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. 2025 May;173(1):147-156.
doi: 10.1007/s11060-025-04973-7. Epub 2025 Feb 20.

Neurocognitive function in lower grade glioma patients selected for proton radiotherapy: real-world data from a prospective cohort study

Hiska L van der Weide  1   2 , Anne M Buunk  3   4 , Femke F Siebenga  3   5 , Johannes A Langendijk  6 , Agata Bannink-Gawryszuk  6 , Ingeborg Bosma  5 , Roelien H Enting  5 , Anouk van der Hoorn  7 , Hanne-Rinck Jeltema  4 , Michiel Wagemakers  4 , Rob J M Groen  4   8 , Annemiek M E Walenkamp-Hageman  9 , Janine Nuver  9 , Miranda C A Kramer  6 , Jacoba M Spikman  3   5
Affiliations

Neurocognitive function in lower grade glioma patients selected for proton radiotherapy: real-world data from a prospective cohort study

Hiska L van der Weide et al. J Neurooncol. 2025 May.

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Low grade glioma; Neurocognitive function; Proton therapy; Radiotherapy.

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Conflict of interest statement

Declarations. Ethical approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the University Medical Center Groningen, the Netherlands [METc 2017.478; Research Register 201700619]. Written informed consent was obtained from all individual participants in the study. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
a Total and domain NCF composite Z-scores prior to PRT. The boxes represent the interquartile range (IQR) and the whiskers the range, the median is indicated with a horizontal line. The median and IQR values are depicted in the boxes. A Z-score of 0 represents the mean in the normal population, and each unit a standard deviation. An ‘*’ indicates a significant difference of the patient cohort from the normal population. b Heatmap of individual NCF scores of patients prior to PRT. Each row represents an individual patient, and each column the test measures grouped into cognitive domains as specified in Table 1. Green fields indicate Z-scores higher than 0, and orange-red fields a negative Z-score. Patients are sorted by the total composite Z-score. VTS-RT = Computerized Vienna Test System Reaction Time, SDMT = Symbol Digit Modality Test, TMT = Trail Making Test, COWAT = Controlled Oral Word Association Test, RAVLT = Rey’s Auditory Verbal Learning Test, IR = Immediate Recall, DR = Delayed Recall
See this image and copyright information in PMC

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