Neil Osterweil

May 18, 2011

May 18, 2011 (Fort Lauderdale, Florida) — The posters and papers dedicated to research and to the treatment of ocular melanoma that were presented here at the Association for Research in Vision and Ophthalmology (ARVO) 2011 Annual Meeting suggest that sometimes it takes all the running one can do to stay in the same place.

"Whether you remove the eye, whether you use brachytherapy, iodine, or ruthenium — it doesn't matter how you treat. The survival outcome is the same," said Arun Singh, MD, director of ophthalmic oncology at the Cole Eye Institute at The Cleveland Clinic, Ohio, in an interview with Medscape Medical News.

"It doesn't really matter what you do to the eye," echoed Evangelos S. Gragoudas, MD, director of retina service at the Massachusetts Eye and Ear Infirmary in Boston.

Nonetheless, indefatigable investigators are looking not just for more effective treatment methods, but also for better methods of identifying patients and tumors at high risk for recurrence and metastasis.

The following is a round-up of some of the ocular tumor research presented at this year's ARVO meeting.

Long-Term European Follow-Up

A retrospective study of 10 years of follow-up data on 948 eyes (948 patients) with uveal melanoma treated with the 106 isotope of ruthenium (106Ru brachytherapy) showed a 5-year disease-specific survival rate of 95% and a 10-year rate of 91%, which compare favorably to those of other studies using iodine 125 (125I) brachytherapy, reported Nona Lakotka, MD, from the Charité-University Medicine Berlin, Germany.

Local tumor control rates were 91.3% and 89.7% at 5 and 10 years, respectively, and globe preservation rates were 95.0% and 93.7%. Of the 36 eyes requiring enucleation during the 10 years of follow-up, 24 were for tumor recurrence and 12 were for complications.

"We can conclude that ruthenium brachytherapy is a relatively safe treatment with an acceptable complication rate," Dr. Lakotka said.

The 5- and 10-year tumor-related survival rates were slightly better than those seen in the Collaborative Ocular Melanoma Study, in which ocular melanoma was treated with 125I seeds and enucleation, when necessary. That study had respective survival rates of 90% and 82%, respectively.

"I don't think there is a direct comparison, but their results are quite good," Dr. Gragoudas told Medscape Medical News in reference to the German study. "The only difference between the 2 methods is that iodine can treat taller tumors than ruthenium, and the larger the tumor, the higher the chance of metastasis."

Biomarker Search

Investigators from the University of Santiago de Compostela, Spain, suggest that elevated levels of the gp100 protein predict the metastatic potential of ocular melanoma.

"gp100 is a specific protein in the cell membrane of melanocytes and is overexpressed when melanocytes transform to cancer cells," said Maria Pardo, PhD, a senior scientist in the ocular oncology unit at the University of Santiago de Compostela.

She and her colleagues measured gp100 levels in the sera of 20 patients with small melanocytic choroidal tumors (SMCT), 7 with untreated uveal melanoma, and 12 with uveal melanoma who were treated with 125I brachytherapy with good results, and compared their results with gp100 levels in 15 healthy age- and sex-matched control subjects.

They found that levels of the protein were significantly lower in patients with SMCT than in those with untreated uveal melanoma, and in patients with treated uveal melanoma than in those with untreated uveal melanoma. Levels were also significantly lower in control subjects than in patients with untreated uveal melanoma, and there was a significant exponential correlation between protein levels and tumor height (Pearson's correlation = 0.75; < .01).

In related research, Italian investigators followed 41 patients with uveal melanoma over 5 years, looking for levels of messenger RNA tyrosinase as a peripheral blood marker for potential outcomes. They found increased levels of the enzyme in 20 patients, and saw that the levels correlated significantly with tumor dimension (< .01) and disease-free survival (< .05).

These "results indicate the need for larger prospective studies with a number of purposes, including whether circulating tumor cells may predict the behavior of the entire pool of occult tumor cells and the drug sensitivity of the corresponding tissue, write Cinzia Mazzini, MD, and colleagues from the University of Florence, Italy, in their poster presentation.

Vitrectomy Safe

To determine whether surgical penetration of the globe in eyes with ocular tumors carries the risk of seeding metastases, Rithwick Rajagopal, MD, and colleagues at Washington University in St. Louis, Missouri, took a retrospective look at 23 patients with treated choroidal melanoma who underwent subsequent pars plana vitrectomy. At a mean follow-up of 2 years (range, 2 to 123 months) after vitrectomy and 59.5 months after melanoma treatment (range, 11.0 to 141.0 months), they saw no evidence of local recurrence. Three patients went on to develop systemic metastases; 2 of these patients had tumors with high-grade molecular features suggestive of poor outcome.

"The rate of metastasis was not above that of eyes that did not undergo vitrectomy, and we have a larger series now that seems to back up those same findings," said Dr. Rajagopal in an interview. He is a third-year resident in ophthalmology and fellow-to-be at Washington University.

Depressing Prognosis

Dr. Singh and colleagues examined whether patients with uveal melanoma, about half of whom have undetectable micrometastasis at the time of diagnosis, regret the decision to have (or not to have) prognostic testing to evaluate monosomy 3 status, which has been shown to be a significant predictor of both relapse-free and overall survival.

They screened 29 patients with uveal melanoma with the Hospital Anxiety and Depression Scale (HADS) preoperatively and at 3 months, and with a decision-regret scale. They found that more than one third of the patients (38%) had a HADS score suggestive of probable anxiety or depression, possibly related to concerns about the surgery.

Three months after surgery, even though prognosis was associated depression or anxiety in 38% of patients, only 9% were found to be positive for monosomy 3.

"Three patients completely regretted their decision to undergo prognostication prior to having the surgery. [None] of these patients had scores on the HADS suggestive of depression or anxiety. It may be useful for physicians to review decisions preoperatively and to be aware that these patients may need a higher level of support," they write in their poster presentation.

The investigators have disclosed no relevant financial relationships.

Association for Research in Vision and Ophthalmology (ARVO) 2011 Annual Meeting: Abstracts 1440, 1456, 1457, 2104, and 3274. Presented May 2, 2011.

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