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1. Meningioma: International Consortium on Meningiomas consensus review on scientific advances and treatment paradigms for clinicians, researchers, and patients.

Author

Wang, Justin, Landry, Alexander, Raleigh, David, Sahm, Felix, Walsh, Kyle, Goldbrunner, Roland, Yefet, Leeor, Tonn, Jörg, Gui, Chloe, Ostrom, Quinn, Barnholtz-Sloan, Jill, Perry, Arie, Ellenbogen, Yosef, Hanemann, C, Jungwirth, Gerhard, Jenkinson, Michael, Tabatabai, Ghazaleh, Mathiesen, Tiit, McDermott, Mike, Tatagiba, Marcos, la Fougère, Christian, Maas, Sybren, Galldiks, Norbert, Albert, Nathalie, Brastianos, Priscilla, Ehret, Felix, Minniti, Giuseppe, Lamszus, Katrin, Ricklefs, Franz, Schittenhelm, Jens, Drummond, Katharine, Dunn, Ian, Pathmanaban, Omar, Cohen-Gadol, Aaron, Sulman, Erik, Tabouret, Emeline, Le Rhun, Emelie, Mawrin, Christian, Moliterno, Jennifer, Weller, Michael, Bi, Wenya, Gao, Andrew, Yip, Stephen, Niyazi, Maximilian, Aldape, Kenneth, Wen, Patrick, Short, Susan, Preusser, Matthias, Nassiri, Farshad, and Zadeh, Gelareh

Subjects
extra-axial, meningioma, methylation, molecular, neurofibromatosis 2, nonmalignant, radiotherapy, Humans, Meningioma, Meningeal Neoplasms, Consensus, Biomarkers, Tumor
Abstract

Meningiomas are the most common primary intracranial tumors in adults and are increasing in incidence due to the aging population and increased access to neuroimaging. While most exhibit nonmalignant behavior, a subset of meningiomas are biologically aggressive and are associated with treatment resistance, resulting in significant neurologic morbidity and even mortality. In recent years, meaningful advances in our understanding of the biology of these tumors have led to the incorporation of molecular biomarkers into their grading and prognostication. However, unlike other central nervous system (CNS) tumors, a unified molecular taxonomy for meningiomas has not yet been established and remains an overarching goal of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy-Not Official World Health Organization (cIMPACT-NOW) working group. Additionally, clinical equipoise still remains on how specific meningioma cases and patient populations should be optimally managed. To address these existing gaps, members of the International Consortium on Meningiomas including field-leading experts, have prepared this comprehensive consensus narrative review directed toward clinicians, researchers, and patients. Included in this manuscript are detailed overviews of proposed molecular classifications, novel biomarkers, contemporary treatment strategies, trials on systemic therapies, health-related quality-of-life studies, and management strategies for unique meningioma patient populations. In each section, we discuss the current state of knowledge as well as ongoing clinical and research challenges to road map future directions for further investigation.

Published
2024

2. The biological significance of tumor grade, age, enhancement, and extent of resection in IDH-mutant gliomas: How should they inform treatment decisions in the era of IDH inhibitors?

Author

van den Bent, Martin, French, Pim, Brat, Daniel, Tonn, Joerg, Touat, Mehdi, Ellingson, Benjamin, Young, Robert, Pallud, Johan, von Deimling, Andreas, Sahm, Felix, Figarella Branger, Dominique, Huang, Ruirui, Weller, Michael, Mellinghoff, Ingo, Cloughsey, Tim, Huse, Jason, Aldape, Kenneth, Reifenberger, Guido, Youssef, Gilbert, Karschnia, Philipp, Noushmehr, Houtan, Peters, Katherine, Ducray, Francois, Preusser, Matthias, and Wen, Patrick

Subjects
WHO brain tumor classification, astrocytoma IDH-mutant, oligodendroglioma IDH-mutant and 1p/19q codeleted, prognosis, vorasidenib, Humans, Isocitrate Dehydrogenase, Glioma, Brain Neoplasms, Mutation, Neoplasm Grading, Age Factors, Clinical Decision-Making, Enzyme Inhibitors
Abstract

The 2016 and 2021 World Health Organization 2021 Classification of central nervous system tumors have resulted in a major improvement in the classification of isocitrate dehydrogenase (IDH)-mutant gliomas. With more effective treatments many patients experience prolonged survival. However, treatment guidelines are often still based on information from historical series comprising both patients with IDH wild-type and IDH-mutant tumors. They provide recommendations for radiotherapy and chemotherapy for so-called high-risk patients, usually based on residual tumor after surgery and age over 40. More up-to-date studies give a better insight into clinical, radiological, and molecular factors associated with the outcome of patients with IDH-mutant glioma. These insights should be used today for risk stratification and for treatment decisions. In many patients with IDH-mutant grades 2 and 3 glioma, if carefully monitored postponing radiotherapy and chemotherapy is safe, and will not jeopardize the overall outcome of patients. With the INDIGO trial showing patient benefit from the IDH inhibitor vorasidenib, there is a sizable population in which it seems reasonable to try this class of agents before recommending radio-chemotherapy with its delayed adverse event profile affecting quality of survival. Ongoing trials should help to further identify the patients that are benefiting from this treatment.

Published
2024

3. Meningioma transcriptomic landscape demonstrates novel subtypes with regional associated biology and patient outcome.

Author

Thirimanne, H, Almiron-Bonnin, Damian, Nuechterlein, Nicholas, Arora, Sonali, Jensen, Matt, Parada, Carolina, Qiu, Chengxiang, Szulzewsky, Frank, English, Collin, Chen, William, Sievers, Philipp, Nassiri, Farshad, Wang, Justin, Klisch, Tiemo, Aldape, Kenneth, Patel, Akash, Cimino, Patrick, Zadeh, Gelareh, Sahm, Felix, Raleigh, David, Shendure, Jay, Ferreira, Manuel, and Holland, Eric

Subjects
Oncoscape, UMAP, brain tumor, bulk RNA-seq, meningioma, meningioma subtypes, patient prognosis prediction, recurrent, Meningioma, Humans, Transcriptome, Meningeal Neoplasms, Male, Female, Middle Aged, Gene Expression Regulation, Neoplastic, Algorithms, Gene Expression Profiling
Abstract

Meningiomas, although mostly benign, can be recurrent and fatal. World Health Organization (WHO) grading of the tumor does not always identify high-risk meningioma, and better characterizations of their aggressive biology are needed. To approach this problem, we combined 13 bulk RNA sequencing (RNA-seq) datasets to create a dimension-reduced reference landscape of 1,298 meningiomas. The clinical and genomic metadata effectively correlated with landscape regions, which led to the identification of meningioma subtypes with specific biological signatures. The time to recurrence also correlated with the map location. Further, we developed an algorithm that maps new patients onto this landscape, where the nearest neighbors predict outcome. This study highlights the utility of combining bulk transcriptomic datasets to visualize the complexity of tumor populations. Further, we provide an interactive tool for understanding the disease and predicting patient outcomes. This resource is accessible via the online tool Oncoscape, where the scientific community can explore the meningioma landscape.

