Which is the best treatment for melanoma brain metastases? A Bayesian network meta-analysis and systematic review

Objective: Melanoma has a high degree of central nervous system tropism, and there are many treatment modalities for melanoma brain metastases (MBM). The efficacy and toxicity of various treatments are still controversial. Therefore, they were evaluated by direct and indirect comparison to assist clinical decision-making in this study.

Method: A total of 7 therapeutic modalities for MBM were studied. Retrieval was conducted through Embase, PubMed, Cochrane Library and Web of science databases and the quality of the included literature was evaluated. Meta-analysis and Bayesian network meta-analysis were performed using Review Manager and R language.

Results: A total of 10 articles were included with 836 MBM patients. Direct comparison showed that stereotactic radiotherapy combined with immunotherapy (SRS + IT) was superior to IT (HR = 0.66, 95%CI = 0.52-0.84) or SRS (HR = 0.81, 95%CI = 0.63-1.03) alone in improving intracranial progression-free survival (PFS). In terms of overall survival (OS), SRS + IT was superior to SRS alone (HR = 0.64, 95%CI = 0.49-0.83), or IT (HR = 0.59, 95%CI = 0.29-1.21). Rank probability and surface under the cumulative ranking curve (SUCRA) by indirect comparison showed that SRS + IT had the best effect on improving intracranial PFS (0.88) and OS (0.98). Additionally, various combination therapies, especially SRS + IT (0.72), increased the incidence of radiation necrosis (RN). In direct comparisons, SRS + IT (RR = 0.93, 95%CI = 0.47-1.83) and SRS + TT (targeted therapy) (RR = 0.24, 95%CI = 0.10-0.56) did not increase intracranial hemorrhage (ICH) compared with SRS.

Conclusions: SRS + IT treatment was the best choice for MBM patients in both intracranial PFS and OS, even though it also led to an increased probability of RN.