Mathilde C M Kouwenhoven

Mathilde C M Kouwenhoven
Amsterdam University Medical Center | VUmc · Department of Neurology

MD, PhD

About

110
Publications
9,878
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5,823
Citations
Additional affiliations
June 2008 - April 2014
Erasmus MC
Position
  • Intern neurology
April 2004 - May 2008
Erasmus MC
June 1998 - September 2001
Karolinska Institutet

Publications

Publications (110)
Article
Background Protocols for assessment of (neuro)psychological outcomes in lower-grade glioma patients vary between hospitals. This potentially complicates generalization of these outcomes. We compared standardized scores on tests of two frequently impaired cognitive domains (attention and executive functioning (EF)), and two relevant patient-reported...
Article
Background About 10% of the glioma patients need antiepileptic drug (AED) tripletherapy due to refractory epilepsy. This study aimed to determine whether levetiracetam combined with valproic acid and clobazam (LEV+VPA+CLB), a commonly prescribed tripletherapy, has favourable effectiveness compared to other tripletherapy combinations in glioma patie...
Article
Background Many patients with glioma suffer from deficits in executive functioning (EF), regardless of tumor location and size. While some patients experience improving EF after tumor resection, others deteriorate over time. This variability in cognitive trajectories is still poorly understood, but neuroscientific approaches that view the brain as...
Article
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the basis of the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, publ...
Article
Full-text available
Background About 30% of glioma patients need an add-on antiepileptic drug (AED) due to uncontrolled seizures on AED monotherapy. This study aimed to determine whether levetiracetam combined with valproic acid (LEV+VPA), a commonly prescribed duotherapy, is more effective than other duotherapy combinations including either LEV or VPA in glioma patie...
Article
Full-text available
Background Adolescents and young adults (AYAs, aged 18-39 years) with advanced cancer have an increased life expectancy due to improvements and refinements in cancer therapies, resulting in a growing group of AYAs living with an uncertain and/or poor cancer prognosis (UPCP). To date, no studies have examined the difficulties of health care professi...
Preprint
Background: Glioma patients experience a multitude of symptoms, impacting health-related quality of life. We aimed to assess frequency and burden of patient-reported symptoms in glioma patients with stable disease and whether patients would consider treatment. We also explored how symptoms co-occur and interact within a network.Methods: Patients ra...
Article
An oculogyric crisis is a tonic conjugated deviation of the eyes, usually upward. We present two cases with a drug induced oculogyric crisis. The differential diagnoses should include epilepsy, a functional neurological movement disorder, ocular tics, ocular dyskinesia or ocular bobbing. Typically, in an oculogyric crisis the patient's awareness is...
Article
BACKGROUND Patients with low-grade gliomas (LGGs) often survive for many years, yet little is known about patients’ health-related quality of life (HRQOL) in long-term survivorship. We previously investigated HRQOL in LGG patients diagnosed on average 6 years prior to assessment (T1, N=195) with a follow-up in stable patients on average 12 years af...
Article
The GLASS-NL consortium, was initiated to gain insight into the molecular mechanisms underlying glioma evolution and to identify markers of progression in IDH-mutant astrocytomas. Here, we present the first results of genome-wide DNA-methylation profiling of GLASS-NL samples. 110 adult patients were identified with an IDH-mutant astrocytoma at firs...
Article
BACKGROUND Uncontrolled seizures on antiepileptic drug (AED) monotherapy are common in glioma patients and about a third of patients need an add-on AED. The aim of this study was to determine whether levetiracetam combined with valproic acid (LEV+VPA), a commonly prescribed duotherapy, was more effective than other duotherapy combinations, which in...
Poster
BACKGROUND Over the past years, increasing worldwide attention towards centralization of complex cancer care has been pursued as higher volume centers have shown improved outcomes. Changes in distribution of care and the impact on travel distance in glioblastoma patients have not been determined yet. In this study, we determine trends in distributi...
Poster
BACKGROUND Delay in cancer care may adversely affect emotional distress, treatment outcome and survival. Optimal timings in multidisciplinary glioblastoma care are a matter of debate and clear national guidelines only exist for time to neurosurgery. We evaluated the between-hospital variation in timings to neurosurgery and adjuvant radiotherapy and...
Article
Full-text available
Non-invasively measured brain activity is related to progression-free survival in glioma patients, suggesting its potential as a marker of glioma progression. We therefore assessed the relationship between brain activity and increasing tumor volumes on routine clinical magnetic resonance imaging (MRI) in glioma patients. Postoperative magnetoenceph...
Article
BACKGROUND Optimal treatment with antiepileptic drugs (AEDs) is an important part of care for brain tumor patients with epileptic seizures. Lamotrigine and lacosamide are both examples of frequently used non-enzyme inducing AEDs with limited to no drug-drug interactions, reducing the risk of unfavorable side effects. This study aimed to compare the...
