title: Experience with targeted next generation sequencing for the care of lung cancer: insights into promises and limitations of genomic oncology in day-to-day practice.
abstract: BACKGROUND
  Tumor genotyping using single gene assays (SGAs) is standard practice in advanced non-small-cell lung cancer (NSCLC). We evaluated how the introduction of next generation sequencing (NGS) into day-to-day clinical practice altered therapeutic decision-making.
  
  
  METHODS
  Clinicopathologic data, tumor genotype, and clinical decisions were retrospectively compiled over 6 months following introduction of NGS assay use at our institution in 82 patient-tumor samples (7 by primary NGS, 22 by sequential SGAs followed by NGS, and 53 by SGAs).
  
  
  RESULTS
  SGAs identified abnormalities in 34 samples, and all patients with advancedEGFR-mutated orALK-rearranged tumors received approved tyrosine kinase inhibitors (TKIs) or were consented for clinical trials. NGS was more commonly requested forEGFR,ALK, andKRAS-negative tumors (p<0.0001). NGS was successful in 24/29 (82.7%) tumors. Of 17 adenocarcinomas (ACs), 11 (7 from patients with ≤15 pack-years of smoking) had abnormalities in a known driver oncogene. This led to a change in decision-making in 8 patients, trial consideration in 6, and off-label TKI use in 2. Of 7 squamous cell (SC) carcinomas, 1 had a driver aberration (FGFR1); 6 had other genomic events (all withTP53mutations). In no cases were clinical decisions altered (p=0.0538 when compared to ACs).
  
  
  CONCLUSIONS
  Targeted NGS can identify a significant number of therapeutically-relevant driver events in lung ACs; particularly in never or light smokers. For SC lung cancers, NGS is less likely to alter current practice. Further research into the cost effectiveness and optimal use of NGS and improved provider training in genomic oncology are warranted.
authors.affiliation: Department of Medicine, 330 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Deepa
authors.initials: D
authors.lastname: Rangachari
authors.affiliation: Department of Pathology, 330 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: VanderLaan
authors.affiliation: Department of Medicine, 330 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Xiuning
authors.initials: X
authors.lastname: Le
authors.affiliation: Department of Medicine, 330 Brookline Avenue, Boston, MA 02215, USA ; Department of Surgery, 330 Brookline Avenue, Boston, MA 02215, USA; all at Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Folch
authors.affiliation: Department of Surgery, 330 Brookline Avenue, Boston, MA 02215, USA; all at Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kent
authors.affiliation: Department of Surgery, 330 Brookline Avenue, Boston, MA 02215, USA; all at Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Sidharta P
authors.initials: SP
authors.lastname: Gangadharan
authors.affiliation: Department of Medicine, 330 Brookline Avenue, Boston, MA 02215, USA ; Department of Surgery, 330 Brookline Avenue, Boston, MA 02215, USA; all at Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Adnan
authors.initials: A
authors.lastname: Majid
authors.affiliation: Department of Pathology, 330 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Haspel
authors.affiliation: Department of Pathology, 330 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Loren J
authors.initials: LJ
authors.lastname: Joseph
authors.affiliation: Department of Medicine, 330 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Huberman
authors.affiliation: Department of Medicine, 330 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Costa
keywords: ALK; EGFR; MET; Non-small-cell lung cancer; ROS1; adenocarcinoma; driver oncogene; genotype; next generation sequencing; squamous cell carcinomas