Published
2024

4. Molecular classification to refine surgical and radiotherapeutic decision-making in meningioma

Author

Wang, Justin Z., Patil, Vikas, Landry, Alexander P., Gui, Chloe, Ajisebutu, Andrew, Liu, Jeff, Saarela, Olli, Pugh, Stephanie L., Won, Minhee, Patel, Zeel, Yakubov, Rebeca, Kaloti, Ramneet, Wilson, Christopher, Cohen-Gadol, Aaron, Zaazoue, Mohamed A., Tabatabai, Ghazaleh, Tatagiba, Marcos, Behling, Felix, Almiron Bonnin, Damian A., Holland, Eric C., Kruser, Tim J., Barnholtz-Sloan, Jill S., Sloan, Andrew E., Horbinski, Craig, Chotai, Silky, Chambless, Lola B., Gao, Andrew, Rebchuk, Alexander D., Makarenko, Serge, Yip, Stephen, Sahm, Felix, Maas, Sybren L. N., Tsang, Derek S., Rogers, C. Leland, Aldape, Kenneth, Nassiri, Farshad, and Zadeh, Gelareh

Published
2024
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7. A prognostic neural epigenetic signature in high-grade glioma

Author

Drexler, Richard, Khatri, Robin, Sauvigny, Thomas, Mohme, Malte, Maire, Cecile L., Ryba, Alice, Zghaibeh, Yahya, Dührsen, Lasse, Salviano-Silva, Amanda, Lamszus, Katrin, Westphal, Manfred, Gempt, Jens, Wefers, Annika K., Neumann, Julia E., Bode, Helena, Hausmann, Fabian, Huber, Tobias B., Bonn, Stefan, Jütten, Kerstin, Delev, Daniel, Weber, Katharina J., Harter, Patrick N., Onken, Julia, Vajkoczy, Peter, Capper, David, Wiestler, Benedikt, Weller, Michael, Snijder, Berend, Buck, Alicia, Weiss, Tobias, Göller, Pauline C., Sahm, Felix, Menstel, Joelle Aline, Zimmer, David Niklas, Keough, Michael B., Ni, Lijun, Monje, Michelle, Silverbush, Dana, Hovestadt, Volker, Suvà, Mario L., Krishna, Saritha, Hervey-Jumper, Shawn L., Schüller, Ulrich, Heiland, Dieter H., Hänzelmann, Sonja, and Ricklefs, Franz L.

Published
2024
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8. Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses

Author

Chen, William C, Choudhury, Abrar, Youngblood, Mark W, Polley, Mei-Yin C, Lucas, Calixto-Hope G, Mirchia, Kanish, Maas, Sybren LN, Suwala, Abigail K, Won, Minhee, Bayley, James C, Harmanci, Akdes S, Harmanci, Arif O, Klisch, Tiemo J, Nguyen, Minh P, Vasudevan, Harish N, McCortney, Kathleen, Yu, Theresa J, Bhave, Varun, Lam, Tai-Chung, Pu, Jenny Kan-Suen, Li, Lai-Fung, Leung, Gilberto Ka-Kit, Chan, Jason W, Perlow, Haley K, Palmer, Joshua D, Haberler, Christine, Berghoff, Anna S, Preusser, Matthias, Nicolaides, Theodore P, Mawrin, Christian, Agnihotri, Sameer, Resnick, Adam, Rood, Brian R, Chew, Jessica, Young, Jacob S, Boreta, Lauren, Braunstein, Steve E, Schulte, Jessica, Butowski, Nicholas, Santagata, Sandro, Spetzler, David, Bush, Nancy Ann Oberheim, Villanueva-Meyer, Javier E, Chandler, James P, Solomon, David A, Rogers, C Leland, Pugh, Stephanie L, Mehta, Minesh P, Sneed, Penny K, Berger, Mitchel S, Horbinski, Craig M, McDermott, Michael W, Perry, Arie, Bi, Wenya Linda, Patel, Akash J, Sahm, Felix, Magill, Stephen T, and Raleigh, David R

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Cancer, Clinical Research, Brain Disorders, Brain Cancer, Rare Diseases, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Humans, Biomarkers, Gene Expression Profiling, Meningeal Neoplasms, Meningioma, Neoplasm Recurrence, Local, Prospective Studies, Medical and Health Sciences, Immunology, Biomedical and clinical sciences, Health sciences
Abstract

Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and indications for postoperative radiotherapy are controversial. Here we develop a targeted gene expression biomarker that predicts meningioma outcomes and radiotherapy responses. Using a discovery cohort of 173 meningiomas, we developed a 34-gene expression risk score and performed clinical and analytical validation of this biomarker on independent meningiomas from 12 institutions across 3 continents (N = 1,856), including 103 meningiomas from a prospective clinical trial. The gene expression biomarker improved discrimination of outcomes compared with all other systems tested (N = 9) in the clinical validation cohort for local recurrence (5-year area under the curve (AUC) 0.81) and overall survival (5-year AUC 0.80). The increase in AUC compared with the standard of care, World Health Organization 2021 grade, was 0.11 for local recurrence (95% confidence interval 0.07 to 0.17, P

Published
2023

10. Correlation between natural history and multi-omics profiling of meningiomas in NF2-related schwannomatosis suggests role of methylation group and immune microenvironment in tumor growth rate

Author

Teranishi, Yu, Yurchenko, Andrey, Tran, Suzanne, Sievers, Philipp, Rajabi, Fatemeh, Ruchith, Singhabahu, Abi-Jaoude, Samiya, Blouin, Antoine, Bielle, Franck, Cazals-Hatem, Dominique, Sahm, Felix, Nikolaev, Sergey, Kalamarides, Michel, and Peyre, Matthieu

Published
2024
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13. Plasma extracellular vesicles in meningioma patients following radiotherapy as liquid biopsy- a prospective explorative biomarker study (ARO 2023-05/AG-NRO-07)

Author

Deng, Maximilian Y., da Silva, Amanda Salviano, Göller, Pauline Carlotta, König, Laila, Schäfer, Henning, Maire, Cecile, Lentz-Hommertgen, Adriane, Held, Thomas, Regnery, Sebastian, Eichkorn, Tanja, Stritzke, Florian, Bauer, Lukas, Schnell, Daniel, Herfarth, Klaus, von Deimling, Andreas, Krieg, Sandro, Wick, Antje, Wick, Wolfgang, Grosu, Anca, Debus, Jürgen, Sahm, Felix, and Ricklefs, Franz

Published
2024
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14. CNS tumors with PLAGL1-fusion: beyond ZFTA and YAP1 in the genetic spectrum of supratentorial ependymomas

Author

Tauziède-Espariat, Arnault, Nicaise, Yvan, Sievers, Philipp, Sahm, Felix, von Deimling, Andreas, Guillemot, Delphine, Pierron, Gaëlle, Duchesne, Mathilde, Edjlali, Myriam, Dangouloff-Ros, Volodia, Boddaert, Nathalie, Roux, Alexandre, Dezamis, Edouard, Hasty, Lauren, Lhermitte, Benoît, Hirsch, Edouard, Hirsch, Maria Paola Valenti, Ardellier, François-Daniel, Karnoub, Mélodie-Anne, Csanyi, Marie, Maurage, Claude-Alain, Mokhtari, Karima, Bielle, Franck, Rigau, Valérie, Roujeau, Thomas, Abad, Marine, Klein, Sébastien, Bernier, Michèle, Horodyckid, Catherine, Adam, Clovis, Brandal, Petter, Niehusmann, Pitt, Vannod-Michel, Quentin, Provost, Corentin, de Champfleur, Nicolas Menjot, Nichelli, Lucia, Métais, Alice, Mariet, Cassandra, Chrétien, Fabrice, Blauwblomme, Thomas, Beccaria, Kévin, Pallud, Johan, Puget, Stéphanie, Uro-Coste, Emmanuelle, and Varlet, Pascale

