Melanoma Brain Metastases

The majority of melanoma patients with metastatic disease stage IV is also affected by brain metastases, which are the main cause of death. If there is suspicion of brain metastases, staging diagnostics including cranial magnetic resonance imaging (cMRI) and a neurological examination are indicated. Prognostic factors, such as the number and symptoms of brain metastases, serum LDH and S100, existence of extracerebral metastases and ECOG status, should be considered in treatment planning. In addition, therapeutic interventions should be based on an interdisciplinary and multimodal approach. In case of a single brain metastasis, treatment by neurosurgical resection or stereotactic radiotherapy is standard of care. Until recently, the sole option for controlling brain metastases was local treatment. However, the spectrum of therapies has significantly expanded by approval of effective immune checkpoint (CTLA-4 and PD-1 antibody) and targeted therapies (BRAF and MEK inhibitors). In case of multiple symptomatic brain metastases, palliative whole-brain radiotherapy is used although there is no significant prolongation of overall survival (OS) but only some improvement of neurological symptoms and quality of life. Corticosteroids and anticonvulsants are indicated for increased intracranial pressure and epileptic seizures. New treatment options in melanoma with brain metastasis such as PD-1 antibodies and several combination strategies (e.g. ipilimumab plus nivolumab, BRAF inhibitors plus MEK inhibitors, or stereotactic radiotherapy plus immune or targeted therapy) will be evaluated in ongoing clinical trials.