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2. Joint EANM/EANO/RANO/SNMMI practice guideline/procedure standards for diagnostics and therapy (theranostics) of meningiomas using radiolabeled somatostatin receptor ligands: version 1.0

Author

Albert, Nathalie L., Preusser, Matthias, Traub-Weidinger, Tatjana, Tolboom, Nelleke, Law, Ian, Palmer, Joshua D., Guedj, Eric, Furtner, Julia, Fraioli, Francesco, Huang, Raymond Y., Johnson, Derek R., Deroose, Christophe M., Herrmann, Ken, Vogelbaum, Michael, Chang, Susan, Tonn, Joerg-Christian, Weller, Michael, Wen, Patrick Y., van den Bent, Martin J., Verger, Antoine, Ivanidze, Jana, and Galldiks, Norbert

Published
2024
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4. A framework for standardised tissue sampling and processing during resection of diffuse intracranial glioma: joint recommendations from four RANO groups

Author

Karschnia, Philipp, Smits, Marion, Reifenberger, Guido, Le Rhun, Emilie, Ellingson, Benjamin M, Galldiks, Norbert, Kim, Michelle M, Huse, Jason T, Schnell, Oliver, Harter, Patrick N, Mohme, Malte, Panel, Rater, Aldape, Kenneth, Baehring, Joachim M, Bello, Lorenzo, Brat, Daniel J, Cahill, Daniel P, Chung, Caroline, Colman, Howard, Dietrich, Jorg, Drummond, Katharine, Esquenazi, Yoshua, Gerstner, Elizabeth R, Furtner, Julia, Garibotto, Valentina, Kaufmann, Timothy J, Komori, Takashi, Kotecha, Rupesh, Liau, Linda M, Lupo, Janine M, Minniti, Giuseppe, Narita, Yoshitaka, Niyazi, Maximilian, Perry, Arie, Preusser, Matthias, Rudà, Roberta, Sanai, Nader, Schmidt, Nils-Ole, Steinbach, Joachim P, Thust, Stefanie C, Tolboom, Nelleke, van der Hoorn, Anouk, van der Vaart, Thijs, Verger, Antoine, Vik-Mo, Einar Osland, Watts, Colin, Westphal, Manfred, Wesseling, Pieter, Young, Jacob S, von Baumgarten, Louisa, Albert, Nathalie L, Huang, Raymond Y, Mehta, Minesh P, van den Bent, Martin, Weller, Michael, Vogelbaum, Michael A, Chang, Susan M, Berger, Mitchel S, and Tonn, Joerg-Christian

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Brain Cancer, Brain Disorders, Rare Diseases, Neurosciences, Cancer, Humans, Brain Neoplasms, Prospective Studies, Biological Specimen Banks, Neoplasm Recurrence, Local, Glioma, Expert Rater Panel, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

Surgical resection represents the standard of care for people with newly diagnosed diffuse gliomas, and the neuropathological and molecular profile of the resected tissue guides clinical management and forms the basis for research. The Response Assessment in Neuro-Oncology (RANO) consortium is an international, multidisciplinary effort that aims to standardise research practice in neuro-oncology. These recommendations represent a multidisciplinary consensus from the four RANO groups: RANO resect, RANO recurrent glioblastoma, RANO radiotherapy, and RANO/PET for a standardised workflow to achieve a representative tumour evaluation in a disease characterised by intratumoural heterogeneity, including recommendations on which tumour regions should be surgically sampled, how to define those regions on the basis of preoperative imaging, and the optimal sample volume. Practical recommendations for tissue sampling are given for people with low-grade and high-grade gliomas, as well as for people with newly diagnosed and recurrent disease. Sampling of liquid biopsies is also addressed. A standardised workflow for subsequent handling of the resected tissue is proposed to avoid information loss due to decreasing tissue quality or insufficient clinical information. The recommendations offer a framework for prospective biobanking studies.

Published
2023

5. 7 Tesla magnetic resonance spectroscopic imaging predicting IDH status and glioma grading

Author

Cadrien, Cornelius, Sharma, Sukrit, Lazen, Philipp, Licandro, Roxane, Furtner, Julia, Lipka, Alexandra, Niess, Eva, Hingerl, Lukas, Motyka, Stanislav, Gruber, Stephan, Strasser, Bernhard, Kiesel, Barbara, Mischkulnig, Mario, Preusser, Matthias, Roetzer-Pejrimovsky, Thomas, Wöhrer, Adelheid, Weber, Michael, Dorfer, Christian, Trattnig, Siegfried, Rössler, Karl, Bogner, Wolfgang, Widhalm, Georg, and Hangel, Gilbert

Published
2024
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6. Segmentation of glioblastomas in early post-operative multi-modal MRI with deep neural networks

Author

Helland, Ragnhild Holden, Ferles, Alexandros, Pedersen, André, Kommers, Ivar, Ardon, Hilko, Barkhof, Frederik, Bello, Lorenzo, Berger, Mitchel S., Dunås, Tora, Nibali, Marco Conti, Furtner, Julia, Hervey-Jumper, Shawn, Idema, Albert J. S., Kiesel, Barbara, Tewari, Rishi Nandoe, Mandonnet, Emmanuel, Müller, Domenique M. J., Robe, Pierre A., Rossi, Marco, Sagberg, Lisa M., Sciortino, Tommaso, Aalders, Tom, Wagemakers, Michiel, Widhalm, Georg, Witte, Marnix G., Zwinderman, Aeilko H., Majewska, Paulina L., Jakola, Asgeir S., Solheim, Ole, Hamer, Philip C. De Witt, Reinertsen, Ingerid, Eijgelaar, Roelant S., and Bouget, David

