Chemotherapy for the Treatment of Patients With Newly Diagnosed Very Low-Risk and Low Risk Fusion Negative Rhabdomyosarcoma
Start Date
8/4/2022
Completion Date
6/30/2030
Summary
Rhabdomyosarcoma is a type of cancer that occurs in the soft tissues in the body. This phase III trial aims to maintain excellent outcomes in patients with very low risk rhabdomyosarcoma (VLR-RMS) while decreasing the burden of therapy using treatment with 24 weeks of vincristine and dactinomycin (VA) and examines the use of centralized molecular risk stratification in the treatment of rhabdomyosarcoma. Another aim of the study it to find out how well patients with low risk rhabdomyosarcoma (LR-RMS) respond to standard chemotherapy when patients with VLR-RMS and patients who have rhabdomyosarcoma with DNA mutations get separate treatment. Finally, this study examines the effect of therapy intensification in patients who have RMS cancer with DNA mutations to see if their outcomes can be improved.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the failure free survival (FFS) of patients with very low-risk (VLR) rhabdomyosarcoma (RMS) (fusion negative \[FN\], stage 1, clinical group \[CG\] I, MYOD1 wildtype \[WT\], TP53 \[WT\]) when treated with 24 weeks of vincristine and dactinomycin (VA). II. To evaluate the FFS of patients with low-risk (LR) RMS (FN, stage 1 CG II, or stage 2 CG I/II or CG III \[orbit only\], MYOD1 WT, TP53 WT) when treated with 12 weeks of vincristine, dactinomycin and cyclophosphamide (VAC) followed by 12 weeks of VA. SECONDARY OBJECTIVES: I. To evaluate the overall survival (OS) of patients with VLR RMS treated with 24 weeks of VA. II. To evaluate the OS of patients with LR RMS treated with 12 weeks of VAC followed by 12 weeks of VA. III. To demonstrate the feasibility of central molecular risk stratification of patients with newly diagnosed RMS in the context of a prospective clinical trial. EXPLORATORY OBJECTIVES: I. To collect blood and tissue samples for banking at baseline, during treatment, at the end of therapy, and at the time of progression to bank for future research. II. To describe the methylation array profile of patients with fusion negative, low-risk rhabdomyosarcoma. III. To describe the outcomes of patients with VLR or LR RMS and MYOD1 or TP53 mutations treated with intensified therapy. OUTLINE: Patients are assigned to 1 of 2 regimens based on clinical features. Patients with positive mutation status are transitioned to a third regimen, Regimen M. REGIMEN VA: Patients with VLR RMS receive vincristine intravenously (IV) on day 1 of each cycle and days 8 and 15 of cycles 1, 3, 5, and 7 and dactinomycin IV over 1-5 minutes or over 10-15 minutes on day 1 of each cycle. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients with MYOD1 or TP53 mutated tumors transition to Regimen M at cycle 2 (if mutation status is determined to be positive at week 3) or cycle 3 (if mutation status is determined to be positive after week 3). REGIMEN VAC/VA: Patients with LR RMS receive vincristine IV on day 1 of each cycle and days 8 and 15 of cycles 1-3. Patients also receive dactinomycin IV over 1-5 minutes or 10-15 minutes and cyclophosphamide IV over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive vincristine IV on day 1 of each cycle and days 8 and 15 of cycles 5-7 and dactinomycin IV over 1-5 minutes or over 10-15 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with MYOD1 or TP53 mutated tumors transition to Regimen M at cycle 2 (if mutation status is determined to be positive at week 3) or cycle 3 (if mutation status is determined to be positive after week 3). Patients may also undergo radiation therapy at cycle 5. REGIMEN M: Patients receive vincristine IV on day 1 of each cycle and days 8 and 15 of cycles 2-4, 7-8, and 11-12 and dactinomycin IV over 1-5 minutes or 10-15 minutes on day 1 of cycles 2-5 and 8-14. Patients also receive cyclophosphamide IV over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for 12-13 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo radiation therapy at cycle 5. Patients undergo computed tomography (CT) scan, magnetic resonance imaging (MRI), bone scan, positron emission tomography (PET) scan and tumor biopsy throughout the study.
