Clinical Investigation
Dry Eye Syndrome After Proton Therapy of Ocular Melanomas

https://doi.org/10.1016/j.ijrobp.2017.01.199Get rights and content

Purpose

To investigate whether proton therapy (PT) performs safely in superotemporal melanomas, in terms of risk of dry-eye syndrome (DES).

Methods and Materials

Tumor location, DES grade, and dose to ocular structures were analyzed in patients undergoing PT (2005-2015) with 52 Gy (prescribed dose, not accounting for biologic effectiveness correction of 1.1). Prognostic factors of DES and severe DES (sDES, grades 2-3) were determined with Cox proportional hazard models. Visual acuity deterioration and enucleation rates were compared by sDES and tumor locations.

Results

Median follow-up was 44 months (interquartile range, 18-60 months). Of 853 patients (mean age, 64 years), 30.5% had temporal and 11.4% superotemporal tumors. Five-year incidence of DES and sDES was 23.0% (95% confidence interval [CI] 19.0%-27.7%) and 10.9% (95% CI 8.2%-14.4%), respectively. Multivariable analysis showed a higher risk for sDES in superotemporal (hazard ratio [HR] 5.82, 95% CI 2.72-12.45) and temporal tumors (HR 2.63, 95% CI 1.28-5.42), age ≥70 years (HR 1.90, 95% CI 1.09-3.32), distance to optic disk ≥5 mm (HR 2.71, 95% CI 1.52-4.84), ≥35% of retina receiving 12 Gy (HR 2.98, 95% CI 1.54-5.77), and eyelid rim irradiation (HR 2.68, 95% CI 1.49-4.80). The same risk factors were found for DES. Visual acuity deteriorated more in patients with sDES (0.86 ± 1.10 vs 0.64 ± 0.98 logMAR, P=.034) but not between superotemporal/temporal and other locations (P=.890). Enucleation rates were independent of sDES (P=.707) and tumor locations (P=.729).

Conclusions

Severe DES was more frequent in superotemporal/temporal melanomas. Incidence of vision deterioration and enucleation was no higher in patients with superotemporal melanoma than in patients with tumors in other locations. Tumor location should not contraindicate PT.

Introduction

High-dose brachytherapy and proton therapy (PT) are now standard treatment for uveal melanomas. Enucleation is now reserved for failure of conservative treatment or very large ocular melanomas 1, 2, 3, 4, 5, 6, 7, 8, 9, 10. The choice of technique is guided by local staff expertise and equipment (11). Currently, one controversial issue is the use of PT for uveal melanomas in the superotemporal (ST) location owing to proximity of the lacrimal gland (LG) and risk of severe radiation-induced dry eye syndrome (DES). Some teams have contraindicated PT for such tumor locations, whereas others consider them a relevant indication for PT. Such data are increasingly relevant to cancer centers as PT facilities are expanding rapidly worldwide. The International Dry Eye Workshop defines DES as a disease affecting tears and ocular surface, resulting in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface 12, 13, 14, 15. Although mild to moderate DES is often successfully managed with supportive therapy, severe DES (sDES) may result in irreversible corneal damage with compromised vision, severe pain, and eye loss. Ocular morbidity after external beam radiation therapy is rarely reported but can severely affect patient quality of life 12, 13.

This study aimed to determine the DES rate and risk factors for DES and sDES in patients treated with PT. It also aimed to determine whether irradiation of melanomas in ST locations led to more frequent vision loss and enucleation, thus precluding PT.

Section snippets

Methods and Materials

All uveal melanoma patients underwent PT at our institution with a dose of 52 Gy (prescribed dose, not allowing for the relative biologic effectiveness correction of 1.1) during 4 days. The study was approved by our institutional review board. Patients underwent physical examination, ultrasound eye examination, and retinography/angiography before and after treatment, as per follow-up. Treatment planning and irradiation have been described elsewhere (14). Our uveal melanoma database has been

Results

From 2005 to 2015, 853 consecutive patients were recorded in the uveal melanoma database. Median follow-up time was 44 months, with an interquartile range of 18 to 60 months (range, 0.5-118 months). Patient, tumor, and treatment characteristics are presented in Table 1. Of the 853 patients, 30.5% (260) had a temporal tumor and 11.4% (97) an ST tumor. Mean (±SD) age was 64 ± 14 years. The sex ratio was approximately 1:1, with 48.2% (411) males. The prevalence of diabetes and high blood pressure

Discussion

This study is the largest study reporting on radiation-induced DES in uveal melanoma patients and irradiated patients in general. Some onco-ophthalmology centers contraindicate PT in ST uveal melanomas because of the risk of DES, despite the lack of published PT data in this population. In contrast, sDES has been found to be responsible for secondary enucleation after various forms of ionizing radiation and in up to 23% of patients treated with external beam radiation therapy for head and neck

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