Stouten-Kemperman Myrle M, de Ruiter Michiel B, Koppelmans Vincent, Boogerd Willem, Reneman Liesbeth, Schagen Sanne B
Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
Brain Imaging Behav. 2015 Jun;9(2):275-84. doi: 10.1007/s11682-014-9305-0.
Adjuvant chemotherapy (CT) for breast cancer (BC) is associated with very late side-effects on brain function and structure. However, little is known about neurotoxicity of specific treatment regimens. To compare neurotoxicity profiles after different treatment strategies, we used neurocognitive testing and multimodality MRI in BC survivors randomized to high-dose (HI), conventional-dose (CON-) CT or radiotherapy (RT) only and a healthy control (HC) group. BC survivors who received CON-CT (n = 20) and HC (n = 20) were assessed using a neurocognitive test battery and multimodality MRI including 3D-T1, Diffusion Tensor Imaging (DTI) and 1H-MR spectroscopy (1H-MRS) to measure various aspects of cerebral white (WM) and gray matter (GM). Data were compared to previously assessed groups of BC survivors who received HI-CT (n = 17) and RT-only (n = 15). Testing took place on average 11.5 years post-CT. 3D-T1 showed focal GM volume reductions both for HI-CT and CON-CT compared to RT-only (p < .004). DTI-derived mean diffusivity and 1H-MRS derived N-acetyl aspartate showed WM injury specific to HI-CT but not CON-CT (p < .05). Residual effects were revealed in the RT-only group compared to HC on MRI and neurocognitive measurements (p < .05). Ten years after adjuvant CT for BC lower cerebral GM volume was found in HI as well as CON-CT BC survivors whereas injury to WM is restricted to HI-CT. This might indicate that WM brain changes after BC treatment may show more pronounced (partial) recovery than GM. Furthermore, our results suggest residual neurotoxicity in the RT-only group, which warrants further investigation.
乳腺癌辅助化疗（CT）会对脑功能和结构产生非常迟发的副作用。然而，对于特定治疗方案的神经毒性了解甚少。为比较不同治疗策略后的神经毒性特征，我们对随机分为高剂量（HI）、常规剂量（CON-）CT或单纯放疗（RT）的乳腺癌幸存者以及健康对照组（HC）进行了神经认知测试和多模态磁共振成像（MRI）。使用神经认知测试组合以及包括三维T1加权成像（3D-T1）、扩散张量成像（DTI）和氢质子磁共振波谱（1H-MRS）在内的多模态MRI对接受CON-CT（n = 20）的乳腺癌幸存者和HC（n = 20）进行评估，以测量脑白质（WM）和灰质（GM）的各个方面。将数据与之前评估的接受HI-CT（n = 17）和单纯RT（n = 15）的乳腺癌幸存者组进行比较。测试平均在CT后11.5年进行。与单纯RT相比，3D-T1显示HI-CT和CON-CT组均有局灶性GM体积减少（p < 0.004）。DTI衍生的平均扩散率和1H-MRS衍生的N-乙酰天门冬氨酸显示HI-CT存在特异性WM损伤，而CON-CT不存在（p < 0.05）。与HC相比，单纯RT组在MRI和神经认知测量方面显示出残留效应（p < 0.05）。在乳腺癌辅助CT治疗十年后，HI以及CON-CT乳腺癌幸存者均出现较低的脑GM体积，而WM损伤仅限于HI-CT。这可能表明乳腺癌治疗后脑WM变化可能比GM显示出更明显的（部分）恢复。此外，我们的结果表明单纯RT组存在残留神经毒性，这值得进一步研究。
