Retinopathy, Optic Neuropathy and Cataract in Childhood Cancer Survivors Treated with Radiotherapy: A Report from the Pediatric Normal Tissue Effects in the Clinic (PENTEC) Initiative

Abstract

<h3>Purpose/Objective(s)</h3> Few reports describe the risks of late ocular toxicities following radiation therapy (RT) for childhood cancers despite their impact on 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, optic neuropathy, and cataract in childhood cancer survivors who received cranial RT. <h3>Materials/Methods</h3> 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. Treatment and outcome data were extracted and used to generate normal tissue complication probability (NTCP) models. <h3>Results</h3> We identified sufficient data to generate NTCP models for three endpoints: retinopathy, optic neuropathy, and cataract. Based on limited data, the model for development of retinopathy suggests 5% and 50% risk of toxicity at 42 Gy and 62 Gy, respectively. The model for development of optic neuropathy suggests 5% and 50% risk of toxicity at 57 Gy and 64 Gy, respectively. More extensive data were available to evaluate the risk of cataract, which we separated into self-reported versus ophthalmologist-diagnosed cataract. The models suggest 5% and 50% risk of self-reported cataract at 12 Gy and >40Gy, respectively, and of ophthalmologist-diagnosed cataract at 0 Gy and 9 Gy, respectively. <h3>Conclusion</h3> Radiation dose effects in the eye are poorly studied in the pediatric population. Based on limited published data, this PENTEC comprehensive review establishes relationships between radiotherapy dose and subsequent risks of retinopathy, optic neuropathy, and cataract. A lack of consistent radiotherapy data and outcome reporting in the literature prevented investigation of other ocular endpoints.