The risk of radiation-induced neurocognitive impairment and the impact of sparing the hippocampus during pediatric proton cranial irradiation

Hippocampus is a central component for neurocognitive function and memory. We investigated the predicted risk of neurocognitive impairment of craniospinal irradiation (CSI) and the deliverability and effects of hippocampal sparing. The risk estimates were derived from published NTCP models. Specifically, we leveraged the estimated benefit of reduced neurocognitive impairment with the risk of reduced tumor control. For this dose planning study, a total of 504 hippocampal sparing intensity modulated proton therapy (HS-IMPT) plans were generated for 24 pediatric patients whom had previously received CSI. Plans were evaluated with respect to target coverage and homogeneity index to target volumes, maximum and mean dose to OARs. Paired t-tests were used to compare hippocampal mean doses and normal tissue complication probability estimates. The median mean dose to the hippocampus could be reduced from 31.3 GyRBE to 7.3 GyRBE (p RBE was possible with all plans considered as clinically acceptable treatment plans. By sparing the hippocampus to the lowest dose level, the risk estimation of neurocognitive impairment could be reduced from 89.6%, 62.1% and 51.1% to 41.0% (p p p We present estimates of potential clinical benefit in terms of neurocognitive impairment and demonstrate the possibility of considerably reducing neurocognitive adverse effects, minimally compromising target coverage locally using HS-IMPT.