Brain Microstructural Changes Associated With Neurocognitive Outcome in Intracranial Germ Cell Tumor Survivors

Abstract

BackgroundChildhood intracranial germ cell tumor (GCT) survivors are prone to radiotherapy-related neurotoxicity, which can lead to neurocognitive dysfunctions. Diffusion kurtosis imaging (DKI) is a diffusion MRI technique that is sensitive to brain microstructural changes. This study aimed to investigate the association between DKI metrics versus cognitive and functional outcomes of childhood intracranial GCT survivors.MethodsDKI was performed on childhood intracranial GCT survivors (n = 20) who had received cranial radiotherapy, and age and gender-matched healthy control subjects (n = 14). Neurocognitive assessment was performed using the Hong Kong Wechsler Intelligence Scales, and functional assessment was performed using the Lansky/Karnofsky performance scales (KPS). Survivors and healthy controls were compared using mixed effects model. Multiple regression analyses were performed to determine the effects of microstructural brain changes of the whole brain as well as the association between IQ and Karnofsky scores and the thereof.ResultsThe mean Intelligence Quotient (IQ) of GCT survivors was 91.7 (95% CI 84.5 – 98.8), which was below the age-specific normative expected mean IQ (P = 0.013). The mean KPS score of GCT survivors was 85.5, which was significantly lower than that of controls (P < 0.001). Cognitive impairments were significantly associated with the presence of microstructural changes in white and grey matter, whereas functional impairments were mostly associated with microstructural changes in white matter. There were significant correlations between IQ versus the mean diffusivity (MD) and mean kurtosis (MK) of specific white matter regions. The IQ scores were negatively correlated with the MD of extensive grey matter regions.ConclusionOur study identified vulnerable brain regions whose microstructural changes in white and grey matter were significantly associated with impaired cognitive and physical functioning in survivors of pediatric intracranial GCT.

A systematic review on the use of quantitative imaging to detect cancer therapy adverse effects in normal-appearing brain tissue

“…The latter study also showed no changes in myelin water fraction, or ODI, NDI, or isotropic volume (Viso) derived from NODDI [ 115 ]. However, 11–12% decreases in mean kurtosis in the temporal lobe were measured in GM and WM in patients with nasopharyngeal carcinoma 1 week after RCTx with a further decrease to 34–39% after 1 year [ 116 ], and a decrease in WM, but not in GM was also found 1.2–12.2y after pediatric germ cell tumor [ 117 ]. An increase of radial kurtosis by 9% in NAWM was reported in testicular cancer survivors after CTx [ 118 ].…”

“…One of the rare studies that looked at baseline values reported that memory recover at follow-up correlated both with pre-operative NDI and NDI recovery on follow-up [ 113 ]. In survivors of pediatric germ cell tumors, mean kurtosis correlated positively with Karnofsky’s performance score and IQ in several cortical regions, but not on the whole-brain level [ 117 ].…”

“…However, the correlation with imaging biomarkers was not always corrected for multiple comparisons, possibly invalidating the positive findings. Only nine studies have either described that a proper correction for multiple comparisons was used [ 44 , 51 , 79 , 90 , 117 ] or examined a correlation with a single test only [ 69 , 91 , 116 , 126 ].…”

Neurobehavioral Impairment in Pediatric Brain Tumor Survivors: A Meta-Analysis

“…Because of the improved survival, there are new challenges in the long-term management of childhood cancer survivors, who often require multi-disciplinary care, particularly for their medical and psychosocial sequalae that might adversely impact their quality of life [3]. Moreover, pediatric brain tumor survivors (PBTS) typically also have neurocognitive and behavioral problems [4][5][6][7][8][9]. Given that cranial radiotherapy (RT) is associated with a high risk of neurotoxicity in PBTS, many survivorship studies have focused on the cognitive outcomes of PBTS [8][9][10][11][12][13][14], but very few studies have investigated the neurobehavioral outcomes.…”

“…Moreover, pediatric brain tumor survivors (PBTS) typically also have neurocognitive and behavioral problems [4][5][6][7][8][9]. Given that cranial radiotherapy (RT) is associated with a high risk of neurotoxicity in PBTS, many survivorship studies have focused on the cognitive outcomes of PBTS [8][9][10][11][12][13][14], but very few studies have investigated the neurobehavioral outcomes.…”