M J van den Bent

Publications (90)399.2 Total impact

• Article: Anaplastic oligodendroglial tumors.

  M J van den Bent, J E C Bromberg
  Handbook of Clinical Neurology 01/2012; 105:467-84.
• Article: Gene expression profiles of gliomas in formalin-fixed paraffin-embedded material.

  L A M Gravendeel, J J de Rooi, P H C Eilers, M J van den Bent, P A E Sillevis Smitt, P J French
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  ABSTRACT: We have recently demonstrated that expression profiling is a more accurate and objective method to classify gliomas than histology. Similar to most expression profiling studies, our experiments were performed using fresh frozen (FF) glioma samples whereas most archival samples are fixed in formalin and embedded in paraffin (FFPE). Identification of the same, expression-based intrinsic subtypes in FFPE-stored samples would enable validation of the prognostic value of these subtypes on these archival samples. In this study, we have therefore determined whether the intrinsic subtypes identified using FF material can be reproduced in FFPE-stored samples. We have performed expression profiling on 55 paired FF-FFPE glioma samples using HU133 plus 2.0 arrays (FF) and Exon 1.0 ST arrays (FFPE). The median time in paraffin of the FFPE samples was 14.1 years (range 6.6-26.4 years). In general, the correlation between FF and FFPE expression in a single sample was poor. We then selected the most variable probe sets per gene (n=17,583), and of these, the 5000 most variable probe sets on FFPE expression profiles. This unsupervised selection resulted in a better concordance (R(2)=0.54) between expression of FF and FFPE samples. Importantly, this probe set selection resulted in a correct assignment of 87% of FFPE samples into one of seven intrinsic subtypes identified using FF samples. Assignment to the same molecular cluster as the paired FF tissue was not correlated to time in paraffin. We are the first to examine a large cohort of paired FF and FFPE samples. We show that expression data from FFPE material can be used to assign samples to intrinsic molecular subtypes identified using FF material. This assignment allows the use of archival material, including material derived from large-randomised clinical trials, to determine the predictive and/or prognostic value of 'intrinsic glioma subtypes' on Exon arrays. This would enable clinicians to provide patients with an objective and accurate diagnosis and prognosis, and a personalised treatment strategy.
  British Journal of Cancer 12/2011; 106(3):538-45. · 5.04 Impact Factor
• Article: Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma.

  M Weller, T Gorlia, J G Cairncross, M J van den Bent, W Mason, K Belanger, A A Brandes, U Bogdahn, D R Macdonald, P Forsyth, A O Rossetti, D Lacombe, R-O Mirimanoff, C J Vecht, R Stupp
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  ABSTRACT: This analysis was performed to assess whether antiepileptic drugs (AEDs) modulate the effectiveness of temozolomide radiochemotherapy in patients with newly diagnosed glioblastoma. The European Organization for Research and Treatment of Cancer (EORTC) 26981-22981/National Cancer Institute of Canada (NCIC) CE.3 clinical trial database of radiotherapy (RT) with or without temozolomide (TMZ) for newly diagnosed glioblastoma was examined to assess the impact of the interaction between AED use and chemoradiotherapy on survival. Data were adjusted for known prognostic factors. When treatment began, 175 patients (30.5%) were AED-free, 277 (48.3%) were taking any enzyme-inducing AED (EIAED) and 135 (23.4%) were taking any non-EIAED. Patients receiving valproic acid (VPA) only had more grade 3/4 thrombopenia and leukopenia than patients without an AED or patients taking an EIAED only. The overall survival (OS) of patients who were receiving an AED at baseline vs not receiving any AED was similar. Patients receiving VPA alone (97 [16.9%]) appeared to derive more survival benefit from TMZ/RT (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.24-0.63) than patients receiving an EIAED only (252 [44%]) (HR 0.69, 95% CI 0.53-0.90) or patients not receiving any AED (HR 0.67, 95% CI 0.49-0.93). VPA may be preferred over an EIAED in patients with glioblastoma who require an AED during TMZ-based chemoradiotherapy. Future studies are needed to determine whether VPA increases TMZ bioavailability or acts as an inhibitor of histone deacetylases and thereby sensitizes for radiochemotherapy in vivo.
  Neurology 08/2011; 77(12):1156-64. · 8.31 Impact Factor
• Source

  Available from: Jeanette K Doorduijn

  Article: Acute painful lumbosacral paresthesia after intrathecal rituximab.