Published
2024
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15. EpiDiP/NanoDiP: a versatile unsupervised machine learning edge computing platform for epigenomic tumour diagnostics

Author

Hench, Jürgen, Hultschig, Claus, Brugger, Jon, Mariani, Luigi, Guzman, Raphael, Soleman, Jehuda, Leu, Severina, Benton, Miles, Stec, Irenäus Maria, Hench, Ivana Bratic, Hoffmann, Per, Harter, Patrick, Weber, Katharina J, Albers, Anne, Thomas, Christian, Hasselblatt, Martin, Schüller, Ulrich, Restelli, Lisa, Capper, David, Hewer, Ekkehard, Diebold, Joachim, Kolenc, Danijela, Schneider, Ulf C., Rushing, Elisabeth, della Monica, Rosa, Chiariotti, Lorenzo, Sill, Martin, Schrimpf, Daniel, von Deimling, Andreas, Sahm, Felix, Kölsche, Christian, Tolnay, Markus, and Frank, Stephan

Published
2024
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16. A clinically applicable connectivity signature for glioblastoma includes the tumor network driver CHI3L1

Author

Hai, Ling, Hoffmann, Dirk C., Wagener, Robin J., Azorin, Daniel D., Hausmann, David, Xie, Ruifan, Huppertz, Magnus-Carsten, Hiblot, Julien, Sievers, Philipp, Heuer, Sophie, Ito, Jakob, Cebulla, Gina, Kourtesakis, Alexandros, Kaulen, Leon D., Ratliff, Miriam, Mandelbaum, Henriette, Jung, Erik, Jabali, Ammar, Horschitz, Sandra, Ernst, Kati J., Reibold, Denise, Warnken, Uwe, Venkataramani, Varun, Will, Rainer, Suvà, Mario L., Herold-Mende, Christel, Sahm, Felix, Winkler, Frank, Schlesner, Matthias, Wick, Wolfgang, and Kessler, Tobias

Published
2024
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17. LOGGIC/FIREFLY-2: a phase 3, randomized trial of tovorafenib vs. chemotherapy in pediatric and young adult patients with newly diagnosed low-grade glioma harboring an activating RAF alteration

Author

van Tilburg, Cornelis M., Kilburn, Lindsay B., Perreault, Sébastien, Schmidt, Rene, Azizi, Amedeo A., Cruz-Martínez, Ofelia, Zápotocký, Michal, Scheinemann, Katrin, Meeteren, Antoinette Y. N. Schouten-van, Sehested, Astrid, Opocher, Enrico, Driever, Pablo Hernáiz, Avula, Shivaram, Ziegler, David S., Capper, David, Koch, Arend, Sahm, Felix, Qiu, Jiaheng, Tsao, Li-Pen, Blackman, Samuel C., Manley, Peter, Milde, Till, Witt, Ruth, Jones, David T. W., Hargrave, Darren, and Witt, Olaf

Published
2024
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23. Increased mRNA expression of CDKN2A is a transcriptomic marker of clinically aggressive meningiomas.

Author

Wang, Justin Z, Patil, Vikas, Liu, Jeff, Dogan, Helin, Tabatabai, Ghazaleh, Yefet, Leeor S, Behling, Felix, Hoffman, Elgin, Bunda, Severa, Yakubov, Rebecca, Kaloti, Ramneet, Brandner, Sebastian, Gao, Andrew, Cohen-Gadol, Aaron, Barnholtz-Sloan, Jill, Skardelly, Marco, Tatagiba, Marcos, Raleigh, David R, Sahm, Felix, Boutros, Paul C, Aldape, Kenneth, International Consortium on Meningiomas (ICOM), Nassiri, Farshad, and Zadeh, Gelareh

Subjects
International Consortium on Meningiomas, Humans, Meningioma, Meningeal Neoplasms, Sequence Deletion, Homozygote, Genes, p16, Cyclin-Dependent Kinase Inhibitor p16, DNA Copy Number Variations, Transcriptome, CDK inhibitor, CDKN2A, Copy number alterations, Meningiomas, Multiomic, Retinoblastoma, Cancer, Human Genome, Genetics, Brain Disorders, Biotechnology, Clinical Sciences, Neurosciences, Neurology & Neurosurgery
Abstract

Homozygous deletion of CDKN2A/B was recently incorporated into the World Health Organization classification for grade 3 meningiomas. While this marker is overall rare in meningiomas, its relationship to other CDKN2A alterations on a transcriptomic, epigenomic, and copy number level has not yet been determined. We therefore utilized multidimensional molecular data of 1577 meningioma samples from 6 independent cohorts enriched for clinically aggressive meningiomas to comprehensively interrogate the spectrum of CDKN2A alterations through DNA methylation, copy number variation, transcriptomics, and proteomics using an integrated molecular approach. Homozygous CDKN2A/B deletions were identified in only 7.1% of cases but were associated with significantly poorer outcomes compared to tumors without these deletions. Heterozygous CDKN2A/B deletions were identified in 2.6% of cases and had similarly poor outcomes as those with homozygous deletions. Among tumors with intact CDKN2A/B (without a homozygous or heterozygous deletion), we found a distinct difference in outcome based on mRNA expression of CDKN2A, with meningiomas that had elevated mRNA expression (CDKN2Ahigh) having a significantly shorter time to recurrence. The expression of CDKN2A was independently prognostic after accounting for copy number loss and consistently increased with WHO grade and more aggressive molecular and methylation groups irrespective of cohort. Despite the discordant and mutually exclusive status of the CDKN2A gene in these groups, both CDKN2Ahigh meningiomas and meningiomas with CDKN2A deletions were enriched for similar cell cycle pathways but at different checkpoints. High mRNA expression of CDKN2A was also associated with gene hypermethylation, Rb-deficiency, and lack of response to CDK inhibition. p16 immunohistochemistry could not reliably differentiate between meningiomas with and without CDKN2A deletions but appeared to correlate better with mRNA expression. These findings support the role of CDKN2A mRNA expression as a biomarker of clinically aggressive meningiomas with potential therapeutic implications.

Published
2023

24. Hypermitotic meningiomas harbor DNA methylation subgroups with distinct biological and clinical features.

Author

Choudhury, Abrar, Lucas, Calixto-Hope, Bayley, James, Harmanci, Akdes, Maas, Sybren, Santagata, Sandro, Klisch, Tiemo, Bi, Wenya, Sahm, Felix, Patel, Akash, Magill, Stephen, Perry, Arie, Raleigh, David, and Chen, William

Subjects
DNA methylation, cancer, central nervous system, meningioma, tumor, Humans, Meningioma, Meningeal Neoplasms, Neurofibromin 2, DNA Methylation, Transcriptome
Abstract

BACKGROUND: Meningiomas, the most common primary intracranial tumors, can be separated into 3 DNA methylation groups with distinct biological drivers, clinical outcomes, and therapeutic vulnerabilities. Alternative meningioma grouping schemes using copy number variants, gene expression profiles, somatic short variants, or integrated molecular models have been proposed. These data suggest meningioma DNA methylation groups may harbor subgroups unifying contrasting theories of meningioma biology. METHODS: A total of 565 meningioma DNA methylation profiles from patients with comprehensive clinical follow-up at independent discovery (n = 200) or validation (n = 365) institutions were reanalyzed and classified into Merlin-intact, Immune-enriched, or Hypermitotic DNA methylation groups. RNA sequencing from the discovery (n = 200) or validation (n = 302) cohort were analyzed in the context of DNA methylation groups to identify subgroups. Biological features and clinical outcomes were analyzed across meningioma grouping schemes. RESULTS: RNA sequencing revealed differential enrichment of FOXM1 target genes across two subgroups of Hypermitotic meningiomas. Differential expression and ontology analyses showed the subgroup of Hypermitotic meningiomas without FOXM1 target gene enrichment was distinguished by gene expression programs driving macromolecular metabolism. Analysis of genetic, epigenetic, gene expression, or cellular features revealed Hypermitotic meningioma subgroups were concordant with Proliferative or Hypermetabolic meningiomas, which were previously reported alongside Merlin-intact and Immune-enriched tumors using an integrated molecular model. The addition of DNA methylation subgroups to clinical models refined the prediction of postoperative outcomes compared to the addition of DNA methylation groups. CONCLUSIONS: Meningiomas can be separated into three DNA methylation groups and Hypermitotic meningiomas can be subdivided into Proliferative and Hypermetabolic subgroups, each with distinct biological and clinical features.

