Impact of EGFR mutations and KRAS amino acid substitution on the response to radiotherapy for brain metastasis of non-small-cell lung cancer

Future Oncol. 2016 Jan;12(1):59-70. doi: 10.2217/fon.15.273. Epub 2015 Nov 30.

Abstract

Background: Our study aimed to evaluate response rate (RR) to brain metastasis radiotherapy (RT), depending on the genomic status of non-small-cell lung cancer.

Material & methods: We retrospectively reviewed 1971 non-small-cell lung cancer files of patients with EGFR and KRAS testing and focused on 157 patients who had undergone RT for brain metastasis.

Results: A total of 16 patients (10.2%) harbored EGFR mutations (mEGFR) and 45 patients (28.7%) KRAS (mKRAS). In univariate analysis, RR was significantly higher for mEGFR compared with wild-type EGFR/KRAS (odds ratio [OR]: 4.96; p = 0.05) or mKRAS (OR: 1.81; p = 0.03). In multivariate analysis, KRAS G12V or G12C status was associated with both poor RR (OR: 0.1; p < 0.0001) and overall survival (OR: 3.41; p < 0.0001).

Conclusion: mEGFR are associated with higher RR to brain RT than wild-type EGFR/RAS or mKRAS.

Keywords: EGFR; G12C; G12V; KRAS; brain metastases; non-small-cell lung cancer; radiotherapy.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amino Acid Substitution / genetics
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Brain Neoplasms / radiotherapy*
  • Brain Neoplasms / secondary
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / radiotherapy*
  • Disease-Free Survival
  • ErbB Receptors / genetics*
  • Female
  • Genetic Association Studies
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Mutation
  • Polymorphism, Single Nucleotide
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Radiation Tolerance / genetics

Substances

  • KRAS protein, human
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)