Eligibility Criteria
Age Range: No minimum to 21 years
Interventions
Biopsy Procedure
Bone Scan
Computed Tomography
Cyclophosphamide
Dactinomycin
Magnetic Resonance Elastography
Positron Emission Tomography
Radiation Therapy
Vincristine
Conditions
Locations
Children's Hospital of Alabama
Birmingham, Alabama 35233
United States
USA Health Strada Patient Care Center
Mobile, Alabama 36604
United States
Phoenix Childrens Hospital
Phoenix, Arizona 85016
United States
Arkansas Children's Hospital
Little Rock, Arkansas 72202-3591
United States
Kaiser Permanente Downey Medical Center
Downey, California 90242
United States
Loma Linda University Medical Center
Loma Linda, California 92354
United States
Miller Children's and Women's Hospital Long Beach
Long Beach, California 90806
United States
Children's Hospital Los Angeles
Los Angeles, California 90027
United States
Cedars-Sinai Medical Center
Los Angeles, California 90048
United States
Mattel Children's Hospital UCLA
Los Angeles, California 90095
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Valley Children's Hospital
Madera, California 93636
United States
UCSF Benioff Children's Hospital Oakland
Oakland, California 94609
United States
Kaiser Permanente-Oakland
Oakland, California 94611
United States
Children's Hospital of Orange County
Orange, California 92868
United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California 94304
United States
University of California Davis Comprehensive Cancer Center
Sacramento, California 95817
United States
Rady Children's Hospital - San Diego
San Diego, California 92123
United States
Naval Medical Center -San Diego
San Diego, California 92134
United States
UCSF Medical Center-Mission Bay
San Francisco, California 94158
United States
Children's Hospital Colorado
Aurora, Colorado 80045
United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado 80218
United States
Connecticut Children's Medical Center
Hartford, Connecticut 06106
United States
Yale University
New Haven, Connecticut 06520
United States
Alfred I duPont Hospital for Children
Wilmington, Delaware 19803
United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia 20007
United States
Children's National Medical Center
Washington D.C., District of Columbia 20010
United States
Broward Health Medical Center
Fort Lauderdale, Florida 33316
United States
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida 33908
United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida 32610
United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida 33021
United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida 32207
United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida 33136
United States
Nicklaus Children's Hospital
Miami, Florida 33155
United States
AdventHealth Orlando
Orlando, Florida 32803
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Arnold Palmer Hospital for Children
Orlando, Florida 32806
United States
Nemours Children's Hospital
Orlando, Florida 32827
United States
Nemours Children's Clinic - Pensacola
Pensacola, Florida 32504
United States
Sacred Heart Hospital
Pensacola, Florida 32504
United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida 33701
United States
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida 33607
United States
Saint Mary's Medical Center
West Palm Beach, Florida 33407
United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia 30329
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Atrium Health Navicent
Macon, Georgia 31201
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Memorial Health University Medical Center
Savannah, Georgia 31404
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Kapiolani Medical Center for Women and Children
Honolulu, Hawaii 96826
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Saint Luke's Cancer Institute - Boise
Boise, Idaho 83712
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Lurie Children's Hospital-Chicago
Chicago, Illinois 60611
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University of Illinois
Chicago, Illinois 60612
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University of Chicago Comprehensive Cancer Center
Chicago, Illinois 60637
United States
Loyola University Medical Center
Maywood, Illinois 60153
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Advocate Children's Hospital-Oak Lawn
Oak Lawn, Illinois 60453
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Advocate Children's Hospital-Park Ridge
Park Ridge, Illinois 60068
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Saint Jude Midwest Affiliate
Peoria, Illinois 61637
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Southern Illinois University School of Medicine
Springfield, Illinois 62702
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Northwestern Medicine Central DuPage Hospital
Winfield, Illinois 60190
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Riley Hospital for Children
Indianapolis, Indiana 46202
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Ascension Saint Vincent Indianapolis Hospital
Indianapolis, Indiana 46260
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Blank Children's Hospital
Des Moines, Iowa 50309
United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa 52242
United States