Published
2023

28. PLAG1 fusions extend the spectrum of PLAG(L)-altered CNS tumors

Author

Tauziède-Espariat, Arnault, Siegfried, Aurore, Nicaise, Yvan, Dghayem, Delphine, Laprie, Anne, Lubrano, Vincent, Richard, Pomone, Gauchotte, Guillaume, Malczuk, Joséphine, Klein, Olivier, Hasty, Lauren, Métais, Alice, Chrétien, Fabrice, Dangouloff-Ros, Volodia, Boddaert, Nathalie, Sahm, Felix, Sievers, Philipp, Varlet, Pascale, and Uro-Coste, Emmanuelle

Published
2023
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29. Independent prognostic impact of DNA methylation class and chromosome 1p loss in WHO grade 2 and 3 meningioma undergoing adjuvant high-dose radiotherapy: comprehensive molecular analysis of EORTC 22042–26042

Author

Maas, Sybren L. N., Sievers, Philipp, Weber, Damien C., Weller, Michael, van den Bent, Martin J., Mair, Maximilian J., Kros, Johan M., Carparrotti, Fransesca, von Deimling, Andreas, Salvador, Villà Freixa, Peerdeman, Saskia Marguerite, Casas-Martin, Jose, Gorlia, Thierry, Sahm, Felix, and Preusser, Matthias

Published
2023
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30. Genetical and epigenetical profiling identifies two subgroups of pineal parenchymal tumors of intermediate differentiation (PPTID) with distinct molecular, histological and clinical characteristics

Author

Rahmanzade, Ramin, Pfaff, Elke, Banan, Rouzbeh, Sievers, Philipp, Suwala, Abigail K., Hinz, Felix, Bogumil, Henri, Cherkezov, Asan, Kaan, Aras Fuat, Schrimpf, Daniel, Friedel, Dennis, Göbel, Kirsten, Keller, Felix, Saenz-Sardà, Xavier, Lossos, Alexander, Sill, Martin, Witt, Olaf, Sakowitz, Oliver W., Korshunov, Andrey, Reuss, David E., Etminan, Nima, Unterberg, Andreas, Ratliff, Miriam, Herold-Mende, Christel, Wick, Wolfgang, Pfister, Stefan M., von Deimling, Andreas, Jones, David T. W., and Sahm, Felix

Published
2023
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31. Amplification of the PLAG-family genes—PLAGL1 and PLAGL2—is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification

Author

Keck, Michaela-Kristina, Sill, Martin, Wittmann, Andrea, Joshi, Piyush, Stichel, Damian, Beck, Pengbo, Okonechnikow, Konstantin, Sievers, Philipp, Wefers, Annika K, Roncaroli, Federico, Avula, Shivaram, McCabe, Martin G, Hayden, James T, Wesseling, Pieter, Øra, Ingrid, Nistér, Monica, Kranendonk, Mariëtte EG, Tops, Bastiaan BJ, Zapotocky, Michal, Zamecnik, Josef, Vasiljevic, Alexandre, Fenouil, Tanguy, Meyronet, David, von Hoff, Katja, Schüller, Ulrich, Loiseau, Hugues, Figarella-Branger, Dominique, Kramm, Christof M, Sturm, Dominik, Scheie, David, Rauramaa, Tuomas, Pesola, Jouni, Gojo, Johannes, Haberler, Christine, Brandner, Sebastian, Jacques, Tom, Sexton Oates, Alexandra, Saffery, Richard, Koscielniak, Ewa, Baker, Suzanne J, Yip, Stephen, Snuderl, Matija, Ud Din, Nasir, Samuel, David, Schramm, Kathrin, Blattner-Johnson, Mirjam, Selt, Florian, Ecker, Jonas, Milde, Till, von Deimling, Andreas, Korshunov, Andrey, Perry, Arie, Pfister, Stefan M, Sahm, Felix, Solomon, David A, and Jones, David TW

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Pediatric, Genetics, Rare Diseases, Pediatric Cancer, Cancer, Pediatric Research Initiative, Neurosciences, Brain Cancer, Brain Disorders, Child, Child, Preschool, Female, Humans, Infant, Male, Cell Cycle Proteins, Central Nervous System Neoplasms, DNA Methylation, DNA-Binding Proteins, Neuroectodermal Tumors, Primitive, RNA-Binding Proteins, Transcription Factors, Tumor Suppressor Proteins, Wnt Signaling Pathway, PLAGL1, PLAGL2, Molecular neuro-oncology, Pediatric cancer, Clinical Sciences, Neurology & Neurosurgery
Abstract

Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0-14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal high-level amplification and resultant overexpression of either PLAGL1 or PLAGL2, and an absence of recurrent genetic alterations characteristic of other pediatric CNS tumor types. Both genes act as transcription factors for a regulatory subset of imprinted genes (IGs), components of the Wnt/β-Catenin pathway, and the potential drug targets RET and CYP2W1, which are also specifically overexpressed in this tumor type. A derived PLAGL-specific gene expression signature indicates dysregulation of imprinting control and differentiation/development. These tumors occurred throughout the neuroaxis including the cerebral hemispheres, cerebellum, and brainstem, and were predominantly composed of primitive embryonal-like cells lacking robust expression of markers of glial or neuronal differentiation (e.g., GFAP, OLIG2, and synaptophysin). Tumors with PLAGL1 amplification were typically diagnosed during adolescence (median age 10.5 years), whereas those with PLAGL2 amplification were diagnosed during early childhood (median age 2 years). The 10-year overall survival was 66% for PLAGL1-amplified tumors, 25% for PLAGL2-amplified tumors, 18% for male patients, and 82% for female patients. In summary, we describe a new type of biologically distinct CNS tumor characterized by PLAGL1/2 amplification that occurs predominantly in infants and toddlers (PLAGL2) or adolescents (PLAGL1) which we consider best classified as a CNS embryonal tumor and which is associated with intermediate survival. The cell of origin and optimal treatment strategies remain to be defined.

