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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)

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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 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.

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Abbreviations

BM:

Brain metastases

EGFR:

Epidermal growth factor receptor

JLGK:

Japanese Leksell Gamma Knife

NCI-CTCAE:

National Cancer Institute Common Terminology Criteria for Adverse Events

NSCLC:

Non-small cell lung cancer

OS:

Overall survival

PSM:

Propensity score matching

SRS:

Stereotactic radiosurgery

TKI:

Tyrosine kinase inhibitors

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Acknowledgements

We are grateful to Bierta Barfod, M.D., M.P.H. for her help with the language editing of this manuscript.

Funding

11,000,000 Japanese Yen were provided to the JLGK0901 study by the Japan Brain Foundation.

Author information

Author notes

  1. Toru Serizawa, Masaaki Yamamoto have contributed equally to this study.

Authors and Affiliations

  1. Division of Radiation Oncology, Aizawa Comprehensive Cancer Center, Aizawa Hospital, 2-5-1, Honjo, Matsumoto, Nagano Prefecture, 390-0814, Japan

    Shoji Yomo

  2. Tokyo Gamma Unit Center, Tsukiji Neurological Clinic, Tokyo, Japan

    Toru Serizawa

  3. Katsuta Hospital Mito Gamma House, Hitachinaka, Japan

    Masaaki Yamamoto

  4. Department of Neurological Surgery, Chiba University Graduate School of Medicine, Chiba, Japan

    Yoshinori Higuchi

  5. Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan

    Yasunori Sato

  6. Department of Neurosurgery, Yokohama Rosai Hospital, Yokohama, Japan

    Takashi Shuto

  7. Gamma Knife Center, NTT Medical Center Tokyo, Tokyo, Japan

    Atsuya Akabane

  8. Jiro Suzuki Memorial Gamma House, Furukawa Seiryo Hospital, Osaki, Japan

    Hidefumi Jokura & Jun Kawagishi

  9. Department of Radiology, Niigata University Graduate School of Medicine and Dental Sciences, Niigata, Japan

    Hidefumi Aoyama

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  1. Shoji Yomo
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Corresponding author

Correspondence to Shoji Yomo.

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The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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The institutional review board of each facility participating in the JLGK0901 study approved all aspects of this study, and patients provided written informed consent before enrolment.

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Yomo, S., Serizawa, T., Yamamoto, M. et al. 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). J Neurooncol 145, 151–157 (2019). https://doi.org/10.1007/s11060-019-03282-0

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