Wesley Medical Center
Wichita, Kansas 67214
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University of Kentucky/Markey Cancer Center
Lexington, Kentucky 40536
United States
Norton Children's Hospital
Louisville, Kentucky 40202
United States
Children's Hospital New Orleans
New Orleans, Louisiana 70118
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Ochsner Medical Center Jefferson
New Orleans, Louisiana 70121
United States
Maine Children's Cancer Program
Scarborough, Maine 04074
United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland 21201
United States
Sinai Hospital of Baltimore
Baltimore, Maryland 21215
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Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland 21287
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Massachusetts General Hospital Cancer Center
Boston, Massachusetts 02114
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Dana-Farber Cancer Institute
Boston, Massachusetts 02215
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UMass Memorial Medical Center - University Campus
Worcester, Massachusetts 01655
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C S Mott Children's Hospital
Ann Arbor, Michigan 48109
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Children's Hospital of Michigan
Detroit, Michigan 48201
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Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan 49503
United States
Bronson Methodist Hospital
Kalamazoo, Michigan 49007
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Corewell Health Children's
Royal Oak, Michigan 48073
United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota 55404
United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota 55455
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Mayo Clinic in Rochester
Rochester, Minnesota 55905
United States
University of Mississippi Medical Center
Jackson, Mississippi 39216
United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri 64108
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Cardinal Glennon Children's Medical Center
St Louis, Missouri 63104
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Washington University School of Medicine
St Louis, Missouri 63110
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Mercy Hospital Saint Louis
St Louis, Missouri 63141
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Children's Hospital and Medical Center of Omaha
Omaha, Nebraska 68114
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University of Nebraska Medical Center
Omaha, Nebraska 68198
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Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada 89135
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Summerlin Hospital Medical Center
Las Vegas, Nevada 89144
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Renown Regional Medical Center
Reno, Nevada 89502
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Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire 03756
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Hackensack University Medical Center
Hackensack, New Jersey 07601
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Morristown Medical Center
Morristown, New Jersey 07960
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Jersey Shore Medical Center
Neptune City, New Jersey 07753
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Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey 08903
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Newark Beth Israel Medical Center
Newark, New Jersey 07112
United States
University of New Mexico Cancer Center
Albuquerque, New Mexico 87106
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Albany Medical Center
Albany, New York 12208
United States
Roswell Park Cancer Institute
Buffalo, New York 14263
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The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York 11040
United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York 10016
United States
Mount Sinai Hospital
New York, New York 10029
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NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York 10032
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Memorial Sloan Kettering Cancer Center
New York, New York 10065
United States
University of Rochester
Rochester, New York 14642
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State University of New York Upstate Medical University
Syracuse, New York 13210
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Montefiore Medical Center - Moses Campus
The Bronx, New York 10467
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New York Medical College
Valhalla, New York 10595
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UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina 27599
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Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina 28203
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Novant Health Presbyterian Medical Center
Charlotte, North Carolina 28204
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Duke University Medical Center
Durham, North Carolina 27710
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East Carolina University
