Academic Center for Adult and Pediatric Brain Tumor

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To improve the outcome of brain and intracranial tumor patients, by improving both care and treatment, including the development of a value based outcome research program. To achieve this aim the center conducts clinical, translational and fundamental research into brain tumors and is actively involved in the education of health care providers and researchers

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Research activities Type of collaborations Educational programs Patient care activities Societal Relevance Viability Publications PhD theses Non-scientific publications Employees
Academic Center of Excellence

Research Activities

The research focus of the ACE is basically on three lines: clinical studies, translational and biomarker studies, and fundamental studies. The ACE has a track record on clinical studies on gliomas, from phase I to III. These studies include projects on translational research, aiming at predictive and prognostic markers. To achieve this the ACE puts major emphasis on clinical studies either initiated by academia of by industry.

An important focus of the ACE is the molecular analysis of tumor samples in order to select patients for specific treatment approaches, and the integration of genomic data with MR and radiology findings (development of radiogenomics). On a more fundamental level, ongoing research focusses on the development of novel treatment approaches for brain tumors (immunotherapy using vaccination strategies, viro-immunotherapy) and the use of patient derived glioblastoma cell cultures for the identification of active agents in glioblastoma and unraveling the mechanisms of actions.

This research is carried out by varying collaborations involving the departments of Neurology, Neurosurgery, Pathology, Radiology, Medical Oncology, and Pediatric Oncology. Collaborations exist with the EORTC, the Zurich University Hospital, Dana Farber Cancer Institute/Brighams and Women Hospital, MD Anderson CC, UCSF, MC Haaglanden/LUMC, Elizabeth Ziekenhuis Tilburg, VUMC and UMCU. The ACE actively participates with the EORTC Brain Tumor Group, HOVON, the SIOP Brain Tumor Committee and the ITCC c

List of scientific projects with PhD's and departments, external collaborations

Adoptive T-cell therapy for gliomas. PI: Sillevis Smitt. PhD Bas Weenink. Partners: neurologie, neurochirurgie, ACE Tumor Immunology (ACE TI-IT). Outside collaboration: Charite Berlin.

KWF 2017-1/11026. Glioma Longitudinal AnalySiS in the Netherlands (GLASS-NL): Molecular markers for malignant evolution of IDH mutant astrocytomas. PI French, Kros, Smits, van den Bent. PhD students W Vallentgoed, Karin van Gardern. Partners: Afd pathologie, radiologie, neurologie. Outside collaboration: VUMC, Erasmus MC, UMCU, The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA

KWF 2015-2019 Non-invasive phenotyping of molecular brain tumour profiles using novel advanced MR imaging and analysis (projectnumber EMCR 2015-7859). PI M Smits, PhD students F Incekara, S van der Voort. Partners: radiology, pathology, neurology, neurosurgery

KWF 2016: 10685. Biomarkers for chemotherapy sensitivity and prognosis of 1p/19q non-codeleted anaplastic glioma: analysis of the intercontinental CATNON trial. PhD M Tesileanu. Partners: afd pathologie, neurologie, ACE: MOlBIM. External: EORTC

Brain Tumor Charity Grant GN-000577 - Identifying 1p/19q intact anaplastic glioma patients benefitting from adding temozolomide to radiotherapy. PI van den Bent, French. Partners: neurology, pathology, ACE MOLBIM

KWF 2018: 11562. De SAFE-Trial: Wakkere hersentumoroperatie vergeleken met hersentumoroperatie onder narcose. PI A Vincent. Partners: neurosurgery, anesthesiology. External: multicenter Dutch trial

TELEVIE Project . GSAM: evolution of glioblastoma. PhD K Draaisma. Partners: neurology, ACE MolBim. Outside partners: UMCU, Universite de Liege, EORTC

Int EU Consortium GLIOTRAIN. Horizon 2020 program, lead institute RCSI Dublin, Ireland . PI M Lamfers, S Leenstra . PhD students F Fabro, E Ntafoulis. Partners: neurosurgery, radiology, gernetics, neurology. External: 23 EU organisations, Stanford Boston.

OVIT consortium (ACE VICER, TI-IT) PhD Stavrakaki. Partners: virologie, radiologie, chirurgie, neurochirurgie, , pathologie. External: Harvard, Boston

Role of BMP signaling in glioblastoma (ACE Celbiology dept) PhD I. Verploegh. Partners: Cell Biology, Genetics

Development of in vitro models of IDH mutant glioma (STOPhersentumoren) PhD C. Verheul. Partners: Neurology, Genetics (ACE NeMo), External: Norlux, Luxemburg

Circulating Tissue macrophages as novel diagnostic tool (MRace promotie). PhD Wouter van den Bossche (ACE Immunology dept)

Combination studies with immune checkpoint inhibitors for brain and skin cancer (Mrace promotie) PhD Zineb Belcaid (ACE: TI-IT), External Johns Hopkins

Exosomes as biomarkers oand therapeutic carriers (STOPhersentumoren) post-doc Thomas Hartjes. Partners: ACE VICER, TI-IT, dept of Optical Imaging, dept of Urology

Validation in vitro model system (Erasmus HDM Award) Technician: Trisha Kers.

Long-term survivors study (STOPhersentumoren) PhD: Jochem Spoor

Glioma Proteomics (EuroStars) Technician: Tessa Pierson Partners: Neurology, Pepscope (Company)

Brain Tumour Charity 2018 (role: main applicant): Making the invisible visible - in vivo mapping of molecular biomarkers in adult diffuse glioma with CEST MRI. PI Smits. PhD Yulun Wu Afd radiology, neurology. External: King's College London, Medical delta (radiomics)

ZonMW Veni van Esther Warnert 2018: Food for thought: Oxygen delivery to the brain. Partners: Radiology, neurology, pathology. External: Kings College London, Medical delta (radiomics)

Response assessment of glioma, PI Smits, van den Bent. PhD R Gahrmann. Partners: radiology, neurology

Interaction between molecular markers and outcome in relation to extent of resection in low grade glioma. PI van den Bent, Dirven. PhD: M Wijnenga. Afdelingen neurologie, neurochirurgie, pathologie, radiologie

Protonen treatment of glioma. PI A Mendez Romero. Departments: radiotherapy, Neurology, Neurochirurgy, Radiology. Extern: Holland PTC, LUMC, MCH, Miami Cancer Institute, European Particle Therapy Netwerk (EPTN); PROTRAIT: Landelijke registratie voor protonen- en fotonentherapie in NL voor het ontwikkelen van voorspel-modellen om de behandeling te optimaliseren.

HOVON 105: HOVON 105 PCNSL / ALLG NHL 24. Rituximab in Primary Central Nervous system Lymphoma. PI Doorduijn, Bromberg. PhD M van der Meulen. Partners dept Hematology, neurology. External: LUMC, MCH, HOVON

Analyses of fatigue in glioma patients (AFIG). PI G Ribbers. PhD E van Coevorden. Partners: Dept rehabilitation, neurology, neurosurgery.

Treatment of adult NF1 patients. Klinische samenwerking voor deze multisysteemaandoening binnen Erasmus MC Internal partners: EBCORE; departments pediatrics, internal medicin, medical oncology, endocrinology, dematology, cosmetic surgery, plastische chirurgie, surgical oncology, neurosurgery, clinical genetics, psychology, psychiatry, ophthalmology, rehabilitation. External partners: Zorgnetwerk NF1 (Erasmus MC, UMCG, UMCU, LUMC, MUMC+, Radboud UMC, Isala Zwolle, Medisch Spectrum Twente, Elisabeth Tweesteden, Amphia.