  J E C Bromberg, J K Doorduijn, J W Baars, G W van Imhoff, R Enting, M J van den Bent
  Journal of Neurology 08/2011; 259(3):559-61. · 3.47 Impact Factor
• Article: Minimal clinically meaningful differences for the EORTC QLQ-C30 and EORTC QLQ-BN20 scales in brain cancer patients.

  J Maringwa, C Quinten, M King, J Ringash, D Osoba, C Coens, F Martinelli, B B Reeve, C Gotay, E Greimel, H Flechtner, C S Cleeland, J Schmucker-Von Koch, J Weis, M J Van Den Bent, R Stupp, M J Taphoorn, A Bottomley
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  ABSTRACT: We aimed to determine the smallest changes in health-related quality of life (HRQoL) scores in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire core 30 and the Brain Cancer Module (QLQ-BN20), which could be considered as clinically meaningful in brain cancer patients. World Health Organisation performance status (PS) and mini-mental state examination (MMSE) were used as clinical anchors appropriate to related subscales to determine the minimal clinically important differences (MCIDs) in HRQoL change scores (range 0-100) in the QLQ-C30 and QLQ-BN20. A threshold of 0.2 standard deviation (SD) (small effect) was used to exclude anchor-based MCID estimates considered too small to inform interpretation. Based on PS, our findings support the following integer estimates of the MCID for improvement and deterioration, respectively: physical (6, 9), role (14, 12), and cognitive functioning (8, 8); global health status (7, 4*), fatigue (12, 9), and motor dysfunction (4*, 5). Anchoring with MMSE, cognitive functioning MCID estimates for improvement and deterioration were (11, 2*) and for communication deficit were (9, 7). Estimates with asterisks were <0.2 SD and were excluded from our MCID range of 5-14. These estimates can help clinicians evaluate changes in HRQoL over time, assess the value of a health care intervention and can be useful in determining sample sizes in designing future clinical trials.
  Annals of Oncology 02/2011; 22(9):2107-12. · 6.43 Impact Factor
• Source

  Available from: Herbert Wiesinger

  Article: Sagopilone (ZK-EPO, ZK 219477) for recurrent glioblastoma. A phase II multicenter trial by the European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumor Group.

  R Stupp, A Tosoni, J E C Bromberg, P Hau, M Campone, J Gijtenbeek, M Frenay, L Breimer, H Wiesinger, A Allgeier, M J van den Bent, U Bogdahn, W van der Graaf, H J Yun, T Gorlia, D Lacombe, A A Brandes
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  ABSTRACT: Sagopilone (ZK 219477), a lipophylic and synthetic analog of epothilone B, that crosses the blood-brain barrier has demonstrated preclinical activity in glioma models. Patients with first recurrence/progression of glioblastoma were eligible for this early phase II and pharmacokinetic study exploring single-agent sagopilone (16 mg/m(2) over 3 h every 21 days). Primary end point was a composite of either tumor response or being alive and progression free at 6 months. Overall survival, toxicity and safety and pharmacokinetics were secondary end points. Thirty-eight (evaluable 37) patients were included. Treatment was well tolerated, and neuropathy occurred in 46% patients [mild (grade 1) : 32%]. No objective responses were seen. The progression-free survival (PFS) rate at 6 months was 6.7% [95% confidence interval (CI) 1.3-18.7], the median PFS was just over 6 weeks, and the median overall survival was 7.6 months (95% CI 5.3-12.3), with a 1-year survival rate of 31.6% (95% CI 17.7-46.4). Maximum plasma concentrations were reached at the end of the 3-h infusion, with rapid declines within 30 min after termination. No evidence of relevant clinical antitumor activity against recurrent glioblastoma could be detected. Sagopilone was well tolerated, and moderate-to-severe peripheral neuropathy was observed in despite prolonged administration.
  Annals of Oncology 02/2011; 22(9):2144-9. · 6.43 Impact Factor
• Source

  Available from: Jeanette K Doorduijn

  Article: EBV related cerebral lymphoma in a leukemia patient treated with alemtuzumab.

