title: The Rationale for Targeted Therapies and Stereotactic Radiosurgery in the Treatment of Brain Metastases.
abstract: Brain metastases are the most common intracranial malignancy. Many approaches, including radiation therapy, surgery, and cytotoxic chemotherapy, have been used to treat patients with brain metastases depending on the patient's disease burden and symptoms. However, stereotactic surgery (SRS) has revolutionized local treatment of brain metastases. Likewise, targeted therapies, including small-molecule inhibitors and monoclonal antibodies that target cancer cell metabolism or angiogenesis, have transformed managing systemic disease. Prospective data on combining these treatments for synergistic effect are limited, but early data show favorable safety and efficacy profiles. The combination of SRS and targeted therapy will further individualize treatment, potentially obviating the need for cytotoxic chemotherapy or whole-brain radiation. There is a great need to pursue research into these exciting modalities and novel combinations to further improve the treatment of patients with brain metastases. This article discusses reported and ongoing clinical trials assessing the safety and efficacy of targeted therapy during SRS.
  
  
  CONCLUSIONS
  Treatment of patients with brain metastases requires a multidisciplinary approach. Stereotactic radiosurgery is increasingly used in the upfront setting to treat new brain metastasis. Targeted therapies have revolutionized systemic treatment of many malignancies and may sometimes be used as initial treatment in metastatic patients. There is sparse literature regarding safety and efficacy of combining these two treatment modalities. This article summarizes the supporting literature and highlights ongoing clinical trials in combining radiosurgery with targeted therapy.
authors.affiliation: Department of Radiation Oncology, Hospital Sírio-Libanês, São Paulo, Brazil Department of Radiation Oncology, Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil.
authors.forename: Fabio Ynoe
authors.initials: FY
authors.lastname: Moraes
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Neil K
authors.initials: NK
authors.lastname: Taunk
authors.affiliation: Department of Radiation Oncology, Hospital Sírio-Libanês, São Paulo, Brazil Department of Radiation Oncology, Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil.
authors.forename: Gustavo Nader
authors.initials: GN
authors.lastname: Marta
authors.affiliation: Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Suh
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA yamadaj@mskcc.org.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000556:secondary; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D006801:Humans; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D016634:Radiosurgery
keywords: Brain metastasis; Stereotactic radiosurgery; Targeted therapy