Brain Tumour Charity 2018 (role: main applicant): Making the invisible visible - in vivo mapping of molecular biomarkers in adult diffuse glioma with CEST MRI. PI Smits. PhD Yulun Wu Afd radiology, neurology. External: King's College London, Medical delta (radiomics)

ZonMW Veni van Esther Warnert 2018: Food for thought: Oxygen delivery to the brain. Partners: Radiology, neurology, pathology. External: Kings College London, Medical delta (radiomics)

Response assessment of glioma, PI Smits, van den Bent. PhD R Gahrmann. Partners: radiology, neurology

Interaction between molecular markers and outcome in relation to extent of resection in low grade glioma. PI van den Bent, Dirven. PhD: M Wijnenga. Afdelingen neurologie, neurochirurgie, pathologie, radiologie

Protonen treatment of glioma. PI A Mendez Romero. Departments: radiotherapy, Neurology, Neurochirurgy, Radiology. Extern: Holland PTC, LUMC, MCH, Miami Cancer Institute, European Particle Therapy Netwerk (EPTN); PROTRAIT: Landelijke registratie voor protonen- en fotonentherapie in NL voor het ontwikkelen van voorspel-modellen om de behandeling te optimaliseren.

HOVON 105: HOVON 105 PCNSL / ALLG NHL 24. Rituximab in Primary Central Nervous system Lymphoma. PI Doorduijn, Bromberg. PhD M van der Meulen. Partners dept Hematology, neurology. External: LUMC, MCH, HOVON

Analyses of fatigue in glioma patients (AFIG). PI G Ribbers. PhD E van Coevorden. Partners: Dept rehabilitation, neurology, neurosurgery.

Treatment of adult NF1 patients. Klinische samenwerking voor deze multisysteemaandoening binnen Erasmus MC Internal partners: EBCORE; departments pediatrics, internal medicin, medical oncology, endocrinology, dematology, cosmetic surgery, plastische chirurgie, surgical oncology, neurosurgery, clinical genetics, psychology, psychiatry, ophthalmology, rehabilitation. External partners: Zorgnetwerk NF1 (Erasmus MC, UMCG, UMCU, LUMC, MUMC+, Radboud UMC, Isala Zwolle, Medisch Spectrum Twente, Elisabeth Tweesteden, Amphiaonsortium, and its members have been the PI opf several international phase II and III studies.

Type of

Collaborations

Within the ACE, many departments collaborate on the research and treatment of brain tumors

The ACE has collaborations with several other ACE’s: VICER, TI-IT, NeMo, ENCORE, MOLBIM.

To continue the care for pediatric brain tumor patients at Erasmus MC, a collaboration has been developed with the PMC Utrecht.

Collaborations exist with the the Zurich University Hospital, Dana Farber Cancer Institute/Brighams and Women Hospital, MD Anderson CC, UCSF, The Miami cancer Institute , MC Haaglanden/LUMC, Elizabeth Ziekenhuis Tilburg, VUMC and UMCU

The ACE actively participates with the EORTC Brain Tumor Group, HOVON, the SIOP Brain Tumor Committee and the ITCC consortium, and its members have been the PI opf several international phase II and III studies.

The ACE is represented in the international Response Assessment in NeuroOncology (RANO) core group, the EANO and participates to ASCO guideline committees.

Educational

Contributions

In view of the infrequent nature of brain tumors, the participation of the ACE to the general training for medical students (Ba/MSc) is limited (VO2 Neurotumoren). There is a dedicated internal traineeship neuro-oncology for medical residents neurology in the Cancer Institute, which is for 50% of the time filled by medical residents neurology from other Neurology Training programs ('etalage stage'). Brain tumor surgery is part of the general training of neurosurgical residents, residents are involved in hands-on trainingscourses organized by the dept of neurosurgery at Erasmus MC the skills lab.

The dept of pediatric oncology contributes to the curriculum with the minor pediatric oncology/hematology. The various departments that participate in the ACE have a total of 17PhD students (dept neurology, neurosurgery, pathology, radiology and rehabilitation) on topics of brain tumors; three of which are supervised by two departments as a 'co-project'.

