Comparison of Symptom Burden/Toxicity, Neurocognitive Change, and Functional Outcomes in Pediatric Brain Tumor Patients Treated with Proton vs. Photon Radiotherapy.

项目总结 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。尤其是儿童脑瘤幸存者，面临着患脑肿瘤的风险 神经认知障碍、教育困难、社会问题和医学残疾。颅骨辐射 治疗是一种基本的挽救生命的治疗方法，但与认知能力下降有关。质子束辐射 治疗(PBRT)是近年来儿童脑肿瘤治疗中最有希望的进展之一。建议数 PBRT的医学优势在于质子束辐射传输的精确度，最大限度地沉积 对临床靶点的辐射剂量，同时最大限度地减少对周围组织的辐射。通过减少对健康大脑的剂量 组织，PBRT可以节省认知功能，减轻症状负担，比传统的光子或 X射线照射(XRT)导致更大的功能独立性的生存。 使用基于模型的加速纵向队列比较设计，我们将比较症状 从放疗开始的多个数据点的负荷/毒性、神经认知变化和功能结果 通过接受PBRT和XRT治疗的患者的晚期生存期。提出了以下目标：(1) 按RT类型比较儿童脑肿瘤患者和幸存者的症状负担和毒性，(2) 通过RT类型比较神经认知结果随时间的变化，(3)比较 (4)检查症状负担/毒性之间的关系； 神经认知功能和功能结果作为RT类型的函数。 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症状、负担和后症状相关的痛苦 治疗神经认知功能衰退。我们的结果将具有临床价值，提供了一个及时的比较 PBRT和XRT组之间的症状、神经认知变化和功能结果将指导 临床医生和家庭对PBRT后预期结果的范围。

PROJECT SUMMARY Most children treated for cancer in the US will achieve long-term survival, and survivorship presents unique challenges for this growing population. Pediatric brain tumor survivors, in particular, are at risk for neurocognitive impairments, educational difficulties, social problems, and medical disabilities. 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 reducing dose to healthy brain tissue, PBRT may spare cognitive functioning and reduce symptom burden better than conventional photon or x-ray irradiation (XRT) leading to greater functional independence in survivorship. Using a model-based, accelerated longitudinal cohort comparison design, we will compare symptom burden/toxicity, neurocognitive change, and functional outcomes at multiple data points from start of radiation through late survivorship in patients treated with PBRT versus XRT. The following aims are proposed: (1) to compare symptom burden and toxicity by RT type in pediatric brain tumor patients and survivors, (2) to compare change in neurocognitive outcomes over time by RT type, (3) to compare functional outcomes in early and late survivorship by RT type, and (4) to examine relations among symptom burden/toxicity, neurocognitive function, and functional outcomes as a function of RT type. 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 symptom burden and post- treatment neurocognitive decline. Our results will have clinical value, providing a timely comparison of symptoms, neurocognitive changes, and functional outcomes between PBRT and XRT groups that will guide clinicians and families on the range of outcomes to expect after PBRT.