Central endocrine complications among childhood cancer survivors treated with radiation therapy: a pentec comprehensive review

Wheeler G; Grassberger C; Samers J; Dwyer M; Wiltshire K; Daly P; Alvarez B; Campbell BA; Kerr AJ; Kron T; Duane FK; Zacharin M; Downie P; Kyriakou E; Ronckers CM; Constine LS; Hiniker SM

doi:10.1530/ey.22.9.2

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ESPE Yearbook of Paediatric Endocrinology (2025) 22 9.2 | DOI: 10.1530/ey.22.9.2

ESPEYB25 9. Oncology and Chronic Disease Late Endocrine Toxicity of Cancer Therapy (3 abstracts)

9.2. Central endocrine complications among childhood cancer survivors treated with radiation therapy: a pentec comprehensive review

Wheeler G , Grassberger C , Samers J , Dwyer M , Wiltshire K , Daly P , Alvarez B , Campbell BA , Kerr AJ , Kron T , Duane FK , Zacharin M , Downie P , Kyriakou E , Ronckers CM , Constine LS & Hiniker SM

Int J Radiat Oncol Biol Phys. 2024 Jun 1;119(2):457-466. PMID: 37269265. doi: 10.1016/j.ijrobp.2023.04.024. [email protected]

Brief summary: This review was conducted within the Pediatric Normal Tissue Effects in the Clinic (PENTEC) project to clarify the risk and incidence of central endocrine toxicity and the resulting pituitary hormone deficiencies in patients undergoing radiotherapy (RT).

Data from 16 papers (19 separate cohorts, totaling 570 patients) reporting toxicity scoring and individual dose levels, or their estimation, were included, with median follow-up ranging from 3.9 to 17.8 years. Since the risk of injury was related to age at RT in previous studies, a subgroup analysis was conducted on cohorts where the patients’ median age was over 5 years. The rate of endocrine toxicity increased during the initial few years post-RT, and stabilized at 3 to 5 years, even if this information was reported only by few studies.

The normal tissue complication probability (NTCP) model estimated a 20% risk of GHD in patients with median age >5 years who received 21-Gy in 2-Gy fraction to the HPA. The risk of central hypothyroidism was 20% in children receiving 22-Gy in 2-Gy fraction, while the 20% risk of ACTH deficiency was related to a dose of 34-Gy in 2-Gy fraction; in both these two deficits, the results were just minimally influenced by patient’s age.

Comment: In many cases, RT plays a crucial role in treating pediatric cancers located near or involving the hypothalamic-pituitary axis (HPA). Due to the necessity of effectively targeting the tumor, radiation doses to these areas cannot be reduced. This comprehensive review offers valuable insights into the risk of toxicity at specific RT doses to the HPA and should be taken into account during treatment planning. However, it is essential to carefully balance adequate tumor coverage with minimizing radiation exposure to critical organs. This balance must be considered on a case-by-case basis and clearly communicated when advising patients and their families. The primary limitations of this review arise from the heterogeneity of data reported in the included studies. This heterogeneity pertains to: inconsistencies in the definitions of hormone deficiencies, the lack of quantitative hormone measurements or detailed information regarding the severity of deficiencies, reliance on estimated radiation therapy (RT) doses, frequently based on whole-brain irradiation rather than specifically targeting the hypothalamic-pituitary axis, variability in tumor grading at diagnosis, which in some cases necessitated higher RT doses, concomitant therapies such as hormone replacement or chemotherapy, and the baseline endocrine status of patients prior to cancer diagnosis.