You may not be aware that Vermont ranks top on the list of states with a high incidence of melanoma, a potentially lethal form of skin cancer that accounts for less than 5 percent of all skin cancers, but is responsible for the majority of skin cancer-related deaths. According to the Center for Disease Control, Vermont has one of the highest rates of melanoma in the country. Between 2001 and 2005 the rate of new melanoma cases diagnosed in Vermont was 63 percent higher than the national average. Bennington Country was found to have the highest rate of melanoma among counties nationwide, 179 percent above the national average.
The good news is that many cases of melanoma in Vermont present at an early stage where therapy is most effective. Surgical excision is frequently all that is required in the management of very early stage melanoma. However, there are still occasional cases of late stage presentation and advanced disease, where effective treatments options are limited. Fortunately, new discoveries have provided improved treatment options for patients diagnosed with melanoma. Patients with advanced melanoma may now benefit from novel immunotherapies and targeted therapies. The UVM Medical Center is involved in many of the trials exploring these new therapies for advanced melanoma.
Advanced melanoma has proven difficult to treat for many years, with no effective therapies shown to improve survival; however, recent clinical trials have demonstrated that the drug Ipilimumab is capable of improving survival in some patients with advanced stage melanoma. Ipilimumab is a monoclonal antibody that binds to a particular protein (CTLA-4) on T-cells (a type of white blood cell), resulting in the amplification of T-cell-mediated immunity, which enhances an individual’s ability to mount an anti-tumor immune response. In essence it releases the brakes on the immune system, enabling it to more effectively react against the melanoma. Other new drugs, such as pembrolizumab and nivolumab, block another protein (PD-1) on T-cells allowing them to better recognize and respond to melanoma cells that have otherwise found a way to evade and escape detection from the immune system.
Also, approximately 50 percent of all melanomas are associated with mutations to the growth promoter gene BRAF. Newer therapies, including vemurafenib and dabrafenib, target BRAF and have been shown to cause regression of melanoma. Other drugs called MEK inhibitors (e.g. trametinib) can block cell growth and induce cell death in BRAF-mutated melanoma cells. These drugs are now often used in melanomas that test positive for the BRAF gene mutation.
Although there are draw backs to these therapies (limited duration of response before the melanoma becomes resistant to therapy, and potential toxic side-effects), they represent a breakthrough in our ability to provide new options to people with advanced melanoma. Another promising new approach is the combination of BRAF and MEK inhibition, which has been show to delay resistance and reduce toxic effects in patients who have melanoma with certain BRAF mutations. Hopefully, as research discoveries continue to be made, we will be able to eliminate the burden of suffering from melanoma and other cancers.
To learn more, visit the American Cancer Society’s research and treatment web page.
Ted James, MD, is an Associate Professor of Surgery and Director of the Skin and Soft Tissue Surgical Oncology program at The University of Vermont Medical Center. He is a Board member and medical director of the New England American Cancer Society.