Background To describe cognitive function and to evaluate the association between potentially predictive factors and cognitive outcome in an unselected population of survivors of childhood brain tumors. Procedure We studied a consecutive sample of 133 patients (76 had received radiotherapy (RT)) who had a brain tumor diagnosed before the age of 15 years and were treated during the period January 1970 through February 1997 in the Eastern part of Denmark. Biologic effective dose of irradiation (BED) was assessed in 71 patients. One hundred twenty‐seven patients were able to cooperate to WISC‐R and WAIS‐R. Multiple regression models were constructed to evaluate relationships between possible risk factors and cognitive outcome. Results and Conclusions The mean intelligence (IQ) scores were substantially lower than the expected means of the general population. Younger age at diagnosis, tumor site in cerebral hemisphere, hydrocephalus treated with shunt, and treatment with RT were found to be significant predictors of lower cognitive functions. RT was the most important risk factor for impaired intellectual outcome. The mean observed full scale IQ was 97.1 (SD = 14.3) for the non‐irradiated patients and 78.8 (SD = 14.3) for the irradiated patients (adjusted P < 0.001). Verbal IQ, but not performance and full scale IQ, had a significant negative correlation to BED to the tumor site (P < 0.05). These results can be used to identify subgroups of children who are at increased risk for cognitive deficits allowing early and goal‐directed intervention. Med Pediatr Oncol 2003;40:26–34, © 2003 Wiley‐Liss, Inc.

The data of this study suggest that the majority of long-term survivors of brain tumours develop GH deficiency following radiotherapy in childhood and that the adverse effects of radiotherapy may be directly related to the biologically effective dose. With longer follow-up fewer patients might respond normally to GH stimulation tests.

The effect of craniospinal irradiation (CSI) vs. cranial irradiation (CIR) only with or without chemotherapy (CT) on the hypothalamus/pituitary (HP) thyroid axis was assessed in a population-based study of patients treated for a childhood brain tumor not directly involving the HP axis. Thyroid function was evaluated and compared with that in healthy controls (n = 27), measuring TSH, free T4, total T4, total T3, and TRH. The biological effective dose (BED) of radiotherapy, determined for the HP region and spine and expressed in grays (Gy) as BED, gives a means of expressing the biological effects of different dosage schedules in a uniform way. Seventy-one children (45 males and 26 females), less than 15 yr of age when diagnosed between 1970-1997 in the eastern part of Denmark, were included. Twenty-nine had received CSI, and 42 had received CIR only. The median age at time of radiotherapy was 8.4 yr (range, 0.8-14.9). The median length of follow-up was 12.0 yr (range, 2.0-28.0). There was no significant difference between CSI and the CIR only patients with respect to median BED to the HP region. Primary hypothyroidism was found in 24%, of whom 71% had been treated with CSI and 29% with CIR only; 73% had compensated hypothyroidism, and 27% had overt primary hypothyroidism. Central hypothyroidism was found in 6%. Free T4 and total T3 were significantly lower in the CSI and CIR only groups compared with controls. As the CIR only group had significantly higher median basal TSH levels compared with controls and as the CSI compared with the CIR only group and controls had significantly higher median basal TSH levels, we speculate that this was probably due to scattered irradiation from both cranial and spinal fields to the thyroid gland. There was a significant relation between basal TSH and time of follow-up (r(s) = -0.39; P = 0.001). Stepwise backward multiple linear regression analysis showed that the best-fit model to predict basal TSH was free T4 (P < 0.0001), the length of follow-up (P = 0.02), and total T3 (P = 0.06). In contrast, age at radiotherapy, BED to the HP region and spine, and whether the patient had been treated with CT were not included in the model. The TRH test showed significantly exaggerated and prolonged TSH responses for the CSI and CIR only groups compared with controls, indicating HP dysfunction. In conclusion, these data suggest that both CSI and CIR for childhood brain tumor may affect the HP-thyroid axis, resulting in hypothyroidism. CT had no significant influence on HP-thyroid function. We recommend prolonged surveillance of pituitary-thyroid function in long-term survivors of childhood brain tumor and institution of thyroid hormone replacement if the levels of TSH and free T4 are above and below the normal range, respectively, to ensure normal growth and metabolism.

A B S T R A C T PurposePreconception radiation and chemotherapy have the potential to produce germ cell mutations leading to genetic disease in the next generation. Dose-response relationships were evaluated between cancer treatments and untoward pregnancy outcomes. Patients and MethodsA case-cohort study was conducted involving 472 Danish survivors of childhood and adolescent cancer and their 1,037 pregnancies. Adverse outcomes included 159 congenital malformations, six chromosomal abnormalities, seven stillbirths, and nine neonatal deaths. Preconception radiation doses to the gonads, uterus, and pituitary gland and administered chemotherapy were quantified based on medical records and related to adverse outcomes using a generalized estimating equation model. ResultsNo statistically significant associations were found between genetic disease in children and parental treatment with alkylating drugs or preconception radiation doses to the testes in male and ovaries in female cancer survivors. Specifically, the risk of genetic disease was similar among the children of irradiated survivors when compared with nonirradiated survivors (relative risk [RR], 1.02; 95% CI, 0.59 to 1.44; P ϭ .94). A statistically significant association between abdominopelvic irradiation and malformations, stillbirths, and neonatal deaths was not seen in the children of female survivors overall (P ϭ .07) or in the children of mothers receiving high uterine doses (mean, 13.5 Gy; max, 100 Gy; RR, 2.3; 95% CI, 0.95 to 5.56). ConclusionMutagenic chemotherapy and radiotherapy doses to the gonads were not associated with genetic defects in children of cancer survivors. However, larger studies need to be conducted to further explore potential associations between high-dose pelvic irradiation and specific adverse pregnancy outcomes.