Combinations of radiation therapy and immunotherapy for melanoma: a review of clinical outcomes

Abstract

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.

Figure 1

Halo depigmentation surrounding irradiated dermal metastases from cutaneous melanoma. A 53 year-old man receiving ipilimumab for recurrent unresectable dermal metastases of melanoma on the right flank (A). Three weeks after receiving 36 Gy in 6 fractions to the right flank (B). Three months after completing radiotherapy hyperpigmentation of the irradiated skin and halo depigmentation surrounding the irradiated metastases were noted (C).

Figure 2

Halo depigmentation surrounding irradiated dermal metastases from cutaneous melanoma. A 69 year-old man receiving 5% imiquimod cream for recurrent unresectable dermal metastasis (circled in green) of melanoma on the left upper leg (A). Electron beam radiotherapy fields were demarcated on the skin surface (B). Eight weeks after completing 45 Gy in 15 fractions (C). Six months after completing radiotherapy hyperpigmentation of the irradiated skin and halo depigmentation surrounding the irradiated metastases were noted (D).

Figure 3

Abscopal effect of radiotherapy in a melanoma receiving systemic immunotherapy. A 66 year-old man receiving ipilimumab on clinical trial for recurrent, metastatic melanoma with no evidence of disease 24 months after starting treatment (A). Three months later a right internal mammary lymph node (circled in orange) increased in size to 1.5 × 1.6 cm and a left axillary lymph node (circled in blue) increased in size to 1.1 × 1.0 cm (B). He received external beam radiotherapy to 27 Gy in 3 fractions to the internal mammary lymph node (C, yellow represents 100% isodose line, pink represents 10% isodose line). Three months after radiotherapy, the right internal mammary lymph node decreased in size to 1.2 × 0.7 cm, and the non-irradiated left axillary lymph node decreased to 0.6 × 0.5 cm (D). Six months after radiotherapy, complete resolution of the enlarged lymph nodes was noted (E). Nineteen months after radiotherapy, he continues to receive ipilimumab (F).