Exploration of the radiation dose-toxicity relationship for multiple ophthalmological organs at risk for pediatric patients assessed in long-term head and neck rhabdomyosarcoma survivors

Objectives: Ophthalmological adverse events (OAE) are prevalent after local treatment for pediatric head and neck rhabdomyosarcoma (HNRMS). We examine the relation between radiation dose to multiple ophthalmological organs at risk (OAR) and associated clinical OAE in HNRMS survivors. Methods: Clinical data on OAE were systematically assessed in an international cross-sectional cohort study including survivors of primary pediatric HNRMS with ≥ 2 years follow-up. Included survivors were treated with either external beam radiation therapy with photons (XRT) or protons (PBT), or with brachytherapy (BT). BT was always delivered in conjunction with surgery (AMORE strategy), whereas XRT and PBT were sometimes combined with surgery. Dosimetric data were collected from the original radiotherapy treatment plans. OAR were delineated on the 3D radiotherapy planning CT. Radiation dose was recalculated into the equivalent dose in 2 Gy fractions (GyEQD2). Results: A total of 74 eyes in 38 survivors were assessed. Median follow-up time was 9 years. Following mean doses > 40, >10, and > 6 GyEQD2 to the orbit, lacrimal gland, and lens, respectively, survivors had a > 20% probability of globe displacement, dry eyes, or cataract (any grade) at follow-up. Retinopathy and optic neuropathy only occurred following maximum doses of > 40 and > 53 GyEQD2 to the retina and optic nerve, respectively. Conclusion: We offer the first description of specific dose-toxicity relationship for multiple OAR in children, based on clinically assessed OAE in long-term survivors. These results can help to quantify and inform physicians and future patients about expected probability of clinical toxicity and help to avoid OAE occurrence for future patients.