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Feasibility of dose escalation using intraoperative radiotherapy following resection of large brain metastases compared to post-operative stereotactic radiosurgery


Background and purpose

Post-operative SRS (stereotactic radiosurgery) for large brain metastases is challenged by risks of radiation necrosis that limit SRS dose. Intraoperative radiotherapy (IORT) is a potential alternative, however standard dose recommendations are lacking.

Methods and materials

Twenty consecutive brain metastases treated with post-operative SRS were retrospectively compared to IORT plans generated for 10–30 Gy in 1 fraction to 0–5 mm by estimating the applicator size and distance from critical organs using pre-operative and post-operative MRI. Additionally, 7 consecutive patients treated with IORT 30 Gy to surface were compared to retrospectively generated SRS plans using the post-operative MRI to 15–20 Gy and 30 Gy in 1 fraction marginal dose.


For the 20 resection cavities treated with SRS and retrospectively compared to IORT, IORT from 10 to 30Gy resulted in lower or not significantly different doses to the optic apparatus and brainstem. Comparatively for the 7 patients treated with IORT 30 Gy to retrospective SRS plans to standard 15–20 Gy and 30 Gy marginal dose, IORT resulted in significantly lower doses to the optic apparatus and brainstem. At a median follow-up of 6.2 months, 86% of patients treated with surgery and IORT achieved local control and 0% developed radiographic or symptomatic radiation necrosis.


Critical organ dosimetry for IORT remains generally lower than that achieved with single fraction SRS following resection of large brain metastases. We recommend 30 Gy to surface as the preferred prescription, consistent with the dose recommendation for IORT in glioblastoma used in the ongoing INTRAGO-II phase-III trial. Early clinical outcomes appear promising for surgery and IORT.

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Correspondence to John A. Vargo.

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Conflict of interest

John A Vargo, MD receives speaking honoraria from BrainLAB. All remaining authors declare 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.

Informed consent

Informed consent was obtained from all individual participants included in the study for treatment delivery.

Additional information

Data was accepted for presentation in abstract format at The Annual Meeting of the Leksell GammaKnife Society 2018 (Dubai, UAE), World Congress of Brachytherapy 2018 (San Francisco, USA), and International Society of Intraoperative Radiation Therapy 2018 (Mannheim, Germany).

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Vargo, J.A., Sparks, K.M., Singh, R. et al. Feasibility of dose escalation using intraoperative radiotherapy following resection of large brain metastases compared to post-operative stereotactic radiosurgery. J Neurooncol 140, 413–420 (2018).

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  • Brain metastases
  • Stereotactic radiosurgery
  • GammaKnife
  • Intraoperative radiation
  • Resection cavity