Proton Therapy of Uveal Melanomas: Thirty years Experience

Reporter: James M. Metz, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 13, 2006

Presenter: Evangelos Gragoudas, MD
Affiliation: Massachusetts Eye and Ear Infirmary


Uveal melanoma is a rare malignancy with a rate in the United States of 6 cases per million per year. However, it is the most common intraocular primary malignancy. This tumor is a threat to both the sight and life of the patient. Radiation therapy has replaced enucleation as standard therapy due to the ability to preserve the eye, retain useful vision in many patients, and without an increase incidence of metastatic dieasease. Options for radiation include radioactive plaques placed surgically versus external beam irradiation with proton therapy or gamma knife. Proton therapy offers advantages when the tumor is close to the macula or optic nerve and in the case of large tumors to give a more uniform and localized dose. This presentation reports on the experience of protons for the treatment of uveal melanoma at the Massachusetts Eye and Ear Infirmary.

Materials and Methods

This was a retrospective review of 2069 patients treated for uveal melanoma at a single institution between 1975-1997. In general, this was a group of patients with very unfavorable features including 68% located within two disc diameters of the optic nerve or macula. Many were also large tumors that were not amenable to plaque brachytherapy. Tumors were localized through the placement of surgical clips made of titanium. Patients were treated to a median dose of 70 CGE over 5 fractions.


The local recurrence rate was 2.9 % (n=60) with the earliest recurrence at 5.2 months and the latest at 10.5 years. 408 patients (23%) died of metastatic melanoma. Survival after developing metastatic disease was 20% at 1 year and 6% at 2 years. Enucleation was performed in 8.7% of patients after proton beam therapy. Vision loss with scores of > 20/200 ranged from 50% (10 years) to 70% (15 years). Complications of treatment cumulative at 10 years of follow up included neovascular glaucoma (17%), posterior subcapsular cataract (35%), maculopathy (48%) and papillopathy (27%).


This series shows excellent local control rates and comparable metastatic rates with proton therapy compared to enucleation series for uveal melanoma. Many patients retain useful vision. Proton therapy should be considered a standard treatment for any tumors close to the macula or optic nerve, moderate size tumors and most large tumors of the eye. Enucleation should be reserved for large tumors with extrascleral extension, tumors filling greater then half of the eye, and painful eye syndromes.

Clinical and Scientific Implications

This is one of the largest experiences in the world for the treatment of uveal melanomas with proton therapy. Protons are now considered the standard of care for the indications listed above by the authors. Tumors that are small with a posterior location should still be considered for brachytherapy. The authors should be commended on the extensive follow up provided. Although the complication rates at 10 years are not trivial, many patients are spared enucleation and a significant number retain useful vision. Although a rare tumor, protons should continue to be a standard treatment option in this disease.