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

项目摘要 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。特别是儿童脑肿瘤幸存者， 神经认知障碍、教育困难、社会问题和医学残疾。颅放射 治疗是一种重要的救生治疗，但与认知能力下降有关。质子束放射 PBRT是儿科脑肿瘤治疗中最有前途的最新进展之一。拟议 PBRT的医疗优势在于质子束的辐射输送精度， 对临床目标的剂量，同时最大限度地减少对周围组织的辐射。通过减少健康大脑的剂量 组织，PBRT可以节省认知功能，并减少症状负担比传统的光子或 X射线照射（XRT）导致生存率更大的功能独立性。 使用基于模型的加速纵向队列比较设计，我们将比较症状 放射治疗开始后多个数据点的负荷/毒性、神经认知变化和功能结局 通过PBRT与XRT治疗患者的晚期生存率。建议的目标如下：（1） 比较儿童脑肿瘤患者和幸存者的RT类型的症状负担和毒性，（2） 按RT类型比较神经认知结果随时间的变化，（3）比较 RT类型的早期和晚期生存率，以及（4）检查症状负荷/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 确定哪些治疗方法最能限制与症状负担和术后相关的痛苦， 治疗神经认知能力下降。我们的结果将具有临床价值，提供及时的比较， PBRT和XRT组之间的症状、神经认知变化和功能结局， 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.