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Increasing knowledge of the biology of melanoma has led to significant advances in drug development to fight this disease. Surgery is the primary treatment for localized disease and is an integral part of management in patients with more advanced disease. The last decade has become the era of targeted therapy in melanoma and has revolutionized the treatment of this disease. Since 2011, 4 new agents have been approved for the treatment of patients with metastatic melanoma: ipilimumab, vemurafenib, dabrafenib, and trametinib. Several new agents are currently in phase 3 trials with hopes of even more agents being approved for this once "untreatable" disease. How to integrate surgical options with more effective systemic therapies has become a new challenge for physicians. This review will provide an update on current surgical options, highlight the pathway to the development of the newly approved agents, and further discuss new treatments that are on the horizon.

Background: Metastatic neuroendocrine tumors of the thymus are exceedingly rare with an annual incidence of approximately 0.2 per 1,000,000. They are highly resistant to therapy and there have been no reports of an objective radiographic response to treatment. Materials and Methods: The authors retrospectively evaluated 3 patients with progressive, metastatic neuroendocrine tumors of the thymus who were treated with a combination of capecitabine and temozolomide. Radiographic scans were evaluated and response assessed using RECIST criteria. Results: One patient experienced a partial radiographic response, another patient experienced a minor response and the third patient experienced stable disease as the best response to treatment. Conclusion: The combination of capecitabine and temozolomide appears to be active in a rare neuroendocrine malignancy that is generally refractory to systemic therapy. Prospective multicenter trials are needed to validate this strategy.

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