Combination Chemotherapy Alone or With Radiation Therapy in Treating Children With Kidney Cancer

• ClinicalTrials.gov Identifier: NCT00002611
• Recruitment Status: Completed
• First Posted: January 27, 2003
• Last Update Posted: February 25, 2021
• Sponsor: Children's Oncology Group
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Children's Oncology Group

Study Description

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. It is not yet known whether combination chemotherapy alone or combination chemotherapy plus radiation therapy is more effective for childhood kidney cancer.

PURPOSE: Phase III trial to compare the effectiveness of combination chemotherapy with or without radiation therapy in treating children who have kidney cancer.

Condition or disease	Intervention/treatment	Phase
Kidney Cancer	Biological: dactinomycin; Biological: filgrastim; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: vincristine sulfate; Procedure: conventional surgery; Radiation: radiation therapy	Phase 3

Detailed Description:

OBJECTIVES:

• Increase survival rate of children with favorable histology (FH) Wilms' tumor and other childhood renal tumors.
• Determine whether loss of heterozygosity for chromosome 16q or 1p in tumor tissue is associated with a poorer prognosis in children with FH Wilms' tumor.
• Determine whether increased DNA content in tumor cells is associated with a poorer prognosis in children with FH Wilms' tumor.
• Decrease the acute and long-term morbidity in children with Wilms' tumor by limiting initial therapy and consistently using the same regimen (protocol NWTS-5/R) for patients who relapse following initial treatment.
• Improve overall and disease-free survival of patients with renal tumors of unfavorable histology, including Wilms' tumor with diffuse anaplasia and clear cell sarcoma of the kidney, using a new treatment regimen that includes etoposide (VP-16) and cyclophosphamide (CTX).
• Improve overall and disease-free survival in patients with malignant rhabdoid tumor of the kidney using a new treatment regimen that includes carboplatin, VP-16, and CTX. (The rhabdoid tumor stratum closed to accrual effective 07/13/2001)
• Provide data regarding loss of heterozygosity for chromosomes 11p15, 16q, and 1p, age at diagnosis, precursor lesions (perilobar, intralobar, nephroblastomatosis), bilaterality, and presence of congenital anomalies required for the completion of protocol A0026 (a case-control study of risk factors for Wilms' tumor).

OUTLINE: This is a multicenter study. Patients are assigned to one of nine strata based on tumor histology, stage, tumor weight, and age.

• Stratum 1 (stage I favorable histology (FH) Wilms' tumor, under 24 months of age, and tumor weight less than 550 g): After nephrectomy, patients receive regimen EE-4A comprising dactinomycin (DACT) IV weekly on weeks 0, 3, 6, 9, 12, 15, and 18 and vincristine (VCR) IV weekly on weeks 1-10, 12, 15, and 18.
• Stratum 2 (stage I FH Wilms' tumor and age 24 months and over or tumor weight at least 550 g; stage I focal anaplastic (FA) or diffuse anaplastic (DA) Wilms' tumor): Patients receive therapy as in stratum 1.
• Stratum 3 (stage II FH Wilms' tumor): Patients receive therapy as in stratum 1.
• Stratum 4 (stage III FH Wilms' tumor; stage II or III FA Wilms' tumor): After nephrectomy, patients receive regimen DD-4A comprising DACT IV weekly on weeks 0, 6, 12, 18, and 24; doxorubicin IV weekly on weeks 3, 9, 15, and 21; and VCR IV weekly on weeks 1-10, 12, 15, 18, 21, and 24. Patients also undergo abdominal radiotherapy.
• Stratum 5 (stage IV FH or FA Wilms' tumor): Patients receive chemotherapy as in stratum 4, abdominal radiotherapy, and whole lung radiotherapy (at the discretion of the investigator).
• Stratum 6 (stage V FH, FA, or DA Wilms' tumor ): After bilateral biopsy, patients with FH receive chemotherapy as in stratum 1 or 4. Patients with FA or DA receive chemotherapy as in stratum 7.
• Stratum 7 (stages I-IV clear cell sarcoma): After nephrectomy, patients receive VCR IV weekly on weeks 1, 2, 4-8, 10-13, 18, and 24; cyclophosphamide (CTX) IV over 1 hour on days 1-3 of weeks 6, 12, 18, and 24 and on days 1-5 of weeks 3, 9, 15, and 21; doxorubicin IV (beginning after CTX infusion) weekly on weeks 0, 6, 12, 18, and 24; and etoposide (VP-16) IV over 1 hour (beginning after CTX infusion) on days 1-5 of weeks 3, 9, 15, and 21. Filgrastim (G-CSF) is administered subcutaneously (SC) beginning 24 hours after completion of chemotherapy and continuing until blood counts recover. Patients also undergo abdominal radiotherapy and whole lung radiotherapy (if pulmonary metastases are present).
• Stratum 8 (stages II-IV DA Wilms' tumor): Patients receive treatment as in stratum 7.
• Stratum 9 (stages I-IV rhabdoid tumor): After nephrectomy, patients receive carboplatin IV on days 1-2 and VP-16 IV over 1 hour (beginning after carboplatin infusion) on days 1-3 of weeks 0, 3, 9, 12, 18, and 21 and CTX IV over 1 hour on days 1-5 of weeks 6, 15, and 24. G-CSF is administered as in stratum 7. Patients also undergo radiotherapy. (The rhabdoid tumor stratum closed to accrual effective 07/13/2001.) After completion of chemotherapy, patients undergo second-look laparotomy and partial nephrectomy or wedge excision (if feasible). After second-look surgery, patients without persistent or residual disease resume chemotherapy.

Patients are followed every 3 months for 5 years, every 6 months for 2 years, and then annually for 3 years.

PROJECTED ACCRUAL: A total of 207 patients will be accrued for the treatment portion of this study. (The rhabdoid tumor stratum closed to accrual effective 07/13/2001.)

