Originally published as JCO Early Release 10.1200/JCO.2008.21.2738 on July 6 2009

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Late Effects of Conformal Radiation Therapy for Pediatric Patients With Low-Grade Glioma: Prospective Evaluation of Cognitive, Endocrine, and Hearing Deficits

From the Departments of Radiological Sciences, Behavioral Medicine, Biostatistics, and Endocrinology, St Jude Children's Research Hospital, Memphis, TN; and Division of Pediatric Endocrinology, University of California, San Francisco, CA.

Corresponding author: Thomas E. Merchant, DO, PhD, Department of Radiological Sciences, Mail Stop 220, St Jude Children's Research Hospital, 262 Danny Thomas Pl, Memphis, TN 38105-3678; e-mail: thomas.merchant{at}stjude.org.

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.

Supported in part by the National Cancer Institute, Cancer Center Support Grant No. 5 P30 CA21765-28, by the American Cancer Society, and by the American Lebanese Syrian Associated Charities.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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				T. E. Merchant, L. E. Kun, S. Wu, X. Xiong, R. A. Sanford, and F. A. Boop Phase II Trial of Conformal Radiation Therapy for Pediatric Low-Grade Glioma J. Clin. Oncol., August 1, 2009; 27(22): 3598 - 3604. [Abstract] [Full Text] [PDF]