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Neurocognitive Functions Before and After Radiotherapy in Pediatric Brain Tumor Survivors
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatric oncology research with a special focus on side effects.
Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.ORCID iD: 0000-0002-4310-3224
Department of Clinical Neuroscience, Centre for Psychiatry Research and Department of Molecular Medicine and Surgery, Karolinska Institutet & Stockholm Health Care Services, Stockholm, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
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2022 (English)In: Pediatric Neurology, ISSN 0887-8994, E-ISSN 1873-5150, Vol. 133, p. 21-29Article in journal (Refereed) Published
Abstract [en]

Background The numbers of pediatric brain tumor survivors are increasing due to improved treatment protocols and multimodal treatments. Many survivors have neurocognitive sequelae, especially after radiotherapy. Neuropsychologic assessment is therefore essential to interpret clinical outcome, evaluate treatments protocol, and implement rehabilitation interventions. The overall aim of this study was to describe neurocognitive functions before and after radiotherapy. We also aimed to explore potential confounding risk factors that could affect the interpretation of radiotherapy-induced neurocognitive decline. Methods Fifty pediatric brain tumor survivors who had received radiotherapy (five years or more ago) were included. Clinical characteristics, potential confounding risk factors, radiotherapy plans, and neurocognitive functions on intelligence quotient (IQ) and neuropsychologic measurements were analyzed before and after radiotherapy. Results Neurocognitive functions were affected before radiotherapy and were progressively aggravated thereafter. The last neuropsychologic assessment after radiotherapy varied between two and 139 months. Nineteen patients were tested five years after radiotherapy, and 90% of them performed ≥1 S.D. below the normative mean on IQ measurements. Several potential confounding risk factors including those induced by radiotherapy were associated with lower performance on perceptual function, working memory, and processing speed. Longer time after radiotherapy was particularly associated with lower performance on working memory and processing speed. Importantly, the neuropsychologic assessments revealed more comprehensive problems than could be inferred from IQ measurements alone. Conclusions Our study underpins the importance of systematic and structured neuropsychologic assessment before and after radiotherapy. The timing of the assessment is important, and potential confounding risk factors need to be identified to better evaluate radiotherapy-induced neurocognitive decline.

Place, publisher, year, edition, pages
Elsevier, 2022. Vol. 133, p. 21-29
Keywords [en]
Pediatric brain tumor, Neurocognition, Radiotherapy, Risk factors
National Category
Neurology Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-479055DOI: 10.1016/j.pediatrneurol.2022.05.006ISI: 000912839100005Scopus ID: 2-s2.0-85132518944OAI: oai:DiVA.org:uu-479055DiVA, id: diva2:1677627
Available from: 2022-06-28 Created: 2022-06-28 Last updated: 2026-01-27Bibliographically approved
In thesis
1. Pediatric Brain Tumor Survivors after Radiotherapy: Long-Term Neurocognitive Outcomes, Oculomotor Function, and Arousal
Open this publication in new window or tab >>Pediatric Brain Tumor Survivors after Radiotherapy: Long-Term Neurocognitive Outcomes, Oculomotor Function, and Arousal
2026 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.  

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2026. p. 83
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 2229
Keywords
Pediatric brain tumor, radiotherapy, organs at risk, mean dose, neurocognition, processing speed, fatigue, eye-tracking, pupillometry
National Category
Pediatrics Cancer and Oncology
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-577656 (URN)978-91-513-2726-6 (ISBN)
Public defence
2026-03-13, Universitetshuset, sal IV, Biskopsgatan 3, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Funder
Swedish Childhood Cancer Foundation, PR2013-0062,PR2018-0042, TJ2018-0046
Available from: 2026-02-19 Created: 2026-01-27 Last updated: 2026-02-20

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Söderström, HelenaBrocki, Karin C.Martinsson, UllaLjungman, Gustaf

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