title: Lymphovascular invasion in non-small-cell lung cancer: implications for staging and adjuvant therapy.
abstract: BACKGROUND
  Lymphovascular space invasion (LVI) is an established negative prognostic factor and an indication for postoperative radiation therapy in many malignancies. The purpose of this study was to evaluate LVI in patients with early-stage non-small-cell lung cancer, undergoing surgical resection.
  
  
  METHODS
  All patients who underwent initial surgery for pT1-3N0-2 non-small-cell lung cancer at Duke University Medical Center from 1995 to 2008 were identified. A multivariate ordinal regression was used to assess the relationship between LVI and pathologic hilar and/or mediastinal lymph node (LN) involvement. A multivariate Cox regression analysis was used to evaluate the relationship of LVI and other clinical and pathologic factors on local failure (LF), freedom from distant metastasis (FFDM), and overall survival (OS). Kaplan-Meier methods were used to generate estimates of LF, FFDM, and OS in patients with and without LVI.
  
  
  RESULTS
  One thousand five hundred and fifty-nine patients were identified. LVI was independently associated with the presence of regional LN involvement (p < 0.001) along with lobar (versus sublobar) resections (p < 0.001), and an open thoracotomy (versus video-assisted thoracoscopic surgery). LVI was not independently associated with LF on multivariate analysis (hazard ratio [HR] = 1.23, p = 0.25), but was associated with a lower FFDM (HR 1.52, p = 0.005) and OS (HR 1.26, p = 0.015). In addition, multivariate analysis showed that LVI was strongly associated with increased risk of developing distant metastases (HR = 1.75, p = 0.006) and death (HR = 1.53, p = 0.003) in adenocarcinomas but not in squamous carcinomas.
  
  
  CONCLUSIONS
  LVI is associated with an increased risk of harboring regional LN involvement. LVI is also an adverse prognostic factor for the development of distant metastases and long-term survival.
authors.affiliation: Department of Radiation Oncology, Emory University, Atlanta, GA, USA. kristin.higgins@emory.edu
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Higgins
authors.forename: Junzo P
authors.initials: JP
authors.lastname: Chino
authors.forename: Neal
authors.initials: N
authors.lastname: Ready
authors.forename: Thomas A
authors.initials: TA
authors.lastname: D'Amico
authors.forename: Mark F
authors.initials: MF
authors.lastname: Berry
authors.forename: Thomas
authors.initials: T
authors.lastname: Sporn
authors.forename: Jessamy
authors.initials: J
authors.lastname: Boyd
authors.forename: Chris R
authors.initials: CR
authors.lastname: Kelsey
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018287:Carcinoma, Large Cell / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008198:Lymph Nodes / Q000473:pathology* / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000601:surgery; D009367:Neoplasm Staging; D011013:Pneumonectomy; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D055815:Young Adult