title: Updates in the management of brain metastases.
abstract: The clinical management/understanding of brain metastases (BM) has changed substantially in the last 5 years, with key advances and clinical trials highlighted in this review. Several of these changes stem from improvements in systemic therapy, which have led to better systemic control and longer overall patient survival, associated with increased time at risk for developing BM. Development of systemic therapies capable of preventing BM and controlling both intracranial and extracranial disease once BM are diagnosed is paramount. The increase in use of stereotactic radiosurgery alone for many patients with multiple BM is an outgrowth of the desire to employ treatments focused on local control while minimizing cognitive effects associated with whole brain radiotherapy. Complications from BM and their treatment must be considered in comprehensive patient management, especially with greater awareness that the majority of patients do not die from their BM. Being aware of significant heterogeneity in prognosis and therapeutic options for patients with BM is crucial for appropriate management, with greater attention to developing individual patient treatment plans based on predicted outcomes; in this context, recent prognostic models of survival have been extensively revised to incorporate molecular markers unique to different primary cancers.
authors.affiliation: St. Luke's Radiation Oncology Associates, St. Luke's Cancer Center, Whiteside Institute for Clinical Research and University of Minnesota Duluth, Duluth, Minnesota (N.D.A.); Center for Neuro-Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, Massachusetts (E.Q.L., P.Y.W.); Harvard Medical School, Boston, Massachusetts (E.Q.L., B.M.A., N.U.L., I.F.D., P.Y.W.); Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (M.P.M.); Department of Medical Oncology, City of Hope, Duarte, California (K.M.); Department of Radiation Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, Massachusetts (B.M.A.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (N.U.L.); Department of Medicine, Division of Hematology-Oncology, University of North Carolina, Chapel Hill, North Carolina (C.K.A.); Department of Neurology/Neuro-Oncology, University of Turin, Turin, Italy (R.S.); Division of Medical Oncology, University of Colorado Denver, Denver, Colorado (D.R.C.); Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio (M.A.V.); Department of Neurosurgery, Brigham & Women's Hospital, Boston, Massachusetts (I.F.D.).
authors.forename: Nils D
authors.initials: ND
authors.lastname: Arvold
authors.affiliation: St. Luke's Radiation Oncology Associates, St. Luke's Cancer Center, Whiteside Institute for Clinical Research and University of Minnesota Duluth, Duluth, Minnesota (N.D.A.); Center for Neuro-Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, Massachusetts (E.Q.L., P.Y.W.); Harvard Medical School, Boston, Massachusetts (E.Q.L., B.M.A., N.U.L., I.F.D., P.Y.W.); Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (M.P.M.); Department of Medical Oncology, City of Hope, Duarte, California (K.M.); Department of Radiation Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, Massachusetts (B.M.A.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (N.U.L.); Department of Medicine, Division of Hematology-Oncology, University of North Carolina, Chapel Hill, North Carolina (C.K.A.); Department of Neurology/Neuro-Oncology, University of Turin, Turin, Italy (R.S.); Division of Medical Oncology, University of Colorado Denver, Denver, Colorado (D.R.C.); Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio (M.A.V.); Department of Neurosurgery, Brigham & Women's Hospital, Boston, Massachusetts (I.F.D.).
authors.forename: Eudocia Q
authors.initials: EQ
authors.lastname: Lee
authors.affiliation: St. Luke's Radiation Oncology Associates, St. Luke's Cancer Center, Whiteside Institute for Clinical Research and University of Minnesota Duluth, Duluth, Minnesota (N.D.A.); Center for Neuro-Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, Massachusetts (E.Q.L., P.Y.W.); Harvard Medical School, Boston, Massachusetts (E.Q.L., B.M.A., N.U.L., I.F.D., P.Y.W.); Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (M.P.M.); Department of Medical Oncology, City of Hope, Duarte, California (K.M.); Department of Radiation Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, Massachusetts (B.M.A.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (N.U.L.); Department of Medicine, Division of Hematology-Oncology, University of North Carolina, Chapel Hill, North Carolina (C.K.A.); Department of Neurology/Neuro-Oncology, University of Turin, Turin, Italy (R.S.); Division of Medical Oncology, University of Colorado Denver, Denver, Colorado (D.R.C.); Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio (M.A.V.); Department of Neurosurgery, Brigham & Women's Hospital, Boston, Massachusetts (I.F.D.).
authors.forename: Minesh P
authors.initials: MP
authors.lastname: Mehta
authors.affiliation: St. Luke's Radiation Oncology Associates, St. Luke's Cancer Center, Whiteside Institute for Clinical Research and University of Minnesota Duluth, Duluth, Minnesota (N.D.A.); Center for Neuro-Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, Massachusetts (E.Q.L., P.Y.W.); Harvard Medical School, Boston, Massachusetts (E.Q.L., B.M.A., N.U.L., I.F.D., P.Y.W.); Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (M.P.M.); Department of Medical Oncology, City of Hope, Duarte, California (K.M.); Department of Radiation Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, Massachusetts (B.M.A.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (N.U.L.); Department of Medicine, Division of Hematology-Oncology, University of North Carolina, Chapel Hill, North Carolina (C.K.A.); Department of Neurology/Neuro-Oncology, University of Turin, Turin, Italy (R.S.); Division of Medical Oncology, University of Colorado Denver, Denver, Colorado (D.R.C.); Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio (M.A.V.); Department of Neurosurgery, Brigham & Women's Hospital, Boston, Massachusetts (I.F.D.).