The ACE contributes to several master programs (infection and immunology, pain). The ACE participates to PhD education in Molecular Medicine graduate school, both at the teaching and at the management level (Board, courses). The ACE constitutes the MolMed subtheme Neuro-oncology and Pain (EMC MM-03-44-06) and participated in the recent MolMed SEP evaluation (result: 'excellent'). Several leading investigators play active roles in CME educational programs and educational days of as of major scientific meetings (depts radiology, neuro-oncology, and neurosurgery). The ACE is involved in the educational program of the BSc and the MSc Technical Medicine of the TH Delft

Roel Verhaak, partner and head of the International GLASS project is visiting professor 2018; theme: computational approaches in cancer biology (symposium October 30th; sponsored by Daniel den Hoed Fund),

Patient

Care Activities

More than 80% of the care within the ACE is labeled as academic and specialized care. Multidisciplinary clinical pathways have been developed for glioma, vestibular schwannoma, pituitary tumors, skull base tumors and pediatric brain tumors, which ensure a high level of diagnostics and care.

Specialized nurses hired by both the dept of neurosurgery and neurology guarantee an effective and efficient transition of the patients through the care process. A Value Based Health Care program with implementation in the e-CRF of patients has been developed. In 2015 a first patient feedback session was held and recommendations are being implemented. Factors predicting outcome to treatment are being evaluated in clinical trials initiated by the ACE, and once validated implemented in daily practice, the ACE is an early adaptor of novel treatments/treatment concepts and novel diagnostics. This spans the entire array of treatment options for patients: novel surgical techniques, new radiotherapy approaches, use of systemic treatment and use of genetic markers for treatment selection and outcome prediction.

In pediatrics a value based health care system is due to start in the summer 2016. Important factors in care are improvement of outcome and minimizing late effects on growth, endocrine function and development. Transition of care in young adults is an important focus within this ACE. A quality audit of the dept of Neurology by the 'Nederlandse Vereniging voor Neurologie' on 31st March 2016 expressed confidence in the quality of past and future patient care delivered by the department, including the Neuro-oncology sector.

Societal Relevance to Research, Education and Patient Care

Several of the clinical trials in which the ACE had a major leading role as primary (co-)investigator have had a lasting impact on the internationally accepted standard of care for brain tumor patients. These concern in particular studies on adjuvant chemotherapy in diffuse glioma. Current projects are on the treatment of newly diagnosed anaplastic glioma and low grade glioma.

The ACE has played an important role on defining prognostic and predictive markers in diffuse glioma, and in the introduction of these markers in routine clinical use in the Netherlands. The ACE was the first Dutch site routinely using awake craniotomy for brain tumor surgery. The ACE has contributed to both national and international guidelines on the management of glioma and other neuro-oncological diseases.

The ACE is represented in the core group of the Response Assessment in Neuro-Oncology group, that defines current standards for research in brain tumors and in the neuro-oncology section of the European Association of Neurological Surgeons. (Co-) Investigators in pediatrics contribute significantly to Dutch Childhood Oncology Group disease and protocol committees as well as specialist groups such as neuro-surgery, and also at the European level in the SIOP Brain Tumor Committees, which leads to development of protocols and guidelines for children with brain tumors.

Viability of Research, Education and Patient Care

The various departments in the ACE are working together on patient care, development of treatments, diagnostics and PhD students. Patient care is multidisciplinary, with twice weekly meetings on both individual patients and a separate monthly meeting on guidelines/study protocols.

Several joint clinics exist (and the ACE considers strong central support for this concept in the new cancer center very important!). The laboratories of neurology, neurosurgery and pathology work closely together, illustrated by joint bi-weekly and annual lab meetings. Many PhD students are MD, and past PhD students are currently active as medical specialists in the field of brain tumors. Medical specialists, researchers ,PhD and master students routinely attend international meetings on brain tumors (SNO, EANO, AACR) as part of their training program, and present their research at these meetings.

In the past years, 3 PhD students spent each 6 months in US institutions for their research and training. All PhD students have published and are publishing in international journals as 1st and 2nd authors. PhD students are actively recruited to the ACE, as they provide both current research for the ACE and the future generation of brain tumor specialists. Researchers and MDs actively participate in scientific boards and educational sessions of international conferences (EANO, SNO, int conference on viro-immunotherapies). The CWTS (mean normalized citation score MNCS) analysis for the period 2010 – 2013 indicated a score of 1.94 for 'Neuro-oncology and Pain' (EMC MM-03-44-06).

