Treatment of Melanoma

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Surgery: For early stage of melanoma that has not spread to distant sites yet, a wide local excision to completely remove the cancer with a wide margin is usually performed.  In highly selected metastatic setting, complete resection of disseminated disease might improve the survival time of the patient. Whether a patient is a candidate for surgery or not depends on factors such as the type, size, location, grade and stage of the tumor, as well as general health factors such as age, physical fitness and other coexisting medical conditions the patient may have. Sometimes surgery can be done to relieve the discomfort that a patient might have.

Lymphatic mapping and sentinel lymph node biopsy:
if the melanoma is equal to or more than 0.75 mm in thickness, or has high risk features (ulceration, high growth rate, or evidence of invasion into the lymphatic or vascular system), then the surgeon will inject a traceable dye into the tumor to determine which lymph node it drains to, and evaluate this lymph node for any evidence of tumor cells. If tumor cells are found in this lymph node, more extensive resection of the surrounding lymph nodes will be performed.

Radiation therapy: Radiation therapy is to use X-rays or radioactive substances to destroy cancer cells. It may be used alone or in combination with other treatments. It can be used before another treatment to reduce the size of a tumor (for example to make surgery feasible) or after another treatment to kill any remaining cancer cells.
Sometimes radiation therapy can be used to relieve the discomfort that a patient might have.

Chemotherapy: Cytotoxic chemotherapy is to use drugs designed to slow or stop the growth of rapidly dividing cancer cells in the body. Melanoma does not respond well to chemotherapy. Only up to one in five patients would respond to chemotherapy but no improved survival.

Immunotherapy: Melanoma is one of the few tumors types that can be eliminated by a strong immune system. Immunotherapy works by stimulating the patient’s own immune system to attack cancer cells. This can be accomplished by either helping the immune system to recognize the tumor, or by taking away the inhibitory signals that prevent the immune system from attacking the tumor. In the past several years, significant advances has been made and several classes of immunotherapy drugs were approved to treat advanced melanoma, including checkpoint inhibitors (inhibit brakes of the immune system) such as ipilimumab (anti-CTLA4), pembrolizumab and nivolumab (anti-PD1), and talimogene laherparepvec (T-VEC, a genetically engineered herpes simplex virus that can specifically kill the tumor cells and activate the immune system). Sustained control of the tumor growth and prolonged patient survival has been observed with these immunotherapy agents. Many other drugs that modulate the immune system are in clinical testing (clinical trials) to treat melanoma and other types of cancer. One common side effect of immunotherapy is autoimmunity against the patient’s normal organs, such as the thyroid, pituitary glands, skin, guts, lungs, etc., therefore, close monitoring of the patients while on treatment is very important.

Targeted therapy: Genetic mutations are common in melanoma. Some of these gene mutations are key contributors to make a melanoma cell cancerous, and we have drugs that can target these mutations. For example, for patients whose tumor has BRAF gene mutation (approximately 50% of cutaneous melanoma), BRAF inhibitors vemurafenib and dabrafenib can block the growth and spread of cancer by preventing cancer cells from dividing or destroying them directly. Majority of patients with BRAF mutation positive melanoma would benefit from this treatment; however, the cancer can become resistant to this therapy quickly. In addition, patients receiving BRAF inhibitor treatment can develop another form of skin cancer called cutaneous squamous cell carcinoma. Fortunately his type of skin cancer rarely spreads to other parts of the body and can be treated with surgical resection. Combining BRAF inhibitors with another targeted therapy call MEK inhibitors (trametinib or cobimetinib) can help eliminate this side effect of cutaneous squamous cell carcinoma, and further control the tumor growth and spread.

The optimal treatment of melanoma in each individual patient depends on many factors including the cancer stage, the subtype of cancer, BRAF mutation status, the location of cancer, patient’s age, patient’s general health status, and patient’s preferences. Surgery and radiation therapy are types of local treatment because the goal of these therapies (in stage 0-III) is to remove the tumor and prevent the tumor from recurring. Systemic treatment such as immunotherapy, targeted therapy and rarely chemotherapy, are medicine that goes throughout the body to try to kill any cancer cells that have spread from the original site. For patients whose cancer has not spread to distant sites but do have high risk factors for cancer recurrence, such as positive lymph nodes or surgical margins, or deep tumors, adjuvant treatment can help eliminate the residual tumor cells after surgery is completed. The FDA approved drugs that can be used in this situation for melanoma are interferon and ipilimumab (anti-CTLA4).