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.

Abstract

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 (>or= 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.

• Authors: 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
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 26 Issue 7 Pg. 1112-8 (Mar 01 2008) ISSN: 1527-7755 [Electronic] United States
• PMID: 18309946 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Human Growth Hormone
• Adrenocorticotropic Hormone
• Thyrotropin

Topics

• Adolescent
• Adrenocorticotropic Hormone (deficiency)
• Adult
• Brain Neoplasms (complications, drug therapy, radiotherapy)
• Child
• Child, Preschool
• Cohort Studies
• Cranial Irradiation
• Female
• Hematopoietic Stem Cells
• Human Growth Hormone (deficiency)
• Humans
• Hypothyroidism (epidemiology, etiology)
• Male
• Neoplasms, Germ Cell and Embryonal (complications, drug therapy, radiotherapy)
• Pituitary Gland (drug effects, radiation effects)
• Prospective Studies
• Risk Factors
• Spinal Cord (radiation effects)
• Thyrotropin (deficiency)