Wefel Jeffrey S, Lenzi Renato, Theriault Richard L, Davis Robert N, Meyers Christina A
Department of Neuro-Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer. 2004 Jun 1;100(11):2292-9. doi: 10.1002/cncr.20272.
Retrospective trials have reported that chemotherapy-induced cognitive dysfunction was experienced by a subset of patients with breast carcinoma. However, recent evidence indicated that a subset also exhibited impaired cognitive function at baseline, before the start of chemotherapy. A prospective, longitudinal trial that incorporates baseline neuropsychologic evaluations is necessary to determine to what extent cognitive dysfunction is attributable to chemotherapy in this population.
Eighteen women with breast carcinoma underwent a comprehensive neuropsychologic evaluation before treatment and at short-term and long-term intervals after chemotherapy. The incidence, nature, severity, and chronicity of cognitive dysfunction developing in patients with breast carcinoma treated with a standard dose of adjuvant chemotherapy were assessed.
Before the start of systemic therapy, 33% of women in the current cohort exhibited cognitive impairment. At the short-term postchemotherapy time point, 61% of the cohort exhibited a decline relative to baseline in 1 or more domains of cognitive functioning and reported greater difficulty in maintaining their ability to work. The most common domains of cognitive dysfunction were related to attention, learning, and processing speed. At the long-term postchemotherapy time point, approximately 50% of patients who experienced declines in cognitive function demonstrated improvement, whereas 50% remained stable. Self-reported ability to perform work-related activities also improved over this interval. Neither impairment at baseline nor subsequent treatment-related cognitive decline exhibited any statistically significant correlation with affective well-being or with demographic or clinical characteristics.
The current study is the first longitudinal trial to report evidence of an association between cognitive dysfunction and chemotherapy in a subgroup of women with nonmetastatic breast carcinoma. The importance of using prospective research designs, appropriate cognitive measures, and statistical methods to evaluate subgroup effects was discussed. Identification of mechanisms associated with cognitive dysfunction and of risk factors contributing to subgroup vulnerability is necessary.
回顾性试验报告称，一部分乳腺癌患者会出现化疗引起的认知功能障碍。然而，最近的证据表明，一部分患者在化疗开始前的基线时就已表现出认知功能受损。有必要进行一项纳入基线神经心理学评估的前瞻性纵向试验，以确定该人群中认知功能障碍在多大程度上可归因于化疗。
18名乳腺癌女性患者在治疗前以及化疗后的短期和长期阶段接受了全面的神经心理学评估。评估了接受标准剂量辅助化疗的乳腺癌患者发生认知功能障碍的发生率、性质、严重程度和慢性情况。
在全身治疗开始前，当前队列中的33%女性表现出认知障碍。在化疗后的短期时间点，该队列中有61%的人在1个或更多认知功能领域相对于基线出现下降，并报告在维持工作能力方面有更大困难。认知功能障碍最常见的领域与注意力、学习和处理速度有关。在化疗后的长期时间点，认知功能下降的患者中约50%有所改善，而50%保持稳定。自我报告的与工作相关活动的能力在此期间也有所改善。基线时的损伤以及随后与治疗相关的认知下降与情感幸福感或人口统计学或临床特征均无任何统计学上的显著相关性。
本研究是第一项纵向试验，报告了在一组非转移性乳腺癌女性患者中认知功能障碍与化疗之间存在关联的证据。讨论了使用前瞻性研究设计、适当的认知测量方法和统计方法来评估亚组效应的重要性。确定与认知功能障碍相关的机制以及导致亚组易感性的危险因素是必要的。
