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

Zhangqi Dou,Hemmings Wu,Jinghong Xu,Baizhou Li,Biao Jiang,Chongran Sun,Qi Xie,Gao Chen,Qian Yu,Chenguang Li,Jiawei Wu,Feng Yan

doi:10.3390/cancers13020324

Abstract

Simple SummaryBrain 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.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.

Highlights

Brain metastases (BMs) are one of the major causes of cancer mortality
Treatment data were available in 402 patients, showing 48.3% received whole-brain radiotherapy (WBRT) alone and 36.3% received surgery alone
For magnetic resonance imaging (MRI) data processing, format conversion, normalization, and semi-automatic segmentation were successfully conducted to obtain the regions of interest (ROIs, Figure 1B)

Summary

Introduction

Brain metastases (BMs) are one of the major causes of cancer mortality. The incidence of BMs is reported to be 10 times higher than that of primary brain tumors. 7–14 individuals per 100,000 or 10–30% of patients with systemic cancer may be affected [1,2,3]. The resistance of the blood-brain barrier to systemic chemotherapy and approximately 40% of patients affected by multiple metastatic lesions make BMs a challenging disease with a dismal prognosis [4]. Therein, the spatial distribution of BMs, which largely impacts the symptoms of patients, is an important biological factor to determine the local therapy regimens, and, subsequently, relates to the prognosis [7,8]. Melanoma BMs were described as presenting aversion to the cerebellum [15,16]. These results benefited differential diagnoses and raised the attention of applying prophylactic cranial irradiation (PCI) for high-risk regions to develop BMs [10,14]

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Conclusion