Late effects of conformal radiation therapy for pediatric patients with low-grade glioma: prospective evaluation of cognitive, endocrine, and hearing deficits

Abstract

Purpose: We conducted a prospective trial to evaluate late effects in pediatric patients with low-grade glioma (LGG) treated with conformal radiation therapy (CRT).

Patients and methods: Between August 1997 and August 2006, 78 pediatric patients with LGG (mean age, 9.7 years; standard deviation, +/-4.4 years) received 54 Gy of CRT with a 10-mm clinical target volume margin. Tumor locations were diencephalon (n = 58), cerebral hemisphere (n = 3), and cerebellum (n = 17). Baseline and serial evaluations were performed to identify deficits in cognition, endocrine function, and hearing. Deficits were correlated with clinical factors and radiation dose within specific normal tissue volumes.

Results: Cognitive effects of CRT through 5 years after CRT correlated with patient age, neurofibromatosis type 1 status, tumor location and volume, extent of resection, and radiation dose. The effect of age exceeded that of radiation dose; patients younger than 5 years experienced the greatest decline in cognition. Before CRT, growth hormone (GH) secretion abnormality was diagnosed in 24% of tested patients, and 12% had precocious puberty. The 10-year cumulative incidence of GH replacement was 48.9%; of thyroid hormone replacement, 64.0%; of glucocorticoid replacement, 19.2%; and of gonadotropin-releasing hormone analog therapy, 34.2%. The mean +/- standard errors of the cumulative incidence of hearing loss at 10 years did not exceed 5.7% +/- 3.3% at any frequency.

Conclusion: To our knowledge, this is the largest series of prospectively followed children with LGG to undergo irradiation. Adverse effects are limited and predictable for most patients; however, this study provides additional evidence that CRT should be delayed for young patients and identifies the potential benefits of reducing radiation dose to normal brain.

Fig 1.

Modeled intelligence quotient (IQ) scores after conformal radiation therapy (CRT) by age for pediatric low-grade glioma. Age is measured in years, and time is measured in months after the start of CRT.

Fig 2.

Modeled intelligence quotient (IQ) scores after conformal radiation therapy (CRT) by age and supratentorial brain dose-volume intervals for pediatric low-grade glioma. Age is measured in years, and time is measured in months after CRT. The dose-volume intervals V_0-30Gy and V_30-60Gy represent the percent volume of the supratentorial brain that received dose within the specified interval.

Fig 3.

CI of hormone replacement therapy and therapy for precocious puberty after conformal radiation therapy (CRT) for pediatric low-grade glioma. CI, cumulative incidence; GnRH, gonadotropin-releasing hormone; DDAVP, desmopressin acetate.

Fig A1.

Modeled intelligence quotient (IQ) scores after conformal radiation therapy (CRT) by age and infratentorial brain dose-volume intervals for pediatric low-grade glioma. Age is measured in years, and time is measured in months after CRT. The dose-volume intervals V_0-30Gy and V_30-60Gy represent the percent volume of the infratentorial brain that received a dose within the specified interval. CBCL, Child Behavior Checklist.