Vol.:(0123456789) 1 3 Journal of Neuro-Oncology (2019) 145:151–157 https://doi.org/10.1007/s11060-019-03282-0 CLINICAL STUDY 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 1  · Toru Serizawa 2  · Masaaki Yamamoto 3  · Yoshinori Higuchi 4  · Yasunori Sato 5  · Takashi Shuto 6  · Atsuya Akabane 7  · Hidefumi Jokura 8  · Jun Kawagishi 8  · Hidefumi Aoyama 9 Received: 16 July 2019 / Revised: 28 August 2019 / Accepted: 29 August 2019 / Published online: 5 September 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract 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 effi- cacy 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 identi- fied 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 intrac- ranial 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 treat- ment efficacy and toxicity of SRS did not differ between patients with/without EGFR-TKI use. Keywords Non-small cell lung cancer · Epidermal growth factor receptor · Tyrosine kinase inhibitors · Brain metastases · Gamma knife radiosurgery · Propensity score matching analysis Abbreviations BM Brain metastases EGFR Epidermal growth factor receptor Toru Serizawa, Masaaki Yamamoto have contributed equally to this study. * Shoji Yomo yomoshoji@gmail.com 1 Division of Radiation Oncology, Aizawa Comprehensive Cancer Center, Aizawa Hospital, 2-5-1, Honjo, Matsumoto, Nagano Prefecture 390-0814, Japan 2 Tokyo Gamma Unit Center, Tsukiji Neurological Clinic, Tokyo, Japan 3 Katsuta Hospital Mito Gamma House, Hitachinaka, Japan 4 Department of Neurological Surgery, Chiba University Graduate School of Medicine, Chiba, Japan 5 Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan 6 Department of Neurosurgery, Yokohama Rosai Hospital, Yokohama, Japan 7 Gamma Knife Center, NTT Medical Center Tokyo, Tokyo, Japan 8 Jiro Suzuki Memorial Gamma House, Furukawa Seiryo Hospital, Osaki, Japan 9 Department of Radiology, Niigata University Graduate School of Medicine and Dental Sciences, Niigata, Japan Author's personal copy