NCT Research

CCRP Brain & CNS

Summary

The Heidelberg Neurooncology Program holds a leading international position in terms of patient numbers, basic and translational research and innovative trial activity. More than 20 clinical departments and research groups of the Heidelberg University Hospital, the German Cancer Research Center (DKFZ) and the National Center for Tumor Diseases (NCT) support the program. The combination of chairs and young investigators in neuropathology, molecular and clinical neurooncology, as well as research units in molecular genetics and diagnostics, neuroimaging, and radiation oncology, have enabled to assemble a critical mass and install neurooncology as a prototypical interdisciplinary profile area.

CCRP Brain Tumors
 

The program ensures a multidisciplinary, comprehensive research, molecular diagnostics, translational, and clinical portfolio for adult and pediatric patients with brain tumors and neurological problems associated with cancer. Every year, we consult more than 3.000 patients and treat more than 1.500 patients with tumors of the nervous system. The program has contributed to the outstanding data generated in the National Genome Research Network (NGFN) program on glial brain tumors, various next generation sequencing projects within the Heidelberg Center for Personalized Oncology (DKFZ-HIPO), and several national and international collaborative initiatives (e.g. the International Cancer Genome Consortium (ICGC)). The overall aim is to enable practice changes by precision medicine in immunotherapy, radiation oncology, targeted therapies, and, probably most importantly, combinations thereof.

Member designated as Contact Person

Prof. Dr. Wick
Neurooncology

 
 
 

Dr. Dr. Amir Abdollahi
Max-Eder-Junior Research Group Translational Radiation Oncology, German Cancer Research Center (DKFZ)

Prof. Dr. Martin Bendszus
Dept. of Neuroradiology, Heidelberg University Hospital

Prof. Dr. Dr. Jürgen Debus
Dept. of Radiation Oncology, Heidelberg University Hospital;
Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ)

Prof. Dr. Christel Herold-Mende
Division of Experimental Neurosurgery, Heidelberg University Hospital

Prof. Dr. Peter Lichter/ Dr. Bernhard Radlwimmer
Division of Molecular Genetics, German Cancer Research Center (DKFZ)

Dr. Hai-Kun Liu
Young Investigator Group-Normal and neoplastic CNS stem cells, German Cancer Research Center (DKFZ)

Prof. Dr. Ana Martin-Villalba
Division of Molecular Neurobiology, German Cancer Research Center (DKFZ)

Dr. Christiane Opitz
Junior Group Brain Cancer Metabolism, German Cancer Research Center (DKFZ)

Prof. Dr. Stefan Pfister
Division of Pediatric Neurooncology and Center for Individualized Pediatric Oncology (ZIPO) and Brain Tumors, German Cancer Research Center (DKFZ)

Prof. Dr. Michael Platten
Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ)

PD Dr. Ass. jur. Alexander Radbruch
Young Investigator Group Neuroradiology, German Cancer Research Center (DKFZ)    

Dr. Sevin Turcan
Max-Eder Research Group Neuro-oncology of Lower Grade Gliomas, Heidelberg University Hospital

Prof. Dr. Andreas Unterberg
Dept. of Neurosurgery, Heidelberg University Hospital

Prof. Dr. Andreas von Deimling
Dept. of Neuropathology, Heidelberg University Hospital;
Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ)

Prof. Dr. Wolfgang Wick
Dept. of Neurology/Neurooncology, Heidelberg University Hospital;
Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ)

Prof. Dr. Frank Winkler
Research Group Experimental Neurooncology, DKFZ/Heidelberg University Hospital

Prof. Dr. Olaf Witt
Clinical Cooperation Unit Pediatric Oncology and Center for Individualized Pediatric Oncology (ZIPO) and Brain Tumors, German Cancer Research Center (DKFZ)

Scientific Aims

  • Develop molecularly based brain tumor diagnostics, current and future focus are methylation and proteomics based assays
  • Improve definitions of brain tumors on basis of molecular parameters
  • Implement novel definitions in diagnostic standards and translate the respective analyses to diagnostic routine settings
  • Characterization of the genetic and epigenetic landscape of brain tumors
  • Functional validation of genetic events in faithful preclinical models & investigation of tumor heterogeneity
  • Identification of specific vulnerabilities and systematic preclinical testing of these in a saturated repertoire of preclinical models
  • Studying hereditary predisposition and establishing methods for minimal residual disease diagnostics
  • Develop and validate deep-learning (artificial intelligence) based methods for automated brain tumor diagnostics (longitudinal quantitative response assessment)
  • Integrative assessment of imaging and molecular analytics for patient stratification & predictive modeling
  • Application of molecular imaging methods (3D chemical shift imaging) for longitudinal quantification of 2-hydroxyglutarate (2HG) levels as imaging biomarker in IDH-directed (immunotherapy) trials
  • Validate advanced computational and high-throughput methods (radiomics) for imaging based predictive modeling in the EORTC-26101 trial
  • Radiomics-based prediction of recurrence-pattern in patients with GBM as well as determining uncertainties of radiation dose distributions and of relative biological efficacy (RBE) models for ion beams
  • Understanding the mechanisms of radioresistance and investigating strategies to overcome radioresistance e.g. via novel proton, carbon, helium and oxygen ion beams
  • Development of predictive markers for radiotherapy outcome by radiomics-based approaches and biomarker discovery in patient derived material using multi-scale omics e.g. next generation sequencing,  methylome and functional genomics analysis
  • Development of new personalized models for dose prescription based on the biologically effective dose
  • Develop local therapies in neurosurgery  
  • Provide evidence for the feasibility and efficacy of personalized immunotherapy, e.g. by advancing IDH-directed immunotherapy Further develop targeted therapy by finding master regulators
  • Generate a database building on genomic and proteomic data from the Gene Glioma Network of the German Cancer Consortium
  • Establishment of a unique national (Gliom Network DKTK-ROG) multiscale repository for outcome research, the RadPlanBio, which aims to link patient radiotherapy information (prescribed dose volumes) with biological data e.g. genomic/proteomics and imaging based follow-up, e.g. functional MRI or FDG-PET


Clinical Aims

  • Tight integration of all participating disciplines (Neurology, Neuroradiology, Neuropathology, Neurosurgery, Pediatric Neurooncology, Radiation Oncology) within the Brain Cancer Program to meet the specific needs of Neurooncology Patients
  • Develop joint efforts for pediatric and young adult patients with shared molecular profiles
  • Provide and expand a diagnostic platform which is capable to cope with the needs of all clinical partners. This extends far beyond clinical standard analyses as it aims to fulfill the requirements in ambitious clinical studies (N2M2, INFORM; MNP2.0, LOGGIC)
  • Integrate immunotherapy in the care of patients with brain metastases of RCC, 3 neg. BC and NSCLC (Roche-funded)
  • Translate novel research findings into clinical practice by implementing molecularly stratified trials with targeted substances, e.g. NCT Neuro Master Match (N2M2; a HIPO, NCT and German Cancer Aid funded umbrella trial for patients with MGMT unmethylated glioblastoma).
  • Setting up a portfolio of innovative early phase clinical trials and translation of successful concepts into frontline studies
  • Define clinically meaningful outcomes for brain tumor patients with relatively good prognosis, i.e. cognition, function and health-related quality of life within the new IMPROVE CODEL BMBF-funded consortium

