Clinical and Translational Approaches to Cognitive Impairments in Cancer

癌症认知障碍的临床和转化方法

• 批准号: 8756447
• 负责人: Michelle C Janelsins
• 金额: $ 230.25万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-22 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8756447
• 关键词: Address; Adverse effects; Affect; Aftercare; Animal Model; Area; Attention Concentration; Basic Science; Behavioral Research; Biological; Brain; Cancer Control; Cancer Control Research; Cancer Intervention; Cancer Patient; Cancer Survivor; Cancer Survivorship; Chemotherapy-Oncologic Procedure; Clinical; Clinical Research; Cognitive; Cognitive Science; Etiology; Immune; Immunologics; Immunology; Impaired cognition; Inflammation; Inflammatory Response; Intervention; K-Series Research Career Programs; Knowledge; Laboratories; Lead; Life; Malignant Neoplasms; Memory; Modeling; Nature; Neuropsychology; Neurosciences; Patients; Public Health; Quality of life; Research; Research Personnel; Research Training; Role; Survivors; Testing; chemobrain; chemotherapy; cohort; effective therapy; executive function; experience; improved; malignant breast neoplasm; neuroimmunology; neuroinflammation; neurotoxic; patient oriented research; public health relevance; research study; successful intervention; therapy development; translational approach; treatment adherence

DESCRIPTION (provided by applicant): While chemotherapy has helped to improve survival for cancer patients, the side effects lead to substantial detrimental effects on quality of life tht can be debilitating; these side effects, including cognitive impairments, have become a major focus of research. Chemotherapy-related cognitive impairment (CRCI) is characterized by difficulty in memory, attention, concentration and executive function. CRCI is most pronounced and severe during chemotherapy (in up to 80% of patients), however, it can last for years following treatment in up to 35% of survivors. With over 13 million cancer survivors in the US, it is estimated that up to 4 million survivors could be living with long-lasting effects of CRCI. CRCI is particularly significant because long-term cognitive impairment can develop, CRCI negatively impacts quality of life, and CRCI can affect treatment adherence. I'm currently conducting a NCI K Award in patient-oriented research investigating interventions targeting inflammation to alleviate cognitive difficulties in breast cancer patients receiving chemotherapy; my laboratory focuses solely on CRCI research. One of the main hypotheses in our field is that inflammation may drive cognitive impairment in these patients. While this is becoming well-accepted in our field, there is a gap in understanding the nature of this inflammatory response as most clinical research studies have limited access to biological correlates of CRCI. There is also a lack of investigators that can carefully assess neuro-immune factors in basic science models as well as in people. I am proposing to use my knowledge in basic immunology, neuroimmunology, and neuroscience with my behavioral research training in cognitive science, neuropsychology and clinical cancer control to address these gaps in the field. While this research focuses on CRCI, it has broad implications for many areas of cancer control and survivorship. Part I of this application involves careful assessment and understanding of the role of inflammation on brain function and neuroinflammation in chemotherapy animal models (using a breast cancer chemotherapy paradigm; Part IA) and following up with analyzing possible etiological factors in a breast cancer patient cohort that is being treated with the same chemotherapy regimen (Part IB). In Part II of this application, we will utilize animal models to develop and test intervention for cancer-related cognitive impairment (this is not commonly done in cancer control research) which will allow us to move forward with the most successful interventions for testing in clinical research. Overall, this proposal will allow us to better understand immunologic and neurotoxic effects of CRCI, develop interventions for CRCI, and improve the overall public health burden of this troublesome side effect.

描述（由申请人提供）：虽然化疗有助于提高癌症患者的生存率，但副作用会对生活质量产生实质性的不利影响，可能会使人衰弱;这些副作用，包括认知障碍，已成为研究的主要焦点。化疗相关的认知功能障碍（CRCI）的特征是记忆、注意力、集中力和执行功能的困难。CRCI在化疗期间最明显和严重（高达80%的患者），然而，在高达35%的幸存者中，它可以在治疗后持续数年。在美国有超过1300万癌症幸存者，据估计，多达400万幸存者可能生活在CRCI的长期影响下。crci 尤其重要，因为长期认知障碍可能发展，CRCI对生活质量产生负面影响，CRCI可能影响治疗依从性。我目前正在进行一项以患者为导向的研究，调查针对炎症的干预措施，以减轻接受化疗的乳腺癌患者的认知困难;我的实验室只专注于CRCI研究。我们领域的主要假设之一是炎症可能导致这些患者的认知障碍。虽然这在我们的领域中被广泛接受，但在理解这种炎症反应的性质方面存在差距，因为大多数临床研究对CRCI的生物学相关性的访问有限。也缺乏能够仔细评估基础科学模型和人体神经免疫因素的研究人员。我建议利用我在基础免疫学，神经免疫学和神经科学方面的知识，以及我在认知科学，神经心理学和临床癌症控制方面的行为研究培训，以解决该领域的这些差距。虽然这项研究的重点是CRCI， 对癌症控制和生存的许多领域具有广泛的影响。本申请的第I部分涉及在化疗动物模型中仔细评估和理解炎症对脑功能和神经炎症的作用（使用乳腺癌化疗范例;第IA部分），并在用相同化疗方案治疗的乳腺癌患者队列中分析可能的病因学因素（第IB部分）。在本申请的第二部分中，我们将利用动物模型开发和测试癌症相关认知障碍的干预措施（这在癌症控制研究中并不常见），这将使我们能够在临床研究中进行最成功的干预措施测试。总的来说，这项提案将使我们能够更好地了解CRCI的免疫和神经毒性作用，开发CRCI的干预措施，并改善这种令人烦恼的副作用的整体公共卫生负担。

项目成果

Cognitive function in cancer survivors: analysis of the 1999-2002 National Health and Nutrition Examination Survey.

• DOI: 10.1007/s00520-015-2992-2
• 发表时间: 2016-05
• 期刊: Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
• 作者: Williams AM;Janelsins MC;van Wijngaarden E
• 通讯作者: van Wijngaarden E

What is known and unknown about chemotherapy-related cognitive impairment in patients with haematological malignancies and areas of needed research.

• DOI: 10.1111/bjh.14211
• 发表时间: 2016-09
• 期刊: British journal of haematology
• 影响因子: 6.5
• 作者: Williams AM;Zent CS;Janelsins MC
• 通讯作者: Janelsins MC