NIRA-09 PERIPHERAL RIM ENHANCEMENT IN BRAIN METASTASES: AN IMAGING BIOMARKER OF IMMUNE EXCLUSION?
Jingwen Yao, Shivani Baisiwala, Francesco Sanvito, Madeline Ho, Andrea Liang, Lu Sun, Jorge Salcedo-Sifuentes, William Delery, Cassia Maniquis, Stuart Harper, Lisa Liff, Ryan Shih, Yashaar Hafizka, Jieun Park, Alexander Boyarko, Alan Lee, Noriko Salamon, Robert Prins, Won KimAbstract
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.