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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-? 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.

SUBMITTER: Barker CA

PROVIDER: S-EPMC4667362 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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

Barker Christopher A CA Postow Michael A MA

International journal of radiation oncology, biology, physics 20140401 5

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 i ...[more]

PMID: 24661650

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Project description:PurposeLocal radiation therapy (RT) combined with systemic anti-cytotoxic T-lymphocyte-associated protein-4 immunotherapy may enhance induction of systemic antimelanoma immune responses. The primary objective of the present trial was to assess the safety and efficacy of combining ipilimumab with RT in patients with stage IV melanoma. The secondary objectives included laboratory assessment of induction of antimelanoma immune responses.Methods and materialsIn our prospective clinical trial, 22 patients with stage IV melanoma were treated with palliative RT and ipilimumab for 4 cycles. RT to 1 to 2 disease sites was initiated within 5 days after starting ipilimumab. Patients had ≥1 nonirradiated metastasis measuring ≥1.5 cm available for response assessment. Tumor imaging studies were obtained at baseline, 2 to 4 weeks after cycle 4 of ipilimumab, and every 3 months until progression. Laboratory immune response parameters were measured before and during treatment.ResultsCombination therapy was well-tolerated without unexpected toxicities. Eleven patients (50.0%) experienced clinical benefit from therapy, including complete and partial responses and stable disease at median follow-up of 55 weeks. Three patients (27.3%) achieved an ongoing systemic complete response at a median follow-up of 55 weeks (range 32-65), and 3 (27.3%) had an initial partial response for a median of 40 weeks. Analysis of immune response data suggested a relationship between elevated CD8-activated T-cells and response.ConclusionThis is the second prospective clinical trial of treatment of metastatic melanoma using the combination of RT and systemic immunotherapy and the first using this sequence of therapy. The results from the present trial demonstrate that a subset of patients may benefit from combination therapy, arguing for continued clinical investigation of the use of RT combined with immunotherapy, including programmed cell death 1 inhibitors, which might have the potential to be even more effective in combination with RT.

Project description:Clinical data that support stereotactic body radiation therapy (SBRT) metastatic malignant melanoma (MM) are limited. Furthermore, functional imaging with 18F-fludeoxyglucose positron emission tomography (PET) may offer a more accurate post-SBRT assessment. Therefore, we assessed the clinical outcomes and metabolic response of metastatic MM after SBRT.Patients with MM who were treated with SBRT and had pre- and post-PET scans (>1) were included in this study. A total of 390 pre- and post-SBRT PET/computed tomography (CT) scans for 80 metastases were analyzed. The PET metabolic response was evaluated per the PET Response Criteria in Solid Tumors (PERCIST), version 1.0, criteria. Single-fraction equivalent dose (SFED) was calculated as per the standard. The Kaplan-Meier method was used for estimates of overall survival (OS) and progression-free survival. The cumulative incidence method was used to estimate metastasis control (MC). A Wilcoxon test was used to compare survival estimates. The prognostic factors for MC and OS were assessed using the Cox proportional hazards model, and the Likelihood Ratio was also used for comparisons between groups.A median of 6 PET scans (range, 2-6 scans) was evaluated for each metastasis. The median SFED was 42.8 Gy (range, 18-56.4 Gy) and the median biologically effective dose was 254.4 Gy2.5 (range, 100.8-540 Gy2.5). Twenty percent of patients received chemotherapy and 59% received immunotherapy: granulocyte-macrophage colony-stimulating factor (64%) and ipilimumab (34%). MC was 94% and 90% at 1 year and 3 years, respectively. The OS was 74% and 27% and 1 year and 3 years, respectively. Complete response was achieved in 90% at a median of 2.8 months (range, 0.4-25.2 months). SFED >24 Gy correlated with improved MC (93% vs 75%, P = .01). Acute and late grade 3+ toxicities were 4% and 11%, respectively, with no grade 5 toxicity.Post-SBRT PET/CT for extracranial metastatic MM resulted in high rates of complete response at a median of 2.8 months, and durable MC was achieved with SFED >24 Gy. SBRT, in addition to surgery and ablation, should be discussed with patients with MM, especially those with oligometastases.

Dataset Information

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

Publications

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

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