Assessment of imaging risks for recurrence after stereotactic radiosurgery for brain metastases (IRRaS-BM)

Abstract

Background: The identification of viable tumors and radiation necrosis after stereotactic radiosurgery (SRS) is crucial for patient management. Tumor habitat analysis involving the grouping of similar voxels can identify subregions that share common biology and enable the depiction of areas of tumor recurrence and treatment-induced change. This study aims to validate an imaging biomarker for tumor recurrence after SRS for brain metastasis by conducting tumor habitat analysis using multi-parametric MRI.

Methods: In this prospective study (NCT05868928), patients with brain metastases will undergo multi-parametric MRI before SRS, and then follow-up MRIs will be conducted every 3 months until 24 months after SRS. The multi-parametric MRI protocol will include T2-weighted and contrast-enhanced T1-weighted imaging, diffusion-weighted imaging, and dynamic susceptibility contrast imaging. Using k-means voxel-wise clustering, this study will define three structural MRI habitats (enhancing, solid low-enhancing, and nonviable) on T1- and T2-weighted images and three physiologic MRI habitats (hypervascular cellular, hypovascular cellular, and nonviable) on apparent diffusion coefficient maps and cerebral blood volume maps. Using RANO-BM criteria as the reference standard, via Cox proportional hazards analysis, the study will prospectively evaluate associations between parameters of the tumor habitats and the time to recurrence. The DICE similarity coefficients between the recurrence site and tumor habitats will be calculated.

Discussion: The tumor habitat analysis will provide an objective and reliable measure for assessing tumor recurrence from brain metastasis following SRS. By identifying subregions for local recurrence, our study could guide the next therapeutic targets for patients after SRS.

Trial registration: This study is registered at ClinicalTrials.gov (NCT05868928).

Keywords: Brain metastasis; MRI; Recurrence; Stereotactic radiosurgery; Tumor habitat analysis.

Fig. 1

Study schema. SRS, stereotactic radiosurgery; RANO-BM, response assessment in neuro-oncology brain metastases

Fig. 2

Example of tumor habitat analysis using multi-parametric MRI, as per the study protocol. To construct structural habitats, k-means clustering is applied to CE-T1WI and T2WI and the resulting habitats are color-coded as follows: enhancing habitats (red), solid low-enhancing habitats (green), and nonviable tissue habitats (blue). Similarly, for physiologic habitats, k-means clustering is applied to ADC and CBV images, and the representing habitats are color-coded as follows: hypervascular cellular habitats (red), hypovascular cellular habitats (green), and nonviable tissue habitats (blue). In this case, a patient was treated with stereotactic radiosurgery for brain metastasis in the right cingulate gyrus. Compared with the baseline MRI, the follow-up structural MRI analysis shows that the solid low-enhancing habitat increased (from 1597 voxels to 4493 voxels), whereas the other habitats decreased. In the physiologic MRI analysis, all habitats exhibited a decrease in voxel numbers, but the percentage of hypovascular cellular habitat increased from 32.04–42.21%. CE-T1WI, contrast-enhanced T1 weighted imaging; T2WI, T2-weighted imaging; ADC, apparent diffusion coefficient; CBV, cerebral blood volume