101 results on '"Pietsch, T."'
Search Results
2. Gliosarcoma with extensive extracranial metastatic spread and familial coincidence: A case report
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Friker, L.L., primary, Tzaridis, T., additional, Enkirch, S.J., additional, Lüders, C., additional, Hattingen, E., additional, Kristiansen, G., additional, Goschzik, T., additional, Waha, A., additional, Lütter, C., additional, Weller, J., additional, Herrlinger, U., additional, Pietsch, T., additional, Gessi, M., additional, Baumert, B.G., additional, and Gielen, G.H., additional
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- 2023
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3. Gender and the invisibility of care on Wikipedia
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Ford, H, Pietsch, T, Tall, K, Ford, H, Pietsch, T, and Tall, K
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Digital platforms produce bias and inequality that have a significant impact on peoples’ sense of self, agency and life chances. Wikipedia has largely evaded the criticism of other algorithmic systems like Google search and training databases like ImageNet, but Wikipedia is a critical source of representation in our current era – not only because it is one of the world's most popular websites, but because its data are being used as training data for the AI systems that are increasingly used for decision-making. We conducted an analysis of Wikipedia biographies in a national context, comparing the temporality and subjects of notability between English Wikipedia and the Australian Honours system in order to understand Wikipedia's unique role in the production of notability over the site's 20-year history. Framing Wikipedia as an active producer (rather than a reflection) of notability, we demonstrate that women are more likely to be awarded a Wikipedia page after the award announcements or not at all if their contribution is for labour relating to the caring professions than if their service is for sports, arts and films, politics or the judiciary. We argue that Wikipedia's inability to recognise gendered care work as noteworthy is mirrored in its own practices.
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- 2023
4. Placing Darlinghurst
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Clark, A, Pietsch, T, Kemmis, G, Clark, A, Pietsch, T, and Kemmis, G
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My Darlinghurst profiles this colourful neighbourhood, revealing the stories of its migrant and Indigenous residents, the razor gangs and brothels, the soldiers and wharfies, and the artists and LGBTQIA+ communities who have made - and ...
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- 2023
5. Underworlds, Everyday Offending and Darlinghurst
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Clark, A, Kemmis, G, Pietsch, T, Piper, A, Clark, A, Kemmis, G, Pietsch, T, and Piper, A
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- 2023
6. The Floating University Experience, Empire, and the Politics of Knowledge
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Pietsch, T and Pietsch, T
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In 1926, New York University professor James E. Lough—an educational reformer with big dreams—embarked on a bold experiment he called the Floating University. Lough believed that taking five hundred American college students around the globe by ship would not only make them better citizens of the world but would demonstrate a model for responsible and productive education amid the unprecedented dangers, new technologies, and social upheavals of the post–World War I world. But the Floating University’s maiden voyage was also its last: when the ship and its passengers returned home, the project was branded a failure—the antics of students in hotel bars and port city back alleys that received worldwide press coverage were judged incompatible with educational attainment, and Lough was fired and even put under investigation by the State Department. In her new book, Tamson Pietsch excavates a rich and meaningful picture of Lough’s grand ambition, its origins, and how it reveals an early-twentieth-century America increasingly defined both by its imperialism and the professionalization of its higher education system. As Pietsch argues, this voyage—powered by an internationalist worldview—traced the expanding tentacles of US power, even as it tried to model a new kind of experiential education. She shows that this apparent educational failure actually exposes a much larger contest over what kind of knowledge should underpin university authority, one in which direct personal experience came into conflict with academic expertise. After a journey that included stops at nearly fifty international ports and visits with figures ranging from Mussolini to Gandhi, what the students aboard the Floating University brought home was not so much knowledge of the greater world as a demonstration of their nation’s rapidly growing imperial power.
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- 2023
7. Histories of Australian Democracy
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Pietsch, T, Bongiorno, F, Clark, A, Flanagan, F, Rubenstein, K, Schultz, J, Wallace, C, Pietsch, T, Bongiorno, F, Clark, A, Flanagan, F, Rubenstein, K, Schultz, J, and Wallace, C
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Research Report for Dept. Home Affairs
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- 2023
8. What we wore then: Dressing for the streets of gay and queer Darlinghurst
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Clark, A, Pietsch, T, Kemmis, G, McNeil, P, Clark, A, Pietsch, T, Kemmis, G, and McNeil, P
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264 study of Darlinghurst
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- 2023
9. Curating Empowerment
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Puis, Du, Getman, J., Green, R., Hesselbein, D., Christopher, Lorenz, Pietsch, T., and Xepolas, L
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- 2023
10. Universities, their publics, and climate change
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Pietsch, T, Horne, J, and Thomas, MAM
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A conversation about public good Dr Julia Horne, Dr Matthew A.M. Thomas. underpinning the social contract, or settlement, between knowledge institutions, publics and the state. John Dewey was not, of course, an advocate of classical ...
