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Research Article: Association between radiotherapy timing and intracranial outcomes in EGFR-mutant NSCLC with brain metastases treated with EGFR-TKIs

Date Published: 2026-06-22

Abstract:
This study evaluated the treatment outcomes and prognostic factors that influence the overall survival (OS) and intracranial progression-free survival (iPFS) in patients with epidermal growth factor receptor ( EGFR )-mutated non-small cell lung cancer (NSCLC) and brain metastases (BMs) who were treated with radiotherapy (RT) combined with EGFR tyrosine kinase inhibitors (EGFR-TKIs). The clinical data obtained from patients diagnosed with EGFR -mutated NSCLC and BMs who underwent local or whole-brain RT between January 2015 and December 2020 were retrospectively reviewed. Statistical analysis was performed using SPSS version 26.0. A total of 135 patients were included. Among them, 70 patients (51.9%) received early RT, while 65 patients (48.1%) received delayed RT. All patients were treated with EGFR-TKIs, either before or during RT. In the univariate analysis, the EGFR mutation subtype and the extent of metastases were associated with OS ( p < 0.05), while the mutation subtype and the timing of RT were linked to iPFS. The multivariate analysis confirmed that exon 19 deletions and limited metastatic disease were independent prognostic factors for OS and that early RT independently improved iPFS ( p < 0.05). Patients who received early RT had longer iPFS compared with patients who received delayed RT (14.6 vs. 10.4 months, p = 0.010). The median OS was also superior in patients with exon 19 deletions compared to patients with exon 21 L858R mutations (37.5 vs. 25.1 months, p = 0.009). The combination of EGFR-TKIs with early RT can enhance the intracranial disease control in patients with EGFR -mutated NSCLC and BMs. Furthermore, patients with exon 19 deletions had a more favorable prognosis compared with patients who harbored exon 21 L858R mutations.

Introduction:
Lung cancer remains the leading cause of cancer incidence and mortality worldwide ( 1 ). Non-small cell lung cancer (NSCLC) accounts for roughly 85% of all cases, with adenocarcinoma and squamous cell carcinoma being the most frequent histological types ( 2 ). Among patients with adenocarcinoma, mutations in the epidermal growth factor receptor ( EGFR ) gene are the most common, followed by rearrangements in the anaplastic lymphoma kinase ( ALK ) gene ( 3 ). In Asian populations, the prevalence of EGFR mutations…

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