Results from a phase II trial of conformal radiation therapy (CRT)for pediatric patients with localized ependymoma and quantification of radiation-related CNS effects

Reviewer: Walter Sall, MD
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Last Modified: June 2, 2003

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Presenter: T.E. Merchant
Presenter's Affiliation: St. Jude Children's Research Hospital
Type of Session: Scientific

Background

  • Radiation therapy (RT) following maximal resection is the standard treatment for localized ependymoma in children.
  • In very young children, avoiding or delaying RT with systemic chemotherapy has been justified by the significant CNS toxicity associated with irradiation of large fields.
  • This study intended to determine if the irradiated volume can be reduced without affecting the failure rate in pediatric ependymoma patients.
  • A seconday goal was to carefully evaluate patients pre and post-therapy for CNS morbidity.

Materials and Methods

  • Phase II enrollment trial.
  • between 1997 and 2002, 88 children with localized ependymoma were treated with CRT at St. Jude's Children's Research Hospital. Median age 2.8 years.
  • Eligible patients were 12 months to 21 years old. Prior chemotherapy was allowed. No time interval from surgery to radiation was specified.
  • Treatment volume respected anatomic boundaries and included the resection cavity and any residual tumor with a 10mm margin.
  • Dose = 59.4 Gy, or 54 Gy for age < 18 months and GTR (n=14). Spinal cord tolerance was 54 Gy, optic chiasm tolerance was 55.8 Gy.
  • Careful IQ, endocrine and audiometric testing was performed both pre and post-RT.

Results

  • Patients were stratified by extent of resection(GTR rate >90%), prior chemotherapy, grade and location.
  • With median follow-up of 30 months, 3 year actuarial EFS and local control were 80.6% and 89.5% respectively.
  • 31 failures occurred, 3 local, 3 local and distant, and 7 distant only.
  • No change in IQ occurred with testing out to 48 months from RT. Hearing loss was observed only in patients receiving prior chemotherapy. Pre-CRT endocrinopathy was seen in 50%. Only 5 additional children required hormone replacement following CRT.
  • Negative prognostic factors included: sub-total resection, anaplastic histology and delivery of pre-RT chemotherapy.

Author's Conclusions

  • Radiation volume may be safely reduced without worsening local control.
  • With improved local control, distant failure is becoming a more significant problem. Historically, local failure was predominant.
  • Side effects at 4 years were minimal with no detectable IQ change. A high risk of pre-CRT endocrinopathy was noted.
  • The very high local control rate in this study is likely due to: the high rate of GTR, high RT dose and high tolerance doses for the chiasm and spinal cord.

Clinical/Scientific Implications

    This trial provides very encouraging results for the treatment of ependymoma. The local control rate is significantly higher than historical data with a very low incidence of side effects. It is unclear if these results can be translated to other centers where resection might be less aggressive and experience with CRT is less. The excellent results in this trial appear to extend to very young patients. Longer follow-up is needed to evaluate late toxicity in this study. Continued examination of dose/volume issues in ependymoma is currently underway in the ACNS0121 study.

Oncolink's ASCO Coverage made possible by an unrestricted Educational Grant from Bristol-Myers Squibb Oncology.


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