Treating Uveal Melanomas Effectively With Less

Brianne N. Hobbs, OD


November 03, 2014

Uveal Melanoma Treated With Iodine-125 Episcleral Plaque: An Analysis of Dose on Disease Control and Visual Outcomes

Perez BA, Mettu P, Vajzovic L, et al
Int J Radiat Oncol Biol Phys. 2014;89:127-136

A Rare but Devastating Condition

Uveal melanomas are one of the most feared and respected entities in optometry. These invaders threaten the eye and potentially the life of patients. Although rare, with an incidence of approximately 5.1 per 1 million, the risk for metastasis is relatively high, approaching 50%.[1]

The recent discovery of the role of mutations in several genes, including GNAQ, GNA11, BAP1, and SF3B1, has greatly increased our understanding of the mechanism of melanomas. Through molecular mapping, uveal melanomas are now often classified into two tiers: class 1 and class 2. The distinction between these classes is beneficial because class 1 tumors carry a low risk for metastasis, whereas class 2 tumors are much more ominous. Despite these recent advances in understanding how melanomas develop, the overall survival rates of melanoma have not risen substantially. In short, better science has not yet led to better outcomes.

The Collaborative Ocular Melanoma Study[2] provided solid evidence on the efficacy of plaque brachytherapy and enucleation in treating melanomas. Unfortunately, both of these standard treatments are highly invasive and carry substantial risk. A standard radiation dose of 85 Gy was administered to patients in this study, but 49% of these patients lost six or more lines of acuity within 3 years of treatment. This high rate of toxicity highlighted the need for a treatment that can control metastasis while preserving the eye.

Study Summary

Perez and colleagues sought to effectively treat uveal melanomas while minimizing collateral damage. This retrospective review included 190 patients treated with 125iodine plaques between 1988 and 2010. The quantity and the location of the radiation were analyzed to determine whether these factors had any influence on the primary endpoints of time to local failure (tumor growth), time to distant failure (metastasis), and death. Radiation-related complications, including enucleation and visual acuity, were secondary endpoints. The amount of radiation and the location were stratified into four groups, with the lowest-dose group receiving < 69 Gy and the highest-dose group receiving > 89 Gy at the tumor apex. The penetration of the radiation may also be predictive of collateral damage, so patients were also stratified into four groups by dose penetrating 5 mm below the sclera.

There was no relationship between the radiation dose and the likelihood of local failure or metastasis, indicating that more aggressive treatment is not always more effective.

The 5-year survival rate was 84% among all patients, and 91% of tumors were locally controlled. The most alarming statistic was that 73% of patients who were treated experienced side effects. Radiation retinopathy and cataract formation were the most common complications of treatment. Ocular toxicity was proportional to the radiation dose. The patients who received the most aggressive doses of radiation had the highest mortality rate (P = .04) and were more likely to have 20/200 or worse vision (P = .02). The patients who received the lowest amounts of radiation fared much better; they had better visual acuity (P = .02), fewer radiation-related complications (P < .0001), and lower rates of enucleation than the high-dose group (P < .01).


This study raises questions about the current treatment of melanomas. Is less more? This question warrants further study, because in some cases, treatment does not actually improve the patient's prognosis.

The primary goals of ocular melanoma treatment should be obtaining local control of the tumor and reducing the risk for metastasis, but this objective should also be met with the fewest iatrogenic effects possible. The discovery of genetic markers allowing targeted therapy, combined with lower, less toxic doses of radiation, may brighten the prognosis for patients with uveal melanoma in the future.



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