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Fractionated pre-operative stereotactic radiotherapy for patients with brain metastases: a multi-institutional analysis



The current standard of care for patients with a large brain metastasis and limited intracranial disease burden is surgical resection and post-operative single fraction stereotactic radiosurgery (SRS). However, post-operative SRS can still lead to substantial rates of local failure (LF), radiation necrosis (RN), and meningeal disease (MD). Pre-operative SRS may reduce the risk of RN and MD, while fractionated treatments may improve local control by allowing delivery of higher biological effective dose. We hypothesize that pre-operative fractionated stereotactic radiation therapy (FSRT) can minimize rates of LF, RN, and MD.


A retrospective, multi-institutional analysis was conducted and included patients who had pre-operative FSRT for a large or symptomatic brain metastasis. Pertinent demographic, clinical, radiation, surgical, and follow up data were collected for each patient. A primary measurement was the rate of a composite endpoint of (1) LF, (2) MD, and/or (3) Grade 2 or higher (symptomatic) RN.


53 patients with 55 lesions were eligible for analysis. FSRT was prescribed to a dose of 24–25 Gy in 3–5 fractions. There were 0 LFs, 3 Grade 2–3 RN events, and 1 MD occurrence, which corresponded to an 8% per-patient composite endpoint event rate.


In this study, the composite endpoint of 8% for pre-operative FSRT was improved compared to previously reported rates with post-operative SRS of 49–60% (N107C, Mahajan etal. JCOG0504) and pre-operative SRS endpoints of 20.6% (PROPS-BM). Pre-operative FSRT appears to be safe, effective, and may decrease the incidence of adverse outcomes. Prospective validation is needed.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.


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Authors and Affiliations



All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by HKP, JDP, JM, CH, BK, and RP. BK: responsible for Statistical Analysis. The first draft of the manuscript was written by HKP, JDP, JM, CH, BK, and RP, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Joshua D. Palmer.

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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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Palmer, J.D., Perlow, H.K., Matsui, J.K. et al. Fractionated pre-operative stereotactic radiotherapy for patients with brain metastases: a multi-institutional analysis. J Neurooncol (2022).

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  • Stereotactic radiosurgery
  • Fractionated stereotactic radiosurgery
  • Pre-operative
  • Surgery
  • Brain metastasis
  • Leptomeningeal disease