title: Neuroblastoma in older children, adolescents and young adults: a report from the International Neuroblastoma Risk Group project.
abstract: BACKGROUND
  Neuroblastoma in older children and adolescents has a distinctive, indolent phenotype, but little is known about the clinical and biological characteristics that distinguish this rare subgroup. Our goal was to determine if an optimal age cut-off exists that defines indolent disease and if accepted prognostic factors and treatment approaches are applicable to older children.
  
  
  METHODS
  Using data from the International Neuroblastoma Risk Group, among patients ≥18 months old (n = 4,027), monthly age cut-offs were tested to determine the effect of age on survival. The prognostic effect of baseline characteristics and autologous hematopoietic cell transplant (AHCT) for advanced disease was assessed within two age cohorts; ≥5 to <10 years (n = 730) and ≥10 years (n = 200).
  
  
  RESULTS
  Older age was prognostic of poor survival, with outcome gradually worsening with increasing age at diagnosis, without statistical evidence for an optimal age cut-off beyond 18 months. Among patients ≥5 years, factors significantly prognostic of lower event-free survival (EFS) and overall survival (OS) in multivariable analyses were INSS stage 4, MYCN amplification and unfavorable INPC histology classification. Among stage 4 patients, AHCT provided a significant EFS and OS benefit. Following relapse, patients in both older cohorts had prolonged OS compared to those ≥18 months to <5 years (P < 0.0001).
  
  
  CONCLUSIONS
  Despite indolent disease and infrequent MYCN amplification, older children with advanced disease have poor survival, without evidence for a specific age cut-off. Our data suggest that AHCT may provide a survival benefit in older children with advanced disease. Novel therapeutic approaches are required to more effectively treat these patients.
authors.affiliation: Division of Oncology, Children's Hospital of Philadelphia and Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Yaël P
authors.initials: YP
authors.lastname: Mossé
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Deyell
authors.forename: Frank
authors.initials: F
authors.lastname: Berthold
authors.forename: Akira
authors.initials: A
authors.lastname: Nagakawara
authors.forename: Peter F
authors.initials: PF
authors.lastname: Ambros
authors.forename: Tom
authors.initials: T
authors.lastname: Monclair
authors.forename: Susan L
authors.initials: SL
authors.lastname: Cohn
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Pearson
authors.forename: Wendy B
authors.initials: WB
authors.lastname: London
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Matthay
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001859:Bone Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D017353:Gene Deletion; D006801:Humans; D007223:Infant; D007390:International Agencies; D008297:Male; D000071447:N-Myc Proto-Oncogene Protein; D060787:Neoplasm Grading; D009447:Neuroblastoma / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins
keywords: adolescents; autologous hematopoietic cell transplant; neuroblastoma; young adults