title: Hyperdiploidy plus nonamplified MYCN confers a favorable prognosis in children 12 to 18 months old with disseminated neuroblastoma: a Pediatric Oncology Group study.
abstract: OBJECTIVE
  To determine predictive strength of tumor cell ploidy and MYCN gene amplification on survival of children older than 12 months with disseminated neuroblastoma (NB).
  
  
  METHODS
  Of 648 children with stage D NB enrolled onto the Pediatric Oncology Group NB Biology Study 9047 (1990-2000), 560 children were assessable for ploidy and MYCN amplification. Treatment of patients older than 12 months varied; most receiving high-dose chemotherapy with stem-cell rescue. Infants received standard chemotherapy, depending on MYCN status and ploidy.
  
  
  RESULTS
  Among stage D MYCN-amplified patients, 4-year event-free survival (EFS) +/- SE had no prognostic significance for tumor cell ploidy for patients either younger than 12 months or > or = 12 months old. However, among stage D nonamplified-MYCN patients, 4-year EFS for those with tumor hyperdiploidy (DNA index [DI] > 1) was clearly superior to those with diploidy (DI < or = 1): younger than 12 months, 83.7% +/- 4.4% (n = 87) versus 46.2% +/- 13.8% (n = 13; P = .0003); and for 12- to 24-month-old children, 72.7% +/- 10.2% (n = 22) versus 26.7% +/- 13.2% (n = 16; P = .0092). Further analysis suggested better prognoses in the 12- to 18-month-old subgroup with hyperdiploid tumors (4-year EFS, 92.9% +/- 7.2%) compared with the 19- to 24-month-old subgroup (4-year EFS, 37.5% +/- 21.0%; P = .0037). In children older than 24 months, outcome was dire (< 20% long-term survival), regardless of ploidy or MYCN status.
  
  
  CONCLUSIONS
  Children 12 to 18 months old with metastatic NB had favorable outcomes with high-dose therapy if their tumors were hyperdiploid and lacked MYCN amplification. This subgroup may respond well to contemporary chemotherapy, and could be spared intensive myeloablative therapy with stem-cell rescue.
authors.affiliation: Department of Pediatric Hematology and Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. rani_george@dfci.harvard.edu
authors.forename: Rani E
authors.initials: RE
authors.lastname: George
authors.forename: Wendy B
authors.initials: WB
authors.lastname: London
authors.forename: Susan L
authors.initials: SL
authors.lastname: Cohn
authors.forename: John M
authors.initials: JM
authors.lastname: Maris
authors.forename: Cynthia
authors.initials: C
authors.lastname: Kretschmar
authors.forename: Lisa
authors.initials: L
authors.lastname: Diller
authors.forename: Garrett M
authors.initials: GM
authors.lastname: Brodeur
authors.forename: Robert P
authors.initials: RP
authors.lastname: Castleberry
authors.forename: A Thomas
authors.initials: AT
authors.lastname: Look
mesh_terms: D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002675:Child, Preschool; D004171:Diploidy; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D018570:Risk Assessment; D033581:Stem Cell Transplantation; D016019:Survival Analysis
chemical_list: D005819:Genetic Markers; D016271:Proto-Oncogene Proteins c-myc