺🇸Lansing, Michigan, United States
Helen F Graham Cancer Center
🇺🇸Newark, Delaware, United States
McLaren Cancer Institute-Central Michigan
🇺🇸Mount Pleasant, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Prisma Health Cancer Institute - Eastside
🇺🇸Greenville, South Carolina, United States
Saint Joseph Mercy Canton
🇺🇸Canton, Michigan, United States
McLaren Cancer Institute-Northern Michigan
🇺🇸Petoskey, Michigan, United States
Weisberg Cancer Treatment Center
🇺🇸Farmington Hills, Michigan, United States
Henry Ford Macomb Hospital-Clinton Township
🇺🇸Clinton Township, Michigan, United States
Henry Ford West Bloomfield Hospital
🇺🇸West Bloomfield, Michigan, United States
McGill University Department of Oncology
🇨🇦Montreal, Quebec, Canada
Singh and Arora Hematology Oncology PC
🇺🇸Flint, Michigan, United States
Prisma Health Cancer Institute - Greer
🇺🇸Greer, South Carolina, United States
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Marshfield Medical Center-EC Cancer Center
🇺🇸Eau Claire, Wisconsin, United States
Memorial Sloan Kettering Basking Ridge
🇺🇸Basking Ridge, New Jersey, United States
Marshfield Clinic-Minocqua Center
🇺🇸Minocqua, Wisconsin, United States
The Research Institute of the McGill University Health Centre (MUHC)
🇨🇦Montreal, Quebec, Canada
Centro Comprensivo de Cancer de UPR
🇵🇷San Juan, Puerto Rico
Renown Regional Medical Center
🇺🇸Reno, Nevada, United States
Marshfield Medical Center-Marshfield
🇺🇸Marshfield, Wisconsin, United States
Marshfield Medical Center-Rice Lake
🇺🇸Rice Lake, Wisconsin, United States
McLaren Cancer Institute-Lapeer Region
🇺🇸Lapeer, Michigan, United States
Memorial Sloan Kettering Monmouth
🇺🇸Middletown, New Jersey, United States
Saint James Community Hospital and Cancer Treatment Center
🇺🇸Butte, Montana, United States
Pamela Youde Nethersole Eastern Hospital
🇭🇰Chai Wan, Hong Kong
Saint Joseph Mercy Oakland
🇺🇸Pontiac, Michigan, United States
McLaren-Port Huron
🇺🇸Port Huron, Michigan, United States
HSHS Sacred Heart Hospital
🇺🇸Eau Claire, Wisconsin, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Aspirus Cancer Care - Wisconsin Rapids
🇺🇸Wisconsin Rapids, Wisconsin, United States
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
Ascension Saint Michael's Hospital
🇺🇸Stevens Point, Wisconsin, United States
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
Marshfield Medical Center-River Region at Stevens Point
🇺🇸Stevens Point, Wisconsin, United States
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Montefiore Medical Center-Einstein Campus
🇺🇸Bronx, New York, United States
Montefiore Medical Center - Moses Campus
🇺🇸Bronx, New York, United States
University of Wisconsin Carbone Cancer Center
🇺🇸Madison, Wisconsin, United States
Mills-Peninsula Medical Center
🇺🇸Burlingame, California, United States
Sandra L Maxwell Cancer Center
🇺🇸Cedar City, Utah, United States