A Look at the ‘Collateral Damage’ From Uveal Melanoma Treatment

While uveal melanoma — a rare type of cancer that occurs in the eye — is highly treatable, many patients may experience disease metastasis or treatment-related complications, highlighting the importance of continued follow-up after treatment, according to Dr. Arun Singh.

“This tumor will spread to the liver more than any other place,” Singh, director in the department of ophthalmic oncology at the Cole Eye Institute at the Cleveland Clinic, said in an interview with CURE®. “So many times, as patients are treated, they are prospectively examined; the liver is examined by imaging (like) ultrasound, CT or MRI, something to make sure there are no metastases.”

Singh explained that patients face the highest risk for dying from metastatic melanoma within the first five to 10 years after treatment, so surveillance during this time is critical.

“(Approximately) 15 years after treatment, the risk of dying from other causes overtakes the risk of dying from melanoma,” Singh said. “The average age of diagnosis is 65. They're already 80 years old, and chances are dying from stroke, heart attack, diabetes and other things, or even other cancers for that matter increases. Statistically speaking, if patients have survived 15 years after melanoma and nothing has spread, one can say that you're potentially cured from melanoma.”

Even if patients with uveal melanoma are cured, there are still late and long-term complications that may result from their treatment.

Singh mentioned that approximately 30% to 40% of patients with uveal melanoma will lose a significant proportion of their vision from radiation treatment. Radiation could also cause radiation retinopathy or optic neuropathy, which is radiation damage to the retina and the optic nerve.

“If the tumor is closer to the vision structures like macula or optic nerve, then there’s risk of vision loss. Radiation retinopathy or optic neuropathy cannot be treated,” Singh said, mentioning that some patients may experience central vision loss (loss of the central part of the vision field), while others may experience peripheral vision loss (when a patient cannot see items unless they are right in front of them). “At present, we do not know (how to treat it, but) there are some trials being done, but we do have good treatments for this condition.”

Some patients may also undergo an enucleation — the surgical removal of the eye — to treat their cancer.

Enucleation is typically recommended for patients with large tumors, meaning that they are more than 16 millimeters in the base and 10 millimeters in height, Singh explained. He noted that radiation complications are particularly high for this group of patients, and they may end up with vision issues or other complications that lead to the removal of the eye anyway.

Singh also mentioned that patients may be a candidate for eye removal if their tumor is on the optic nerve. In that case, they may lose their vision either way, so eye removal may be the best course of action.

Finally, Singh noted that if there are tumor-related complications such as a hemorrhage from the tumor, a tumor starts growing outside the eye or if the tumor has broken into pieces, then these patients may want to consider eye removal as well.

Looking ahead Singh said that researchers are continuously looking for new and less toxic treatments for uveal melanoma. For example, in January 2022, the Food and Drug Administration approved Kimmtrak (tebentafusp-tebn) for the treatment of patients with unresectable or metastatic uveal melanoma that is HLA-A*02:01 positive.

Continued research is looking at alternative for radiation treatment, or therapies that will delay when radiation therapy will be needed in the treatment trajectory.

“There are newer methods or new drugs being considered for treatment or prevention of radiation damage,” Singh said. “So, we know the radiation is highly effective, the problem is the collateral damage. (Researchers are) trying to come up with new drugs and new methods of preventing and delaying or reversing radiation damage.”

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