Skull base location has been associated with poorer progression-free survival (PFS), but whether specific anatomical locations within the skull base provide additional prognostic information beyond WHO grade and extent of resection (EOR) remains less well defined. Here, we evaluated the association between anatomical location and long-term tumor control in surgically treated skull base meningiomas (SBMs). Descriptive voxel-based heatmaps were generated to visualize the spatial distribution of tumors and recurrent/progressive cases. We retrospectively screened patients with SBMs who underwent surgical resection with complete follow-up data. Anatomical subgroups were consolidated into four regions for survival analysis. Kaplan–Meier analysis and Firth-penalized Cox regression were used to evaluate factors associated with PFS. Preoperative tumors were manually segmented and registered to the MNI152 template to generate spatial heatmaps. A total of 135 patients were included. Median age was 58 years, 83

Background: The vestibular schwannoma (VS) is the most common cerebellopontine angle tumor in adults, exhibiting a highly variable natural history, from stability to rapid growth. Accurate, the non-invasive prediction of tumor behavior is essential to guide personalized management and avoid overtreatment or delayed intervention. Objective: To systematically review and synthesize the evidence on MRI-based biomarkers for predicting VS growth and treatment responses. Methods: We conducted a PRISMA-compliant search of PubMed, EMBASE, and Cochrane databases for studies published between 1 January 2000 and 1 January 2025, addressing MRI predictors of VS growth. Cohort studies evaluating texture features, signal intensity ratios, perfusion parameters, and apparent diffusion coefficient (ADC) metrics were included. Study quality was assessed using the NOS (Newcastle-Ottawa Scale) score, GRADE (Grading of Recommendations, Assessment, Development and Evaluation), and ROBIS (Risk of Bias in Systematic reviews) tool. Data on diagnostic performance, including the area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, specificity, and p value, were extracted and descriptively analyzed. Results: Ten cohort studies (five retrospective, five prospective, total n = 525 patients) met the inclusion criteria. Texture analysis metrics, such as kurtosis and gray-level co-occurrence matrix (GLCM) features, yielded AUCs of 0.65-0.99 for predicting volumetric or linear growth thresholds. Signal intensity ratios on gadolinium-enhanced T1-weighted images for tumor/temporalis muscle achieved a 100% sensitivity and 93.75% specificity. Perfusion MRI parameters (Ktrans, ve, ASL, and DSC derived blood-flow metrics) differentiated growing from stable tumors with AUCs up to 0.85. ADC changes post-gamma knife surgery predicted a favorable response, though the baseline ADC had limited value for natural growth prediction. The heterogeneity in growth definitions, MRI protocols, and retrospective designs remains a key limitation. Conclusions: MRI-based biomarkers may provide exploratory signals associated with VS growth and treatment responses. However, substantial heterogeneity in growth definitions and MRI protocols, small single-center cohorts, and the absence of external validation currently limit clinical implementation.

Background:Glioblastoma (GBM) is an aggressive malignancy with poor outcomes, particularly when resection is infeasible. Laser Interstitial Thermal Therapy (LITT) offers a minimally invasive cytoreductive option, though robust evidence remains limited. The aim of the EMITT trial (NCT05318612) was to evaluate LITT in these patients. However, the study was terminated early following funding retraction due to slow patient inclusion. Despite being underpowered, its findings provide valuable insights into LITT's potential role. Methods:In this non-blinded multicentre randomised controlled trial, adult patients with unresectable GBM were randomised 1:1 to biopsy or biopsy with same-session LITT followed by standard of care. Patients were recruited by seven Dutch neurosurgical hospitals. Primary outcomes were overall survival and health-related quality of life (HR-QoL) at 5 months post-randomization. Minimum follow-up was 18 months or until death. Findings:Patients were included between April 19, 2022, and March 19, 2024. Twenty-nine patients were included; three were excluded post-randomization, leaving twenty-six for intention-to-treat analyses: fourteen in the control group and twelve in the intervention group. Median survival was 4.8 months (95%CI 3.4-not estimable) in controls and 7.8 months (95%CI 2.58-not estimable) in intervention. Mean QLQ-C30 summary scores at 5 months were 77 (SD 11) and 81 (SD 11). Interpretation:Definitive conclusions regarding (cost-)effectiveness are precluded by small sample size and baseline imbalances. This work highlights the need for larger prospective studies to establish LITT's effectiveness in this population and lessons learned may inform the design of future trials. Funding:Funding by the Dutch Healthcare Institute and ZonMw.

