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Modern and Novel Radiotherapy Approaches for the Treatment of Uveal Melanoma.

Uveal melanoma (UM) is the most common primary malignant intraocular tumor in adults and comprises approximately 5% of all melanoma diagnoses in the United States each year. The overall longterm rate of metastasis for UM is approximately 50%, resulting in a 15year mortality rate that approaches 40% to 50%, as a result of metastatic disease. Historically, all UMs were treated by enucleation to prevent metastases and death. In the 1970s, Zimmerman et al challenged the traditional treatment of UMs by theorizing that enucleation may worsen prognosis by promoting dissemination of tumor cells—and therefore increasing metastases—during the act of enucleating the eye. The socalled ‘‘Zimmerman hypothesis’’ partly inspired the multicenter Collaborative Ocular Melanoma Study (COMS), which ultimately disproved this theory. As a result of the various findings of the COMS, most primary UMs are no longer enucleated, but are instead treated with radiotherapy. Plaque brachytherapy remains the most commonly used treatment for COMS medium-size tumors, with apical heights <10 mm. In this setting, the goal of treatment for UMs has shifted from enucleation to preservation of the eye and vision, whenever possible, by treating locally with radiotherapy. Enucleation is now reserved for larger tumors where radiation delivery would lead to excessive morbidity including injury to the normal tissues and/or significant visual morbidity. However, over the past few decades, alternative forms of radiation