Abstract

BACKGROUND AND AIMS: Pediatric brain tumors are the second most common type of pediatric cancer, and these patients face the worst health related quality of life (HRQOL) outcomes. Adult studies show increased inflammation association with lower HRQOL in adult brain tumor survivors. This relationship has not been explored in pediatric brain tumor survivors (PBTS). We conducted a case-control study to explore the relationship between inflammatory biomarkers and psychological sequela (i.e., sleep disturbance, fatigue, pain, negative affect) in PBTS. METHODS: Survivors aged 7-14 years with a primary brain tumor diagnosis were recruited from UMMC (N=29) and UAB (N=4) between 2016-2019. A control group (N=12) was recruited from UMMC well-child appointments. Parents and children completed self-reported surveys of pain, sleep, fatigue, and mood. The primary aims were to: (1) examine levels of C-reactive protein (CRP) inflammation in PBTS compared to controls (2) examine if higher CRP and SOX2 (from tumor tissue) were associated with psychological sequela. Independent samples T-Tests and spearman correlations evaluated aims. RESULTS: The final sample included 33 PBTS: median age=12.42 years; sex=51.5% female; race=63.6% Caucasian, 33.3% African American; pathologic diagnoses=67% astrocytoma/glioma, 11% medulloblastoma, 6% ependymoma, 12% other. Twelve controls had a median age=11.98 years; sex=41.7% female; race=16.7% Caucasian, 83.8% African American. There were marginal elevations in CRP for PBTS (44%, n=13) compared to controls (13%, n=1) (p=0.06). In PBTS, higher CRP levels were associated with greater parent-reported fatigue (p=0.035), sleep-wake disorders (p=0.017), excessive somnolence (p=0.042) and longer pain duration (p=0.037). From 13 tumor samples, positive SOX2 (69% of samples) was associated with increased parent-reported sleep-wake disorders (p=0.016), excessive somnolence (p=0.036), and both child and parent-reported sleep disturbance (child: p=0.014; parent: p=0.034). CONCLUSIONS: Elevated inflammation in PBTS, up to 9 years post-treatment, is consistently associated with increased sleep disturbance and fatigue. These relationships warrant further investigation in PBTS.

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