ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This paper reviewed the toxicity of radiation therapy (RT) on ovarian, uterine and vaginal tissue in childhood cancer survivors (CCSs), using data published from 1970 to 2017. Overall, 11 studies reported data on ovarian damage, 8 on uterine volume related to treatment, and 3 on vaginal effects. Most studies did not report accurate dosimetric data and dose-volume relationships, and the confounder role of chemotherapy was not considered. In general, published data confirmed that ovarian sensitivity to RT increases with age. Follicle sensitivity followed a linear model, with 2 Gy representing the lethal dose (50% of primordial follicles destroyed). The “effective sterilizing dose” (residual oocyte population <1000) decreased as age increased.

The Pediatric Normal Tissue Effects in the Clinic (PENTEC) task force produced this comprehensive review with the purpose of quantifying the effects of RT dose to the female reproductive organs after treatment for childhood cancer. They recommend to minimize RT dose and (if possble) to preserve one ovary, considering that the maximum tolerable RT dose decreases with patient’s age and total dose of alkylating agents.

Several studies have defined acute ovarian failure (AOF) as the loss of oestrogen production within 5 years from RT, and premature ovarian insufficiency (POI) when the loss of oestrogen production and oocyte reserve become evident later during follow up, but before 40 years of age. The ‘Dovary’ model designed by the Childhood Cancer Survivorship study and the St. Jude Lifetime (SJLIFE) cohort to predict AOF showed that the risk of AOF increased with the mean RT dose to the least affected ovary: cyclophosphamide equivalent dose of alkylating agents (CED), and age at RT. The model designed by SJLIFE study to predict POI reported that the risk of POI increased with survivor age, Dovary, and dose of alkylating agents.

Uterine toxicity, in term of reduced volume, impaired arterial blood flow, fibrosis, endometrial dysfunction, early pregnancy loss, preterm birth and delivery of low-birthweight infants has been described in some studies. Available data were insufficient to design a model of RT-associated risk, but in general a small uterine volume was described when RT doses >12 Gy were used in younger patients.

Data on vaginal toxicity are scant: vaginal dryness, mucosal thinning, and fibrous stenosis up to complete closure requiring surgical procedures have been described. Similarly to adults, RT risk was confirmed to be related to dose (>5 Gy in adults) and field of application.