Key and relevant publications of the last five years

  • Taal W, Oosterkamp HM, Walenkamp AM, Dubbink HJ, Beerepoot LV, Hanse MC, Buter J, Honkoop AH, Boerman D, de Vos FY, Dinjens WN, Enting RH, Taphoorn MJ, van den Berkmortel FW, Jansen RL, Brandsma D, Bromberg JE, van Heuvel I, Vernhout RM, van der Holt B, van den Bent MJ. Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial. Lancet Oncol. 2014;15:943-53
  • Kros JM, Huizer K, Hernández-Laín A, Marucci G, Michotte A, Pollo B, Rushing EJ, Ribalta T, French P, Jaminé D, Bekka N, Lacombe D, van den Bent MJ, Gorlia T. Evidence-Based Diagnostic Algorithm for Glioma: Analysis of the Results of Pathology Panel Review and Molecular Parameters of EORTC 26951 and 26882 Trials. J Clin Oncol. 2015 Jun 10;33(17):1943-50
  • van den Bent MJ, Klein M, Smits M, Reijneveld JC, French PJ, Clement P, de Vos FYF, Wick A, Mulholland PJ, Taphoorn MJB, Lewis J, Weller M, Chinot OL, Kros JM, de Heer I, Verschuere T, Coens C, Golfinopoulos V, Gorlia T, Idbaih A. Bevacizumab and temozolomide in patients with first recurrence of WHO grade II and III glioma, without 1p/19q co-deletion (TAVAREC): a randomised controlled phase 2 EORTC trial. Lancet Oncol. 2018 Sep;19(9):1170-1179
  • Wick W, Gorlia T, Bendszus M, Taphoorn M, Sahm F, Harting I, Brandes AA, Taal W, Domont J, Idbaih A, Campone M, Clement PM, Stupp R, Fabbro M, Le Rhun E, Dubois F, Weller M, von Deimling A, Golfinopoulos V, Bromberg JC, Platten M, Klein M, van den Bent MJ. Lomustine and Bevacizumab in Progressive Glioblastoma. N Engl J Med. 2017 Nov 16;377(20):1954-1963
  • van den Bent MJ, Baumert B, Erridge SC, Vogelbaum MA, Nowak AK, Sanson M, Brandes AA, Clement PM, Baurain JF, Mason WP, Wheeler H, Chinot OL, Gill S, Griffin M, Brachman DG, Taal W, Rudà R, Weller M, McBain C, Reijneveld J, Enting RH, Weber DC, Lesimple T, Clenton S, Gijtenbeek A, Pascoe S, Herrlinger U, Hau P, Dhermain F, van Heuvel I, Stupp R, Aldape K, Jenkins RB, Dubbink HJ, Dinjens WNM, Wesseling P, Nuyens S, Golfinopoulos V, Gorlia T, Wick W, Kros JM. Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study. Lancet. 2017 Oct 7;390(10103):1645-1653.
  • van den Bent MJ, Smits M, Kros JM, Chang SM. Diffuse Infiltrating Oligodendroglioma and Astrocytoma. J Clin Oncol. 2017 Jul 20;35(21):2394-2401
  • Jacoline E.C. Bromberg MD, Samar Issa MD, Katerina Bakunina, Monique C. Minnema, Tatjana Seute, Marc Durian, Gavin Cull, Harry C. Schouten, Wendy B.C. Stevens, Josee M. Zijlstra, Joke W. Baars, Marcel Nijland, Kylie D.Mason, Aart Beeker, Martin J van den Bent, M.Beijert, Michael Gonzales, Daphne de Jong PhD17, Jeanette K. Doorduijn. Role of Rituximab in Primary Central Nervous System Lymphoma Patients: Results of the Randomised Phase III HOVON 105 / ALLG NHL 24 Intergroup Study. Lancet Oncology, in press
  • Gahrmann R, Van den Bent M, Van der Holt B, Vernhout RM, Taal W, Vos M, De Groot JC, Beerepoot LV, Buter J, Flach HZ, Hanse M, Jasperse B, Smits M. Comparison of 2D (RANO) and volumetric methods for assessment of recurrent glioblastoma treated with bevacizumab - a report from the BELOB trial. Neuro Oncol 2017;19:853-861
