The Infratentorial Localization of Brain Metastases May Correlate with Specific Clinical Characteristics and Portend Worse Outcomes Based on Voxel-Wise Mapping

SIMPLE SUMMARY: Brain metastases (BMs) are cancerous lesions that originated from cancers outside the brain. Specific types of BMs are found distributing in specific brain areas. The infratentorial regions are frequently affected, causing severe neurological symptoms. Thus, it is necessary to investigate what types of tumors tend to form infratentorial BMs and whether these lesions are more fatal. By analyzing substantial brain imaging data of BMs, we found the vulnerability of infratentorial regions to most types of BMs, and found the infratentorial localization of BMs was significantly associated with young age, male sex, lung neuroendocrine and squamous cell carcinomas, more active cell division of the tumors, and patients with poorer outcomes. Additionally, infratentorial involvement might predict worse outcomes for patients who received surgery. Our findings underlined the distinctive role of infratentorial localization of BMs and its potential relationship with specific clinical characteristics, which may assist diagnosis, treatment choice, and prognostic prediction of BMs. ABSTRACT: The infratentorial regions are vulnerable to develop brain metastases (BMs). However, the associations between the infratentorial localization of BMs and clinical characteristics remained unclear. We retrospectively studied 1102 patients with 4365 BM lesions. Voxel-wise mapping of MRI was applied to construct the tumor frequency heatmaps after normalization and segmentation. The analysis of differential involvement (ADIFFI) was further used to obtain statistically significant clusters. Kaplan-Meier method and Cox regression were used to analyze the prognosis. The parietal, insular and left occipital lobes, and cerebellum were vulnerable to BMs with high relative metastatic risks. Infratentorial areas were site-specifically affected by the lung, breast, and colorectal cancer BMs, but inversely avoided by melanoma BMs. Significant infratentorial clusters were associated with young age, male sex, lung neuroendocrine and squamous cell carcinomas, high expression of Ki-67 of primaries and BMs, and patients with poorer prognosis. Inferior OS was observed in patients with ≥3 BMs and those who received whole-brain radiotherapy alone. Infratentorial involvement of BMs was an independent risk factor of poor prognosis for patients who received surgery (p = 0.023, hazard ratio = 1.473, 95% confidence interval = 1.055–2.058). The current study may add valuable clinical recognition of BMs and provide references for BMs diagnosis, treatment evaluation, and prognostic prediction.