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 3031 participants
• Primary Purpose: Treatment
• Official Title: NATIONAL WILMS TUMOR STUDY-5 -- THERAPEUTIC TRIAL AND BIOLOGY STUDY
• Study Start Date: July 1995
• Actual Primary Completion Date: June 2002
• Actual Study Completion Date: August 2003

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Stratum 1; Stage I favorable histology (FH) Wilms' tumor, under 24 months of age, and tumor weight less than 550 g: After conventional surgery (nephrectomy), patients receive regimen EE-4A comprising dactinomycin (DACT) IV weekly on weeks 0, 3, 6, 9, 12, 15, and 18 and vincristine sulfate (VCR) IV weekly on weeks 1-10, 12, 15, and 18.	Biological: dactinomycin; Drug: vincristine sulfate; Procedure: conventional surgery
Active Comparator: Stratum 2; Stage I FH Wilms' tumor and age 24 months and over or tumor weight at least 550 g; stage I focal anaplastic (FA) or diffuse anaplastic (DA) Wilms' tumor: Patients receive regimen EE-4A comprising dactinomycin (DACT) IV weekly on weeks 0, 3, 6, 9, 12, 15, and 18 and vincristine sulfate (VCR) IV weekly on weeks 1-10, 12, 15, and 18.	Biological: dactinomycin; Drug: vincristine sulfate
Active Comparator: Stratum 3; Stage II FH Wilms' tumor: Patients receive regimen EE-4A comprising dactinomycin (DACT) IV weekly on weeks 0, 3, 6, 9, 12, 15, and 18 and vincristine sulfate (VCR) IV weekly on weeks 1-10, 12, 15, and 18.	Biological: dactinomycin; Drug: vincristine sulfate
Active Comparator: Stratum 4; Stage III FH Wilms' tumor; stage II or III FA Wilms' tumor: After conventional surgery (nephrectomy), patients receive regimen DD-4A comprising dactinomycin DACT IV weekly on weeks 0, 6, 12, 18, and 24; doxorubicin hydrochloride IV weekly on weeks 3, 9, 15, and 21; and vincristine sulfate VCR IV weekly on weeks 1-10, 12, 15, 18, 21, and 24. Patients also undergo abdominal radiation therapy.	Biological: dactinomycin; Drug: doxorubicin hydrochloride; Source and Pharmacology: An anthracycline antibiotic isolated from cultures of Streptomyces peucetius. Binds to DNA and inhibits nucleic acid synthesis, with its major lethal effect occurring during the S phase of the cell cycle. Has some topoisomerase II inhibitory activity. Since it is primarily excreted by the liver, any liver impairment may enhance toxicity. 40% to 50% is excreted in the bile; <5% in the urine. The drug has a very short initial t½ of <20 minutes and a terminal t½ of 17 hours. Animal studies indicate cytotoxic levels persist in tissue for as long as 24 hours.; Other Names: NSC #123127; (Adriamycin); Drug: vincristine sulfate; Procedure: conventional surgery; Radiation: radiation therapy
Active Comparator: Stratum 5; Stage IV FH or FA Wilms' tumor: patients receive regimen DD-4A comprising dactinomycin DACT IV weekly on weeks 0, 6, 12, 18, and 24; doxorubicin hydrochloride IV weekly on weeks 3, 9, 15, and 21; and vincristine sulfate VCR IV weekly on weeks 1-10, 12, 15, 18, 21, and 24. Patients also undergo abdominal radiation therapy, and whole lung radiation therapy (at the discretion of the investigator).	Biological: dactinomycin; Drug: doxorubicin hydrochloride; Source and Pharmacology: An anthracycline antibiotic isolated from cultures of Streptomyces peucetius. Binds to DNA and inhibits nucleic acid synthesis, with its major lethal effect occurring during the S phase of the cell cycle. Has some topoisomerase II inhibitory activity. Since it is primarily excreted by the liver, any liver impairment may enhance toxicity. 40% to 50% is excreted in the bile; <5% in the urine. The drug has a very short initial t½ of <20 minutes and a terminal t½ of 17 hours. Animal studies indicate cytotoxic levels persist in tissue for as long as 24 hours.; Other Names: NSC #123127; (Adriamycin); Drug: vincristine sulfate
Active Comparator: Stratum 6; Stage V FH, FA, or DA Wilms' tumor: After bilateral conventional surgery (biopsy), patients with FH receive chemotherapy as in stratum 1 (dactinomycin IV weeks 0, 3, 6, 9, 12, 15, and 18 and vincristine sulfate IV weeks 1-10, 12, 15, and 18) or 4 (dactinomycin IV weeks 0, 6, 12, 18, and 24; doxorubicin hydrochloride IV weeks 3, 9, 15, and 21; and vincristine sulfate VCR IV weeks 1-10, 12, 15, 18, 21, and 24). Patients with FA or DA receive chemotherapy as in stratum 7 (vincristine sulfate VCR IV weeks 1, 2, 4-8, 10-13, 18, and 24; cyclophosphamide sulfate (CTX) IV over 1 hour on days 1-3 of weeks 6, 12, 18, and 24 and on days 1-5 of weeks 3, 9, 15, and 21; doxorubicin hydrochloride IV (beginning after CTX infusion) weeks 0, 6, 12, 18, and 24; and etoposide (VP-16) IV over 1 hour (beginning after CTX infusion) on days 1-5 of weeks 3, 9, 15, and 21. Filgrastim (G-CSF) is administered subcutaneously (SC) beginning 24 hours after completion of chemotherapy.	