Subcortical alterations following pediatric posterior fossa brain tumor treatment: A longitudinal MRI study

Increasing survival rates in pediatric brain tumor patients highlight the importance of understanding treatment-related neurodevelopmental consequences. The posterior fossa is a primary site for many of these tumors, which are treated with surgery, chemotherapy, and/or radiation therapy that could impact brain function and structure. This retrospective longitudinal study examines changes in subcortical brain structures of pediatric posterior fossa tumor patients over five years post-diagnosis and compares patients who were treated for low- and high-grade tumors.

We analyzed 558 T1-weighted (T1w) brain MR images of 57 pediatric posterior fossa tumor patients (mean age at diagnosis = 9.65 (SD 4.06), 44 % female). There were 39 patients with a low-grade tumor treated with surgery and/or chemotherapy and 18 patients with a high-grade tumor treated with surgery, chemotherapy, and radiation treatment. Volumes of the globus pallidus, caudate, putamen, nucleus accumbens, amygdala, thalamus and hippocampus were calculated using SPM CAT12 (Statistical Parametric Mapping Computational Anatomy Toolbox). Linear mixed effect models were estimated to study the association between volumetric changes and time for these 7 subcortical structures.

Significant interactions between time and group were shown in the hippocampus (β = -0.06, SE = 0.02, p < .001) and globus pallidus (β = 0.01, SE = 0.00, p = .016). Patients treated for low-grade tumors exhibited increasing hippocampal volume over time, while those treated for high-grade tumors experienced a decline. In the globus pallidus, volume decreased over time for the low-grade tumor group but remained stable for the high-grade tumor group. Patients with a history of hydrocephalus had smaller thalamic (β = -0.40, SE = 0.14, p = .004) and hippocampal (β = -0.31, SE = 0.12, p = .012) volumes. Younger age at diagnosis was associated with smaller putamen and thalamus, and male sex was associated with larger volumes of the putamen, nucleus accumbens and amygdala.

These findings suggest that children who received treatment for low- or high-grade tumors had different subcortical volumes over time, which may be related to treatment, complications, or demographic factors such as age and sex. These results suggest that while brain tumor treatment primarily aims to cure patients, it may inevitably affect neural development and may contribute to a range of cognitive, behavioral, and emotional long-term deficits. This emphasizes the need for long-term monitoring and prospective longitudinal studies into structural and functional brain changes after treatment for pediatric brain tumor.