Published
2023

32. Federated Learning Enables Big Data for Rare Cancer Boundary Detection

Author

Pati, Sarthak, Baid, Ujjwal, Edwards, Brandon, Sheller, Micah, Wang, Shih-Han, Reina, G Anthony, Foley, Patrick, Gruzdev, Alexey, Karkada, Deepthi, Davatzikos, Christos, Sako, Chiharu, Ghodasara, Satyam, Bilello, Michel, Mohan, Suyash, Vollmuth, Philipp, Brugnara, Gianluca, Preetha, Chandrakanth J, Sahm, Felix, Maier-Hein, Klaus, Zenk, Maximilian, Bendszus, Martin, Wick, Wolfgang, Calabrese, Evan, Rudie, Jeffrey, Villanueva-Meyer, Javier, Cha, Soonmee, Ingalhalikar, Madhura, Jadhav, Manali, Pandey, Umang, Saini, Jitender, Garrett, John, Larson, Matthew, Jeraj, Robert, Currie, Stuart, Frood, Russell, Fatania, Kavi, Huang, Raymond Y, Chang, Ken, Balana, Carmen, Capellades, Jaume, Puig, Josep, Trenkler, Johannes, Pichler, Josef, Necker, Georg, Haunschmidt, Andreas, Meckel, Stephan, Shukla, Gaurav, Liem, Spencer, Alexander, Gregory S, Lombardo, Joseph, Palmer, Joshua D, Flanders, Adam E, Dicker, Adam P, Sair, Haris I, Jones, Craig K, Venkataraman, Archana, Jiang, Meirui, So, Tiffany Y, Chen, Cheng, Heng, Pheng Ann, Dou, Qi, Kozubek, Michal, Lux, Filip, Michálek, Jan, Matula, Petr, Keřkovský, Miloš, Kopřivová, Tereza, Dostál, Marek, Vybíhal, Václav, Vogelbaum, Michael A, Mitchell, J Ross, Farinhas, Joaquim, Maldjian, Joseph A, Yogananda, Chandan Ganesh Bangalore, Pinho, Marco C, Reddy, Divya, Holcomb, James, Wagner, Benjamin C, Ellingson, Benjamin M, Cloughesy, Timothy F, Raymond, Catalina, Oughourlian, Talia, Hagiwara, Akifumi, Wang, Chencai, To, Minh-Son, Bhardwaj, Sargam, Chong, Chee, Agzarian, Marc, Falcão, Alexandre Xavier, Martins, Samuel B, Teixeira, Bernardo C A, Sprenger, Flávia, Menotti, David, Lucio, Diego R, LaMontagne, Pamela, Marcus, Daniel, Wiestler, Benedikt, Kofler, Florian, Ezhov, Ivan, Metz, Marie, Jain, Rajan, Lee, Matthew, Lui, Yvonne W, McKinley, Richard, Slotboom, Johannes, Radojewski, Piotr, Meier, Raphael, Wiest, Roland, Murcia, Derrick, Fu, Eric, Haas, Rourke, Thompson, John, Ormond, David Ryan, Badve, Chaitra, Sloan, Andrew E, Vadmal, Vachan, Waite, Kristin, Colen, Rivka R, Pei, Linmin, Ak, Murat, Srinivasan, Ashok, Bapuraj, J Rajiv, Rao, Arvind, Wang, Nicholas, Yoshiaki, Ota, Moritani, Toshio, Turk, Sevcan, Lee, Joonsang, Prabhudesai, Snehal, Morón, Fanny, Mandel, Jacob, Kamnitsas, Konstantinos, Glocker, Ben, Dixon, Luke V M, Williams, Matthew, Zampakis, Peter, Panagiotopoulos, Vasileios, Tsiganos, Panagiotis, Alexiou, Sotiris, Haliassos, Ilias, Zacharaki, Evangelia I, Moustakas, Konstantinos, Kalogeropoulou, Christina, Kardamakis, Dimitrios M, Choi, Yoon Seong, Lee, Seung-Koo, Chang, Jong Hee, Ahn, Sung Soo, Luo, Bing, Poisson, Laila, Wen, Ning, Tiwari, Pallavi, Verma, Ruchika, Bareja, Rohan, Yadav, Ipsa, Chen, Jonathan, Kumar, Neeraj, Smits, Marion, van der Voort, Sebastian R, Alafandi, Ahmed, Incekara, Fatih, Wijnenga, Maarten MJ, Kapsas, Georgios, Gahrmann, Renske, Schouten, Joost W, Dubbink, Hendrikus J, Vincent, Arnaud JPE, Bent, Martin J van den, French, Pim J, Klein, Stefan, Yuan, Yading, Sharma, Sonam, Tseng, Tzu-Chi, Adabi, Saba, Niclou, Simone P, Keunen, Olivier, Hau, Ann-Christin, Vallières, Martin, Fortin, David, Lepage, Martin, Landman, Bennett, Ramadass, Karthik, Xu, Kaiwen, Chotai, Silky, Chambless, Lola B, Mistry, Akshitkumar, Thompson, Reid C, Gusev, Yuriy, Bhuvaneshwar, Krithika, Sayah, Anousheh, Bencheqroun, Camelia, Belouali, Anas, Madhavan, Subha, Booth, Thomas C, Chelliah, Alysha, Modat, Marc, Shuaib, Haris, Dragos, Carmen, Abayazeed, Aly, Kolodziej, Kenneth, Hill, Michael, Abbassy, Ahmed, Gamal, Shady, Mekhaimar, Mahmoud, Qayati, Mohamed, Reyes, Mauricio, Park, Ji Eun, Yun, Jihye, Kim, Ho Sung, Mahajan, Abhishek, Muzi, Mark, Benson, Sean, Beets-Tan, Regina G H, Teuwen, Jonas, Herrera-Trujillo, Alejandro, Trujillo, Maria, Escobar, William, Abello, Ana, Bernal, Jose, Gómez, Jhon, Choi, Joseph, Baek, Stephen, Kim, Yusung, Ismael, Heba, Allen, Bryan, Buatti, John M, Kotrotsou, Aikaterini, Li, Hongwei, Weiss, Tobias, Weller, Michael, Bink, Andrea, Pouymayou, Bertrand, Shaykh, Hassan F, Saltz, Joel, Prasanna, Prateek, Shrestha, Sampurna, Mani, Kartik M, Payne, David, Kurc, Tahsin, Pelaez, Enrique, Franco-Maldonado, Heydy, Loayza, Francis, Quevedo, Sebastian, Guevara, Pamela, Torche, Esteban, Mendoza, Cristobal, Vera, Franco, Ríos, Elvis, López, Eduardo, Velastin, Sergio A, Ogbole, Godwin, Oyekunle, Dotun, Odafe-Oyibotha, Olubunmi, Osobu, Babatunde, Shu'aibu, Mustapha, Dorcas, Adeleye, Soneye, Mayowa, Dako, Farouk, Simpson, Amber L, Hamghalam, Mohammad, Peoples, Jacob J, Hu, Ricky, Tran, Anh, Cutler, Danielle, Moraes, Fabio Y, Boss, Michael A, Gimpel, James, Veettil, Deepak Kattil, Schmidt, Kendall, Bialecki, Brian, Marella, Sailaja, Price, Cynthia, Cimino, Lisa, Apgar, Charles, Shah, Prashant, Menze, Bjoern, Barnholtz-Sloan, Jill S, Martin, Jason, and Bakas, Spyridon

Subjects
Computer Science - Machine Learning, Electrical Engineering and Systems Science - Image and Video Processing
Abstract

