Helena Söderström: Pediatric Brain Tumor Survivors after Radiotherapy: Long-Term Neurocognitive Outcomes, Oculomotor Function, and Arousal

Abstract

Pediatric brain tumor survivors (PBTS) are at increased risk of long-term neurocognitive late effects, particularly following radiotherapy (RT), with processing speed being one of the domains most commonly impaired. The developing brain is particularly vulnerable to RT, and long-term neuropsychological follow-up is therefore recommended. Most studies addressing this topic have primarily focused on prescribed dose, planning target volume (PTV), and whole-brain radiotherapy (WBRT) dose, whereas the association between mean radiation dose to organs at risk (OAR) and neurocognitive outcomes remains insufficiently explored. Although neurocognitive functioning is routinely assessed through standardized neuropsychological testing, eye-tracking measures—including eye movements and pupillometry—may serve as sensitive complementary indicators of attention, processing speed, arousal, and executive functioning.

This thesis investigated neurocognitive outcomes in relation to different RT dose measures, including PTV dose and mean RT dose to established and potential new OAR, using both neuropsychological assessment and eye-tracking metrics. Additional clinical risk factors were also explored. Both retrospective and prospective studies of PBTS treated with RT between 2003-2015 were included. Neurocognitive function was assessed before, after, and 8–20 years post-RT. Long-term outcomes were related to RT dose parameters, and eye-tracking and fatigue were compared with age-matched controls.

Neurocognitive impairments were present prior to RT and became more prevalent with increasing time after treatment. Higher PTV dose was associated with lower working memory performance. Higher mean RT doses to several established and potential new OAR were associated with lower intelligence quotient and processing speed, as well as impaired oculomotor performance, altered pupil responses, and higher fatigue. WBRT and larger tumor size were also linked to poorer outcomes. 

In conclusion, the findings from this thesis show that PBTS are at elevated risk of long-term neurocognitive, oculomotor, and arousal-related difficulties following RT. Mean RT dose to OAR provides valuable information on radiation-related impairment beyond PTV dose. These findings underscore the need of structured neuropsychological follow-up. They further demonstrate the value of mean RT dose metrics an eye-tracking measures in evaluating radiation-related neurocognitive outcomes and guiding targeted treatment and rehabilitation strategies.