High 1-year overall survival (OS) rate was associated with stereotactic radiosurgery (SRS) followed by either immunotherapy or targeted therapy, according to results of a retrospective study of patients with melanoma characterized by brain metastases. This study was published in the European Journal of Cancer.

Although the combination of local therapies (ie, whole brain radiation therapy [WBRT], stereotactic radiation surgery [SRS]) with systemic therapies (ie, immunotherapy, targeted therapies) is associated with favorable survival outcomes in patients with melanoma that has metastasized to the brain, specific aspects related to the optimal modality, systemic agent, and sequence for individual patients are still unclear. 

A total of 208 patients treated at 14 German skin cancer centers were included in this study, with 62% of the study cohort having disease characterized by a BRAF mutation. Median follow-up was 7.3 months.

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One-year OS rates from radiation therapy to death or last follow-up were 69% (SRS with immunotherapy), 65% (SRS with targeted therapy), 33% (WBRT with immunotherapy), and 18% (WBRT with targeted therapy; P <.001). Although a median OS benefit was seen in patients treated with SRS compared with WBRT (19.7 vs 7.1 months; P <.001), those in the latter group had more extensive brain metastases.

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Interestingly, the highest 1-year OS rates (88%) was seen in the subgroup of patients with BRAF-mutant disease receiving SRS with immunotherapy; those in this subgroup receiving SRS with targeted therapy had a 1-year OS rate of 65%. Furthermore, in this subgroup, median OS was significantly improved with targeted therapy after radiation therapy compared with targeted therapy before radiation therapy (P =.03).

Reported toxicities following administration of either immunotherapy or targeted therapy included hepatitis, pruritus, and colitis. Radiation-associated adverse events included intracerebral edema and bleeding; low rates of radionecrosis and skin toxicity/alopecia following SRS and WBRT, respectively, were also reported.

In their concluding statements, the authors wrote that the results of this study “support previous findings on synergistic effects of SRS and active systemic agents.”  They also emphasized the need to evaluate these therapeutic approaches in prospective clinical trials.


Rauschenberg R, Bruns J, Brütting J, et al. Impact of radiation, systemic therapy and treatment sequencing on survival of patients with melanoma brain metastases. Eur J Cancer. 2019;110:11-20.