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1. 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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2. 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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3. Glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA): a molecularly distinct brain tumor type with recurrent NTRK gene fusions

Author

Bogumil, Henri, Sill, Martin, Schrimpf, Daniel, Ismer, Britta, Blume, Christina, Rahmanzade, Ramin, Hinz, Felix, Cherkezov, Asan, Banan, Rouzbeh, Friedel, Dennis, Reuss, David E., Selt, Florian, Ecker, Jonas, Milde, Till, Pajtler, Kristian W., Schittenhelm, Jens, Hench, Jürgen, Frank, Stephan, Boldt, Henning B., Kristensen, Bjarne Winther, Scheie, David, Melchior, Linea C., Olesen, Viola, Sehested, Astrid, Boué, Daniel R., Abdullaev, Zied, Satgunaseelan, Laveniya, Kurth, Ina, Seidlitz, Annekatrin, White, Christine L., Ng, Ho-Keung, Shi, Zhi-Feng, Haberler, Christine, Deckert, Martina, Timmer, Marco, Goldbrunner, Roland, Tauziède-Espariat, Arnault, Varlet, Pascale, Brandner, Sebastian, Alexandrescu, Sanda, Snuderl, Matija, Aldape, Kenneth, Korshunov, Andrey, Witt, Olaf, Herold-Mende, Christel, Unterberg, Andreas, Wick, Wolfgang, Pfister, Stefan M., von Deimling, Andreas, Jones, David T. W., Sahm, Felix, and Sievers, Philipp

Published
2023
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4. Glioblastomas with primitive neuronal component harbor a distinct methylation and copy-number profile with inactivation of TP53, PTEN, and RB1

Author

Suwala, Abigail K, Stichel, Damian, Schrimpf, Daniel, Maas, Sybren LN, Sill, Martin, Dohmen, Hildegard, Banan, Rouzbeh, Reinhardt, Annekathrin, Sievers, Philipp, Hinz, Felix, Blattner-Johnson, Mirjam, Hartmann, Christian, Schweizer, Leonille, Boldt, Henning B, Kristensen, Bjarne Winther, Schittenhelm, Jens, Wood, Matthew D, Chotard, Guillaume, Bjergvig, Rolf, Das, Anirban, Tabori, Uri, Hasselblatt, Martin, Korshunov, Andrey, Abdullaev, Zied, Quezado, Martha, Aldape, Kenneth, Harter, Patrick N, Snuderl, Matija, Hench, Jürgen, Frank, Stephan, Acker, Till, Brandner, Sebastian, Winkler, Frank, Wesseling, Pieter, Pfister, Stefan M, Reuss, David E, Wick, Wolfgang, von Deimling, Andreas, Jones, David TW, and Sahm, Felix

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Brain Disorders, Human Genome, Brain Cancer, Neurosciences, Cancer, Rare Diseases, Genetics, 2.1 Biological and endogenous factors, Aetiology, Brain Neoplasms, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 7, Cohort Studies, Cyclin-Dependent Kinase Inhibitor p16, DNA Copy Number Variations, DNA Methylation, Female, Gene Deletion, Glial Fibrillary Acidic Protein, Glioblastoma, Humans, Male, Middle Aged, Neuroectodermal Tumors, Primitive, PTEN Phosphohydrolase, Retinoblastoma Binding Proteins, Tumor Suppressor Protein p53, Ubiquitin-Protein Ligases, GBM, PNET, DNA methylation, Phenotype, Classification, Plasticity, Neurology & Neurosurgery
Abstract

Glioblastoma IDH-wildtype presents with a wide histological spectrum. Some features are so distinctive that they are considered as separate histological variants or patterns for the purpose of classification. However, these usually lack defined (epi-)genetic alterations or profiles correlating with this histology. Here, we describe a molecular subtype with overlap to the unique histological pattern of glioblastoma with primitive neuronal component. Our cohort consists of 63 IDH-wildtype glioblastomas that harbor a characteristic DNA methylation profile. Median age at diagnosis was 59.5 years. Copy-number variations and genetic sequencing revealed frequent alterations in TP53, RB1 and PTEN, with fewer gains of chromosome 7 and homozygous CDKN2A/B deletions than usually described for IDH-wildtype glioblastoma. Gains of chromosome 1 were detected in more than half of the cases. A poorly differentiated phenotype with frequent absence of GFAP expression, high proliferation index and strong staining for p53 and TTF1 often caused misleading histological classification as carcinoma metastasis or primitive neuroectodermal tumor. Clinically, many patients presented with leptomeningeal dissemination and spinal metastasis. Outcome was poor with a median overall survival of only 12 months. Overall, we describe a new molecular subtype of IDH-wildtype glioblastoma with a distinct histological appearance and genetic signature.

