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不断提高，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，而认知障碍是生活质量和日常功能的重要决定因素。然而，现有研究主要对患者进行治疗后一年的随访。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重要危险因素，初步数据表明化疗对大脑健康的影响可能会在治疗后数年出现。最后，流行病学研究主要集中在乳腺癌上，尽管其他癌症（例如结直肠癌）的化疗药物表现出神经毒性。我们在此建议利用护士健康研究认知子队列中 20,000 名女性的现有数据，其中通过 6 项认知测试收集了 4 项重复的认知功能测量结果。 1995 年至 2000 年，对当时 70 岁及以上的所有女性进行了初步认知测试。其中包括 1239 名有浸润性乳腺癌病史的患者、210 名患有 DCIS 的患者、317 名患有结直肠癌的患者以及 15,000 名没有癌症病史的患者。这些数据将有助于对系统性癌症治疗和长期风险进行首次更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组最近报告中确定的关键问题，我们的目标将解决：（1）接受乳腺癌或结直肠癌全身治疗（化疗、激素治疗）的女性整体认知功能是否有更大的下降（与未接受全身治疗的对照患者或未患癌症的对照患者相比，我们的电池组中所有认知测试的平均值）；（2）全身治疗是否与特定的治疗相关 由于文献中的初步发现，工作组确定需要进一步研究的认知领域（情景记忆、执行功能）。我们特别关注的治疗方案包括： (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； (ii) 环磷酰胺，在我们的乳腺癌幸存者被诊断期间乳腺癌治疗的支柱（分别探索两种最常见的治疗方案） （当时为环磷酰胺/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：对最近的患者启动认知测试以解决更新的治疗方法；并评估接受全身治疗的患者认知能力下降的生物和生活方式危险因素。因此，我们的研究最终将告知幸存者和临床医生是否需要筛查认知能力下降 甚至在治疗后数年，并且能够确定干预措施以维持治疗后的长期认知。