Biological: dactinomycin; Biological: filgrastim; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Source and Pharmacology: An anthracycline antibiotic isolated from cultures of Streptomyces peucetius. Binds to DNA and inhibits nucleic acid synthesis, with its major lethal effect occurring during the S phase of the cell cycle. Has some topoisomerase II inhibitory activity. Since it is primarily excreted by the liver, any liver impairment may enhance toxicity. 40% to 50% is excreted in the bile; <5% in the urine. The drug has a very short initial t½ of <20 minutes and a terminal t½ of 17 hours. Animal studies indicate cytotoxic levels persist in tissue for as long as 24 hours.; Other Names: NSC #123127; (Adriamycin); Drug: etoposide; Drug: vincristine sulfate; Procedure: conventional surgery
Active Comparator: Stratum 7; Stages I-IV clear cell sarcoma): After conventional surgery (nephrectomy), patients receive vincristine sulfate VCR IV weekly on weeks 1, 2, 4-8, 10-13, 18, and 24; cyclophosphamide sulfate (CTX) IV over 1 hour on days 1-3 of weeks 6, 12, 18, and 24 and on days 1-5 of weeks 3, 9, 15, and 21; doxorubicin hydrochloride IV (beginning after CTX infusion) weekly on weeks 0, 6, 12, 18, and 24; and etoposide (VP-16) IV over 1 hour (beginning after CTX infusion) on days 1-5 of weeks 3, 9, 15, and 21. Filgrastim (G-CSF) is administered subcutaneously (SC) beginning 24 hours after completion of chemotherapy and continuing until blood counts recover. Patients also undergo abdominal radiotherapy and whole lung radiotherapy (if pulmonary metastases are present).	Biological: filgrastim; Drug: doxorubicin hydrochloride; Source and Pharmacology: An anthracycline antibiotic isolated from cultures of Streptomyces peucetius. Binds to DNA and inhibits nucleic acid synthesis, with its major lethal effect occurring during the S phase of the cell cycle. Has some topoisomerase II inhibitory activity. Since it is primarily excreted by the liver, any liver impairment may enhance toxicity. 40% to 50% is excreted in the bile; <5% in the urine. The drug has a very short initial t½ of <20 minutes and a terminal t½ of 17 hours. Animal studies indicate cytotoxic levels persist in tissue for as long as 24 hours.; Other Names: NSC #123127; (Adriamycin); Drug: etoposide; Procedure: conventional surgery; Radiation: radiation therapy
Active Comparator: Stratum 8; Stages II-IV DA Wilms' tumor: After conventional surgery (nephrectomy), Patients receive treatment as in stratum 7 (patients receive vincristine sulfate VCR IV weekly on weeks 1, 2, 4-8, 10-13, 18, and 24; cyclophosphamide sulfate (CTX) IV over 1 hour on days 1-3 of weeks 6, 12, 18, and 24 and on days 1-5 of weeks 3, 9, 15, and 21; doxorubicin hydrochloride IV (beginning after CTX infusion) weekly on weeks 0, 6, 12, 18, and 24; and etoposide (VP-16) IV over 1 hour (beginning after CTX infusion) on days 1-5 of weeks 3, 9, 15, and 21. Filgrastim (G-CSF) is administered subcutaneously (SC) beginning 24 hours after completion of chemotherapy and continuing until blood counts recover. Patients also undergo abdominal radiotherapy and whole lung radiotherapy (if pulmonary metastases are present).	Biological: filgrastim; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Source and Pharmacology: An anthracycline antibiotic isolated from cultures of Streptomyces peucetius. Binds to DNA and inhibits nucleic acid synthesis, with its major lethal effect occurring during the S phase of the cell cycle. Has some topoisomerase II inhibitory activity. Since it is primarily excreted by the liver, any liver impairment may enhance toxicity. 40% to 50% is excreted in the bile; <5% in the urine. The drug has a very short initial t½ of <20 minutes and a terminal t½ of 17 hours. Animal studies indicate cytotoxic levels persist in tissue for as long as 24 hours.; Other Names: NSC #123127; (Adriamycin); Drug: etoposide; Drug: vincristine sulfate; Procedure: conventional surgery; Radiation: radiation therapy
Active Comparator: Stratum 9; Stages I-IV rhabdoid tumor: After conventional surgery (nephrectomy), patients receive carboplatin IV on days 1-2 and VP-16 IV over 1 hour (beginning after carboplatin infusion) on days 1-3 of weeks 0, 3, 9, 12, 18, and 21 and CTX IV over 1 hour on days 1-5 of weeks 6, 15, and 24. Filgrastim G-CSF is administered as on stratum 7. Patients also undergo radiation therapy. After completion of chemotherapy, patients undergo second-look conventional surgery (laparotomy) and conventional surgery (partial nephrectomy or wedge excision if feasible). After conventional surgery (second-look surgery), patients without persistent or residual disease resume chemotherapy.	Biological: filgrastim; Drug: etoposide; Procedure: conventional surgery; Radiation: radiation therapy

