title: Biologic factors determine prognosis in infants with stage IV neuroblastoma: A prospective Children's Cancer Group study.
abstract: OBJECTIVE
  A prospective Children's Cancer Group study, CCG-3881, has been completed to determine if a more accurate prediction of prognosis by biologic features can identify subgroups of infants with stage IV neuroblastoma (NBL) who require differing intensities of treatment.
  
  
  METHODS
  One hundred thirty-four infants were registered from June 1989 to August 1995, with a median follow-up of 47.1 months (range, 0 to 88 months). The biologic factors examined were tumor MYCN copy number, Shimada histopathologic classification, serum ferritin, and bone marrow immunocytology (sensitivity, one tumor cell per 10(5) bone marrow cells). Patients treated on CCG-3881 (n = 116) received four-drug chemotherapy for 9 months (cisplatin, cyclophosphamide, doxorubicin, and etoposide), with surgery and local radiation to residual disease. After January 1991, all subsequent infants with tumor MYCN amplification (n = 18) were transferred after one cycle of therapy to the high-risk CCG-3891 protocol (open January 1991 to April 1996) for more intensive treatment.
  
  
  RESULTS
  The 3-year event-free survival (EFS) and overall survival (mean +/- SD) for the 134 infants were 63% +/- 5% and 71% +/- 5%, respectively. Patients whose tumors were without MYCN amplification had a 93% +/- 4% 3-year EFS, whereas those with amplified MYCN had a 10% +/- 7% 3-year EFS (P <. 0001). Each of the other biologic features studied had prognostic significance in univariate analysis but not after stratifying by MYCN copy number.
  
  
  CONCLUSIONS
  Infants less than 1 year of age at diagnosis with stage IV NBL have a much improved outcome compared with children >/= 1 year of age. Nonamplified MYCN tumors identify a group of infants with a 93% +/- 4% EFS, whereas amplified MYCN copy number clearly identifies patients who are unlikely to survive despite intensive chemotherapy.
authors.affiliation: Department of Pediatrics, University of Illinois at Chicago College of Medicine, Chicago, IL, USA. mls3@uic.edu
authors.forename: M L
authors.initials: ML
authors.lastname: Schmidt
authors.forename: J N
authors.initials: JN
authors.lastname: Lukens
authors.forename: R C
authors.initials: RC
authors.lastname: Seeger
authors.forename: G M
authors.initials: GM
authors.lastname: Brodeur
authors.forename: H
authors.initials: H
authors.lastname: Shimada
authors.forename: R B
authors.initials: RB
authors.lastname: Gerbing
authors.forename: D O
authors.initials: DO
authors.lastname: Stram
authors.forename: C
authors.initials: C
authors.lastname: Perez
authors.forename: G M
authors.initials: GM
authors.lastname: Haase
authors.forename: K K
authors.initials: KK
authors.lastname: Matthay
mesh_terms: D001685:Biological Factors / Q000378:metabolism*; D001853:Bone Marrow / Q000473:pathology; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D005293:Ferritins / Q000097:blood; D006801:Humans; D007223:Infant; D008297:Male; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*
chemical_list: D001685:Biological Factors; D016271:Proto-Oncogene Proteins c-myc; D005293:Ferritins