Systemic cancer treatment and subsequent cognitive decline

全身癌症治疗和随后的认知能力下降

• 批准号: 8489489
• 负责人: FRANCINE GRODSTEIN
• 金额: $ 8.81万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8489489
• 关键词: Address; Adriamycin PFS; Advisory Committees; Affect; Aftercare; Age; Animals; Blood - brain barrier anatomy; Brain; Breast; Breast Cancer Treatment; Cancer Patient; Cancer Survivor; Chemotherapy-Oncologic Procedure; Clinical Trials Cooperative Group; Cognition; Cognitive; Colorectal; Colorectal Cancer; Control Groups; Cyclophosphamide; Data; Diagnosis; Dose; Elderly; Epidemiologic Studies; Episodic memory; Female; Fluorouracil; Funding; Goals; Health; Impaired cognition; International; Intervention; Investigation; Lead; Life; Life Style; Literature; Malignant Neoplasms; Measures; Mentors; Methotrexate; Neuropsychological Tests; Noninfiltrating Intraductal Carcinoma; Nurses' Health Study; Patients; Population; Principal Investigator; Prospective Studies; Public Health; Quality of life; Radiosurgery; Recording of previous events; Regimen; Reporting; Research; Research Personnel; Risk; Risk Factors; Screening for cancer; Survival Rate; Survivors; Systemic Therapy; Testing; Time; Treatment Protocols; Vertebral column; Woman; anticancer research; cancer therapy; chemotherapeutic agent; chemotherapy; clinically significant; cognitive function; cohort; cost; daily functioning; early life exposure; executive function; experience; high risk; hormone therapy; improved; malignant breast neoplasm; middle age; neurotoxicity; prospective; public health relevance

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.

描述（由申请人提供）：随着许多癌症的存活率提高，评估长期治疗并发症已变得至关重要。增长的数据表明，化学疗法和激素疗法可能与认知障碍有关，这是生活质量和日常功能的强大决定因素。但是，现有的研究在很大程度上遵循了治疗后仅一年的患者。大量数据表明，中年的不良暴露可能是后来生活认知能力下降的强大风险因素，而初始数据表明化学疗法对脑健康的影响可能会在治疗后几年出现。最后，尽管其他癌症的化学治疗剂（例如结直肠癌）表现出神经毒性，但流行病学研究主要集中在乳腺癌上。我们在这里提议在护士健康研究的认知子群中利用20,000名女性的现有数据，其中通过6种认知测试的电池收集了四个重复的认知功能测量。当时的所有70岁及以上的女性在1995 - 2000年进行了初始认知测试。其中包括1239年，患有侵入性乳腺癌史，210例DCI，317例结直肠癌和15,000个没有癌症史。这些数据将允许对全身性癌症治疗和长期风险进行首次大规模的前瞻性研究 认知能力下降。我们将重点关注国际认知和癌症工作队最近报告所确定的关键问题，我们的目标将解决：（1）如果对乳腺癌进行全身治疗（化学疗法，荷尔蒙治疗）或结直肠癌的妇女或结直肠癌的全球认知功能的下降较大（我们对电池对照的患者的平均水平以及癌症的平均水平），则与系统性治疗的平均水平相关，如果是系统性治疗的平均水平，则是癌症的平均水平；由于最初的发现，我们将重点介绍：（i）5-FU，因为该药物的跨性别阶层比许多其他人跨越了乳腺癌，因此，认知领域（情节记忆，执行功能）需要进一步的研究。当时，环磷酰胺/甲氨蝶呤/5-FU和adrimycin/cyctophophamide）取决于发现，该应用的结果将支持未来的研究：启动认知验证，以解决更新的患者，以解决新的治疗方法；并评估接受全身治疗的患者认知能力下降的生物学和生活方式危险因素。因此，我们的研究最终将为幸存者和临床医生提供任何需要在治疗后几年筛查认知能力下降的必要性，并能够确定干预措施以维持治疗后的长期认知。