authors.forename: Kim
authors.initials: K
authors.lastname: Margolin
authors.affiliation: St. Luke's Radiation Oncology Associates, St. Luke's Cancer Center, Whiteside Institute for Clinical Research and University of Minnesota Duluth, Duluth, Minnesota (N.D.A.); Center for Neuro-Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, Massachusetts (E.Q.L., P.Y.W.); Harvard Medical School, Boston, Massachusetts (E.Q.L., B.M.A., N.U.L., I.F.D., P.Y.W.); Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (M.P.M.); Department of Medical Oncology, City of Hope, Duarte, California (K.M.); Department of Radiation Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, Massachusetts (B.M.A.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (N.U.L.); Department of Medicine, Division of Hematology-Oncology, University of North Carolina, Chapel Hill, North Carolina (C.K.A.); Department of Neurology/Neuro-Oncology, University of Turin, Turin, Italy (R.S.); Division of Medical Oncology, University of Colorado Denver, Denver, Colorado (D.R.C.); Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio (M.A.V.); Department of Neurosurgery, Brigham & Women's Hospital, Boston, Massachusetts (I.F.D.).
authors.forename: Brian M
authors.initials: BM
authors.lastname: Alexander
authors.affiliation: St. Luke's Radiation Oncology Associates, St. Luke's Cancer Center, Whiteside Institute for Clinical Research and University of Minnesota Duluth, Duluth, Minnesota (N.D.A.); Center for Neuro-Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, Massachusetts (E.Q.L., P.Y.W.); Harvard Medical School, Boston, Massachusetts (E.Q.L., B.M.A., N.U.L., I.F.D., P.Y.W.); Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (M.P.M.); Department of Medical Oncology, City of Hope, Duarte, California (K.M.); Department of Radiation Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, Massachusetts (B.M.A.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (N.U.L.); Department of Medicine, Division of Hematology-Oncology, University of North Carolina, Chapel Hill, North Carolina (C.K.A.); Department of Neurology/Neuro-Oncology, University of Turin, Turin, Italy (R.S.); Division of Medical Oncology, University of Colorado Denver, Denver, Colorado (D.R.C.); Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio (M.A.V.); Department of Neurosurgery, Brigham & Women's Hospital, Boston, Massachusetts (I.F.D.).
authors.forename: Nancy U
authors.initials: NU
authors.lastname: Lin
authors.affiliation: St. Luke's Radiation Oncology Associates, St. Luke's Cancer Center, Whiteside Institute for Clinical Research and University of Minnesota Duluth, Duluth, Minnesota (N.D.A.); Center for Neuro-Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, Massachusetts (E.Q.L., P.Y.W.); Harvard Medical School, Boston, Massachusetts (E.Q.L., B.M.A., N.U.L., I.F.D., P.Y.W.); Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (M.P.M.); Department of Medical Oncology, City of Hope, Duarte, California (K.M.); Department of Radiation Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, Massachusetts (B.M.A.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (N.U.L.); Department of Medicine, Division of Hematology-Oncology, University of North Carolina, Chapel Hill, North Carolina (C.K.A.); Department of Neurology/Neuro-Oncology, University of Turin, Turin, Italy (R.S.); Division of Medical Oncology, University of Colorado Denver, Denver, Colorado (D.R.C.); Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio (M.A.V.); Department of Neurosurgery, Brigham & Women's Hospital, Boston, Massachusetts (I.F.D.).
authors.forename: Carey K
authors.initials: CK
authors.lastname: Anders
authors.affiliation: St. Luke's Radiation Oncology Associates, St. Luke's Cancer Center, Whiteside Institute for Clinical Research and University of Minnesota Duluth, Duluth, Minnesota (N.D.A.); Center for Neuro-Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, Massachusetts (E.Q.L., P.Y.W.); Harvard Medical School, Boston, Massachusetts (E.Q.L., B.M.A., N.U.L., I.F.D., P.Y.W.); Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (M.P.M.); Department of Medical Oncology, City of Hope, Duarte, California (K.M.); Department of Radiation Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, Massachusetts (B.M.A.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (N.U.L.); Department of Medicine, Division of Hematology-Oncology, University of North Carolina, Chapel Hill, North Carolina (C.K.A.); Department of Neurology/Neuro-Oncology, University of Turin, Turin, Italy (R.S.); Division of Medical Oncology, University of Colorado Denver, Denver, Colorado (D.R.C.); Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio (M.A.V.); Department of Neurosurgery, Brigham & Women's Hospital, Boston, Massachusetts (I.F.D.).
