TY - JOUR
T1 - 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
AU - Laughton, Stephen J.
AU - Merchant, Thomas E.
AU - Sklar, Charles A.
AU - Kun, Larry E.
AU - Fouladi, Maryam
AU - Broniscer, Alberto
AU - Morris, E. Brannon
AU - Sanders, Robert P.
AU - Krasin, Matthew J.
AU - Shelso, John
AU - Xiong, Zang
AU - Wallace, Dana
AU - Gajjar, Amar
PY - 2008/3/1
Y1 - 2008/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=41949088635&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=41949088635&partnerID=8YFLogxK
U2 - 10.1200/JCO.2008.13.5293
DO - 10.1200/JCO.2008.13.5293
M3 - Article
C2 - 18309946
AN - SCOPUS:41949088635
SN - 0732-183X
VL - 26
SP - 1112
EP - 1118
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 7
ER -