Preventing radiation retinopathy with hyperfractionation

Abstract

The purpose of this study was to determine factors associated with the development of radiation retinopathy in a large series of patients with head and neck cancer. In particular, we addressed whether the use of hyperfractionated radiation therapy was effective in reducing the risk of retinopathy. One hundred eighty-six patients received a significant dose to the retina as part of curative radiotherapy. Primary sites were: nasopharyngeal, 46; paranasal sinus tumors, 64; nasal cavity, 69; and palate, 7. Prescription doses varied depending on primary site and histology. Hyperfractionated (twice-daily) radiation was delivered to 42% of the patients in this study, typically at 110 to 120 cGy per fraction. The remainder were treated once-daily. Retinal doses were determined from computerized dosimetry plans when available. For all other patients, retinal doses were retrospectively calculated using reconstructed off-axis dosimetry taken from contours through the center of the globes. Retinal dose was defined as the minimum dose received by at least 25% of the globe. The median retinal dose was 5685 cGy (range). Patients were followed for a median of 7.6 years. Thirty-one eyes in 30 patients developed radiation retinopathy, resulting in monocular blindness in 25, bilateral blindness in one, and decreased visual acuity in four. The median time to the diagnosis of retinopathy was 2.6 years (range, 10 months to 5.3 years). The actuarial incidence of developing radiation retinopathy was 20% at both 5 and 10 years. The incidence of developing ipsilateral blindness due to retinopathy was 16% at 5 years and 17% at 10 years. Site-specific incidences varied significantly with ethmoid sinus (9 of 25, 36%), nasal cavity (13 of 69, 19%), and maxillary sinus (6 of 35, 17%) being the most common sites associated with radiation retinopathy. Three of seventy-two patients (4%) receiving retinal doses less than 5000 cGy developed retinopathy. Higher retinal doses resulted in a steady increase in the incidence of retinopathy, with twenty-five of the thirty cases occurring after 6000 cGy or more. Of the patients receiving more than 5000 cGy to the retina, hyperfractionation was associated with a significantly lower incidence of radiation retinopathy (55% vs. 15%; p = 0.0020). On multivariate analysis, retinal dose (p < 0.0001), fractionation schedule (p = 0.0005), age (p = 0.027), and overall treatment time (p = 0.028) were significant predictors of radiation retinopathy. The incidence of radiation retinopathy following treatment of nasal cavity paranasal tumors is 20% at five and ten years. Retinal dose and fractionation schedule are the strongest predictors of retinopathy. Hyperfractionated radiotherapy is associated with a significant reduction in the incidence of radiation retinopathy, especially when the retina receives more than 5000 cGy