Published
2021

5. Rare germline variants in the E-cadherin gene CDH1 are associated with the risk of brain tumors of neuroepithelial and epithelial origin

Author

Förster, Alisa, Brand, Frank, Banan, Rouzbeh, Hüneburg, Robert, Weber, Christine A. M., Ewert, Wiebke, Kronenberg, Jessica, Previti, Christopher, Elyan, Natalie, Beyer, Ulrike, Martens, Helge, Hong, Bujung, Bräsen, Jan H., Erbersdobler, Andreas, Krauss, Joachim K., Stangel, Martin, Samii, Amir, Wolf, Stephan, Preller, Matthias, Aretz, Stefan, Wiese, Bettina, Hartmann, Christian, and Weber, Ruthild G.

Published
2021
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6. Infratentorial IDH-mutant astrocytoma is a distinct subtype

Author

Banan, Rouzbeh, Stichel, Damian, Bleck, Anja, Hong, Bujung, Lehmann, Ulrich, Suwala, Abigail, Reinhardt, Annekathrin, Schrimpf, Daniel, Buslei, Rolf, Stadelmann, Christine, Ehlert, Karoline, Prinz, Marco, Acker, Till, Schittenhelm, Jens, Kaul, David, Schweizer, Leonille, Capper, David, Harter, Patrick N., Etminan, Nima, Jones, David T. W., Pfister, Stefan M., Herold-Mende, Christel, Wick, Wolfgang, Sahm, Felix, von Deimling, Andreas, Hartmann, Christian, and Reuss, David E.

Published
2020
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8. Supplementary Figure S1 from Proinflammatory Macrophage Activation by the Polysialic Acid-Siglec-16 Axis Is Linked to Increased Survival of Patients with Glioblastoma

Author

Thiesler, Hauke, primary, Gretenkort, Lina, primary, Hoffmeister, Leonie, primary, Albers, Iris, primary, Ohlmeier, Luisa, primary, Röckle, Iris, primary, Verhagen, Andrea, primary, Banan, Rouzbeh, primary, Köpcke, Nora, primary, Krönke, Nicole, primary, Feuerhake, Friedrich, primary, Behling, Felix, primary, Barrantes-Freer, Alonso, primary, Mielke, Dorothee, primary, Rohde, Veit, primary, Hong, Bujung, primary, Varki, Ajit, primary, Schwabe, Kerstin, primary, Krauss, Joachim K., primary, Stadelmann, Christine, primary, Hartmann, Christian, primary, and Hildebrandt, Herbert, primary

Published
2023
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9. Supplementary Methods S1 from Proinflammatory Macrophage Activation by the Polysialic Acid-Siglec-16 Axis Is Linked to Increased Survival of Patients with Glioblastoma

Author

Thiesler, Hauke, primary, Gretenkort, Lina, primary, Hoffmeister, Leonie, primary, Albers, Iris, primary, Ohlmeier, Luisa, primary, Röckle, Iris, primary, Verhagen, Andrea, primary, Banan, Rouzbeh, primary, Köpcke, Nora, primary, Krönke, Nicole, primary, Feuerhake, Friedrich, primary, Behling, Felix, primary, Barrantes-Freer, Alonso, primary, Mielke, Dorothee, primary, Rohde, Veit, primary, Hong, Bujung, primary, Varki, Ajit, primary, Schwabe, Kerstin, primary, Krauss, Joachim K., primary, Stadelmann, Christine, primary, Hartmann, Christian, primary, and Hildebrandt, Herbert, primary

Published
2023
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10. Supplementary Tables S1-S14 from Proinflammatory Macrophage Activation by the Polysialic Acid-Siglec-16 Axis Is Linked to Increased Survival of Patients with Glioblastoma

Author

Thiesler, Hauke, primary, Gretenkort, Lina, primary, Hoffmeister, Leonie, primary, Albers, Iris, primary, Ohlmeier, Luisa, primary, Röckle, Iris, primary, Verhagen, Andrea, primary, Banan, Rouzbeh, primary, Köpcke, Nora, primary, Krönke, Nicole, primary, Feuerhake, Friedrich, primary, Behling, Felix, primary, Barrantes-Freer, Alonso, primary, Mielke, Dorothee, primary, Rohde, Veit, primary, Hong, Bujung, primary, Varki, Ajit, primary, Schwabe, Kerstin, primary, Krauss, Joachim K., primary, Stadelmann, Christine, primary, Hartmann, Christian, primary, and Hildebrandt, Herbert, primary

