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.

项目总结/摘要 在美国，大多数接受癌症治疗的儿童将获得长期生存， 这对不断增长的人口构成了挑战。脑肿瘤幸存者在一系列功能性疾病中处于特别危险的地位。 障碍，包括认知、教育和社交困难。头部放射治疗是必不可少的 但与认知能力下降有关。质子束放射治疗（PBRT）是一种 最有希望的儿科脑肿瘤治疗的最新进展。建议的医疗优势 PBRT在于质子束的辐射输送精度，将最大剂量沉积到临床目标 同时最小化对周围组织的辐射。通过消除对周围健康的不必要的辐射， 脑组织，PBRT可能比传统的光子或X射线照射（XRT）更好地保留认知功能。 利用容积测量和扩散张量成像（DTI），我们将检查白色物质之间的联系 (WM)PBRT治疗儿童脑肿瘤患者的毒性和神经认知结局。研究1是 儿童脑肿瘤患者WM改变及相关神经认知结局的前瞻性纵向研究 从诊断到早期生存率，对接受PBRT与仅手术治疗的患者进行随访。具体目标 包括：（1）通过治疗组比较WM体积/完整性随时间的变化（PBRT与仅手术 与健康对照（HC）），（2）检查WM毒性与神经认知测试之间的关联 随着时间的推移。研究2是一项关于工作记忆与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间生存期结局 仅具有以下特定目的：（1）按治疗类型（PBRT）比较存活者的WM体积/完整性 vs.仅手术和与HC），以及（2）检查WM毒性与神经认知测试之间的相关性 成绩.研究3是一项关于晚期脑梗死患者WM与神经认知结果相关性的横断面研究。 接受PBRT与XRT治疗的儿童脑肿瘤幸存者的生存率，包括以下具体指标 目的：（1）按治疗组比较存活者的WM体积/完整性（PBRT与XRT和HC），以及 (2)研究WM毒性和神经认知测试分数之间的关联。 这一建议与NCI的目标是一致的，即“减少癌症的长期不良影响及其对健康的影响”。 治疗”的儿童和“提高癌症患者，幸存者和他们的家庭的生活质量。” 神经认知迟发效应导致许多人在教育、社会和职业方面受到严重限制。 幸存者，大大影响他们的生活质量和功能的独立性长期。的研究需要 确定哪些治疗最能限制治疗后神经认知相关的痛苦 下降我们的研究结果将有临床价值，提供了一个及时的报告WM相关的神经认知 功能和治疗方式之间的比较。