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Combinations of Radiation Therapy and Immunotherapy for Melanoma: A Review of Clinical Outcomes

Christopher A. Barker, Michael A. Postow

International Journal of Radiation Oncology*Biology*Physics, Volume 88, Issue 5, 1 April 2014, Pages 986-997

Editors' comments: Dr. James Larkin
Barker and Postow review the topical and important area of interaction between radiotherapy and immunotherapy. This has historically not been an intensive area of research in melanoma but the activity of T-cell checkpoint inhibitors in the clinic has invigorated the area and this is a timely and comprehensive summary.

Radiation therapy has long played a role in the management of melanoma. Recent advances have also demonstrated the efficacy of immunotherapy in the treatment of melanoma. Preclinical data suggest a biologic interaction between radiation therapy and immunotherapy. Several clinical studies corroborate these findings. This review will summarize the outcomes of studies reporting on patients with melanoma treated with a combination of radiation therapy and immunotherapy. Vaccine therapies often use irradiated melanoma cells, and may be enhanced by radiation therapy. The cytokines interferon-α and interleukin-2 have been combined with radiation therapy in several small studies, with some evidence suggesting increased toxicity and/or efficacy. Ipilimumab, a monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, has been combined with radiation therapy in several notable case studies and series. Finally, pilot studies of adoptive cell transfer have suggested that radiation therapy may improve the efficacy of treatment. The review will demonstrate that the combination of radiation therapy and immunotherapy has been reported in several notable case studies, series and clinical trials. These clinical results suggest interaction and the need for further study.