AIM:To evaluate clinical and radiological outcome in surgically treated Koos 4 vestibular schwannomas. MATERIAL AND METHODS:Volumetric analysis of the tumour volumes before surgery, after surgery (before radiation), and at follow-up time-points after radiation was performed. Clinical data on facial nerve function and complications were collected. Approximately 6 months after surgery, all patients were treated with a single fraction of stereotactic radiosurgery using the gamma knife radiosurgery with a mean marginal dose of 12.9 Gy to the residual tumour volume. RESULTS:Mean tumour volume was 11.64 cm3 which was reduced to a mean volume of 4.17 cm3 after partial resection. After a mean follow-up of 100 months, residual tumour showed a decrease in volume in 20 patients, stable disease in one patient and two patients showed progressive tumour volume requiring a second operation in one patient. Facial nerve function was preserved in all patients. One patient suffered from a trigeminal neuralgia after radiation. CONCLUSION:Planned partial resection followed by radiation for patients with Koos 4 vestibular schwannoma is an effective strategy to preserve facial nerve function and achieve tumour control. Residual tumours after planned partial resection showed a mean decrease in volume of 50% at the last follow-up time point.

Glioblastoma remains a highly malignant, inevitably recurring brain tumor with dismal prognosis. Tumor progression is influenced by cellular interactions between the tumor and its microenvironment, yet quantitative data on these interactions, particularly under standard of care therapy, remains sparse. We utilized spatial, single-cell, multiome profiling to map therapy-induced changes in the architecture of >700 paired glioblastoma samples derived from 101 patients at diagnosis and recurrence. This approach categorized patients into groups reflecting specific evolutionary responses to therapy, with implications for prognosis and treatment. Favourable outcomes were linked to shifts towards enriched perivascular, oligodendrocyte-progenitor-like niches with deep tissue infiltration of activated immune cells, whereas poor outcomes correlated with shifts towards an immunosuppressive mesenchymal environment with poor immune infiltration. Finally, while mutations in EGFR/PTEN, or MGMT-promoter methylation influenced tumor evolution, we also identified a defined subset of patients that were more responsive to lomustine after early recurrence. Our findings offer a framework to stratify patient treatment based on tumor and microenvironmental evolution. Maxime Vanmechelen, Pouya Nazari, Jan Beckervordersandforth, Daphne Leunissen, Basiel Cole, Brecht Decraene, Yanti De Visser, Gautam Shankar, Maikel Verduin, Daniele Pantano, Carmen Bravo Gonzalez-Blas, Chiara Caprioli, Sien Bevers, Tom Moors, Jayesh Telang, Ivey Sebasstian, Julie Messiaen, Yannick Van Herck, Emma Geens, Danielle Eekers, Annelies Claeys, Marleen Derweduwe, Axel Zur Hausen, Francesca Bosisio, Frank Weyns, Thomas Daenekindt, Peter Van Eyken, Mieke Govers, Ferdinand Mennens, Koos Hovinga, Steven De Vleeschouwer, Paul Clement, Martijn Broen, Marc Vooijs, Raf Sciot, Asier Antoranz, Jon Pey, Ernst-Jan Speel, Ann Hoeben, Frederik De Smet. Characterization of therapeutic effects in glioblastoma through integrated spatial single-cell multiome profiling of longitudinal samples: Unveiling clinically relevant subtypes of pathological changes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6362.

This registry-based study aims to examine the variation in biopsy and resection indications for glioblastoma patients across Dutch hospitals and to identify patient- and hospital-related factors associated with the surgical treatment. Data from all 7443 adults with first-time glioblastoma surgery at 12 hospitals were obtained from the prospective population-based Quality Registry Neurosurgery in the Netherlands between 2011 and 2021. Patients were stratified by either biopsy or resection. We analyzed variation in American Association of Anesthesiologist (ASA) classification, Karnofsky Performance Score (KPS), gender and age distribution between the different centers. Between-hospital variation in biopsy percentage was analyzed using a funnel plot. Logistic regression was used to identify associated patient- and hospital-related factors. In total, 32

