title: The risk of second primary tumors after resection of stage I nonsmall cell lung cancer.
abstract: BACKGROUND
  The incidence of second primary lung cancers (SPLC) after resection of nonsmall cell lung cancer (NSCLC) is estimated to be 1% to 4% per patient year. The overall effect of SPLC on survival after resection of stage I NSCLC is unknown. Here we report the incidence, management, and outcome of SPLC in a large prospective cohort of patients who underwent careful follow-up.
  
  
  METHODS
  National Cancer Institute Intergroup Trial NCI #I91-0001 examined the effectiveness of isotretinoin A for chemoprevention of second primary tumors, the primary endpoint in that trial. Prospective data from patients randomly assigned to the placebo arm were analyzed.
  
  
  RESULTS
  Five hundred sixty-nine patients underwent complete resection of pathologic stage I NSCLC. The median follow-up was 5.9 years. Second primary tumors developed in 88 (15%) patients. Of these, 49 (56%) were SPLC (incidence = 1.99/100 patient-years), with a median interval from initial surgery of 4.2 years. Second primary lung cancer never developed in patients who had never smoked (n = 44, p = 0.046; never versus ever smokers). Current smokers had a higher incidence of SPLC than former smokers (hazard ratio = 1.91, p = 0.03). Age, sex, stage, histology, tumor location and initial surgery had no effect on SPLC development. Despite semiannual follow-up with chest radiographs, 12 (24%) patients had metastatic disease at the time of diagnosis of SPLC. Surgical resection was performed in 31 (63%) SPLC patients. Median survival was 4.1 years in those who underwent surgery and 1.4 years in those who did not (p = 0.003). Overall SPLC-related mortality in the original cohort was 3.7%.
  
  
  CONCLUSIONS
  Patients who undergo surgery for SPLC can achieve prolonged survival. Despite close follow-up however many patients with SPLC present with advanced disease. That indicates a need for continued lifelong postoperative surveillance.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. drice@mdanderson.org
authors.forename: David
authors.initials: D
authors.lastname: Rice
authors.forename: Hyung-Woo
authors.initials: HW
authors.lastname: Kim
authors.forename: Anita
authors.initials: A
authors.lastname: Sabichi
authors.forename: Scott
authors.initials: S
authors.lastname: Lippman
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.forename: Brendell
authors.initials: B
authors.lastname: Williams
authors.forename: Ara
authors.initials: A
authors.lastname: Vaporciyan
authors.forename: W Roy
authors.initials: WR
authors.lastname: Smythe
authors.forename: Stephen
authors.initials: S
authors.lastname: Swisher
authors.forename: Garrett
authors.initials: G
authors.lastname: Walsh
authors.forename: Joe B
authors.initials: JB
authors.lastname: Putnam
authors.forename: Waun Ki
authors.initials: WK
authors.lastname: Hong
authors.forename: Jack
authors.initials: J
authors.lastname: Roth
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D015474:Isotretinoin / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology* / Q000517:prevention & control / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000401:mortality / Q000473:pathology* / Q000517:prevention & control; D011446:Prospective Studies
chemical_list: D015474:Isotretinoin