Introduction: Preservation of language functioning in patients undergoing brain tumor surgery is essential because language impairments negatively impact the quality of life. Brain tumor patients have alterations in functional connectivity (FC), the extent to which brain areas functionally interact. We studied FC networks in relation to language functioning in glioma and meningioma patients.Method: Patients with a low-grade glioma (N = 15) or meningioma (N = 10) infiltrating into/pressing on the language-dominant hemisphere underwent extensive language testing before and 1 year after surgery. Resting-state EEG was registered preoperatively, postoperatively (glioma patients only), and once in healthy individuals. After analyzing FC in theta and alpha frequency bands, weighted networks and Minimum Spanning Trees were quantified by various network measures.Results: Pre-operative FC network characteristics did not differ between glioma patients and healthy individuals. However, hub presence and higher local and global FC are associated with poorer language functioning before surgery in glioma patients and predict worse language performance at 1 year after surgery. For meningioma patients, a greater small worldness was related to worse language performance and hub presence; better average clustering and global integration were predictive of worse outcome on language function 1 year after surgery. The average eccentricity, diameter and tree hierarchy seem to be the network metrics with the more pronounced relation to language performance.Discussion: In this exploratory study, we demonstrated that preoperative FC networks are informative for pre- and postoperative language functioning in glioma patients and to a lesser extent in meningioma patients.

Background: Pseudoprogression is known to occur after immune-checkpoint inhibitor (ICI) therapy in brain metastasis and can complicate clinical decision-making. Still, its incidence, timing, and clinical presentation remain unclear. A retrospective cohort study in melanoma and non-small cell lung cancer brain metastasis patients was conducted to address this. Materials and Methods: Brain metastasis patients showing progression on MRI according to response assessment in neuro-oncology brain metastases criteria after starting ICI therapy were included, irrespective of prior irradiation. Lesions were classified as tumour progression (TP) or pseudoprogression based on three-month radiological follow-up or histopathology. TP was assigned if progression was again shown at three months. Pseudoprogression was assigned if lesions showed stability, partial, or complete response at three months. ‘Non-classified’ lesions were those with new or changed treatment during follow-up. Results: A cohort of 98 patients with 233 lesions was included over a 13-year period; 170 lesions were considered non-classified, and 41 and 22 lesions were classified as TP and pseudoprogression respectively. This resulted in a lesion- and patient-specific incidence for pseudoprogression of 9.4% and 17.3% respectively. Due to the large number of lesions that could not be classified, as is the case in clinical practice, the reported incidence in this study is likely an underestimation and can be seen as a ‘minimum’ incidence rate. Ten pseudoprogression (45.5%) and 13 (31.7%) TP lesions were previously irradiated. Pseudoprogression occurred at a median of 2.7 months after starting ICI therapy. The only clinical feature distinguishing patients with TP from pseudoprogression was that TP patients were more likely to need dexamethasone for neurological symptoms. Conclusions: Pseudoprogression has a lesion-specific incidence rate of at least 9.4% and occurs at a median of 2.7 months after starting ICI therapy. Severe neurological symptoms requiring dexamethasone may be a clinical feature typical for TP.

Background: Diffusion weighted imaging (DWI) is used for monitoring purposes for lower-grade glioma (LGG). While the apparent diffusion coefficient (ADC) is clinically used, various DWI models have been developed to better understand the micro-environment. However, the validity of these models and how they relate to each other is currently unknown. Therefore, this study assesses the validity and agreement of these models. Methods: Fourteen post-treatment LGG patients and six healthy controls (HC) underwent DWI MRI on a 3T MRI scanner. DWI processing included diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), white matter tract integrity (WMTI), neurite orientation dispersion and density imaging (NODDI), and fixel-based analysis (FBA). Validity was assessed by delineating surgical cavity, peri-surgical cavity, and normal-appearing white matter (NAWM) in LGG patients, and white matter (WM) in HC. Spearman correlation assessed the agreement between DWI parameters. Results: All obtained parameters differed significantly across tissue types. Remarkably, WMTI showed that intra-axonal diffusivity was high in the surgical cavity and low in NAWM and WM. Most DWI parameters correlated well with each other, except for WMTI-derived intra-axonal diffusivity. Conclusion: This study shows that all parameters relevant for tumour monitoring and DWI-derived parameters for axonal fibre-bundle integrity (except WMTI-IAS-D_a) could be used interchangeably, enhancing inter-DWI model interpretability.

Introduction. Pseudoprogression (PsP) after proton therapy (PT) can mimic tumour progression and may cause neurological morbidity. We characterised PsP incidence, risk factors, spatial distribution and longitudinal dynamics in adults with IDH-mutated grade 2–3 glioma treated with PT.Methods. Patients treated between 2018–2022 were included. Post-PT MRIs were centrally reviewed for contrast-enhancing PsP. We estimated actuarial incidence (Kaplan–Meier), evaluated clinical risk factors using Cox regression, and analysed lesion location and volumetric behaviour over time.Results. PsP occurred in 33/137 (24.1%) patients; 8 (5.8%) developed symptomatic PsP (CTCAE grade ≥2). Mean time to first PsP was 18.1 months, and 2-year actuarial incidence was 18.1% overall (14.7% in grade 2 and 29.0% in grade 3 glioma). Independent risk factors were age >50 years (Hazard Ratio (HR) 2.5), Fazekas grade ≥2 on pre-PT MRI (HR 3.6), and treatment in 2021 (HR 3.2).In total, 115 PsP lesions were identified: 53 (46.1%) in the periventricular space (PVS) and 5 (4.3%) in the optic pathway. All symptomatic lesions involved the PVS and/or optic pathway. Symptomatic PVS-PsP showed multifocality, earlier onset (mean 14 months), faster growth (>0.5 cc/month) and larger cumulative volumes (>1.75 cc).Conclusion. Clinically consequential PsP after PT clustered in the PVS and optic pathway. Baseline clinical factors and simple volumetric dynamics may support risk-adapted surveillance and earlier multidisciplinary review, but proposed volumetric triggers require external validation.