Neurocognition after brain irradiation: dose-volume effects and regional radiosensitivity - a systematic review by the ESTRO CNS focus group.

Abstract

Radiotherapy (RT) represents a cornerstone treatment for brain and head-and-neck (H&N) tumours. Radiation-associated neurocognitive decline (ND) is a clinically relevant late effect. Dose-response relationships for ND and the contribution of specific brain substructures are incompletely characterized. This systematic review summarises current evidence on neurocognitive assessments, ND dose-volume predictors, and imaging correlates of radiation-induced injury. A systematic search of PubMed and Scopus/Embase identified studies reporting neurocognitive outcomes, dose-effect relationships, and imaging biomarkers in adults with brain and H&N tumours. Following PRISMA methodology, study selection was performed independently by three reviewers. Data on study design, RT characteristics, neurocognitive testing, and imaging findings were extracted and synthesised descriptively. Twenty-eight studies met the inclusion criteria. Most were small cohorts with heterogeneous neurocognitive testing. Verbal Learning Tests and Trail Making Test A/B were the most frequently used. ND was reported in 17 studies, with variable incidence (21%-79%). Memory was the most consistently affected domain and showed the strongest association with hippocampal dose. Higher doses to the temporal lobes, thalamus, amygdala, cerebellum, and corpus callosum were associated with deficits in executive function, processing speed, attention, and motor coordination. Advanced imaging demonstrated dose-dependent atrophy, white-matter disruption, perfusion changes, and metabolic alterations correlating with ND. ND after brain irradiation appears to be associated with dose-dependent injury involving multiple brain structures beyond the hippocampus. Current exploratory evidence requires validation in larger prospective studies with standardized neurocognitive assessment, imaging protocols, and long-term follow-up to refine dose constraints and improve neurocognitive preservation.