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2. The impact of etiology in lesion-symptom mapping: A direct comparison between tumor and stroke

Author

Grinsven, E.E. van, Smits, A.R., Kessel, E. van, Raemaekers, M.A.H.L.L., Haan, E.H.F. de, Huenges Wajer, I.M.C., Ruijters, V.J., Philippens, M.E.P., Verhoeff, J.J.C., Ramsey, N.F., Robe, P.A.J.T., Snijders, T.J., Zandvoort, M.J.E. van, Grinsven, E.E. van, Smits, A.R., Kessel, E. van, Raemaekers, M.A.H.L.L., Haan, E.H.F. de, Huenges Wajer, I.M.C., Ruijters, V.J., Philippens, M.E.P., Verhoeff, J.J.C., Ramsey, N.F., Robe, P.A.J.T., Snijders, T.J., and Zandvoort, M.J.E. van

Abstract

Contains fulltext : 293093.pdf (Publisher’s version ) (Open Access), Introduction: Lesion-symptom mapping is a key tool in understanding the relationship between brain structures and behavior. However, the behavioral consequences of lesions from different etiologies may vary because of how they affect brain tissue and how they are distributed. The inclusion of different etiologies would increase the statistical power but has been critically debated. Meanwhile, findings from lesion studies are a valuable resource for clinicians and used across different etiologies. Therefore, the main objective of the present study was to directly compare lesion-symptom maps for memory and language functions from two populations, a tumor versus a stroke population. Methods: Data from two different studies were combined. Both the brain tumor (N = 196) and stroke (N = 147) patient populations underwent neuropsychological testing and an MRI, pre-operatively for the tumor population and within three months after stroke. For this study, we selected two internationally widely used standardized cognitive tasks, the Rey Auditory Verbal Learning Test and the Verbal Fluency Test. We used a state-of-the-art machine learning-based, multivariate voxel-wise approach to produce lesion-symptom maps for these cognitive tasks for both populations separately and combined. Results: Our lesion-symptom mapping results for the separate patient populations largely followed the expected neuroanatomical pattern based on previous literature. Substantial differences in lesion distribution hindered direct comparison. Still, in brain areas with adequate coverage in both groups, considerable LSM differences between the two populations were present for both memory and fluency tasks. Post-hoc analyses of these locations confirmed that the cognitive consequences of focal brain damage varied between etiologies. Conclusion: The differences in the lesion-symptom maps between the stroke and tumor population could partly be explained by differences in lesion volume and topography. Despite

Published
2023

3. The Aftercare Survey: Assessment and intervention practices after brain tumor surgery in Europe

Author

Sierpowska, J.M., Rofes, A., Dahlslätt, K.P.G., Mandonnet, E., Laan, M. ter, Polczynska, M., De Witt Hamer, P.C., Halaj, M., Spena, G., Meling, T.R., Motomura, K., Reyes, A.F., Campos, A.R., Robe, P.A.J.T., Zigiotto, L., Freyschlag, C.F., Broen, M.P.G., Sarubbo, S., Stranjalis, G., Papadopoulos, K., liouta, E., Rutten, G.J., Viegas, C.P., Silvestre, A., Perrote, F., Brochero, N., Cáceres, C., Zdun-Ryzewska, A., Kloc, W., Satoer, D., Dragoy, O., Hendriks, M.P.H., Alvarez-Carriles, J.C., Piai, V., Sierpowska, J.M., Rofes, A., Dahlslätt, K.P.G., Mandonnet, E., Laan, M. ter, Polczynska, M., De Witt Hamer, P.C., Halaj, M., Spena, G., Meling, T.R., Motomura, K., Reyes, A.F., Campos, A.R., Robe, P.A.J.T., Zigiotto, L., Freyschlag, C.F., Broen, M.P.G., Sarubbo, S., Stranjalis, G., Papadopoulos, K., liouta, E., Rutten, G.J., Viegas, C.P., Silvestre, A., Perrote, F., Brochero, N., Cáceres, C., Zdun-Ryzewska, A., Kloc, W., Satoer, D., Dragoy, O., Hendriks, M.P.H., Alvarez-Carriles, J.C., and Piai, V.

