OGCT-04 PROSPECTIVE IMAGING-GUIDED BIOPSY TRIAL OF THE MACRO METASTASIS-BRAIN PARENCHYMA INTERFACE (METINFILT STUDY)

Abstract PURPOSE The histological growth pattern (HGP) in brain metastases is often overlooked despite evidence suggesting its prognostic significance. This may stem from the lack of a standardized method for assessing the HGP at the macro-metastasis/brain parenchyma interface (MMPIbrain). MetInfilt is the first prospective, image-guided trial aimed at standardizing the collection and analysis of HGP at the MMPIbrain. METHODS We recruited 50 patients (21 female, 29 male, median age 62.2 years) undergoing microsurgical BM resection. The most frequent primary tumor was lung cancer (n = 23; 46%). Based on the previous trials, the Metinfilt protocol consisted of 4 elements: A. The determination of target areas on the preoperative MRI scan, which appeared suspicious for tumor cell infiltration B. Identification of these target areas using the neuronavigation system C. Employment of fluorescein sodium (FL) as a tracer to detect tumor borders and D. Use of laser confocal endomicroscopy for direct visualization of the MMPI intraoperatively. At least 70% successful MMPI-specific tissue acquisition was determined as primary endpoint. RESULTS The MetInfilt protocol successfully acquired tissue from the MMPIbrain in 93.2% of patients. Therefore, the study met its primary endpoint. The study protocol induced no additional morbidity or prolongation of operative time. Significant tumor cell infiltration was found in 72.5% of the analyzed MMPI samples. Pre-operative MRI patterns strongly correlated with infiltrative HGPs, and the confocal microscopy accurately visualized the MMPI intraoperatively. Infiltrative MMPIs correlated with significantly worse overall survival (HR: 4.61; p = 0.0001). Notably, all patients who developed meningeal metastasis had infiltrative HGPs. CONCLUSION Our results demonstrate that the study protocol, through pre-surgical imaging, intra-operative microscopy, and fluorescence-assisted sampling, was feasible and confirmed the clinical impact of infiltration at the MMPIbrain in our limited patient cohort. In addition, this highlights the potential importance of supramarginal resection in infiltrative BM.