Timing of Whole Brain Radiotherapy on Survival of Patients with EGFR-mutated 
Non-small Cell Lung Cancer and Brain Metastases

Abstract

Background and objective There is no high-level evidence for the time of whole brain radiotherapy (WBRT) for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) and brain metastases. The aim of this study is to assess the appropriate timing of WBRT for patients with EGFR-mutated NSCLC and brain metastases (BM). Methods There were 78 patients diagnosed with EGFR-mutated NSCLC and BM in Beijing Chest Hospital between August 2009 and May 2015. 48 untreated patients who received both WBRT and EGFR-tyrosine kinase inhibitors (TKIs) therapy. Prognostic factors of intracranial progression-free survival (PFS) and overall survival (OS) were identified by Cox proportional hazards modeling. Results Intracranial objective response rate was 81.3% and disease control rate was 93.8%. Median intracranial PFS was 10 months. Median OS was 18 months. Multivariate analysis of intracranial PFS revealed that Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 (HR=30.436, 95%CI: 4.721-196.211, P<0.001) and early WBRT (HR=3.663, 95%CI: 1.657-8.098, P=0.001) had a better intracranial PFS. Multivariate analysis of OS revealed that PS 0-1 (HR=57.607, 95%CI: 6.135-540.953, P<0.001), early WBRT (HR=2.757, 95%CI: 1.140-6.669, P=0.024), and stereotactic radiosurgery (HR=5.964, 95%CI: 1.895-18.767, P=0.002) were independent prognostic factors of OS. Conclusion Early WBRT combined with EGFR-TKIs can improve outcomes of patients with EGFR-mutated NSCLC and BM, but it needs to be confirmed by large-sample-size and multicenter prospective clinical trials.

Keywords

• Whole brain radiotherapy
• Tyrosine kinase inhibitors
• Epidermal growth factor receptor mutation
• Lung neoplasms
• Brain metastasis