Abstract
Brain metastases arise in the central nervous system (CNS) following spread of circulating mesenchymal-type cells from primary tumors. While accumulating evidence underlines the importance of the neural niche in the establishment and progression of metastases, there still remains ambiguity over CNS anatomical spatial distribution from primary cancers. We evaluated 973 patients with brain metastases (breast, colorectal, lung, melanoma, renal) totaling 2,106 lesions treated from 1994–2015 with gamma knife radiosurgery at the University of Southern California Keck Medical Center for topographical distribution analysis. MRI images of the brain were taken and used in conjunction with the frame to precisely localize tumors and measure their size. Each tumor was given an x, y, and z-coordinate derived from the head frame that corresponded to its volumetric center within a 3-dimensional Cartesian field. Topographical analyses were conducted using logistic and multinomial spatial generalized additive models (GAM). For each cancer origin type we compared the observed brain metastases to set of randomly generated spatial observations to determine whether there were statistically significant localization patterns. Spatial pattern results show: 1) melanoma has highest probability to metastasize to the right frontal (74.5%, 95% confidence interval [Cl] = 63.6%- 85.4%) and to occipital lobe (72.4%, 95% Cl = 65.8%-78.9%), 2) while breast cancers have highest proclivity to metastasize to left cerebellar hemisphere (25%, 95% Cl=16.0%-34.1%) and brainstem (16.6%, 95% Cl= 10.8%-22.4%), 3) with lung tumors metastasizing to the left (23.7%, 95% Cl= 16.0–31.3%) and right parietal (24.7%, 95% Cl=16.7–32.8%), left temporal lobe (25.2%, 95% Cl=21.4%-29.1%). Colon and renal metastases show weak spatial patterns across the CNS. We conclude there is evidence of non-uniform spatial distribution of metastasis in the brain. These tumor-specific CNS topography patterns may underlie the ability of cancer cells to adapt to the regional neural microenvironments in order to facilitate colonization and establishment of metastasis.
Gamma knife radiosurgery for breast cancer metastases to the brain: outcomes and prognostic factors from a large prospectively collected database
