title: Significance of clinical and biologic features in Stage 3 neuroblastoma: a report from the International Neuroblastoma Risk Group project.
abstract: BACKGROUND
  International Neuroblastoma Staging System (INSS) Stage 3 neuroblastoma is a heterogeneous disease. Data from the International Neuroblastoma Risk Group (INRG) database were analyzed to define patient and tumor characteristics predictive of outcome.
  
  
  METHODS
  Of 8,800 patients in the INRG database, 1,483 with INSS Stage 3 neuroblastoma and complete follow-up data were analyzed. Secondary analysis was performed in 1,013 patients (68%) with MYCN-non-amplified (NA) tumors. Significant prognostic factors were identified via log-rank test comparisons of survival curves. Multivariable Cox proportional hazards regression model was used to identify factors independently predictive of event-free survival (EFS).
  
  
  RESULTS
  Age at diagnosis (P < 0.0001), tumor MYCN status (P < 0.0001), and poorly differentiating/undifferentiated histology (P = 0.03) were independent predictors of EFS. Compared to other Stage 3 subgroups, outcome was inferior for patients ≥ 547 days with MYCN-NA neuroblastoma (P < 0.0001), and within this cohort, serum ferritin ≥ 96 ng/ml was associated with inferior EFS (P = 0.02). For patients <547 days of age with MYCN-NA tumors, serum ferritin levels were prognostic of overall survival (OS) (P = 0.04) and chromosome 11q aberration was prognostic of EFS (P = 0.03).
  
  
  CONCLUSIONS
  Among patients with INSS Stage 3 neuroblastoma patients, age at diagnosis, MYCN status and histology predict outcome. Patients <547 days of age with MYCN-NA tumors that lack chromosome 11q aberrations or those with serum ferritin <96 ng/ml have excellent prognosis and should be considered for therapy reduction. Prospective clinical trials are needed to identify optimal therapy for those patients ≥ 547 days of age with undifferentiated histology or elevated serum ferritin.
authors.affiliation: Department of Hematology/Oncology, Children's National Medical Center, Washington, District of Columbia.
authors.forename: Holly J
authors.initials: HJ
authors.lastname: Meany
authors.forename: Wendy B
authors.initials: WB
authors.lastname: London
authors.forename: Peter F
authors.initials: PF
authors.lastname: Ambros
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Matthay
authors.forename: Tom
authors.initials: T
authors.lastname: Monclair
authors.forename: Thorsten
authors.initials: T
authors.lastname: Simon
authors.forename: Alberto
authors.initials: A
authors.lastname: Garaventa
authors.forename: Frank
authors.initials: F
authors.lastname: Berthold
authors.forename: Akira
authors.initials: A
authors.lastname: Nakagawara
authors.forename: Susan L
authors.initials: SL
authors.lastname: Cohn
authors.forename: Andrew D J
authors.initials: AD
authors.lastname: Pearson
authors.forename: Julie R
authors.initials: JR
authors.lastname: Park
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D005784:Gene Amplification; D006801:Humans; D007223:Infant; D000071447:N-Myc Proto-Oncogene Protein; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D016016:Proportional Hazards Models
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins
keywords: biologic factor; neuroblastoma; treatment outcome