  B van de Langerijt, J K Doorduijn, K H Lam, M J van den Bent
  Journal of Neurology 12/2010; 258(5):944-5. · 3.47 Impact Factor
• Article: Human chorionic gonadotropin treatment of anti-Hu-associated paraneoplastic neurological syndromes.

  F van Broekhoven, M T de Graaf, J E Bromberg, H Hooijkaas, M J van den Bent, J W de Beukelaar, N A Khan, J W Gratama, J N van der Geest, M Frens, R Benner, P A Sillevis Smitt
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  ABSTRACT: Paraneoplastic neurological syndromes associated with anti-Hu antibodies (Hu-PNS) are mediated by a T-cell immune response that is directed against the Hu antigens. In pregnancy, many Th1-mediated autoimmune diseases such as rheumatoid arthritis and multiple sclerosis regress. We hypothesised that this decreased disease activity during pregnancy may be related to high human chorionic gonadotropin (hCG) levels. 15 Hu-PNS patients were treated in a prospective, uncontrolled and unblinded trial with 10,000 IU daily of hCG administered by intramuscular injection during 12 weeks. Primary outcome measures were functional improvement defined as a decrease of one or more points on the modified Rankin Scale (mRS) or stabilisation in patients with mRS score ≤3 and improvement of neurological impairment assessed with the Edinburgh Functional Impairment Tests (EFIT). Secondary end points included the change in activities of daily living as evaluated using the Barthel Index. Seven of 15 patients (47%) improved on the mRS or stabilised at mRS score ≤3. Four patients (27%) showed significant improvement of neurological impairment as indicated by an overall Edinburgh Functional Impairment Tests score of ≥1 point. Five patients improved on the Barthel Index (33%). Comparison with previous studies suggests that hCG may have immunomodulatory activity and may modify the course of Hu-PNS, although well-established confounding factors may have contributed in this uncontrolled trial.
  Journal of neurology, neurosurgery, and psychiatry 12/2010; 81(12):1341-4. · 4.87 Impact Factor
• Article: The CASPR2 cell adhesion molecule functions as a tumor suppressor gene in glioma.

  L B C Bralten, A M Gravendeel, N K Kloosterhof, A Sacchetti, T Vrijenhoek, J A Veltman, M J van den Bent, J M Kros, C C Hoogenraad, P A E Sillevis Smitt, P J French
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  ABSTRACT: Genomic translocations have been implicated in cancer. In this study, we performed a screen for genetic translocations in gliomas based on exon-level expression profiles. We identified a translocation in the contactin-associated protein-like 2 (CASPR2) gene, encoding a cell adhesion molecule. CASPR2 mRNA was fused to an expressed sequence tag that likely is part of the nuclear receptor coactivator 1 gene. Despite high mRNA expression levels, no CASPR2 fusion protein was detected. In a set of 25 glioblastomas and 22 oligodendrogliomas, mutation analysis identified two additional samples with genetic alterations in the CASPR2 gene and all three identified genetic alterations are likely to reduce CASPR2 protein expression levels. Methylation of the CASPR2 gene was also observed in gliomas and glioma cell lines. CASPR2-overexpressing cells showed decreased proliferation rates, likely because of an increase in apoptosis. Moreover, high CASPR2 mRNA expression level is positively correlated with survival and is an independent prognostic factor. These results indicate that CASPR2 acts as a tumor suppressor gene in glioma.
  Oncogene 11/2010; 29(46):6138-48. · 6.37 Impact Factor
• Source

  Available from: Walter Taal

  Article: IDH1 mutations in low-grade astrocytomas predict survival but not response to temozolomide.

