title: Two heads better than one? Ipilimumab immunotherapy and radiation therapy for melanoma brain metastases.
abstract: Melanoma is an aggressive malignancy with a deplorable penchant for spreading to the brain. While focal therapies such as surgery and stereotactic radiosurgery can help provide local control, the majority of patients still develop intracranial progression. Novel therapeutic combinations to improve outcomes for melanoma brain metastases (MBM) are clearly needed. Ipilimumab, the anticytotoxic T-lymphocyte-associated antigen 4 monoclonal antibody, has been shown to improve survival in patients with metastatic melanoma, but many of these trials either excluded or had very few patients with MBM. This article will review the efficacy and limitations of ipilimumab therapy for MBM, describe the current evidence for combining ipilimumab with radiation therapy, illustrate potential mechanisms for synergy, and discuss emerging clinical trials specifically investigating this combination in MBM.
authors.affiliation: Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (K.R.P., D.O.-D., M.K.K.); Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (D.H.L., R.R.K., B.C.C.); School of Medicine, Emory University, Atlanta, Georgia (D.E.O.); Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia (R.A.).
authors.forename: Kirtesh R
authors.initials: KR
authors.lastname: Patel
authors.affiliation: Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (K.R.P., D.O.-D., M.K.K.); Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (D.H.L., R.R.K., B.C.C.); School of Medicine, Emory University, Atlanta, Georgia (D.E.O.); Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia (R.A.).
authors.forename: David H
authors.initials: DH
authors.lastname: Lawson
authors.affiliation: Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (K.R.P., D.O.-D., M.K.K.); Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (D.H.L., R.R.K., B.C.C.); School of Medicine, Emory University, Atlanta, Georgia (D.E.O.); Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia (R.A.).
authors.forename: Ragini R
authors.initials: RR
authors.lastname: Kudchadkar
authors.affiliation: Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (K.R.P., D.O.-D., M.K.K.); Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (D.H.L., R.R.K., B.C.C.); School of Medicine, Emory University, Atlanta, Georgia (D.E.O.); Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia (R.A.).
authors.forename: Bradley C
authors.initials: BC
authors.lastname: Carthon
authors.affiliation: Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (K.R.P., D.O.-D., M.K.K.); Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (D.H.L., R.R.K., B.C.C.); School of Medicine, Emory University, Atlanta, Georgia (D.E.O.); Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia (R.A.).
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Oliver
authors.affiliation: Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (K.R.P., D.O.-D., M.K.K.); Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (D.H.L., R.R.K., B.C.C.); School of Medicine, Emory University, Atlanta, Georgia (D.E.O.); Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia (R.A.).
authors.forename: Derick
authors.initials: D
authors.lastname: Okwan-Duodu
authors.affiliation: Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (K.R.P., D.O.-D., M.K.K.); Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (D.H.L., R.R.K., B.C.C.); School of Medicine, Emory University, Atlanta, Georgia (D.E.O.); Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia (R.A.).
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
authors.affiliation: Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (K.R.P., D.O.-D., M.K.K.); Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (D.H.L., R.R.K., B.C.C.); School of Medicine, Emory University, Atlanta, Georgia (D.E.O.); Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia (R.A.).
authors.forename: Mohammad K
authors.initials: MK
authors.lastname: Khan
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001812:Blood-Brain Barrier / Q000276:immunology; D001932:Brain Neoplasms / Q000276:immunology / Q000532:radiotherapy / Q000556:secondary / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D006801:Humans; D007167:Immunotherapy; D000074324:Ipilimumab; D008545:Melanoma / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000074324:Ipilimumab
keywords: Brain metastases; ipilimumab; melanoma; radiation