Radiation Therapy for Ocular Melanoma – a Narrative Review with Insides from TRIUMF, Canada’s Only Proton Beam Therapy Center

Abstract

"Ocular melanoma (OM) originates from melanocytes in the eye, predominantly in the uvea, particularly the choroid. The yearly incidence is around six cases per million. OM is not primarily driven by ultraviolet exposure like skin melanoma, but is usually caused by mutations in GNAQ or GNA11. Symptoms like blurry vision and visual field defects appear late. Diagnosis is often made via eye exams, specialized ultrasound, and rarely biopsy. This narrative review describes the radiation treatment modalities of OM and highlights the landscape of proton beam irradiation in Canada. Historically, enucleation was the standard of care for OM. However, current strategies consider tumor size, location, patient age, visual potential, and metastatic presence. Primary treatments include radiation therapy and surgery. Radiation therapy includes plaque brachytherapy (PB), proton beam irradiation (PBI), stereotactic radiosurgery (SRS), and stereotactic radiotherapy (SRT). Surgery includes endoresection, exoresection, and enucleation. Tebentafusp-tebn has been FDA-approved for metastatic cases. PB, the most common radiation therapy for OM, involves radioisotopes delivering radiation into the tumor. Comparable survival rates between PB and enucleation for medium choroidal melanoma have made PB the standard of care. PB has certain limitations, mainly surgical complications. PBI uses a particle accelerator for focused, high-energy proton radiation, yielding high tumor control and survival rates, though the availability of proton facilities is a significant limitation. Vancouver is the only center in Canada for PBI, administered not in a healthcare facility but at TRIUMF (Tri-University Meson Facility). TRIUMF, the world's largest cyclotron particle accelerator, in partnership with BC Cancer and UBC Department of Ophthalmology and Eye Care Center, has treated over 200 ocular melanoma patients between 1995 and 2017, achieving a 91% tumor control rate and 82% five-year survival rate. Emerging combination therapies like Ataxia Telangiectasia Mutated (ATM) protein kinase inhibition before PBI show potential, possibly reducing radiation dose and resistance."