Neurotoxic Effects of Anthracycline- vs Nonanthracycline-Based Chemotherapy on Cognition in Breast Cancer Survivors.
Neurotoxic Effects of Anthracycline- vs Nonanthracycline-Based Chemotherapy on Cognition in Breast Cancer Survivors.
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蒽环类药物与非人性差的化学疗法对乳腺癌幸存者认知的神经毒性作用。
DOI：
10.1001/jamaoncol.2015.4333
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发表时间：
2016-02
期刊：
影响因子：
28.4
通讯作者：
Blayney DW
中科院分区：
文献类型：
--
作者：
Kesler SR;Blayney DW
化疗暴露是癌症相关认知障碍的已知风险因素。基于蒽环类药物的方案是常用的化疗药物，在临床研究中已显示与认知障碍和大脑变化相关。直接比较蒽环类和非蒽环类方案对认知状态和功能性脑连接的影响。在这项观察性研究中，我们回顾性研究了62例原发性乳腺癌幸存者（平均[SD]年龄，54.7 [8.5]岁）的认知和静息状态功能磁共振成像数据，这些患者平均停止治疗超过2年。这些妇女中有20人接受了蒽环类化疗作为其主要治疗的一部分，19人接受了非蒽环类方案，23人未接受任何化疗。参与者于2008年至2014年在单一学术机构（斯坦福大学）注册，并在此时进行研究分析。认知状态使用标准化神经心理学测试进行测量，功能性大脑连接使用静息状态功能性磁共振成像进行评估，重点是大脑的默认模式网络。与其他两组相比，蒽环类药物组表现出显著较低的言语记忆表现，包括即时回忆（F = 3.73; P = .03）和延迟回忆（F = 11.11; P < .001）以及左下楔前叶连接（F = 7.48; P = .001）。两个化疗组患者报告的认知功能障碍（F = 7.27; P = 0.002）和心理困扰（F = 5.64; P = 0.006）相关结局与非化疗对照组相比相似。这些结果表明，蒽环类药物可能比非蒽环类药物对特定的认知领域和大脑网络连接有更大的负面影响。蒽环类和非蒽环类方案可能对其他认知领域以及某些患者报告的结局产生非特异性影响。需要进一步的研究来确定保护大脑免受各种化疗药物影响的潜在方法。
Chemotherapy exposure is a known risk factor for cancer-related cognitive impairments. Anthracycline-based regimens are commonly used chemotherapies that have been shown to be associated with cognitive impairment and brain changes in clinical studies. To directly compare the effects of anthracycline and nonanthracycline regimens on cognitive status and functional brain connectivity. In this observational study, we retrospectively examined cognitive and resting state functional magnetic resonance imaging data acquired from 62 primary breast cancer survivors (mean [SD] age, 54.7 [8.5] years) who were more than 2 years off-therapy, on average. Twenty of these women received anthracycline-based chemotherapy as part of their primary treatment, 19 received nonanthracycline regimens, and 23 did not receive any chemotherapy. Participants were enrolled at a single academic institution (Stanford University) from 2008 to 2014, and the study analyses were performed at this time. Cognitive status was measured using standardized neuropsychological tests, and functional brain connectivity was evaluated using resting state functional magnetic resonance imaging with a focus on the brain’s default mode network. The anthracycline group demonstrated significantly lower verbal memory performance including immediate recall (F = 3.73; P = .03) and delayed recall (F = 11.11; P < .001) as well as lower left precuneus connectivity (F = 7.48; P = .001) compared with the other 2 groups. Patient-reported outcomes related to cognitive dysfunction (F = 7.27; P = .002) and psychological distress (F = 5.64; P = .006) were similarly elevated in both chemotherapy groups compared with the non–chemotherapy-treated controls. These results suggest that anthracyclines may have greater negative effects than nonanthracycline regimens on particular cognitive domains and brain network connections. Both anthracycline and nonanthracycline regimens may have nonspecific effects on other cognitive domains as well as certain patient reported outcomes. Further research is needed to identify potential methods for protecting the brain against the effects of various chemotherapeutic agents.