Mathilde C M Kouwenhoven

Amsterdam University Medical Center | VUmc · Department of Neurology

BACKGROUND DNA methylation-based classification of diffuse glioma is increasingly used in daily practice. Yet, little is known regarding the prognostic and predictive value of DNA methylation-based subclasses of IDH-wildtype glioblastoma. A recent study found a predictive value for the effect of extent or resection (EOR) on survival for DNA methyla...

BACKGROUND Withdrawal of antiseizure medication treatment (ASM) can be considered after completion of antitumour treatment in glioma patients who no longer suffer from seizures. We compared the risk of recurrent seizures after ASM withdrawal between patients with short-term, medium-term versus long-term seizure freedom after antitumour treatment....

Purpose Medulloblastoma is a rare tumor in adults. The objective of this nationwide, multicenter study was to evaluate the toxicity and efficacy of the Dutch treatment protocol for adult medulloblastoma patients. Methods Adult medulloblastoma patients diagnosed between 2010 and 2018 were identified in the Dutch rare tumors registry or nationwide p...

Glioblastoma multiforme is the most common primary central nervous system tumor, with an incidence of 3 [...]

Background & aims: Glioma patients experience a multitude of symptoms that negatively affect their health-related quality of life. Symptoms vary greatly across disease phases, and the patients' stable phase might be particularly suitable for assessing and treating symptoms. Identifying symptoms and patients' needs is a first step toward improving...

Background About 10% of glioma patients with epilepsy need antiseizure medication (ASM) triple-therapy due to refractory epilepsy. Aim of this study was to evaluate whether levetiracetam combined with valproic acid and clobazam (LEV+VPA+CLB), a frequently prescribed triple-therapy, has favorable effectiveness compared to other triple-therapy combin...

Data management in transmural care is complex. Without digital innovations like Health Information Exchange (HIE), patient information is often dispersed and inaccessible across health information systems between hospitals. The extent of information loss and consequences remain unclear. We aimed to quantify patient information availability of refer...

BACKGROUND Many patients with glioma suffer from poorly understood executive functioning deficits before and/or after tumor resection. In the past decade, it has become increasingly clear that there is a complex interplay between glioma and both local and global functional activity and connectivity. Moreover, multilayer network integration of the f...

BACKGROUND About 10% of glioma patients with epilepsy need antiseizure medication (ASM) 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 favorable effectiveness compared to other tripletherapy combinations in...

Introduction Increasingly more adolescent and young adult (AYA, aged 18–39 years) patients with an uncertain and/or poor cancer prognosis (UPCP) are gaining life-years because of novel treatments or refinement of established therapies, and sometimes even face the prospect of long-term disease control. This study aims to examine the challenges of AY...

Adolescent and young adult (AYA) cancer survivors (18–39 years at diagnosis) often experience negative body changes such as scars, amputation, and disfigurement. Understanding which factors influence body image among AYA survivors can improve age-specific care in the future. Therefore, we aim to examine the prevalence, and association of a negative...

Background The evolutionary processes that drive tumor progression in patients with IDH-mutant astrocytoma remain largely unclear. 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. Ultimately, such markers can assist clin...

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...

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...

Background The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS 5), includes molecular parameters for both diagnosis and grading in addition to histological features. For IDH-mutant astrocytoma, homozygous deletion (HD) of CDKN2A/B now results in WHO grade 4, even in the absence of microvascular proliferation...

Background In the Netherlands, 1,200 persons are annually diagnosed with a glioma, of whom many are of working age. Studies regarding cancer and work often exclude primary brain tumour patients, due to specific problems these patients may experience. Hence, the aim was to explore the experiences and unmet needs regarding return to work, work retent...

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...

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood...

Background While patients with diffuse low-grade glioma (LGG) often survive for years, there is a risk of tumour progression which may impact on patients’ long-term health-related quality of life (HRQOL) and neurocognitive functioning (NCF). We present a follow-up of LGG patients and their informal caregivers (T3) who took part in our previous HRQO...

Background: Participation of Adolescents and Young Adults with cancer (AYAs: 18-39 years at time of diagnosis) in patient-reported outcome studies is warranted given the limited knowledge of (long-term) physical and psychosocial health outcomes. We examined the representativeness of AYAs participating in the study, to observe the impact of various...

Many patients with glioma, primary brain tumors, suffer from poorly understood executive functioning deficits before and/or after tumor resection. We aimed to test whether frontoparietal network centrality of multilayer networks, which allow for integration across multiple frequencies, relates to and predicts executive functioning in glioma patient...

Background Cannabinoids have been suggested to alleviate frequently experienced symptoms of reduced mental well-being such as anxiety and depression. Mental well-being is an important subdomain of health-related quality of life (HRQoL). Reducing symptoms and maintaining HRQoL are particularly important in malignant primary brain tumor patients, as...

Background Fatigue is the most frequent and burdensome symptom of patients with diffuse glioma. It is closely linked to decreased health-related quality of life and symptoms such as depression and sleep disturbances. Currently, there is no evidence-based treatment that targets severe fatigue in patients with brain tumours. Cognitive behavioural the...

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...

INTRODUCTION. Diffuse gliomas are the most frequent and devastating primary CNS tumors in adults. Standard treatment has limited efficacy and without exception these gliomas recur. The evolutionary processes that drive progression in glioma of the IDH-mutant astrocytoma subgroup, remain unclear. The GLASS-NL consortium was initiated to gain insight...

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...

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...

The factors driving therapy resistance in diffuse glioma remain poorly understood. To identify treatment-associated cellular and genetic changes, we analyzed RNA and/or DNA sequencing data from the temporally separated tumor pairs of 304 adult patients with isocitrate dehydrogenase (IDH)-wild-type and IDH-mutant glioma. Tumors recurred in distinct...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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,...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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 ef...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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....

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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,...

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...

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...