  H J Dubbink, W Taal, R van Marion, J M Kros, I van Heuvel, J E Bromberg, B A Zonnenberg, C B L Zonnenberg, T J Postma, J M M Gijtenbeek, W Boogerd, F H Groenendijk, P A E Sillevis Smitt, W N M Dinjens, M J van den Bent
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  ABSTRACT: Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) have been implicated in tumorigenesis of gliomas. Patients with high-grade astrocytomas with IDH1 or IDH2 mutations were reported to have a better survival, but it is unknown if this improved survival also holds for low-grade astrocytoma and whether these mutations predict outcome to specific treatment. We retrospectively investigated the correlation of IDH1 and IDH2 mutations with overall survival and response to temozolomide in a cohort of patients with dedifferentiated low-grade astrocytomas treated with temozolomide at the time of progression after radiotherapy. IDH1 mutations were present in 86% of the 49 progressive astrocytomas. No mutations in IDH2 were found. Presence of IDH1 mutations were early events and significantly improved overall survival (median survival 48 vs 98 months), but did not affect outcome of temozolomide treatment. These results indicate that IDH1 mutations identify a subgroup of gliomas with an improved survival, but are unrelated to the temozolomide response.
  Neurology 11/2009; 73(21):1792-5. · 8.31 Impact Factor
• Source

  Available from: brainlife.org

  Article: Frequently asked questions in the medical management of high-grade glioma: a short guide with practical answers.

  R Stupp, A F Hottinger, M J van den Bent, P-Y Dietrich, A A Brandes
  Annals of Oncology 09/2008; 19 Suppl 7:vii209-16. · 6.43 Impact Factor
• Source

  Available from: PubMed Central

  Article: The prognostic value of health-related quality-of-life data in predicting survival in glioblastoma cancer patients: results from an international randomised phase III EORTC Brain Tumour and Radiation Oncology Groups, and NCIC Clinical Trials Group study.

  M Mauer, R Stupp, M J B Taphoorn, C Coens, D Osoba, C Marosi, R Wong, O de Witte, J G Cairncross, F Efficace, R O Mirimanoff, P Forsyth, M J van den Bent, M Weller, A Bottomley
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  ABSTRACT: This is one of the few studies that have explored the value of baseline symptoms and health-related quality of life (HRQOL) in predicting survival in brain cancer patients. Baseline HRQOL scores (from the EORTC QLQ-C30 and the Brain Cancer Module (BN 20)) were examined in 490 newly diagnosed glioblastoma cancer patients for the relationship with overall survival by using Cox proportional hazards regression models. Refined techniques as the bootstrap re-sampling procedure and the computation of C-indexes and R(2)-coefficients were used to try and validate the model. Classical analysis controlled for major clinical prognostic factors selected cognitive functioning (P=0.0001), global health status (P=0.0055) and social functioning (P<0.0001) as statistically significant prognostic factors of survival. However, several issues question the validity of these findings. C-indexes and R(2)-coefficients, which are measures of the predictive ability of the models, did not exhibit major improvements when adding selected or all HRQOL scores to clinical factors. While classical techniques lead to positive results, more refined analyses suggest that baseline HRQOL scores add relatively little to clinical factors to predict survival. These results may have implications for future use of HRQOL as a prognostic factor in cancer patients.
  British Journal of Cancer 08/2007; 97(3):302-7. · 5.04 Impact Factor
• Source

  Available from: cytometry.cn

  Article: CSF flow cytometry greatly improves diagnostic accuracy in CNS hematologic malignancies.

