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Endocrine Outcomes for Children With Embryonal Brain Tumors After Risk-Adapted Craniospinal and Conformal Primary-Site Irradiation and High-Dose Chemotherapy With Stem-Cell Rescue on the SJMB-96 Trial

Stephen J. Laughton, Thomas E. Merchant, Charles A. Sklar, Larry E. Kun, Maryam Fouladi, Alberto Broniscer, E. Brannon Morris, Robert P. Sanders, Matthew J. Krasin, John Shelso, Zang Xiong, Dana Wallace, Amar Gajjar

From the Division of Neuro-Oncology, Department of Oncology, Division of Radiation Oncology, Department of Radiological Sciences, Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY; and Division of Endocrinology, Department of Biostatistics, St Jude Children's Research Hospital, Memphis, TN

Corresponding author: Amar Gajjar, MD, Division of Neuro-Oncology, Department of Oncology, St Jude Children's Research Hospital, 332 North Lauderdale St, Memphis, TN 38105; e-mail: amar.gajjar{at}stjude.org

Purpose To estimate the cumulative incidence of specific hormone deficiencies and the influence of hypothalamic-pituitary (HP) axis radiation dose in a cohort of children with embryonal brain tumors treated with risk-adapted craniospinal irradiation (CSI), conformal primary site irradiation, and high-dose chemotherapy.

Patients and Methods Clinical data and HP axis radiation dosimetry data were obtained from 88 eligible children. All patients received regular endocrine follow-up that included screening tests of thyroid function and stimulation testing for growth hormone deficiency (GHD), and adrenocorticotropin hormone deficiency.

Results The cumulative incidence of GHD, thyroid-stimulating hormone (TSH) deficiency, adrenocorticotropic hormone deficiency, and primary hypothyroidism at 4 years from diagnosis was 93% ± 4%, 23% ± 8%, 38% ± 6%, and 65% ± 7%, respectively. Radiation dosimetry to the HP axis was associated only with the development of TSH deficiency; the 4-year cumulative incidence was 44% ± 19% and 11% ± 8% (P = .014) for those receiving more or less than the median dose to the hypothalamus ( 42 v < 42 Gy), respectively. The median dose of CSI for the average-risk (AR) patients was 23.4 and 39.6 Gy (36 to 40.5 Gy) for the high-risk patients. The estimated mean decline in height Z-score after radiation therapy was greater in high-risk patients (–0.65 units/yr) when compared with AR patients (–0.54 units/yr; P = .039).

Conclusion Pediatric patients with CNS embryonal tumors are at high risk for treatment-related hormone deficiencies. GHD and primary hypothyroidism were diagnosed in a majority of subjects relatively soon after the completion of therapy. Radiation dose to the hypothalamus in excess of 42 Gy was associated with an increase in the risk of developing TSH deficiency.

Supported by the Cancer Center (CORE) support Grant No. CA 21765 from the National Institutes of Health, Musicians Against Childhood Cancer (MACC), the Noyes Brain Tumor Foundation, and the American Lebanese Syrian Associated Charities (ALSAC).

Presented in part at the 12th International Symposium on Pediatric Neuro-Oncology, June 6-9, 2006, Nara, Japan, and at the 40th Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL.

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

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