Combination Chemotherapy With or Without Peripheral Stem Cell Transplantation, Radiation Therapy, and/or Surgery in Treating Patients With Ewing's Sarcoma
- Conditions
- Sarcoma
- Interventions
- Biological: dactinomycinProcedure: conventional surgeryRadiation: radiation therapyProcedure: autologous hematopoietic stem cell transplantation
- Registration Number
- NCT00020566
- Lead Sponsor
- University of Leicester
- Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy and kill more tumor cells. It is not yet known if combination chemotherapy is more effective with or without radiation therapy and/or surgery in treating Ewing's sarcoma.
PURPOSE: This randomized phase III trial is studying different combination chemotherapy regimens to see how well they work when given with or without peripheral stem cell transplantation, radiation therapy, and/or surgery in treating patients with Ewing's sarcoma.
- Detailed Description
OBJECTIVES:
Primary
* Compare the event-free and overall survival of patients with tumor of the Ewing's family treated with standard induction chemotherapy comprising vincristine, dactinomycin, ifosfamide and etoposide (VIDE) followed by consolidation chemotherapy comprising vincristine, dactinomycin, and ifosfamide versus high-dose busulfan and melphalan (Bu-Mel) followed by autologous peripheral blood stem cell (PBSC) transplantation with or without radiotherapy and/or surgery.
Secondary
* Determine the prognostic significance of EWS-Flil transcript in these patients.
* Determine the frequency and prognostic value of minimal disease in bone marrow and PBSC, as determined by the presence or absence of EWS-Flil transcript, in these patients.
* Determine the feasibility and toxicity of VIDE induction chemotherapy in these patients.
* Determine the response of these patients to VIDE induction chemotherapy.
* Determine the feasibility and toxicity of VAI consolodation chemotherapy in these patients.
* Determine the feasibility and toxicity of Bu-Mel consolodation chemotherapy in these patients.
* Determine event-free survival and overall survival of patients treated with these regimens by prognostic group analysis.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age and local treatment of the primary tumor (yes vs no).
Patients receive induction chemotherapy comprising vincristine IV on day 1 and ifosfamide IV over 3 hours, doxorubicin IV over 4 hours, and etoposide IV over 1 hour on days 1-3 (VIDE). Treatment repeats every 21 days for 4 courses in the absence of unacceptable toxicity. Peripheral blood stem cells (PBSC) are collected after course 3 and/or 4. Patients are evaluated after course 4. Patients in need of early radiotherapy due to an axial tumor or patients who require radiotherapy to the brain and/or spinal cord (at any time during study) are assigned to group 1. Patients not needing early radiotherapy are assigned to group 2.
* Group 1: Patients receive 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Patients requiring radiotherapy to the axial tumor also undergo concurrent radiotherapy 5 days a week. Some patients may then undergo surgical resection of the tumor. All patients will then receive vincristine IV on day 1 and dactinomycin IV and ifosfamide IV over 3 hours on days 1 and 2 (VAI). Treatment repeats every 21 days for 8 courses (courses 7-14). Patients requiring radiotherapy to the brain and/or spinal cord also undergo concurrent radiotherapy.
* Group 2: Patients undergo 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Some patients may then undergo surgical resection of the tumor. All patients receive VAI chemotherapy as in group 1 for 1 course. Patients are randomized to 1 of 2 consolidation therapy arms.
* Arm I: Patients receive 7 additional courses of VAI chemotherapy (courses 8-14). Patients with unresectable, partially resected, or inadequately resected disease undergo concurrent whole-lung radiotherapy for 6-12 days.
* Arm II: Patients receive high-dose chemotherapy comprising oral busulfan every 6 hours on days -6 to -3 and melphalan IV over 30 minutes on day -2. Patients receive autologous PBSC IV on day 0. Patients with unresectable, partially resected, or inadequately resected disease undergo concurrent radiotherapy 5 days a week for at least 5 weeks.
