title: Shorter-duration therapy using vincristine, dactinomycin, and lower-dose cyclophosphamide with or without radiotherapy for patients with newly diagnosed low-risk rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group.
abstract: OBJECTIVE
  Intergroup Rhabdomyosarcoma Study Group (IRSG) studies III and IV showed improved failure-free survival (FFS) rates with vincristine, dactinomycin, and cyclophosphamide (VAC; total cumulative cyclophosphamide dose, 26.4 g/m(2)) compared with vincristine and dactinomycin (VA) for patients with subset-one low-risk embryonal rhabdomyosarcoma (ERMS; stage 1/2 group I/II ERMS or stage 1 group III orbit ERMS). The objective of Children's Oncology Group ARST0331 was to reduce the length of therapy without compromising FFS for this subset of low-risk patients by using VA in combination with lower-dose cyclophosphamide (total cumulative dose, 4.8 g/m(2)) plus radiotherapy (RT).
  
  
  METHODS
  This noninferiority prospective clinical trial enrolled newly diagnosed patients with subset-one clinical features. Therapy included four cycles of VAC followed by four cycles of VA over 22 weeks. Patients with microscopic or gross residual disease at study entry received RT.
  
  
  RESULTS
  With a median follow-up of 4.3 years, we observed 35 failures among 271 eligible patients versus 48.4 expected failures, calculated using a fixed outcome based on the FFS expected for similar patients treated on the IRSG D9602 protocol. The estimated 3-year FFS rate was 89% (95% CI, 85% to 92%), and the overall survival rate was 98% (95% CI, 95% to 99%). Patients with paratesticular tumors had the most favorable outcome. Three-year cumulative incidence rates for any local, regional, or distant failures were 7.6%, 1.5%, and 3.4%, respectively.
  
