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

描述（由申请人提供）：大多数在美国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。脑肿瘤幸存者特别容易出现一系列功能障碍，包括认知、教育、社会和医疗残疾。颅放射治疗（RT）仍然是一种重要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功能障碍的风险。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。PBRT的医疗优势在于质子束的辐射输送精度，在最大限度地减少对周围组织的辐射的同时，将最大剂量沉积到临床目标。通过消除对周围健康脑组织不必要的辐射，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，没有经验数据证明PBRT比XRT有神经保护作用。我们将评估儿童脑肿瘤患者和幸存者在PBRT后神经认知改变的质量、严重程度和功能影响。研究1是对接受PBRT治疗与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、纵向研究，其具体目的如下：(1)检查PBRT治疗后神经认知随时间的变化，(2)比较不同治疗类型（PBRT与单纯手术治疗）的神经认知随时间的变化。研究2是对接受PBRT与XRT治疗的儿童脑肿瘤长期幸存者的神经认知结果进行纵向比较，其具体目的如下：(1)检查RT后神经认知随时间的变化，(2)比较不同治疗类型（PBRT与XRT）的神经认知随时间的变化，以及(3)确定治疗后神经认知衰退的临床危险因素。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童神经肿瘤学项目之一，并且可以进入美国仅有的11个质子治疗中心中的1个治疗儿童脑肿瘤。这一提议与NCI“提高癌症患者、幸存者和家属的生活质量”的承诺相一致，以促进“安全、以患者为中心、有效”的高质量癌症治疗。及时、高效、公平”，以及“在知情决策的基础上促进患者选择”。神经认知晚期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，以确定哪种治疗方法最能限制与rt后神经认知能力下降相关的痛苦。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，将指导临床医生在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.