title: Risk factors for brain metastases in locally advanced non-small cell lung cancer with definitive chest radiation.
abstract: OBJECTIVE
  We intended to identify risk factors that affect brain metastases (BM) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving definitive radiation therapy, which may guide the choice of selective prevention strategies.
  
  
  METHODS
  The characteristics of 346 patients with stage III NSCLC treated with thoracic radiation therapy from January 2008 to December 2010 in our institution were retrospectively reviewed. BM rates were analyzed by the Kaplan-Meier method. Multivariate Cox regression analysis was performed to determine independent risk factors for BM.
  
  
  RESULTS
  The median follow-up time was 48.3 months in surviving patients. A total of 74 patients (21.4%) experienced BM at the time of analysis, and for 40 (11.7%) of them, the brain was the first site of failure. The 1-year and 3-year brain metastasis rates were 15% and 28.1%, respectively. In univariate analysis, female sex, age ≤60 years, non-squamous cell carcinoma, T3-4, N3, >3 areas of lymph node metastasis, high lactate dehydrogenase and serum levels of tumor markers (CEA, NSE, CA125) before treatment were significantly associated with BM (P<.05). In multivariate analysis, age ≤60 years (P=.004, hazard ratio [HR] = 0.491), non-squamous cell carcinoma (P=.000, HR=3.726), NSE >18 ng/mL (P=.008, HR=1.968) and CA125 ≥ 35 U/mL (P=.002, HR=2.129) were independent risk factors for BM. For patients with 0, 1, 2, and 3 to 4 risk factors, the 3-year BM rates were 7.3%, 18.9%, 35.8%, and 70.3%, respectively (P<.001).
  
  
  CONCLUSIONS
  Age ≤60 years, non-squamous cell carcinoma, serum NSE >18 ng/mL, and CA125 ≥ 35 U/mL were independent risk factors for brain metastasis. The possibilities of selectively using prophylactic cranial irradiation in higher-risk patients with LA-NSCLC should be further explored in the future.
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Ji
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Bi
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
authors.forename: Jingbo
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
authors.forename: Zhouguang
authors.initials: Z
authors.lastname: Hui
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
authors.forename: Zefen
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
authors.forename: Qinfu
authors.initials: Q
authors.lastname: Feng
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
authors.forename: Zongmei
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
authors.forename: Dongfu
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
authors.forename: Jima
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Fan
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
authors.forename: Lipin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China. Electronic address: wlhwq@yahoo.com.
authors.forename: Luhua
authors.initials: L
authors.lastname: Wang
mesh_terms: D000367:Age Factors; D014408:Biomarkers, Tumor / Q000097:blood; D001932:Brain Neoplasms / Q000401:mortality / Q000517:prevention & control / Q000556:secondary*; D018394:CA-125 Antigen / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000556:secondary*; D016371:Cranial Irradiation; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008175:Lung Neoplasms / Q000097:blood / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010751:Phosphopyruvate Hydratase / Q000097:blood; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal; D012044:Regression Analysis; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D007770:L-Lactate Dehydrogenase; D010751:Phosphopyruvate Hydratase