  • van den Bossche WBL, Kleijn A, Teunissen CE, Voerman JSA, Teodosio C, Noske DP, van Dongen JJM, Dirven CMF, Lamfers MLM. Oncolytic virotherapy in glioblastoma patients induces a tumor macrophage phenotypic shift leading to an altered glioblastoma microenvironment. Neuro Oncol. 2018 May 15 . doi: 10.1093/neuonc/noy082
  • van der Meulen M, Dirven L, Habets EJJ, van den Bent MJ, Taphoorn MJB, Bromberg JEC. Cognitive functioning and health-related quality of life in patients with newly diagnosed primary CNS lymphoma: a systematic review. Lancet Oncol. 2018 Aug;19(8):e407-e418
  • Venkatesan S, Hoogstraat M, Caljouw E, Pierson T, Spoor JK, Zeneyedpour L, Dubbink HJ, Dekker LJ, van der Kaaij M, Kloezeman J, Berghauser Pont LM, Besselink NJ, Luider TM, Joore J, Martens JW, Lamfers ML, Sleijfer S, Leenstra S. TP53 mutated glioblastoma stem-like cell cultures are sensitive to dual mTORC1/2 inhibition while resistance in TP53 wild type cultures can be overcome by combined inhibition of mTORC1/2 and Bcl-2. Oncotarget. 2016 Sep 6;7(36):58435-58444
  • Berghauser Pont LM, Balvers RK, Kloezeman JJ, Nowicki MO, van den Bossche W, Kremer A, Wakimoto H, van den Hoogen BG, Leenstra S, Dirven CM, Chiocca EA, Lawler SE, Lamfers ML. In vitro screening of clinical drugs identifies sensitizers of oncolytic viral therapy in glioblastoma stem-like cells. Gene Ther. 2015 Dec;22(12):947-59
  • Kleijn A, van den Bossche W, Haefner ES, Belcaid Z, Burghoorn-Maas C, Kloezeman JJ, Pas SD, Leenstra S, Debets R, de Vrij J, Dirven CMF, Lamfers MLM. The Sequence of Delta24-RGD and TMZ Administration in Malignant Glioma Affectsthe Role of CD8(+)T Cell Anti-tumor Activity. Mol Ther Oncolytics. 2017 Mar 1;5:11-19
  • Smits M, Van den Bent M. Imaging correlates of adult glioma genotypes. Radiology 2017;284:316-331.
  • Wijnenga MMJ, French PJ, Dubbink HJ, Dinjens WNM, Atmodimedjo PN, Kros JM, Smits M, Gahrmann R, Rutten GJ, Verheul JB, Fleischeuer R, Dirven CMF, Vincent AJPE, van den Bent MJ. The impact of surgery in molecularly defined low-grade glioma: an integrated clinical, radiological, and molecular analysis. Neuro Oncol. 2018 Jan 10;20(1):103-112

PhD theses of the last five years

  • Th Gorlia. Thesis “Diagnosis and prognosis of brain tumors in clinical trials” (13/101/ 2013)
  • W Taal. Thesis “Chemotherapy of glioma”(30/10/2015)
  • D Satoer. Thesis “Speaking on the edge. The protection of cognition after glioma surgery in eloquent areas” (20/6/2012)
  • R.K. Balvers. Thesis “Modeling of Malignant Glioma and Investigations into Novel Treatments” (13/10/2015)
  • N.K. Kloosterhof. Thesis “Functional Analysis of Molecular Alterations in Brain Tumours: from fishing to function” (24/9/2013)
  • L.M.E. Berghauser Pont. Thesis “Combination Therapies in a Patient-derived Glioblastoma Model” (02/09/2015)
  • L Erdem-Eraslan. Thesis “Identification of Predictive Response Markers and Novel Treatment Targets for Gliomas” (14/03/2016)
  • C. Zhu. Thesis “On the immune regulation of glioma angiogenesis”. (16/5/2017, cumlaude)

Non-scientific publications related to the ACE

Principal coordinator(s)

Collaborating investigator(s)

Last updated: 365 days ago.