Abstract

04 april 2022, Item does not contain fulltext, People with gliomas need specialized neurosurgical, neuro-oncological, psycho-oncological, and neuropsychological care. The role of language and cognitive recovery and rehabilitation in patients’ well-being and resumption of work is crucial, but there are no clear guidelines for the ideal timing and character of assessments and interventions. The goal of the present work was to describe representative (neuro)psychological practices implemented after brain surgery in Europe.An online survey was addressed to professionals working with individuals after brain surgery. We inquired about the assessments and interventions and the involvement of caregivers. Additionally, we asked about recommendations for an ideal assessment and intervention plan.Thirty-eight European centers completed the survey. Thirty of them offered at least one postsurgical (neuro)psychological assessment, mainly for language and cognition, especially during the early recovery stage and at long term. Twenty-eight of the participating centers offered postsurgical therapies. Patients who stand the highest chances of being included in evaluation and therapy postsurgically are those who underwent awake brain surgery, harbored a low-grade glioma, or showed poor recovery. Nearly half of the respondents offer support programs to caregivers, and all teams recommend them. Treatments differed between those offered to individuals with low-grade glioma vs those with high-grade glioma. The figure of caregiver is not yet fully recognized in the recovery phase.We stress the need for more complete rehabilitation plans, including the emotional and health-related aspects of recovery. In respondents’ opinions, assessment and rehabilitation plans should also be individually tailored and goal-directed (eg, professional reinsertion).

Published
2022

4. CXCR4 expression in glioblastoma tissue and the potential for PET imaging and treatment with [(68)Ga]Ga-Pentixafor /[(177)Lu]Lu-Pentixather

Author

Jacobs, S.M., Wesseling, P., Keizer, B. de, Tolboom, N., Ververs, F.F.T., Krijger, G.C., Westerman, B.A., Snijders, T.J., Robe, P.A.J.T., Kolk, A.G. van der, Jacobs, S.M., Wesseling, P., Keizer, B. de, Tolboom, N., Ververs, F.F.T., Krijger, G.C., Westerman, B.A., Snijders, T.J., Robe, P.A.J.T., and Kolk, A.G. van der

Abstract

Item does not contain fulltext, PURPOSE: CXCR4 (over)expression is found in multiple human cancer types, while expression is low or absent in healthy tissue. In glioblastoma it is associated with a poor prognosis and more extensive infiltrative phenotype. CXCR4 can be targeted by the diagnostic PET agent [(68)Ga]Ga-Pentixafor and its therapeutic counterpart [(177)Lu]Lu-Pentixather. We aimed to investigate the expression of CXCR4 in glioblastoma tissue to further examine the potential of these PET agents. METHODS: CXCR4 mRNA expression was examined using the R2 genomics platform. Glioblastoma tissue cores were stained for CXCR4. CXCR4 staining in tumor cells was scored. Stained tissue components (cytoplasm and/or nuclei of the tumor cells and blood vessels) were documented. Clinical characteristics and information on IDH and MGMT promoter methylation status were collected. Seven pilot patients with recurrent glioblastoma underwent [(68)Ga]Ga-Pentixafor PET; residual resected tissue was stained for CXCR4. RESULTS: Two large mRNA datasets (N = 284; N = 540) were assesed. Of the 191 glioblastomas, 426 cores were analyzed using immunohistochemistry. Seventy-eight cores (23 tumors) were CXCR4 negative, while 18 cores (5 tumors) had both strong and extensive staining. The remaining 330 cores (163 tumors) showed a large inter- and intra-tumor variation for CXCR4 expression; also seen in the resected tissue of the seven pilot patients-not directly translatable to [(68)Ga]Ga-Pentixafor PET results. Both mRNA and immunohistochemical analysis showed CXCR4 negative normal brain tissue and no significant correlation between CXCR4 expression and IDH or MGMT status or survival. CONCLUSION: Using immunohistochemistry, high CXCR4 expression was found in a subset of glioblastomas as well as a large inter- and intra-tumor variation. Caution should be exercised in directly translating ex vivo CXCR4 expression to PET agent uptake. However, when high CXCR4 expression can be identified with [(68)Ga]Ga-Pentixafor, these p

Published
2022

7. P01.04.A Lesion-symptom mapping based on stroke or glioma: Etiology matters!

Author

Grinsven, E.E. van, Smits, A.R., Kessel, E. van, Raemaekers, M., Haan, E.H.F. de, Huenges-Wajer, I.M.C., Ruijters, V.J., Philippens, M.E.P., Verhoeff, J.J.C., Ramsey, N.F., Robe, P.A.J.T., Snijders, T.J., Zandvoort, M.J.E. van, Grinsven, E.E. van, Smits, A.R., Kessel, E. van, Raemaekers, M., Haan, E.H.F. de, Huenges-Wajer, I.M.C., Ruijters, V.J., Philippens, M.E.P., Verhoeff, J.J.C., Ramsey, N.F., Robe, P.A.J.T., Snijders, T.J., and Zandvoort, M.J.E. van

Abstract

Item does not contain fulltext

Published
2022

9. Between-hospital variation in mortality and survival after glioblastoma surgery in the Dutch Quality Registry for Neuro Surgery

Author

Hamer, P.C.D., Ho, V.K.Y., Zwinderman, A.H., Ackermans, L., Ardon, H., Boomstra, S., Bouwknegt, W., Brink, W.A. van den, Dirven, C.M., Gaag, N.A. van der, Veer, O. van der, Idema, A.J.S., Kloet, A., Koopmans, J., Laan, M. ter, Verstegen, M.J.T., Wagemakers, M., Robe, P.A.J.T., Dutch Soc Neurosurg, Neurosurgery, CCA - Cancer Treatment and quality of life, MUMC+: MA Med Staf Spec Neurochirurgie (9), RS: MHeNs - R3 - Neuroscience, Epidemiology and Data Science, and APH - Methodology

Subjects
Male, Cancer Research, Survival, Logistic regression, Neurosurgical Procedures, 0302 clinical medicine, Outcome Assessment, Health Care, Hospital Mortality, Prospective Studies, Registries, ELDERLY-PATIENTS, Netherlands, education.field_of_study, OUTCOMES, medicine.diagnostic_test, Brain Neoplasms, Middle Aged, Hospitals, 3. Good health, Survival Rate, Neurology, Oncology, 030220 oncology & carcinogenesis, GLIOMA, Female, Neurosurgery, NEWLY-DIAGNOSED GLIOBLASTOMA, medicine.medical_specialty, Funnel plot, RESECTION, Population, UNITED-STATES, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Glioma, Biopsy, medicine, Humans, Mortality, education, Proportional hazards model, business.industry, CARE, medicine.disease, PHASE-III, Surgery, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], TEMOZOLOMIDE ERA, Outcome assessment, PATTERNS, Clinical Study, Quality of health care, Neurology (clinical), business, Glioblastoma, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

Purpose Standards for surgical decisions are unavailable, hence treatment decisions can be personalized, but also introduce variation in treatment and outcome. National registrations seek to monitor healthcare quality. The goal of the study is to measure between-hospital variation in risk-standardized survival outcome after glioblastoma surgery and to explore the association between survival and hospital characteristics in conjunction with patient-related risk factors. Methods Data of 2,409 adults with first-time glioblastoma surgery at 14 hospitals were obtained from a comprehensive, prospective population-based Quality Registry Neuro Surgery in The Netherlands between 2011 and 2014. We compared the observed survival with patient-specific risk-standardized expected early (30-day) mortality and late (2-year) survival, based on age, performance, and treatment year. We analyzed funnel plots, logistic regression and proportional hazards models. Results Overall 30-day mortality was 5.2% and overall 2-year survival was 13.5%. Median survival varied between 4.8 and 14.9 months among hospitals, and biopsy percentages ranged between 16 and 73%. One hospital had lower than expected early mortality, and four hospitals had lower than expected late survival. Higher case volume was related with lower early mortality (P = 0.031). Patient-related risk factors (lower age; better performance; more recent years of treatment) were significantly associated with longer overall survival. Of the hospital characteristics, longer overall survival was associated with lower biopsy percentage (HR 2.09, 1.34–3.26, P = 0.001), and not with academic setting, nor with case volume. Conclusions Hospitals vary more in late survival than early mortality after glioblastoma surgery. Widely varying biopsy percentages indicate treatment variation. Patient-related factors have a stronger association with overall survival than hospital-related factors. Electronic supplementary material The online version of this article (10.1007/s11060-019-03229-5) contains supplementary material, which is available to authorized users.

