P11.30.A IMMUNOMODULATORY EFFECTS OF PREOPERATIVE STEREOTACTIC RADIOSURGERY IN BRAIN METASTASES: PROSPECTIVE INTEGRATION OF TISSUE AND CEREBROSPINAL FLUID PROFILING

Abstract BACKGROUND Brain metastases (BM) are among the most common malignant brain tumors in adults, associated with poor prognosis and limited therapeutic options. Preoperative stereotactic radiosurgery (SRS) is emerging as a novel local treatment strategy, promising advantages in reducing perioperative tumor cell dissemination, radiation necrosis, and facilitating corticosteroid tapering. Beyond local control, SRS may also modulate the tumor immune microenvironment (TIME), and potentially synergize with CNS-active systemic therapies. However, the immunomodulatory mechanisms of SRS and its impact on the TIME and neurovascular niche of BM remain poorly understood. Liquid biopsy approaches, particularly from cerebrospinal fluid (CSF), may provide a minimally invasive window into treatment-induced changes and biomarker discovery. MATERIAL AND METHODS This study leverages tissue and serial CSF samples from the prospective biomarker study BMX-Rad (Immunomodulatory effects of preoperative radiosurgery in patients with brain metastases; n=20 patients). Analyses include histological and immunohistochemical assessment (e.g., necrosis, hypoxia, immune infiltrates), spatial tissue profiling via multiplex immunofluorescence, and single-cell RNA sequencing on selected cases. Longitudinal CSF samples are analyzed for immune cell phenotypes, cytokine profiling, and circulating tumor DNA. A comprehensive integration of scRNA-seq with tissue and CSF-derived data aims to delineate key SRS-induced alterations in the TIME. All findings are correlated with clinical outcomes. RESULTS Preliminary BM tissue analyses after SRS demonstrate entity-specific differences of the TIME, with melanoma BMs showing highest T-cell infiltration. Particularly dense lymphocytic infiltrates are observed after simultaneous SRS and immune checkpoint inhibition suggest synergistic effects. Spatial tissue profiling and scRNA-seq are currently being integrated to resolve spatial and functional immune cell distributions. In parallel, immune response dynamics in the CSF are being analyzed in corresponding serial CSF samples. CONCLUSION This study aims to unravel the immunomodulatory effects of SRS on BM, bridging local tissue responses with minimally invasive CSF-based profiling. This may inform biomarker-driven patient stratification and pave the way for rationally designed, personalized combination therapies integrating SRS and systemic treatments in BM.