  • Wick W, Platten M, Meisner C, Felsberg J, Tabatabai G, Simon M, Nikkhah G, Papsdorf K, Steinbach JP, Sabel M, Combs SE, Vesper M, Braun C, Meixensberger J, Ketter R, Mayer-Steinacker R, Reifenberger G, Weller M, for the Neurooncology Working Group (NOA) of the German Cancer Society Chemotherapy versus radiotherapy for malignant astrocytoma in the elderly. Lancet Oncol 2012;13(7):707-15
  • Osswald M, Jung E, Sahm F, Solecki G, Venkataramani V, Blaes J, Weil S, Horstmann H, Wiestler B, Syed M, Huang L, Ratliff M, Karimian Jazi K, Kurz FT, Schmenger T, Lemke D, Gömmel M, Pauli M, Liao Y, Häring P, Pusch S, Herl V, Steinhäuser C, Krunic D, Jarahian M, Miletic H, Berghoff AS, Griesbeck O, Kalamakis G, Garaschuk O, Preusser M, Weiss S, Liu H, Heiland S, Platten M, Huber PE, Kuner T, von Deimling A, Wick W, Winkler F. Brain tumour cells interconnect to a functional and resistant network. Nature. 2015;528(7580):93-8.
  • European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Weller M, van den Bent M, Tonn JC, Stupp R, Preusser M, Cohen-Jonathan-Moyal E, Henriksson R, Rhun EL, Balana C, Chinot O, Bendszus M, Reijneveld JC, Dhermain F, French P, Marosi C, Watts C, Oberg I, Pilkington G, Baumert BG, Taphoorn MJB, Hegi M, Westphal M, Reifenberger G, Soffietti R, Wick W; European Association for Neuro-Oncology (EANO) Task Force on Gliomas. Lancet Oncol. 2017 May 5. pii: S1470-2045(17)30194-8. doi: 10.1016/S1470-2045(17)30194-8.
  • Lin, C.Y., Erkek, S. et al., …and Pfister, S.M.*, Bradner, J.E.*, Northcott, P.A.* Active medulloblastoma enhancers reveal subgroup-specific cellular origins. Nature 2016;  530(7588):57-62.
  • Pajtler KW, Witt H, Sill M et al., …and von Deimling A, Lichter P, Taylor MD, Gilbertson R, Ellison DW, Aldape K, Korshunov A, Kool, M.*, Pfister, S.M.* Molecular Classification of Ependymal Tumors across All CNS Compartments, Histopathological Grades, and Age Groups. Cancer Cell 2015; 27(5):728-43.
  • Sturm, D., Witt, H., and Hovestadt, V. et al.,…, and Plass C*, Jabado N* & Pfister, S.M.* Hotspot Mutations in H3F3A and IDH1 Define Distinct Epigenetic and Biological Subgroups of Glioblastoma. Cancer Cell 2012; 22(4):425-37.
  • Schwartzentruber, J.*, Korshunov, A.*, Liu, X.Y.* et al., … and Majewski, J.*, Pfister, S.M.*, Jabado, N.* Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 2012; 482(7384):226-31.
  • Kickingereder P, Götz M, Muschelli J, Wick A, Neuberger U, Shinohara RT, Sill M, Nowosielski M, Schlemmer HP, Radbruch A, Wick W, Bendszus M, Maier-Hein KH, Bonekamp D. Large-scale Radiomic Profiling of Recurrent Glioblastoma Identifies an Imaging Predictor for Stratifying Anti-Angiogenic Treatment Response. Clin Cancer Res 2016 Dec 1;22(23):5765-5771.
  • Sahm F, Schrimpf D, Stichel D, Jones DT, Hielscher T, Schefzyk S, Okonechnikov K, Koelsche C, Reuss DE, Capper D, Sturm D, Wirsching HG, Berghoff AS, Baumgarten P, Kratz A, Huang K, Wefers AK, Hovestadt V, Sill M, Ellis HP, Kurian KM, Okuducu AF, Jungk C, Drueschler K, Schick M, Bewerunge-Hudler M, Mawrin C, Seiz-Rosenhagen M, Ketter R, Simon M, Westphal M, Lamszus K, Becker A, Koch A, Schittenhelm J, Rushing EJ, Collins VP, Brehmer S, Chavez L, Platten M, Hanggi D, Unterberg A, Paulus W, Wick W, Pfister SM, Mittelbronn M, Preusser M, Herold-Mende C, Weller M, von Deimling A: DNA methylation-based classification and grading system for meningioma: a multicentre, retrospective analysis. Lancet Oncol 2017; Epub ahead of print.
  • Pusch S, Krausert S, Fischer V, Balss J, Ott M, Schrimpf D, Capper D, Sahm F, Eisel J, Beck AC, Jugold M, Eichwald V, Kaulfuss S, Panknin O, Rehwinkel H, Zimmermann K, Hillig RC, Guenther J, Toschi L, Neuhaus R, Haegebart A, Hess-Stumpp H, Bauser M, Wick W, Unterberg A, Herold-Mende C, Platten M, von Deimling A: Pan-mutant IDH1 inhibitor BAY 1436032 for effective treatment of IDH1 mutant astrocytoma in vivo. Acta Neuropathol 2017; 133 (4), 629-44
  • Sturm D, Orr BA, Toprak UH, Hovestadt V, Jones DT, Capper D, Sill M, Buchhalter I, Northcott PA, Leis I, Ryzhova M, Koelsche C, Pfaff E, Allen SJ, Balasubramanian G, Worst BC, Pajtler KW, Brabetz S, Johann PD, Sahm F, Reimand J, Mackay A, Carvalho DM, Remke M, Phillips JJ, Perry A, Cowdrey C, Drissi R, Fouladi M, Giangaspero F, Lastowska M, Grajkowska W, Scheurlen W, Pietsch T, Hagel C, Gojo J, Lotsch D, Berger W, Slavc I, Haberler C, Jouvet A, Holm S, Hofer S, Prinz M, Keohane C, Fried I, Mawrin C, Scheie D, Mobley BC, Schniederjan MJ, Santi M, Buccoliero AM, Dahiya S, Kramm CM, von Bueren AO, von Hoff K, Rutkowski S, Herold-Mende C, Fruhwald MC, Milde T, Hasselblatt M, Wesseling P, Rossler J, Schuller U, Ebinger M, Schittenhelm J, Frank S, Grobholz R, Vajtai I, Hans V, Schneppenheim R, Zitterbart K, Collins VP, Aronica E, Varlet P, Puget S, Dufour C, Grill J, Figarella-Branger D, Wolter M, Schuhmann MU, Shalaby T, Grotzer M, van Meter T, Monoranu CM, Felsberg J, Reifenberger G, Snuderl M, Forrester LA, Koster J, Versteeg R, Volckmann R, van Sluis P, Wolf S, Mikkelsen T, Gajjar A, Aldape K, Moore AS, Taylor MD, Jones C, Jabado N, Karajannis MA, Eils R, Schlesner M, Lichter P, von Deimling A, Pfister SM, Ellison DW, Korshunov A, Kool M: New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs. Cell 2016; 164 (5), 1060-72(joint last)
  • Rapp C, Warta R, Stamova S, Nowrouzi A, Geisenberger C, Gal Z, Roesch S, Dettling S, Juenger S, Bucur M, Jungk C, DaoTrong P, Ahmadi R, Sahm F, Reuss D, Fermi V, Herpel E, Eckstein V, Grabe N, Schramm C, Weigand MA, Debus J, von Deimling A, Unterberg A, Abdollahi A*, Beckhove P*, Herold-Mende C*. Identification of T cell target antigens in glioblastoma stem-like cells using an integrated proteomics-based approach in patient specimens. Acta Neuropathol. 2017 Mar 22.
  • Means and methods for treating and/or preventing cancer associated with increased tryptophan-2,3-dioxygenase (TDO) activity (UH10702USPROV)
  • Treatment of Kynurenin-producing Tumors with AhR Antagonists (DKFZ, P1014)
  • Means and methods for treating or diagnosing IDH1 R132H mutant-positive cancers (DKFZ, 12150298.3)
  • BRAF mutation-specific antibody (V600E)
  • Method for detection von 2-Hydroxyglutarate
  • Combination of CD99/CD95L inhibitor and Cancer Immunotherapy
  • Method of predicting the responsiveness of a cancer disease to treatment on the basis of DNA methylation at the CD95 ligand gene

