Exploration of dose-toxicity for ophthalmological adverse events in pediatric head and neck rhabdomyosarcoma survivors

Abstract

<h3>Objectives</h3> Ophthalmological adverse events (OAEs) following local treatment for pediatric head and neck rhabdomyosarcoma (HNRMS) are prevalent. More knowledge on specific radiation dose-toxicity relationships for ophthalmological organs at risk (OARs) in children can help to avoid these OAEs. The aim of the present study is to explore the dose-toxicity probability for multiple OAEs seen in long term HNRMS survivors. <h3>Methods</h3> Clinical data on OAEs were systematically assessed in an international cross-sectional cohort that included survivors of pediatric HNRMS with ≥2 years follow-up. Dosimetric data were collected from the original radiotherapy treatment plans. OARs were delineated on the 3D radiotherapy planning CTs. Dose-toxicity probability curves were constructed using binary logistic regression. <h3>Results</h3> 74 eyes in 38 survivors with a median follow-up time of 9 years (range 2 – 27) were analyzed. With the exception of epiphora, dose-toxicity probability curves with good model-fit (AUC under ROC ≥0.8) were constructed for all OAEs. A >20% probability of globe displacement, dry eyes and/or cataract (any grade) at follow-up was seen for mean doses of >40, 10 and 6 GyEQD2 to the orbital bones, lacrimal gland and lens respectively. Retinopathy and optic neuropathy only occurred in eyes receiving maximum doses > 40 and 53 GyEQD2 to the retina and optic nerve respectively. No multivariable analyses were conducted because of low numbers of events per OAE. <h3>Conclusion</h3> We offer the first detailed description of specific dose-toxicity probability for ophthalmological OARs in children derived from clinically assessed OAEs in long-term survivors. These results are critical to: 1) quantify expected variation in clinical toxicity between different treatment techniques, 2) understand the additional OAEs children will incur if prescription dose for orbital RMS is increased from 45 Gy to 50.4 Gy on future clinical trials, and 3) inform physicians and future patients about expected long-term toxicity and necessary surveillance.