title: KRAS Status as an Independent Prognostic Factor for Survival after Yttrium-90 Radioembolization Therapy for Unresectable Colorectal Cancer Liver Metastases.
abstract: OBJECTIVE
  To evaluate Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status as a prognostic factor for survival after yttrium-90 ((90)Y) radioembolization for colorectal cancer (CRC) liver metastases.
  
  
  METHODS
  Consecutive patients with unresectable CRC liver metastases and documented KRAS mutation status who were treated with (90)Y radioembolization during the period 2007-2014 were investigated. Patient demographics, disease characteristics, therapy regimens, and overall survival (OS) from first (90)Y radioembolization were compared between patients with KRAS wild-type (wt) and mutant status. Kaplan-Meier estimation and Cox regression were used for survival analysis and to assess independent prognostic factors for OS.
  
  
  RESULTS
  Of 186 patients, 104 underwent KRAS mutation analysis before (90)Y radioembolization, with 45 (43.3%) identified as mutant. The wt and mutant groups were similar in demographics, liver status, overall performance status, and tumor characteristics (all P > .05). Mean time from liver metastasis to (90)Y radioembolization was greater in patients with KRAS wt status (P = .033). A greater percentage of wt patients received anti-epidermal growth factor receptor therapies before (90)Y radioembolization (66.1% vs 8.9%; P < .001). Median OS from first (90)Y radioembolization was significantly greater in KRAS wt patients (9.5 mo vs 4.8 mo; P = .041). Univariate analysis identified Child-Pugh class, carcinoembryonic antigen (CEA), chemotherapy after (90)Y radioembolization, KRAS status, and treatment-induced toxicity as prognostic factors for OS. Multivariate Cox regression analysis demonstrated Child-Pugh class, CEA, and KRAS status to be independent prognostic factors for OS, even when correcting for the effect of chemotherapy after (90)Y radioembolization.
  
  
  CONCLUSIONS
  Patients with CRC and KRAS wt may derive greater survival benefit from (90)Y radioembolization therapy than patients with KRAS mutant.
authors.affiliation: Division of Interventional Radiology, Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Lahti
authors.affiliation: Division of Interventional Radiology, Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Minzhi
authors.initials: M
authors.lastname: Xing
authors.affiliation: Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Di
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.; Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Division of Interventional Radiology, Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Magnetta
authors.affiliation: Division of Interventional Radiology, Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.; Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.. Electronic address: kevin.kim@yale.edu.
authors.forename: Hyun S
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics / Q000401:mortality* / Q000532:radiotherapy*; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality* / Q000532:radiotherapy / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D010414:Pennsylvania / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D016016:Proportional Hazards Models; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D017678:Sex Distribution; D016019:Survival Analysis; D016896:Treatment Outcome; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; D016283:Proto-Oncogene Proteins p21(ras)