title: Prognostic impact of central nervous system metastases after acquired resistance to EGFR-TKI: poorer prognosis associated with T790M-negative status and leptomeningeal metastases.
abstract: OBJECTIVE
  The aim of the present study was to investigate the prognostic impact of central nervous system metastases (CNS) after acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) in EGFR-mutant non-small cell lung cancer (NSCLC).
  
  
  METHODS
  We defined CNS-collapse as death due to uncontrolled and progressive CNS metastases. Post-progression survival (PPS) after initial TKI failure and T790M status were retrospectively compared in 92 patients with or without CNS collapse.
  
  
  RESULTS
  The median PPS in 32 patients with CNS-collapse (16.7 months) was significantly shorter than that of 60 without (26.8 months) (p=0.0002). T790M was detected in four (12%) out of the 32 CNS-collapse patients and in 26 (43%) out of 60 without (p=0.0026). Median PPS in 39 patients with leptomeningeal metastases (LM) (11.4 months) was significantly shorter versus 53 without (26.8 months) (p=0.0006). The median PPS was 25.1 months in 40 patients with brain metastases and 11.2 months in 52 without (p=0.0387). T790M was detected in 4/5 resected brain tumors (80%) and in 1/26 cerebrospinal fluid (CSF) samples (4%) (p=0.0008).
  
  
  CONCLUSIONS
  CNS-collapse represented poorer prognosis, which was associated with T790M-negative status and LM. Controlling CNS metastases, especially LM, is important to achieve longer survival.
authors: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe, Japan a-hata@fbri.org.
authors: Akito
authors: A
authors: Hata
authors: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe, Japan.
authors: Nobuyuki
authors: N
authors: Katakami
authors: Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan.
authors: Hiroshige
authors: H
authors: Yoshioka
authors: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe, Japan.
authors: Jumpei
authors: J
authors: Takeshita
authors: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe, Japan.
authors: Kosuke
authors: K
authors: Tanaka
authors: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe, Japan.
authors: Katsuhiro
authors: K
authors: Masago
authors: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe, Japan.
authors: Shiro
authors: S
authors: Fujita
authors: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe, Japan.
authors: Reiko
authors: R
authors: Kaji
authors: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe, Japan.
authors: Yukihiro
authors: Y
authors: Imai
authors: Department of Respiratory Medicine, Kobe City Medical Center, General Hospital, Kobe, Japan.
authors: Kazuya
authors: K
authors: Monden
authors: Department of Respiratory Medicine, Kobe City Medical Center, General Hospital, Kobe, Japan.
authors: Takeshi
authors: T
authors: Matsumoto
authors: Department of Respiratory Medicine, Kobe City Medical Center, General Hospital, Kobe, Japan.
authors: Kazuma
authors: K
authors: Nagata
authors: Department of Respiratory Medicine, Kobe City Medical Center, General Hospital, Kobe, Japan.
authors: Kyoko
authors: K
authors: Otsuka
authors: Department of Respiratory Medicine, Kobe City Medical Center, General Hospital, Kobe, Japan.
authors: Ryo
authors: R
authors: Tachikawa
authors: Department of Respiratory Medicine, Kobe City Medical Center, General Hospital, Kobe, Japan.
authors: Keisuke
authors: K
authors: Tomii
authors: Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan.
authors: Kei
authors: K
authors: Kunimasa
authors: Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan.
authors: Masahiro
authors: M
authors: Iwasaku
authors: Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan.
authors: Akihiro
authors: A
authors: Nishiyama
authors: Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan.
authors: Tadashi
authors: T
authors: Ishida
authors: Department of Respiratory Medicine, Kobe University School of Medicine, Kobe, Japan.
authors: Yoshihiro
authors: Y
authors: Nishimura
mesh_terms: D000368:Aged; D016543:Central Nervous System Neoplasms / Q000556:secondary*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D008297:Male; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012189:Retrospective Studies
chemical_list: D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors
keywords: Central nervous system; T790M; acquired resistance; brain metastases; epidermal growth factor receptor-tyrosine kinase inhibitor; leptomeningeal metastases