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Computer Vision and Pattern Recognition, Computer Science - Machine Learning, I.4.6, J.3
Abstract

Extent of resection after surgery is one of the main prognostic factors for patients diagnosed with glioblastoma. To achieve this, accurate segmentation and classification of residual tumor from post-operative MR images is essential. The current standard method for estimating it is subject to high inter- and intra-rater variability, and an automated method for segmentation of residual tumor in early post-operative MRI could lead to a more accurate estimation of extent of resection. In this study, two state-of-the-art neural network architectures for pre-operative segmentation were trained for the task. The models were extensively validated on a multicenter dataset with nearly 1000 patients, from 12 hospitals in Europe and the United States. The best performance achieved was a 61\% Dice score, and the best classification performance was about 80\% balanced accuracy, with a demonstrated ability to generalize across hospitals. In addition, the segmentation performance of the best models was on par with human expert raters. The predicted segmentations can be used to accurately classify the patients into those with residual tumor, and those with gross total resection., Comment: 13 pages, 4 figures, 4 tables

Published
2023

7. A comparison of 7 Tesla MR spectroscopic imaging and 3 Tesla MR fingerprinting for tumor localization in glioma patients

Author

Lazen, Philipp, Cardoso, Pedro Lima, Sharma, Sukrit, Cadrien, Cornelius, Roetzer-Pejrimovsky, Thomas, Furtner, Julia, Strasser, Bernhard, Hingerl, Lukas, Lipka, Alexandra, Preusser, Matthias, Marik, Wolfgang, Bogner, Wolfgang, Widhalm, Georg, Rössler, Karl, Trattnig, Siegfried, and Hangel, Gilbert

Subjects
Physics - Medical Physics
Abstract

This paper investigates the correlation between magnetic resonance spectroscopic imaging (MRSI) and magnetic resonance fingerprinting (MRF) in glioma patients by comparing neuro-oncological markers obtained from MRSI to T1/T2 maps from MRF. Data from 12 consenting patients with gliomas were analyzed by defining hotspots for T1, T2 and various metabolic ratios, and comparing them using S{\o}rensen-Dice Similarity Coefficients (DSCs) and the distances between their centers of intensity (COIDs). Median DSCs between MRF and the tumor segmentation were 0.73 (T1) and 0.79 (T2). The DSCs between MRSI and MRF were highest for Gln/tNAA (T1: 0.75, T2: 0.80, tumor: 0.78), followed by Gly/tNAA (T1: 0.57, T2: 0.62, tumor: 0.54) and tCho/tNAA (T1: 0.61, T2: 0.58, tumor: 0.45). The median values in the tumor hotspot were T1=1724 ms, T2=86 ms, Gln/tNAA=0.61, Gly/tNAA=0.28, Ins/tNAA=1.15, and tCho/tNAA=0.48, and, in the peritumoral region, were T1=1756 ms, T2=102ms, Gln/tNAA=0.38, Gly/tNAA=0.20, Ins/tNAA=1.06, and tCho/tNAA=0.38, and, in the NAWM, were T1=950 ms, T2=43 ms, Gln/tNAA=0.16, Gly/tNAA=0.07, Ins/tNAA=0.54, and tCho/tNAA=0.20. The results of this study constitute the first comparison of 7T MRSI and 3T MRF, showing a good correspondence between these methods., Comment: Includes 3 tables, 6 figures, 3 supplementary tables, and 4 supplementary figures

Published
2023
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8. Somatostatin analogues in treatment-refractory meningioma: a systematic review with meta-analysis of individual patient data

Author

Jensen, Lasse Rehné, Maier, Andrea Daniela, Lomstein, Atle, Graillon, Thomas, Hrachova, Maya, Bota, Daniela, Ruiz-Patiño, Alejandro, Arrieta, Oscar, Cardona, Andrés Felipe, Rudà, Roberta, Furtner, Julia, Roeckle, Ulrich, Clement, Paul, Preusser, Matthias, Scheie, David, Broholm, Helle, Kristensen, Bjarne Winther, Skjøth-Rasmussen, Jane, Ziebell, Morten, Munch, Tina Nørgaard, Fugleholm, Kåre, Walter, Martin A, Mathiesen, Tiit, and Mirian, Christian

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Brain Disorders, Cancer, Neurosciences, Clinical Research, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Everolimus, Humans, Meningeal Neoplasms, Meningioma, Prospective Studies, Receptors, Somatostatin, Somatostatin, Meta-analysis, Neuro-oncology, Treatment-refractory, Progressive, Neurology & Neurosurgery, Clinical sciences, Dentistry
Abstract

Treatment-refractory meningiomas have a dismal prognosis and limited treatment options. Meningiomas express high-densities of somatostatin receptors (SSTR), thus potentially susceptible to antitumorigenic effects of somatostatin analogues (SSA). Evidence for SSA in meningiomas is scarce, and it is unclear if published literature would either (1) support wider use of SSA, if (2) more evidence is desirable, or if (3) available evidence is sufficient to discard SSA. We addressed the need for more evidence with a systematic review and meta-analysis. We performed an individual patient data (IPD) meta-analysis. Main outcomes were toxicity, best radiological response, progression-free survival, and overall survival. We applied multivariable logistic regression models to estimate the effect of SSA on the probability of obtaining radiological disease control. The predictive performance was evaluated using area under the curve and Brier scores. We included 16 studies and compiled IPD from 8/9 of all previous cohorts. Quality of evidence was overall ranked "very low." Stable disease was reported in 58% of patients as best radiological response. Per 100 mg increase in total SSA dosage, the odds ratios for obtaining radiological disease control was 1.42 (1.11 to 1.81, P = 0.005) and 1.44 (1.00 to 2.08, P = 0.05) for patients treated with SSA as monodrug therapy vs SSA in combination with everolimus, respectively. Low quality of evidence impeded exact quantification of treatment efficacy, and the association between response and treatment may represent reverse causality. Yet, the SSA treatment was well tolerated, and beneficial effect cannot be disqualified. A prospective trial without bias from inconsistent study designs is warranted to assess SSA therapy for well-defined meningioma subgroups.

Published
2022

9. Multi-class glioma segmentation on real-world data with missing MRI sequences: comparison of three deep learning algorithms

Author

Pemberton, Hugh G., Wu, Jiaming, Kommers, Ivar, Müller, Domenique M. J., Hu, Yipeng, Goodkin, Olivia, Vos, Sjoerd B., Bisdas, Sotirios, Robe, Pierre A., Ardon, Hilko, Bello, Lorenzo, Rossi, Marco, Sciortino, Tommaso, Nibali, Marco Conti, Berger, Mitchel S., Hervey-Jumper, Shawn L., Bouwknegt, Wim, Van den Brink, Wimar A., Furtner, Julia, Han, Seunggu J., Idema, Albert J. S., Kiesel, Barbara, Widhalm, Georg, Kloet, Alfred, Wagemakers, Michiel, Zwinderman, Aeilko H., Krieg, Sandro M., Mandonnet, Emmanuel, Prados, Ferran, de Witt Hamer, Philip, Barkhof, Frederik, and Eijgelaar, Roelant S.

Published
2023
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10. Clinical applicability of miR517a detection in liquid biopsies of ETMR patients

Author

Madlener, Sibylle, Furtner, Julia, Stepien, Natalia, Senfter, Daniel, Mayr, Lisa, Zeyda, Maximilian, Gramss, Leon, Aistleitner, Barbara, Spiegl-Kreinecker, Sabine, Rivelles, Elisa, Dorfer, Christian, Rössler, Karl, Czech, Thomas, Azizi, Amedeo A., Peyrl, Andreas, Lötsch-Gojo, Daniela, Müllauer, Leonhard, Haberler, Christine, Slavc, Irene, and Gojo, Johannes

Published
2023
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13. 5-ALA Fluorescence Is a Powerful Prognostic Marker during Surgery of Low-Grade Gliomas (WHO Grade II)-Experience at Two Specialized Centers.

Author

Hosmann, Arthur, Millesi, Matthias, Wadiura, Lisa I, Kiesel, Barbara, Mercea, Petra A, Mischkulnig, Mario, Borkovec, Martin, Furtner, Julia, Roetzer, Thomas, Wolfsberger, Stefan, Phillips, Joanna J, Berghoff, Anna S, Hervey-Jumper, Shawn, Berger, Mitchel S, and Widhalm, Georg

Subjects
5-ALA, fluorescence, low-grade gliomas, patient prognosis, Oncology and Carcinogenesis
Abstract

The prediction of the individual prognosis of low-grade glioma (LGG) patients is limited in routine clinical practice. Nowadays, 5-aminolevulinic acid (5-ALA) fluorescence is primarily applied for improved intraoperative visualization of high-grade gliomas. However, visible fluorescence is also observed in rare cases despite LGG histopathology and might be an indicator for aggressive tumor behavior. The aim of this study was thus to investigate the value of intraoperative 5-ALA fluorescence for prognosis in LGG patients. We performed a retrospective analysis of patients with newly diagnosed histopathologically confirmed LGG and preoperative 5-ALA administration at two independent specialized centers. In this cohort, we correlated the visible intraoperative fluorescence status with progression-free survival (PFS), malignant transformation-free survival (MTFS) and overall survival (OS). Altogether, visible fluorescence was detected in 7 (12%) of 59 included patients in focal intratumoral areas. At a mean follow-up time of 5.3 ± 2.9 years, patients with fluorescing LGG had significantly shorter PFS (2.3 ± 0.7 vs. 5.0 ± 0.4 years; p = 0.01), MTFS (3.9 ± 0.7 vs. 8.0 ± 0.6 years; p = 0.03), and OS (5.4 ± 1.0 vs. 10.3 ± 0.5 years; p = 0.01) than non-fluorescing tumors. Our data indicate that visible 5-ALA fluorescence during surgery of pure LGG might be an already intraoperatively available marker of unfavorable patient outcome and thus close imaging follow-up might be considered.

Published
2021

14. A framework for standardised tissue sampling and processing during resection of diffuse intracranial glioma: joint recommendations from four RANO groups

Author

Aldape, Kenneth, Baehring, Joachim M., Bello, Lorenzo, Brat, Daniel J., Cahill, Daniel P., Chung, Caroline, Colman, Howard, Dietrich, Jorg, Drummond, Katharine, Esquenazi, Yoshua, Gerstner, Elizabeth R., Furtner, Julia, Garibotto, Valentina, Kaufmann, Timothy J., Komori, Takashi, Kotecha, Rupesh, Liau, Linda M., Lupo, Janine M., Minniti, Giuseppe, Narita, Yoshitaka, Niyazi, Maximilian, Perry, Arie, Preusser, Matthias, Rudà, Roberta, Sanai, Nader, Schmidt, Nils-Ole, Steinbach, Joachim P., Thust, Stefanie C., Tolboom, Nelleke, van der Hoorn, Anouk, van der Vaart, Thijs, Verger, Antoine, Vik-Mo, Einar Osland, Watts, Colin, Westphal, Manfred, Wesseling, Pieter, Young, Jacob S., Karschnia, Philipp, Smits, Marion, Reifenberger, Guido, Le Rhun, Emilie, Ellingson, Benjamin M, Galldiks, Norbert, Kim, Michelle M, Huse, Jason T, Schnell, Oliver, Harter, Patrick N, Mohme, Malte, von Baumgarten, Louisa, Albert, Nathalie L, Huang, Raymond Y, Mehta, Minesh P, van den Bent, Martin, Weller, Michael, Vogelbaum, Michael A, Chang, Susan M, Berger, Mitchel S, and Tonn, Joerg-Christian

Published
2023
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16. Reply to Stummer, W.; Thomas, C. Comment on “Hosmann et al. 5-ALA Fluorescence Is a Powerful Prognostic Marker during Surgery of Low-Grade Gliomas (WHO Grade II)—Experience at Two Specialized Centers. Cancers 2021, 13, 2540”

Author

Hosmann, Arthur, Millesi, Matthias, Wadiura, Lisa I, Kiesel, Barbara, Mercea, Petra A, Mischkulnig, Mario, Borkovec, Martin, Furtner, Julia, Roetzer, Thomas, Wolfsberger, Stefan, Phillips, Joanna J, Berghoff, Anna S, Hervey-Jumper, Shawn, Berger, Mitchel S, and Widhalm, Georg

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Neurosciences, Rare Diseases, Cancer, Brain Disorders, Brain Cancer, Oncology and Carcinogenesis, Oncology and carcinogenesis
Abstract

We greatly appreciate Dr. Stummer's and Dr. Thomas's interest in our study and their important comments [...].

Published
2021

17. Trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases: a single-arm, phase 2 trial

Author

Bartsch, Rupert, Berghoff, Anna Sophie, Furtner, Julia, Marhold, Maximilian, Bergen, Elisabeth Sophie, Roider-Schur, Sophie, Starzer, Angelika Martina, Forstner, Heidrun, Rottenmanner, Beate, Dieckmann, Karin, Bago-Horvath, Zsuzsanna, Haslacher, Helmuth, Widhalm, Georg, Ilhan-Mutlu, Aysegül, Minichsdorfer, Christoph, Fuereder, Thorsten, Szekeres, Thomas, Oehler, Leopold, Gruenberger, Birgit, Singer, Christian F., Weltermann, Ansgar, Puhr, Rainer, and Preusser, Matthias

Published
2022
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21. Corrigendum to “Zotiraciclib (TG02) for newly diagnosed glioblastoma in the elderly or for recurrent glioblastoma: The EORTC 1608 STEAM trial” [Eur J Cancer 198 (2024) 113475]

Author

Le Rhun, Emilie, primary, Gorlia, Thierry, additional, Felsberg, Jörg, additional, Jongen, Joost, additional, Maurage, Claude-Alain, additional, Ducray, François, additional, Gramatzki, Dorothee, additional, Hau, Peter, additional, Chinot, Olivier L., additional, Preusser, Matthias, additional, Cartalat, Stephanie, additional, Roth, Patrick, additional, van den Bent, Martin, additional, Furtner, Julia, additional, Collienne, Maike, additional, Reifenberger, Guido, additional, and Weller, Michael, additional

Published
2024
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22. Inequalities in access to neuro-oncology supportive care and rehabilitation: A survey of healthcare professionals’ perspectives

Author

Boele, Florien, primary, Rosenlund, Lena, additional, Nordentoft, Sara, additional, Melhuish, Sara, additional, Nicklin, Emma, additional, Rydén, Isabelle, additional, Williamson, Aoife, additional, Donders-Kamphuis, Marike, additional, Preusser, Matthias, additional, Le Rhun, Emilie, additional, Kiesel, Barbara, additional, Minniti, Giuseppe, additional, Furtner, Julia, additional, Dirven, Linda, additional, Taphoorn, Martin, additional, Galldiks, Norbert, additional, Rudà, Roberta, additional, Chalmers, Anthony, additional, Short, Susan C, additional, and Piil, Karin, additional

Published
2024
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24. Joint EANM/EANO/RANO/SNMMI practice guideline/procedure standards for diagnostics and therapy (theranostics) of meningiomas using radiolabeled somatostatin receptor ligands:version 1.0

Author

Albert, Nathalie L., Preusser, Matthias, Traub-Weidinger, Tatjana, Tolboom, Nelleke, Law, Ian, Palmer, Joshua D., Guedj, Eric, Furtner, Julia, Fraioli, Fracesco, Huang, Raymond Y., Johnson, Derek R., Deroose, Christophe M., Hermann, Ken, Vogelbaum, Michael, Chang, Susan, Tonn, Joerg-Christian, Weller, Michael, Wen, Patrick Y., van den Bent, Martin J., Verger, Antoine, Ivanidze, Jana, Galldiks, Norbert, Albert, Nathalie L., Preusser, Matthias, Traub-Weidinger, Tatjana, Tolboom, Nelleke, Law, Ian, Palmer, Joshua D., Guedj, Eric, Furtner, Julia, Fraioli, Fracesco, Huang, Raymond Y., Johnson, Derek R., Deroose, Christophe M., Hermann, Ken, Vogelbaum, Michael, Chang, Susan, Tonn, Joerg-Christian, Weller, Michael, Wen, Patrick Y., van den Bent, Martin J., Verger, Antoine, Ivanidze, Jana, and Galldiks, Norbert

Abstract

Purpose To provide practice guideline/procedure standards for diagnostics and therapy (theranostics) of meningiomas using radiolabeled somatostatin receptor (SSTR) ligands.Methods This joint practice guideline/procedure standard was collaboratively developed by the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the European Association of Neurooncology (EANO), and the PET task force of the Response Assessment in Neurooncology Working Group (PET/RANO).Results Positron emission tomography (PET) using somatostatin receptor (SSTR) ligands can detect meningioma tissue with high sensitivity and specificity and may provide clinically relevant information beyond that obtained from structural magnetic resonance imaging (MRI) or computed tomography (CT) imaging alone. SSTR-directed PET imaging can be particularly useful for differential diagnosis, delineation of meningioma extent, detection of osseous involvement, and the differentiation between posttherapeutic scar tissue and tumour recurrence. Moreover, SSTR-peptide receptor radionuclide therapy (PRRT) is an emerging investigational treatment approach for meningioma.Conclusion These practice guidelines will define procedure standards for the application of PET imaging in patients with meningiomas and related SSTR-targeted PRRTs in routine practice and clinical trials and will help to harmonize data acquisition and interpretation across centers, facilitate comparability of studies, and to collect larger databases. The current document provides additional information to the evidence-based recommendations from the PET/RANO Working Group regarding the utilization of PET imaging in meningiomas Galldiks (Neuro Oncol. 2017;19(12):1576-87). The information provided should be considered in the context of local conditions and regulations.

Published
2024

25. Zotiraciclib (TG02) for newly diagnosed glioblastoma in the elderly or for recurrent glioblastoma:The EORTC 1608 STEAM trial

Author

Le Rhun, Emilie, Gorlia, Thierry, Felsberg, Jörg, Jongen, Joost, Maurage, Claude Alain, Ducray, François, Gramatzki, Dorothee, Hau, Peter, Chinot, Olivier L., Preusser, Matthias, Cartalat, Stephanie, Roth, Patrick, van den Bent, Martin, Furtner, Julia, Collienne, Maike, Reifenberger, Guido, Weller, Michael, Le Rhun, Emilie, Gorlia, Thierry, Felsberg, Jörg, Jongen, Joost, Maurage, Claude Alain, Ducray, François, Gramatzki, Dorothee, Hau, Peter, Chinot, Olivier L., Preusser, Matthias, Cartalat, Stephanie, Roth, Patrick, van den Bent, Martin, Furtner, Julia, Collienne, Maike, Reifenberger, Guido, and Weller, Michael

Abstract

Background: Zotiraciclib (TG02) is an oral multi-cyclin dependent kinase (CDK) inhibitor thought to inhibit tumor growth via CDK-9-dependent depletion of survival proteins such as c-MYC and MCL-1 which are frequently overexpressed in glioblastoma. Methods: EORTC 1608 (NCT03224104) (STEAM) had a three parallel group (A,B,C) phase Ib, open-label, non-randomized, multicenter design in IDH wild-type newly diagnosed glioblastoma or anaplastic astrocytoma. Groups A and B explored the maximum tolerated dose (MTD) of TG02 in elderly patients, in combination with hypofractionated radiotherapy alone (group A) or temozolomide alone (group B), according to O6-methylguanine DNA methyltransferase promoter methylation status determined centrally. Group C explored single agent activity of TG02 at first relapse after temozolomide chemoradiotherapy with a primary endpoint of progression-free survival at 6 months (PFS-6). Tumor expression of CDK-9, c-MYC and MCL-1 was determined by immunohistochemistry.Results: The MTD was 150 mg twice weekly in combination with radiotherapy alone (group A) or temozolomide alone (group B). Two dose-limiting toxicities were observed at 150 mg: one in group A (grade 3 seizure), one in group B (multiple grade 1 events). Main toxicities included neutropenia, gastrointestinal disorders and hepatotoxicity. PFS-6 in group C was 6.7%. CDK-9, c-MYC and MCL-1 were confirmed to be expressed and their expression was moderately cross-correlated. High protein levels of MCL-1 were associated with inferior survival. Conclusions: TG02 exhibits overlapping toxicity with alkylating agents and low single agent clinical activity in recurrent glioblastoma. The role of CDK-9 and its down-stream effectors as prognostic factors and therapeutic targets in glioblastoma warrants further study.

Published
2024

27. Zotiraciclib (TG02) for newly diagnosed glioblastoma in the elderly or for recurrent glioblastoma: The EORTC 1608 STEAM trial

Author

Le Rhun, Emilie; https://orcid.org/0000-0002-9408-3278, Gorlia, Thierry, Felsberg, Jörg; https://orcid.org/0000-0001-9652-1799, Jongen, Joost, Maurage, Claude-Alain, Ducray, François, Gramatzki, Dorothee; https://orcid.org/0000-0002-9054-5498, Hau, Peter; https://orcid.org/0000-0003-3894-5053, Chinot, Olivier L; https://orcid.org/0000-0001-6317-9691, Preusser, Matthias; https://orcid.org/0000-0003-3541-2315, Cartalat, Stéphanie, Roth, Patrick; https://orcid.org/0000-0003-3897-214X, van den Bent, Martin; https://orcid.org/0000-0001-5710-5127, Furtner, Julia, Collienne, Maike, Reifenberger, Guido; https://orcid.org/0000-0002-1419-9837, Weller, Michael; https://orcid.org/0000-0002-1748-174X, Le Rhun, Emilie; https://orcid.org/0000-0002-9408-3278, Gorlia, Thierry, Felsberg, Jörg; https://orcid.org/0000-0001-9652-1799, Jongen, Joost, Maurage, Claude-Alain, Ducray, François, Gramatzki, Dorothee; https://orcid.org/0000-0002-9054-5498, Hau, Peter; https://orcid.org/0000-0003-3894-5053, Chinot, Olivier L; https://orcid.org/0000-0001-6317-9691, Preusser, Matthias; https://orcid.org/0000-0003-3541-2315, Cartalat, Stéphanie, Roth, Patrick; https://orcid.org/0000-0003-3897-214X, van den Bent, Martin; https://orcid.org/0000-0001-5710-5127, Furtner, Julia, Collienne, Maike, Reifenberger, Guido; https://orcid.org/0000-0002-1419-9837, and Weller, Michael; https://orcid.org/0000-0002-1748-174X

Abstract

BACKGROUND Zotiraciclib (TG02) is an oral multi-cyclin dependent kinase (CDK) inhibitor thought to inhibit tumor growth via CDK-9-dependent depletion of survival proteins such as c-MYC and MCL-1 which are frequently overexpressed in glioblastoma. METHODS EORTC 1608 (NCT03224104) (STEAM) had a three parallel group (A,B,C) phase Ib, open-label, non-randomized, multicenter design in IDH wild-type newly diagnosed glioblastoma or anaplastic astrocytoma. Groups A and B explored the maximum tolerated dose (MTD) of TG02 in elderly patients, in combination with hypofractionated radiotherapy alone (group A) or temozolomide alone (group B), according to O$^{6}$-methylguanine DNA methyltransferase promoter methylation status determined centrally. Group C explored single agent activity of TG02 at first relapse after temozolomide chemoradiotherapy with a primary endpoint of progression-free survival at 6 months (PFS-6). Tumor expression of CDK-9, c-MYC and MCL-1 was determined by immunohistochemistry. RESULTS The MTD was 150 mg twice weekly in combination with radiotherapy alone (group A) or temozolomide alone (group B). Two dose-limiting toxicities were observed at 150 mg: one in group A (grade 3 seizure), one in group B (multiple grade 1 events). Main toxicities included neutropenia, gastrointestinal disorders and hepatotoxicity. PFS-6 in group C was 6.7%. CDK-9, c-MYC and MCL-1 were confirmed to be expressed and their expression was moderately cross-correlated. High protein levels of MCL-1 were associated with inferior survival. CONCLUSIONS TG02 exhibits overlapping toxicity with alkylating agents and low single agent clinical activity in recurrent glioblastoma. The role of CDK-9 and its down-stream effectors as prognostic factors and therapeutic targets in glioblastoma warrants further study.

Published
2024

37. A Comparison of 7 Tesla MR Spectroscopic Imaging and 3 Tesla MR Fingerprinting for Tumor Localization in Glioma Patients.

Author

Lazen, Philipp, Lima Cardoso, Pedro, Sharma, Sukrit, Cadrien, Cornelius, Roetzer-Pejrimovsky, Thomas, Furtner, Julia, Strasser, Bernhard, Hingerl, Lukas, Lipka, Alexandra, Preusser, Matthias, Marik, Wolfgang, Bogner, Wolfgang, Widhalm, Georg, Rössler, Karl, Trattnig, Siegfried, and Hangel, Gilbert

Subjects
STATISTICAL correlation, NUCLEAR magnetic resonance spectroscopy, GLIOMAS, RESEARCH funding, MAGNETIC resonance imaging, TUMOR markers, LONGITUDINAL method, RESEARCH, COMPARATIVE studies
Abstract

Simple Summary: This study compared two brain imaging methods, 7T magnetic resonance spectroscopic imaging (MRSI), which can image metabolic processes, and 3T magnetic resonance fingerprinting (MRF), which can image magnetic relaxation times, in 12 people with brain tumors called gliomas. Our goal was to understand how well these two approaches corresponded to each other, and which metabolite or relaxation time map was closest to the clinical standard, a neuroradiologist's tumor segmentation. In order to do this, we defined hotspots for each method and compared their overlaps. Additionally, we investigated the region around the tumor to look for evidence of possible tumor infiltration. The results of this study could improve how we use magnetic resonance imaging to monitor gliomas in patients. This paper investigated the correlation between magnetic resonance spectroscopic imaging (MRSI) and magnetic resonance fingerprinting (MRF) in glioma patients by comparing neuro-oncological markers obtained from MRSI to T1/T2 maps from MRF. Data from 12 consenting patients with gliomas were analyzed by defining hotspots for T1, T2, and various metabolic ratios, and comparing them using Sørensen–Dice similarity coefficients (DSCs) and the distances between their centers of intensity (COIDs). The median DSCs between MRF and the tumor segmentation were 0.73 (T1) and 0.79 (T2). The DSCs between MRSI and MRF were the highest for Gln/tNAA (T1: 0.75, T2: 0.80, tumor: 0.78), followed by Gly/tNAA (T1: 0.57, T2: 0.62, tumor: 0.54) and tCho/tNAA (T1: 0.61, T2: 0.58, tumor: 0.45). The median values in the tumor hotspot were T1 = 1724 ms, T2 = 86 ms, Gln/tNAA = 0.61, Gly/tNAA = 0.28, Ins/tNAA = 1.15, and tCho/tNAA = 0.48, and, in the peritumoral region, were T1 = 1756 ms, T2 = 102 ms, Gln/tNAA = 0.38, Gly/tNAA = 0.20, Ins/tNAA = 1.06, and tCho/tNAA = 0.38, and, in the NAWM, were T1 = 950 ms, T2 = 43 ms, Gln/tNAA = 0.16, Gly/tNAA = 0.07, Ins/tNAA = 0.54, and tCho/tNAA = 0.20. The results of this study constitute the first comparison of 7T MRSI and 3T MRF, showing a good correspondence between these methods. [ABSTRACT FROM AUTHOR]

Published
2024
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38. Segmentation of glioblastomas in early post-operative multi-modal MRI with deep neural networks

Author

Helland, Ragnhild Holden, primary, Ferles, Alexandros, additional, Pedersen, André, additional, Kommers, Ivar, additional, Ardon, Hilko, additional, Barkhof, Frederik, additional, Bello, Lorenzo, additional, Berger, Mitchel S., additional, Dunås, Tora, additional, Nibali, Marco Conti, additional, Furtner, Julia, additional, Hervey-Jumper, Shawn, additional, Idema, Albert J. S., additional, Kiesel, Barbara, additional, Tewari, Rishi Nandoe, additional, Mandonnet, Emmanuel, additional, Müller, Domenique M. J., additional, Robe, Pierre A., additional, Rossi, Marco, additional, Sagberg, Lisa M., additional, Sciortino, Tommaso, additional, Aalders, Tom, additional, Wagemakers, Michiel, additional, Widhalm, Georg, additional, Witte, Marnix G., additional, Zwinderman, Aeilko H., additional, Majewska, Paulina L., additional, Jakola, Asgeir S., additional, Solheim, Ole, additional, Hamer, Philip C. De Witt, additional, Reinertsen, Ingerid, additional, Eijgelaar, Roelant S., additional, and Bouget, David, additional

Published
2023
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39. CTNI-34. ZOTIRACICLIB (TG02) FOR NEWLY DIAGNOSED GLIOBLASTOMA IN THE ELDERLY OR FOR RECURRENT GLIOBLASTOMA: FINAL RESULTS OF THE EORTC 1608 STEAM TRIAL

Author

Rhun, Emilie Le, primary, Gorlia, Thierry, additional, Felsberg, Jörg, additional, Furtner, Julia, additional, Jongen, Joost, additional, Maurage, Claude-Alain, additional, Ducray, Francois, additional, Roth, Patrick, additional, Hau, Peter, additional, Chinot, Olivier, additional, Preusser, Matthias, additional, Cartalat, Stephanie, additional, van den Bent, Martin, additional, Collienne, Maike, additional, Reifenberger, Guido, additional, and Weller, Michael, additional

Published
2023
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40. Radiomic features define risk and are linked to DNA methylation attributes in primary CNS lymphoma

Author

Nenning, Karl-Heinz, primary, Gesperger, Johanna, additional, Furtner, Julia, additional, Nemc, Amelie, additional, Roetzer-Pejrimovsky, Thomas, additional, Choi, Seung-Won, additional, Mitter, Christian, additional, Leber, Stefan L, additional, Hofmanninger, Johannes, additional, Klughammer, Johanna, additional, Erguener, Bekir, additional, Bauer, Marlies, additional, Brada, Martina, additional, Chong, Kyuha, additional, Brandner-Kokalj, Tanisa, additional, Freyschlag, Christian F, additional, Grams, Astrid, additional, Haybaeck, Johannes, additional, Hoenigschnabl, Selma, additional, Hoffermann, Markus, additional, Iglseder, Sarah, additional, Kiesel, Barbara, additional, Kitzwoegerer, Melitta, additional, Kleindienst, Waltraud, additional, Marhold, Franz, additional, Moser, Patrizia, additional, Oberndorfer, Stefan, additional, Pinggera, Daniel, additional, Scheichel, Florian, additional, Sherif, Camillo, additional, Stockhammer, Guenther, additional, Stultschnig, Martin, additional, Thomé, Claudius, additional, Trenkler, Johannes, additional, Urbanic-Purkart, Tadeja, additional, Weis, Serge, additional, Widhalm, Georg, additional, Wuertz, Franz, additional, Preusser, Matthias, additional, Baumann, Bernhard, additional, Simonitsch-Klupp, Ingrid, additional, Nam, Do-Hyun, additional, Bock, Christoph, additional, Langs, Georg, additional, and Woehrer, Adelheid, additional

Published
2023
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41. The Site of Origin of Medulloblastoma: Surgical Observations Correlated to Molecular Groups

Author

Ciobanu-Caraus, Olga, primary, Czech, Thomas, additional, Peyrl, Andreas, additional, Haberler, Christine, additional, Kasprian, Gregor, additional, Furtner, Julia, additional, Kool, Marcel, additional, Sill, Martin, additional, Frischer, Josa M., additional, Cho, Anna, additional, Slavc, Irene, additional, Rössler, Karl, additional, Gojo, Johannes, additional, and Dorfer, Christian, additional

Published
2023
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43. HGG-19. CLINICAL RESPONSE TO THE PDGFRA/KIT INHIBITOR AVAPRITINIB IN PEDIATRIC AND YOUNG ADULT HIGH-GRADE GLIOMA PATIENTS WITH H3K27M OR PDGFRA GENOMIC ALTERATIONS

Author

Trissal, Maria, primary, Mayr, Lisa, additional, Schwark, Kallen, additional, LaBelle, Jenna, additional, Kong, Seongbae, additional, Furtner, Julia, additional, Weiler-Wichtl, Liesa, additional, Supko, Jeffrey, additional, Rozowsky, Jacob, additional, Hack, Olivia, additional, Groves, Andrew, additional, Marques, Joana, additional, Leiss, Ulrike, additional, Rosenmayr, Verena, additional, Dubois, Frank, additional, Greenwald, Noah F, additional, Madlener, Sibylle, additional, Guntner, Armin Sebastian, additional, Pálová, Hana, additional, Stepien, Natalia, additional, Lötsch-Gojo, Daniela, additional, Dorfer, Christian, additional, Dieckmann, Karen, additional, Peyrl, Andreas, additional, Azizi, Amadeo A, additional, Baumgartner, Alicia, additional, Slabý, Ondřej, additional, Pokorná, Petra, additional, Bandopadhayay, Pratiti, additional, Rameen_Beroukhim@dfci.harvard.edu Beroukhim, Rameen Beroukhim, additional, Ligon, Keith L, additional, Kramm, Christof M, additional, Bronsema, Annika, additional, Bailey, Simon, additional, Stucklin, Ana Guerreiro, additional, Mueller, Sabine Mueller, additional, Jones, David T W, additional, Jäger, Natalie, additional, Mullauer, Leonhard, additional, Haberler, Christine, additional, Kumar-Sinha, Chandan, additional, Chinnaiyan, Arul, additional, Mody, Rajen, additional, Sterba.Jaroslav@fnbrno.cz Štěrba, Jaroslav Štěrba, additional, Skrypek, Mary, additional, Martinez, Nina, additional, Bowers, Daniel C, additional, Koschmann, Carl Koschmann, additional, Gojo, Johannes, additional, and Filbin, Mariella, additional

Published
2023
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44. Distributed changes of the functional connectome in patients with glioblastoma

Author

Nenning, Karl-Heinz, Furtner, Julia, Kiesel, Barbara, Schwartz, Ernst, Roetzer, Thomas, Fortelny, Nikolaus, Bock, Christoph, Grisold, Anna, Marko, Martha, Leutmezer, Fritz, Liu, Hesheng, Golland, Polina, Stoecklein, Sophia, Hainfellner, Johannes A., Kasprian, Gregor, Prayer, Daniela, Marosi, Christine, Widhalm, Georg, Woehrer, Adelheid, and Langs, Georg

Published
2020
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47. The DNA methylation landscape of glioblastoma disease progression shows extensive heterogeneity in time and space

Author

Klughammer, Johanna, Kiesel, Barbara, Roetzer, Thomas, Fortelny, Nikolaus, Nemc, Amelie, Nenning, Karl-Heinz, and Furtner, Julia

Subjects
Methylation -- Genetic aspects, DNA sequencing -- Usage, Transcription (Genetics) -- Research, Glioblastomas -- Genetic aspects -- Development and progression -- Care and treatment -- Risk factors, Medical schools, Recurrence (Disease), Gliomas, Cancer, Genomics, Tumors, DNA, Genetic research, Radiology, Genomes, Sulfites, Epigenetic inheritance, Formaldehyde, Biological sciences, Health
Abstract

Glioblastoma is characterized by widespread genetic and transcriptional heterogeneity, yet little is known about the role of the epigenome in glioblastoma disease progression. Here, we present genome-scale maps of DNA methylation in matched primary and recurring glioblastoma tumors, using data from a highly annotated clinical cohort that was selected through a national patient registry. We demonstrate the feasibility of DNA methylation mapping in a large set of routinely collected FFPE samples, and we validate bisulfite sequencing as a multipurpose assay that allowed us to infer a range of different genetic, epigenetic, and transcriptional characteristics of the profiled tumor samples. On the basis of these data, we identified subtle differences between primary and recurring tumors, links between DNA methylation and the tumor microenvironment, and an association of epigenetic tumor heterogeneity with patient survival. In summary, this study establishes an open resource for dissecting DNA methylation heterogeneity in a genetically diverse and heterogeneous cancer, and it demonstrates the feasibility of integrating epigenomics, radiology, and digital pathology for a national cohort, thereby leveraging existing samples and data collected as part of routine clinical practice. In-depth methylation analysis of formalin-fixed paraffin-embedded glioblastoma samples demonstrates heterogeneity between primary and recurring tumors and enables prediction of composition of the tumor microenvironment and insights into progression., Author(s): Johanna Klughammer [sup.1] , Barbara Kiesel [sup.2] [sup.3] , Thomas Roetzer [sup.3] [sup.4] , Nikolaus Fortelny [sup.1] , Amelie Nemc [sup.1] , Karl-Heinz Nenning [sup.5] , Julia Furtner [sup.3] [...]

Published
2018
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50. Supplementary Data from Early Postoperative Treatment versus Initial Observation in CNS WHO Grade 2 and 3 Oligodendroglioma: Clinical Outcomes and DNA Methylation Patterns

Author

Mair, Maximilian J., primary, Leibetseder, Annette, primary, Heller, Gerwin, primary, Puhr, Rainer, primary, Tomasich, Erwin, primary, Goldberger, Sebastian, primary, Hatziioannou, Teresa, primary, Wöhrer, Adelheid, primary, Widhalm, Georg, primary, Dieckmann, Karin, primary, Aichholzer, Martin, primary, Weis, Serge, primary, von Oertzen, Tim, primary, Furtner, Julia, primary, Pichler, Josef, primary, Preusser, Matthias, primary, and Berghoff, Anna S., primary

Published
2023
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