Stouten-Kemperman Myrle M, de Ruiter Michiel B, Boogerd Willem, Veltman Dick J, Reneman Liesbeth, Schagen Sanne B
1Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital,Division of Psychosocial Research and Epidemiology,Amsterdam,The Netherlands.
3Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital,Department of Neuro-Oncology,Amsterdam,The Netherlands.
J Int Neuropsychol Soc. 2015 Jan;21(1):50-61. doi: 10.1017/S1355617714001015. Epub 2014 Dec 22.
Although adjuvant chemotherapy (CT) for breast cancer (BC) is associated with very late side-effects on cognition and brain function, studies on adverse effects of specific treatment regimens are scarce. Here, neurotoxicity profiles after different treatment strategies were compared in BC survivors randomized to high-dose (HI) or conventional-dose (CON-) CT, in women treated with radiotherapy (RT) -only and a healthy control (HC) group. We administered a neurocognitive test battery, a planning fMRI task (Tower of London) and episodic memory fMRI task (Paired Associates paradigm) in BC survivors who received CON-CT (n=24) and HC (n=27). Data were compared to BC survivors who received HI-CT (n=17) and RT-only (n=15) and who were previously assessed. Testing took place ±11.5 years post-CT. Furthermore, neurocognitive data were compared to neurocognitive data acquired ≤2 years post-treatment. Cognitive assessment revealed sustained cognitive decline in 10.5% of HI-CT, 8.3% of CON-CT, 6.7% of RT-only patients and 0% in the HC. Hypoactivation was found in task-related prefrontal and parietal areas for both CT-groups versus RT-only, with HI-CT showing more pronounced hypoactivation than CON-CT, combined with worse task performance. RT-only survivors performed at a similar level to HC while showing hyperactivation in task-related brain areas. Long after treatment, CT is associated with cognitive problems and task-related hypoactivation that depend on the specific cytotoxic regimen. This worse performance in patients who received CT could be explained by impaired brain functioning that is more severe with more intense CT.
尽管乳腺癌辅助化疗（CT）会对认知和脑功能产生非常晚期的副作用，但关于特定治疗方案不良反应的研究却很稀少。在此，我们对随机接受高剂量（HI）或常规剂量（CON-）CT的乳腺癌幸存者、仅接受放疗（RT）的女性以及健康对照组（HC），比较了不同治疗策略后的神经毒性特征。我们对接受CON-CT（n=24）和HC（n=27）的乳腺癌幸存者进行了神经认知测试组合、一项计划功能磁共振成像任务（伦敦塔任务）和情景记忆功能磁共振成像任务（配对联想范式）。将数据与接受HI-CT（n=17）和仅接受RT（n=15）且先前已评估的乳腺癌幸存者进行比较。测试在CT后±11.5年进行。此外，将神经认知数据与治疗后≤2年获取的神经认知数据进行比较。认知评估显示，HI-CT组中有10.5%、CON-CT组中有8.3%、仅接受RT的患者中有6.7%出现持续认知下降，而HC组中这一比例为0%。与仅接受RT的患者相比，两个CT组在与任务相关的前额叶和顶叶区域均出现激活不足，HI-CT组的激活不足比CON-CT组更明显，且任务表现更差。仅接受RT的幸存者表现与HC组相似，但在与任务相关的脑区出现激活过度。在治疗后很长时间，CT与认知问题和与任务相关的激活不足有关，这取决于具体的细胞毒性治疗方案。接受CT治疗的患者表现较差，可能是由于脑功能受损，且更强的CT会导致更严重的脑功能受损。
