Effect of radiation dose on ocular complications after iodine brachytherapy for large uveal melanoma: empirical data and simulation of collimating plaques.

PURPOSE To calculate radiation doses to intraocular tissues in iodine brachytherapy (IBT) for large uveal melanoma, to study their relationship to ocular complications, and to assess a modified plaque design to reduce doses to the macula and optic nerve. METHODS Ninety-six patients with a uveal melanoma, classified as large according to the Collaborative Ocular Melanoma Study criteria, underwent primary IBT. Median tumor height and diameter were 10.7 (range, 4.5-16.8) and 16.5 (range, 7.3-25.0) mm, respectively, and median follow-up was 3.5 years (range, 0.3-10.4). Each IBT was retrospectively modeled with a plaque simulator to calculate doses and dose rates to ocular tissues. Cox proportional hazards regression was used to assess their association with time to ocular complications, low vision, and blindness (20/70 or worse and loss of 20/400, respectively). A collimating plaque design was assessed by replacing the actual plaque with the modified one in each model. RESULTS Median doses to tumor apex and base were 81 (range, 40-158 Gy) and 384 (range, 188-1143) Gy, respectively, and the median dose rates at these points were 53 (range, 11-204) and 289 (range, 84-1213) cGy/h, respectively. Median doses to the lens, macula, and optic disc were 69 (range, 20-141), 79 (range, 12-632), and 83 (range, 10-377) Gy, respectively. Dose to the lens was associated with cataract (hazard ratio [HR] 1.15 for each 10-Gy increase, P = 0.002), and dose to the optic disc with optic neuropathy (HR 1.08, P = 0.001). Dose to the macula predicted low vision (HR 1.06, P = 0.025) and blindness (HR 1.10, P < 0.001). A collimating design provided a median reduction of 36 (range, +19 to -198) and 30 (range, +9 to -160) Gy in modeled doses to the macula and optic disc, respectively. CONCLUSIONS Simulated dose distribution together with tumor height predicts major complications and vision loss after IBT. Simulation suggests that clinically meaningful dose reduction to normal tissues is feasible with a redesigned brachytherapy protocol, which may help to reduce complications and vision loss after IBT of large uveal melanoma.