TY - JOUR

T1 - The risk of radiation-induced neurocognitive impairment and the impact of sparing the hippocampus during pediatric proton cranial irradiation

AU - Gram, Daniel

AU - Brodin, N. Patrik

AU - Bjork-Eriksson, Thomas

AU - Nysom, Karsten

AU - af Rosenschold, Per Munck

PY - 2023/2/24

Y1 - 2023/2/24

N2 - Background and purposeHippocampus 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.Material and methodsFor 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.ResultsThe median mean dose to the hippocampus could be reduced from 31.3 Gy(RBE) to 7.3 Gy(RBE) (p < .001), though 20% of these plans were not considered clinically acceptable as they failed one or more acceptance criterion. Reducing the median mean hippocampus dose to 10.6 Gy(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 < .001), 20.1% (p < .001) and 29.9% (p < .001) for task efficiency, organization and memory, respectively. Estimated tumor control probability was not adversely affected by HS-IMPT, ranging from 78.5 to 80.5% for all plans.ConclusionsWe 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.

AB - Background and purposeHippocampus 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.Material and methodsFor 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.ResultsThe median mean dose to the hippocampus could be reduced from 31.3 Gy(RBE) to 7.3 Gy(RBE) (p < .001), though 20% of these plans were not considered clinically acceptable as they failed one or more acceptance criterion. Reducing the median mean hippocampus dose to 10.6 Gy(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 < .001), 20.1% (p < .001) and 29.9% (p < .001) for task efficiency, organization and memory, respectively. Estimated tumor control probability was not adversely affected by HS-IMPT, ranging from 78.5 to 80.5% for all plans.ConclusionsWe 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.

KW - Neurocognitive impairment

KW - normal tissue complication probability

KW - tumor control probability

KW - craniospinal irradiation

KW - hippocampal avoidance

KW - pediatric hippocampus

KW - WHOLE-BRAIN RADIOTHERAPY

KW - PHASE-III TRIAL

KW - CRANIOSPINAL IRRADIATION

KW - THERAPY

KW - MEDULLOBLASTOMA

KW - AVOIDANCE

KW - ONCOLOGY

KW - TUMORS

KW - NEUROGENESIS

KW - DELINEATION

U2 - 10.1080/0284186X.2023.2176253

DO - 10.1080/0284186X.2023.2176253

M3 - Journal article

C2 - 36847433

VL - 62

SP - 134

EP - 140

JO - Acta Oncologica

JF - Acta Oncologica

SN - 1100-1704

IS - 2

ER -