EGFR mutant status and tyrosine-kinase inhibitors affect the GKRS outcomes for NSCLC brain metastases

Hung Ruei Liao, Chi Lu Chiang, Chia I. Shen, Ching Jen Chen, Huai Che Yang, Hsiu Mei Wu, Yung Hung Luo, Yong Sin Hu, Chung Jung Lin, Wen Yuh Chung, Cheng Ying Shiau, Wan Yuo Guo, David Hung Chi Pan, Cheng Chia Lee

Research output: Contribution to journalArticlepeer-review


Objective: Tyrosine kinase inhibitors (TKIs) is the first-line treatment for EGFR-positive non-small cell lung cancer (NSCLC); however, its applicability to patients with wild-type NSCLC remains an issue of contention. This study compared the effects of gamma knife radiosurgery (GKRS) alone versus combining GKRS and TKIs in treating two genetic forms of NSCLC. Methods: This retrospective study examined 479 NSCLC patients with 1982 brain metastases who underwent GKRS and for whom imaging follow-up data or death records were available. All our patients were consecutive. All gene mutations were confirmed by lung biopsy. The three main endpoints in this study were overall survival (OS), local intracranial tumor control (LC), and distal intracranial tumor control (DC). Results: There were 296 NSCLC patients with EGFR positive: TKI treatment (n = 262) and without TKI treatment (n = 34). GKRS + TKIs was more effective than GKRS alone in terms of OS (HR 0.53, p = 0.085) and DC (HR 0.51, p < 0.001). There were 150 NSCLC patients with wild-type EGFR: TKI treatment (n = 50) and without TKI treatment (n = 100). GKRS + TKIs was less effective than GKRS alone in terms of OS (HR 1.82, p = 0.049) and DC (HR: 1.40, p = 0.011). We observed no difference in terms of LC in both genetic groups. Conclusions: Combining GKRS with TKIs proved effective in EGFR positive NSCLC patients; however, we do not observe the similar results when combining GKRS with TKIs for patients with wild-type NSCLC.

Original languageEnglish
Pages (from-to)675-684
Number of pages10
JournalJournal of Neuro-Oncology
Issue number3
Publication statusPublished - Sept 2022


  • Brain metastasis
  • EGFR
  • Gamma knife
  • Mutations
  • Non-small cell lung cancer
  • Radiosurgery
  • Stereotactic surgery
  • Survival
  • Tumor control
  • Tyrosine-kinase inhibitor
  • Wild type

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research


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