title: Prognostic molecular assay might improve identification of patients at risk for recurrence in early-stage non-small-cell lung cancer.
abstract: BACKGROUND
  Adjuvant chemotherapy improves survival for some patients with NSCLC and is recommended in NCCN guidelines for stage Ib to IIa patients with certain "high-risk" characteristics. An internationally validated, 14-gene expression assay has been shown to better stratify mortality risk in nonsquamous NSCLC than either conventional staging or these high risk clinicopathologic features.
  
  
  METHODS
  A blinded chart review of 52 patients with prospective molecular risk stratification using the 14-gene test compared recurrence outcomes with a mean follow-up of 15.2 ± 11.7 months of patients with high- or low-risk determined according to either NCCN criteria or the molecular assay.
  
  
  RESULTS
  Molecular risk assessment was discordant from NCCN criteria in 14 of 23 patients in stages Ib and IIa (61%). Recurrence was not observed among any of 31 molecular intermediate- or low-risk patients, including 10 NCCN high-risk patients, whereas 2 of 6 recurrences (33%) occurred among NCCN low-risk patients. Recurrences in stages I or IIa were seen in 2 of 18 NCCN high-risk patients (11%; both were stage IIa and both received a high-risk molecular designation), and in 4 of 18 patients (22%) with a high-risk molecular score, including 1 stage Ia and 1 stage Ib patient.
  
  
  CONCLUSIONS
  This small cohort study suggests that a 14-gene prognostic assay more accurately stratifies risk among early-stage NSCLC patients than current NCCN criteria. NCCN guidelines already advocate risk stratification within tumor, node, metastases stages. This molecular assay has clinical utility in better identifying high-risk patients and might improve NCCN adjuvant chemotherapy recommendations.
authors.affiliation: Department of Surgery, University of California at San Francisco, San Francisco, CA.
authors.forename: Gavitt A
authors.initials: GA
authors.lastname: Woodard
authors.affiliation: Department of Medicine, University of California at San Francisco, San Francisco, CA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Gubens
authors.affiliation: Department of Medicine, University of California at San Francisco, San Francisco, CA.
authors.forename: Thierry M
authors.initials: TM
authors.lastname: Jahan
authors.affiliation: Department of Pathology, University of California at San Francisco, San Francisco, CA.
authors.forename: Kirk D
authors.initials: KD
authors.lastname: Jones
authors.affiliation: Department of Surgery, University of California at San Francisco, San Francisco, CA.
authors.forename: Jasleen
authors.initials: J
authors.lastname: Kukreja
authors.affiliation: Department of Surgery, University of California at San Francisco, San Francisco, CA.
authors.forename: Pierre R
authors.initials: PR
authors.lastname: Theodore
authors.affiliation: Department of Surgery, University of California at San Francisco, San Francisco, CA.
authors.forename: Shayne
authors.initials: S
authors.lastname: Cardozo
authors.affiliation: Department of Surgery, University of California at San Francisco, San Francisco, CA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Jew
authors.affiliation: Department of Surgery, University of California at San Francisco, San Francisco, CA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Clary-Macy
authors.affiliation: Department of Surgery, University of California at San Francisco, San Francisco, CA. Electronic address: david.jablons@ucsfmedctr.org.
authors.forename: David M
authors.initials: DM
authors.lastname: Jablons
authors.affiliation: Department of Surgery, University of California at San Francisco, San Francisco, CA. Electronic address: michael.mann@ucsfmedctr.org.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mann
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000453:epidemiology* / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012306:Risk; D016019:Survival Analysis
keywords: Genetic signature; NCCN guidelines; Recurrence predictors; Risk stratification; Tumor profile