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- 2022
11. JS04.4.A Beyond β-catenin: Genetic alterations ofTP53 andOTX2 and older age indicate increased risk of relapse in WNT medulloblastomas
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Goschzik, T, primary, Mynarek, M, additional, Doerner, E, additional, Spier, I, additional, Warmuth-Metz, M, additional, Bison, B, additional, Obrecht, D, additional, Struve, N, additional, Kortmann, R, additional, Hau, P, additional, Aretz, S, additional, Rutkowski, S, additional, and Pietsch, T, additional
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- 2022
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12. The history of knowledge and the history of education
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Barnes, J, Pietsch, T, Barnes, J, and Pietsch, T
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Purpose: The purpose of this article is to introduce the themed section of History of Education Review on “The History of Knowledge and the History of Education”, comprising four empirical articles that together seek to bring the history of education into fuller dialogue with the approaches and methods of the nascent field of the history of knowledge. Design/methodology/approach: This introductory article provides a broad overview of the history of knowledge for the benefit of historians of education, introduces the four themed section articles that follow, and draws out some of their overarching themes and concepts. Findings: The history of knowledge concept of “arenas of knowledge” emerges as generative across the themed section. Authors also engage with problems of the legitimacy of knowledges, and with pedagogy as practice. In addition, focusing on colonial and postcolonial contexts raises reflexive questions about history of knowledge approaches that have so far largely been developed in European and North American scholarship. Originality/value: The history of education has not previously been strongly represented among the fields that have gone into the formation of the history of knowledge as a synthetic, interdisciplinary approach to historical studies. Nor have historians of education much engaged with its distinguishing concepts and methodologies. The themed section also extends the history of knowledge itself through its strong focus on colonial and postcolonial histories.
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- 2022
13. Universities, their publics, and climate change
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Horne, J, Thomas, MAM, Pietsch, T, Horne, J, Thomas, MAM, and Pietsch, T
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A conversation about public good Dr Julia Horne, Dr Matthew A.M. Thomas. underpinning the social contract, or settlement, between knowledge institutions, publics and the state. John Dewey was not, of course, an advocate of classical ...
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- 2022
14. Genetic landscape of large cell/anaplastic medulloblastoma – more than one disease
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Krause, K, additional, Goschzik, T, additional, Dörner, E, additional, and Pietsch, T, additional
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- 2022
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15. Identification of RBMS1 in the amplified region 2q24 as a major driver of cellular growth in childhood hepatoblastoma
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Rodemann, M, additional, Dreschmann, V, additional, Dörner, E, additional, von Schweinitz, D, additional, Vokuhl, C, additional, and Pietsch, T, additional
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- 2022
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16. 508MO Spatial remodeling of the immune tumor microenvironment after radiotherapy and CXCL12 inhibition in glioblastoma in the phase I/II GLORIA trial
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Leonardelli, S., Layer, J.P., Friker, L.L., Turiello, R., van der Voort, G., Corvino, D., Schaub, C., Müller, W., Sperk, E., Schmeel, L.C., Sahm, K., Kebir, S., Hambsch, P., Pietsch, T., Thurley, K., Glas, M., Seidel, C., Herrlinger, U., Giordano, F.A., and Hölzel, M.
