KRAS Status as an Independent Prognostic Factor for Survival after Yttrium-90 Radioembolization Therapy for Unresectable Colorectal Cancer Liver Metastases

J Vasc Interv Radiol. 2015 Aug;26(8):1102-11. doi: 10.1016/j.jvir.2015.05.032.

Abstract

Purpose: 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.

Materials and 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.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Age Distribution
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality*
  • Colorectal Neoplasms / radiotherapy*
  • Disease-Free Survival
  • Female
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Liver Neoplasms / mortality*
  • Liver Neoplasms / radiotherapy
  • Liver Neoplasms / secondary*
  • Male
  • Middle Aged
  • Pennsylvania / epidemiology
  • Polymorphism, Single Nucleotide / genetics
  • Prognosis
  • Proportional Hazards Models
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Radiopharmaceuticals / therapeutic use
  • Reproducibility of Results
  • Risk Factors
  • Sensitivity and Specificity
  • Sex Distribution
  • Survival Analysis
  • Treatment Outcome
  • Yttrium Radioisotopes / therapeutic use*

Substances

  • Biomarkers, Tumor
  • KRAS protein, human
  • Radiopharmaceuticals
  • Yttrium Radioisotopes
  • Proto-Oncogene Proteins p21(ras)