title: Risk of Second Primary Malignancies in Lung Cancer Survivors - The Influence of Different Treatments.
abstract: Currently, no large study addressing the relationship between lung cancer patients with different therapies and second primary malignancies (SPMs) is available.
  
  
  
  Using the Taiwan National Health Insurance Research Database, we conducted a population-based cohort study. Patients with newly diagnosed lung cancer between 1997 and 2005 were enrolled and followed up until Dec. 31, 2011. The endpoint of the study was SPM occurrence. Standardized incidence ratios (SIRs) of cancers were calculated to compare the cancer incidence of the study cohort to that of the general population.
  
  
  
  We identified 52,639 patients with lung cancer and excluded 34,267 patients who had expired within one year after diagnosis. The study included 18,372 subjects with a median follow-up period of 2.24 years. 590 patients developed an SPM. The overall cancer risk was significantly increased (SIR 1.33, 95% confidence interval [CI]: 1.22-1.44, p < 0.001), and there was a significant increase in the incidences of head and neck (SIR 1.60, 95% CI 1.21-2.07, p = 0.001), bone and soft tissue (SIR 2.65, 95% CI 1.27-4.87, p = 0.011), genitourinary (SIR 1.50, 95% CI 1.27-1.76, p < 0.001), and thyroid (SIR 3.85, 95% CI 2.28-6.08, p < 0.001) cancers. Importantly, after multivariate adjustment, the use of tyrosine kinase inhibitors (TKIs) statistically significantly reduced SPM incidence (HR, 0.41; 95% CI, 0.21-0.79; p = 0.008).
  
  
  
  Our study indicates that lung cancer may be a risk factor for SPM. TKI use was associated with a significantly lower risk of SPM development. However, because patients with epidermal growth factor receptor mutant lung adenocarcinoma (associated with non-smokers) tend to receive TKI treatment, they might have fewer smoking-related SPMs.
authors.affiliation: Department of Critical Care Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.|Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Vincent Yi-Fong
authors.initials: VY
authors.lastname: Su
authors.affiliation: Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.|Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|Institute of Public Health, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chia-Jen
authors.initials: CJ
authors.lastname: Liu
authors.affiliation: Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.|Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yuh-Min
authors.initials: YM
authors.lastname: Chen
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.|Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.|Molecular Pathology, Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Teh-Ying
authors.initials: TY
authors.lastname: Chou
authors.affiliation: Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.|Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Tzeng-Ji
authors.initials: TJ
authors.lastname: Chen
authors.affiliation: Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.|Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan.|Department of Biomedical Imaging and Radiological Sciences, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Sang-Hue
authors.initials: SH
authors.lastname: Yen
authors.affiliation: Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.|Division of Transfusion Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|National Defense Medical Center, Taipei, Taiwan.
authors.forename: Tzeon-Jye
authors.initials: TJ
authors.lastname: Chiou
authors.affiliation: Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.|Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Jin-Hwang
authors.initials: JH
authors.lastname: Liu
authors.affiliation: Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan. mimicx@gmail.com.|Institute of Public Health, National Yang-Ming University, Taipei, Taiwan. mimicx@gmail.com.|Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan. mimicx@gmail.com.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Hu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000209:etiology* / Q000628:therapy; D012307:Risk Factors; D055815:Young Adult