title: Different spatial distributions of brain metastases from lung cancer by histological subtype and mutation status of epidermal growth factor receptor.
abstract: The purpose of this study was to test the hypothesis that the genetic backgrounds of lung cancers could affect the spatial distribution of brain metastases.
  
  
  
  CT or MR images of 200 patients with a total of 1033 treatment-naive brain metastases from lung cancer were retrospectively reviewed (23 by CT and 177 by MRI). All images were standardized to the human brain MRI atlas provided by the Montreal Neurological Institute 152 database. Locations, depths from the brain surface, and sizes of the lesions after image standardization were analyzed.
  
  
  
  The posterior fossa, the anatomic "watershed areas," and the gray-white matter junction were confirmed to be more commonly affected by lung cancer brain metastases, and brain metastases with epidermal growth factor receptor (EGFR) L858R mutation occurred more often in the caudate, cerebellum, and temporal lobe than those with exon 19 deletion of EGFR. Median depths of the lesions from the brain surface were 13.7 mm (range, 8.6-21.9) for exon 19 deleted EGFR, 11.5 mm (6.6-16.8) for L858R mutated, and 15.0 mm (10.0-20.7) for wild-type EGFR. Lesions with L858R mutated EGFR were located significantly closer to the brain surface than lesions with exon 19 deleted or wild-type EGFR (P = .0032 and P < .0001, respectively). Furthermore, brain metastases of adenocarcinoma lung cancer patients with a history of chemotherapy but not molecular targeted therapy were located significantly deeper from the brain surface (P = .0002).
  
  
  
  This analysis is the first to reveal the relationship between EGFR mutation status and the spatial distribution of brain metastases of lung cancer.
authors.affiliation: Department of Neurosurgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.T., M.K., M.T., T.A.); Department of Radiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (M.S., S.T., K.N.); Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.N., J.U., T.K., F.I.); Department of General Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (J.O., M.H.); Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Japan (R.H., N.H., T.Y.); Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan (A.K.).
authors.forename: Koji
authors.initials: K
authors.lastname: Takano
authors.affiliation: Department of Neurosurgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.T., M.K., M.T., T.A.); Department of Radiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (M.S., S.T., K.N.); Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.N., J.U., T.K., F.I.); Department of General Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (J.O., M.H.); Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Japan (R.H., N.H., T.Y.); Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan (A.K.).
authors.forename: Manabu
authors.initials: M
authors.lastname: Kinoshita
authors.affiliation: Department of Neurosurgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.T., M.K., M.T., T.A.); Department of Radiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (M.S., S.T., K.N.); Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.N., J.U., T.K., F.I.); Department of General Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (J.O., M.H.); Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Japan (R.H., N.H., T.Y.); Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan (A.K.).
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takagaki
authors.affiliation: Department of Neurosurgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.T., M.K., M.T., T.A.); Department of Radiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (M.S., S.T., K.N.); Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.N., J.U., T.K., F.I.); Department of General Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (J.O., M.H.); Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Japan (R.H., N.H., T.Y.); Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan (A.K.).
authors.forename: Mio
authors.initials: M
authors.lastname: Sakai
authors.affiliation: Department of Neurosurgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.T., M.K., M.T., T.A.); Department of Radiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (M.S., S.T., K.N.); Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.N., J.U., T.K., F.I.); Department of General Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (J.O., M.H.); Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Japan (R.H., N.H., T.Y.); Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan (A.K.).
authors.forename: Souichirou
authors.initials: S
authors.lastname: Tateishi
authors.affiliation: Department of Neurosurgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.T., M.K., M.T., T.A.); Department of Radiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (M.S., S.T., K.N.); Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.N., J.U., T.K., F.I.); Department of General Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (J.O., M.H.); Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Japan (R.H., N.H., T.Y.); Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan (A.K.).
authors.forename: Takamune
authors.initials: T
authors.lastname: Achiha
authors.affiliation: Department of Neurosurgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.T., M.K., M.T., T.A.); Department of Radiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (M.S., S.T., K.N.); Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.N., J.U., T.K., F.I.); Department of General Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (J.O., M.H.); Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Japan (R.H., N.H., T.Y.); Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan (A.K.).
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Hirayama
authors.affiliation: Department of Neurosurgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.T., M.K., M.T., T.A.); Department of Radiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (M.S., S.T., K.N.); Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.N., J.U., T.K., F.I.); Department of General Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (J.O., M.H.); Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Japan (R.H., N.H., T.Y.); Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan (A.K.).
authors.forename: Kazumi
authors.initials: K
authors.lastname: Nishino
authors.affiliation: Department of Neurosurgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.T., M.K., M.T., T.A.); Department of Radiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (M.S., S.T., K.N.); Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.N., J.U., T.K., F.I.); Department of General Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (J.O., M.H.); Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Japan (R.H., N.H., T.Y.); Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan (A.K.).
authors.forename: Junji
authors.initials: J
authors.lastname: Uchida
authors.affiliation: Department of Neurosurgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.T., M.K., M.T., T.A.); Department of Radiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (M.S., S.T., K.N.); Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.N., J.U., T.K., F.I.); Department of General Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (J.O., M.H.); Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Japan (R.H., N.H., T.Y.); Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan (A.K.).
authors.forename: Toru
authors.initials: T
authors.lastname: Kumagai
authors.affiliation: Department of Neurosurgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.T., M.K., M.T., T.A.); Department of Radiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (M.S., S.T., K.N.); Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.N., J.U., T.K., F.I.); Department of General Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (J.O., M.H.); Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Japan (R.H., N.H., T.Y.); Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan (A.K.).
authors.forename: Jiro
authors.initials: J
authors.lastname: Okami
authors.affiliation: Department of Neurosurgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.T., M.K., M.T., T.A.); Department of Radiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (M.S., S.T., K.N.); Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.N., J.U., T.K., F.I.); Department of General Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (J.O., M.H.); Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Japan (R.H., N.H., T.Y.); Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan (A.K.).
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawaguchi
authors.affiliation: Department of Neurosurgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.T., M.K., M.T., T.A.); Department of Radiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (M.S., S.T., K.N.); Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.N., J.U., T.K., F.I.); Department of General Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (J.O., M.H.); Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Japan (R.H., N.H., T.Y.); Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan (A.K.).
authors.forename: Naoya
authors.initials: N
authors.lastname: Hashimoto
authors.affiliation: Department of Neurosurgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.T., M.K., M.T., T.A.); Department of Radiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (M.S., S.T., K.N.); Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.N., J.U., T.K., F.I.); Department of General Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (J.O., M.H.); Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Japan (R.H., N.H., T.Y.); Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan (A.K.).
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Nakanishi
authors.affiliation: Department of Neurosurgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.T., M.K., M.T., T.A.); Department of Radiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (M.S., S.T., K.N.); Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.N., J.U., T.K., F.I.); Department of General Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (J.O., M.H.); Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Japan (R.H., N.H., T.Y.); Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan (A.K.).
authors.forename: Fumio
authors.initials: F
authors.lastname: Imamura
authors.affiliation: Department of Neurosurgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.T., M.K., M.T., T.A.); Department of Radiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (M.S., S.T., K.N.); Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.N., J.U., T.K., F.I.); Department of General Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (J.O., M.H.); Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Japan (R.H., N.H., T.Y.); Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan (A.K.).
authors.forename: Masahiko
authors.initials: M
authors.lastname: Higashiyama
authors.affiliation: Department of Neurosurgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.T., M.K., M.T., T.A.); Department of Radiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (M.S., S.T., K.N.); Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (K.N., J.U., T.K., F.I.); Department of General Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan (J.O., M.H.); Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Japan (R.H., N.H., T.Y.); Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan (A.K.).
authors.forename: Toshiki
authors.initials: T
authors.lastname: Yoshimine
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000368:Aged; D001932:Brain Neoplasms / Q000556:secondary*; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D055752:Small Cell Lung Carcinoma / Q000235:genetics / Q000473:pathology; D014057:Tomography, X-Ray Computed
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR; MRI; location analysis; lung cancer brain metastasis