LAUSR

Brain metastases are an increasing clinical problem, causing significant morbidity and mortality in patients with solid organ cancer. Diffusion along white matter tracts can be assessed by diffusion tensor MRI (DTI) and disruption of white matter tract integrity generally indicates tumor invasion and inflammation in the brain. Matched preoperative DTI and image-guided neurosurgical sampling of the brain-brain metastasis interface was performed in 26 adult patients undergoing resection of a brain metastasis, uniquely yielding paired MRI and biological data from the same regions. Patients were followed prospectively from imaging diagnosis until death. In this surgical series patients were mostly of excellent performance status with no or stable primary disease. We consistently observed dense, activated macrophage infiltration at the brain-brain metastasis interface across tumors from different primaries. CD20-positive, B cell infiltration was sparse (with no significant difference from control white matter). CD3-positive lymphocytes were seen in the peritumoral region in all except 1 case (median 16 cells per high power field (HPF), significantly greater than control white matter, p 25 immunoreactive cells/HPF), those with moderate peritumoral infiltration were at no survival advantage compared to those with low infiltration, whereas those with the highest infiltrates lived over twice as long (median 11.7 months, vs. 5.1 and 5.2 months for moderate and low groups respectively, log rank test=10.06, p=0.007). Using image analysis of the paired MRI data, average fractional anisotropy (FA) readings in the peritumoral region were significantly lower than the unaffected, contralateral hemisphere indicating white matter disruption (related samples Wilcoxon-signed rank test, p Citation Format: Rasheed Zakaria, Michael D. Jenkinson, Philip S. Rudland. Peritumoral CD3+ lymphocyte infiltration at the brain-brain metastasis interface is detectable by diffusion MRI and independently associated with prolonged survival. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr B20.