Diffusion tensor imaging indices as biomarkers for cognitive changes following paediatric radiotherapy: a systematic review and meta-analysis.

Diffusion tensor imaging (DTI) can detect subtle manifestations of white matter (WM) injury following paediatric radiotherapy, which may be a potential biomarker for cognitive changes. This study aimed to synthesise the relationships between DTI indices and cognitive changes following paediatric radiotherapy through systematic review and meta-analysis. PubMed and Scopus electronic databases were used to identify eligible studies. Quality assessment was performed using the National Institute of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Information on demographics, DTI changes, and associations to cognitive outcomes were extracted. Meta-analyses were performed on DTI changes in specific anatomical locations. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in the preparation of this report. Eighteen studies were included (median study size: 21; range 18-146). 17/18 studies showed significant cognitive decline following irradiation. Meta-analyses found significant cognitive changes within patient's group of acute lymphoblastic leukaemia (ALL; standard mean differences [SMD] = -0.075, P = 0.01) and brain tumours (BT; SMD = -1.037, P ≤ 0.001) compared to control/baseline. Both groups also had significantly lower fractional anisotropy (FA) scores in the corpus callosum (ALL: SMD = -0.979, P = 0.002; BT: SMD = -1.025, P < 0.001). Decreased FA was consistently associated with cognitive decline. Correlation on WMFA integrity to cognitive domains was statistically significant (Z = 9.86, P < 0.001) with a large effect size (r = 0.52). White matter tract integrity of the corpus callosum measured with FA has the potential to be a biomarker for radiotherapy-related cognitive decline. Inclusion of DTI in follow-up imaging should be encouraged.