Outcome Measures

Primary Outcome Measures :

1. Progression free survival

Eligibility Criteria

• Ages Eligible for Study: 0 Years to 15 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed stage I-V kidney cancer of one of the following histologies:

  • Wilms' tumor, favorable histology
  • Wilms' tumor, focal or diffuse anaplastic
  • Clear cell sarcoma

  • Rhabdoid tumor

    • (The rhabdoid tumor stratum closed to accrual effective 07/13/2001)

• Prior nephrectomy or biopsy required

  • Prior bilateral biopsy (preferably open) with bilateral staging and pathologic evaluation required for bilateral tumor
• Must begin study therapy within 5 days after nephrectomy (unless medically contraindicated)

PATIENT CHARACTERISTICS:

Age:

• Under 16

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• Not pregnant
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy

Surgery:

• See Disease Characteristics

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham Comprehensive Cancer Center

Birmingham, Alabama, United States, 35233

University of South Alabama Medical Center

Mobile, Alabama, United States, 36604

United States, Arizona

Phoenix Children's Hospital

Phoenix, Arizona, United States, 85016-7710

Arizona Cancer Center

Tucson, Arizona, United States, 85724

United States, Arkansas

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States, 72205

United States, California

Southern California Permanente Medical Group

Downey, California, United States, 90242

City of Hope Comprehensive Cancer Center

Duarte, California, United States, 91010-3000

Rebecca and John Moores UCSD Cancer Center

La Jolla, California, United States, 92093-0658

Loma Linda University Medical Center

Loma Linda, California, United States, 92354

Jonathan Jaques Children's Cancer Center

Long Beach, California, United States, 90801-1428

Children's Hospital Los Angeles

Los Angeles, California, United States, 90027-0700

Cedars-Sinai Medical Center

Los Angeles, California, United States, 90048

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, United States, 90095-1781

Children's Hospital Central California

Madera, California, United States, 93638-8762

Children's Hospital of Oakland

Oakland, California, United States, 94609-1809

Chao Family Comprehensive Cancer Center

Orange, California, United States, 92868

Children's Hospital of Orange County

Orange, California, United States, 92868

Lucile Packard Children's Hospital at Stanford

Palo Alto, California, United States, 94304

Sutter Cancer Center

Sacramento, California, United States, 95816

University of California Davis Medical Center

Sacramento, California, United States, 95817

Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego

San Diego, California, United States, 92120

Children's Hospital San Diego

San Diego, California, United States, 92123-4282

Kaiser Permanente Medical Center - San Francisco Geary Campus

San Francisco, California, United States, 94115

UCSF Comprehensive Cancer Center

San Francisco, California, United States, 94143-0128

Santa Barbara Cottage Hospital

Santa Barbara, California, United States, 93102

Kaiser Permanente Medical Center - Santa Clara

Santa Clara, California, United States, 95051-5386

David Grant Medical Center

Travis Air Force Base, California, United States, 94535

United States, Colorado

Children's Hospital of Denver

Denver, Colorado, United States, 80218-1088

Childhood Hematology/Oncology Associates

Denver, Colorado, United States, 80218

Presbyterian-St Luke's Medical Center

Denver, Colorado, United States, 80218

United States, Connecticut

University of Connecticut Health Center

Farmington, Connecticut, United States, 06360-7106

Yale Comprehensive Cancer Center

New Haven, Connecticut, United States, 06520-8028

United States, Delaware

Alfred I. Dupont Institute

Wilmington, Delaware, United States, 19899

United States, District of Columbia

Lombardi Cancer Center

Washington, District of Columbia, United States, 20007

Children's National Medical Center

Washington, District of Columbia, United States, 20010-2970

Walter Reed Army Medical Center

Washington, District of Columbia, United States, 20307-5000

United States, Florida

Broward General Medical Center

Fort Lauderdale, Florida, United States, 33316

Children's Hospital of Southwest Florida

Fort Myers, Florida, United States, 33908

Shands Hospital and Clinics, University of Florida

Gainesville, Florida, United States, 32610-100277

Joe DiMaggio Children's Hospital at Memorial

Hollywood, Florida, United States, 33021

Nemours Children's Clinic

Jacksonville, Florida, United States, 32207

University of Miami-Jackson Memorial Hospital

Miami, Florida, United States, 33136

Miami Children's Hospital

Miami, Florida, United States, 33155-4069

Baptist Hospital of Miami

Miami, Florida, United States, 33176-2197

Florida Hospital Cancer Institute

Orlando, Florida, United States, 32803

Nemours Children's Clinic-Orlando

Orlando, Florida, United States, 32806

Sacred Heart Children's Hospital

Pensacola, Florida, United States, 32504

All Children's Hospital

Saint Petersburg, Florida, United States, 33701

Tampa Children's Hospital

Tampa, Florida, United States, 33677-4227

St. Mary's Hospital

West Palm Beach, Florida, United States, 33407

United States, Georgia

Emory University Hospital - Atlanta

Atlanta, Georgia, United States, 30322

Children's Healthcare of Atlanta - Scottish Rite

Atlanta, Georgia, United States, 30342

Medical College of Georgia Comprehensive Cancer Center

Augusta, Georgia, United States, 30912-4000

Medical Center of Central Georgia

Macon, Georgia, United States, 31201

Memorial Health University Medical Center, Inc.