Although machine learning (ML) has shown promise in numerous domains, there are concerns about generalizability to out-of-sample data. This is currently addressed by centrally sharing ample, and importantly diverse, data from multiple sites. However, such centralization is challenging to scale (or even not feasible) due to various limitations. Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here we present findings from the largest FL study to-date, involving data from 71 healthcare institutions across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, utilizing the largest dataset of such patients ever used in the literature (25,256 MRI scans from 6,314 patients). We demonstrate a 33% improvement over a publicly trained model to delineate the surgically targetable tumor, and 23% improvement over the tumor's entire extent. We anticipate our study to: 1) enable more studies in healthcare informed by large and diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further quantitative analyses for glioblastoma via performance optimization of our consensus model for eventual public release, and 3) demonstrate the effectiveness of FL at such scale and task complexity as a paradigm shift for multi-site collaborations, alleviating the need for data sharing., Comment: federated learning, deep learning, convolutional neural network, segmentation, brain tumor, glioma, glioblastoma, FeTS, BraTS

Published
2022
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33. Integration of transcriptomics, proteomics and loss-of-function screening reveals WEE1 as a target for combination with dasatinib against proneural glioblastoma

Author

Alhalabi, Obada T., Göttmann, Mona, Gold, Maxwell P., Schlue, Silja, Hielscher, Thomas, Iskar, Murat, Kessler, Tobias, Hai, Ling, Lokumcu, Tolga, Cousins, Clara C., Herold-Mende, Christel, Heßling, Bernd, Horschitz, Sandra, Jabali, Ammar, Koch, Philipp, Baumgartner, Ulrich, Day, Bryan W., Wick, Wolfgang, Sahm, Felix, Krieg, Sandro M., Fraenkel, Ernest, Phillips, Emma, and Goidts, Violaine

Published
2024
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34. Benchmarking whole exome sequencing in the German network for personalized medicine

Author

Menzel, Michael, Martis-Thiele, Mihaela, Goldschmid, Hannah, Ott, Alexander, Romanovsky, Eva, Siemanowski-Hrach, Janna, Seillier, Lancelot, Brüchle, Nadina Ortiz, Maurer, Angela, Lehmann, Kjong-Van, Begemann, Matthias, Elbracht, Miriam, Meyer, Robert, Dintner, Sebastian, Claus, Rainer, Meier-Kolthoff, Jan P., Blanc, Eric, Möbs, Markus, Joosten, Maria, Benary, Manuela, Basitta, Patrick, Hölscher, Florian, Tischler, Verena, Groß, Thomas, Kutz, Oliver, Prause, Rebecca, William, Doreen, Horny, Kai, Goering, Wolfgang, Sivalingam, Sugirthan, Borkhardt, Arndt, Blank, Cornelia, Junk, Stefanie V., Yasin, Layal, Moskalev, Evgeny A., Carta, Maria Giulia, Ferrazzi, Fulvia, Tögel, Lars, Wolter, Steffen, Adam, Eugen, Matysiak, Uta, Rosenthal, Tessa, Dönitz, Jürgen, Lehmann, Ulrich, Schmidt, Gunnar, Bartels, Stephan, Hofmann, Winfried, Hirsch, Steffen, Dikow, Nicola, Göbel, Kirsten, Banan, Rouzbeh, Hamelmann, Stefan, Fink, Annette, Ball, Markus, Neumann, Olaf, Rehker, Jan, Kloth, Michael, Murtagh, Justin, Hartmann, Nils, Jurmeister, Phillip, Mock, Andreas, Kumbrink, Jörg, Jung, Andreas, Mayr, Eva-Maria, Jacob, Anne, Trautmann, Marcel, Kirmse, Santina, Falkenberg, Kim, Ruckert, Christian, Hirsch, Daniela, Immel, Alexander, Dietmaier, Wolfgang, Haack, Tobias, Marienfeld, Ralf, Fürstberger, Axel, Niewöhner, Jakob, Gerstenmaier, Uwe, Eberhardt, Timo, Greif, Philipp A., Appenzeller, Silke, Maurus, Katja, Doll, Julia, Jelting, Yvonne, Jonigk, Danny, Märkl, Bruno, Beule, Dieter, Horst, David, Wulf, Anna-Lena, Aust, Daniela, Werner, Martin, Reuter-Jessen, Kirsten, Ströbel, Philipp, Auber, Bernd, Sahm, Felix, Merkelbach-Bruse, Sabine, Siebolts, Udo, Roth, Wilfried, Lassmann, Silke, Klauschen, Frederick, Gaisa, Nadine T., Weichert, Wilko, Evert, Matthias, Armeanu-Ebinger, Sorin, Ossowski, Stephan, Schroeder, Christopher, Schaaf, Christian P., Malek, Nisar, Schirmacher, Peter, Kazdal, Daniel, Pfarr, Nicole, Budczies, Jan, and Stenzinger, Albrecht

Published
2024
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35. A H3K27M-targeted vaccine in adults with diffuse midline glioma

Author

Grassl, Niklas, Poschke, Isabel, Lindner, Katharina, Bunse, Lukas, Mildenberger, Iris, Boschert, Tamara, Jähne, Kristine, Green, Edward W., Hülsmeyer, Ingrid, Jünger, Simone, Kessler, Tobias, Suwala, Abigail K., Eisele, Philipp, Breckwoldt, Michael O., Vajkoczy, Peter, Grauer, Oliver M., Herrlinger, Ulrich, Tonn, Joerg-Christian, Denk, Monika, Sahm, Felix, Bendszus, Martin, von Deimling, Andreas, Winkler, Frank, Wick, Wolfgang, Platten, Michael, and Sahm, Katharina

Published
2023
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40. Overview of European standard clinical practice recommendations for multidiscplinary teams involved in the treatment of central nervous system tumours in children and adolescents – SIOPE Brain Tumour Group

Author

Otth, Maria, Scheinemann, Katrin, Ajithkumar, Thankamma, Aquilina, Kristian, Avula, Shivaram, Gan, Hoong-Wei, Janssens, Geert O., Lemiere, Jurgen, Morana, Giovanni, Opocher, Enrico, Pfister, Stefan M., Porro, Giorgio, Sahm, Felix, Thomale, Ulrich-Wilhelm, van Egmond-Ebbeling, Michelle, van Santen, Hanneke M., Pizer, Barry, and Rutkowski, Stefan

Published
2024
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41. Concurrent gliomas in patients with multiple sclerosis

Author

Sahm, Katharina, Kessler, Tobias, Eisele, Philipp, Ratliff, Miriam, Sperk, Elena, König, Laila, Breckwoldt, Michael O., Seliger, Corinna, Mildenberger, Iris, Schrimpf, Daniel, Herold-Mende, Christel, Zeiner, Pia S., Tabatabai, Ghazaleh, Meuth, Sven G., Capper, David, Bendszus, Martin, von Deimling, Andreas, Wick, Wolfgang, Sahm, Felix, and Platten, Michael

Published
2023
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43. INTERCEPT H3: a multicenter phase I peptide vaccine trial for the treatment of H3-mutated diffuse midline gliomas

Author

Grassl, Niklas, Sahm, Katharina, Süße, Heike, Poschke, Isabel, Bunse, Lukas, Bunse, Theresa, Boschert, Tamara, Mildenberger, Iris, Rupp, Anne-Kathleen, Ewinger, Max Philipp, Lanz, Lisa-Marie, Denk, Monika, Tabatabai, Ghazaleh, Ronellenfitsch, Michael W., Herrlinger, Ulrich, Glas, Martin, Krex, Dietmar, Vajkoczy, Peter, Wick, Antje, Harting, Inga, Sahm, Felix, von Deimling, Andreas, Bendszus, Martin, Wick, Wolfgang, and Platten, Michael

Published
2023
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45. MAPK inhibitor sensitivity scores predict sensitivity driven by the immune infiltration in pediatric low-grade gliomas

Author

Sigaud, Romain, Albert, Thomas K., Hess, Caroline, Hielscher, Thomas, Winkler, Nadine, Kocher, Daniela, Walter, Carolin, Münter, Daniel, Selt, Florian, Usta, Diren, Ecker, Jonas, Brentrup, Angela, Hasselblatt, Martin, Thomas, Christian, Varghese, Julian, Capper, David, Thomale, Ulrich W., Hernáiz Driever, Pablo, Simon, Michèle, Horn, Svea, Herz, Nina Annika, Koch, Arend, Sahm, Felix, Hamelmann, Stefan, Faria-Andrade, Augusto, Jabado, Nada, Schuhmann, Martin U., Schouten-van Meeteren, Antoinette Y. N., Hoving, Eelco, Brummer, Tilman, van Tilburg, Cornelis M., Pfister, Stefan M., Witt, Olaf, Jones, David T. W., Kerl, Kornelius, and Milde, Till

Published
2023
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46. Pediatric-type high-grade neuroepithelial tumors with CIC gene fusion share a common DNA methylation signature

Author

Sievers, Philipp, Sill, Martin, Schrimpf, Daniel, Abdullaev, Zied, Donson, Andrew M., Lake, Jessica A., Friedel, Dennis, Scheie, David, Tynninen, Olli, Rauramaa, Tuomas, Vepsäläinen, Kaisa L., Samuel, David, Chapman, Rebecca, Grundy, Richard G., Pajtler, Kristian W., Tauziède-Espariat, Arnault, Métais, Alice, Varlet, Pascale, Snuderl, Matija, Jacques, Thomas S., Aldape, Kenneth, Reuss, David E., Korshunov, Andrey, Wick, Wolfgang, Pfister, Stefan M., von Deimling, Andreas, Sahm, Felix, and Jones, David T. W.

Published
2023
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47. Author Correction: Federated learning enables big data for rare cancer boundary detection

Author

Pati, Sarthak, Baid, Ujjwal, Edwards, Brandon, Sheller, Micah, Wang, Shih-Han, Reina, G. Anthony, Foley, Patrick, Gruzdev, Alexey, Karkada, Deepthi, Davatzikos, Christos, Sako, Chiharu, Ghodasara, Satyam, Bilello, Michel, Mohan, Suyash, Vollmuth, Philipp, Brugnara, Gianluca, Preetha, Chandrakanth J., Sahm, Felix, Maier-Hein, Klaus, Zenk, Maximilian, Bendszus, Martin, Wick, Wolfgang, Calabrese, Evan, Rudie, Jeffrey, Villanueva-Meyer, Javier, Cha, Soonmee, Ingalhalikar, Madhura, Jadhav, Manali, Pandey, Umang, Saini, Jitender, Garrett, John, Larson, Matthew, Jeraj, Robert, Currie, Stuart, Frood, Russell, Fatania, Kavi, Huang, Raymond Y., Chang, Ken, Balaña, Carmen, Capellades, Jaume, Puig, Josep, Trenkler, Johannes, Pichler, Josef, Necker, Georg, Haunschmidt, Andreas, Meckel, Stephan, Shukla, Gaurav, Liem, Spencer, Alexander, Gregory S., Lombardo, Joseph, Palmer, Joshua D., Flanders, Adam E., Dicker, Adam P., Sair, Haris I., Jones, Craig K., Venkataraman, Archana, Jiang, Meirui, So, Tiffany Y., Chen, Cheng, Heng, Pheng Ann, Dou, Qi, Kozubek, Michal, Lux, Filip, Michálek, Jan, Matula, Petr, Keřkovský, Miloš, Kopřivová, Tereza, Dostál, Marek, Vybíhal, Václav, Vogelbaum, Michael A., Mitchell, J. Ross, Farinhas, Joaquim, Maldjian, Joseph A., Yogananda, Chandan Ganesh Bangalore, Pinho, Marco C., Reddy, Divya, Holcomb, James, Wagner, Benjamin C., Ellingson, Benjamin M., Cloughesy, Timothy F., Raymond, Catalina, Oughourlian, Talia, Hagiwara, Akifumi, Wang, Chencai, To, Minh-Son, Bhardwaj, Sargam, Chong, Chee, Agzarian, Marc, Falcão, Alexandre Xavier, Martins, Samuel B., Teixeira, Bernardo C. A., Sprenger, Flávia, Menotti, David, Lucio, Diego R., LaMontagne, Pamela, Marcus, Daniel, Wiestler, Benedikt, Kofler, Florian, Ezhov, Ivan, Metz, Marie, Jain, Rajan, Lee, Matthew, Lui, Yvonne W., McKinley, Richard, Slotboom, Johannes, Radojewski, Piotr, Meier, Raphael, Wiest, Roland, Murcia, Derrick, Fu, Eric, Haas, Rourke, Thompson, John, Ormond, David Ryan, Badve, Chaitra, Sloan, Andrew E., Vadmal, Vachan, Waite, Kristin, Colen, Rivka R., Pei, Linmin, Ak, Murat, Srinivasan, Ashok, Bapuraj, J. Rajiv, Rao, Arvind, Wang, Nicholas, Yoshiaki, Ota, Moritani, Toshio, Turk, Sevcan, Lee, Joonsang, Prabhudesai, Snehal, Morón, Fanny, Mandel, Jacob, Kamnitsas, Konstantinos, Glocker, Ben, Dixon, Luke V. M., Williams, Matthew, Zampakis, Peter, Panagiotopoulos, Vasileios, Tsiganos, Panagiotis, Alexiou, Sotiris, Haliassos, Ilias, Zacharaki, Evangelia I., Moustakas, Konstantinos, Kalogeropoulou, Christina, Kardamakis, Dimitrios M., Choi, Yoon Seong, Lee, Seung-Koo, Chang, Jong Hee, Ahn, Sung Soo, Luo, Bing, Poisson, Laila, Wen, Ning, Tiwari, Pallavi, Verma, Ruchika, Bareja, Rohan, Yadav, Ipsa, Chen, Jonathan, Kumar, Neeraj, Smits, Marion, van der Voort, Sebastian R., Alafandi, Ahmed, Incekara, Fatih, Wijnenga, Maarten M. J., Kapsas, Georgios, Gahrmann, Renske, Schouten, Joost W., Dubbink, Hendrikus J., Vincent, Arnaud J. P. E., van den Bent, Martin J., French, Pim J., Klein, Stefan, Yuan, Yading, Sharma, Sonam, Tseng, Tzu-Chi, Adabi, Saba, Niclou, Simone P., Keunen, Olivier, Hau, Ann-Christin, Vallières, Martin, Fortin, David, Lepage, Martin, Landman, Bennett, Ramadass, Karthik, Xu, Kaiwen, Chotai, Silky, Chambless, Lola B., Mistry, Akshitkumar, Thompson, Reid C., Gusev, Yuriy, Bhuvaneshwar, Krithika, Sayah, Anousheh, Bencheqroun, Camelia, Belouali, Anas, Madhavan, Subha, Booth, Thomas C., Chelliah, Alysha, Modat, Marc, Shuaib, Haris, Dragos, Carmen, Abayazeed, Aly, Kolodziej, Kenneth, Hill, Michael, Abbassy, Ahmed, Gamal, Shady, Mekhaimar, Mahmoud, Qayati, Mohamed, Reyes, Mauricio, Park, Ji Eun, Yun, Jihye, Kim, Ho Sung, Mahajan, Abhishek, Muzi, Mark, Benson, Sean, Beets-Tan, Regina G. H., Teuwen, Jonas, Herrera-Trujillo, Alejandro, Trujillo, Maria, Escobar, William, Abello, Ana, Bernal, Jose, Gómez, Jhon, Choi, Joseph, Baek, Stephen, Kim, Yusung, Ismael, Heba, Allen, Bryan, Buatti, John M., Kotrotsou, Aikaterini, Li, Hongwei, Weiss, Tobias, Weller, Michael, Bink, Andrea, Pouymayou, Bertrand, Shaykh, Hassan F., Saltz, Joel, Prasanna, Prateek, Shrestha, Sampurna, Mani, Kartik M., Payne, David, Kurc, Tahsin, Pelaez, Enrique, Franco-Maldonado, Heydy, Loayza, Francis, Quevedo, Sebastian, Guevara, Pamela, Torche, Esteban, Mendoza, Cristobal, Vera, Franco, Ríos, Elvis, López, Eduardo, Velastin, Sergio A., Ogbole, Godwin, Soneye, Mayowa, Oyekunle, Dotun, Odafe-Oyibotha, Olubunmi, Osobu, Babatunde, Shu’aibu, Mustapha, Dorcas, Adeleye, Dako, Farouk, Simpson, Amber L., Hamghalam, Mohammad, Peoples, Jacob J., Hu, Ricky, Tran, Anh, Cutler, Danielle, Moraes, Fabio Y., Boss, Michael A., Gimpel, James, Veettil, Deepak Kattil, Schmidt, Kendall, Bialecki, Brian, Marella, Sailaja, Price, Cynthia, Cimino, Lisa, Apgar, Charles, Shah, Prashant, Menze, Bjoern, Barnholtz-Sloan, Jill S., Martin, Jason, and Bakas, Spyridon

Published
2023
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49. Genomic characterization of DICER1-associated neoplasms uncovers molecular classes

Author

Kommoss, Felix K. F., Chong, Anne-Sophie, Chong, Anne-Laure, Pfaff, Elke, Jones, David T. W., Hiemcke-Jiwa, Laura S., Kester, Lennart A., Flucke, Uta, Gessler, Manfred, Schrimpf, Daniel, Sahm, Felix, Clarke, Blaise A., Stewart, Colin J. R., Wang, Yemin, Gilks, C. Blake, Kommoss, Friedrich, Huntsman, David G., Schüller, Ulrich, Koelsche, Christian, Glenn McCluggage, W., von Deimling, Andreas, and Foulkes, William D.

Published
2023
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50. Development of ‘Core Outcome Sets’ for Meningioma in Clinical Studies (The COSMIC Project): protocol for two systematic literature reviews, eDelphi surveys and online consensus meetings

Author

Millward, Christopher P, Armstrong, Terri S, Barrington, Heather, Bell, Sabrina, Brodbelt, Andrew R, Bulbeck, Helen, Crofton, Anna, Dirven, Linda, Georgious, Theo, Grundy, Paul L, Islim, Abdurrahman I, Javadpour, Mohsen, Keshwara, Sumirat M, Koszdin, Shelli D, Marson, Anthony G, McDermott, Michael W, Meling, Torstein R, Oliver, Kathy, Plaha, Puneet, Preusser, Matthias, Santarius, Thomas, Srikandarajah, Nisaharan, Taphoorn, Martin JB, Turner, Carole, Watts, Colin, Weller, Michael, Williamson, Paula R, Zadeh, Gelareh, Najafabadi, Amir H Zamanipoor, Jenkinson, Michael D, Aldape, Kenneth, Au, Karolyn, Barnhartz-Sloan, Jill, Bi, Wenya Linda, Behling, Felix, Brastianos, Priscilla K, Brodie, Chaya, Butowski, Nicholas, Carlotti, Carlos, Castro, Ana, Cohen-Gadol, Aaron, Couce, Marta, Cusimano, Michael D, DiMeco, Francesco, Drummond, Katharine, Dunn, Ian F, Erker, Craig, Felicella, Michelle, Fountain, Daniel M, Galanis, Evanthia, Galldiks, Norbert, Giannini, Caterina, Goldbrunner, Roland, Griffith, Brent, Hashizume, Rintaro, Hanemann, C Oliver, Herold-Mende, Christel, Hnenny, Luke, Horbinski, Craig, Huang, Raymond Y, James, David, Jungk, Christine, Jungwirth, Gerhard, Kaufmann, Timothy J, Krischek, Boris, Kurz, Sylvia, Lachance, Daniel, Lafougère, Christian, Lamszus, Katrin, Lee, Ian, Liu, Jeff C, Makarenko, Serge, Malta, Tathiana, Mamatjan, Yasin, Mansouri, Alireza, Mawrin, Christian, McDermott, Michael, Moliterno-Gunel, Jennifer, Morokoff, Andrew, Munoz, David, Nassiri, Farshad, Noushmehr, Houtan, Ng, Ho-Keung, Perry, Arie, Pirouzmand, Farhad, Poisson, Laila M, Pollo, Bianca, Ragunathan, Aditya, Raleigh, David, Renovanz, Mirjam, Ricklefs, Franz, Sahm, Felix, Saladino, Andrea, Santacroce, Antonio, Schittenhelm, Jens, and Schichor, Christian

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Neurosciences, Brain Disorders, Clinical Research, Clinical Trials and Supportive Activities, Cancer, Consensus, Delphi Technique, Humans, Meningeal Neoplasms, Meningioma, Research Design, Systematic Reviews as Topic, Treatment Outcome, EORTC BTG, ICOM, EANO, SNO, RANO-PRO, BNOS, SBNS, BIMS, TBTC, International Brain Tumour Alliance, Brainstrust, and Brain Tumour Foundation of Canada, clinical trial, core outcome set, meningioma, Public Health and Health Services, Other Medical and Health Sciences, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

IntroductionMeningioma is the most common primary intracranial tumour in adults. The majority are non-malignant, but a proportion behave more aggressively. Incidental/minimally symptomatic meningioma are often managed by serial imaging. Symptomatic meningioma, those that threaten neurovascular structures, or demonstrate radiological growth, are usually resected as first-line management strategy. For patients in poor clinical condition, or with inoperable, residual or recurrent disease, radiotherapy is often used as primary or adjuvant treatment. Effective pharmacotherapy treatments do not currently exist. There is heterogeneity in the outcomes measured and reported in meningioma clinical studies. Two 'Core Outcome Sets' (COS) will be developed: (COSMIC: Intervention) for use in meningioma clinical effectiveness trials and (COSMIC: Observation) for use in clinical studies of incidental/untreated meningioma.Methods and analysisTwo systematic literature reviews and trial registry searches will identify outcomes measured and reported in published and ongoing (1) meningioma clinical effectiveness trials, and (2) clinical studies of incidental/untreated meningioma. Outcomes include those that are clinician reported, patient reported, caregiver reported and based on objective tests (eg, neurocognitive tests), as well as measures of progression and survival. Outcomes will be deduplicated and categorised to generate two long lists. The two long lists will be prioritised through two, two-round, international, modified eDelphi surveys including patients with meningioma, healthcare professionals, researchers and those in caring/supporting roles. The two final COS will be ratified through two 1-day online consensus meetings, with representation from all stakeholder groups.Ethics and disseminationInstitutional review board (University of Liverpool) approval was obtained for the conduct of this study. Participant eConsent will be obtained prior to participation in the eDelphi surveys and consensus meetings. The two systematic literature reviews and two final COS will be published and freely available.Trial registration numberCOMET study ID 1508.

Published
2022

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