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 在美国接受癌症治疗的大多数儿童都将实现长期生存，而生存态度独特 对这个人口不断增长的挑战。脑肿瘤存活特别有一系列功能的风险 障碍，包括认知，教育和社会困难。颅放射疗法是必不可少的 救生治疗，但与认知能力下降有关。质子束辐射疗法（PBRT）是 小儿脑肿瘤治疗最近最有希望的进步。提议的医疗优势 PBRT在于用质子束递送辐射的精度，将最大剂量沉积到临床靶标 同时最大程度地减少对周围组织的辐射。通过消除不必要的辐射到周围的健康 脑组织，PBRT可以比常规光子或X射线照射（XRT）更好地避免认知功能。 使用体积和扩散张量成像（DTI），我们将检查白质之间的关联 （WM）用PBRT治疗的小儿脑肿瘤患者的毒性和神经认知结果。研究1是 WM变化的前瞻性，纵向研究和小儿脑肿瘤中相关的神经认知结果 接受PBRT与手术治疗的患者仅在诊断过程中通过早期生存治疗。具体目标 包括：（1）比较按治疗组随时间变化/完整性的变化（仅PBRT与手术 和健康对照（HCS））和（2）检查WM毒性与神经认知测试之间的关联 随着时间的流逝得分。研究2是WM与神经认知之间关联的横断面研究 用PBRT与手术治疗的小儿脑肿瘤幸存者中间生存期间的结果 仅具有以下特定目的：（1）比较按治疗类型比较生存中的WM量/完整性（PBRT 仅与手术和HCS）和（2）检查WM毒性与神经认知测试之间的关联 分数。研究3是WM与神经认知结果的横断面研究 用PBRT与XRT治疗的小儿脑肿瘤幸存者的生存 目的：（1）比较治疗组（PBRT与XRT和HCS）生存中的WM体积/完整性，以及 （2）检查WM毒性与神经认知测试评分之间的关​​联。 该提案与NCI的目标一致，以“减少癌症的长期不利影响 在儿童中的治疗”，并“改善癌症患者，幸存者及其家人的生活质量”。 神经认知的后期作用导致许多人的重大教育，社会和职业限制 幸存者，长期影响他们的生活质量和功能独立性。需要研究 确定哪些治疗方法最能限制与后处理后神经认知相关的痛苦 衰退。我们的结果将具有临床价值，提供了及时报告神经认知的WM相关性 治疗方式之间的功能和比较。