Cognitive Change after Proton RT vs. Photon or Surgery for Pediatric Brain Tumor

描述(申请人提供)：在美国，大多数接受癌症治疗的儿童将实现长期生存，生存对这一不断增长的人口提出了独特的挑战。脑瘤幸存者尤其有可能出现一系列功能障碍，包括认知、教育、社交和医学方面的残疾。颅脑放射治疗(RT)仍然是一种基本的挽救生命的治疗方法，但显著增加了儿童脑肿瘤患者认知障碍的风险。质子束放射治疗(PBRT)是儿童脑肿瘤治疗中最有前途的进展之一。提出的PBRT的医学优势在于质子束可能提供的辐射传输的精确度，在最大限度地减少对周围组织的辐射的同时，向临床靶点沉积最大剂量。通过消除对周围健康脑组织的不必要辐射，人们认为PBRT可能比传统的光子或X射线照射(XRT)更好地保护认知功能。然而，到目前为止，还没有经验数据证明PBRT比XRT具有神经保护作用。我们将评估儿童脑肿瘤患者和幸存者PBRT后神经认知改变的质量、严重性和功能影响。研究1是对接受PBRT和单纯手术治疗的儿童脑肿瘤患者的神经认知结果进行前瞻性、纵向的检查，目的如下：(1)检查PBRT后随时间的神经认知变化，以及(2)比较不同治疗类型(PBRT和仅手术)随时间的神经认知变化。研究2是对接受PBRT和XRT治疗的儿童脑肿瘤长期存活者的神经认知结果进行纵向比较，具体目的如下：(1)检查放疗后随时间的神经认知变化，(2)比较不同治疗类型(PBRT和XRT)随时间的神经认知变化，以及(3)确定与治疗后神经认知下降相关的临床危险因素。这些研究将在德克萨斯儿童医院进行，该医院拥有全国最大的儿科神经肿瘤学项目之一，可以使用美国仅有的11个治疗儿童脑瘤的质子治疗中心中的1个。这项建议与NCI的承诺是一致的，即“提高癌症患者、幸存者和家庭的生活质量”，促进“安全、以患者为中心、有效、及时、高效和公平的高质量癌症护理”，以及“促进基于知情决策的患者选择”。神经认知迟发效应极大地影响了许多儿童脑肿瘤幸存者的长期生活质量和功能独立性。因此，需要进行研究来确定哪些治疗方法能够最好地限制放疗后神经认知功能下降所带来的痛苦。我们的结果将具有临床价值，提供神经认知功能的及时报告和治疗之间的比较，将指导临床医生对PBRT后预期的结果范围。

DESCRIPTION (provided by applicant): 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, social, and medical disabilities. Cranial radiation therapy (RT) remains an essential lifesaving treatment but significantly increases the risk of cognitive impairment for pediatric brain tumor patients. Proton beam radiation therapy (PBRT) is one of the most promising advances in pediatric brain tumor treatment. The proposed medical advantage of PBRT lies in the precision of radiation delivery possible with proton beams, depositing maximum dose to clinical targets while minimizing radiation to surrounding tissues. By eliminating unnecessary radiation to surrounding healthy brain tissue, it is believed that PBRT may spare cognitive functioning better than conventional photon or x-ray irradiation (XRT). However, to date, there is no empirical data documenting the neuroprotective benefits of PBRT over XRT. We will assess the quality, severity, and functional impact of neurocognitive changes following PBRT in pediatric brain tumor patients and survivors. Study 1 is a prospective, longitudinal examination of neurocognitive outcomes among pediatric brain tumor patients treated with PBRT versus surgery alone with the following specific aims: (1) to examine neurocognitive change over time following PBRT, and (2) to compare neurocognitive change over time by treatment type (PBRT vs. Surgery Only). Study 2 is a longitudinal comparison of neurocognitive outcomes between long-term survivors of pediatric brain tumors treated with PBRT versus XRT with the following specific aims: (1) to examine neurocognitive change over time following RT, (2) to compare neurocognitive change over time by treatment type (PBRT vs. XRT), and (3) to identify clinical risk factors associated with neurocognitive decline following treatment. These studies will be conducted at Texas Children's Hospital, which has one of the largest pediatric neuro-oncology programs in the country and access to 1 of only 11 proton therapy centers in the US treating pediatric brain tumors. This proposal is consistent with NCI's commitment to "improve the quality of life for cancer patients, survivors, and families," to promote quality cancer care that is "safe, patient-centered, effective.timely, efficient, and equitable," and to "foster patient choice based on informed decision making." Neurocognitive late effects greatly affect the long-term quality of life and functional independence of many pediatric brain tumor survivors. Thus, research is needed to determine which treatments are best able to limit suffering associated with post-RT neurocognitive decline. Our results will have clinical value, providing a timely report of neurocognitive functioning and comparison between treatments that will guide clinicians on the range of outcomes to expect after PBRT.