Patients are followed every 3 months for 4 years, every 6 months for 1 year, and then periodically thereafter.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
PROJECTED ACCRUAL: Approximately 1,200 patients will be accrued for this study within approximately 7 years.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 1200
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Group 1 dactinomycin Patients receive 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Patients requiring radiotherapy to the axial tumor also undergo concurrent radiotherapy 5 days a week. Some patients may then undergo surgical resection of the tumor. All patients will then receive vincristine IV on day 1 and dactinomycin IV and ifosfamide IV over 3 hours on days 1 and 2 (VAI). Treatment repeats every 21 days for 8 courses (courses 7-14). Patients requiring radiotherapy to the brain and/or spinal cord also undergo concurrent radiotherapy. Group 1 conventional surgery Patients receive 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Patients requiring radiotherapy to the axial tumor also undergo concurrent radiotherapy 5 days a week. Some patients may then undergo surgical resection of the tumor. All patients will then receive vincristine IV on day 1 and dactinomycin IV and ifosfamide IV over 3 hours on days 1 and 2 (VAI). Treatment repeats every 21 days for 8 courses (courses 7-14). Patients requiring radiotherapy to the brain and/or spinal cord also undergo concurrent radiotherapy. Group 1 radiation therapy Patients receive 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Patients requiring radiotherapy to the axial tumor also undergo concurrent radiotherapy 5 days a week. Some patients may then undergo surgical resection of the tumor. All patients will then receive vincristine IV on day 1 and dactinomycin IV and ifosfamide IV over 3 hours on days 1 and 2 (VAI). Treatment repeats every 21 days for 8 courses (courses 7-14). Patients requiring radiotherapy to the brain and/or spinal cord also undergo concurrent radiotherapy. Group 2, arm I dactinomycin Patients undergo 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Some patients may then undergo surgical resection of the tumor. All patients receive VAI chemotherapy as in group 1 for 1 course. Patients then receive 7 additional courses of VAI chemotherapy (courses 8-14). Patients with unresectable, partially resected, or inadequately resected disease undergo concurrent whole-lung radiotherapy for 6-12 days. Group 2, arm I conventional surgery Patients undergo 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Some patients may then undergo surgical resection of the tumor. All patients receive VAI chemotherapy as in group 1 for 1 course. Patients then receive 7 additional courses of VAI chemotherapy (courses 8-14). Patients with unresectable, partially resected, or inadequately resected disease undergo concurrent whole-lung radiotherapy for 6-12 days. Group 2, arm I radiation therapy Patients undergo 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Some patients may then undergo surgical resection of the tumor. All patients receive VAI chemotherapy as in group 1 for 1 course. Patients then receive 7 additional courses of VAI chemotherapy (courses 8-14). Patients with unresectable, partially resected, or inadequately resected disease undergo concurrent whole-lung radiotherapy for 6-12 days. Group 2, arm II dactinomycin Patients undergo 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Some patients may then undergo surgical resection of the tumor. All patients receive VAI chemotherapy as in group 1 for 1 course. Patients then receive high-dose chemotherapy comprising oral busulfan every 6 hours on days -6 to -3 and melphalan IV over 30 minutes on day -2. Patients receive autologous PBSC IV on day 0. Patients with unresectable, partially resected, or inadequately resected disease undergo concurrent radiotherapy 5 days a week for at least 5 weeks. Group 2, arm II autologous hematopoietic stem cell transplantation Patients undergo 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Some patients may then undergo surgical resection of the tumor. All patients receive VAI chemotherapy as in group 1 for 1 course. Patients then receive high-dose chemotherapy comprising oral busulfan every 6 hours on days -6 to -3 and melphalan IV over 30 minutes on day -2. Patients receive autologous PBSC IV on day 0. Patients with unresectable, partially resected, or inadequately resected disease undergo concurrent radiotherapy 5 days a week for at least 5 weeks. Group 2, arm II conventional surgery Patients undergo 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Some patients may then undergo surgical resection of the tumor. All patients receive VAI chemotherapy as in group 1 for 1 course. Patients then receive high-dose chemotherapy comprising oral busulfan every 6 hours on days -6 to -3 and melphalan IV over 30 minutes on day -2. Patients receive autologous PBSC IV on day 0. Patients with unresectable, partially resected, or inadequately resected disease undergo concurrent radiotherapy 5 days a week for at least 5 weeks. Group 