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）：随着许多癌症的生存率提高，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，这是生活质量和日常功能的一个重要决定因素。然而，现有的研究在很大程度上只对治疗后一年的患者进行了随访。大量数据表明，中年时的不良暴露可能是晚年认知能力下降的重要风险因素，初步数据表明，化疗对大脑健康达特影响可能在治疗后数年出现。最后，流行病学研究主要集中在乳腺癌上，尽管用于其他癌症的化疗剂（例如，结肠直肠）表现出神经毒性。我们建议在这里利用现有的数据，从20,000名妇女在认知子队列的护士健康研究，其中四个重复测量的认知功能，通过一组6认知测试收集。1995年至2000年，对当时70岁及以上的所有妇女进行了初步认知测试。这包括1239例浸润性乳腺癌病史，210例DCIS，317例结直肠癌，15，000例无癌症病史。这些数据将允许第一次更大规模的，前瞻性的研究系统性癌症治疗和长期风险 认知能力下降我们将专注于国际认知和癌症工作组最近报告中确定的关键问题，我们的目标将解决：（1）如果妇女接受了系统治疗，（化疗，激素治疗）乳腺癌，或结直肠癌，有更大的整体认知功能下降（我们的一系列认知测试的平均值与未接受全身治疗的对照组患者，或与未患癌症的对照组相比;以及（2）系统治疗是否与特定的认知领域（情景记忆、执行功能）相关，由于文献中的初步发现，特别工作组认为需要进一步研究。特别是，我们将集中在治疗方案，包括：（i）5-FU，因为这种药物比许多其他药物更容易穿过血脑屏障;以及（ii）环磷酰胺，在我们的乳腺癌幸存者被诊断出患有乳腺癌期间，（通过对当时两种最常见的方案的单独探索，环磷酰胺/甲氨蝶呤/5-FU和阿霉素/环磷酰胺）根据研究结果，该应用的结果将支持未来的研究：在最近的患者中启动认知测试以解决新的治疗方法;并评估接受系统治疗患者认知功能下降的生物学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，即使在治疗后数年也需要筛查认知能力下降，并能够确定干预措施，以维持治疗后的长期认知能力。