Treatment of children over the age of one year with unresectable localised neuroblastoma without MYCN amplification: results of the SIOPEN study

Eur J Cancer. 2013 Nov;49(17):3671-9. doi: 10.1016/j.ejca.2013.07.002. Epub 2013 Jul 29.

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.

Patients and 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.

Conclusion: 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.

Keywords: Children; Conventional chemotherapy; Localised neuroblastoma; Unresectable.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Cyclophosphamide / administration & dosage
  • Doxorubicin / administration & dosage
  • Etoposide / administration & dosage
  • Female
  • Gene Amplification*
  • Humans
  • Infant
  • Male
  • N-Myc Proto-Oncogene Protein
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / genetics
  • Neuroblastoma / mortality
  • Nuclear Proteins / genetics*
  • Oncogene Proteins / genetics*
  • Survival Analysis
  • Vincristine / administration & dosage

Substances

  • MYCN protein, human
  • N-Myc Proto-Oncogene Protein
  • Nuclear Proteins
  • Oncogene Proteins
  • Vincristine
  • Etoposide
  • Doxorubicin
  • Cyclophosphamide
  • Carboplatin