To determine neurocognitive function (NCF) profiles of patients with lower grade glioma (LGG) eligible to undergo proton radiotherapy (PRT), and how these relate to clinical and radiological characteristics. PRT is offered to those patients for whom sparing of NCF is considered important given their favorable prognosis. To date it is unknown to which extent their NCF profiles are favorable as well.

A consecutive cohort of 151 LGG patients eligible for PRT according to prevailing Dutch criteria, referred between 2018 and 2023, were assessed with standardized neuropsychological tests prior to PRT. Scores were compared to norm-scores. Composite scores were calculated for the total NCF and 6 separate cognitive domains, and profiles were related to tumor location. Clinical and radiological factors characterizing overall NCF impaired patients were investigated, comparing 3 definitions for impairment.

Patients had on average significantly lower NCF than their norm-group, but interindividual variability was large. For 100/151 patients (66.2%), all cognitive domains were intact, whereas 15/151 patients (9.9%) displayed multiple domain impairments. Poorer NCF was related to right-sided LGG laterality, larger PRT target volume, no Wait & Scan policy, worse neurological function and worse radiological indices (Fazekas and global cortical atrophy, respectively). LGG involvement of the left temporal and occipital lobes was associated with, respectively, lower verbal memory and processing speed.

Prior to PRT, the majority of selected LGG patients display favorable NCF profiles. However, a subgroup showed NCF impairments, with multiple relevant clinical and radiological covariates.