Greenville, North Carolina 27834
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Wake Forest University Health Sciences
Winston-Salem, North Carolina 27157
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Sanford Broadway Medical Center
Fargo, North Dakota 58122
United States
Children's Hospital Medical Center of Akron
Akron, Ohio 44308
United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio 45229
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Rainbow Babies and Childrens Hospital
Cleveland, Ohio 44106
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Cleveland Clinic Foundation
Cleveland, Ohio 44195
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Nationwide Children's Hospital
Columbus, Ohio 43205
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Dayton Children's Hospital
Dayton, Ohio 45404
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ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio 43606
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University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
United States
Oregon Health and Science University
Portland, Oregon 97239
United States
Lehigh Valley Hospital-Cedar Crest
Allentown, Pennsylvania 18103
United States
Geisinger Medical Center
Danville, Pennsylvania 17822
United States
Penn State Children's Hospital
Hershey, Pennsylvania 17033
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Children's Hospital of Philadelphia
Philadelphia, Pennsylvania 19104
United States
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania 19134
United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania 15224
United States
Rhode Island Hospital
Providence, Rhode Island 02903
United States
Prisma Health Richland Hospital
Columbia, South Carolina 29203
United States
BI-LO Charities Children's Cancer Center
Greenville, South Carolina 29605
United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota 57117-5134
United States
East Tennessee Childrens Hospital
Knoxville, Tennessee 37916
United States
Saint Jude Children's Research Hospital
Memphis, Tennessee 38105
United States
The Children's Hospital at TriStar Centennial
Nashville, Tennessee 37203
United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee 37232
United States
Dell Children's Medical Center of Central Texas
Austin, Texas 78723
United States
Driscoll Children's Hospital
Corpus Christi, Texas 78411
United States
Medical City Dallas Hospital
Dallas, Texas 75230
United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas 75390
United States
El Paso Children's Hospital
El Paso, Texas 79905
United States
Cook Children's Medical Center
Fort Worth, Texas 76104
United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas 77030
United States
M D Anderson Cancer Center
Houston, Texas 77030
United States
Covenant Children's Hospital
Lubbock, Texas 79410
United States
UMC Cancer Center / UMC Health System
Lubbock, Texas 79415
United States
Children's Hospital of San Antonio
San Antonio, Texas 78207
United States
Methodist Children's Hospital of South Texas
San Antonio, Texas 78229
United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas 78229
United States
Scott and White Memorial Hospital
Temple, Texas 76508
United States
Primary Children's Hospital
Salt Lake City, Utah 84113
United States
University of Virginia Cancer Center
Charlottesville, Virginia 22908
United States
Inova Fairfax Hospital
Falls Church, Virginia 22042
United States
Children's Hospital of The King's Daughters
Norfolk, Virginia 23507
United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia 23298
United States
Carilion Children's
Roanoke, Virginia 24014
United States
Seattle Children's Hospital
Seattle, Washington 98105
United States
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington 99204
United States
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington 98405
United States
Madigan Army Medical Center
Tacoma, Washington 98431
United States
West Virginia University Charleston Division
Charleston, West Virginia 25304
United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin 53792
United States
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin 54449
United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin 53226
United States
Sydney Children's Hospital
Randwick, New South Wales 2031
Australia
The Children's Hospital at Westmead
Westmead, New South Wales 2145
Australia
Perth Children's Hospital
Perth, Western Australia 6009
Australia
Alberta Children's Hospital
Calgary, Alberta T3B 6A8
Canada
University of Alberta Hospital
Edmonton, Alberta T6G 2B7
Canada
British Columbia Children's Hospital
Vancouver, British Columbia V6H 3V4
Canada
CancerCare Manitoba
Winnipeg, Manitoba R3E 0V9
Canada
IWK Health Centre
Halifax, Nova Scotia B3K 6R8
Canada
Hospital for Sick Children
Toronto, Ontario M5G 1X8
Canada
The Montreal Children's Hospital of the MUHC
Montreal, Quebec H3H 1P3
Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec H3T 1C5
Canada
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
Sherbrooke, Quebec J1H 5N4
Canada
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
Québec, G1V 4G2
Canada
Starship Children's Hospital
Grafton, Auckland 1145
New Zealand
Christchurch Hospital
Christchurch, 8011
New Zealand