Cognitive Sparing in Proton versus Photon Radiotherapy for Pediatric Brain Tumor Is Associated with White Matter Integrity: An Exploratory Study

SIMPLE SUMMARY: Research has shown that children who undergo radiotherapy for brain tumors are at risk for long-term changes in both their thinking and brain structure. Compared to photon radiotherapy (i.e., X-rays), proton radiotherapy may cause less damage to healthy brain tissue and result in fewer cognitive problems. This study compared cognitive functioning and white matter damage in survivors of pediatric brain tumors who were treated with proton or photon therapy. The results showed that patients who received photon therapy had more cognitive problems and showed more white matter change than those who received proton therapy. Patients who underwent proton therapy, on the other hand, were similar to healthy individuals with no history of brain tumors. This study suggests that proton therapy may protect healthy brain tissue, leading to better long-term cognitive outcomes. ABSTRACT: Radiotherapy for pediatric brain tumors is associated with reduced white matter structural integrity and neurocognitive decline. Superior cognitive outcomes have been reported following proton radiotherapy (PRT) compared to photon radiotherapy (XRT), presumably due to improved sparing of normal brain tissue. This exploratory study examined the relationship between white matter change and late cognitive effects in pediatric brain tumor survivors treated with XRT versus PRT. Pediatric brain tumor survivors treated with XRT (n = 10) or PRT (n = 12) underwent neuropsychological testing and diffusion weighted imaging >7 years post-radiotherapy. A healthy comparison group (n = 23) was also recruited. Participants completed age-appropriate measures of intellectual functioning, visual-motor integration, and motor coordination. Tractography was conducted using automated fiber quantification (AFQ). Fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) were extracted from 12 tracts of interest. Overall, both white matter integrity (FA) and neuropsychological performance were lower in XRT patients while PRT patients were similar to healthy control participants with respect to both FA and cognitive functioning. These findings support improved long-term outcomes in PRT versus XRT. This exploratory study is the first to directly support for white matter integrity as a mechanism of cognitive sparing in PRT.