Savannah, Georgia, United States, 31403-3089

United States, Hawaii

Cancer Research Center of Hawaii

Honolulu, Hawaii, United States, 96813

MBCCOP - Hawaii

Honolulu, Hawaii, United States, 96813

Tripler Army Medical Center

Honolulu, Hawaii, United States, 96859-5000

United States, Idaho

Mountain States Tumor Institute

Boise, Idaho, United States, 83712

United States, Illinois

University of Chicago Cancer Research Center

Chicago, Illinois, United States, 60601

Rush-Presbyterian-St. Luke's Medical Center

Chicago, Illinois, United States, 60612

University of Illinois at Chicago

Chicago, Illinois, United States, 60612

Children's Memorial Hospital - Chicago

Chicago, Illinois, United States, 60614

Hope Children's Hospital

Oak Lawn, Illinois, United States, 60453

Lutheran General Hospital

Park Ridge, Illinois, United States, 60068-1174

Saint Jude Midwest Affiliate

Peoria, Illinois, United States, 61637

Southern Illinois University School of Medicine

Springfield, Illinois, United States, 62794-9658

United States, Indiana

Indiana University Cancer Center

Indianapolis, Indiana, United States, 46202-5289

St. Vincent Hospital and Health Care Center

Indianapolis, Indiana, United States, 46260

United States, Iowa

Raymond Blank Memorial Hospital for Children

Des Moines, Iowa, United States, 50308

John Stoddard Cancer Center

Des Moines, Iowa, United States, 50309

Holden Comprehensive Cancer Center

Iowa City, Iowa, United States, 52242-1009

United States, Kansas

Wesley Medical Center

Wichita, Kansas, United States, 67214

United States, Kentucky

Albert B. Chandler Medical Center, University of Kentucky

Lexington, Kentucky, United States, 40536-0284

Kosair Children's Hospital

Louisville, Kentucky, United States, 40202-3830

United States, Louisiana

Tulane University School of Medicine

New Orleans, Louisiana, United States, 70112

Children's Hospital of New Orleans

New Orleans, Louisiana, United States, 70118

Ochsner Clinic

New Orleans, Louisiana, United States, 70121

United States, Maine

Eastern Maine Medical Center

Bangor, Maine, United States, 04401

Maine Children's Cancer Program

Scarborough, Maine, United States, 04074

United States, Maryland

Marlene and Stewart Greenebaum Cancer Center, University of Maryland

Baltimore, Maryland, United States, 21201-1595

Sinai Hospital of Baltimore

Baltimore, Maryland, United States, 21225

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States, 21231-2410

United States, Massachusetts

Floating Hospital for Children

Boston, Massachusetts, United States, 02111

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02115

Baystate Medical Center

Springfield, Massachusetts, United States, 01107

University of Massachusetts Memorial Medical Center - University Campus

Worcester, Massachusetts, United States, 01655

United States, Michigan

Mott Children's Hospital

Ann Arbor, Michigan, United States, 48109-0914

Children's Hospital of Michigan

Detroit, Michigan, United States, 48201

Henry Ford Hospital

Detroit, Michigan, United States, 48202

St. John Hospital and Medical Center

Detroit, Michigan, United States, 48236

Michigan State University

East Lansing, Michigan, United States, 48824

Hurley Medical Center

Flint, Michigan, United States, 48503

Spectrum Health and DeVos Children's Hospital

Grand Rapids, Michigan, United States, 49503

Bronson Methodist Hospital

Kalamazoo, Michigan, United States, 49007

CCOP - Beaumont

Royal Oak, Michigan, United States, 48073-6769

William Beaumont Hospital

Royal Oak, Michigan, United States, 48073-6769

United States, Minnesota

St. Mary's/Duluth Clinic Cancer Center

Duluth, Minnesota, United States, 55805-1983

Children's Hospitals and Clinics - Minneapolis

Minneapolis, Minnesota, United States, 55404

Mayo Clinic Cancer Center

Rochester, Minnesota, United States, 55905

Children's Hospitals and Clinics of Minnesota

Saint Paul, Minnesota, United States, 55102

United States, Mississippi

University of Mississippi Medical Center

Jackson, Mississippi, United States, 39216-4505

United States, Missouri

Children's Mercy Hospital

Kansas City, Missouri, United States, 64108

Cardinal Glennon Children's Hospital

Saint Louis, Missouri, United States, 63104

St. Louis Children's Hospital

Saint Louis, Missouri, United States, 63110

United States, Nebraska

Children's Hospital of Omaha

Omaha, Nebraska, United States, 68114

University of Nebraska Medical Center

Omaha, Nebraska, United States, 68198-2168

United States, Nevada

Sunrise Hospital and Medical Center

Las Vegas, Nevada, United States, 89109-2306

United States, New Hampshire

Norris Cotton Cancer Center

Lebanon, New Hampshire, United States, 03756-0002

United States, New Jersey

Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

Cancer Institute of New Jersey

New Brunswick, New Jersey, United States, 08903

Newark Beth Israel Medical Center

Newark, New Jersey, United States, 07112-2094

St. Joseph's Hospital and Medical Center

Paterson, New Jersey, United States, 07503

Atlantic Health System

Summit, New Jersey, United States, 07901

United States, New Mexico

University of New Mexico Cancer Research and Treatment Center

Albuquerque, New Mexico, United States, 87131

United States, New York

Cancer Center of Albany Medical Center

Albany, New York, United States, 12208

Albert Einstein Clinical Cancer Center

Bronx, New York, United States, 10461

Brooklyn Hospital Center

Brooklyn, New York, United States, 11201

State University of New York Health Science Center at Brooklyn College of Medicine

