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

Abstract

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.

Results: 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.

Conclusions: 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.

Keywords: Brain metastases; GammaKnife; Intraoperative radiation; Resection cavity; Stereotactic radiosurgery.

Conflict of interest statement

Conflict of interest John A Vargo, MD receives speaking honoraria from BrainLAB. All remaining authors declare they have no conflicts of interest.

Figures

Fig. 1

Case example of the spherical applicator used for IORT for brain tumor patient

Fig. 2

Volume of brain receiving 12 Gy as a function of spherical applicator size and dose prescription. IORT intraoperative radiotherapy, Gy gray, V12 volume of brain receiving 12 Gy

Fig. 3

Clinical example of the potential favorable outcomes for IORT in reducing radiation injury reactions. a Large left frontal brain metastasis secondary to melanoma treated with surgery and IORT 30 Gy to the applicator surface. b MRI follow-up 9 months after IORT, notice the stable left frontal resection cavity compared to adjacent smaller metastases which were treated with SRS and WBRT with interval associated hemorrhage and radiation injury reaction. Finally compare the outcomes for the left frontal resection cavity from panels a, b to the outcome of a left temporoparietal metastases in panels c, d now with significant post-treatment changes and symptomatic mass effect on the adjacent brainstem

Fig. 4

Clinical example of local failure after IORT for a dural-base endometrial cancer brain metastasis. a Large left parietal brain metastasis treated with surgery and IORT 30 Gy to the applicator surface. b Stable resection cavity 2.5 months post-IORT. c Stable to slight increase in enhancement in resection cavity at 5.5 months post-IORT. d Local recurrence at 8.8 month post-IORT