Published
2023
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11. Proinflammatory Macrophage Activation by the Polysialic Acid-Siglec-16 Axis Is Linked to Increased Survival of Patients with Glioblastoma

Author

Thiesler, Hauke, primary, Gretenkort, Lina, additional, Hoffmeister, Leonie, additional, Albers, Iris, additional, Ohlmeier, Luisa, additional, Röckle, Iris, additional, Verhagen, Andrea, additional, Banan, Rouzbeh, additional, Köpcke, Nora, additional, Krönke, Nicole, additional, Feuerhake, Friedrich, additional, Behling, Felix, additional, Barrantes-Freer, Alonso, additional, Mielke, Dorothee, additional, Rohde, Veit, additional, Hong, Bujung, additional, Varki, Ajit, additional, Schwabe, Kerstin, additional, Krauss, Joachim K., additional, Stadelmann, Christine, additional, Hartmann, Christian, additional, and Hildebrandt, Herbert, additional

Published
2023
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12. Data from Proinflammatory Macrophage Activation by the Polysialic Acid-Siglec-16 Axis Is Linked to Increased Survival of Patients with Glioblastoma

Author

Thiesler, Hauke, primary, Gretenkort, Lina, primary, Hoffmeister, Leonie, primary, Albers, Iris, primary, Ohlmeier, Luisa, primary, Röckle, Iris, primary, Verhagen, Andrea, primary, Banan, Rouzbeh, primary, Köpcke, Nora, primary, Krönke, Nicole, primary, Feuerhake, Friedrich, primary, Behling, Felix, primary, Barrantes-Freer, Alonso, primary, Mielke, Dorothee, primary, Rohde, Veit, primary, Hong, Bujung, primary, Varki, Ajit, primary, Schwabe, Kerstin, primary, Krauss, Joachim K., primary, Stadelmann, Christine, primary, Hartmann, Christian, primary, and Hildebrandt, Herbert, primary

Published
2023
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13. Glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA):a molecularly distinct brain tumor type with recurrent NTRK gene fusions

Author

Bogumil, Henri, Sill, Martin, Schrimpf, Daniel, Ismer, Britta, Blume, Christina, Rahmanzade, Ramin, Hinz, Felix, Cherkezov, Asan, Banan, Rouzbeh, Friedel, Dennis, Reuss, David E., Selt, Florian, Ecker, Jonas, Milde, Till, Pajtler, Kristian W., Schittenhelm, Jens, Hench, Jürgen, Frank, Stephan, Boldt, Henning B., Kristensen, Bjarne Winther, Scheie, David, Melchior, Linea C., Olesen, Viola, Sehested, Astrid, Boué, Daniel R., Abdullaev, Zied, Satgunaseelan, Laveniya, Kurth, Ina, Seidlitz, Annekatrin, White, Christine L., Ng, Ho Keung, Shi, Zhi Feng, Haberler, Christine, Deckert, Martina, Timmer, Marco, Goldbrunner, Roland, Tauziède-Espariat, Arnault, Varlet, Pascale, Brandner, Sebastian, Alexandrescu, Sanda, Snuderl, Matija, Aldape, Kenneth, Korshunov, Andrey, Witt, Olaf, Herold-Mende, Christel, Unterberg, Andreas, Wick, Wolfgang, Pfister, Stefan M., von Deimling, Andreas, Jones, David T.W., Sahm, Felix, Sievers, Philipp, Bogumil, Henri, Sill, Martin, Schrimpf, Daniel, Ismer, Britta, Blume, Christina, Rahmanzade, Ramin, Hinz, Felix, Cherkezov, Asan, Banan, Rouzbeh, Friedel, Dennis, Reuss, David E., Selt, Florian, Ecker, Jonas, Milde, Till, Pajtler, Kristian W., Schittenhelm, Jens, Hench, Jürgen, Frank, Stephan, Boldt, Henning B., Kristensen, Bjarne Winther, Scheie, David, Melchior, Linea C., Olesen, Viola, Sehested, Astrid, Boué, Daniel R., Abdullaev, Zied, Satgunaseelan, Laveniya, Kurth, Ina, Seidlitz, Annekatrin, White, Christine L., Ng, Ho Keung, Shi, Zhi Feng, Haberler, Christine, Deckert, Martina, Timmer, Marco, Goldbrunner, Roland, Tauziède-Espariat, Arnault, Varlet, Pascale, Brandner, Sebastian, Alexandrescu, Sanda, Snuderl, Matija, Aldape, Kenneth, Korshunov, Andrey, Witt, Olaf, Herold-Mende, Christel, Unterberg, Andreas, Wick, Wolfgang, Pfister, Stefan M., von Deimling, Andreas, Jones, David T.W., Sahm, Felix, and Sievers, Philipp

