title: Histology, Fusion Status, and Outcome in Alveolar Rhabdomyosarcoma With Low-Risk Clinical Features: A Report From the Children's Oncology Group.
abstract: BACKGROUND
  Distinguishing alveolar rhabdomyosarcoma (ARMS) from embryonal rhabdomyosarcoma (ERMS) is of prognostic and therapeutic importance. Criteria for classifying these entities evolved significantly from 1995 to 2013. ARMS is associated with inferior outcome; therefore, patients with alveolar histology have generally been excluded from low-risk therapy. However, patients with ARMS and low-risk stage and group (Stage 1, Group I/II/orbit III; or Stage 2/3, Group I/II) were eligible for the Children's Oncology Group (COG) low-risk rhabdomyosarcoma (RMS) study D9602 from 1997 to 1999. The characteristics and outcomes of these patients have not been previously reported, and the histology of these cases has not been reviewed using current criteria.
  
  
  METHODS
  We re-reviewed cases that were classified as ARMS on D9602 using current histologic criteria, determined PAX3/PAX7-FOXO1 fusion status, and compared these data with outcome for this unique group of patients.
  
  
  RESULTS
  Thirty-eight patients with ARMS were enrolled onto D9602. Only one-third of cases with slides available for re-review (11/33) remained classified as ARMS by current histologic criteria. Most cases were reclassified as ERMS (17/33, 51.5%). Cases that remained classified as ARMS were typically fusion-positive (8/11, 73%), therefore current classification results in a similar rate of fusion-positive ARMS for all clinical risk groups. In conjunction with data from COG intermediate-risk treatment protocol D9803, our data demonstrate excellent outcomes for fusion-negative ARMS with otherwise low-risk clinical features.
  
  
  CONCLUSIONS
  Patients with fusion-positive RMS with low-risk clinical features should be classified and treated as intermediate risk, while patients with fusion-negative ARMS could be appropriately treated with reduced intensity therapy.
authors.affiliation: Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, Ohio.|Department of Pathology, The Ohio State University College of Medicine, Columbus, Ohio.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Arnold
authors.affiliation: Frontier Science and Technology Research Foundation, Madison, Wisconsin.
authors.forename: James R
authors.initials: JR
authors.lastname: Anderson
authors.affiliation: Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, Ohio.|Department of Pathology, The Ohio State University College of Medicine, Columbus, Ohio.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Gastier-Foster
authors.affiliation: Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland.
authors.forename: Frederic G
authors.initials: FG
authors.lastname: Barr
authors.affiliation: Department of Hematology and Oncology, UT Southwestern Medical Center, Dallas, Texas.
authors.forename: Stephen X
authors.initials: SX
authors.lastname: Skapek
authors.affiliation: Department of Pediatrics, Seattle Children's Hospital, Seattle, Washington.|Clinical Research Division, Fred Hutchinson Cancer Research Center and University of Washington, Seattle, Washington.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Hawkins
authors.affiliation: Children's Cancer Hospital and Division of Pediatrics, UT MD Anderson Cancer Center, Houston, Texas.
authors.forename: R Beverly
authors.initials: RB
authors.lastname: Raney
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: Department of Pathology, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Teot
authors.affiliation: Department of Laboratories, Seattle Children's Hospital, Seattle, Washington.
authors.forename: Erin R
authors.initials: ER
authors.lastname: Rudzinski
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
mesh_terms: D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D051761:Paired Box Transcription Factors / Q000235:genetics; D018232:Rhabdomyosarcoma, Alveolar / Q000145:classification* / Q000235:genetics* / Q000473:pathology*; D018233:Rhabdomyosarcoma, Embryonal / Q000145:classification / Q000235:genetics / Q000473:pathology
chemical_list: D015514:Oncogene Proteins, Fusion; C471563:PAX3-FOXO1A fusion protein, human; C000603228:PAX7-FOXO1A fusion protein, human; D051761:Paired Box Transcription Factors
keywords: D9602; D9803; alveolar rhabdomyosarcoma; embryonal rhabdomyosarcoma; fusion status; histology; low risk; outcomes; rhabdomyosarcoma