title: Reduction of cyclophosphamide dose for patients with subset 2 low-risk rhabdomyosarcoma is associated with an increased risk of recurrence: A report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group.
abstract: BACKGROUND
  Failure-free survival (FFS) and overall survival (OS) rates were found to improve on Intergroup Rhabdomyosarcoma Study (IRS) IV (IRS-IV) compared with IRS-III for patients with subset 2 (IRS stage 1, group III nonorbit or stage 3, group I/II) low-risk embryonal rhabdomyosarcoma with the addition of cyclophosphamide (total cumulative cyclophosphamide dose of 26.4 g/m2) to the combination of vincristine and dactinomycin (VAC). The goal of Children's Oncology Group ARST0331 for subset 2 low-risk patients was to reduce the total cumulative cyclophosphamide dose without compromising FFS.
  
  
  METHODS
  Therapy included 4 cycles of VAC (total cumulative cyclophosphamide dose of 4.8 g/m2) followed by 12 cycles of vincristine and dactinomycin over 46 weeks. Patients with group II or III tumors received radiotherapy, except for girls with group III vaginal tumors who enrolled before September 2009 and achieved a complete response with chemotherapy with or without delayed surgical resection.
  
  
  RESULTS
  Among 66 eligible patients who were followed for a median of 3.5 years, there were 20 failures versus 10.53 expected failures. The estimated 3-year FFS and OS rates were 70% (95% confidence interval [95% CI], 57%-80%) and 92% (95% CI, 83%-97%), respectively. The estimated 3-year FFS rate was 57% (95% CI, 33%-75%) for girls with subset 2 genital tract embryonal rhabdomyosarcoma (21 patients) and 77% (95% CI, 61%-87%) for all other subset 2 patients (45 patients) (P = .02).
  
  
  CONCLUSIONS
  The authors observed suboptimal FFS among patients with subset 2 low-risk rhabdomyosarcoma using reduced total cyclophosphamide. Eliminating radiotherapy for girls with group III vaginal tumors in combination with reduced total cyclophosphamide appeared to contribute to the suboptimal outcome. Cancer 2017;123:2368-2375. © 2017 American Cancer Society.
authors.affiliation: Division of Hematology, Oncology and Stem Cell Transplantation, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: David O
authors.initials: DO
authors.lastname: Walterhouse
authors.affiliation: Division of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Alberto S
authors.initials: AS
authors.lastname: Pappo
authors.affiliation: Department of Biostatistics, University of Nebraska Medical Center College of Public Health, Omaha, Nebraska.
authors.forename: Jane L
authors.initials: JL
authors.lastname: Meza
authors.affiliation: Division of Radiation Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: John C
authors.initials: JC
authors.lastname: Breneman
authors.affiliation: Division of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hayes-Jordan
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: David M
authors.initials: DM
authors.lastname: Parham
authors.affiliation: Division of Hematology/Oncology/Blood and Marrow Transplantation, Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Cripe
authors.affiliation: Oncology Clinical Research, Merck Research Laboratories, North Wales, Pennsylvania.
authors.forename: James R
authors.initials: JR
authors.lastname: Anderson
authors.affiliation: Jimmy Everest Section of Pediatric Hematology and Oncology, University of Oklahoma School of Medicine, Oklahoma City, Oklahoma.
authors.forename: William H
authors.initials: WH
authors.lastname: Meyer
authors.affiliation: Division of Hematology/Oncology, Seattle Children's Hospital, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Hawkins
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D001661:Biliary Tract Neoplasms / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D003609:Dactinomycin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology*; D018714:Radiotherapy, Adjuvant; D012208:Rhabdomyosarcoma / Q000188:drug therapy; D018233:Rhabdomyosarcoma, Embryonal / Q000188:drug therapy*; D014625:Vaginal Neoplasms / Q000188:drug therapy*; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D003609:Dactinomycin; D014750:Vincristine; D003520:Cyclophosphamide
keywords: chemotherapy; cyclophosphamide; female genital tract; radiotherapy; rhabdomyosarcoma