  J E C Bromberg, D A Breems, J Kraan, G Bikker, B van der Holt, P Sillevis Smitt, M J van den Bent, M van't Veer, J W Gratama
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  ABSTRACT: To assess the diagnostic accuracy of flow cytometric immunophenotyping in comparison with classic cytomorphology for diagnosing CNS localizations of hematologic malignancies, and to evaluate the implications of CSF pleocytosis and protein content in this context. We reviewed the results of diagnostic evaluations of all CSF samples analyzed for localization of a hematologic malignancy between 2001 and 2004 at our center. A total of 1,054 samples from 219 patients were available for analysis. Sixty patients had a CSF localization diagnosed by positive flow cytometry, cytomorphology, or both. The first sample was positive by flow cytometry in 44 (73%) patients, by cytomorphology in 19 (32%). Four first samples were positive by cytomorphology but negative by flow cytometry. Patients with positive cytomorphology had more frequent clinical symptomatology (95% vs 58%) and CSF pleocytosis (84% vs 25%), and tended to a poorer progression-free survival than patients with positive flow cytometry only. OR for CNS localization in case of CSF pleocytosis was 10.1 (95% CI 4.9 to 20.8); OR for CNS localization in case of elevated protein content was 2.9 (95% CI 1.5 to 5.4). Nevertheless, 26 of 137 (19%) patients with normal cell count and protein concentration had a CNS localization. The diagnostic value of flow cytometry is more than twice that of cytomorphology. However, cytomorphologic examination of the CSF has additional diagnostic and possibly prognostic value, and should still be performed in conjunction with flow cytometry.
  Neurology 06/2007; 68(20):1674-9. · 8.31 Impact Factor
• Article: [Three patients with a paraneoplastic neurological syndrome: the significance of paraneoplastic antibodies].

  P A E Sillevis Smitt, S K L Polman, J W K de Beukelaar, R H Enting, M J van den Bent, J E Bromberg, J M Kros, H Hooijkaas
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  ABSTRACT: Establishing the presence of paraneoplastic antibodies is important in identifying an often severe neurological syndrome as paraneoplastic and hence directing the search for an underlying neoplasm. A paraneoplastic neurological syndrome was diagnosed in 3 patients. The first was a 64-year-old woman in whom paraneoplastic encephalomyelitis was diagnosed. The diagnosis was strongly supported by a high titre of serum anti-Hu antibodies, despite three negative biopsies from a mediastinal mass. The patient died of a non-convulsive status epilepticus; autopsy revealed not only paraneoplastic encephalomyelitis but also small-cell lung cancer. The second patient was a 55-year-old woman with metastatic breast cancer. After a three-year period of progressive neurological deterioration, a high titre of anti-CV2/CRMP5 antibodies was detected, on the basis of which the clinical syndrome was diagnosed as paraneoplastic. She received immunotherapy and her condition stabilised. The third patient, a 41-year-old man, presented with severe limbic encephalitis. Biopsy from a paraaortic mass was positive for undifferentiated carcinoma. The patient had a high titre ofanti-Ma2 antibodies and was subsequently tested positive for serum alpha-foetoprotein (AFP) and beta-human-chorionic gonadotrophin (bta-HCG). During chemotherapy for a non seminoma testicular cancer, the limbic encephalitis improved both clinically and radiologically, but the patient died as a result of the toxicity of the treatment.
  Nederlands tijdschrift voor geneeskunde 05/2007; 151(15):874-80.
• Source

  Available from: PubMed Central

  Article: Hemangioblastomatosis in a patient with von Hippel-Lindau disease.

  M C J Hanse, A Vincent, M J van den Bent
  Journal of Neuro-Oncology 05/2007; 82(2):163-4. · 3.21 Impact Factor
• Source

  Available from: oxfordjournals.org

  Article: Adjuvant treatment of high grade gliomas.

  M J van den Bent
  Annals of Oncology 10/2006; 17 Suppl 10:x186-90. · 6.43 Impact Factor
• Source

  Available from: Walter Taal

  Article: First-line temozolomide for progressive low-grade astrocytoma after radiotherapy

  W. Taal, C. Zonnenberg, B. A. Zonnenberg, J. E. Bromberg, T. J. Postma, J. M. Geitenbeek, W. Boogerd, J. M. Kros, M. C. M. Kouwenhoven, M. J. van den Bent
  Neuro-Oncology. 01/2006; 8(4):452-453.
• Source

  Available from: Walter Taal

  Article: [Clinical reasoning and decision-making in practice. An older man with prostate carcinoma and a painless paraparesis of the legs].

