title: Prognostic value of the stage 4S metastatic pattern and tumor biology in patients with metastatic neuroblastoma diagnosed between birth and 18 months of age.
abstract: OBJECTIVE
  Patients with neuroblastoma younger than 12 months of age with a 4S pattern of disease (metastases limited to liver, skin, bone marrow) have better outcomes than infants with stage 4 disease. The new International Neuroblastoma Risk Group (INRG) staging system extends age to 18 months for the 4S pattern. Our aim was to determine which prognostic features could be used for optimal risk classification among patients younger than 18 months with metastatic disease.
  
  
  METHODS
  Event-free survival (EFS) and overall survival were analyzed by log-rank tests, Cox models, and survival tree regression for 656 infants with stage 4S neuroblastoma younger than 12 months of age and 1,019 patients with stage 4 disease younger than 18 months of age in the INRG database.
  
  
  RESULTS
  Unfavorable biologic features were more frequent in infants with stage 4 disease than in infants with 4S tumors and higher overall in those age 12 to 18 months (although not different for stage 4 v 4S pattern). EFS was significantly better for infants younger than 12 months with 4S pattern than with stage 4 disease (P < .01) but similar for toddlers age 12 to 18 months with stage 4 versus 4S pattern. Among 717 patients with stage 4S pattern, patients age 12 to 18 months had worse EFS than those age younger than 12 months (P < .01). MYCN, 11q, mitosis-karyorrhexis index (MKI), ploidy, and lactate dehydrogenase were independently statistically significant predictors of EFS and more highly predictive than age or metastatic pattern. MYCN, 11q, MKI, histology, and 1p were combined in a survival tree for improved risk stratification.
  
  
  CONCLUSIONS
  Tumor biology is more critical than age or metastatic pattern for prognosis of patients age younger than 18 months with metastatic neuroblastoma and should be considered for risk stratification.
authors.affiliation: UCSF School of Medicine and Benioff Children’s Hospital, San Francisco, CA 94143-0106, USA.
authors.forename: Denah R
authors.initials: DR
authors.lastname: Taggart
authors.forename: Wendy B
authors.initials: WB
authors.lastname: London
authors.forename: Mary Lou
authors.initials: ML
authors.lastname: Schmidt
authors.forename: Steven G
authors.initials: SG
authors.lastname: DuBois
authors.forename: Tom F
authors.initials: TF
authors.lastname: Monclair
authors.forename: Akira
authors.initials: A
authors.lastname: Nakagawara
authors.forename: Bruno
authors.initials: B
authors.lastname: De Bernardi
authors.forename: Peter F
authors.initials: PF
authors.lastname: Ambros
authors.forename: Andrew D J
authors.initials: AD
authors.lastname: Pearson
authors.forename: Susan L
authors.initials: SL
authors.lastname: Cohn
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Matthay
mesh_terms: D000367:Age Factors; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015999:Multivariate Analysis; D000071447:N-Myc Proto-Oncogene Protein; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000401:mortality / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D011379:Prognosis
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins