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

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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.