Uveal melanoma research and treatment at Mayo Clinic

Mayo Clinic has a long history in the treatment of uveal melanomas. In the early 1980s, Dennis Robertson, M.D., was one of the first to use iodine 125 plaques, the form of brachytherapy most commonly used for treatment of uveal melanomas in the United States today.

Choroidal melanoma

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The plaques used in the Collaborative Ocular Melanoma Study (COMS), a multicenter study initiated in 1985 to evaluate therapeutic interventions for patients with choroidal melanoma, used gold shells made at Mayo Clinic. COMS showed that treatment of medium-sized choroidal melanomas with radioactive plaque brachytherapy was at least 90% successful in local control of the melanoma and had no increase in metastatic risk, compared with enucleation. Unfortunately, radiation retinopathy ultimately limits vision in these patients.

"The question now, however, is what to do with small, medium, and large melanomas in light of COMS data and new molecular information," says Jose S. Pulido, M.D., of the Department of Ophthalmology. At least 50% of uveal melanomas have a mutation in a protein called GNAQ. Unfortunately, this mutation occurs early on, even in what are considered choroidal nevi. Of more importance is that there appear to be two forms of uveal melanomas:

• Class 2, a uveal melanoma associated with monosomy of chromosome 3 and with mRNA that confers a high metastatic risk
• Class 1, a uveal melanoma with disomy 3 or mRNA testing that has a low metastatic risk

"Patients are attuned to these distinctions. Many wish to undergo prognostic testing. It is important to carefully discuss the results and use of the data with patients because at this time there is no prophylactic treatment for clinically undetectable but high-risk uveal melanomas," according to Dr. Pulido. These questions are a focus of intense research at Mayo Clinic and other institutions."

Treatment for large uveal melanomas

Although COMS recommended enucleation for large uveal melanomas, recently such tumors have been treated with larger radioactive plaques, especially if the patient has type 2 melanoma with a poor prognosis. Despite a higher risk of local recurrence and poor vision from radiation retinopathy, local treatment may be a reasonable option because the eye and useful vision are retained for some time.

Radiation retinopathy has been a considerable problem with brachytherapy. Methods of obtaining good local control by combining treatment methods may decrease the development of this complication. Intraoperative ultrasound for precise localization of the plaque in association with combination therapy may be helpful in this regard. Research is in progress to find methods of maintaining local control while minimizing vision loss.

Iris melanoma

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New research

A study conducted by Dr. Pulido in collaboration with the Department of Radiation Oncology evaluated a new plaque design that allows for in situ radiation of an iris melanoma. This innovation precludes removal of the melanomas, yet decreases the amount of radiation to other portions of the eye.

Additional studies conducted with the Department of Molecular Medicine and the Department of Immunology aim to induce autoimmunity for the treatment of ocular melanomas. Initial animal studies have shown promise, and methods to adapt this approach for human trials are in progress.