title: Prognostic impact of KRAS mutation subtypes in 677 patients with metastatic lung adenocarcinomas.
abstract: BACKGROUND
  We previously demonstrated that patients with metastatic KRAS mutant lung cancers have a shorter survival compared with patients with KRAS wild-type cancers. Recent reports have suggested different clinical outcomes and distinct activated signaling pathways depending on KRAS mutation subtype. To better understand the impact of KRAS mutation subtype, we analyzed data from 677 patients with KRAS mutant metastatic lung cancer.
  
  
  METHODS
  We reviewed all patients with metastatic or recurrent lung cancers found to have KRAS mutations over a 6-year time period. We evaluated the associations among KRAS mutation type, clinical factors, and overall survival in univariate and multivariate analyses. Any significant findings were validated in an external multi-institution patient dataset.
  
  
  RESULTS
  Among 677 patients with KRAS mutant lung cancers (53 at codon 13, 624 at codon 12), there was no difference in overall survival for patients when comparing KRAS transition versus transversion mutations (p = 0.99), smoking status (p = 0.33), or when comparing specific amino acid substitutions (p = 0.20). In our dataset, patients with KRAS codon 13 mutant tumors (n = 53) had shorter overall survival compared with patients with codon 12 mutant tumors (n = 624) (1.1 versus 1.3 years, respectively; p = 0.009), and the findings were confirmed in a multivariate Cox model controlling for age, sex, and smoking status (hazard ratio: 1.52, 95% confidence interval: 1.11-2.08; p = 0.008). In an independent validation set of tumors from 682 patients with stage IV KRAS mutant lung cancers, there was no difference in survival between patients with KRAS codon 13 versus codon 12 mutations (1.0 versus 1.1 years, respectively; p = 0.41).
  
  
  CONCLUSIONS
  Among individuals with KRAS mutant metastatic lung cancers treated with conventional therapy, there are no apparent differences in outcome based on KRAS mutation subtype.
authors.affiliation: *Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, †Department of Epidemiology and Biostatistics, ‡Department of Pathology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY; §Department of Medicine, Massachusetts General Hospital Cancer Center, Boston, MA; ‖Department of Medicine, Vanderbilt Ingram Cancer Center, Franklin, TN; and ¶Lowe center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, MA.
authors.forename: Helena A
authors.initials: HA
authors.lastname: Yu
authors.forename: Camelia S
authors.initials: CS
authors.lastname: Sima
authors.forename: Ronglai
authors.initials: R
authors.lastname: Shen
authors.forename: Samantha
authors.initials: S
authors.lastname: Kass
authors.forename: Justin
authors.initials: J
authors.lastname: Gainor
authors.forename: Alice
authors.initials: A
authors.lastname: Shaw
authors.forename: Megan
authors.initials: M
authors.lastname: Hames
authors.forename: Wade
authors.initials: W
authors.lastname: Iams
authors.forename: Jonathan
authors.initials: J
authors.lastname: Aston
authors.forename: Christine M
authors.initials: CM
authors.lastname: Lovly
authors.forename: Leora
authors.initials: L
authors.lastname: Horn
authors.forename: Christine
authors.initials: C
authors.lastname: Lydon
authors.forename: Geoffrey R
authors.initials: GR
authors.lastname: Oxnard
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
authors.forename: Marc
authors.initials: M
authors.lastname: Ladanyi
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Riely
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000556:secondary*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)