  A Ruitenberg, Ch J Vecht, M J van den Bent, W Taal
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  ABSTRACT: A 78-year-old man with metastasised prostate carcinoma presented with a painless paraparesis. His cerebrospinal fluid showed elevated protein and a mononuclear pleiocytosis, but cytology investigations of 5 separate samples revealed no malignant cells in the cerebrospinal fluid. Extensive viral and bacterial tests (including ELISA for Borrelia burgdorferi) of serum and cerebrospinal fluid were negative. On the day radiation therapy for presumed leptomeningeal metastases was due to start the IgG and IgM Western blot for Borrelia were found to be positive, indicating neuroborreliosis. Soon after the start of antibiotic therapy the paraparesis began to improve and after four weeks the patient had made a complete recovery. In patients with a progressive paraparesis, neuroborreliosis should be considered even in the absence of pain.
  Nederlands tijdschrift voor geneeskunde 09/2005; 149(32):1785-90.
• Source

  Available from: Walter Taal

  Article: [A patient with sinus thrombosis associated with paroxysmal nocturnal hemoglobinuria].

  A M Visser, M C Kappers-Klunne, J J Cornelissen, M J van den Bent, W Taal
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  ABSTRACT: A 27-year-old woman with a history of aplastic anaemia complained of poor control of her right arm and hand, unsteady gait, and headache that increased while in a recumbent position. She was diagnosed with cerebral sinus thrombosis. Additional investigation revealed paroxysmal nocturnal haemoglobinuria (PNH). Treatment with heparin was initiated but stopped after the patient developed a brain haemorrhage. The patient recovered with no signs of residual symptoms and began taking oral anticoagulants as maintenance therapy. PNH is a rare acquired clonal disorder due to a defective expression of the glycosylphosphatidyl-inositol anchor membrane protein. It is characterised by haemolytic anaemia, diminished haematopoiesis, increased susceptibility for infections and a hypercoagulable state. Patients with aplastic anaemia have an increased risk of developing PNH. In patients with cerebral sinus thrombosis PNH should be considered as a possible underlying disorder. These patients should be questioned for possible clinical symptoms of PNH, such as acute abdominal pain or dark urine in the morning. For patients with these symptoms and in those with a history of aplastic anaemia or recurrent thrombosis, additional testing for PNH should be conducted.
  Nederlands tijdschrift voor geneeskunde 08/2005; 149(27):1528-32.
• Source

  Available from: Walter Taal

  Article: [Favourable result for temozolomide in recurrent high-grade glioma].

  W Taal, C D D van der Rijt, P A E Sillevis Smitt, J M Kros, I van Heuvel, R H Enting, M J van den Bent
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  ABSTRACT: To describe the results of the treatment of recurrent glioma with temozolomide. Retrospective. This study evaluated 77 patients with a recurrent high-grade glioma who from August 1997-December 2003 were treated with temozolomide (150-200 mg/m2/day for 5 days per 28-day cycle) following surgery and radiotherapy at the Daniel den Hoed Oncology Centre of the Erasmus MC, Rotterdam, the Netherlands. The patients were divided into 4 groups depending on histology and chemotherapy history. 15 patients received temozolomide for a recurrent anaplastic oligodendroglioma or mixed oligo-astrocytoma. The response in this group was 80% and after 12 months in 47% of the patients there was no disease progression. 35 patients underwent second-line chemotherapy with temozolomide after earlier chemotherapy with procarbazine, lomustine and vincristine for recurrent anaplastic oligodendroglioma or mixed oligo-astrocytoma. Response was 26% and after 12 months in 15% of patients there was still no disease progression. 14 patients were treated with temozolomide for a recurrent anaplastic astrocytoma with a response of 35% and after 12 months in 8% of these patients there was no disease progression. Of the 13 patients with a recurrent glioblastoma who were treated with temozolomide 16% responded and after 6 and 12 months 21% were still free from progression. Temozolomide was well-tolerated: 2 patients had to stop because of probable side effects. CONCLUSION. Temozolomide has an acceptable safety profile and may be regarded as the preferred treatment for recurrent anaplastic gliomas after radiotherapy. There is only a limited role for temozolomide in the treatment of recurrent glioblastoma.
  Nederlands tijdschrift voor geneeskunde 07/2005; 149(25):1393-9.