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: 10430157
• 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/10430157
• 关键词: ABCB1 gene; ATM gene; Address; Adjuvant Therapy; Adult; Aftercare; Area; 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; Operative Surgical Procedures; 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; neural repair; neurocognitive test; neurological rehabilitation; neurotransmission; patient population; proton therapy; radiation effect; radiation risk; 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.

项目概要 局部晚期头颈癌 (LAHNC) 的治疗通常需要使用放射治疗 治疗经常暴露大脑的某些部分，特别是小脑和下颞叶， 中等高剂量的辐射。颅脑辐射暴露对认知的负面影响是显而易见的 已在其他类型的恶性肿瘤中建立，但尚未在 LAHNC 患者中进行研究。基础疾病 LAHNC 治疗患者的治疗过程、化疗药物和放射剂量分布 与之前研究的患者群体有根本不同，这表明认知模式 损害也可能不同。这项科学提案将阐明辐射对 LAHNC 认知的影响 患者通过三个具体目标。科学目标 1 将描述 LAHNC 幸存者的认知概况 通过进行神经心理学电池和患者问卷调查。个人辐射剂量测定 小脑和颞叶的区域将根据原始治疗计划进行计算。的影响 术后患者和治疗特征（包括化疗暴露和放射剂量测定） 将评估治疗认知。科学目标 2 将确定认知之间的关联 损伤和种系变异。种系单核苷酸多态性将使用 生物学上合理的、精心策划的候选基因方法，并评估其与 神经认知电池结果。科学目标 3 将探索现代辐射规划技术如何 用于减少 LAHNC 治疗时的脑部辐射暴露。将生成比较辐射计划 使用多标准优化强度调制和质子治疗。这项研究将促进我的长期 提高接受放射治疗的患者的生活质量的职业目标，并将提供机会 以获得额外的培训和职业发展。职业发展计划包括生物统计培训 和研究方法、正常组织并发症概率模型以及分子生物学基础 流行病学和认知评估。科学和培训计划得到了团队的支持 经验丰富的导师和顾问致力于该项目的成功以及我作为一个人的发展 临床医生科学家。主要导师是癌症幸存者神经认知结果方面的专家， 经验丰富的年轻研究者导师，UAB 癌症结果研究所所长 幸存者。该提案的结果将用于构成未来设计的临床试验的基础 通过识别认知风险最高的患者来降低 LAHNC 患者的认知发病率 损伤，最大限度地减少大脑辐射暴露，并实施量身定制的认知补救措施 干涉。这个项目将增强我作为临床研究员的技能，建立独立的研究 平台，并为改善癌症幸存者的临床结果做出真正的贡献。