Risks of Retinopathy and Optic Neuropathy after Radiotherapy for Childhood Cancer: A Report From the Pediatric Normal Tissue Effects in the Clinic (PENTEC) Initiative

Abstract

Few reports describe the risks of late ocular toxicities following radiation therapy (RT) for childhood cancers despite their impact on the quality of life. The Pediatric Normal Tissue Effects in the Clinic (PENTEC) ocular task force aims to quantify the radiation dose dependence of select late ocular adverse effects. Here, we report preliminary results concerning retinopathy and optic neuropathy in childhood cancer survivors who received cranial RT. A systematic literature search was performed using PubMed, Medline, and Cochrane Library databases for peer-reviewed studies published from 1980-2014 related to childhood cancer, radiotherapy, and ocular endpoints including dry eye, eye pain, keratitis/corneal injury, conjunctival injury, cataract, retinopathy, eye muscle damage, eyelid fibrosis/atrophy, and optic neuropathy. This initial search yielded abstracts for 2941 studies, 260 of which were selected as potentially having useful outcomes and RT data. The majority of studies reported on cataract development. We chose to focus on the more life-altering endpoints. Five studies reported on retinopathy following conventionally fractionated external beam RT for pediatric cancers (retinoblastoma, head and neck rhabdomyosarcoma/soft tissue sarcoma, esthesioneuroblastoma) and included radiation dose information that could be used to model risk of retinopathy. Five studies included information on radiation dose to optic nerves/chiasm in children (for craniopharyngioma, optic glioma, esthesioneuroblastoma) following conventionally fractionated external beam RT and were used to evaluate risk of optic neuropathy. RT in these studies was typically delivered in 1.8-2 Gy/fraction. Retinopathy among childhood cancer survivors who received cranial RT was reported in 21 cases, at doses ranging from 44-69 Gy with a latency of 11-72 months. Based on limited data, dose-response modeling suggests 5% and 50% probabilities of developing retinopathy at ∼42 Gy and 62 Gy, respectively. Optic neuropathy was reported in 2 of 103 children treated with external beam RT for craniopharyngioma, optic glioma, or esthesioneuroblastoma, at doses of 55 Gy (latency 27 months) and 61 Gy (latency unknown) to the optic nerve. The remaining 101 children who did not develop optic neuropathy received doses ranging from 34-63 Gy to the optic nerve. Radiation dose effects in the eye are poorly studied in the pediatric population, aside from cataract development. The risk of retinopathy increases above doses of 40-45 Gy at 1.8-2 Gy/fraction. The risk of optic neuropathy is low but has been reported at doses ≥55 Gy at 1.8-2 Gy/fraction in the pediatric population.