Outcome of children with centrally reviewed low-grade gliomas treated with chemotherapy with or without radiotherapy on Children's Cancer Group high-grade glioma study CCG-945

Cancer. 2003 Sep 15;98(6):1243-52. doi: 10.1002/cncr.11637.

Abstract

Background: The objectives of the current study were to determine the outcome of children who were treated with chemotherapy and radiotherapy on the Children's Cancer Group (CCG) high-grade glioma protocol (CCG-945) who were diagnosed with low-grade gliomas on post hoc central pathologic review and to identify clinical and biologic features associated with prognosis.

Methods: Between 1985 and 1991, 250 children with institutionally classified high-grade gliomas were enrolled on CCG-945. Patients older than 24 months with intracranial lesions were assigned randomly to receive either lomustine, vincristine, and prednisone (control regimen) or the 8-drugs-in-1-day regimen (experimental regimen); younger patients and those with primary spinal cord tumors were assigned nonrandomly to the experimental regimen. Central independent review by 5 neuropathologists led to a reclassification of low-grade glioma in 70 patients, who were the focus of the current study.

Results: The study involved 42 males and 28 females (median age, 7.7 years) with a median follow-up of 10.4 years. At 5 years, the progression-free survival (PFS) rate was 63% +/- 6%, and the overall survival (OS) rate was 79% +/- 5%, compared with a PFS rate of 19% +/- 3% (P < 0.0001) and an OS rate of 22% +/- 3% (P < 0.0001) in the remainder of the cohort. Significantly poorer 5-year PFS was seen in children younger than 24 months, those with fibrillary astrocytoma, and those with posterior fossa tumors. Patients demonstrated a modest improvement in PFS but no improvement in OS compared with children with low-grade gliomas who were treated with contemporary chemotherapy-alone approaches.

Conclusions: The current report calls attention to the importance of central pathologic review in large multiinstitutional trials of children with gliomas and suggests that aggressive front-line combined chemoradiotherapy does not confer a survival advantage in this highly selected population of patients.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Brain Neoplasms / radiotherapy
  • Brain Neoplasms / therapy*
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Female
  • Follow-Up Studies
  • Glioma / drug therapy
  • Glioma / pathology
  • Glioma / radiotherapy
  • Glioma / therapy*
  • Humans
  • Infant
  • Infant, Newborn
  • Lomustine / administration & dosage
  • Male
  • Prednisolone / administration & dosage
  • Prognosis
  • Treatment Outcome
  • Vincristine / administration & dosage

Substances

  • Vincristine
  • Lomustine
  • Prednisolone