Clinical Activities

Multidisciplinary patient management

  • Weekly interdisciplinary tumor boards and molecular tumor board
  • Multiprofessional out-patient clinic
  • Multidisciplinary clinical trials
  • Multipdisciplinary NCT-SOP guidelines
  • Interdisciplinary development of biomarkers and targeted treatments


Specific Treatment Options

  • Phase I-III clinical trials including first-in-man agents in combined modality approaches as IITs
  • Immunotherapy clinical trial program
  • Particle therapy clinical trial program
  • High-end molecular diagnostics
  • MRI techniques for diagnosis and follow-up of brain tumor patients
  • Radioomics – advanced imaging
  • Molecularly-guided clinical trials

  • The Department of Neurooncology has contributed significantly to larger international trial activities (Chinot, Wick NEJM 2014; Nowosielski Neurology 2014; Wick ASCO 2016) also focusing on overcoming resistance to radiotherapy (Baumert Lancet Oncol 2016; Perry NEJM 2017, van den Bent Lancet accepted).
  • The Platten and Wick groups have unraveled the mutant IDH protein as target for precision immunotherapy (Schumacher Nature 2014, Bunse J Clin Invest 2015).
  • The Platten and Wick groups have also joined forces to develop the preclinical basis and a first-in-man clinical trial with a peptide-based vaccine that targets mutant isocitrate dehydrogenase (IDH) in grade II-IV gliomas.
  • A pilot immunotherapy trial (NOA-16) has been initiated in Heidelberg and at several partner sites of the German Cancer Consortium (Platten, DKTK).
  • Another Heidelberg-coordinated trial takes advantage of the peptide development within the EU Glioma Actively Personalized Vaccine Consortium (GAPVAC) for personalized immunotherapy.
  • Further work towards clinical translation includes the Wick and Platten groups’ development of the first predictive biomarker for elderly glioblastoma patients (Wick Lancet Oncol 2012).
  • The APG101 trial (W. Wick, M. Platten, A. von Deimling, M. Bendzsus) was the first successfully controlled trial in recurrent glioblastoma in 10 years investigating the soluble CD95 receptor in combination with radiotherapy. It provided the basis for the development of methylation at CpG2 in the CD95 promoter as a predictive biomarker (Wick Clin Cancer Res 2014). 
  • The program provides brain tumor patients with a genome-wide methylation analysis using 450/850k arrays and brain tumor panels (Sahm Acta Neuropathol 2016). This allows a precise molecular diagnosis including assessment of important single biomarkers used for prognosis and therapy prediction.
  • Towards understanding the interaction between molecularly defined treatments and different qualities of radiation, we have developed the NCT Neuro Master Match (N2M2) trial (funded by Deutsche Krebshilfe, NCT 3.0 and DKFZ HIPO; see figure). N2M2 is an open label phase I/II umbrella trial for patients with newly diagnosed glioblastoma without MGMT promoter methylation. It aims at demonstrating safety, feasibility and preliminary efficacy (decision for future randomized phase II/III) of treatment with targeted compounds in addition to radiotherapy based on thorough molecular characterization.
  • The Clinical Pediatric Neurooncology Program and Phase I/II Unit at the KiTZ is headed by Olaf Witt and is one of the leading programs of its kind in Germany and Europe. In addition to a portfolio of early phase clinical trials, many innovative IITs as well as pharma-sponsored studies covering several of the most relevant targets in pediatric brain tumors, the upcoming European phase III trial for pediatric low-grade gliomas, in which for the first time a MEK inhibitor will be randomized against standard of care chemotherapy in an upfront setting is led by Olaf Witt.
  • The molecular diagnostics program is co-coordinated by Stefan Pfister and David Jones together with colleagues from Neuropathology (Andreas von Deimling). MNP2.0, a nation-wide (currently internationally extending) study for advanced molecular diagnostics in childhood brain tumors is currently recruiting approximately 70% of all newly diagnosed brain tumors across the country.
  • Another national and international platform project between the Division of Neurooncology, CCU Pediatric Oncology and Department of Neuropathology is the INFORM (INdividualized Therapy FOr Relapsed Malignancies in Childhood) study, which focuses on relapses of pediatric high risk diseases, as only a small proportion of patients with a relapse (ca. 10%) can be cured. The INFORM Project is addressing this medical need by linking leading pediatric oncologists of entity-specific study groups of the Society of Pediatric Oncology and Hematology (GPOH) and renowned scientists in the field of high content genomics research. The INFORM-program is based on the molecular characterization of tumor samples, by using state-of the art next-generation sequencing technologies which are applied to get a unique fingerprint of each individual tumor (Worst Eur J Cancer, 2016). About one third of patients recruited to this study are brain tumor patients. INFORM also served as the blueprint for the N2M2 molecular biomarker profiling setup.
  • The von Deimling group developed an antibody directed against the R132H mutated protein of IDH1 constituting the vast majority of these disease defining mutations in diffuse astrocytomas and oligodendrogliomas (Capper Acta Neuropathol 2009). This antibody is now used worldwide and has evolved to become the diagnostic backbone for the diagnosis of gliomas.
  • The von Deimling group developed a mutation specific antibody recognizing the BRAFV600E mutation constituting one of the most abundant mutations in all human cancers (Capper Acta Neuropathol 2011). They determined the frequency of this mutation in human tumors (Schindler Acta Neuropathol 2011), thereby adding significant security to the diagnosis of ganglioglioma (Koelsche Acta Neuropathol 2013), pleomorphic xanthoastrocytoma, hairy cell leukemia (Andrulis Am J Surg Pathol 2012) and Langerhans cell histiocytosis (Sahm Blood 2012). The advent of drugs targeting this specific mutation has added much weight to the necessity of determining the BRAF status in position 600.
  • In close cooperation with the Department of Neurology the Department of Neuroradiology has developed novel MRI techniques for diagnosis and follow-up of brain tumor patients (Radbruch J Neurooncol 2012; Kickingereder Radiology 2014; Kickingereder J Neurooncol 2015; Kickingereder Neuro-Oncology 2015; Kickingereder Radiology 2016; Kickingereder Radiology 2016; Kickingereder Radiology 2016; Kickingereder Clin Cancer Res 2016; Bonekamp J Cereb Blood Flow Metab 2017).

