The impact of EGFR-TKI use on clinical outcomes of lung adenocarcinoma patients with brain metastases after Gamma Knife radiosurgery: a propensity score-matched analysis based on extended JLGK0901 dataset (JLGK0901-EGFR-TKI)

Shoji Yomo, Toru Serizawa, Masaaki Yamamoto, Yoshinori Higuchi, Yasunori Sato, Takashi Shuto, Atsuya Akabane, Hidefumi Jokura, Jun Kawagishi, Hidefumi Aoyama

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Purpose: Recent advances in targeted therapy have prolonged overall survival (OS) for patients with lung cancer. The impact of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) on brain metastases (BM) treated with stereotactic radiosurgery (SRS) has not, however, been fully elucidated. We investigated the influence of post-SRS EGFR-TKI use on the efficacy and toxicity of SRS for BM from lung adenocarcinoma. Methods: We used the updated dataset of the Japanese Leksell Gamma Knife (JLGK) 0901 study, which proved the efficacy of Gamma Knife SRS in patients with BM. Propensity score matching (PSM) analysis was employed to determine the impact of concurrent or post-SRS EGFR-TKI use on OS, neurological death, intracranial disease recurrence and SRS-related adverse events. Results: Among 1194 patients registered in the JLGK0901 study, 608 eligible lung adenocarcinoma patients were identified and 238 (39%) had received EGFR-TKI concurrently or during the post-SRS clinical course. After PSM, there were 200 patient pairs with/without post-SRS EGFR-TKI use. EGFR-TKI use was associated with longer OS (median 25.5 vs. 11.0 months, HR 0.60, 95% CI 0.48–0.75, p < 0.001), although the long-term OS curves eventually crossed. Distant intracranial recurrence was more likely in patients receiving EGFR-TKI (HR 1.45, 95% CI 1.12–1.89, p = 0.005). Neurological death, local recurrence and SRS-related adverse event rates did not differ significantly between the two groups. Conclusions: Although patients receiving EGFR-TKI concurrently or after SRS had significantly longer OS, the local treatment efficacy and toxicity of SRS did not differ between patients with/without EGFR-TKI use.

Original languageEnglish
Pages (from-to)151-157
Number of pages7
JournalJournal of Neuro-Oncology
Issue number1
Publication statusPublished - 2019 Oct 1



  • Brain metastases
  • Epidermal growth factor receptor
  • Gamma knife radiosurgery
  • Non-small cell lung cancer
  • Propensity score matching analysis
  • Tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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