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- 2023
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17. Nachweis von BRAF-Mutationen in niedriggradigen Astrozytomen
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Janzarik, WG, Olbrich, H, Pfister, S, Gnekow, A, Pietsch, T, Roggendorf, W, Scheurlen, W, Kratz, C, and Omran, H
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- 2024
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18. Epigenetische Inaktivierung des Tumor-Suppressor Kandidatengens PROX1 beim sporadischen Mammakarzinom
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Versmold, B, Waha, A, Felsberg, J, Pietsch, T, Mallmann, P, and Schmutzler, RK
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- 2024
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19. Glioblastoma centre and periphery: two aspects of the same disease
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Glas, M, Rath, BH, Simon, M, Reinartz, R, Trageser, D, Leinhaas, A, Eisenreich, R, Steinfarz, B, Pietsch, T, Steindler, DA, Schramm, J, Brüstle, O, Herrlinger, U, and Scheffler, B
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- 2024
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20. Neoadjuvante Chemotherapie mit Temozolomid und 13-cis Retinsäure in der Therapie von Patienten mit anaplastischen astrozytären und oligoastrozytären Tumoren (WHO Grad III) – eine Phase-II-Studie
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Grauer, O, Hartmann, C, Proescholdt, M, Pascher, C, Hirschmann, B, Brawanski, A, Pietsch, T, Bogdahn, U, and Hau, P
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- 2024
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21. Epigenetic silencing of the candidate tumor suppressor gene PROX1 in sporadic breast cancer
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Versmold, B, Waha, A, Felsberg, J, Köhler, J, Ehrentraut, D, Pietsch, T, and Schmutzler, RK
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- 2024
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22. LETTERS.
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Betts, Reginald Dwayne, Haslett, Tobi, and Pietsch, T. W.
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- WIDEMAN, John Edgar, 1941-, SEA Trilogy: Under the Sea-Wind, The Sea Around Us, The Edge of the Sea, The (Book)
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- 2023
23. 445MO Dual inhibition of post-radiogenic angio-vasculogenesis in glioblastoma: Results of the phase I/II GLORIA trial.
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Giordano, F.A., Layer, J.P., Friker, L.L., Turiello, R., Zeyen, T., Pregler, B., Mirallas, O., Kebir, S., Renovanz, M., Hambsch, P., Pietsch, T., Gkika, E., Platten, M., Schneider, M., Grauer, O., Tabatabai, G., Glas, M., Seidel, C., Herrlinger, U., and Hölzel, M.
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GLIOBLASTOMA multiforme - Published
- 2024
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24. A0539 - Preclinical evidence for the use of anti-TROP-2 antibody-drug conjugate Sacituzumab govitecan in cerebral metastasized castration-resistant prostate cancer.
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Weiten, R., Niemann, M., Below, E., Friker, L.L., Ralser, D.J., Toma, M., Kristiansen, G., Hahn, O., Zechel, S., Grünwald, V., Bald, T., Siewert, J., Pietsch, T., Ritter, M., Hölzel, M., Eckstein, M., Alajati, A., Krausewitz, P., and Klümper, N.
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CASTRATION-resistant prostate cancer , *ANTIBODY-drug conjugates - Published
- 2024
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25. Treatment response as surrogate to predict risk for disease progression in pediatric medulloblastoma with persistent magnetic resonance imaging lesions after first-line treatment.
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Obrecht-Sturm D, Schömig L, Mynarek M, Bison B, Schwarz R, Pietsch T, Pfister SM, Sill M, Sturm D, Sahm F, Kortmann RD, Gerber NU, von Bueren AO, Fleischhack G, Schüller U, Nussbaumer G, Benesch M, and Rutkowski S
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- Humans, Male, Child, Female, Child, Preschool, Adolescent, Follow-Up Studies, Prognosis, Retrospective Studies, Survival Rate, Infant, Neoplasm, Residual diagnostic imaging, Neoplasm, Residual pathology, Medulloblastoma diagnostic imaging, Medulloblastoma pathology, Magnetic Resonance Imaging methods, Cerebellar Neoplasms diagnostic imaging, Cerebellar Neoplasms pathology, Disease Progression
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Background: This study aims at clarifying the impact of persistent residual lesions following first-line treatment for pediatric medulloblastoma., Methods: Data on 84 pediatric patients with medulloblastoma and persistent residual lesions on centrally reviewed magnetic resonance imaging (MRI) at the end of first-line therapy were analyzed., Results: Twenty patients (23.8%) had residual lesions in the tumor bed (R+/M0), 51 (60.7%) had distant lesions (R0/M+) and 13 (15.5%) had both (R+/M+). Overall response to first-line therapy was minor or partial (≥ 25% reduction, minor response [MR]/PR) for 64 (76.2%) and stable disease (SD) for 20 patients (23.8%). Five-year post-primary-treatment progression-free (pptPFS) and overall survival (pptOS) were superior after MR/PR (pptPFS: 62.5 ± 7.0%[MR/PR] vs. 35.9 ± 12.8%[SD], P = .03; pptOS: 79.7 ± 5.9[MR/PR] vs. 55.5 ± 13.9[SD], P = .04). Furthermore, R+/M + was associated with a higher risk for progression (5-year pptPFS: 22.9 ± 17.9%[R+, M+] vs. 72.4 ± 12.0%[R+, M0]; P = .03). Watch-and-wait was pursued in 58 patients, while n = 26 received additional treatments (chemotherapy only, n = 19; surgery only, n = 2; combined, n = 3; valproic acid, n = 2), and their outcomes were not superior to watch-and-wait (5-year pptPFS: 58.5 ± 7.7% vs. 51.6 ± 10.7% P = .71; 5-year pptOS: 76.3 ± 6.9% vs. 69.8 ± 9.7%, P = .74). For the whole cohort, 5-year pptPFS by molecular subgroup (58 cases) were WNT: 100%, SHH: 50.0 ± 35.4%, group-4, 52.5 ± 10.5, group-3 54.2 ± 13.8%; (P = .08)., Conclusions: Overall response and extent of lesions can function as surrogate parameters to predict outcomes in pediatric MB patients with persistent lesions after first-line therapy. Especially in the case of solitary persistent medulloblastoma MRI lesions, additional therapy was not beneficial. Therefore, treatment response, extent/kind of residual lesions and further diagnostic information need consideration for indication of additional treatments for persisting lesions., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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26. Gliomatosis cerebri in children: A poor prognostic phenotype of diffuse gliomas with a distinct molecular profile.