2, arm II radiation therapy Patients undergo 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Some patients may then undergo surgical resection of the tumor. All patients receive VAI chemotherapy as in group 1 for 1 course. Patients then receive high-dose chemotherapy comprising oral busulfan every 6 hours on days -6 to -3 and melphalan IV over 30 minutes on day -2. Patients receive autologous PBSC IV on day 0. Patients with unresectable, partially resected, or inadequately resected disease undergo concurrent radiotherapy 5 days a week for at least 5 weeks. Group 2, arm I vincristine sulfate Patients undergo 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Some patients may then undergo surgical resection of the tumor. All patients receive VAI chemotherapy as in group 1 for 1 course. Patients then receive 7 additional courses of VAI chemotherapy (courses 8-14). Patients with unresectable, partially resected, or inadequately resected disease undergo concurrent whole-lung radiotherapy for 6-12 days. Group 2, arm II vincristine sulfate Patients undergo 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Some patients may then undergo surgical resection of the tumor. All patients receive VAI chemotherapy as in group 1 for 1 course. Patients then receive high-dose chemotherapy comprising oral busulfan every 6 hours on days -6 to -3 and melphalan IV over 30 minutes on day -2. Patients receive autologous PBSC IV on day 0. Patients with unresectable, partially resected, or inadequately resected disease undergo concurrent radiotherapy 5 days a week for at least 5 weeks. Group 1 vincristine sulfate Patients receive 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Patients requiring radiotherapy to the axial tumor also undergo concurrent radiotherapy 5 days a week. Some patients may then undergo surgical resection of the tumor. All patients will then receive vincristine IV on day 1 and dactinomycin IV and ifosfamide IV over 3 hours on days 1 and 2 (VAI). Treatment repeats every 21 days for 8 courses (courses 7-14). Patients requiring radiotherapy to the brain and/or spinal cord also undergo concurrent radiotherapy. Group 1 doxorubicin hydrochloride Patients receive 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Patients requiring radiotherapy to the axial tumor also undergo concurrent radiotherapy 5 days a week. Some patients may then undergo surgical resection of the tumor. All patients will then receive vincristine IV on day 1 and dactinomycin IV and ifosfamide IV over 3 hours on days 1 and 2 (VAI). Treatment repeats every 21 days for 8 courses (courses 7-14). Patients requiring radiotherapy to the brain and/or spinal cord also undergo concurrent radiotherapy. Group 1 etoposide Patients receive 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Patients requiring radiotherapy to the axial tumor also undergo concurrent radiotherapy 5 days a week. Some patients may then undergo surgical resection of the tumor. All patients will then receive vincristine IV on day 1 and dactinomycin IV and ifosfamide IV over 3 hours on days 1 and 2 (VAI). Treatment repeats every 21 days for 8 courses (courses 7-14). Patients requiring radiotherapy to the brain and/or spinal cord also undergo concurrent radiotherapy. Group 1 ifosfamide Patients receive 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Patients requiring radiotherapy to the axial tumor also undergo concurrent radiotherapy 5 days a week. Some patients may then undergo surgical resection of the tumor. All patients will then receive vincristine IV on day 1 and dactinomycin IV and ifosfamide IV over 3 hours on days 1 and 2 (VAI). Treatment repeats every 21 days for 8 courses (courses 7-14). Patients requiring radiotherapy to the brain and/or spinal cord also undergo concurrent radiotherapy. Group 2, arm I doxorubicin hydrochloride Patients undergo 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Some patients may then undergo surgical resection of the tumor. All patients receive VAI chemotherapy as in group 1 for 1 course. Patients then receive 7 additional courses of VAI chemotherapy (courses 8-14). Patients with unresectable, partially resected, or inadequately resected disease undergo concurrent whole-lung radiotherapy for 6-12 days. Group 2, arm I etoposide Patients undergo 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Some patients may then undergo surgical resection of the tumor. All patients receive VAI chemotherapy as in group 1 for 1 course. Patients then receive 7 additional courses of VAI chemotherapy (courses 8-14). Patients with unresectable, partially resected, or inadequately resected disease undergo concurrent whole-lung radiotherapy for 6-12 days. Group 2, arm I ifosfamide Patients undergo 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Some patients may then undergo surgical resection of the tumor. All patients receive VAI chemotherapy as in group 1 for 1 course. Patients then receive 7 additional courses of VAI chemotherapy (courses 8-14). Patients with unresectable, partially resected, or inadequately resected disease undergo concurrent whole-lung radiotherapy for 