Jorge Barrios, Evan Porter, Dante P. I. Capaldi, Taman Upadhaya, William C. Chen, Julian R. Perks, Aditya Apte, Michalis Aristophanous, Eve LoCastro, Dylan Hsu, Payton H. Stone, Javier E. Villanueva-Meyer, Gilmer Valdes, Fei Jiang, Michael Maddalena, Ase Ballangrud, Kayla Prezelski, Hui Lin, Jinger Y. Sun, Muhtada A. K. Aldin, Oi Wai Chau, Benjamin Ziemer, Maasa Seaberg, Penny K. Sneed, Olivier Morin.

Nature Communications volume 16, Article number: 4536 (2025) 
Published: 15 May 2025

Abstract

Brain metastases are a frequent and debilitating manifestation of advanced cancer. Here, we collect and analyze neuroimaging of 3,065 cancer patients with 13,067 brain metastases, representing an extensive collection for research. We find that metastases predominantly localize to high perfusion areas near the grey-white matter junction, but also identify notable differences depending on the primary cancer histology as well as brain regions which do not conform to this relationship. Lung and breast cancers, in contrast to melanoma, frequently metastasize to the cerebellum, hinting at biological pathways of spread. Additionally, the deep brain structures are relatively spared from metastasis, regardless of primary cancer type. Leveraging this data, we propose a probabilistic brain metastasis risk model to enhance the therapeutic ratio of whole-brain radiotherapy by targeting high risk areas while preserving cortical and subcortical brain regions of functional significance and low metastasis risk, potentially reducing the cognitive side effects of therapy.