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

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.