authors.forename: Riccardo
authors.initials: R
authors.lastname: Soffietti
authors.affiliation: St. Luke's Radiation Oncology Associates, St. Luke's Cancer Center, Whiteside Institute for Clinical Research and University of Minnesota Duluth, Duluth, Minnesota (N.D.A.); Center for Neuro-Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, Massachusetts (E.Q.L., P.Y.W.); Harvard Medical School, Boston, Massachusetts (E.Q.L., B.M.A., N.U.L., I.F.D., P.Y.W.); Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (M.P.M.); Department of Medical Oncology, City of Hope, Duarte, California (K.M.); Department of Radiation Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, Massachusetts (B.M.A.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (N.U.L.); Department of Medicine, Division of Hematology-Oncology, University of North Carolina, Chapel Hill, North Carolina (C.K.A.); Department of Neurology/Neuro-Oncology, University of Turin, Turin, Italy (R.S.); Division of Medical Oncology, University of Colorado Denver, Denver, Colorado (D.R.C.); Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio (M.A.V.); Department of Neurosurgery, Brigham & Women's Hospital, Boston, Massachusetts (I.F.D.).
authors.forename: D Ross
authors.initials: DR
authors.lastname: Camidge
authors.affiliation: St. Luke's Radiation Oncology Associates, St. Luke's Cancer Center, Whiteside Institute for Clinical Research and University of Minnesota Duluth, Duluth, Minnesota (N.D.A.); Center for Neuro-Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, Massachusetts (E.Q.L., P.Y.W.); Harvard Medical School, Boston, Massachusetts (E.Q.L., B.M.A., N.U.L., I.F.D., P.Y.W.); Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (M.P.M.); Department of Medical Oncology, City of Hope, Duarte, California (K.M.); Department of Radiation Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, Massachusetts (B.M.A.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (N.U.L.); Department of Medicine, Division of Hematology-Oncology, University of North Carolina, Chapel Hill, North Carolina (C.K.A.); Department of Neurology/Neuro-Oncology, University of Turin, Turin, Italy (R.S.); Division of Medical Oncology, University of Colorado Denver, Denver, Colorado (D.R.C.); Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio (M.A.V.); Department of Neurosurgery, Brigham & Women's Hospital, Boston, Massachusetts (I.F.D.).
authors.forename: Michael A
authors.initials: MA
authors.lastname: Vogelbaum
authors.affiliation: St. Luke's Radiation Oncology Associates, St. Luke's Cancer Center, Whiteside Institute for Clinical Research and University of Minnesota Duluth, Duluth, Minnesota (N.D.A.); Center for Neuro-Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, Massachusetts (E.Q.L., P.Y.W.); Harvard Medical School, Boston, Massachusetts (E.Q.L., B.M.A., N.U.L., I.F.D., P.Y.W.); Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (M.P.M.); Department of Medical Oncology, City of Hope, Duarte, California (K.M.); Department of Radiation Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, Massachusetts (B.M.A.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (N.U.L.); Department of Medicine, Division of Hematology-Oncology, University of North Carolina, Chapel Hill, North Carolina (C.K.A.); Department of Neurology/Neuro-Oncology, University of Turin, Turin, Italy (R.S.); Division of Medical Oncology, University of Colorado Denver, Denver, Colorado (D.R.C.); Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio (M.A.V.); Department of Neurosurgery, Brigham & Women's Hospital, Boston, Massachusetts (I.F.D.).
authors.forename: Ian F
authors.initials: IF
authors.lastname: Dunn
authors.affiliation: St. Luke's Radiation Oncology Associates, St. Luke's Cancer Center, Whiteside Institute for Clinical Research and University of Minnesota Duluth, Duluth, Minnesota (N.D.A.); Center for Neuro-Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, Massachusetts (E.Q.L., P.Y.W.); Harvard Medical School, Boston, Massachusetts (E.Q.L., B.M.A., N.U.L., I.F.D., P.Y.W.); Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (M.P.M.); Department of Medical Oncology, City of Hope, Duarte, California (K.M.); Department of Radiation Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, Massachusetts (B.M.A.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (N.U.L.); Department of Medicine, Division of Hematology-Oncology, University of North Carolina, Chapel Hill, North Carolina (C.K.A.); Department of Neurology/Neuro-Oncology, University of Turin, Turin, Italy (R.S.); Division of Medical Oncology, University of Colorado Denver, Denver, Colorado (D.R.C.); Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio (M.A.V.); Department of Neurosurgery, Brigham & Women's Hospital, Boston, Massachusetts (I.F.D.).
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Wen
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D002986:Clinical Trials as Topic; D003071:Cognition / Q000528:radiation effects; D016371:Cranial Irradiation / Q000009:adverse effects / Q000379:methods; D004358:Drug Therapy / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D008297:Male; D011878:Radiotherapy / Q000009:adverse effects; D016896:Treatment Outcome
keywords: brain metastases; chemotherapy; stereotactic radiosurgery; surgery; whole brain radiation