6-12 days. Group 2, arm II busulfan Patients undergo 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Some patients may then undergo surgical resection of the tumor. All patients receive VAI chemotherapy as in group 1 for 1 course. Patients then receive high-dose chemotherapy comprising oral busulfan every 6 hours on days -6 to -3 and melphalan IV over 30 minutes on day -2. Patients receive autologous PBSC IV on day 0. Patients with unresectable, partially resected, or inadequately resected disease undergo concurrent radiotherapy 5 days a week for at least 5 weeks. Group 2, arm II etoposide Patients undergo 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Some patients may then undergo surgical resection of the tumor. All patients receive VAI chemotherapy as in group 1 for 1 course. Patients then receive high-dose chemotherapy comprising oral busulfan every 6 hours on days -6 to -3 and melphalan IV over 30 minutes on day -2. Patients receive autologous PBSC IV on day 0. Patients with unresectable, partially resected, or inadequately resected disease undergo concurrent radiotherapy 5 days a week for at least 5 weeks. Group 2, arm II doxorubicin hydrochloride Patients undergo 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Some patients may then undergo surgical resection of the tumor. All patients receive VAI chemotherapy as in group 1 for 1 course. Patients then receive high-dose chemotherapy comprising oral busulfan every 6 hours on days -6 to -3 and melphalan IV over 30 minutes on day -2. Patients receive autologous PBSC IV on day 0. Patients with unresectable, partially resected, or inadequately resected disease undergo concurrent radiotherapy 5 days a week for at least 5 weeks. Group 2, arm II melphalan Patients undergo 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Some patients may then undergo surgical resection of the tumor. All patients receive VAI chemotherapy as in group 1 for 1 course. Patients then receive high-dose chemotherapy comprising oral busulfan every 6 hours on days -6 to -3 and melphalan IV over 30 minutes on day -2. Patients receive autologous PBSC IV on day 0. Patients with unresectable, partially resected, or inadequately resected disease undergo concurrent radiotherapy 5 days a week for at least 5 weeks. Group 2, arm II ifosfamide Patients undergo 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Some patients may then undergo surgical resection of the tumor. All patients receive VAI chemotherapy as in group 1 for 1 course. Patients then receive high-dose chemotherapy comprising oral busulfan every 6 hours on days -6 to -3 and melphalan IV over 30 minutes on day -2. Patients receive autologous PBSC IV on day 0. Patients with unresectable, partially resected, or inadequately resected disease undergo concurrent radiotherapy 5 days a week for at least 5 weeks.
- Primary Outcome Measures
Name Time Method Event-free survival Overall survival
- Secondary Outcome Measures
Name Time Method Feasibility, toxicity, and response at 1 month following induction therapy Feasibility and toxicity of consolidation regimens at 1 month following consolidation therapy
Trial Locations
- Locations (103)
University of Chicago Cancer Research Center
🇺🇸Chicago, Illinois, United States
Rainbow Babies and Children's Hospital
🇺🇸Cleveland, Ohio, United States
West Virginia University Health Sciences Center - Charleston
🇺🇸Charleston, West Virginia, United States
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Children's Hospital and Regional Medical Center - Seattle
🇺🇸Seattle, Washington, United States
Rady Children's Hospital - San Diego
🇺🇸San Diego, California, United States
University of Miami Sylvester Comprehensive Cancer Center - Miami
🇺🇸Miami, Florida, United States
CCOP - Nevada Cancer Research Foundation
🇺🇸Las Vegas, Nevada, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
UCSF Helen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
Duke Cancer Institute
🇺🇸Durham, North Carolina, United States
Masonic Cancer Center at University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Primary Children's Medical Center
🇺🇸Salt Lake City, Utah, United States
Princess Margaret Hospital for Children
🇦🇺Perth, Western Australia, Australia
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
Oklahoma University Cancer Institute
🇺🇸Oklahoma City, Oklahoma, United States
Centre Hospitalier Universitaire de Quebec
🇨🇦Quebec, Canada
St. Joseph's Cancer Institute at St. Joseph's Hospital
🇺🇸Tampa, Florida, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
Midwest Children's Cancer Center at Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Kaplan Cancer Center at St. Mary's Medical Center
🇺🇸West Palm Beach, Florida, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
UAB Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Lucile Packard Children's Hospital at Stanford University Medical Center
🇺🇸Palo Alto, California, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
Southern California Permanente Medical Group
🇺🇸Los Angeles, California, United States
Childrens Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Children's Hospital Colorado Center for Cancer and Blood Disorders
