Brain biomarkers and neuropsychological outcomes of pediatric posterior fossa brain tumor survivors treated with surgical resection with or without adjuvant chemotherapy

Abstract

Purpose: Children with brain tumors experience cognitive late effects, often related to cranial radiation. We sought to determine differential effects of surgery and chemotherapy on brain structure and neuropsychological outcomes in children who did not receive cranial radiation therapy (CRT).

Methods: Twenty-eight children with a history of posterior fossa tumor (17 treated with surgery, 11 treated with surgery and chemotherapy) underwent neuroimaging and neuropsychological assessment a mean of 4.5 years (surgery group) to 9 years (surgery + chemotherapy group) posttreatment, along with 18 healthy sibling controls. Psychometric measures assessed IQ, language, executive functions, processing speed, memory, and social-emotional functioning. Group differences and correlations between diffusion tensor imaging findings and psychometric scores were examined.

Results: The z-score mapping demonstrated fractional anisotropy (FA) values were ≥2 standard deviations lower in white matter tracts, prefrontal cortex gray matter, hippocampus, thalamus, basal ganglia, and pons between patient groups, indicating microstructural damage associated with chemotherapy. Patients scored lower than controls on visuoconstructional reasoning and memory (P ≤ .02). Lower FA in the uncinate fasciculus (R = -0.82 to -0.91) and higher FA in the thalamus (R = 0.73-0.91) associated with higher IQ scores, and higher FA in the thalamus associated with higher scores on spatial working memory (R = 0.82).

Conclusions: Posterior fossa brain tumor treatment with surgery and chemotherapy affects brain microstructure and neuropsychological functioning years into survivorship, with spatial processes the most vulnerable. Biomarkers indicating cellular changes in the thalamus, hippocampus, pons, prefrontal cortex, and white matter tracts associate with lower psychometric scores.

Keywords: diffusion tensor imaging; neuroimaging; neuropsychology; pediatric brain tumor; survivors of childhood cancer.

Figure 1.. Image processing

Details of single subject and group level image processing Abbreviations: AFNI, Analysis of Functional NeuroImages; ANTs, Advanced Neuroimaging Tools; DWI, diffusion-weighted imaging; FSL, FMRIB Software Library; NIHPD, NIH Pediatric MRI Data Repository

Figure 2.. Areas of FA differences between patient groups in composite axial and sagittal diffusion tensor images

Red clusters indicate areas where FA z scores were ≥ 2SD lower in the S+C group than the S group; blue clusters indicate where FA z scores were ≥ 2SD lower in the S group than the S+C group. R and L indicate Right and Left on axial images; A and P indicate Anterior and Posterior. Cluster size is noted for each structure. A FA in bilateral SLF higher in S than S+C; B FA in prefrontal WM lower in S than S+C, FA in prefrontal GM higher in S than S+C; C FA in R thalamus higher in S than S+C, FA in L thalamus lower in S than S+C, FA in L PTR/CC higher in S than S+C; D FA in R putamen and GP higher in S than S+C; E FA in R UF higher in S than S+C; F FA higher in R hippocampus in S than S+C G F FA higher in L hippocampus in S than S+C; H FA higher in R pons in S than S+C; I FA higher in R PLIC and prefrontal WM in S than S+C. Abbreviations: CC, corpus callosum; GM, gray matter; GP, globus pallidus, MFG, middle frontal gyrus; PLIC, posterior limb of internal capsule; PTR, posterior thalamic radiation; SLF, superior longitudinal fasciculus; UF, uncinate fasciculus; WM, white matter