Multimodal study of cognitive impairment following radiation therapy for locally advanced head and neck cancer

局部晚期头颈癌放射治疗后认知障碍的多模式研究

• 批准号: 10197030
• 负责人: Andrew M McDonald
• 金额: $ 25.4万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10197030
• 关键词: ABCB1 gene; ATM gene; Address; Adjuvant Therapy; Adult; Aftercare; Area; Biological; Biometry; Blood - brain barrier anatomy; Brain; Brain region; Cancer Survivor; Candidate Disease Gene; Case Series; Cerebellum; Characteristics; Chemotherapy and/or radiation; Child; Clinical; Clinical Trials Design; Cognition; Cognitive; Cognitive remediation; Complication; Coupled; Cranial Irradiation; Cross-Sectional Studies; DNA Repair; Development; Development Plans; Diagnosis; Disease; Dose; Drug Transport; ERCC3 gene; Epidemiology; Exposure to; Foundations; Future; Genetic Predisposition to Disease; Genetic Variation; Goals; Head and Neck Cancer; Impaired cognition; Impairment; Individual; Inferior; Institutes; Intervention; Investigation; Late Effects; Long-Term Survivors; Malignant Neoplasms; Measures; Memory; Mentors; Modernization; Molecular; Molecular Epidemiology; Morbidity - disease rate; Motor; Nasopharyngeal Neoplasms; Neurocognitive; Neuropsychology; Normal tissue morphology; Organ; Oropharyngeal Neoplasms; Outcome; Patient Outcomes Assessments; Patients; Pattern; Performance; Persons; Photons; Planning Techniques; Population; Process; Prognosis; Proton Radiation; Quality of life; Questionnaires; Radiation; Radiation Dose Unit; Radiation exposure; Radiation therapy; Radiometry; Reporting; Research; Research Methodology; Research Personnel; Risk; Scientist; Severities; Single Nucleotide Polymorphism; Site; Standardization; Statistical Models; Techniques; Temporal Lobe; Training; Treatment Factor; Variant; XRCC1 gene; advanced disease; brain volume; cancer therapy; career; career development; chemotherapeutic agent; chemotherapy; cognitive function; cognitive testing; cohort; drug metabolism; experience; genetic association; genetic variant; head and neck cancer patient; high risk; improved; multimodality; neurocognitive test; neurological rehabilitation; neurotransmission; patient population; proton therapy; radiation effect; radiation risk; relating to nervous system; repaired; skills; success; survivorship; treatment planning

PROJECT SUMMARY Treatment of locally advanced head and neck cancer (LAHNC) commonly entails the use of radiation therapy, which often exposes portions of the brain, particularly the cerebellum and inferior temporal lobes, to moderately high doses of radiation. The negative effects of cranial radiation exposure on cognition are well established in other types of malignancies, but remain unstudied in LAHNC patients. The underlying disease process, chemotherapeutic agents, and radiation dose distribution in patients treated for LAHNC are fundamentally different from the patient populations previously studied, suggesting that patterns of cognitive impairment may also differ. This scientific proposal will elucidate the cognitive effects of radiation in LAHNC patients through three specific aims. Scientific Aim 1 will characterize the cognitive profiles of LAHNC survivors by administering a neuropsychological battery and patient questionnaires. Radiation dosimetry to individual regions of the cerebellum and temporal lobes will be calculated from the original treatment plans. The effects of patient and treatment characteristics (including chemotherapy exposure and radiation dosimetry) on post- treatment cognition will be assessed. Scientific Aim 2 will determine the association between cognitive impairment and germline variants. Germline single nucleotide polymorphisms will be determined using a biologically-plausible, carefully curated candidate gene approach and assessed for association with the neurocognitive battery results. Scientific Aim 3 will explore how modern radiation planning techniques can be utilized to reduce brain radiation exposure for LAHNC treatment. Comparison radiation plans will be generated using Multi-Criteria Optimized intensity modulation and proton therapy. This study will promote my long-term career goal of improving quality of life for patients who received radiation therapy and will provide opportunities for additional training and career development. The career development plan includes training in biostatistical and research methodology, normal tissue complication probability modeling, and fundamentals of molecular epidemiology and cognitive assessment. The scientific and training plans are supported by a team of experienced mentors and advisors who are committed to the success of this project and my development as a clinician scientist. The primary mentor is an expert in neurocognitive outcomes among cancer survivors, an experienced mentor of young investigators, and the director of the UAB Institute for Cancer Outcomes and Survivorship. The results of this proposal will be utilized to form the foundation of a future clinical trial designed to reduce cognitive morbidity in LAHNC patients by identifying those patients at highest risk for cognitive impairment, maximally reducing brain radiation exposure, and implementing a tailored cognitive remediation intervention. This project will strengthen my skills as a clinical researcher, establish an independent research platform, and make a true contribution towards improving clinical outcomes in cancer survivors.

项目摘要 局部高级头颈癌（LAHNC）的治疗通常需要使用辐射 疗法通常暴露于大脑的一部分，尤其是小脑和颞叶下叶 适度高剂量的辐射。颅辐射暴露对认知的负面影响很好 在其他类型的恶性肿瘤中建立，但在LAHNC患者中仍未研究。潜在疾病 在接受LAHNC治疗的患者中的过程，化学治疗剂和辐射剂量分布为 与先前研究的患者人群的根本不同，表明认知模式 损害也可能有所不同。这项科学提议将阐明辐射在lahnc中的认知作用 患者通过三个特定目标。科学目标1将表征Lahnc幸存者的认知概况 通过管理神经心理电池和患者问卷。辐射剂量测定到个体 小脑和颞叶区域将根据原始治疗计划计算。效果 患者和治疗特征（包括化学疗法暴露和放射剂量法） 将评估治疗认知。科学目标2将决定认知之间的关联 损伤和种系变体。种系单核苷酸多态性将使用A确定 具有生物学上的，精心策划的候选基因方法，并评估与 神经认知电池的结果。科学目标3将探讨现代辐射计划技术如何 用于减少LAHNC治疗的脑辐射暴露。将生成比较辐射计划 使用多标准优化的强度调节和质子治疗。这项研究将促进我的长期 改善接受放射疗法并将提供机会的患者生活质量的职业目标 进行额外的培训和职业发展。职业发展计划包括生物统计学的培训 以及研究方法，正常组织并发症概率建模和分子的基础知识 流行病学和认知评估。科学和培训计划得到了一个团队的支持 经验丰富的导师和顾问，他们致力于该项目的成功以及我作为一个 临床医生。主要导师是癌症幸存者神经认知结果的专家 年轻研究人员的经验丰富的导师，UAB癌症结果研究所主任 生存。该提案的结果将用于构成未来临床试验的基础 通过确定那些认知风险最高的患者，降低LAHNC患者的认知发病率 损伤，最大减少脑辐射暴露并实施量身定制的认知补救措施 干涉。该项目将增强我作为临床研究人员的技能，建立独立研究 平台，并为改善癌症幸存者的临床结果做出真正的贡献。