title: Synchronous non-small cell lung cancers: diagnostic yield can be improved by histologic and genetic methods.
abstract: OBJECTIVE
  Current criteria for identification of synchronous non-small cell lung cancers (NSCLCs) may be confusing in patients with lymphatic metastases. This study was aimed at investigating the strategy using both the new histologic classification and driver-mutational testing to define multiple primary lung cancers.
  
  
  METHODS
  Prospectively collected data of surgical patients with synchronous NSCLCs were retrospectively analyzed. Cases were defined using the Martini-Melamed criteria, and validated by histologic subtyping based on the new classification and driver mutation of selected genes. Survival was estimated between patients with multiple primary and metastatic disease controlling by nodal (N) stage. Factors associated with prolonged survival were evaluated using the Cox proportional hazards mode.
  
  
  RESULTS
  A total of 131 patients followed for at least 12 months were included in this study. Controlling by N0 stage, patients who were diagnosed with multiple primary NSCLCs showed better relapse-free survival (RFS) than those with intrapulmonary metastases categorized either by the Martini-Melamed criteria or by histologic-mutational methods (both p < 0.0001). However, at N+ stage, patients stratified by Martini-Melamed criteria showed no difference in survival (p = 0.517), while those defined by histologic-mutational methods maintained superior survival compared with the control group (p = 0.042). On multivariate analysis, only N0 and diagnosis of independent lung lesions by histologic-mutational methods were significant predictors of better RFS (p = 0.031 and 0.001, respectively)
  
  
  CONCLUSIONS
  The histologic-mutational strategy may be an option for identification of synchronous NSCLC when traditional criteria were not applicable, especially in cases with positive lymphatics. N0 stage and the diagnosis of independent pulmonary tumors were associated with better RFS.
authors: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
authors: Yiliang
authors: Y
authors: Zhang
authors: Haichuan
authors: H
authors: Hu
authors: Rui
authors: R
authors: Wang
authors: Ting
authors: T
authors: Ye
authors: Yunjian
authors: Y
authors: Pan
authors: Lei
authors: L
authors: Wang
authors: Yang
authors: Y
authors: Zhang
authors: Hang
authors: H
authors: Li
authors: Yuan
authors: Y
authors: Li
authors: Lei
authors: L
authors: Shen
authors: Yongfu
authors: Y
authors: Yu
authors: Yihua
authors: Y
authors: Sun
authors: Haiquan
authors: H
authors: Chen
authors: David
authors: D
authors: Garfield
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics / Q000401:mortality; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics / Q000401:mortality; D003952:Diagnostic Imaging / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D009378:Neoplasms, Multiple Primary / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor