title: Pharmacotherapeutic options for treating brain metastases in non-small cell lung cancer.
abstract: BACKGROUND
  Central nervous system (CNS) metastases represent an important cause of morbidity and mortality in non-small cell lung cancer (NSCLC) patients. Local approaches of neurosurgery (usually for single brain lesions), whole brain radiotherapy, and stereotactic radiosurgery are often withheld for the treatment of NSCLC-derived brain metastases (BMs). However, systemic treatment is consistently emerging as an option for patients with asymptomatic BMs, which could allow for delaying cranial radiotherapy at symptomatic/radiological progression.
  
  
  METHODS
  Chemotherapy, monoclonal antibodies, tyrosine-kinase inhibitors (TKIs) for molecularly selected NSCLCs, such as epidermal growth factor receptor (EGFR)-mutant and anaplastic lymphoma kinase (ALK)-rearranged diseases, and immune checkpoint inhibitors are all systemic treatments that have shown activity against NSCLC-derived CNS metastases. Among these, EGFR- and ALK-TKIs will be discussed more in detail owing to their superior efficacy in this context.
  
  
  CONCLUSIONS
  Up-front systemic treatment should be considered for patients with asymptomatic, multiple BMs, as recently acknowledged by the European Society of Medical Oncology guidelines. Nevertheless, it must be emphasized that the best treatment strategy for NSCLC-derived BMs has to be defined within a multidisciplinary team.
authors.affiliation: a 1 Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia , Perugia, Italy +39 07 55 78 41 85 ; +39 07 55 78 41 84 ; giulio.metro@yahoo.com.
authors.forename: Giulio
authors.initials: G
authors.lastname: Metro
authors.affiliation: a 1 Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia , Perugia, Italy +39 07 55 78 41 85 ; +39 07 55 78 41 84 ; giulio.metro@yahoo.com.
authors.forename: Rita
authors.initials: R
authors.lastname: Chiari
authors.affiliation: a 1 Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia , Perugia, Italy +39 07 55 78 41 85 ; +39 07 55 78 41 84 ; giulio.metro@yahoo.com.
authors.forename: Biagio
authors.initials: B
authors.lastname: Ricciuti
authors.affiliation: b 2 University of Perugia, Department of Diagnostic Imaging, Santa Maria della Misericordia Hospital , Perugia, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Rebonato
authors.affiliation: c 3 Division of Radiotherapy, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia , Perugia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Lupattelli
authors.affiliation: d 4 Medical Oncology, Sacro Cuore-Don Calabria Hospital , Negrar, VR, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Gori
authors.affiliation: a 1 Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia , Perugia, Italy +39 07 55 78 41 85 ; +39 07 55 78 41 84 ; giulio.metro@yahoo.com.
authors.forename: Chiara
authors.initials: C
authors.lastname: Bennati
authors.affiliation: e 5 Division of Neurosurgery, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia , Perugia, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Castrioto
authors.affiliation: f 6 Neuroradiology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia , Perugia, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Floridi
authors.affiliation: a 1 Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia , Perugia, Italy +39 07 55 78 41 85 ; +39 07 55 78 41 84 ; giulio.metro@yahoo.com.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Minotti
authors.affiliation: f 6 Neuroradiology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia , Perugia, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Chiarini
authors.affiliation: a 1 Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia , Perugia, Italy +39 07 55 78 41 85 ; +39 07 55 78 41 84 ; giulio.metro@yahoo.com.
authors.forename: Lucio
authors.initials: L
authors.lastname: Crinò
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary; D003131:Combined Modality Therapy; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D017211:Treatment Failure
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases
keywords: bevacizumab; brain metastases; central nervous system metastases; cerebro-spinal fluid; chemotherapy; immune checkpoint inhibitors; non-small cell lung cancer; tyrosine-kinase inhibitors