Chromosome arm 11q deletion predicts for neuroblastoma outcome: A Children's Oncology Group study

Reviewer: Ryan Smith , MD
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Ultima Vez Modificado: 16 de mayo del 2005

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Presenter: E.F. Attiyeh
Presenter's Affiliation: Children's Hospital of Philadelphia, COG
Type of Session: Plenary

Background

  • Neuroblastoma (NB) is the most common malignancy of infants
  • The least amount of treatment required to produce equivalent results is desired with any cancer treatment, yet this is amplified in treating childhood malignancies
  • The treatment of NB is dependent on stratification of patients into different prognostic groups based on known risk factors
  • Chromosome 11q loss of heterozygosity (LOH) is a frequent occurrence in NB and has been associated with high risk disease
  • This study attempted to analyze the prognostic impact of 11q LOH in multivariate analyses after adjusting for currently used prognostic factors

Materials and Methods

  • Tissue from 917 NB patients were screened for chromosome 11q LOH with a panel of microsatellite markers
  • Further mapping with up to 52 markers was performed on selected samples
  • These data were correlated with outcome data from the patients
  • Median follow up was 2.7 years

Results

  • The sample set was representative of the overall neuroblastoma population
  • Chromosome 11q LOH was present in 302 (33%) of patients
  • All but two deletions involved 11q23
  • The majority of 11q LOH tumors did not have n-myc amplification, a known poor prognostic factor
  • Despite this, 11q LOH was associated with high risk disease with 3 year event free survival (EFS) of 50% and overall survival (OS) of 65% compared to EFS of 74% and OS of 83% in those without 11q LOH
  • In multivariate analysis, 11q LOH was an independent prognostic factor

Author's Conclusions

  • Chromosome 11q LOH is an prognostic factor in patients with NB
  • In the future, the presence of 11q LOH will be used as a prognostic factor in COG NB protocols
  • These findings support the presence of molecular mutations as prognostic factors in NB

Clinical/Scientific Implications

In pediatric tumors, while cure is the most important outcome, reduction of toxicity through reduction of therapy is almost equally important.  The data of almost 1,000 patients indicates that chromosome 11q LOH is a useful additional marker.  This is important as it adds to the prognostic information from established risk factors, it is feasible and reproducible, and it provides information about the biology of the disease.  The presence of chromosome 11q LOH will be used in the next COG study, as those with the LOH will continue to receive more aggressive treatment, while those without it will have their therapy reduced.

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