Structural brain alterations following adult non-CNS cancers: a systematic review of the neuroimaging literature

Background: Cancer and cancer treatments may impact the brain through several pathways leading to cognitive impairment. Neuroimaging evidence has begun to elucidate the neurobiological underpinnings of cancer-related cognitive impairment. The aim of this paper was to systematically review available literature on structural brain alterations following adult non-central nervous system (CNS) cancers and associated treatments.
Methods: This review followed PRISMA guidelines and was registered in PROSPERO (ID#107387). Comprehensive searches were conducted in June 2018 using PubMed and Web of Science. Inclusion criteria were English peer-reviewed journal articles of formal, controlled studies that examined structural neuroimaging outcomes in adult non-CNS cancer patients and survivors. Selected articles were assessed for quality and risk of bias using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.
Results: Thirty-six publications of prospective and cross-sectional studies met inclusion criteria and were included. Structural brain alterations following cancer and its treatment were reported in a majority of the publications as evidenced by reduced global and local gray matter volumes, impaired white matter microstructural integrity, and brain network alterations. Structural alterations were most often evident when cancer-treated groups were compared with healthy controls, and more subtle when compared with cancer controls. Regarding the existence of pretreatment impairments, the evidence was equivocal. There was significant between-study heterogeneity in imaging analytical approaches and use of statistical adjustments. Over half reported associations with cognitive outcomes, though regions and associated cognitive domains were heterogeneous.
Conclusions: Structural brain alterations following cancer and cancer treatments were reported in a majority of the reviewed studies. However, the extent of observed alterations depended on the choice of comparison groups. Methodological issues exist that will need to be addressed systematically to ensure the validity of findings. Large-scale prospective studies with extended assessment points are warranted to replicate and build upon initial findings.

背景：癌症及其治疗可通过多种途径影响大脑，进而引发认知功能障碍。神经影像学证据已逐步阐明癌症相关认知障碍的神经生物学基础。本研究旨在系统梳理成人非中枢神经系统（CNS）癌症及其治疗后大脑结构改变的相关现有文献。
方法：本综述遵循PRISMA（Preferred Reporting Items for Systematic Reviews and Meta-Analyses，系统综述与荟萃分析优先报告条目）指南，并已在PROSPERO（International Prospective Register of Systematic Reviews，国际前瞻性系统综述注册平台）注册（编号：107387）。研究于2018年6月在PubMed和Web of Science两大数据库中开展全面检索。纳入标准为：经同行评议的英文期刊文献，且为针对成人非中枢神经系统癌症患者及幸存者的正式对照研究，需对其大脑结构神经影像学结局进行评估。采用美国国立卫生研究院（National Institutes of Health, NIH）观察性队列与横断面研究质量评估工具，对纳入文献的质量及偏倚风险进行评价。
结果：共有36项前瞻性及横断面研究文献符合纳入标准并被纳入本综述。多数纳入文献均报道了癌症及其治疗后出现的大脑结构改变，具体表现为全脑及局部灰质体积减小、白质微结构完整性受损以及脑网络结构改变。相较于健康对照组，癌症治疗组的大脑结构改变通常更为显著；而与癌症对照组相比，此类改变则相对轻微。关于治疗前是否已存在认知损害的相关证据尚不明确。不同研究在影像学分析方法及统计校正手段的使用上存在显著异质性。超过半数的文献报道了大脑结构改变与认知结局的关联，但所涉及的脑区及相关认知域存在异质性。
结论：多数纳入的综述研究均报道了癌症及其治疗后出现的大脑结构改变。但此类改变的显著程度取决于对照人群的选择。当前研究仍存在方法学层面的问题，需通过系统方法加以解决以确保研究结果的有效性。未来需开展大规模前瞻性研究，并设置更长的随访评估节点，以重复验证并拓展现有初始研究发现。