  
  CONCLUSIONS
  Shorter-duration therapy that included lower-dose cyclophosphamide and RT did not compromise FFS for patients with subset-one low-risk ERMS.
authors.affiliation: David O. Walterhouse, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL; Alberto S. Pappo, Saint Jude Children's Research Hospital, Memphis, TN; Jane L. Meza, James R. Anderson, University of Nebraska Medical Center College of Public Health, Omaha, NE; John C. Breneman, Children's Hospital Medical Center, Cincinnati; Timothy P. Cripe, Nationwide Children's Hospital, Columbus, OH; Andrea Hayes-Jordan, MD Anderson Cancer Center, Houston, TX; David M. Parham, William H. Meyer, University of Oklahoma School of Medicine, Oklahoma City, OK; Douglas S. Hawkins, Seattle Children's Hospital, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA. d-walterhouse@northwestern.edu.
authors.forename: David O
authors.initials: DO
authors.lastname: Walterhouse
authors.affiliation: David O. Walterhouse, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL; Alberto S. Pappo, Saint Jude Children's Research Hospital, Memphis, TN; Jane L. Meza, James R. Anderson, University of Nebraska Medical Center College of Public Health, Omaha, NE; John C. Breneman, Children's Hospital Medical Center, Cincinnati; Timothy P. Cripe, Nationwide Children's Hospital, Columbus, OH; Andrea Hayes-Jordan, MD Anderson Cancer Center, Houston, TX; David M. Parham, William H. Meyer, University of Oklahoma School of Medicine, Oklahoma City, OK; Douglas S. Hawkins, Seattle Children's Hospital, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA.
authors.forename: Alberto S
authors.initials: AS
authors.lastname: Pappo
authors.affiliation: David O. Walterhouse, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL; Alberto S. Pappo, Saint Jude Children's Research Hospital, Memphis, TN; Jane L. Meza, James R. Anderson, University of Nebraska Medical Center College of Public Health, Omaha, NE; John C. Breneman, Children's Hospital Medical Center, Cincinnati; Timothy P. Cripe, Nationwide Children's Hospital, Columbus, OH; Andrea Hayes-Jordan, MD Anderson Cancer Center, Houston, TX; David M. Parham, William H. Meyer, University of Oklahoma School of Medicine, Oklahoma City, OK; Douglas S. Hawkins, Seattle Children's Hospital, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA.
authors.forename: Jane L
authors.initials: JL
authors.lastname: Meza
authors.affiliation: David O. Walterhouse, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL; Alberto S. Pappo, Saint Jude Children's Research Hospital, Memphis, TN; Jane L. Meza, James R. Anderson, University of Nebraska Medical Center College of Public Health, Omaha, NE; John C. Breneman, Children's Hospital Medical Center, Cincinnati; Timothy P. Cripe, Nationwide Children's Hospital, Columbus, OH; Andrea Hayes-Jordan, MD Anderson Cancer Center, Houston, TX; David M. Parham, William H. Meyer, University of Oklahoma School of Medicine, Oklahoma City, OK; Douglas S. Hawkins, Seattle Children's Hospital, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA.
authors.forename: John C
authors.initials: JC
authors.lastname: Breneman
authors.affiliation: David O. Walterhouse, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL; Alberto S. Pappo, Saint Jude Children's Research Hospital, Memphis, TN; Jane L. Meza, James R. Anderson, University of Nebraska Medical Center College of Public Health, Omaha, NE; John C. Breneman, Children's Hospital Medical Center, Cincinnati; Timothy P. Cripe, Nationwide Children's Hospital, Columbus, OH; Andrea Hayes-Jordan, MD Anderson Cancer Center, Houston, TX; David M. Parham, William H. Meyer, University of Oklahoma School of Medicine, Oklahoma City, OK; Douglas S. Hawkins, Seattle Children's Hospital, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Hayes-Jordan
authors.affiliation: David O. Walterhouse, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL; Alberto S. Pappo, Saint Jude Children's Research Hospital, Memphis, TN; Jane L. Meza, James R. Anderson, University of Nebraska Medical Center College of Public Health, Omaha, NE; John C. Breneman, Children's Hospital Medical Center, Cincinnati; Timothy P. Cripe, Nationwide Children's Hospital, Columbus, OH; Andrea Hayes-Jordan, MD Anderson Cancer Center, Houston, TX; David M. Parham, William H. Meyer, University of Oklahoma School of Medicine, Oklahoma City, OK; Douglas S. Hawkins, Seattle Children's Hospital, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA.
authors.forename: David M
authors.initials: DM
authors.lastname: Parham
authors.affiliation: David O. Walterhouse, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL; Alberto S. Pappo, Saint Jude Children's Research Hospital, Memphis, TN; Jane L. Meza, James R. Anderson, University of Nebraska Medical Center College of Public Health, Omaha, NE; John C. Breneman, Children's Hospital Medical Center, Cincinnati; Timothy P. Cripe, Nationwide Children's Hospital, Columbus, OH; Andrea Hayes-Jordan, MD Anderson Cancer Center, Houston, TX; David M. Parham, William H. Meyer, University of Oklahoma School of Medicine, Oklahoma City, OK; Douglas S. Hawkins, Seattle Children's Hospital, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Cripe
authors.affiliation: David O. Walterhouse, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL; Alberto S. Pappo, Saint Jude Children's Research Hospital, Memphis, TN; Jane L. Meza, James R. Anderson, University of Nebraska Medical Center College of Public Health, Omaha, NE; John C. Breneman, Children's Hospital Medical Center, Cincinnati; Timothy P. Cripe, Nationwide Children's Hospital, Columbus, OH; Andrea Hayes-Jordan, MD Anderson Cancer Center, Houston, TX; David M. Parham, William H. Meyer, University of Oklahoma School of Medicine, Oklahoma City, OK; Douglas S. Hawkins, Seattle Children's Hospital, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA.
authors.forename: James R
authors.initials: JR
authors.lastname: Anderson
authors.affiliation: David O. Walterhouse, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL; Alberto S. Pappo, Saint Jude Children's Research Hospital, Memphis, TN; Jane L. Meza, James R. Anderson, University of Nebraska Medical Center College of Public Health, Omaha, NE; John C. Breneman, Children's Hospital Medical Center, Cincinnati; Timothy P. Cripe, Nationwide Children's Hospital, Columbus, OH; Andrea Hayes-Jordan, MD Anderson Cancer Center, Houston, TX; David M. Parham, William H. Meyer, University of Oklahoma School of Medicine, Oklahoma City, OK; Douglas S. Hawkins, Seattle Children's Hospital, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA.
authors.forename: William H
authors.initials: WH
authors.lastname: Meyer
authors.affiliation: David O. Walterhouse, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL; Alberto S. Pappo, Saint Jude Children's Research Hospital, Memphis, TN; Jane L. Meza, James R. Anderson, University of Nebraska Medical Center College of Public Health, Omaha, NE; John C. Breneman, Children's Hospital Medical Center, Cincinnati; Timothy P. Cripe, Nationwide Children's Hospital, Columbus, OH; Andrea Hayes-Jordan, MD Anderson Cancer Center, Houston, TX; David M. Parham, William H. Meyer, University of Oklahoma School of Medicine, Oklahoma City, OK; Douglas S. Hawkins, Seattle Children's Hospital, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Hawkins
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D003609:Dactinomycin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D012208:Rhabdomyosarcoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000532:radiotherapy; D015996:Survival Rate; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D003609:Dactinomycin; D014750:Vincristine; D003520:Cyclophosphamide