White Matter Toxicity and Neurocognitive Outcomes in Pediatric Brain Tumor Patients Treated with Proton Beam Radiation Therapy

接受质子束放射治疗的小儿脑肿瘤患者的白质毒性和神经认知结果

• 批准号: 9509381
• 负责人: LISA SCHUM KAHALLEY
• 金额: $ 77.89万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-16 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9509381
• 关键词: Address; Adverse effects; Affect; Aftercare; Benefits and Risks; Brain; Brain Neoplasms; Cancer Center; Cancer Patient; Child; Childhood; Childhood Brain Neoplasm; Clinical; Cognitive; Country; Cranial Irradiation; Cross-Sectional Studies; Data; Deposition; Diagnosis; Diffusion Magnetic Resonance Imaging; Dose; Environment; Family; Functional disorder; Impaired cognition; Knowledge; Late Effects; Lead; Literature; Longitudinal Studies; Malignant Neoplasms; Medical; Modality; Neurocognitive; Neurocognitive Deficit; Normal tissue morphology; Occupational; Operative Surgical Procedures; Outcome; Patients; Photons; Physicians; Population; Process; Publishing; Quality of life; Radiation; Radiation therapy; Reporting; Research; Research Infrastructure; Risk; Roentgen Rays; Survivors; Techniques; Texas; Time; Tissues; Toxic effect; Toxicity Tests; Work; brain tissue; cognitive change; cognitive function; cohort; cost; disability; disorder control; experience; follow-up; functional disability; functional independence; functional outcomes; improved; interest; irradiation; multidisciplinary; neuro-oncology; neurocognitive test; neuroimaging; neuropathology; oncology program; preservation; prospective; proton beam; proton therapy; radiation delivery; recruit; sex; social; survivorship; treatment group; white matter; white matter change

PROJECT SUMMARY/ABSTRACT Most children treated for cancer in the US will achieve long-term survival, and survivorship presents unique challenges for this growing population. Brain tumor survivors are at particular risk for a range of functional impairments, including cognitive, educational, and social difficulties. Cranial radiation therapy is an essential lifesaving treatment but is associated with cognitive decline. Proton beam radiation therapy (PBRT) is one of the most promising recent advances in pediatric brain tumor treatment. The proposed medical advantage of PBRT lies in the precision of radiation delivery with proton beams, depositing maximum dose to clinical targets while minimizing radiation to surrounding tissues. By eliminating unnecessary radiation to surrounding healthy brain tissue, PBRT may spare cognitive functioning better than conventional photon or x-ray irradiation (XRT). Using volumetrics and diffusion tensor imaging (DTI), we will examine associations between white matter (WM) toxicity and neurocognitive outcomes in pediatric brain tumor patients treated with PBRT. Study 1 is a prospective, longitudinal study of WM change and associated neurocognitive outcomes in pediatric brain tumor patients treated with PBRT vs. Surgery Only followed from diagnosis through Early Survivorship. Specific aims include: (1) to compare change in WM volume/integrity over time by treatment group (PBRT vs. Surgery Only and vs. healthy controls (HCs)), and (2) to examine associations between WM toxicity and neurocognitive test scores over time. Study 2 is a cross-sectional study of associations between WM and neurocognitive outcomes during Intermediate Survivorship for pediatric brain tumor survivors treated with PBRT vs. Surgery Only with the following specific aims: (1) to compare WM volume/integrity in survivors by treatment type (PBRT vs. Surgery Only and vs. HCs), and (2) to examine associations between WM toxicity and neurocognitive test scores. Study 3 is a cross-sectional study of WM associations with neurocognitive outcomes during Late Survivorship for pediatric brain tumor survivors treated with PBRT vs. XRT including the following specific aims: (1) to compare WM volume/integrity in survivors by treatment group (PBRT vs. XRT and vs. HCs), and (2) to examine associations between WM toxicity and neurocognitive test scores. This proposal is consistent with NCI's objective to “reduce the long-term adverse effects of cancer and its treatment” in children and to “improve the quality of life for cancer patients, survivors, and their families.” Neurocognitive late effects lead to significant educational, social, and occupational limitations for many survivors, greatly affecting their quality of life and functional independence long-term. Research is needed to determine which treatments are best able to limit the suffering associated with post-treatment neurocognitive decline. Our results will have clinical value, providing a timely report of WM correlates of neurocognitive functioning and comparison between treatment modalities.

项目摘要/摘要 在美国，大多数接受癌症治疗的儿童将实现长期存活，而且存活呈现独特的特征 这对不断增长的人口来说是一个挑战。脑瘤幸存者在一系列功能性疾病中的风险尤其高 障碍，包括认知、教育和社交方面的困难。头颅放射治疗是必不可少的 挽救生命的治疗，但与认知能力下降有关。质子束放射治疗(PBRT)是一种 儿童脑肿瘤治疗的最新进展。建议的医疗优势是 PBRT在于质子束放射治疗的精确度，将最大剂量沉积到临床靶区 同时将对周围组织的辐射降至最低。通过消除对周围健康的不必要辐射 在脑组织中，PBRT可能比传统的光子或X射线照射(XRT)更好地保护认知功能。 使用体积测量学和扩散张量成像(DTI)，我们将检查脑白质之间的联系 接受PBRT治疗的儿童脑肿瘤患者的毒性和神经认知结果。研究1是一项 儿童脑肿瘤患者WM改变及其相关神经认知结局的前瞻性纵向研究 接受PBRT治疗的患者与手术治疗的患者相比，只有通过早期生存得到诊断后才获得随访。具体目标 包括：(1)比较治疗组WM体积/完整性随时间的变化(PBRT与仅手术组 和健康对照组(HCS))，以及(2)检查WM毒性和神经认知测试之间的关系 随着时间的推移得分。研究2是关于工作记忆和神经认知之间关系的横断面研究。 接受PBRT与手术治疗的儿童脑肿瘤幸存者的中期生存结果 仅有以下具体目标：(1)比较治疗类型(PBRT)幸存者的WM容量/完整性 以及(2)检查西药毒性和神经认知测试之间的关系 得分。研究3是一项关于WM与晚期神经认知结果之间关系的横断面研究 接受PBRT和XRT治疗的儿童脑肿瘤幸存者的存活率，包括以下特定的 目的：(1)比较不同治疗组幸存者的WM容量/完整性(PBRT与XRT和HCS)，以及 (2)研究西药毒性与神经认知测试成绩之间的关系。 这项建议与NCI的目标是一致的，即“减少癌症和其他疾病的长期不良影响”。 治疗“是为了”改善癌症患者、幸存者及其家人的生活质量“。 神经认知迟发效应会导致许多人在教育、社交和职业方面受到严重限制 长期存活，极大地影响了他们的生活质量和功能独立性。需要研究来 确定哪些治疗最能限制与治疗后神经认知相关的痛苦 拒绝。我们的结果将具有临床价值，为神经认知的WM相关性提供及时的报告。 功能和治疗方式之间的比较。