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: 10054959
• 负责人: LISA SCHUM KAHALLEY
• 金额: $ 77.14万
• 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 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10054959
• 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; 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; 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; x-ray irradiation

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.

项目概要/摘要 在美国，大多数接受癌症治疗的儿童都将实现长期生存，并且生存率具有独特性 这个不断增长的人口所面临的挑战。脑肿瘤幸存者面临一系列功能障碍的特殊风险 障碍，包括认知、教育和社交困难。颅脑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）是其中之一 儿科脑肿瘤治疗中最有希望的最新进展。建议的医疗优势 PBRT 的关键在于质子束辐射传输的精确性，向临床目标沉积最大剂量 同时最大限度地减少对周围组织的辐射。通过消除对周围健康的不必要的辐射 与传统光子或 X 射线照射 (XRT) 相比，PBRT 可以更好地保护脑组织的认知功能。 使用体积测量和扩散张量成像 (DTI)，我们将检查白质之间的关联 (WM) 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 小儿脑肿瘤 WM 变化和相关神经认知结果的前瞻性纵向研究 接受 PBRT 治疗的患者与仅接受手术治疗的患者从诊断到早期生存期进行随访。具体目标 包括：(1) 比较治疗组随时间的 WM 体积/完整性变化（PBRT 与仅手术治疗） 和与健康对照 (HC) 相比），以及 (2) 检查 WM 毒性与神经认知测试之间的关联 随着时间的推移得分。研究 2 是 WM 与神经认知之间关联的横断面研究 接受 PBRT 与手术治疗的儿童脑肿瘤幸存者的中期生存结果 仅具有以下具体目标：（1）按治疗类型比较幸存者的 WM 体积/完整性（PBRT） 与仅手术和 HC 相比），以及 (2) 检查 WM 毒性与神经认知测试之间的关联 分数。研究 3 是一项关于 WM 与晚期神经认知结果关联的横断面研究。 接受 PBRT 与 XRT 治疗的儿童脑肿瘤幸存者的生存率，包括以下具体内容 目的：(1) 按治疗组比较幸存者的 WM 体积/完整性（PBRT 与 XRT 以及与 HC），以及 (2) 检查 WM 毒性与神经认知测试分数之间的关联。 该提案与 NCI 的目标是一致的，即“减少癌症及其相关疾病的长期不良影响”。 儿童的治疗”以及“改善癌症患者、幸存者及其家人的生活质量”。 神经认知迟发效应导致许多人在教育、社会和职业方面受到严重限制 幸存者，极大地影响他们的生活质量和长期功能独立性。需要研究 确定哪些治疗最能限制治疗后神经认知相关的痛苦 衰退。我们的结果将具有临床价值，及时提供 WM 与神经认知的相关性报告 功能和治疗方式之间的比较。