Brooklyn, New York, United States, 11203

Brookdale University Hospital and Medical Center

Brooklyn, New York, United States, 11212

Maimonides Medical Center

Brooklyn, New York, United States, 11219

Roswell Park Cancer Institute

Buffalo, New York, United States, 14263-0001

North Shore University Hospital

Manhasset, New York, United States, 11030

Schneider Children's Hospital

New Hyde Park, New York, United States, 11042

New York Presbyterian Hospital - Cornell Campus

New York, New York, United States, 10021-4885

Memorial Sloan-Kettering Cancer Center

New York, New York, United States, 10021

Mount Sinai School of Medicine

New York, New York, United States, 10029

Columbia Presbyterian Hospital

New York, New York, United States, 10032

James P. Wilmot Cancer Center

Rochester, New York, United States, 14642

State University of New York Health Sciences Center - Stony Brook

Stony Brook, New York, United States, 11790-7775

State University of New York - Upstate Medical University

Syracuse, New York, United States, 13210

New York Medical College

Valhalla, New York, United States, 10595

United States, North Carolina

Mission Saint Joseph's Health System

Asheville, North Carolina, United States, 28801

Lineberger Comprehensive Cancer Center, UNC

Chapel Hill, North Carolina, United States, 27599-7295

Carolinas Medical Center

Charlotte, North Carolina, United States, 28232-2861

Presbyterian Healthcare

Charlotte, North Carolina, United States, 28233-3549

Duke Comprehensive Cancer Center

Durham, North Carolina, United States, 27710

East Carolina University School of Medicine

Greenville, North Carolina, United States, 27858-4354

Comprehensive Cancer Center at Wake Forest University

Winston-Salem, North Carolina, United States, 27157-1081

United States, North Dakota

Dakota Cancer Institute

Fargo, North Dakota, United States, 58103-4940

United States, Ohio

Children's Hospital Medical Center of Akron

Akron, Ohio, United States, 44308

Children's Hospital Medical Center - Cincinnati

Cincinnati, Ohio, United States, 45229-3039

Ireland Cancer Center

Cleveland, Ohio, United States, 44106-5065

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States, 44195

Children's Hospital of Columbus

Columbus, Ohio, United States, 43205-2696

Children's Medical Center - Dayton

Dayton, Ohio, United States, 45404

Toledo Children's Hospital

Toledo, Ohio, United States, 43601

St. Vincent Mercy Medical Center

Toledo, Ohio, United States, 43608

Forum Health-Tod Childrens Hospital

Youngstown, Ohio, United States, 44501

United States, Oklahoma

Children's Hospital of Oklahoma

Oklahoma City, Oklahoma, United States, 73104

CCOP - Oklahoma

Tulsa, Oklahoma, United States, 74136

Natalie Warren Bryant Cancer Center

Tulsa, Oklahoma, United States, 74136

United States, Oregon

Doernbecher Children's Hospital

Portland, Oregon, United States, 97201-3098

Legacy Emanuel Hospital and Health Center

Portland, Oregon, United States, 97227

United States, Pennsylvania

Geisinger Medical Center

Danville, Pennsylvania, United States, 17822-1320

Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States, 17033-0850

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States, 19134-1095

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States, 15213

United States, Rhode Island

Rhode Island Hospital

Providence, Rhode Island, United States, 02818

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 29425-0721

Palmetto Health South Carolina Cancer Center

Columbia, South Carolina, United States, 29203

Children's Hospital of Greenville Hospital System

Greenville, South Carolina, United States, 29605

United States, South Dakota

Avera Cancer Institute

Sioux Falls, South Dakota, United States, 57105-1080

Sioux Valley Hospital

Sioux Falls, South Dakota, United States, 57117

United States, Tennessee

East Tennessee State University Cancer Center at JCMC

Johnson City, Tennessee, United States, 37604

East Tennessee Children's Hospital

Knoxville, Tennessee, United States, 37901

Saint Jude Children's Research Hospital

Memphis, Tennessee, United States, 38105-2794

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States, 37232-6838

United States, Texas

Texas Tech University Health Sciences Center School of Medicine

Amarillo, Texas, United States, 79106

Children's Hospital of Austin

Austin, Texas, United States, 78701

Medical City Dallas Hospital

Dallas, Texas, United States, 75230

Simmons Cancer Center - Dallas

Dallas, Texas, United States, 75235-9154

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, United States, 76104

University of Texas Medical Branch

Galveston, Texas, United States, 77555-0361

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States, 77030-4009

Baylor College of Medicine

Houston, Texas, United States, 77030

San Antonio Military Pediatric Cancer and Blood Disorders Center

Lackland Air Force Base, Texas, United States, 78236-5300

Covenant Children's Hospital

Lubbock, Texas, United States, 79410

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States, 78207

Methodist Health Care System

San Antonio, Texas, United States, 78229-3902

Scott and White Memorial Hospital

Temple, Texas, United States, 76508

United States, Utah

Huntsman Cancer Institute

Salt Lake City, Utah, United States, 84112

United States, Vermont

Vermont Cancer Center

Burlington, Vermont, United States, 05401-3498

United States, Virginia

Cancer Center at the University of Virginia

Charlottesville, Virginia, United States, 22908

Inova Fairfax Hospital

Falls Church, Virginia, United States, 22042-3300

Children's Hospital of the King's Daughters

Norfolk, Virginia, United States, 23507

Naval Medical Center, Portsmouth

Portsmouth, Virginia, United States, 23708-5100

Massey Cancer Center

Richmond, Virginia, United States, 23298-0037

Carilion Medical Center for Children

Roanoke, Virginia, United States, 24013

United States, Washington

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, United States, 98105

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States, 98109-1024

Group Health Cooperative

Seattle, Washington, United States, 98112

Deaconess Medical Center

Spokane, Washington, United States, 99210-0248

Mary Bridge Children's Health Center

Tacoma, Washington, United States, 98415-0299

Madigan Army Medical Center

Tacoma, Washington, United States, 98431-5000

United States, West Virginia

West Virginia University - Charleston

Charleston, West Virginia, United States, 25302

Cabell-Huntington Hospital, Inc

Huntington, West Virginia, United States, 25701

West Virginia University Hospitals

Morgantown, West Virginia, United States, 26506-9300

United States, Wisconsin

