QOL-13. NEUROCOGNITIVE OUTCOMES ACCORDING TO RISK-ADAPTED TREATMENT REGIMENS FOR CHILDREN OLDER THAN 4 WITH MEDULLOBLASTOMA AND POSTERIOR FOSSA EPENDYMOMA – RESULTS OF THE HIT2000 TRIAL

OBJECTIVES: Reduced neuropsychological outcomes are a major concern in pediatric patients with malignant brain tumors. We aimed to estimate decline in cognitive function according to treatment regimens. METHODS: Cross-sectional analysis of cognitive functions tested with the Neuropsychological Basic Diagnostic tool (NBD) in 279 patients >4 years at diagnosis (median: 8.66; range: 4.01–18.98) with medulloblastoma (n=110, 23.7–25.0Gy CSI; n=131, >30Gy CSI) or posterior fossa ependymoma (n=38 local radiotherapy) who participated in the HIT-2000 trial. Multivariable regression analysis was conducted to adjust for postoperative cerebellar mutism syndrome, preoperative hydrocephalus, postoperative shunt placement, the interval between diagnosis and assessment, sex and age. RESULTS: Mean time from diagnosis to assessment was 5.1 years. Increasing CSI-dose was significantly associated with a deterioration in performance of most subtests, particularly in areas of fluid intelligence (mean z-values per test for no CSI/23.4Gy/>30Gy respectively: matrix reasoning:-0.40/-0.52/-0.98, p<.001), short-term memory (number recall: -0.07/-0.58/-0.64, p=.002), visuo-spatial skills (visual-motor integration:-0.49/-0.68/-1.12, p<.001) and fine motor skills (dominant-hand:-1.09/-1.80/-2.12, p=.008; non-dominant-hand:-1.47/-2.59/-2.82, p=.003; bimanual coordination:-1.33/-2.68/-2.76, p=.001). These differences were retained after adjustment for confounding variables. Within medulloblastoma patients treated with >30Gy CSI, selective attention, but no other function was reduced in patients treated with pre-radiotherapy chemotherapy including intraventricular MTX (selective attention (with chemotherapy/without chemotherapy mean z-values: -0.66/0.00, p=.006)). Patients with SHH-activated medulloblastoma did significantly better than WNT or Group3/Group4 medulloblastoma patients in fluid intelligence and fine motor skills. CONCLUSION: CSI dose among other highly relevant factors had significant effects on neuropsychological outcome. Pre-radiotherapy intraventricular MTX had only minor effects. Patients with SHH-activated medulloblastomas showed a more favorable outcome when compared to patients in the other subgroups.