Published
2019
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10. Imaging practice in low-grade gliomas among European specialized centers and proposal for a minimum core of imaging

Author

Freyschlag, C.F., Krieg, S.M., Kerschbaumer, J., Pinggera, D., Forster, M.T., Cordier, D., Rossi, M., Miceli, G., Roux, A., Reyes, A., Sarubbo, S., Smits, A., Sierpowska, J., Robe, P.A.J.T., Rutten, G.J., Santarius, T., Matys, T., Zanello, M., Almairac, F., Mondot, L., Jakola, A.S., Zetterling, M., Rofes, A., Campe, G. von, Guillevin, R., Bagatto, D., Lubrano, V., Rapp, M., Goodden, J., De Witt Hamer, P.C., Pallud, J., Bello, L., Thomé, C., Duffau, H., Mandonnet, E., Freyschlag, C.F., Krieg, S.M., Kerschbaumer, J., Pinggera, D., Forster, M.T., Cordier, D., Rossi, M., Miceli, G., Roux, A., Reyes, A., Sarubbo, S., Smits, A., Sierpowska, J., Robe, P.A.J.T., Rutten, G.J., Santarius, T., Matys, T., Zanello, M., Almairac, F., Mondot, L., Jakola, A.S., Zetterling, M., Rofes, A., Campe, G. von, Guillevin, R., Bagatto, D., Lubrano, V., Rapp, M., Goodden, J., De Witt Hamer, P.C., Pallud, J., Bello, L., Thomé, C., Duffau, H., and Mandonnet, E.

Abstract

Contains fulltext : 195164.pdf (publisher's version ) (Open Access), Objective: Imaging studies in diffuse low-grade gliomas (DLGG) vary across centers. In order to establish a minimal core of imaging necessary for further investigations and clinical trials in the field of DLGG, we aimed to establish the status quo within specialized European centers. Methods: An online survey composed of 46 items was sent out to members of the European Low-Grade Glioma Network, the European Association of Neurosurgical Societies, the German Society of Neurosurgery and the Austrian Society of Neurosurgery. Results: A total of 128 fully completed surveys were received and analyzed. Most centers (n = 96, 75%) were academic and half of the centers (n = 64, 50%) adhered to a dedicated treatment program for DLGG. There were national differences regarding the sequences enclosed in MRI imaging and use of PET, however most included T1 (without and with contrast, 100%), T2 (100%) and TIRM or FLAIR (20, 98%). DWI is performed by 80% of centers and 61% of centers regularly performed PWI. Conclusion: A minimal core of imaging composed of T1 (w/wo contrast), T2, TIRM/FLAIR, PWI and DWI could be identified. All morphologic images should be obtained in a slice thickness of <= 3 mm. No common standard could be obtained regarding advanced MRI protocols and PET. Importance of the study: We believe that our study makes a significant contribution to the literature because we were able to determine similarities in numerous aspects of LGG imaging. Using the proposed "minimal core of imaging" in clinical routine will facilitate future cooperative studies.