Abstract

Glioneuronal tumors are a heterogenous group of CNS neoplasms that can be challenging to accurately diagnose. Molecular methods are highly useful in classifying these tumors—distinguishing precise classes from their histological mimics and identifying previously unrecognized types of tumors. Using an unsupervised visualization approach of DNA methylation data, we identified a novel group of tumors (n = 20) that formed a cluster separate from all established CNS tumor types. Molecular analyses revealed ATRX alterations (in 16/16 cases by DNA sequencing and/or immunohistochemistry) as well as potentially targetable gene fusions involving receptor tyrosine-kinases (RTK; mostly NTRK1-3) in all of these tumors (16/16; 100%). In addition, copy number profiling showed homozygous deletions of CDKN2A/B in 55% of cases. Histological and immunohistochemical investigations revealed glioneuronal tumors with isomorphic, round and often condensed nuclei, perinuclear clearing, high mitotic activity and microvascular proliferation. Tumors were mainly located supratentorially (84%) and occurred in patients with a median age of 19 years. Survival data were limited (n = 18) but point towards a more aggressive biology as compared to other glioneuronal tumors (median progression-free survival 12.5 months). Given their molecular characteristics in addition to anaplastic features, we suggest the term glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA) to describe these tumors. In summary, our findings highlight a novel type of glioneuronal tumor driven by different RTK fusions accompanied by recurrent alterations in ATRX and homozygous deletions of CDKN2A/B. Targeted approaches such as NTRK inhibition might represent a therapeutic option for patients suffering from these tumors.

Published
2023

18. Differences in the MRI Signature and ADC Values of Diffuse Midline Gliomas with H3 K27M Mutation Compared to Midline Glioblastomas

Author

Raab, Peter, primary, Banan, Rouzbeh, additional, Akbarian, Arash, additional, Esmaeilzadeh, Majid, additional, Samii, Madjid, additional, Samii, Amir, additional, Bertalanffy, Helmut, additional, Lehmann, Ulrich, additional, Krauss, Joachim K., additional, Lanfermann, Heinrich, additional, Hartmann, Christian, additional, and Brüning, Roland, additional

Published
2022
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19. Rare germline variants in the tumor suppressor gene CDH1 in glioma families and gastric cancer families with brain tumors

Author

Weber, Ruthild G., primary, Foerster, Alisa, additional, Banan, Rouzbeh, additional, Hueneburg, Robert, additional, Weber, Christine A. M., additional, Ewert, Wiebke, additional, Kronenberg, Jessica, additional, Elyan, Natalie, additional, Beyer, Ulrike, additional, Martens, Helge, additional, Erbersdobler, Andreas, additional, Krauss, Joachim K., additional, Stangel, Martin, additional, Samii, Amir, additional, Wolf, Stephan, additional, Preller, Matthias, additional, Aretz, Stefan, additional, Wiese, Bettina, additional, Hartmann, Christian, additional, and Brand, Frank, additional

Published
2022
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21. Glioblastomas with primitive neuronal component harbor a distinct methylation and copy-number profile with inactivation of TP53, PTEN, and RB1

