Department of Neuro-oncology University of Texas MD Anderson Cancer Center Houston TX USA.
Department of Psychiatry and Behavioral Sciences Stanford University School of Medicine Stanford CA USA.
Brain Behav. 2017 Feb 6;7(3):e00643. doi: 10.1002/brb3.643. eCollection 2017 Mar.
Several previous studies have demonstrated that cancer chemotherapy is associated with brain injury and cognitive dysfunction. However, evidence suggests that cancer pathogenesis alone may play a role, even in non-CNS cancers.
Using a multimodal neuroimaging approach, we measured structural and functional connectome topology as well as functional network dynamics in newly diagnosed patients with breast cancer. Our study involved a novel, pretreatment assessment that occurred prior to the initiation of any cancer therapies, including surgery with anesthesia. We enrolled 74 patients with breast cancer age 29-65 and 50 frequency-matched healthy female controls who underwent anatomic and resting-state functional MRI as well as cognitive testing.
Compared to controls, patients with breast cancer demonstrated significantly lower functional network dynamics ( = .046) and cognitive functioning ( < .02, corrected). The breast cancer group also showed subtle alterations in structural local clustering and functional local clustering ( < .05, uncorrected) as well as significantly increased correlation between structural global clustering and functional global clustering compared to controls ( = .03). This hyper-correlation between structural and functional topologies was significantly associated with cognitive dysfunction ( = .005).
Our findings could not be accounted for by psychological distress and suggest that non-CNS cancer may directly and/or indirectly affect the brain via mechanisms such as tumor-induced neurogenesis, inflammation, and/or vascular changes, for example. Our results also have broader implications concerning the importance of the balance between structural and functional connectome properties as a potential biomarker of general neurologic deficit.
先前的几项研究表明，癌症化疗与脑损伤和认知功能障碍有关。然而，有证据表明，即使是非中枢神经系统癌症，癌症的发病机制本身也可能起作用。
我们使用多模态神经影像学方法，测量了新诊断的乳腺癌患者的结构和功能连接组拓扑以及功能网络动力学。我们的研究涉及一种新的、治疗前评估，即在开始任何癌症治疗（包括麻醉下的手术）之前进行。我们招募了 74 名年龄在 29-65 岁之间的乳腺癌患者和 50 名年龄匹配的健康女性对照者，他们接受了解剖和静息状态功能磁共振成像以及认知测试。
与对照组相比，乳腺癌患者的功能网络动力学（p=0.046）和认知功能（p<0.02，校正）明显降低。乳腺癌组还表现出结构局部聚类和功能局部聚类的细微改变（p<0.05，未校正），以及结构全局聚类和功能全局聚类之间的相关性显著增加（p=0.03）。这种结构和功能拓扑之间的超相关性与认知功能障碍显著相关（p=0.005）。
我们的发现不能用心理困扰来解释，这表明非中枢神经系统癌症可能通过肿瘤诱导的神经发生、炎症和/或血管变化等机制直接和/或间接地影响大脑。我们的结果还对结构和功能连接组特性之间的平衡作为一般神经功能缺陷的潜在生物标志物的重要性具有更广泛的意义。
