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.

Public Health Relevance

Many consider proton beam radiation therapy (PBRT) to be a promising treatment for children with brain tumors as it may preserve cognitive functioning without sacrificing disease control. Currently, there are no published reports of cognitive outcomes for patients treated for pediatric brain tumors with this technology. Ultimately, this lin of research is intended to: (1) help physicians and families better understand the effect of PBRT on cognitive functioning to inform treatment decisions, and (2) provide functional outcome data to be used toward justifying or reconciling the high cost and access limitations currently associated with PBRT.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA187202-06
Application #
9730390
Study Section
Behavioral Medicine, Interventions and Outcomes Study Section (BMIO)
Program Officer
St Germain, Diane
Project Start
2014-08-18
Project End
2020-07-31
Budget Start
2019-08-01
Budget End
2020-07-31
Support Year
6
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Pediatrics
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Antonini, Tanya N; Ris, M Douglas; Grosshans, David R et al. (2017) Attention, processing speed, and executive functioning in pediatric brain tumor survivors treated with proton beam radiation therapy. Radiother Oncol 124:89-97
Kahalley, Lisa S; Winter-Greenberg, Amanda; Stancel, Heather et al. (2016) Utility of the General Ability Index (GAI) and Cognitive Proficiency Index (CPI) with survivors of pediatric brain tumors: Comparison to Full Scale IQ and premorbid IQ estimates. J Clin Exp Neuropsychol 38:1065-76
Kahalley, Lisa S; Ris, M Douglas; Grosshans, David R et al. (2016) Comparing Intelligence Quotient Change After Treatment With Proton Versus Photon Radiation Therapy for Pediatric Brain Tumors. J Clin Oncol 34:1043-9