Weisenfeld Lecture: 30 years of proton beam irradiation for uvealmelanomas

More than 12,000 patients worldwide have been treated with proton beam irradiation for uveal melanomas in the past 30 years, and the therapy has become the standard in place of enucleation. This transition has come about largely through the efforts of Evangelos S. Gragoudas, MD, professor, Harvard Medical School, and director of the retina service, Massachusetts Eye and Ear Infirmary (MEEI), Boston, who pioneered this therapeutic approach and continues to investigate strategies that can improve results.

Dr. Gragoudas was recognized for this and other scholarly contributions to the clinical practice of ophthalmology with the Weisenfeld Award and Lecture, given Monday evening at the annual meeting of the Association for Research in Vision and Ophthalmology.

Proton beam irradiation was first used to treat uveal melanomas in 1975 at the Harvard Cyclotron, and more than 3,000 patients have been treated at Harvard Medical School and MEEI since then.

"We have seen convincing evidence of the advantages of this modality in patients with uveal melanoma, particularly those whose tumor is large or located more posteriorly," Dr. Gragoudas said.

In a study of more than 2,000 patients treated at MEEI from 1975 to 1997, the recurrence rate was only 2.9%. However, proton beam irradiation is far from risk free, Dr. Gragoudas said. Enucleation is still necessary in some patients, and the risk of metastasis persists.

There is currently no effective treatment for metastatic melanoma. A study of low-dose interferon conducted by Dr. Gragoudas showed that it did not reduce the risk of metastasis in patients with at least one high-risk characteristic.

"However, future trials of other adjunctive agents may be worthwhile," Dr. Gragoudas noted.

"We also need better strategies to reduce the cytotoxic effects of radiation," he said.

Another potential line of research he advocated would be to investigate environmental and genetic factors associated with the development and progression of uveal melanoma and, once they have been found, to seek ways of modifying them.