title: Prognosis of synchronous and metachronous multiple primary lung cancers: systematic review and meta-analysis.
abstract: BACKGROUND
  With the development of imaging technology, an increasing number of multiple primary lung cancers (MPLC) are diagnosed in recent years. However, there is still ambiguity in the stage classification rules for patients with MPLC. Our purpose was to access the prognosis of synchronous and metachronous MPLC.
  
  
  METHODS
  A systematic literature search was performed on four databases (EBSCO, Pubmed, OVID and Springer) to obtain relevant articles. We used published hazard ratios (HRs) of overall survival (OS) if available or estimates from the published survival data.
  
  
  RESULTS
  There were 1796 patients with MPLC in 22 relevant studies, who were eligible for analysis. We found that the OS of patients with synchronous MPLC was inferior to the one of metachronous MPLC patients when starting from the diagnosis of the first metachronous tumor (HR 3.36, 95% CI 2.39-4.74; p<0.001). However, there was no difference when starting from the diagnosis of the second metachronous tumor (HR 1.19, 95% CI 0.86-1.66; p=0.29). From further analysis we found the OS of patients with MPLC was superior to that of patients with intrapulmonary metastasis (HR 2.66, 95% CI 1.30-5.44; p=0.007). Besides, we found no difference in OS between synchronous (HR 1.39, 95% CI 0.98-1.96; p=0.06) and metachronous (HR 1.05, 95% CI 0.75-1.47; p=0.77) patients, in spite of the histology. In terms of unilateral and bilateral MPLC patients, the OS had no difference either (HR 1.30, 95% CI 1.00-1.69; p=0.05).
  
  
  CONCLUSIONS
  We found that MPLC had better OS than the lung cancer patients with intrapulmonary metastasis. And despite the tumor-free interval, the OS for metachronous MPLC was as good as that for synchronous MPLC. Furthermore, there was no difference of OS in different subgroups, including histology and position.
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Guangzhou Institute of Respiratory Disease, China State Key Laboratory of Respiratory Disease, Guangzhou, China.
authors.forename: Long
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Guangzhou Institute of Respiratory Disease, China State Key Laboratory of Respiratory Disease, Guangzhou, China.
authors.forename: Jiaxi
authors.initials: J
authors.lastname: He
authors.affiliation: Department of thoracic surgery, Cancer Center of Guangzhou Medical University, China.
authors.forename: Xiaoshun
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Guangzhou Institute of Respiratory Disease, China State Key Laboratory of Respiratory Disease, Guangzhou, China.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Guangzhou Institute of Respiratory Disease, China State Key Laboratory of Respiratory Disease, Guangzhou, China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Liang
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Guangzhou Institute of Respiratory Disease, China State Key Laboratory of Respiratory Disease, Guangzhou, China.
authors.forename: Chenglin
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Guangzhou Institute of Respiratory Disease, China State Key Laboratory of Respiratory Disease, Guangzhou, China. Electronic address: drhe_jianxing@163.com.
authors.forename: Jianxing
authors.initials: J
authors.lastname: He
mesh_terms: D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000401:mortality*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009378:Neoplasms, Multiple Primary / Q000175:diagnosis / Q000401:mortality*; D016609:Neoplasms, Second Primary / Q000175:diagnosis / Q000401:mortality*; D011379:Prognosis; D016016:Proportional Hazards Models
keywords: Histology; Metachronous; Multiple primary lung cancer; Overall survival; Prognosis; Synchronous