Interventions Targeting Inflammation for Chemotherapy-Related Cognitive Problems

描述(申请人提供)：血液治疗相关认知障碍(CRCI)是高达75%的乳腺癌患者出现的严重问题，通常持续多年，严重影响生活质量。CRCI的病因尚不清楚，也没有有效的治疗方法。减少炎症是缓解CRCI的一个有希望的目标，需要精通临床和行为研究、免疫学和神经科学的翻译研究人员来促进这一领域的知识。罗切斯特大学医学中心放射肿瘤学系助理教授Michelle Janelsins博士正在申请K07导师职业发展奖，以扩大她的临床和行为研究技能，并将新技能与她作为一名独立的临床和转化性癌症控制研究员的强大基础科学能力相结合，拥有CRCI干预方面的专业知识。此应用程序为Janelsins博士提供 在临床环境中开发、实施和评估干预措施所需的新培训和技能，并将这些新能力与她在免疫学和神经科学方面已有的技能和知识相结合，成功地进行了我们所知的第一项随机、对照、先导研究，调查了两种新型干预措施(运动和布洛芬)对CRCI和炎症的影响。职业发展规划：Janelsins博士之前的培训提供了一个出色的初始基础，但她需要在进行II-III期临床试验、认知评估和相关生物行为免疫途径以及运动干预开发方面的新培训，才能成为一名成功的独立临床研究员，拥有专注于了解和缓解CRCI的生物行为研究专业知识。她的四个职业发展培训目标是：1)在癌症控制II-III期临床试验中发展专业知识，2)发展认知科学和认知评估以及相关生物行为免疫途径方面的专业知识，3)发展运动生理学、体力活动评估和运动干预方面的专业知识，4)促进独立学术研究事业的发展。Janelsins博士拥有一支杰出的导师团队：Gary Morrow博士是她的资深导师，三十多年来一直为NCI提供资金；Tim Ahles博士和Deborah Cory-Slechta博士提供神经认知测试方面的专业知识，是她的共同导师；Karen Mustian博士提供运动干预方面的专业知识作为联合导师；Jan Moynihan博士(免疫学)、Michelle Shayne博士(内科肿瘤学)和Charles Heckler博士(生物统计学)提供关键领域的专门知识。研究计划：拟议的第二阶段随机对照试验部分基于Janelsins博士的初步数据，是一项三组研究，比较了布洛芬+健康教育(ARM 1)、安慰剂+运动(ARM 2)和安慰剂+健康教育(对照组；ARM 3)对120名接受CRCI化疗的乳腺癌患者CRCI的影响。运动和布洛芬组将分别与对照组(组3)进行比较，主要目标是评估、分析和解释每种干预措施在缓解CRCI方面的初步疗效以及每种干预措施对炎症的影响。这一奖项将使Janelsins博士成为癌症和认知领域的领导者，在她的职业生涯中，她将为患者护理做出有意义的贡献。研究结果将被用于设计未来最终的随机对照试验，确保Janelsins博士成功过渡到一名独立的、由R01资助的临床和翻译研究人员，并最终减少CRCI的公共卫生负担。

DESCRIPTION (provided by applicant): Hemotherapy-related cognitive impairment (CRCI) is a significant problem that develops in up to 75% of breast cancer patients, often persisting for many years and significantly impairing quality of life. The etiology of CRCI is not clearly understood, and there are no effective management approaches. Reduction of inflammation is a promising target to alleviate CRCI, and translational investigators well versed in clinical and behavioral research, immunology and neuroscience are needed to advance knowledge in this area. Dr. Michelle Janelsins, an Assistant Professor in the Department of Radiation Oncology at the University of Rochester Medical Center, is applying for a K07 mentored career development award to expand her clinical and behavioral research skills and to integrate new skills with her strong basic science abilities as an independent clinical and translational cancer control investigator with expertise in interventions for CRCI. This application provides Dr. Janelsins with new training and skills necessary to develop, implement, and assess interventions in a clinical setting and combine these new abilities with her established skills and knowledge in immunology and neuroscience to successfully conduct the first randomized, controlled, pilot study we are aware of investigating the influence of two novel interventions (exercise and ibuprofen) on CRCI and inflammation. Career Development Plan: Dr. Janelsins' previous training provides an outstanding initial foundation, but she needs new training in the conduct of Phase II-III clinical trials, cognitive assessment and related bio behavioral immune pathways, and exercise intervention development to become a successful independent clinical researcher with expertise in bio behavioral research focusing on understanding and alleviating CRCI. Her four career development training goals are: 1) to develop expertise in cancer control Phase II-III clinical trials, 2) to develop expertise in cognitive science and cognitive assessments and related bio behavioral immune pathways, 3) to develop expertise in exercise physiology, physical activity assessments and exercise interventions, and 4) to promote the development of an independent academic research career. Dr. Janelsins has an outstanding mentoring team: Dr. Gary Morrow, a leading cancer control researcher with NCI funding for over thirty years, is her senior mentor; Drs. Tim Ahles and Deborah Cory-Slechta provide expertise in neurocognitive testing as her co-mentors; Dr. Karen Mustian provides expertise in exercise interventions as a co-mentor; and advisors Drs. Jan Moynihan (immunology), Michelle Shayne (medical oncology), and Charles Heckler (biostatistics) provide specific expertise in key areas. Research Plan: The proposed Phase II RCT, based partially on Dr. Janelsins' preliminary data, is a three-arm study comparing the influence of ibuprofen + health education (Arm 1), placebo + exercise (Arm 2) and placebo + health education (control; Arm 3) on CRCI in 120 breast cancer patients undergoing chemotherapy experiencing CRCI. The exercise and ibuprofen arms will each be compared to the control (Arm 3) with the primary goal of assessing, analyzing, and interpreting the preliminary efficacy of each intervention in alleviating CRCI and the effects of each intervention on inflammation. This award will position Dr. Janelsins to become a leader in the cancer and cognition field who, over her career, will make meaningful contributions to patient care. Research findings will be used to design future definitive RCTs, ensure Dr. Janelsins' successful transition to an independent, R01- funded, clinical and translational investigator, and ultimately reduce the public health burden from CRCI.