Abstract 4991: Immunologic analyses of uveal melanoma patients treated with radiation therapy

Abstract

Abstract Early stage uveal melanoma is frequently treated by radiation therapy (RT) alone. Preclinical studies suggest the efficacy of RT in melanoma is dependent on the immune system. We studied the immune system of patients with uveal melanoma before and after RT, hypothesizing there would be associations between these parameters and clinical outcomes. With institutional review board permission, patient, tumor, peripheral blood count characteristics were extracted from medical records of 299 patients with clinically localized uveal melanoma undergoing RT. Similar data was collected for 16 patients who presented with metastatic uveal melanoma at initial diagnosis. A subset of 8 patients treated with RT for uveal melanoma underwent peripheral blood sampling before, one and three months after RT on a prospective biospecimen collection protocol. Flow cytometry was performed to characterize leukocyte populations before and after RT. Serum was analyzed for cytokines and antibody titers before and after RT. Associations between neutrophil-to-lymphocyte ratio (NLR), leukocyte subpopulations, cytokines and antibody titers with tumor response to RT and survival were investigated. NLR was significantly lower in patients presenting with clinically localized uveal melanoma (mean 2.7), compared to those presenting with metastatic uveal melanoma at initial diagnosis (mean 3.4, p<0.05). Among patients with clinically localized uveal melanoma who underwent RT, a multivariable Cox regression model found that age, tumor stage, and NLR were all significantly associated with overall survival. Changes in several leukocyte populations were observed after RT, with the overall CD8 / regulatory T cell ratio increasing by 27% one month after RT. Increases in several cytokines were observed, with C reactive protein and granulocyte-macrophage colony stimulating factor increasing 2-3 fold in the first month after RT. One of eight patients seroconverted to a positive Melan-A antibody titer three months after RT; this was associated with one of the largest reductions in tumor size observed (>60%). In conclusion, several immune system parameters of patients with uveal melanoma treated with RT appeared to change after treatment, and may be associated with tumor response and treatment outcome, including survival. Further study on the development of distant metastasis in an expanded cohort of patients is planned. Additional investigations into the capacity of RT to modulate the immune system of cancer patients are warranted. Citation Format: Christopher A. Barker, Jasmine H. Francis, Robin K. Kuriakose, Ming Lian, Brian P. Marr, David H. Abramson. Immunologic analyses of uveal melanoma patients treated with radiation therapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4991.