Salvage gamma knife radiosurgery for active brain metastases from small-cell lung cancer after whole-brain radiation therapy: a retrospective multi-institutional study (JLGK1701)



To evaluate the efficacy of gamma knife radiosurgery (GKS) for brain metastases (BMs) from small-cell lung cancer after whole-brain radiotherapy (WBRT).


We retrospectively analyzed the usefulness and safety of GKS in 163 patients from 15 institutions with 1–10 active BMs after WBRT. The usefulness and safety of GKS were evaluated using statistical methods.


The median age was 66 years, and 79.1% of patients were men. The median number and largest diameter of BM were 2.0 and 1.4 cm, respectively. WBRT was administered prophylactically in 46.6% of patients. The median overall survival (OS) was 9.3 months, and the neurologic mortality was 20.0%. Crude incidences of local control failure and new lesion appearance were 36.6% and 64.9%, respectively. A BM diameter ≥ 1.0 cm was a significant risk factor for local progression (hazard ratio [HR] 2.556, P = 0.039) and neurologic death (HR 4.940, P = 0.031). Leukoencephalopathy at the final follow-up was more prevalent in the therapeutic WBRT group than in the prophylactic group (P = 0.019). The symptom improvement rate was 61.3%, and neurological function was preserved for a median of 7.6 months. Therapeutic WBRT was not a significant risk factor for OS, neurological death, local control, or functional deterioration (P = 0.273, 0.490, 0.779, and 0.560, respectively). Symptomatic radiation-related adverse effects occurred in 7.4% of patients.


GKS can safely preserve neurological function and prevent neurologic death in patients with 1–10 small, active BMs after prophylactic and therapeutic WBRT.

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We are grateful to Kana Inoue and Tomoko Fukushima at the Brain Attack Ota Memorial Hospital for their help with managing the database.


This study did not receive financial support.

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Correspondence to Kiyoshi Nakazaki.

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The authors report no conflicts of interest concerning the materials or methods used in this study or the findings specified in this paper.

Research involving human participants and/or animals

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee (Brain Attack Center Ota Memorial Hospital institutional review board [approval number 133]) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.”

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Nakazaki, K., Yomo, S., Kondoh, T. et al. Salvage gamma knife radiosurgery for active brain metastases from small-cell lung cancer after whole-brain radiation therapy: a retrospective multi-institutional study (JLGK1701). J Neurooncol (2020).

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  • Gamma knife radiosurgery
  • Brain metastases
  • Small-cell lung cancer
  • Whole-brain radiation therapy
  • Leukoencephalopathy