🇺🇸Aurora, Colorado, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Alfred I. duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
🇺🇸Atlanta, Georgia, United States
Mountain States Tumor Institute at St. Luke's Regional Medical Center
🇺🇸Boise, Idaho, United States
Saint Jude Midwest Affiliate
🇺🇸Peoria, Illinois, United States
Simmons Cooper Cancer Institute
🇺🇸Springfield, Illinois, United States
Holden Comprehensive Cancer Center at University of Iowa
🇺🇸Iowa City, Iowa, United States
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
🇺🇸Baltimore, Maryland, United States
Van Elslander Cancer Center at St. John Hospital and Medical Center
🇺🇸Grosse Pointe Woods, Michigan, United States
Helen DeVos Children's Hospital at Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
CCOP - Duluth
🇺🇸Duluth, Minnesota, United States
University of Mississippi Cancer Clinic
🇺🇸Jackson, Mississippi, United States
Children's Hospitals and Clinics of Minnesota - St. Paul
🇺🇸St. Paul, Minnesota, United States
Hackensack University Medical Center Cancer Center
🇺🇸Hackensack, New Jersey, United States
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
🇺🇸New York, New York, United States
Blumenthal Cancer Center at Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Presbyterian Cancer Center at Presbyterian Hospital
🇺🇸Charlotte, North Carolina, United States
Leo W. Jenkins Cancer Center at ECU Medical School
🇺🇸Greenville, North Carolina, United States
Cleveland Clinic Taussig Cancer Center
🇺🇸Cleveland, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Dayton Children's - Dayton
🇺🇸Dayton, Ohio, United States
Toledo Hospital
🇺🇸Toledo, Ohio, United States
Tod Children's Hospital
🇺🇸Youngstown, Ohio, United States
Lehigh Valley Hospital - Muhlenberg
🇺🇸Bethlehem, Pennsylvania, United States
Greenville Hospital Cancer Center
🇺🇸Greenville, South Carolina, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Penn State Children's Hospital
🇺🇸Hershey, Pennsylvania, United States
Avera Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
Texas Tech University Health Sciences Center School of Medicine - Amarillo
🇺🇸Amarillo, Texas, United States
East Tennessee Children's Hospital
🇺🇸Knoxville, Tennessee, United States
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
🇺🇸Dallas, Texas, United States
Cook Children's Medical Center - Fort Worth
🇺🇸Fort Worth, Texas, United States
University of Virginia Cancer Center
🇺🇸Charlottesville, Virginia, United States
Mary Bridge Children's Hospital and Health Center - Tacoma
🇺🇸Tacoma, Washington, United States
Providence Cancer Center at Sacred Heart Medical Center
🇺🇸Spokane, Washington, United States
St. Vincent Hospital Regional Cancer Center
🇺🇸Green Bay, Wisconsin, United States
Marshfield Clinic - Marshfield Center
🇺🇸Marshfield, Wisconsin, United States
Children's Hospital at Westmead
🇦🇺Westmead, New South Wales, Australia
Women's and Children's Hospital
🇦🇺North Adelaide, South Australia, Australia
Children's and Women's Hospital of British Columbia
🇨🇦Vancouver, British Columbia, Canada
Janeway Children's Health and Rehabilitation Centre
🇨🇦St. John's, Newfoundland and Labrador, Canada
IWK Health Centre
🇨🇦Halifax, Nova Scotia, Canada
Hopital Sainte Justine
🇨🇦Montreal, Quebec, Canada
Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Starship Children's Health
🇳🇿Auckland, New Zealand
Saskatoon Cancer Centre at the University of Saskatchewan
🇨🇦Saskatoon, Saskatchewan, Canada
San Jorge Children's Hospital
🇵🇷Santurce, Puerto Rico
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
🇺🇸St. Louis, Missouri, United States
Nemours Children's Clinic
🇺🇸Jacksonville, Florida, United States
Breslin Cancer Center at Ingham Regional Medical Center
🇺🇸Lansing, Michigan, United States
Legacy Emanuel Children's Hospital
🇺🇸Portland, Oregon, United States
SUNY Upstate Medical University Hospital
🇺🇸Syracuse, New York, United States
Driscoll Children's Hospital
🇺🇸Corpus Christi, Texas, United States
Inova Fairfax Hospital
🇺🇸Falls Church, Virginia, United States
Methodist Children's Hospital of South Texas
🇺🇸San Antonio, Texas, United States
Children's Hospital of The King's Daughters
🇺🇸Norfolk, Virginia, United States
Royal Children's Hospital
🇦🇺Brisbane, Queensland, Australia
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Nemours Children's Clinic - Pensacola
🇺🇸Pensacola, Florida, United States
Hurley Medical Center
🇺🇸Flint, Michigan, United States
James P. Wilmot Cancer Center at University of Rochester Medical Center
🇺🇸Rochester, New York, United States
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Kaiser Permanente Medical Center - Oakland
🇺🇸Sacramento, California, United States
Nemours Children's Clinic - Orlando
🇺🇸Orlando, Florida, United States
Cancer Research Center of Hawaii
🇺🇸Honolulu, Hawaii, United States
Kosair Children's Hospital
🇺🇸Louisville, Kentucky, United States
Children's Hospital of New Orleans
🇺🇸New Orleans, Louisiana, United States
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Albert Einstein Cancer Center at Albert Einstein College of Medicine
🇺🇸Bronx, New York, United States