title: Treatment of children over the age of one year with unresectable localised neuroblastoma without MYCN amplification: results of the SIOPEN study.
abstract: BACKGROUND
  In children older than 1 year with localised unresectable neuroblastoma (NB), treatment strategies are heterogeneous according to the national groups. The objective of this phase III non-randomised study was to evaluate the efficacy of conventional chemotherapy followed by surgery.
  
  
  METHODS
  In the presence of surgical risk factors (SRF), six courses of chemotherapy alternating Carboplatin-Etoposide and Vincristin-Cyclophosphamide-Doxorubicin were given, and surgical resection was attempted after four. Survival analyses were performed using an intention-to-treat approach. The main objective was to achieve a 5-year survival over 80%.
  
  
  RESULTS
  Out of 191 registered children, 160 were evaluable. There were 62.5% older than 18 months and 52.5% had unfavourable histology according to International Neuroblastoma Pathology Classification (INPC). Chemotherapy reduced the number of SRFs by one third. Delayed surgery was attempted in 86.3% of patients and was complete or nearly complete in 74%. The 5-year EFS and OS were 76.4% and 87.6% respectively, with significant better results for patients younger than 18 months or with favourable histology.
  
  
  CONCLUSIONS
  This strategy provides encouraging results in children older than 1 year or 12 months with localised unresectable NB without MYCN amplification. However, in children older than 18 months and with unfavourable histology, additional treatment is recommended.
authors.affiliation: Department of Paediatric Oncology, Southampton General Hospital, Southampton, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Kohler
authors.forename: H
authors.initials: H
authors.lastname: Rubie
authors.forename: V
authors.initials: V
authors.lastname: Castel
authors.forename: K
authors.initials: K
authors.lastname: Beiske
authors.forename: K
authors.initials: K
authors.lastname: Holmes
authors.forename: C
authors.initials: C
authors.lastname: Gambini
authors.forename: F
authors.initials: F
authors.lastname: Casale
authors.forename: C
authors.initials: C
authors.lastname: Munzer
authors.forename: G
authors.initials: G
authors.lastname: Erminio
authors.forename: S
authors.initials: S
authors.lastname: Parodi
authors.forename: S
authors.initials: S
authors.lastname: Navarro
authors.forename: C
authors.initials: C
authors.lastname: Marquez
authors.forename: M
authors.initials: M
authors.lastname: Peuchmaur
authors.forename: C
authors.initials: C
authors.lastname: Cullinane
authors.forename: P
authors.initials: P
authors.lastname: Brock
authors.forename: D
authors.initials: D
authors.lastname: Valteau-Couanet
authors.forename: A
authors.initials: A
authors.lastname: Garaventa
authors.forename: R
authors.initials: R
authors.lastname: Haupt
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007223:Infant; D008297:Male; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D016019:Survival Analysis; D014750:Vincristine / Q000008:administration & dosage
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D016190:Carboplatin
keywords: Children; Conventional chemotherapy; Localised neuroblastoma; Unresectable