title: Treatment of melanoma brain metastases.
abstract: OBJECTIVE
  Melanoma has a tendency to metastasize to the brain. The development of brain metastasis is observed in all mutational subgroups. Overall, they are associated with poor prognosis. They are also associated with pain, neurological deterioration and thus, have a major impact on patients' quality of life. Historically, effective palliation by systemic therapy has been rare. The availability of new therapeutic agents, however, heralds a significant improvement in management options for these patients.
  
  
  RESULTS
  The development of targeted therapies and immune activating checkpoint inhibitors with durable benefit has led to a treatment paradigm change. Several clinical studies in patients with metastatic melanoma have demonstrated improved survival compared to chemotherapy. Many of these studies however excluded patients with brain involvement. Antitumor activity in brain metastasis has now been observed with some agents; further positive data are emerging. Surgery and stereotactic radiotherapy are also used for local control of oligometastatic disease. We discuss the usefulness of the available systemic treatments for management of brain metastases and how these are integrated with local treatments to enable optimal palliation.
  
  
  CONCLUSIONS
  Advances in the treatment of melanoma are providing significant palliative benefit for patients with brain metastases. Further investigations are needed to determine optimal treatment combinations and sequences.
authors.affiliation: aDepartment of Dermatology, University Hospital of Zurich, Zürich, Switzerland bDepartment of Radiooncology, University Hospital of Zurich, Zürich, Switzerland cDepartment of Medical Oncology, Mount Vernon Cancer Centre, Northwood, United Kingdom.
authors.forename: Simone M
authors.initials: SM
authors.lastname: Goldinger
authors.forename: Cédric
authors.initials: C
authors.lastname: Panje
authors.forename: Paul
authors.initials: P
authors.lastname: Nathan
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000401:mortality / Q000556:secondary* / Q000628:therapy*; D003131:Combined Modality Therapy / Q000379:methods*; D018572:Disease-Free Survival; D006801:Humans; D007167:Immunotherapy; D007211:Indoles / Q000627:therapeutic use; D008545:Melanoma / Q000473:pathology*; D058990:Molecular Targeted Therapy; D000077594:Nivolumab; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011728:Pyridones / Q000627:therapeutic use; D011744:Pyrimidinones / Q000627:therapeutic use; D011788:Quality of Life; D012878:Skin Neoplasms / Q000473:pathology*; D013449:Sulfonamides / Q000627:therapeutic use; D000077484:Vemurafenib
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007211:Indoles; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D047428:Protein Kinase Inhibitors; D011728:Pyridones; D011744:Pyrimidinones; D013449:Sulfonamides; D000077484:Vemurafenib; D000077594:Nivolumab; C560077:trametinib; C582435:pembrolizumab