title: Prognostic significance of genotype and number of metastatic sites in advanced non-small-cell lung cancer.
abstract: BACKGROUND
  TNM stage remains the most important prognostic factor in clinical practice. The 7th edition lung cancer staging system has not considered some important prognostic factors, such as the number of metastatic organ sites and the molecular biologic characterization.
  
  
  METHODS
  Using driver gene alternation and tumor burden, advanced NSCLC cases were divided into 3 groups: M1-I group, epidermal growth factor (EGFR)-positive and/or anaplastic lymphoma kinase (ALK)-positive; MI-II, wild-type EGFR and ALK with intrathoracic metastasis or 1 distant metastatic organ with ≤ 3 metastasis lesions; and MI-III, wild-type EGFR and ALK with 1 distant metastatic organ with > 3 metastasis lesions or multiple metastatic organs. Overall survival was comparable between the 7th edition staging system and our category of M descriptors.
  
  
  RESULTS
  A total of 627 patients with stage IV NSCLC newly diagnosed at Guangdong Lung Cancer Institute between January 2009 and July 2012 were enrolled in the present study. The median overall survival (OS) was 22.2 (95% CI, 19.590-24.810), 15.5 (95% CI, 13.176-17.824), and 10.0 (95% CI, 8.033-11.967) months for M1-I, M1-II, and M1-III, respectively (P < .001). According to the 7th edition of the TNM staging system, the median OS of the M1a and M1b groups was 22.8 (95% CI, 19.484-26.116) and 13.7 (95% CI, 11.793-15.607) months, respectively (P < .001). The maximum of the absolute values of the M1 category for our study and the 7th TNM staging system was 5.881 and 5.089, respectively.
  
  
  CONCLUSIONS
  Advanced NSCLC could potentially be further divided into 3 subgroups according to the genotype and number of metastatic organ sites and metastasis lesions.
authors.affiliation: Southern Medical University, Guangzhou, Guangdong, China; Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
authors.forename: Yan-yan
authors.initials: YY
authors.lastname: He
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
authors.forename: Xu-chao
authors.initials: XC
authors.lastname: Zhang
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
authors.forename: Jin-ji
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Southern Medical University, Guangzhou, Guangdong, China; Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
authors.forename: Fei-yu
authors.initials: FY
authors.lastname: Niu
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
authors.forename: Hong-hong
authors.initials: HH
authors.lastname: Yan
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
authors.forename: Chong-rui
authors.initials: CR
authors.lastname: Xu
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
authors.forename: Ji-lin
authors.initials: JL
authors.lastname: Guan
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
authors.forename: Wen-zhao
authors.initials: WZ
authors.lastname: Zhong
authors.affiliation: Southern Medical University, Guangzhou, Guangdong, China; Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
authors.forename: Lu-lu
authors.initials: LL
authors.lastname: Yang
authors.affiliation: Southern Medical University, Guangzhou, Guangdong, China; Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
authors.forename: Long-hua
authors.initials: LH
authors.lastname: Guo
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China. Electronic address: syylwu@live.cn.
authors.forename: Yi-long
authors.initials: YL
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D015331:Cohort Studies; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis; D047368:Tumor Burden
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases
keywords: Genotyping; Metastatic organ site; Non–small-cell lung cancer; Overall survival; Prognosis