Article
BACKGROUND Patients with diffuse glioma experience many tumor- and treatment-related symptoms, including fatigue, cognitive deficits, and anxiety. It remains unclear how the frequency and burden of these symptoms change over time and specifically which symptoms patients experience during the stable phase of the disease. We assessed the frequency an...
Article
BACKGROUND Each year 1.300 new patients are diagnosed with a glioma in the Netherlands. Patients experience a substantial physical and cognitive decline during the course of the disease. The impact of neurological deterioration on social and family life is substantial. Caregivers give high demanding care to their partners for long periods of time,...
Article
BACKGROUND About 30% of glioma patients need an add-on antiepileptic drug (AED) due to uncontrolled seizures on AED monotherapy. This study aimed to determine whether levetiracetam combined with valproic acid (LEV+VPA), a commonly prescribed duotherapy, is more effective than other duotherapy combinations including either LEV or VPA in glioma patie...
Article
BACKGROUND Many patients with low-grade gliomas (LGGs) continue to survive for many years, yet little is known about patients’ health-related quality of life (HRQOL) in long-term survivorship. We previously investigated HRQOL in LGG patients diagnosed on average 6 years prior to assessment (T1, N=195) with a follow-up in stable patients on average...
Article
BACKGROUND Glioma patients experience a high symptom burden contributing to poorer quality of life. Symptoms include depression, cognitive impairment, and fatigue and vary throughout the disease. These symptoms are rarely studied from a comprehensive perspective, while their interdependence may be relevant for their development, perpetuation, and u...
Article
BACKGROUND The evolutionary processes that drive progression in patients with IDH-mutant astrocytoma remain unclear. The GLASS-NL consortium, as part of the larger worldwide GLASS consortium, was initiated to gain insight into the molecular mechanisms underlying glioma evolution and to identify markers of progression in IDH-mutant astrocytomas. Suc...
Article
BACKGROUND Diagnosis of a glioma during pregnancy has ethical and medical dilemmas; treatment of the mother may harm the unborn child, but a too conservative approach towards tumor treatment can compromise the survival of the mother. In patients with a suspected high-grade glioma, postponing tumor treatment is undesirable. We collected published ca...
Article
BACKGROUND Gliomas are primary brain tumors with a dismal prognosis. Reducing symptoms and maintaining quality of life (QoL) are main treatment aims in glioma patients. Mental well-being is an important subdomain of QoL. Cannabinoids have been suggested to alleviate frequently experienced symptoms of reduced mental well-being such as anxiety or dep...
Article
BACKGROUND Besides early tumour progression, standard first-line radiation with concurrent and adjuvant temozolomide in de novo glioblastoma patients is abrogated frequently by severe haematological toxicity. This leads to treatment delays with unknown effect on efficacy and to more hospital visits with increased disease burden. In the present stud...
Article
BACKGROUND Glioblastoma has an infiltrative growth pattern that makes complete resection of the tumor virtually impossible. Sooner or later the tumor progresses, even after aggressive treatment with maximal safe resection, radiotherapy and/or chemotherapy. Hematological toxicity is an important cause of treatment delays during 1st line treatment. H...
Preprint
Full-text available
Tumor adaptation or selection is thought to underlie therapy resistance of gliomas. To investigate the longitudinal epigenetic evolution of gliomas in response to therapeutic pressure, we performed an epigenomic analysis of 143 matched initial and recurrent patients with IDH-wildtype (IDHwt) and IDH-mutant (IDHmut) gliomas. IDHwt gliomas showed a l...
Article
Full-text available
Background Regional collaboration and appropriate referral management are crucial in neuro-oncological care. Lack of electronic access to medical records across healthcare organisations impedes interhospital consultation and may lead to incomplete and delayed referrals. To improve referral management, we have established a multidisciplinary Neuro-O...
Preprint
Full-text available
Purpose: Optimal treatment with antiepileptic drugs (AEDs) is an important part of care for brain tumor patients with epileptic seizures. Lamotrigine and lacosamide are both examples of frequently used non-enzyme inducing AEDs with limited to no drug-drug interactions, reducing the risk of unfavorable side effects. This study aimed to compare the e...
Article
Full-text available
Objective This study aimed at estimating the cumulative incidence of antiepileptic drug (AED) treatment failure of first‐line monotherapy levetiracetam vs valproic acid in glioma patients with epilepsy. Methods In this retrospective observational study, a competing risks model was used to estimate the cumulative incidence of treatment failure, fro...
Preprint
Non-invasively measured brain activity is related to progression-free survival in glioma patients, suggesting its potential as a marker of glioma progression. We therefore assessed the relationship between brain activity and increasing tumor volumes on routine clinical magnetic resonance imaging (MRI) in glioma patients. Postoperative magnetoenceph...
Article
BACKGROUND Levetiracetam and valproic acid are two of the most commonly prescribed antiepileptic drugs (AEDs) in patients with a glioma and epilepsy. This study aimed at estimating the cumulative incidence of treatment failure of first-line monotherapy levetiracetam versus valproic acid in glioma patients with epilepsy. METHODS In this retrospecti...
Article
Purpose: The aim of glioblastoma surgery is to maximize the extent of resection while preserving functional integrity, which depends on the location within the brain. A standard to compare these decisions is lacking. We present a volumetric voxel-wise method for direct comparison between two multidisciplinary teams of glioblastoma surgery decision...
Article
Full-text available
The evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear1,2. Here we analysed temporally separated DNA-sequencing data and matched clinical annotation from 222 adult patients with glioma. By analysing mutations and copy numbers across the three major subtypes of diffuse glioma, we f...
Presentation
As an uncommon cancer, clinical and translational studies of glioma rely on multi-center collaborations, confirmatory studies, and meta-analyses. Unfortunately, interpretation of results across studies is hampered by the absence of uniformly coded clinical data. Common Data Elements (CDE) represent a set of clinical features for which the language...
Article
BACKGROUND Our previous study among 195 low-grade glioma (LGG) patients six years after initial diagnosis, showed that high radiation doses (>2 Gy) were associated with neurocognitive disability. Follow-up at 12 years in 64 LGG patients showed patients without radiotherapy to have stable neurocognitive and radiological status while attentional func...
Article
BACKGROUND Diffuse lower grade gliomas (LGGs) are generally slow growing primary central nervous system tumors that occur in early adult life. The prevalence of isocitrate dehydrogenase (IDH) mutations is high in LGG, and induces excess production of the oncometabolite 2-hydroxyglutarate (2-HG). These gain-of-function mutations play a key role in p...
Article
BACKGROUND Between 1995 and 2002 the EORTC Brain Tumor Group conducted a prospective phase III study on adjuvant procarbazine, CCNU and vincristine (PCV) chemotherapy in anaplastic oligodendroglioma (AOD). A mature follow-up presented in 2012 showed survival benefit of the addition of PCV, in particular in 1p/19q co-deleted tumors and tumors with M...
Article
Background Glioblastoma, the most common primary brain tumour in adults, universally recurs with dismal prognosis. To date, clinical trials with protein kinase inhibitors (PKIs) failed to demonstrate efficacy in glioblastoma, possibly due to the blood-brain barrier, which may prevent adequate drug accumulation in the tumour. However, in a pilot stu...
Article
Treatment options for adult patients with glioma has remained largely unchanged over the past three decades. Targeted inhibitors and immunotherapies have improved outcomes for many cancer types but their relevance in glioma is unclear. The inevitability of glioma disease recurrence demands an understanding of mechanisms driving therapy resistance....
Article
Combination therapies are used in the clinic to achieve cure, better efficacy and to circumvent resistant disease in patients. Initial assessment of the effect of such combinations, usually of two agents, is frequently performed using in vitro assays. In this review, we give a short summary of the types of analyses that were presented during the Pr...
Conference Paper
Background: Glioblastoma, the most common primary brain tumor in adults, universally recurs with dismal prognosis. Treatment of recurrent disease with second-line chemotherapy has limited impact on progression-free and overall survival. To date, clinical trials with newly developed protein kinase inhibitors (PKIs) failed to demonstrate efficacy in...
Conference Paper
Background: Glioblastoma, the most common primary brain tumor in adults, universally recurs with dismal prognosis. Treatment of recurrent disease with second-line chemotherapy has limited impact on progression-free and overall survival. To date, clinical trials with newly developed protein kinase inhibitors (PKIs) failed to demonstrate efficacy in...
Article
Full-text available
Background When glioma patients experience long-term seizure freedom the question arises whether antiepileptic drugs (AEDs) should be continued. As no prospective studies exist on seizure recurrence in glioma patients after AED withdrawal, we evaluated the decision-making process to withdraw AEDs in glioma patients, and seizure outcome after withdr...
Article
Full-text available
Targeted therapy against driver mutations responsible for cancer progression has been shown to be effective in many tumor types. For glioblastoma (GBM), the epidermal growth factor receptor (EGFR) gene is the most frequently mutated oncogenic driver and has therefore been considered an attractive target for therapy. However, so far responses to EGF...
Article
Full-text available
PURPOSE The aim of glioblastoma surgery is to maximize the extent of resection while preserving functional integrity, which depends on the location within the brain. A standard to compare these decisions is lacking. We present a volumetric voxel-wise method for direct comparison between two multidisciplinary teams of glio-blastoma surgery decisions...