Published
2018

11. Drivers and consequences of cognitive functioning in glioma

Author

Kessel, Emma van, Robe, P.A.J.T., Zandvoort, M.J.E. van, Snijders, T.J., and University Utrecht

Subjects
Diffuse gliomen, cognitief functioneren, neuro-oncologie, moleculaire markers, survival
Abstract

1. The occurrence of neurocognitive deficits in diffuse glioma Treatment-naive glioma patients Cognitive impairments occur in the large majority of glioma patients. Because neurocognitive functioning (NCF) in glioma patients mostly has been studied postoperatively in previous literature, neurocognitive deficits were mainly thought to associate with surgery and medical therapies. However, neurocognitive deficits occur prior to any anti-tumor treatment and impairments can be found across all main cognitive domains. In domain-specific analyses, executive functioning and attention, memory, and psychomotor speed appeared to be involved most frequently (chapter 3), which is comparable to previously published literature (chapter 2). An explanation for this finding can be that these cognitive domains rely on widespread neural networks with multiple brain regions involved. For this reason, they can be altered easily by a mechanical conflict between the tumor and important nodes (hubs) or pathways of these networks.2-6 Neurocognitive changes after awake surgery Furthermore, we found that neurocognitive functioning is mostly maintained after awake surgery across different domains (chapter 4). Our results show that the domain psychomotor speed appeared most vulnerable to the effects of surgery, both at group level and at (the proportion of) individual-level deficits. 2. Factors that modulate neurocognitive functioning Treatment-naive glioma patients In the previous paragraph we saw that neurocognitive deficits occur prior to any anti-tumor treatment and impairments can be found across all main cognitive domains. These findings support the hypothesis that, in addition to treatment-related effects, the tumor and the direct effect of this tumor affects NCF in diffuse glioma. Chapter 9 focusses on the relation between the tumoral expression level of several biological markers and cognition in our own cohort of treatment naive patients. Most importantly, we found P-STAT5b, CD163, CD3 and SEMA3 to be independently associated with cognitive performance in different domains after correction for histopathological grade. Furthermore, we found specific associations (after correcting for volume and location) between expression level of CD3, IDH and psychomotor speed; IDH, BDNF, ATRX, CSNK2B, GAT3, SRF and EAAT1 and memory performance and for P-STAT5b, CSNK2B and IDH and executive functioning (chapter 9). So, our results support the hypothesis that in addition to its size and location, the metabolism and tumor genetics of a tumor can alter neural function. 3. Influence of neurocognitive functioning on survival Cognitive functioning is of great influence on quality of life and several studies already revealed that these deficits are significantly associated with survival in diffuse glioma patients25,26. In chapter 5 we focused on the independent relationship between executive functioning and memory, and survival. We found that cognitive impairments in executive functioning and memory are negatively associated with survival in diffuse glioma patients, even after correcting for all known possible confounders. Additionally, we found extensive domain-specific neuropsychological assessment to be more strongly correlated to survival than an often clinically used cognitive screener for cognitive decay, the MMSE.

Published
2022

12. Prognosis in glioblastoma : A clinical and translational approach

Author

Berendsen, Sharon, Robe, PAJT, Snijders, Tom J., University Utrecht, Robe, P.A.J.T., and Snijders, T.J.

Subjects
gene set enrichment analysis, valproic acid, epithelial-mesenchymal transition, epilepsy, subventricular zone, Glioblastoma, fractal dimensionality, nervous system diseases
Abstract

Glioblastoma is a highly malignant brain tumor, and currently remains an incurable disease. Despite intensive treatment strategies, patients have a poor prognosis of 12-16 months. Glioblastoma patients suffer from both an oncological and neurological disease, as the tumor can cause specific neurological symptoms. For instance, in 30-40% of patients, the disease presents with an epileptic seizure. In this thesis, with use of a large patient cohort, we show that an antiepileptic seizure at presentation is associated with a better prognosis in glioblastoma patients. This improved prognosis does not seem fully explained by other clinical factors or treatment with specific antiepileptic drugs, such as valproic acid. We did observe biological differences in tumor tissue from glioblastoma patients with and without epilepsy at presentation, that associate with more aggressive tumor biological characteristics. We also found that glioblastomas that contact the subventricular zone (SVZ) in the brain associate with a worse prognosis. This observation associates with a specific tumor biological profile, that is possibly influenced by this specific brain region. The observations from the research in this thesis resulted in the identification of multiple prognostic factors for glioblastoma patients, a further understanding of the prognostic value of antiepileptic drugs, and further insights in underlying tumor biological mechanisms associated with these prognostic factors. These results might contribute to the identification of new therapeutic strategies in glioblastoma treatment.

Published
2020

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