Treatment of uveal melanoma by accelerated proton beam

Proton beam irradiation of uveal melanoma has great advantages compared to brachytherapy because of the homogenous dose delivered to the tumor and the possibility of sparing normal tissue close to the tumor. We describe the technique of proton beam therapy including the surgical technique of clip positioning, the radiotherapy delivery technique and the dose administered (60 Gy cobalt relative biological effectiveness in 4 fractions). Indications of proton beam are given and the follow-up procedure is described. An inactive residual tumor scar is observed after 2-3 years. Results are given comparing the most recent series of patients treated at the Institut Curie-Orsay proton therapy center with the data published in the literature. The metastasis rate at 10 years varies between 25 and 30%. Local control is excellent. The local recurrence rate at 10 years is usually around 5%. Secondary enucleation is performed in 10-15% of patients either due to complications or local recurrence. Complications such as retinal detachment, maculopathy, papillopathy, cataract, glaucoma, vitreous hemorrhage and dryness are described. The severest complication that usually leads to secondary enucleation is neovascular glaucoma and it is encountered after irradiation of large to extra-large tumors. The toxic tumor syndrome has recently been described. It is hypothesized that the residual tumor scar may produce proinflammatory cytokines and VEGF leading to intraocular inflammation and neovascular glaucoma. Additional treatments after proton beam such as transpupillary thermotherapy, endoresection of the tumor scar or intravitreal injections of anti-VEGF may reduce the rate of these complications.