title: Outcomes by tumor histology and KRAS mutation status after lung stereotactic body radiation therapy for early-stage non-small-cell lung cancer.
abstract: BACKGROUND
  We analyzed outcomes after lung stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung-carcinoma (NSCLC) by histology and KRAS genotype.
  
  
  METHODS
  We included 75 patients with 79 peripheral tumors treated with SBRT (18 Gy × 3 or 10 to 12 Gy × 5) at our institution from 2009 to 2012. Genotyping for KRAS mutations was performed in 10 patients. Outcomes were analyzed by the Kaplan-Meier method/Cox regression, or cumulative incidence method/Fine-Gray analysis.
  
  
  RESULTS
  The median patient age was 74 (range, 46 to 93) years, and Eastern Cooperative Oncology Group performance status was 0 to 1 in 63%. Tumor histology included adenocarcinoma (44%), squamous cell carcinoma (25%), and NSCLC (18%). Most tumors were T1a (54%). Seven patients had KRAS-mutant tumors (9%). With a median follow-up of 18.8 months among survivors, the 1-year estimate of overall survival was 88%, cancer-specific survival (CSS) 92%, primary tumor control 94%, and freedom from recurrence (FFR) 67%. In patients with KRAS-mutant tumors, there was a significantly lower tumor control (67% vs. 96%; P = .04), FFR (48% vs. 69%; P = .03), and CSS (75% vs. 93%; P = .05). On multivariable analysis, histology was not associated with outcomes, but KRAS mutation (hazard ratio, 10.3; 95% confidence interval, 2.3-45.6; P = .0022) was associated with decreased CSS after adjusting for age.
  
  
  CONCLUSIONS
  In this SBRT series, histology was not associated with outcomes, but KRAS mutation was associated with lower FFR on univariable analysis and decreased CSS on multivariable analysis. Because of the small sample size, these hypothesis-generating results need to be studied in larger data sets.
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA. Electronic address: rmak@lroc.harvard.edu.
authors.forename: Raymond H
authors.initials: RH
authors.lastname: Mak
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, MA.
authors.forename: Gretchen
authors.initials: G
authors.lastname: Hermann
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA.
authors.forename: John H
authors.initials: JH
authors.lastname: Lewis
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA; Department of Radiology, Brigham and Women's Hospital, Boston, MA.
authors.forename: Hugo J W L
authors.initials: HJ
authors.lastname: Aerts
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA.
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Baldini
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA.
authors.forename: Aileen B
authors.initials: AB
authors.lastname: Chen
authors.affiliation: Division of Thoracic Surgery, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA.
authors.forename: Yolonda L
authors.initials: YL
authors.lastname: Colson
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA.
authors.forename: Fred H
authors.initials: FH
authors.lastname: Hacker
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA.
authors.forename: David
authors.initials: D
authors.lastname: Kozono
authors.affiliation: Division of Thoracic Surgery, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA.
authors.forename: Jon O
authors.initials: JO
authors.lastname: Wee
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA; Department of Biostatistics, Harvard School of Public Health, Boston, MA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Catalano
authors.affiliation: Lowe Center for Thoracic Oncology and Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA.
authors.forename: Kwok-Kin
authors.initials: KK
authors.lastname: Wong
authors.affiliation: Department of Radiation Oncology, Rush University Medical Center, Chicago, IL.
authors.forename: David J
authors.initials: DJ
authors.lastname: Sher
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000401:mortality / Q000532:radiotherapy; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D016634:Radiosurgery; D016019:Survival Analysis; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: Early stage; KRAS; Non–small-cell lung cancer; Stereotactic body radiotherapy