title: Clinical outcomes of patients with metachronous second primary lung adenocarcinomas.
abstract: BACKGROUND
  The incidence of adenocarcinomas as multiple primary lung cancers (MPLCs) is increasing. How to determine the treatment strategies of MPLCs, especially second primary lung adenocarcinomas (SPLACs), and the prognostic factors associated with it are unclear.
  
  
  METHODS
  The clinical records of patients undergoing surgery for second adenocarcinomas based on Martini-Melamed criteria between 2001 and 2014 were retrospectively reviewed. Survival rates were calculated by the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis was conducted using the Cox proportional hazards model.
  
  
  RESULTS
  A total of 115 patients with SPLACs were identified based on Martini-Melamed criteria. With respect to the second resections, three subgroups with low- (adenocarcinoma in situ, n=6; minimally invasive adenocarcinoma, n=19), intermediate- (lepidic, n=9; acinar, n=40; papillary, n=23), and high-grades (solid, n=9; micropapillary, n=2; invasive mucinous, n=7) were assigned. The 5-year overall survival (OS) rates from the time of the first and the second resections were 86.5% and 69.5%, respectively. Cox multivariate analysis identified computed tomography (CT) morphology of SPLACs (ground glass opacity predominant versus solid predominant; hazard ratio [HR]=0.42;P=0.036), histologic classification (same/similar vs different; HR=0.06;P<0.001), pathologic stage of the primary (stage I vs II; HR=0.20;P=0.015) and second tumors (stage I vs IIIa; HR=0.21;P=0.002), and histologic grade of SPLACs (low- vs high-grade, HR=0.05,P=0.016; intermediate- vs high-grade, HR=0.37,P=0.027) as significantly favorable prognostic factors for OS.
  
  
  CONCLUSIONS
  In addition to pathologic stage of the initial tumors and histologic classification, pathologic stage and CT morphology of SPLACs were identified as predictors of survival. The histologic grade of SPLACs based on the new adenocarcinoma classification could provide additional prognostic information.
authors.affiliation: Department of Cardiovascular Surgery of First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Division of General Thoracic Surgery, Inselspital, Bern University Hospital; Graduate School for Cellular and Biomedical Sciences; Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Haitang
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai.
authors.forename: Ke
authors.initials: K
authors.lastname: Han
authors.affiliation: Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai.
authors.forename: Feng
authors.initials: F
authors.lastname: Yao
authors.affiliation: Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai.
authors.forename: Liwen
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai.
authors.forename: Haiyong
authors.initials: H
authors.lastname: Gu
authors.affiliation: Department of Cardiovascular Surgery of First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
authors.forename: Zhenya
authors.initials: Z
authors.lastname: Shen
keywords: adenocarcinoma; metachronous; multiple primary lung cancer