Anatomical and topographical variations in the distribution of brain metastases based on primary cancer origin and molecular subtypes: a systematic review

Abstract

Background: While it has been suspected that different primary cancers have varying predilections for metastasis in certain brain regions, recent advances in neuroimaging and spatial modeling analytics have facilitated further exploration into this field.

Methods: A systematic electronic database search for studies analyzing the distribution of brain metastases (BMs) from any primary systematic cancer published between January 1990 and July 2020 was conducted using PRISMA guidelines.

Results: Two authors independently reviewed 1957 abstracts, 46 of which underwent full-text analysis. A third author arbitrated both lists; 13 studies met inclusion/exclusion criteria. All were retrospective single- or multi-institution database reviews analyzing over 8227 BMs from 2599 patients with breast (8 studies), lung (7 studies), melanoma (5 studies), gastrointestinal (4 studies), renal (3 studies), and prostate (1 study) cancers. Breast, lung, and colorectal cancers tended to metastasize to more posterior/caudal topographic and vascular neuroanatomical regions, particularly the cerebellum, with notable differences based on subtype and receptor expression. HER-2-positive breast cancers were less likely to arise in the frontal lobes or subcortical region, while ER-positive and PR-positive breast metastases were less likely to arise in the occipital lobe or cerebellum. BM from lung adenocarcinoma tended to arise in the frontal lobes and squamous cell carcinoma in the cerebellum. Melanoma metastasized more to the frontal and temporal lobes.

Conclusion: The observed topographical distribution of BM likely develops based on primary cancer type, molecular subtype, and genetic profile. Further studies analyzing this association and relationships to vascular distribution are merited to potentially improve patient treatment and outcomes.

Keywords: brain metastases; distribution; magnetic resonance imaging; topographical variations.

Figure 1.

PRISMA diagram detailing the database searches, the number of abstracts screened, the full texts reviewed, and the reasons for exclusion.

Figure 2.

Surface renderings illustrating the patterns of anatomical localization of brain metastases reported in several papers included in the review. The images visualize probability estimates of tumor location assessed for each of the frontal, parietal, temporal, and occipital lobes, the brainstem, and the cerebellum (first row, first column). The surfaces are colored to show high probability in red (25% of cases including both hemispheres) and white (approaching zero probability). Probability estimates were computed by aggregating lesion extent from plots and tables of the listed reviews, normalizing by region volume, and normalizing. A composite plot was generated to show the average probability across all studies included in the figure. The data may be visualized in augmented reality using the mobile application Schol-AR, which can be found at https://www.schol-ar.io/. 3D visualizations were made using the Quantitative Imaging Toolkit (QIT) and with augmented reality functionality provided by Schol-AR (https://www.schol-ar.io/).