title: Clinical Management of Multiple Melanoma Brain Metastases: A Systematic Review.
abstract: OBJECTIVE
  The treatment of multiple brain metastases (MBM) from melanoma is controversial and includes surgical resection, stereotactic radiosurgery (SRS), and whole-brain radiation therapy (WBRT). Several new classes of agents have revolutionized the treatment of metastatic melanoma, allowing some subsets of patients to have long-term survival. Given this, management of MBM from melanoma is continually evolving.
  
  
  OBJECTIVE
  To review the current evidence regarding the treatment of MBM from melanoma.
  
  
  METHODS
  The PubMed database was searched using combinations of search terms and synonyms for melanoma, brain metastases, radiation, chemotherapy, immunotherapy, and targeted therapy published between January 1, 1995, and January 1, 2015. Articles were selected for inclusion on the basis of targeted keyword searches, manual review of bibliographies, and whether the article was a clinical trial, large observational study, or retrospective study focusing on melanoma brain metastases. Of 2243 articles initially identified, 110 were selected for full review. Of these, the most pertinent 73 articles were included.
  
  
  RESULTS
  Patients with newly diagnosed MBM can be treated with various modalities, either alone or in combination. Level 1 evidence supports the use of SRS alone, WBRT, and SRS with WBRT. Although the addition of WBRT to SRS improves the overall brain relapse rate, WBRT has no significant impact on overall survival and has detrimental neurocognitive outcomes. Cytotoxic chemotherapy has largely been ineffective; targeted therapies and immunotherapies have been reported to have high response rates and deserve further attention in larger clinical trials. Further studies are needed to fully evaluate the efficacy of these novel regimens in combination with radiation therapy.
  
  
  CONCLUSIONS
  At this time, the standard management for patients with MBM from melanoma includes SRS, WBRT, or a combination of both. Emerging data exist to support the notion that SRS in combination with targeted therapies or immune therapy may obviate the need for WBRT; prospective studies are required to fully evaluate the efficacy of these novel regimens in combination with radiation therapy.
authors.affiliation: Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey and Rutgers Robert Wood Johnson Medical School, New Brunswick.
authors.forename: Sharad
authors.initials: S
authors.lastname: Goyal
authors.affiliation: Division of Medical Oncology, Rutgers Cancer Institute of New Jersey and Rutgers Robert Wood Johnson Medical School, New Brunswick.
authors.forename: Ann W
authors.initials: AW
authors.lastname: Silk
authors.affiliation: Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey and Rutgers Robert Wood Johnson Medical School, New Brunswick.
authors.forename: Sibo
authors.initials: S
authors.lastname: Tian
authors.affiliation: Division of Medical Oncology, Rutgers Cancer Institute of New Jersey and Rutgers Robert Wood Johnson Medical School, New Brunswick.
authors.forename: Janice
authors.initials: J
authors.lastname: Mehnert
authors.affiliation: Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey and Rutgers Robert Wood Johnson Medical School, New Brunswick.
authors.forename: Shabbar
authors.initials: S
authors.lastname: Danish
authors.affiliation: Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey and Rutgers Robert Wood Johnson Medical School, New Brunswick.
authors.forename: Sinthu
authors.initials: S
authors.lastname: Ranjan
authors.affiliation: Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey and Rutgers Robert Wood Johnson Medical School, New Brunswick.
authors.forename: Howard L
authors.initials: HL
authors.lastname: Kaufman
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000276:immunology / Q000401:mortality / Q000556:secondary* / Q000628:therapy*; D016371:Cranial Irradiation; D003399:Craniotomy; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D007167:Immunotherapy; D008545:Melanoma / Q000276:immunology / Q000401:mortality / Q000556:secondary* / Q000628:therapy*; D058990:Molecular Targeted Therapy; D016634:Radiosurgery; D018714:Radiotherapy, Adjuvant; D012307:Risk Factors; D012878:Skin Neoplasms / Q000401:mortality / Q000473:pathology*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents