Background: Brain metastases secondary to melanoma are devastating and often fatal for many patients. Radiation therapy is commonly used to treat brain metastases. Patients are often concurrently treated with non-cytotoxic systemic therapies, including immunotherapy and targeted agents. Immunotherapy releases the modulating checkpoints on the immune system, increasing the immune response to tumor cells. Targeted agents inhibit the protein products that are upregulated by specific mutated oncogenes; these mutations promote the conversion of cells from normal to cancerous. While radiation and systemic therapies are all individually beneficial, the relationship between these treatments is not currently well understood. This study examines the interplay between radiation and non-cytotoxic systemic therapies and their effect on brain metastases secondary to melanoma, with respect to locoregional control, overall survival, and toxicity.
Method: This is a single-institution retrospective study examining patients with brain metastases from melanoma, diagnosed between 2012 and 2017, and treated with radiation therapy. The study included 17 patients with a total of 78 metastases. The lesions were divided into six groups: (1) BRAF-wildtype with no systemic treatment, (2) BRAF-wildtype with immunotherapy, (3) BRAF-mutated with no systemic treatment, (4) BRAF-mutated with immunotherapy, (5) BRAF-mutated with targeted agents, and (6) BRAF-mutated with both immunotherapy and targeted agents. Response to treatment was examined, including tumor progression; tumor regression, both complete and partial response; distant intracranial recurrence; toxicity; and overall patient survival.
Results: There were no statistically significant differences regarding tumor progression, toxicity, and overall survival. The survival distributions for intracranial recurrence demonstrated a significant difference between groups (p=0.03); however, post-hoc pairwise analysis did not reveal any significant individual between-group difference. Finally, the survival distributions for tumor regression were also significantly different (p=0.029). Post-hoc pairwise comparison revealed a significant difference between groups 2 and 5 (p=0.026), with significantly greater tumor regression in group 5.
Conclusion: Combined radiation and non-cytotoxic systemic therapy may differentially impact intracranial recurrence, but the exact variables involved were not elucidated in this study. However, this study did show that tumors treated with targeted agents in combination with radiation therapy regress significantly more than tumors treated with radiation and immunotherapy in BRAF-wildtype patients. Future research with a larger sample size is necessary to further examine the interplay between these treatments.