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Gamma Knife® stereotactic radiosurgery for intracranial cavernous malformations

  • Mihir D. Shanker
    Correspondence
    Corresponding author at: Department of Radiation Oncology, Garry Reichart Gamma Knife Fellow, PA Research Foundation, Princess Alexandra Hospital, 199 Ipswich Rd, Brisbane, QLD, Australia.
    Affiliations
    Garry Reichart Gamma Knife Fellow, PA Research Foundation, Princess Alexandra Hospital, Brisbane, QLD, Australia

    Gamma Knife Centre of Queensland, Princess Alexandra Hospital, Brisbane, QLD, Australia

    Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
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  • Rebecca Webber
    Affiliations
    Gamma Knife Centre of Queensland, Princess Alexandra Hospital, Brisbane, QLD, Australia

    Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
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  • Mark B. Pinkham
    Affiliations
    Gamma Knife Centre of Queensland, Princess Alexandra Hospital, Brisbane, QLD, Australia

    Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
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  • Michael Huo
    Affiliations
    Gamma Knife Centre of Queensland, Princess Alexandra Hospital, Brisbane, QLD, Australia

    Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
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  • Sarah Olson
    Affiliations
    Gamma Knife Centre of Queensland, Princess Alexandra Hospital, Brisbane, QLD, Australia

    Princess Alexandra Hospital, Brisbane, QLD, Australia

    Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
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  • Bruce Hall
    Affiliations
    Gamma Knife Centre of Queensland, Princess Alexandra Hospital, Brisbane, QLD, Australia

    Princess Alexandra Hospital, Brisbane, QLD, Australia

    Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
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  • Rumal Jayalath
    Affiliations
    Princess Alexandra Hospital, Brisbane, QLD, Australia

    Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
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  • Trevor Watkins
    Affiliations
    Princess Alexandra Hospital, Brisbane, QLD, Australia

    Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
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  • Matthew C. Foote
    Affiliations
    Gamma Knife Centre of Queensland, Princess Alexandra Hospital, Brisbane, QLD, Australia

    Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
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      Highlights

      • First reported Australian cohort of patients treated with Gamma Knife stereotactic radiosurgery (GKSRS) for cerebral cavernous malformations (CCMs).
      • Largest pooled analysis of non-randomised studies to date assessing the impact of GKSRS on re-haemorrhage risk in CCMs.
      • Eightfold reduction in haemorrhage events following GKSRS with majority of risk reduction occurring in the initial 2 years following treatment.
      • Significant reduction in matched annual bleed rate from pre-GKSRS (52.1 %) compared to after SRS (12.3 %) (p < 0.001) [OR = 0.07, 95 % 0.008–0.283].
      • Treatment is safe overall with an overall low risk of morbidity (3% in the Australian cohort).

      Abstract

      Introduction

      Gamma Knife® stereotactic radiosurgery (GKSRS) is a non-invasive alternative to surgical resection for cerebral cavernous malformations (CCMs), especially in eloquent locations.

      Methodology

      A retrospective review was performed on an Australian cohort of patients receiving GKSRS for CCMs at a single institution. All patients exhibited symptoms and/or radiological evidence of haemorrhage before therapy. The minimum follow-up was 1-year post-GKSRS. McNemar’s test was used for differences in matched-pair outcomes pre- and post-GKSRS with an α = 0.05. A systematic review and meta-analysis was additionally performed to synthesise the current published evidence on the clinical efficacy of stereotactic radiosurgery in reducing haemorrhage risk in CCMs using a DerSimonian and Laird random effects model.

      Results

      Thirty-five patients (39 cavernomas) underwent GKSRS. 87.2 % of patients had evidence of at least one haemorrhage before GKSRS and the remainder exhibited seizures. The median dose was 12.5 Gy in a single fraction (IQR 12–13). The median follow-up duration from GKSRS was 809 days (IQR 536–960). There was a significant reduction in matched annual bleed rate from pre-GKSRS (52.1 %) compared to after SRS (12.3 %) (p < 0.001) [OR = 0.07, 95 % 0.008–0.283] There was no statistically significant difference in seizure incidence pre- (30.7 %) versus post-GKSRS (17.9 %) (p = 0.13) [OR = 0.167, 95 %CI 0.004–1.37]. One patient (3 %) with a brainstem lesion experienced long-term treatment-related oedema with persistent ipsilateral weakness and tremors. On meta-analysis of 25 pooled studies, radiosurgery for the treatment of CCMs was associated with a statistically significantly relative risk (RR) reduction in haemorrhage events [random effects RR 0.12 (95 % CI 0.074–0.198), p < 0.001)], with most of the proportionate risk reduction occurring in the initial 2 years following SRS.

      Conclusion

      GKSRS significantly reduces the annual rate of haemorrhage for intracranial cavernomas in this cohort and on meta-analysis, particularly in the first 2 years following treatment. The overall risk of treatment-related morbidity is low.

      Keywords

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