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Gamma knife icon based hypofractionated stereotactic radiosurgery (GKI-HSRS) for brain metastases: impact of dose and volume

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Gamma Knife Icon-based hypofractionated stereotactic radiosurgery (GKI-HSRS) is a novel technical paradigm in the treatment of brain metastases that allows for both the dosimetric benefits of the GKI stereotactic radiosurgery (SRS) platform as well as the biologic benefits of fractionation. We report mature local control and adverse radiation effect (ARE) outcomes following 5 fraction GKI-HSRS for intact brain metastases.


Patients with intact brain metastases treated with 5-fraction GKI-HSRS were retrospectively reviewed. Survival, local control, and adverse radiation effect rates were determined. Univariable and multivariable regression (MVA) were performed on potential predictive factors.


Two hundred and ninety-nine metastases in 146 patients were identified. The median clinical follow-up was 10.7 months (range 0.5–47.6). The median total dose and prescription isodose was 27.5 Gy (range, 20–27.5) in 5 daily fractions and 52% (range, 45–93), respectively. The median overall survival (OS) was 12.7 months, and the 1-year local failure rate was 15.2%. MVA identified a total dose of 27.5 Gy vs. ≤ 25 Gy (hazard ratio [HR] 0.59, p = 0.042), and prior chemotherapy exposure (HR 1.99, p = 0.015), as significant predictors of LC. The 1-year ARE rate was 10.8% and the symptomatic ARE rate was 1.8%. MVA identified a gross tumor volume of ≥ 4.5 cc (HR 7.29, p < 0.001) as a significant predictor of symptomatic ARE.


Moderate total doses in 5 daily fractions of GKI-HSRS were associated with high rates of LC and a low incidence of symptomatic ARE.

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The authors would like to acknowledge Collins Yeboah for his direction with physics support, and Pejman Maralani for his guidance with imaging outcomes evaluation.


This study was not supported by any funding.

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EA: author responsible for statistical analysis.

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Correspondence to Zain Husain.

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Conflict of interest

HS reports travel and education grants from Elekta. SD reports research grants from Alkermes Medical and consultant fees from Medexus. SM reports research support and honoraria from AAA/Novartis and Ipsen. CLT reports honoraria from Elekta and serves on the advisory board for Sanofi. AS reports consulting fees and grants from Varian and Elekta, as well as honoraria from Varian, BrainLab, and Elekta. He is also an associate editor for the Journal of Neuro-Oncology. All other authors have no disclosures.

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Yan, M., Holden, L., Wang, M. et al. Gamma knife icon based hypofractionated stereotactic radiosurgery (GKI-HSRS) for brain metastases: impact of dose and volume. J Neurooncol 159, 705–712 (2022).

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