ESPE Yearbook of Paediatric Endocrinology

Pediatr Blood Cancer. 2020; 67: e28617. https://pubmed.ncbi.nlm.nih.gov/32715632/

This retrospective single-centre study aimed to develop a final height prediction model based on data from 212 long-term survivors (aged 5-20.4 years) of childhood central nervous system (CNS) tumors who received craniospinal irradiation (CSI) and with a median follow up of 10.2 years. Mean final height Z-scores at 18 years of age, compared to United States standards, were −1.3 for female and−1.5 for male survivors. Prediction models showed that height was impaired in: females, African American background, high CSI dose (≥ 36 Gy), and younger age at CSI. In contrast, factors associated with higher growth rates before age 15 years were: replacement therapy for growth hormone (GH) deficiency and central adrenal insufficiency. Growth after age 15 years in male survivors was associated with treatment for gonadotropin deficiency.

CSI is a key element for the treatment of childhood CNS tumors that can spread to neuroaxis. The risk of short stature following CSI is well known and is due to both a direct radiation-induced bone damage of the spine and to GH deficiency. A previous study (1) reported that change in height after GH treatment was positively associated with male sex, GH dose, and lower bone age at therapy start; while concurrent endocrine disorders and radiation dose to the spine negatively affected change in height. The same study suggested that early onset of female puberty reduced the available time for effective GH-replacement therapy.

This study is interesting but has some limitations. First, it lacked data on puberty, which is important for both growth spurt and timing of GH treatment. Second, stature was not correlated to parental height, which might account for the differences among ethnicities. Third, the impact of GH dose and duration were not discussed. Moreover, this study did not consider the differences between proton and photon therapy. A recent study (2) showed a significantly reduced incidence of hypothyroidism, sex hormone deficiency and the need of replacement therapy in patients treated with proton therapy, but median follow-up was relatively short. Patients in the proton group were young and puberty had not been reached in many of them. This issue needs to be analyzed in future studies of growth following CSI.

Reference: 1. Brownstein CM, Mertens AC, Mitby PA, et al. Factors that affect final height and change in height standard deviation scores in survivors of childhood cancer treated with growth hormone: a report from the childhood cancer survivor study. J Clin Endocrinol Metab. 2004; 89: 4422–7.2. Eaton BR, Esiashvili N, Kim S, et al. Endocrine outcomes with proton and photon radiotherapy for standard riskmedulloblastoma. Neuro Oncol. 2016; 18: 881–7.