title: Metastatic sites in stage IV and IVS neuroblastoma correlate with age, tumor biology, and survival.
abstract: OBJECTIVE
  The goal of this study was to determine the incidence of metastatic sites in neuroblastoma and the extent to which metastatic sites correlate with age, tumor biology, and survival.
  
  
  METHODS
  All 648 patients with stage IV and IVS neuroblastoma registered on Children's Cancer Group protocols 3881 and 3891 were analyzed. Metastatic site data were provided by treating institutions and reviewed in patients with central nervous system (CNS), intracranial, lung, or "other" metastases.
  
  
  RESULTS
  The incidence of metastatic sites at diagnosis was 70.5% in bone marrow, 55.7% in bone, 30.9% in lymph nodes, 29.6% in liver, 18.2% in intracranial and orbital sites, 3.3% in lung, and 0.6% in CNS. Event-free survival (EFS) was decreased in patients with bone, bone marrow, CNS, intracranial/ orbital, lung, and pleural metastases, and improved in those with liver and skin metastases. In infants, MYCN amplification and unfavorable Shimada histopathology correlated with increased frequencies of bone and intracranial or orbital metastases. In older patients, MYCN amplification correlated with increased frequencies of intracranial or orbital, liver, and lung metastases. Multivariate analysis revealed that metastatic site is not an independent prognostic factor.
  
  
  CONCLUSIONS
  Metastatic pattern in neuroblastoma differs with age and correlates with tumor biological features and EFS. These correlations could reflect changes in host or tumor biological features with age resulting in differences in metastatic capacity or tumor affinity for specific sites.
authors.affiliation: Department of Pediatrics, University of California School of Medicine, San Francisco, USA.
authors.forename: S G
authors.initials: SG
authors.lastname: DuBois
authors.forename: Y
authors.initials: Y
authors.lastname: Kalika
authors.forename: J N
authors.initials: JN
authors.lastname: Lukens
authors.forename: G M
authors.initials: GM
authors.lastname: Brodeur
authors.forename: R C
authors.initials: RC
authors.lastname: Seeger
authors.forename: J B
authors.initials: JB
authors.lastname: Atkinson
authors.forename: G M
authors.initials: GM
authors.lastname: Haase
authors.forename: C T
authors.initials: CT
authors.lastname: Black
authors.forename: C
authors.initials: C
authors.lastname: Perez
authors.forename: H
authors.initials: H
authors.lastname: Shimada
authors.forename: R
authors.initials: R
authors.lastname: Gerbing
authors.forename: D O
authors.initials: DO
authors.lastname: Stram
authors.forename: K K
authors.initials: KK
authors.lastname: Matthay
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000556:secondary*; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D016271:Proto-Oncogene Proteins c-myc