November 27, 2006 — 接受辅助化学疗法的乳癌患者通常抱怨治疗后发生认知功能受损，该症状被称为“化学脑”；研究者表示，现在有一项研究使用核磁共振造影（MRI）已经发现这些病患的脑部结构出现变化，暗示辅助化学疗法对于脑部结构可能的影响；该研究结果来自于日本，线上发表于2006年11月27日
癌症期刊。
研究者表示，这样的变化发生在化学治疗一年后，但在三年后消失，这样的结果使我们推测与化学治疗相关的脑部容积变化可能随着时间恢复。
该试验由来自千叶国家癌症中心医院Masatoshi Inagaki医师领导，利用乳癌幸存者的脑部MRI影像进行分析，该团队比较已经接受过化学治疗病患（包括tegafur-uracil (UFT)、cyclophosphamide、methotrexate与5-fluorouracil）以及那些未接受化学治疗的病患
手术后一年内以及手术三年后影像检查结果。
研究者表示，一年时的试验结果显示，接受过化学治疗病患（共有51位）相较于未接化学疗法病患（共有55位），其灰质与白质区域容积较少；受到影响的脑部区域包括前额皮质、海马回旁脑回、以及楔前叶，这三个部位的容积显著地与注意力／专注力，以及／或是视觉记忆有关。
三年时的试验结果显示，局部脑容积不论是否接受化学疗法（有接受化学疗法共有73位，未接受化学疗法者共有59位）皆无显著差异；从接受辅助化学疗法至MRI的平均时间为4.2年；研究者表示，接受化学疗法的癌症幸存者，其局部脑结构变化与认知功能受损会随着时间恢复。
该团队也观察正常自愿者接受MRI检查的结果，这些健康自愿者透过当地报纸招募；当与未接受化学疗法的乳癌幸存者相比较时，其局部脑部容积并没有显著差异，暗示癌症本身对于脑部并无影响。
Inagak医师向Medscape表示，这些结果使得辅助性化学疗法对于脑部结构是有暂时性影响的想法油然而生，这些影响在癌症手术三年后会逐渐恢复；虽然研究者评估记忆功能，但这不是该试验终点，且需要更多的研究来解释化学脑这个现象；需要的是一项大型且详尽的、断面控制性试验。
安大略多伦多Rotman研究机构Gordon Winocur博士表示，Inagaki等人使用高解析度MRI来研究化学疗法对脑部结构的影响是很重要的，这些对脑部结构的影响，可解释癌症病患接受这些治疗经常抱怨记忆丧失与相关认知功能受损的原因。
他进一步表示，该试验结果提供这些认知功能变化，一般称为“化学脑”的证据，这些变化与疾病及治疗所带来的压力无关。
重要的是，作者将特定认知步骤相关的局部脑部区域变化相连在一起；最有趣的是，作者证实海马回与前额皮质的容积降低，这两个局部脑区域已经在之前的研究，包括作者团队的研究，证实化学疗法造成的认知功能变化有关。
Winocur博士的评论是，一年后脑部发生变化，但三年后并没有这样的现象，暗示了这样的变化可能不是永远的；然而，这样的结果与其他作者所引用的研究、或是癌症病患的长期抱怨不同；因此，未来需要化学疗法对认知功能长期效应的研究来厘清这个问题。
MRI Scans Show Brain Structure Changes After Chemotherapy
By Zosia Chustecka
Medscape Medical News
November 27, 2006 — Breast cancer patients receiving adjuvant chemotherapy often complain of cognitive impairment after the treatment, symptoms that have been termed "chemobrain." Now a study using magnetic resonance imaging (MRI) has found brain changes in such patients, suggesting a potential effect of adjuvant chemotherapy on brain structure, say the researchers. The findings come from a Japanese study in Cancer, published online November 27, 2006.
The changes were seen at 1 year after chemotherapy but were not visible after 3 years. This "can lead us to speculate that the brain volume change related to adjuvant chemotherapy may well recover over the course of time," the researchers comment.
The study was headed by Masatoshi Inagaki, MD, PhD, from the National Cancer Center Hospital East, in Chiba, and relied on databases containing brain MRI scans of breast cancer survivors. The team compared scans from patients who had been exposed to chemotherapy (including tegafur-uracil , cyclophosphamide, methotrexate, and 5-fluorouracil) with those who had not been exposed and looked at scans taken within 1 year of surgery and more than 3 years after surgery.
The 1-year study showed that patients exposed to chemotherapy (n = 51) had smaller regional volumes of both gray and white matter than patients who had not been exposed (n = 55). The brain regions affected included the prefrontal cortex, parahippocampal gyrus, and precuneus, and the volumes of these 3 regions were significantly correlated with indices of attention/concentration and/or visual memory, the researchers comment.
The 3-year study showed no significant differences in regional brain volumes between those exposed to chemotherapy (n = 73) and those not exposed (n = 59). The mean time from completion of adjuvant chemotherapy to this MRI scan was 4.2 years. "Regional brain structural changes and cognitive impairments observed in cancer survivors exposed to adjuvant chemotherapy may recover in time," the researchers comment.
The group also looked at MRI brain scans in healthy volunteers, who were recruited via a local newspaper. These showed no significant differences in regional brain volumes when compared with the scans from breast cancer survivors who had not been exposed to chemotherapy, suggesting that the cancer itself had no effect on the brain.
"These results lead to the idea that adjuvant chemotherapy could have a temporary effect on brain structure, which would recover 3 years after the cancer surgery," Dr. Inagaki told Medscape. Although the researchers measured memory function, it was not the end point of the study, and further studies are needed to explain chemobrain, he added. A detailed, longitudinal controlled study with a large sample is needed.
Approached for comment by Medscape, Gordon Winocur, PhD, from the Rotman Research Institute, in Toronto, Ontario, said; "The study by Inagaki et al is very important in that utilizes high-resolution MRI to show that chemotherapy produces significant structural changes in the brain that could account for the loss of memory and related cognitive function that is frequently reported by cancer patients undergoing such treatment.
"The results provide further evidence that these cognitive changes, commonly termed 'chemobrain,' can be related to changes in brain function independently of the effects of stress associated with the disease and treatment," he continued.
"Importantly, the authors related changes in specific cognitive processes to corresponding changes in localized brain regions. Of particular interest is that the authors report reductions in volume in hippocampus and prefrontal cortex, 2 brain regions that have been implicated by previous research in the cognitive deficits associated with chemotherapy," including studies from his own group.
The finding that brain changes were noted after 1 year, but not at 3 years, is interesting in that it suggests that they may not be permanent, Dr. Winocur commented. However, that is in conflict with other results that the authors cite, as well as long-term complaints of cancer patients. Further research into the long-term effects of chemotherapeutic drugs on cognition is clearly warranted, he concluded.
Cancer. Published online November 27, 2007.
作者：
Zosia Chustecka 2007-6-20