Presentation
A comprehensive characterization of the somatic alterations and molecular subtypes of glioma at diagnosis has been established. However, gliomas undergo significant molecular changes over time, some of these causing malignant progression or associated with therapy. Understanding this molecular evolution may uncover therapeutic vulnerabilities and f...
Article
Full-text available
Adult diffuse gliomas are a diverse group of brain neoplasms that inflict a high emotional toll on patients and their families. The Cancer Genome Atlas (TCGA) and similar projects have provided a comprehensive understanding of the somatic alterations and molecular subtypes of glioma at diagnosis. However, gliomas undergo significant cellular and mo...
Article
Full-text available
INTRODUCTION When glioma patients experience long-term seizure freedom the question arises whether antiepileptic drugs (AEDs) should be continued. We performed a prospective study on the decision-making process to withdraw AEDs in glioma patients with long-term seizure freedom, and on seizure outcome after withdrawal. METHODS Patients with a histo...
Preprint
Full-text available
Adult diffuse glioma are a diverse group of intracranial neoplasms associated with a disproportional large number of productive life years lost, thus imposing a highly emotional and significant financial burden on society. Patient death is the result of an aggressive course of disease following diagnosis. The Cancer Genome Atlas and similar project...
Article
Full-text available
Introduction High-grade chondrosarcoma, high-grade glioma and intrahepatic cholangiocarcinoma are aggressive types of cancer with a dismal outcome. This is due to the lack of effective treatment options, emphasising the need for novel therapies. Mutations in the genes IDH1 and IDH2 (isocitrate dehydrogenase 1 and 2) occur in 60% of chondrosarcoma,...
Article
The prognosis of patients with anaplastic oligodendrogliomas (AOD) and oligoastrocytomas (AOA) is variable. Biomarkers might be helpful to identify more homogeneous disease subtypes and improve therapeutic index. The aim of this study is to develop new clinical, pathological and molecular prognostic models for locally diagnosed anaplastic gliomas w...
Article
Full-text available
PURPOSEAnaplastic oligodendroglioma are chemotherapy-sensitive tumors. We now present the long-term follow-up findings of a randomized phase III study on the addition of six cycles of procarbazine, lomustine, and vincristine (PCV) chemotherapy to radiotherapy (RT). PATIENTS AND METHODS Adult patients with newly diagnosed anaplastic oligodendroglial...
Article
2 Background: AOD are chemotherapy-sensitive tumors especially if 1p/19q co-deleted. Between 1995 and 2002 the EORTC Brain Tumor Group conducted a prospective phase III study on adjuvant procarbazine, CCNU and vincristine chemotherapy (PCV) in AOD. We now present long-term follow-up. Methods: Patients (pts) with locally diagnosed newly diagnosed AO...
Article
2 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Sunday, June 3, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.
Article
To evaluate the prognostic value and clinical utility of Ki67 tumour cell proliferation index in anaplastic oligodendroglial tumours (AOT). We performed anti-Ki67 immunostaining (MIB-1 antibody) of formalin-fixed and paraffin-embedded tumour tissue specimens of 128 patients with newly diagnosed AOT that were treated in a randomized Phase III trial....
Article
Full-text available
Glioblastoma (GBM) is a morphologically heterogeneous tumor type with a median survival of only 15 months in clinical trial populations. However, survival varies greatly among patients. As part of a central pathology review, we addressed the question if patients with GBM displaying distinct morphologic features respond differently to combined chemo...
Article
Full-text available
Despite similar morphological aspects, anaplastic oligodendroglial tumors (AOTs) form a heterogeneous clinical subgroup of gliomas. The chromosome arms 1p/19q codeletion has been shown to be a relevant biomarker in AOTs and to be perfectly exclusive from EGFR amplification in gliomas. To identify new genomic regions associated with prognosis, 60 AO...
Article
Full-text available
Amplification of the epidermal growth factor receptor (EGFR) gene is one of the most common oncogenic alterations in glioblastoma (45%) making it a prime target for therapy. However, small molecule inhibitors of the EGFR tyrosine kinase showed disappointing efficacy in clinical trials for glioblastoma. Here we aimed at investigating the molecular e...
Article
Full-text available
Hypermethylation of the MGMT gene promoter and mutation of the TP53 tumor-suppressor gene are frequently present in diffuse astrocytomas. However, there is only anecdotal information about MGMT methylation status and TP53 mutations during progression of low-grade diffuse astrocytoma (AII) to anaplastic astrocytoma (AIII) and secondary glioblastoma...
Article
Full-text available
Only a few studies examined the effect of temozolomide (TMZ) in recurrent low-grade astrocytoma (LGA) after surgery, none of which included a homogeneous and sufficiently sized group of patients with progression after radiotherapy (RT). We evaluated a cohort of 58 patients treated with TMZ for progression after RT of a previous LGA and investigated...
Article
Full-text available
Gliomas are the most common primary brain tumors with heterogeneous morphology and variable progno