title: Clinical outcome in patients with leptomeningeal metastasis from non-small cell lung cancer: Okayama Lung Cancer Study Group.
abstract: OBJECTIVE
  We examined the prognosis of patients with leptomeningeal metastasis (LM) from non-small cell lung cancer (NSCLC) and that stratified by epidermal growth factor receptor (EGFR) mutation status in LM patients receiving EGFR-tyrosine kinase inhibitors (TKIs).
  
  
  METHODS
  We retrospectively analyzed a series of 91 consecutive NSCLC patients with LM between 2001 and 2010.
  
  
  RESULTS
  Most of the LM patients had adenocarcinoma histology and a poor performance status (PS). The median survival time (MST) for all patients was 3.6 months. Adenocarcinoma and TKI treatment were associated with a better prognosis. Among the patients, 51 received EGFR-TKIs. Of these, the EGFR mutation status was assessed in 30 patients; 7 (23%) showed no mutation (group 1), 10 (33%) had a mutation in exon 21 (group 2), and 13 (43%) had deletions in exon 19 (group 3). Interestingly, PS was significantly improved in groups 2 and 3 but not in group 1. The MST in these subgroups was 1.4, 7.1, and 11.0 months in groups 1, 2, and 3, respectively (p<0.001). The median time to progression or symptom deterioration was 0.9, 2.0, and 7.8 months for groups 1, 2, and 3, respectively (p<0.001). A multivariate analysis showed that EGFR-mutant tumors were associated with a better prognosis in patients receiving EGFR-TKIs.
  
  
  CONCLUSIONS
  The prognosis for patients with LM from NSCLC was still poor. Survival after the initiation of EGFR-TKI treatment differed according to the type of EGFR mutation, suggesting the potential benefit of TKIs for patients with EGFR mutations, even though they suffered from LM.
authors.affiliation: Division of Clinical Oncology, Sumitomo Besshi Hospital, 3-1 Ohji-cho, Niihama, Japan. sumemura@east.ncc.go.jp
authors.forename: Shigeki
authors.initials: S
authors.lastname: Umemura
authors.forename: Kazuya
authors.initials: K
authors.lastname: Tsubouchi
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Yoshioka
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Hotta
authors.forename: Nagio
authors.initials: N
authors.lastname: Takigawa
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Naokatsu
authors.initials: N
authors.lastname: Horita
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Segawa
authors.forename: Noboru
authors.initials: N
authors.lastname: Hamada
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takata
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Yamane
authors.forename: Haruhito
authors.initials: H
authors.lastname: Kamei
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality / Q000556:secondary*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000401:mortality / Q000556:secondary*; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D005260:Female; D000077156:Gefitinib; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D008297:Male; D008577:Meningeal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000556:secondary*; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011799:Quinazolines / Q000627:therapeutic use; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib