Systemic cancer treatment and subsequent cognitive decline

描述(申请人提供)：随着许多癌症存活率的提高，评估治疗的长期并发症变得至关重要。越来越多的数据表明，化疗和激素治疗可能与认知障碍有关，认知障碍是生活质量和日常功能的重要决定因素。然而，现有的研究在很大程度上是对患者进行跟踪调查，直到治疗后一年。大量数据表明，中年时期的不良暴露可能是晚年认知能力下降的强烈风险因素，初步数据表明，化疗对大脑健康的影响可能会在治疗数年后出现。最后，流行病学研究主要集中在乳腺癌上，尽管其他癌症(如结直肠癌)的化疗药物显示出神经毒性。我们建议利用护士健康研究认知亚队列中来自20,000名女性的现有数据，在这些数据中，通过一系列6项认知测试收集了4项重复的认知功能测量。最初的认知测试是在1995-2000年对当时所有70岁及以上的妇女进行的。这包括有浸润性乳腺癌病史的1239人，患有DCIS的210人，患有结直肠癌的317人，以及没有癌症病史的15,000人。这些数据将使首次对系统性癌症治疗和长期风险进行更大规模的前瞻性调查成为可能。 认知能力下降的症状。我们将集中讨论国际认知与癌症工作组最近的报告提出的关键问题，我们的目标将解决：(1)接受系统治疗(化疗、激素治疗)治疗乳腺癌或结直肠癌的女性，是否有更大的整体认知功能下降(在我们的电池中所有认知测试的平均值与未接受系统治疗的对照组患者相比，或者与未接受系统治疗的对照组相比；以及(2)由于文献中的初步发现，系统治疗是否与工作组确定的需要进一步研究的特定认知领域(情节记忆、执行功能)有关。特别是，我们将重点研究治疗方案，包括：(I)5-FU，因为这种药物比许多其他药物更容易通过血脑屏障；(Ii)环磷酰胺，在我们的乳腺癌幸存者被诊断为乳腺癌幸存者期间的乳腺癌治疗的支柱(分别探索当时最常见的两种方案，环磷酰胺/甲氨蝶呤/5-FU和阿霉素/环磷酰胺)，根据研究结果，这项应用的结果将支持未来的研究：在更新的患者中启动认知测试，以解决新的治疗方法；以及评估接受系统治疗的患者认知功能下降的生物和生活方式风险因素。因此，我们的研究最终将告知幸存者和临床医生是否需要在治疗后数年筛查认知能力下降，并能够确定治疗后维持长期认知能力的干预措施。

DESCRIPTION (provided by applicant): With increasing survival rates for many cancers, evaluating long-term complications of treatment has become critical. Growing data indicate that chemotherapy and hormonal therapy may be associated with cognitive impairment, a strong determinant of quality of life and daily function. However, existing studies have largely followed patients up to just one year post-treatment. Extensive data indicate that adverse exposures at mid-life may be strong risk factors for cognitive decline in later life, and initial data suggest tat effects of chemotherapy on brain health may emerge years after treatment. Finally, epidemiologic studies have focused largely on breast cancer, although chemotherapeutic agents for other cancers (e.g., colorectal) demonstrate neurotoxicity. We propose here to take advantage of existing data from 20,000 women in the Cognitive Sub cohort of the Nurses' Health Study, in which four repeated measures of cognitive function were collected via a battery of 6 cognitive tests. Initial cognitive testing was conducted in 1995-2000 in all women age 70 years and older at that time. This included 1239 with a history of invasive breast cancer, 210 with DCIS, 317 with colorectal cancer, and 15,000 with no cancer history. These data will allow the first larger-scale, prospective investigation of systemic cancer treatment and longer-term risk of cognitive decline. We will focus on key questions identified by the recent report from the International Cognition and Cancer Task Force, and our Aims will address: (1) if women given systemic therapy (chemotherapy, hormonal therapy) for breast cancer, or for colorectal cancer, have greater decline in global cognitive function (an average of all cognitive tests in our battery versus control patients not given systemic therapy, or versus controls with no cancer; and (2) if systemic therapy is related to specific cognitive domains (episodic memory, executive function) identified by the Task Force as requiring further research, due to initial findings in the literatue. In particular, we will focus on treatment regimens including: (i) 5-FU, as this agent crosses the blood brain barrier more readily than many others; and (ii) cyclophosphamide, the backbone of breast cancer treatment during the period our breast cancer survivors were diagnosed (with separate exploration of the two most common regimens at the time, cyclophosphamide/methotrexate/5-FU and Adriamycin/ cyclophosphamide) Depending on findings, results from this application will support future research: to initiate cognitive testingin more recent patients to address newer treatments; and to evaluate biologic and lifestyle risk factors for cognitive decline in patients given systemic therapy. Thus, our research will eventually inform survivors and clinicians of any need to screen for cognitive decline even years after treatment, and, enable identification of interventions to maintain long-term cognition after treatment.