MetInfilt: A prospective trial highlighting the importance of the histological growth pattern in brain metastases

Background: While the histological growth pattern (HGP) of liver metastases is frequently evaluated, the same attention is often absent for brain metastases despite evidence suggesting its prognostic significance. This oversight 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, imaging-guided trial aimed at standardizing the collection and analysis of the HGP at the MMPIbrain. Methods: We recruited fifty patients. The MMPIbrain was identified using preoperative contrast-enhanced T1weighted MRI. Intraoperative confocal microscopy (CONVIVO) visualized the MMPIbrain, while a YELLOW 560 nm filter in the surgical microscope facilitated precise tissue sampling. Samples from the MMPIbrain and the core of the metastasis were collected for postoperative histological confirmation. Results: The protocol achieved successful tissue acquisition from the MMPIbrain in 93.2 % of patients, meeting the study's primary endpoint. Preoperative MRI patterns strongly correlated with infiltrative HGPs, and CONVIVO accurately visualized the MMPIbrain intraoperatively. Exploratory analyses suggest that infiltrative HGPs might negatively impact patient prognosis and represent a potential risk of meningeal metastasis. Conclusions: Our neurosurgical protocol allows the successful and precise acquisition of tissue from the MMPIbrain through presurgical imaging, intraoperative microscopy, and fluorescence-assisted sampling. The evaluation of the HGP in our limited patient cohort highlights its potential clinical significance and supports the urgent necessity to investigate it further for the benefit of patients with brain metastases. Clinical trial registration number: Z-2019-1307-9.