Late effects of high-dose adjuvant chemotherapy on white and gray matter in breast cancer survivors: Converging results from multimodal magnetic resonance imaging
Late effects of high-dose adjuvant chemotherapy on white and gray matter in breast cancer survivors: Converging results from multimodal magnetic resonance imaging
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DOI：
10.1002/hbm.21422
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发表时间：
2012-12-01
影响因子：
4.8
通讯作者：
Schagen, Sanne B.
中科院分区：
文献类型：
--
作者：
de Ruiter, Michiel B.;Reneman, Liesbeth;Schagen, Sanne B.
化疗后认知障碍的神经基础在很大程度上是未知的。在这里，我们研究了非常晚（>9年）的辅助大剂量化疗对原发性乳腺癌幸存者（n = 17）的脑白色和灰质的影响，多模式磁共振成像（MRI）。一组未接受化疗的乳腺癌幸存者进行扫描以进行比较（n = 15）。神经心理学测试显示化疗组的认知障碍。弥散张量成像（DTI）和基于束的空间统计显示，化疗与DTI值的局灶性变化相关，提示白色完整性降低。左侧半卵圆中心（白色物质）的单体素质子磁共振波谱（1H-MRS）显示N-乙酰丙酸/肌酸减少，提示轴突损伤。基于体素的形态学显示灰质体积减少，与功能磁共振成像低激活重叠（如以前的出版物中所报道的），在后顶叶区域和共定位与DTI异常。仅化疗组DTI与1H-MRS相关。这些结果表明，乳腺癌的高剂量辅助化疗与白色物质的长期损伤有关，可能反映了轴突变性和脱髓鞘的组合，以及灰质损伤与相关的功能缺陷。激素治疗与他莫昔芬也可能有助于观察到的效果，虽然其他研究的结果表明，这是不可能的，他莫昔芬是唯一或主要负责。使用这种多模态的方法，我们提供了第一次深入了解神经基板的认知功能障碍后，全身给予细胞毒性药物治疗后多年。《脑地图》33：2971-2983，2012年。(C)2011 Wiley Periodicals，Inc.
The neural substrate underlying cognitive impairments after chemotherapy is largely unknown. Here, we investigated very late (>9 years) effects of adjuvant high-dose chemotherapy on brain white and gray matter in primary breast cancer survivors (n = 17) with multimodal magnetic resonance imaging (MRI). A group of breast cancer survivors who did not receive chemotherapy was scanned for comparison (n = 15). Neuropsychological tests demonstrated cognitive impairments in the chemotherapy group. Diffusion tensor imaging (DTI) with tract-based spatial statistics showed that chemotherapy was associated with focal changes in DTI values indicative for reduced white matter integrity. Single voxel proton MR spectroscopy (1H-MRS) in the left centrum semiovale (white matter) showed a reduction of N-acetylasparate/creatine indicative of axonal injury. Voxel-based morphometry demonstrated a reduction of gray matter volume that overlapped with fMRI hypoactivation (as reported in a previous publication) in posterior parietal areas and colocalized with DTI abnormalities. Also, DTI correlated with 1H-MRS only in the chemotherapy group. These results converge to suggest that high-dose adjuvant chemotherapy for breast cancer is associated with long-term injury to white matter, presumably reflecting a combination of axonal degeneration and demyelination, and damage to gray matter with associated functional deficits. Hormonal treatment with tamoxifen may also have contributed to the observed effects, although results from other studies indicate that it is unlikely that tamoxifen is solely or largely responsible. Using this multimodality approach we provide for the first time insight into the neural substrate underlying cognitive impairments following systemic administration of cytotoxic agents many years after treatment. Hum Brain Mapp 33:2971-2983, 2012. (C) 2011 Wiley Periodicals, Inc.