Preclinical Activities

Established Technologies

  • Two-photon microscopy
  • Multimodal high-field MRI imaging
  • Preclinical brain tumor models
  • Immunotherapy and immune monitoring
  • Particle therapy
  • NGS
  • In vivo siRNA screens


Technologies to be established

  • Tandem mass tag spectrometry
  • MALDI imaging
  • Tissue FAXs

  • The groups headed by M. Platten, C. Opitz, and W. Wick unravelled the relevance of the tryptophan metabolite kynurenine as an immunosuppressive and cancer-promoting agent and the first known endogenous ligand of the arylhydrocarbon receptor (Opitz, Litzenburger Nature 2011).
  • The groups of A. von Deimling and W. Wick have spearheaded the translation of new molecular parameters in brain tumors into biomarkers, including the development of diagnostic tests (Sahm Blood 2012; Capper Acta Neuropathol 2013; Wiestler Acta Neuropathol 2013; Wick Neurology 2013; Wiestler Acta Neuropathol 2014; Sahm et al. Acta Neuropathol 2017 ) and inhibitors (Pusch Acta Neuropathol 2017).
  • The Neurooncology and Neuroradiology departments have integrated novel MRI techniques into diagnosis and follow-up of brain tumor patients (Radbruch J Neurooncol 2012; Radbruch PlosOne 2013; Lutz J Magn Reson Imaging 2013; Kickingereder Radiology 2014; Kickingereder Neuro-Oncology 2015; Kickingereder Radiology 2016).
  • A recent project applied advanced computational and high-throughput methods to convert MRI raw data of cancerous tissue into a large number of quantitative descriptors highlighting the potential of novel imaging analytics for predictive modeling in neurooncology (Kickingereder Clin Cancer Res 2016).
  • Most recently, the Winkler, Wick and Platten groups discovered a novel growth and resistance mechanism in gliomas. Membrane nanotubes were shown to be the basic constituents of infiltrative gliomas creating an adaptive and communicating network of the tumor within the brain explaining resistance and allowing the consideration of gliomas not as focal but rather whole brain disease (Osswald Nature 2015). The recently funded Hopp-Children´s Comprehensive Cancer Center at NCT Heidelberg (KiTZ) provides an ideal framework for translational preclinical and clinical research in Pediatric Neurooncology.
  • The Division of Pediatric Neurooncology closely works with the Clinical Cooperation Unit (CCU) Pediatric Oncology (Olaf Witt) to advance the therapy for children and adolescence with brain tumors (e.g., Pajtler Cancer Cell 2015).
  • The Division of Pediatric Neurooncology collaborates with the Clinical Cooperation Unit Neuropathology (Andreas von Deimling) focusing on molecular genetics of pediatric and adult tumors of the central nervous system (e.g., Capper and Jones et al. Cell, under review).
  • Together with the Division of Molecular Genetics (Peter Lichter) the Division of Pediatric Neurooncology runs the International Cancer Genome Consortium (ICGC) PedBrainTumor project focusing on the genetic characterization of childhood brain tumors (e.g., Bender, Nature Medicine 2016).
  • The von Deimling group recently participated in the development of a methylation based diagnostic approach to brain tumors. This diagnostic system (www.molecularneuropathology.org) has been made available to the diagnostic community and is heavily used by many other institutions.