Glioblastoma is the most common and treatment-resistant primary malignant brain tumor, with high morbidity and mortality despite standard treatment protocols. This study aims to evaluate survival and prognostic factors, and introduce two pragmatic prognostic models to inform individualized, patient-centered decision-making, using a large Dutch registry. We analyzed a prospective cohort of 7621 patients (2012–2022) in 12 Dutch centers via the Dutch Quality Registry Neurosurgery. Univariate analysis of prognostic factors, Kaplan–Meier survival curves, and funnel plots comparing center performance (30-day and 2-year mortality) were conducted. Two prognostic models using multivariate Cox regression were developed. Glioblastoma incidence was 3.9/100.000 in The Netherlands. Overall, 30-day mortality was 5.1

Background: GKRS shows a high success rate in controlling growth of vestibular schwannoma, but a small number of tumors still grow after treatment. However, only a few studies have investigated the predictive factors of this growth. Objective: Here, we aim to explore the growth determinants of vestibular schwannoma after GKRS. Methods: This paper has analyzed literature published between 2000 and 2024 from PubMed, EMBASE, and Cochrane databases. Potential determinants, including age, gender, tumor volume, radiation dose, tumor location, and imaging characteristics, have been reviewed. Conclusions: We have found that initial tumor volume, pretreatment growth rate, and imaging ADC value potentially predict growth after GKRS. These findings provide a reference for further optimizing personalized treatment in vestibular schwannoma care.

The authors have requested that this preprint be removed from Research Square.

The growth rate of sporadic VS varies considerably, posing challenges for consistent clinical management. This systematic review examines data on factors associated with VS growth, following a protocol registered in the PROSPERO database. The analysis reveals that key predictors of tumor growth include tumor location, initial size, and specific clinical symptoms such as hearing loss and imbalance. Additionally, several studies suggest that growth observed within the first year may serve as an indicator of subsequent progression, enabling the earlier identification of high-risk cases. Emerging factors such as the posture swing test and MRI signal intensity have also been identified as novel predictors that could further refine growth assessments. Our meta-analysis confirms that tumor location, initial size, cystic components, and vestibular symptoms are closely linked to the likelihood of VS growth. This review provides valuable guidance for clinicians in identifying patients who may require closer monitoring or early intervention. By integrating these predictive factors into clinical practice, this review supports more personalized treatment and contributes to the development of more accurate prognostic models for managing untreated sporadic VS.

Chordomas are malignant tumors of the axial spine and skull base, and they are notorious for their poor treatment response. Differentiating these tumors from comparatively less malignant chondrosarcomas is crucial for treatment and prognostication. Both tumor types differ in their developmental origin. Chordomas are considered to be derived from notochordal remnants and chondrosarcomas from mesenchymal cells. Here, we evaluated the differential expression of developmental transcription factors in these skull base tumors. Histopathologically-confirmed tumor biopsies were obtained from 12 chordoma and 7 chondrosarcoma patients. Following RNA extraction, samples were submitted to real-time quantitative PCR (RT-qPCR) for the evaluation of 32 evolutionary conserved genes that are known to associate with notochord, mesoderm, and axial spine development. Gene expression levels were normalized to housekeeping genes ACTB and RS27a. Fifteen genes were either exclusively expressed (n = 12) or overexpressed (n = 3; 2.21–4.43 fold increase) in chordoma, compared to chondrosarcoma. Brachyury and CD24 were highly and exclusively expressed in chordoma. Other novel genes exclusive to chordomas included chordin, HOXA5 and ACAN. Vice versa, ten genes were either exclusively expressed (n = 2) or overexpressed (n = 8; 0.01–0.66 fold increase) in chondrosarcoma, compared to chordoma. As chordoma patients demonstrate a worse prognosis compared to chondrosarcoma patients, the differential expression of chordin, HOXA5 and ACAN and CD24 could be relevant for the pathophysiology of chordomas and may have diagnostic and treatment value. Further study on role of these genes in tumorigenesis is therefore warranted.

