Age as a continuous variable in predicting outcome for neuroblastoma patients with metastatic disease: Impact of tumor biological features

Reviewer: Ryan Smith, MD
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Last Modified: June 2, 2003

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Presenter: R. George
Presenter's Affiliation: COG
Type of Session: Scientific

Background

  • Infants (age 0-12 months) with stage D disease, with single copy n-myc and hyperdiploidy tumors have an excellent prognosis (84% 4 yr EFS vs. 46% 4 year EFS in infants with diploid (i.e. non-hyperdiploid tumors)
  • Older children (>2 years) with metastatic disease have a poor prognosis (<30% EFS), regardless of DNA index or n-myc status
  • Patients between 1-2 years old are classically thought to have an intermediate prognosis
  • This study was performed to determine if n-myc copy number and DNA index (diploid or hyperdiploid status) could be used to identify a subset of children 12-24 months old who have a better survival

Materials and Methods

  • Patients studied were from POG 9047, which was a biologic study investigating n-myc status and DNA index in patients with NBL
  • 1667 patients were enrolled, with 538 patients identified with Stage D disease
  • Most patients were enrolled in POG 9243, which treated patients who were >12 months old with aggressive platinum and alkylating based chemotherapy. Many of these patients underwent bone marrow transplant
  • Those patients, age 12-24 months with single copy n-myc, were evaluated based on their DNA index status to determine, if by subset analysis, subgroups could be identified who had superior prognosis disease

Results

  • Patients age 12-24 months with single copy n-myc status and stage D disease had variable outcomes based on their DNA index. Patients with hyperploidy tumors (DNA index >1) had a 73% 4 year EFS compared to those with diploid disease (DNA index <=1) who had a 27% 4 year EFS (p=.0092)
  • Subgroup analysis was performed: -12-18 month old patients with DNA index >1 had a 93% 4 year EFS -12-18 month old patients with DNA index <=1 had a 67% 4 year EFS -18-24 month old patients with DNA index >1 had a 37.5% 4 year EFS -18-24 month old patients with a DNA index <=1 had a 11.1% 4 year EFS

Author's Conclusions

  • In patients with Stage D, single copy of n-myc disease, patients with hyperdiploid tumors had a better prognosis
  • Patients 12-18 months old with hyperdiploid, single copy n-myc disease have very favorable disease if treated with dose intensive therapy
  • These patients could be treated with less intensive chemotherapy (similar to patients <12 months old)

Clinical/Scientific Implications

    Advancements in NBL therapy have come from enrolling patients in multi-institutional trials. For this reason, protocols have stipulated (rightly so) that strict age cut-offs between treatment groups are maintained. In recent trials, this cut-off has been at 12 months, with the feeling that patients greater than 12 months have a poorer prognosis. This study and Abstract #3214 at ASCO 2003 show similar results: That patients who are 12-18 months with hyperdiploid tumors show superior survivals, with similar outcomes to younger patients. Therefore, perhaps these patients should be treated on protocol similar to infants. These data should be used cautiously, however. Like most pediatric oncology studies, there are small numbers of patients in each group when subset analysis is done. In addition, this is a very select group of patients (12-18 months old, hyperdiploid, and (in this study) single copy n-myc--in Abstract 3214 it was regardless of n-myc status). Also, in terms of clinical outcome, age is a continuous variable, not with strict cut-off points as described. These cut-offs are required for protocol. In terms of treating patients as per the new CCG protocol, it was advised at the meeting that, if a patient qualifies for the subset described in this study, the study chairman should be contacted for advisement on how to proceed with treatment.

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