Author

Suwala, Abigail K., Stichel, Damian, Schrimpf, Daniel, Maas, Sybren L. N., Sill, Martin, Dohmen, Hildegard, Banan, Rouzbeh, Reinhardt, Annekathrin, Sievers, Philipp, Hinz, Felix, Blattner-johnson, Mirjam, Hartmann, Christian, Schweizer, Leonille, Boldt, Henning B., Kristensen, Bjarne Winther, Schittenhelm, Jens, Wood, Matthew D., Chotard, Guillaume, Bjergvig, Rolf, Das, Anirban, Tabori, Uri, Hasselblatt, Martin, Korshunov, Andrey, Abdullaev, Zied, Quezado, Martha, Aldape, Kenneth, Harter, Patrick N., Snuderl, Matija, Hench, Jürgen, Frank, Stephan, Acker, Till, Brandner, Sebastian, Winkler, Frank, Wesseling, Pieter, Pfister, Stefan M., Reuss, David E., Wick, Wolfgang, Von Deimling, Andreas, Jones, David T. W., Sahm, Felix, Suwala, Abigail K., Stichel, Damian, Schrimpf, Daniel, Maas, Sybren L. N., Sill, Martin, Dohmen, Hildegard, Banan, Rouzbeh, Reinhardt, Annekathrin, Sievers, Philipp, Hinz, Felix, Blattner-johnson, Mirjam, Hartmann, Christian, Schweizer, Leonille, Boldt, Henning B., Kristensen, Bjarne Winther, Schittenhelm, Jens, Wood, Matthew D., Chotard, Guillaume, Bjergvig, Rolf, Das, Anirban, Tabori, Uri, Hasselblatt, Martin, Korshunov, Andrey, Abdullaev, Zied, Quezado, Martha, Aldape, Kenneth, Harter, Patrick N., Snuderl, Matija, Hench, Jürgen, Frank, Stephan, Acker, Till, Brandner, Sebastian, Winkler, Frank, Wesseling, Pieter, Pfister, Stefan M., Reuss, David E., Wick, Wolfgang, Von Deimling, Andreas, Jones, David T. W., and Sahm, Felix

Abstract

Glioblastoma IDH-wildtype presents with a wide histological spectrum. Some features are so distinctive that they are considered as separate histological variants or patterns for the purpose of classification. However, these usually lack defined (epi-)genetic alterations or profiles correlating with this histology. Here, we describe a molecular subtype with overlap to the unique histological pattern of glioblastoma with primitive neuronal component. Our cohort consists of 63 IDH-wildtype glioblastomas that harbor a characteristic DNA methylation profile. Median age at diagnosis was 59.5 years. Copy-number variations and genetic sequencing revealed frequent alterations in TP53, RB1 and PTEN, with fewer gains of chromosome 7 and homozygous CDKN2A/B deletions than usually described for IDH-wildtype glioblastoma. Gains of chromosome 1 were detected in more than half of the cases. A poorly differentiated phenotype with frequent absence of GFAP expression, high proliferation index and strong staining for p53 and TTF1 often caused misleading histological classification as carcinoma metastasis or primitive neuroectodermal tumor. Clinically, many patients presented with leptomeningeal dissemination and spinal metastasis. Outcome was poor with a median overall survival of only 12 months. Overall, we describe a new molecular subtype of IDH-wildtype glioblastoma with a distinct histological appearance and genetic signature.

Published
2021

26. Incorporating Supramaximal Resection into Survival Stratification of IDH-Wildtype Glioblastoma: A Refined Multi-institutional Recursive Partitioning Analysis.

Author

Park YW, Choi KS, Foltyn-Dumitru M, Brugnara G, Banan R, Kim S, Han K, Park JE, Kessler T, Bendszus M, Krieg S, Wick W, Sahm F, Choi SH, Kim HS, Chang JH, Kim SH, Wongsawaeng D, Pollock JM, Lee SK, Barajas RF, Vollmuth P, and Ahn SS

Abstract

Purpose: To propose a novel recursive partitioning analysis (RPA) classification model in patients with IDH-wildtype glioblastomas that incorporates the recently expanded conception of the extent of resection (EOR) in terms of both supramaximal and total resections., Experimental Design: This multicenter cohort study included a developmental cohort of 622 patients with IDH-wildtype glioblastomas from a single institution (Severance Hospital) and validation cohorts of 536 patients from three institutions (Seoul National University Hospital, Asan Medical Center, and Heidelberg University Hospital). All patients completed standard treatment including concurrent chemoradiotherapy and underwent testing to determine their IDH mutation and MGMTp methylation status. EORs were categorized into either supramaximal, total, or non-total resections. A novel RPA model was then developed and compared to a previous RTOG RPA model., Results: In the developmental cohort, the RPA model included age, MGMTp methylation status, KPS, and EOR. Younger patients with MGMTp methylation and supramaximal resections showed a more favorable prognosis (class I: median overall survival [OS] 57.3 months), while low-performing patients with non-total resections and without MGMTp methylation showed the worst prognosis (class IV: median OS 14.3 months). The prognostic significance of the RPA was subsequently confirmed in the validation cohorts, which revealed a greater separation between prognostic classes for all cohorts compared to the previous RTOG RPA model., Conclusions: The proposed RPA model highlights the impact of supramaximal versus total resections and incorporates clinical and molecular factors into survival stratification. The RPA model may improve the accuracy of assessing prognostic groups.

Published
2024
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