Radiation therapy in melanoma: a review

This review explored the effects of radiation therapy (RT) to treat melanoma. Researchers suggested that RT is useful in high risk melanoma to prevent recurrence (when the cancer comes back), however without increasing survival.

RT has long been used as a treatment for skin cancer. New surgery methods and knowledge of the toxicities associated with RT have led to decreased use. However, new advances in RT methods have decreased the side effects.

The objective of this review was to present the indications for RT in melanoma and to investigate the new advances in RT as a treatment option.

Melanomas are among the most resistant cells to radiation. The exposure to radiation during RT may be associated with increased resistance of the tumor cells to this treatment. RT can be fractionated (dividing the total radiation into smaller doses over time) to reduce the cells gain of resistance.

RT is associated with toxicity that depends on radiation and tumor sensitivity. Beside skin, exposure of the lymphatic organs to RT is associated with lymphedema (retention of lymph fluid in tissues causing swelling) and with a significant loss in quality of life.

Head and neck mucosal melanoma represents 8-15% of all head and neck cancers. The first-line treatment for this is surgery. Different previous studies showed that, in these cases, treatment with RT improves tumor shrinkage with no impact on survival.

Spread of cancer to the lymph nodes is present in 15% to 20% of melanoma patients. This is known to negatively affect outcomes. Surgery is often considered as a treatment option, but the risk of local recurrence is between 30% and 50%. Previous studies have shown that RT to lymph nodes improves tumor shrinkage, but does not impact survival. One study noted local control of the cancer in 94% of patients who had both surgery and RT, compared to 81% of those who just had surgery. There was no impact on survival. Another study noted an 89% response rate after RT in patients who could not undergo surgery.

Non-skin melanomas can be harder to treat and may be more aggressive than skin melanomas. RT may help to improve local control in these patients. In one study of patients with mucosal melanoma, RT led to a 69% decrease in the risk of local recurrence compared to surgery alone. Several studies have shown that high tumor shrinkage rates can be achieved in ocular (eye) melanoma treated with RT. RT has also been found to improve local control in patients with lentigo or desmoplastic melanomas.

Intensity-modulated RT (IMRT) is a type of RT that allows very precise delivery of a dose of radiation to a particular area. IMRT can decrease the risk of damage to the healthy tissue surrounding a tumor. One small study included 8 patients with mucosal melanoma. IMRT led to a 5-year overall survival rate (time from treatment until death from any cause) of 80%, with manageable side effects.

Studies are now examining the possibility of combining RT with targeted therapies. Targeted therapies are drugs or small molecules that block the growth and spread of cancer by interfering with certain molecules. Vemurafenib (Zelboraf), for example, is a therapy that inhibits BRAF, a gene involved in melanoma growth. These combinations, however, can lead to many negative effects.

Modern RT methods for the treatment of brain metastases, such as stereotactic radiosurgery (non-surgical radiation therapy used to treat brain tumors) and stereotactic RT (non-surgical radiation therapy used to treat tumors is other parts of the body) can be effective for local control. They did not significantly improve survival. 

This study suggested that RT may be useful in high risk melanomas to prevent local recurrence, without improving survival. Targeted therapies should be used carefully when combined to RT due to the increased risk of toxicity.