Brain Metastasis of Patients with Lung Adenocarcinoma: Epidermal Growth Factor Receptor Mutations and Response to Whole-Brain Radiation Therapy

Brain metastases develop frequently in non-small cell lung cancers (NSCLC), and cause poor prognosis and rapid deterioration in neurologic function. Whole brain radiotherapy (WBRT) is the standard treatment for brain metastasis. Epidermal growth factor receptor (EGFR) is a determinant factor for the radiation response of cells. Overexpression of EGFR results in radioresistance, and non-homologous end-joining (NHEJ) plays an important role for repair of radiation-induced DNA damage. However, EGFR mutation cell lines show radiosensitive characteristics. After radiation, mutant EGFR could not translocate to the nucleus and failed to bind to the DNA-dependent protein kinase. This reduces radioresistance to lung cancer cell lines. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) may be active on brain metastases in NSCLC patients. A combination of WBRT and EGFR-TKIs seems to result in a favorable response rate and better overall survival of lung cancer patients. Further advances in the understanding of the metastatic cascade and the mechanism of radiation-induced cell damage may lead to new treatment modalities and better survival for lung patients with metastatic brain disease. ? 2014 Elsevier Inc. All rights reserved.