Bellin Memorial Hospital

Green Bay, Wisconsin, United States, 54301

CCOP - St. Vincent Hospital Cancer Center, Green Bay

Green Bay, Wisconsin, United States, 54301

St. Vincent Hospital

Green Bay, Wisconsin, United States, 54307-9070

Gundersen Lutheran Medical Center

La Crosse, Wisconsin, United States, 54601

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States, 53792-0001

Marshfield Clinic

Marshfield, Wisconsin, United States, 54449-5772

Midwest Children's Cancer Center

Milwaukee, Wisconsin, United States, 53226

Australia, New South Wales

Sydney Children's Hospital

Randwick, New South Wales, Australia, 2031

Children's Hospital at Westmead

Westmead, New South Wales, Australia, 2145

Australia, Queensland

Royal Children's Hospital

Brisbane, Queensland, Australia, 4029

Australia, South Australia

Women's and Children's Hospital

North Adelaide, South Australia, Australia, 5006

Australia, Victoria

Royal Children's Hospital

Parkville, Victoria, Australia, 3052

Australia, Western Australia

Princess Margaret Hospital for Children

Perth, Western Australia, Australia, 6001

Canada, Alberta

Alberta Children's Hospital

Calgary, Alberta, Canada, T2T 5C7

Cross Cancer Institute

Edmonton, Alberta, Canada, T6G 1Z2

Canada, British Columbia

British Columbia Children's Hospital

Vancouver, British Columbia, Canada, V6H 3V4

Canada, Manitoba

CancerCare Manitoba

Winnipeg, Manitoba, Canada, R3E 0V9

Canada, Newfoundland and Labrador

Janeway Children's Health and Rehabilitation Centre

St. John's, Newfoundland and Labrador, Canada, A1B 3V6

Canada, Nova Scotia

IWK Health Centre

Halifax, Nova Scotia, Canada, B3J 3G9

Canada, Ontario

Children's Hospital

Hamilton, Ontario, Canada, L8N 3Z5

Children's Hospital of Western Ontario

London, Ontario, Canada, N6C 2V5

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada, K1H 8L1

Hospital for Sick Children

Toronto, Ontario, Canada, M5G 1X8

Canada, Quebec

McGill University Health Center - Montreal Children's Hospital

Montreal, Quebec, Canada, H3H 1P3

Hopital Sainte Justine

Montreal, Quebec, Canada, H3T 1C5

Centre Hospitalier de L'Universite Laval

Sainte Foy, Quebec, Canada, GIV 4G2

Laval University Medical Center

Sainte-Foy, Quebec, Canada, G1V 4G2

Canada, Saskatchewan

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada, S4T 7T1

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, Canada, S7N 4H4

Netherlands

Academisch Ziekenhuis Groningen

Groningen, Netherlands, 9700 RB

New Zealand

Starship Children's Hospital

Auckland, New Zealand

Puerto Rico

University of Puerto Rico School of Medicine Medical Sciences Campus

San Juan, Puerto Rico, 00936-5067

San Jorge Childrens Hospital

Santurce, Puerto Rico, 00912

Switzerland

Swiss Pediatric Oncology Group Bern

Bern, Switzerland, CH 3010

Swiss Pediatric Oncology Group Geneva

Geneva, Switzerland, CH 1211

Swiss Pediatric Oncology Group Lausanne

Lausanne, Switzerland, CH 1011

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

• Study Chair: Daniel M. Green, MD; Roswell Park Cancer Institute

More Information

Additional Information:

Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive 

Publications of Results:

Gadd S, Huff V, Huang CC, Ruteshouser EC, Dome JS, Grundy PE, Breslow N, Jennings L, Green DM, Beckwith JB, Perlman EJ. Clinically relevant subsets identified by gene expression patterns support a revised ontogenic model of Wilms tumor: a Children's Oncology Group Study. Neoplasia. 2012 Aug;14(8):742-56. doi: 10.1593/neo.12714.

Perlman EJ, Grundy PE, Anderson JR, Jennings LJ, Green DM, Dome JS, Shamberger RC, Ruteshouser EC, Huff V. WT1 mutation and 11P15 loss of heterozygosity predict relapse in very low-risk wilms tumors treated with surgery alone: a children's oncology group study. J Clin Oncol. 2011 Feb 20;29(6):698-703. doi: 10.1200/JCO.2010.31.5192. Epub 2010 Dec 28.

Fernandez CV, Anderson J, Breslow NE, Dome JS, Grundy PE, Perlman EJ, Green DM; National Wilms Tumor Study Group/Children's Oncology Group. Anthropomorphic measurements and event-free survival in patients with favorable histology Wilms tumor: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2009 Feb;52(2):254-8. doi: 10.1002/pbc.21809.

Huang CC, Gadd S, Breslow N, Cutcliffe C, Sredni ST, Helenowski IB, Dome JS, Grundy PE, Green DM, Fritsch MK, Perlman EJ. Predicting relapse in favorable histology Wilms tumor using gene expression analysis: a report from the Renal Tumor Committee of the Children's Oncology Group. Clin Cancer Res. 2009 Mar 1;15(5):1770-8. doi: 10.1158/1078-0432.CCR-08-1030. Epub 2009 Feb 10.

Malogolowkin M, Cotton CA, Green DM, Breslow NE, Perlman E, Miser J, Ritchey ML, Thomas PR, Grundy PE, D'Angio GJ, Beckwith JB, Shamberger RC, Haase GM, Donaldson M, Weetman R, Coppes MJ, Shearer P, Coccia P, Kletzel M, Macklis R, Tomlinson G, Huff V, Newbury R, Weeks D; National Wilms Tumor Study Group. Treatment of Wilms tumor relapsing after initial treatment with vincristine, actinomycin D, and doxorubicin. A report from the National Wilms Tumor Study Group. Pediatr Blood Cancer. 2008 Feb;50(2):236-41. doi: 10.1002/pbc.21267.

Dome JS, Cotton CA, Perlman EJ, Breslow NE, Kalapurakal JA, Ritchey ML, Grundy PE, Malogolowkin M, Beckwith JB, Shamberger RC, Haase GM, Coppes MJ, Coccia P, Kletzel M, Weetman RM, Donaldson M, Macklis RM, Green DM. Treatment of anaplastic histology Wilms' tumor: results from the fifth National Wilms' Tumor Study. J Clin Oncol. 2006 May 20;24(15):2352-8. doi: 10.1200/JCO.2005.04.7852.

Ehrlich PF, Hamilton TE, Grundy P, Ritchey M, Haase G, Shamberger RC; National Wilms' Tumor Study Group (National Wilms' Tumor Study 5). The value of surgery in directing therapy for patients with Wilms' tumor with pulmonary disease. A report from the National Wilms' Tumor Study Group (National Wilms' Tumor Study 5). J Pediatr Surg. 2006 Jan;41(1):162-7; discussion 162-7. doi: 10.1016/j.jpedsurg.2005.10.020.

Seibel NL, Sun J, Anderson JR, et al.: Outcome of clear cell sarcoma of the kidney (CCSK) treated on the National Wilms Tumor Study-5 (NWTS). [Abstract] J Clin Oncol 24 (Suppl 18): A-9000, 502s, 2006.

Dome JS, Bockhold CA, Li SM, Baker SD, Green DM, Perlman EJ, Hill DA, Breslow NE. High telomerase RNA expression level is an adverse prognostic factor for favorable-histology Wilms' tumor. J Clin Oncol. 2005 Dec 20;23(36):9138-45. doi: 10.1200/JCO.2005.00.562. Epub 2005 Sep 19.

Ehrlich PF, Ritchey ML, Hamilton TE, Haase GM, Ou S, Breslow N, Grundy P, Green D, Norkool P, Becker J, Shamberger RC. Quality assessment for Wilms' tumor: a report from the National Wilms' Tumor Study-5. J Pediatr Surg. 2005 Jan;40(1):208-12; discussion 212-3. doi: 10.1016/j.jpedsurg.2004.09.044.