  • The Department of Neuroradiology developed a novel high-throughput approach for automated quantitative analyses of medical imaging data using radiomics. This is a non-invasive approach that applies advanced computational methods to convert medical image data from a lesion-of-interest into a large number of quantitative descriptors encompassing a wealth of hidden information, much more than what is visible with the naked eye. They highlighted the potential of this technique for predictive modeling in neurooncology (Kickingereder Radiology 2016; Kickingereder Clin Cancer Res 2016) and beyond (Kickingereder RSNA 2016; Bickelhaupt J Magn Reson Imaging 2017).
  • The Department of Neuroradiology is actively developing artificial intelligence and deep-learning based methods for automated assessment of medical imaging data, especially in the context of neurooncology for automated, quantitative and user-independent assessment of tumor response (Isensee BVM 2017). Also, due to the relevance of targeting angiogenesis in malignant gliomas, the department has actively developed novel MRI post-processing methods for reliable and non-invasive assessment of tumor oxygenation and response prediction to anti-angiogenic therapy (Kickingereder J Neurooncol 2015; Kickingereder Neuro-Oncology 2015, Kickingereder Radiology 2016, Bonekamp J Cereb Blood Flow Metab 2017).
  • The Department of Neuroradiology has recently implemented (in collaboration with the Neurooncology department as well as the MGH/HST Center for Biomedical Imaging) a molecular imaging method (3D chemical shift imaging) into the clinical workflow that allows reliable non-invasive quantification of 2-hydroxyglutarate (2HG) levels and consecutive treatment monitoring of patients receiving IDH-directed therapies.
  • The Department of Radiation Oncology has established the radiobiological characteristics of all four novel ion sources at HIT (Dokic Oncotarget 2016, Mairani Phys Med Biol. 2017) including phosphoproteome responses (Winter Mol Cell Proteomics. 2017) and demonstrated improved eradication of radioresistant patients derived glioma stem cells with carbon ions (Chiblak Int J Radiat Oncol Biol Phys. 2016).
  • The Department of Radiation Oncology identified T cell target antigens in glioblastoma stem-like cells using an integrated proteomics-based approach in patient specimens and ultra-low input whole transcriptome analysis (Rapp Acta Neuropathol 2017).
  • The Department of Radiation Oncology discovered biomarkers and prognosticators of radiochemotherapy response in the Heidelberg IDHwt GBM using multi-scale omics approaches (Geisenberger Acta Neuropathol. 2015, Mock Int J Cancer. 2016).
  • The Department of Radiation Oncology identified subventricular zone derived glioma as a poor prognosis and radioresistant subgroup via radiomics, transcriptomics and methylome analysis (Adeberg Int J Radiat Oncol Biol Phys. 2014, Jung BMC Med. 2016).
  • The Department of Radiation Oncology aims to integrate tumor biology into models for radiotherapy planning to improve dose prescription and develop multimodal treatment strategies for brain tumors and rapidly translate these insights into clinical application (Debus and Abdollahi Am Soc Clin Oncol Educ Book 2014).