Glioblastoma (GBM) remains a highly malignant, intrinsically resistant and inevitably recurring brain tumor with dismal prognosis. The aggressiveness and lack of effective GBM treatments can be attributed to the highly heterogeneous and plastic nature of GBM tumor cells, which easily confer resistance to standard-of-care (SOC) therapy. While tumor progression has also been attributed to interactions with the tumor microenvironment, quantitative data describing these interactions are still largely missing. Here, we used high-dimensional, multiplexed immunohistochemistry to map evolutions in the spatial, single-cell tissue architecture of 120 paired adult GBM tumor samples derived from 60 patients at diagnosis (ND) and upon recurrence (REC) following SOC treatment. We mapped the spatial distribution of a multitude of GBM tumoral subtypes across this multicentric cohort, through which we identified a high level of heterogeneity defined by specific tumoral niches within and across patients and which evolved when subjected to SOC therapy. In addition, we describe the relationship of the various tumoral niches with their local immune-infiltrates, highlighting an even more immunosuppressive environment following SOC resistance. Finally, by aligning these findings to the observed genomic aberrations and the clinical data of the patients, we are now able to more precisely describe the heterogeneous landscape of glioblastoma and how it evolves under SOC treatment at spatial, single-cell resolution.

Objectives  Malignant tumors of the sinonasal cavities with extension to the frontal skull base are rare and challenging pathologies. Combined-approach surgery using a frontobasal craniotomy and endoscopic sinus surgery with reconstruction of the anterior skull base followed by adjuvant radiotherapy is a preferred treatment strategy in selected cases. Morbidity and mortality rates are high in this population. We aim to add our experience to the current literature. Design  We performed a retrospective cross-sectional single center study of the long-term clinical outcome in a tertiary university referral hospital in the Netherlands between 2010 and 2021. Descriptive statistics and frequency distributions were performed Participants  Patient, tumor, treatment, complications and survival characteristics of eighteen consecutive patients were extracted from the electronic health records. Main Outcome Measures  The primary outcome measures are progression free survival, overall survival and complication rate. Results  Eighteen consecutive patients were included with a mean age of 61 (SD ± 10) years (range 38-80); ten males and eight females. Gross total resection was achieved in 14 (77%) patients. Eleven (61%) patients underwent local radiotherapy, one (5%) chemotherapy and three (17%) a combination of both. Mean follow-up duration was 49 months (range 3 - 138). Three (17%) patients died in hospital due to post-operative complications. Six (33%) patients died during follow-up due to disease progression. Mean progression-free survival was 47 months (range 0 - 113). Conclusion  In conclusion, the overall survival was 50% for this group of patients with large sinonasal tumors. Progressive disease affects survival rate severely. Surgical complications were seen in five (28%) patients. Radiotherapy is associated with high complication rates. Radiation necrosis was a serious complication in two patients and could be treated with high dose steroids.

Supp. Fig.1. CONSORT Flow Diagram Supp. Fig.2. MRI Perfusion Parameters Supp. Fig. 3. Immunohistochemistry Supp. Fig. 4. Gene Expression Profile Supp. Table 1. Adverse Events Supp. Table 2. Pharmacokinetic Data Supp. Table 3. Molar Drug Levels Supplemental Methods

Background:In our center, large vestibular schwannoma (VS) is typically managed by a planned partial resection through the translabyrinthine route. Here, we report on a rare complication of VS surgery and severe neurogenic pulmonary edema.Case Description:A 33-year-old male was referred to our skull-base center with a large VS. A planned partial resection was performed. The surgery was without complications and the patient showed good recovery without facial nerve dysfunction. In the evening of the 2nd day after surgery, the patient showed rapid neurological deterioration, accompanied by cardiac arrest. After the patient was resuscitated, a computed tomography (CT) was made, which showed generalized (infra- and supratentorial) brain edema and hematoma in the resection cavity. Despite rapid removal of the hematoma, there was no change in the neurological situation. The next CT scan showed a further increase of brain edema and the patient died eventually. Autopsy revealed generalized lung edema, brain edema, and Hashimoto's thyroiditis. The pathologist diagnosed neurogenic lung edema.Conclusion:Neurogenic lung edema can occur on the 2nd day after surgery and induce rapid deterioration of the patient with massive brain edema.