Grundy PE, Breslow NE, Li S, Perlman E, Beckwith JB, Ritchey ML, Shamberger RC, Haase GM, D'Angio GJ, Donaldson M, Coppes MJ, Malogolowkin M, Shearer P, Thomas PR, Macklis R, Tomlinson G, Huff V, Green DM; National Wilms Tumor Study Group. Loss of heterozygosity for chromosomes 1p and 16q is an adverse prognostic factor in favorable-histology Wilms tumor: a report from the National Wilms Tumor Study Group. J Clin Oncol. 2005 Oct 10;23(29):7312-21. doi: 10.1200/JCO.2005.01.2799. Epub 2005 Aug 29.

Miller MA, Karacay B, Breslow NE, Li S, O'Dorisio MS, Grundy PE, Sandler AD. Prognostic value of quantifying apoptosis factor expression in favorable histology wilms tumors. J Pediatr Hematol Oncol. 2005 Jan;27(1):11-4. doi: 10.1097/01.mph.0000149961.71266.27.

Other Publications:

Grundy PE, Green DM, Dirks AC, Berendt AE, Breslow NE, Anderson JR, Dome JS. Clinical significance of pulmonary nodules detected by CT and Not CXR in patients treated for favorable histology Wilms tumor on national Wilms tumor studies-4 and -5: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2012 Oct;59(4):631-5. doi: 10.1002/pbc.24123. Epub 2012 Mar 15.

Kieran K, Anderson JR, Dome JS, Ehrlich PF, Ritchey ML, Shamberger RC, Perlman EJ, Green DM, Davidoff AM. Lymph node involvement in Wilms tumor: results from National Wilms Tumor Studies 4 and 5. J Pediatr Surg. 2012 Apr;47(4):700-6. doi: 10.1016/j.jpedsurg.2011.08.017.

Lange J, Peterson SM, Takashima JR, Grigoriev Y, Ritchey ML, Shamberger RC, Beckwith JB, Perlman E, Green DM, Breslow NE. Risk factors for end stage renal disease in non-WT1-syndromic Wilms tumor. J Urol. 2011 Aug;186(2):378-86. doi: 10.1016/j.juro.2011.03.110. Epub 2011 Jun 17.

Kalapurakal JA, Green DM, Haase G, Anderson JR, Dome JS, Grundy PE. Outcomes of children with favorable histology wilms tumor and peritoneal implants treated in National Wilms Tumor Studies-4 and -5. Int J Radiat Oncol Biol Phys. 2010 Jun 1;77(2):554-8. doi: 10.1016/j.ijrobp.2009.04.081.

Ehrlich PF, Ferrer FA, Ritchey ML, Anderson JR, Green DM, Grundy PE, Dome JS, Kalapurakal JA, Perlman EJ, Shamberger RC. Hepatic metastasis at diagnosis in patients with Wilms tumor is not an independent adverse prognostic factor for stage IV Wilms tumor: a report from the Children's Oncology Group/National Wilms Tumor Study Group. Ann Surg. 2009 Oct;250(4):642-8. doi: 10.1097/SLA.0b013e3181b76f20.

Ritchey M, Daley S, Shamberger RC, Ehrlich P, Hamilton T, Haase G, Sawin R; National Wilms' Tumor Study Group. Ureteral extension in Wilms' tumor: a report from the National Wilms' Tumor Study Group (NWTSG). J Pediatr Surg. 2008 Sep;43(9):1625-9. doi: 10.1016/j.jpedsurg.2008.01.067.

van den Heuvel-Eibrink MM, Grundy P, Graf N, Pritchard-Jones K, Bergeron C, Patte C, van Tinteren H, Rey A, Langford C, Anderson JR, de Kraker J. Characteristics and survival of 750 children diagnosed with a renal tumor in the first seven months of life: A collaborative study by the SIOP/GPOH/SFOP, NWTSG, and UKCCSG Wilms tumor study groups. Pediatr Blood Cancer. 2008 Jun;50(6):1130-4. doi: 10.1002/pbc.21389.

Breslow NE, Beckwith JB, Perlman EJ, Reeve AE. Age distributions, birth weights, nephrogenic rests, and heterogeneity in the pathogenesis of Wilms tumor. Pediatr Blood Cancer. 2006 Sep;47(3):260-7. doi: 10.1002/pbc.20891.

Kalapurakal JA, Nan B, Norkool P, Coppes M, Perlman E, Beckwith B, Ritchey M, Breslow N, Grundy P, D'angio GJ, Green DM, Thomas PR. Treatment outcomes in adults with favorable histologic type Wilms tumor-an update from the National Wilms Tumor Study Group. Int J Radiat Oncol Biol Phys. 2004 Dec 1;60(5):1379-84. doi: 10.1016/j.ijrobp.2004.05.057.

• Responsible Party: Children's Oncology Group
• ClinicalTrials.gov Identifier: NCT00002611
• Other Study ID Numbers: 9440; COG-Q9401 ( Other Identifier: Children's Oncology Group ); NWTS-Q9401 ( Other Identifier: NWTS ); CCG-4941 ( Other Identifier: Children's Cancer Group ); POG-9440 ( Other Identifier: Pediatric Oncology Group ); INT-0150; NWTS-5 ( Other Identifier: NWTS ); CDR0000063901 ( Other Identifier: NCI )
• First Posted: January 27, 2003
• Last Update Posted: February 25, 2021
• Last Verified: July 2014

Keywords provided by Children's Oncology Group:

stage I Wilms tumor; stage II Wilms tumor; stage III Wilms tumor; stage IV Wilms tumor; stage V Wilms tumor; clear cell sarcoma of the kidney

Additional relevant MeSH terms:

Kidney Neoplasms; Carcinoma, Renal Cell; Wilms Tumor; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Complex and Mixed; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Dactinomycin; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Etoposide; Vincristine; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents