NIRA-09 PERIPHERAL RIM ENHANCEMENT IN BRAIN METASTASES: AN IMAGING BIOMARKER OF IMMUNE EXCLUSION?

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Abstract Background Brain metastases frequently exhibit immune exclusion, in which immune cells are spatially restricted to the tumor stroma rather than infiltrating the parenchyma. Noninvasive identification of immune-excluded tumors could improve patient stratification and treatment decision-making. We hypothesized that a peripheral radiographic signature on routine MRI may reflect a biologically distinct, immune-enriched compartment. Methods We retrospectively analyzed 234 patients with surgically resected brain metastases. Pre-operative MRI scans were reviewed by two experienced readers to identify the radiographic signature as a peripheral, bulging region of post-contrast T1-weighted hyperintensity contiguous with the contrast-enhancing tumor core, showing distinct and more avid enhancement on post-contrast T1-weighted image, as well as hyperintensity on T2-weighted imaging similar to the peritumoral hyperintensity. VASARI qualitative features, ADC, and rCBV were compared between signature-positive and -negative lesions, and between perilesional and core subregions. In four patients with spatially matched core and peripheral tissue samples, CO-Detection by Indexing (CODEX) multiplexed immunofluorescence with a 27-marker panel was performed. Survival analysis used multivariate Cox regression. Results The signature was identified in 29 patients (12.4%). Signature-positive lesions more frequently demonstrated extensive edema and deep white matter involvement (p < 0.05). Perilesional regions exhibited significantly higher ADC (p < 0.0001) and lower rCBV (p < 0.001) versus the tumor core, suggesting a biologically distinct entity. CODEX revealed immune enrichment in perilesional versus core regions (immune-to-tumor ratio geomean: 9.1 vs. 0.44), with myeloid cells predominating (85.1% of immune cells in the perilesion vs. 72.1% in core). The signature was independently associated with worse overall survival (HR = 2.38[1.31-4.31], p < 0.01). Conclusions This novel radiographic phenotype identifies a peripheral compartment spatially distinct from the tumor core, with unique quantitative imaging features, poor survival association, and in a limited subset, a myeloid-dominant immune composition often devoid of tumor. This visually identifiable MRI signature has potential as a noninvasive biomarker for immune microenvironment characterization and patient stratification.

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