Purpose Chordomas are malignant tumors that develop along the neuraxis between skull-base and sacrum. Chondrosarcomas show similarities with chordomas, yet show less malignant behavior. LIM and SH3 protein 1 (LASP1) is a cytoskeletal protein known to promote the malignant behavior of tumors. LASP1 was previously identified as a possibly overexpressed protein in a chordoma proteomics experiment. In this study we compare LASP1 expression in chordoma and chondrosarcoma tissue. Methods Biopsies of primary tumors were collected from surgically treated chordoma (n = 6) and chondrosarcoma (n = 6) patients, flash-frozen upon collection and collectively analyzed for LASP1 RNA (real-time PCR) and protein expression (western blotting). Additionally, tissue micro array (TMA)-based immunohistochemistry was applied to an archive of 31 chordoma and 1 chondrosarcoma specimen. Results In chordoma samples, LASP1 mRNA was detected in 4/6 cases and a strong 36 kDa immunoreactive protein band was observed in 4/5 cases. In contrast, 0/6 chondrosarcoma samples showed detectable levels of LASP1 mRNA and only a weak 36 kDa band was observed in 4/5 cases. Immunohistochemical analysis showed LASP1 expression in all chordoma samples, whereas chondrosarcoma specimen did not show immunoreactivity. Conclusion LASP1 is strongly expressed in the majority of chordoma cases and shows low expression in chondrosarcoma tissue. Since LASP1 is known to function as oncogene and regulate cell proliferation in other tumor types, this study implicates a role for LASP1 in chordoma biology. Further studies are warranted to improve understanding of LASP1's expression and functioning within chordoma, both in vitro and in vivo.

Gliomas are the most frequent primary tumors of the brain. They can be divided into grade II-IV astrocytomas and grade II-III oligodendrogliomas, based on their histomolecular profile. The prognosis and treatment is highly dependent on grade and well-identified prognostic and/or predictive molecular markers. Multi-parametric MRI, including diffusion weighted imaging, perfusion, and MR spectroscopy, showed increasing value in the non-invasive characterization of specific molecular subsets of gliomas. Radiolabeled amino-acid analogues, such as 18F-FET, have also been proven valuable in glioma imaging. These tracers not only contribute in the diagnostic process by detecting areas of dedifferentiation in diffuse gliomas, but this technique is also valuable in the follow-up of gliomas, as it can differentiate pseudo-progression from real tumor progression. Since multi-parametric MRI and 18F-FET PET are complementary imaging techniques, there may be a synergistic role for PET-MRI imaging in the neuro-oncological imaging of primary brain tumors. This could be of value for both primary staging, as well as during treatment and follow-up.

OBJECTIVE Patients with glioblastoma are often scheduled for urgent elective surgery. Currently, the impact of the waiting period until glioblastoma surgery is undetermined. In this national quality registry study, the authors determined the wait times until surgery for patients with glioblastoma, the risk factors associated with wait times, and the risk-standardized variation in time to surgery between Dutch hospitals. The associations between time to surgery and patient outcomes were also explored. METHODS Data from all 4589 patients who underwent first-time glioblastoma surgery between 2014 and 2019 in the Netherlands were collected by 13 hospitals in the Quality Registry Neuro Surgery. Time to surgery comprised 1) the time from first MR scan to surgery (MTS), and 2) the time from first neurosurgical consultation to surgery (CTS). Long MTS was defined as more than 21 days and long CTS as more than 14 days. Potential risk factors were analyzed in multivariable logistic regression models. The standardized rate of long time to surgery was analyzed using funnel plots. Patient outcomes including Karnofsky Performance Scale (KPS) score change, complications, and survival were analyzed by multivariable logistic regression and proportional hazards models. RESULTS The median overall MTS and CTS were 18 and 9 days, respectively. Overall, 2576 patients (56%) had an MTS within 3 weeks and 3069 (67%) had a CTS within 2 weeks. Long MTS was significantly associated with older age, higher preoperative KPS score, higher American Society of Anesthesiologists comorbidity class, season, lower hospital case volume, university affiliation, and resection. Long CTS was significantly associated with higher baseline KPS score, university affiliation, resection, more recent year of treatment, and season. In funnel plots, considerable practice variation was observed between hospitals in patients with long times to surgery. Fewer patients with KPS score improvement were observed after a long time until resection. Long CTS was associated with longer survival. Complications and KPS score decline were not associated with time to surgery. CONCLUSIONS Considerable between-hospital variation among Dutch hospitals was observed in the time to glioblastoma surgery. A long time to resection impeded KPS score improvement, and therefore, patients who may improve should be identified for more urgent resection. Longer survival was observed in patients selected for longer time until surgery after neurosurgical consultation (CTS).

Supplementary Data from Tumor Drug Concentration and Phosphoproteomic Profiles After Two Weeks of Treatment With Sunitinib in Patients with Newly Diagnosed Glioblastoma