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Nussbaumer G, Benesch M, Grabovska Y, Mackay A, Castel D, Grill J, Alonso MM, Antonelli M, Bailey S, Baugh JN, Biassoni V, Blattner-Johnson M, Broniscer A, Carai A, Colafati GS, Colditz N, Corbacioglu S, Crampsie S, Entz-Werle N, Eyrich M, Friker LL, Frühwald MC, Garrè ML, Gerber NU, Giangaspero F, Gil-da-Costa MJ, Graf N, Hargrave D, Hauser P, Herrlinger U, Hoffmann M, Hulleman E, Izquierdo E, Jacobs S, Karremann M, Kattamis A, Kebudi R, Kortmann RD, Kwiecien R, Massimino M, Mastronuzzi A, Miele E, Morana G, Noack CM, Pentikainen V, Perwein T, Pfister SM, Pietsch T, Roka K, Rossi S, Rutkowski S, Schiavello E, Seidel C, Štěrba J, Sturm D, Sumerauer D, Tacke A, Temelso S, Valentini C, van Vuurden D, Varlet P, Veldhuijzen van Zanten SEM, Vinci M, von Bueren AO, Warmuth-Metz M, Wesseling P, Wiese M, Wolff JEA, Zamecnik J, Morales La Madrid A, Bison B, Gielen GH, Jones DTW, Jones C, and Kramm CM
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- Humans, Child, Male, Female, Adolescent, Retrospective Studies, Prognosis, Child, Preschool, Phenotype, Survival Rate, DNA Methylation, Infant, Biomarkers, Tumor genetics, Mutation, Follow-Up Studies, Neoplasm Grading, Neoplasms, Neuroepithelial pathology, Neoplasms, Neuroepithelial genetics, Brain Neoplasms genetics, Brain Neoplasms pathology, Glioma genetics, Glioma pathology
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Background: The term gliomatosis cerebri (GC), a radiology-defined highly infiltrating diffuse glioma, has been abandoned since molecular GC-associated features could not be established., Methods: We conducted a multinational retrospective study of 104 children and adolescents with GC providing comprehensive clinical and (epi-)genetic characterization., Results: Median overall survival (OS) was 15.5 months (interquartile range, 10.9-27.7) with a 2-year survival rate of 28%. Histopathological grading correlated significantly with median OS: CNS WHO grade II: 47.8 months (25.2-55.7); grade III: 15.9 months (11.4-26.3); grade IV: 10.4 months (8.8-14.4). By DNA methylation profiling (n = 49), most tumors were classified as pediatric-type diffuse high-grade glioma (pedHGG), H3-/IDH-wild-type (n = 31/49, 63.3%) with enriched subclasses pedHGG_RTK2 (n = 19), pedHGG_A/B (n = 6), and pedHGG_MYCN (n = 5), but only one pedHGG_RTK1 case. Within the pedHGG, H3-/IDH-wild-type subgroup, recurrent alterations in EGFR (n = 10) and BCOR (n = 9) were identified. Additionally, we observed structural aberrations in chromosome 6 in 16/49 tumors (32.7%) across tumor types. In the pedHGG, H3-/IDH-wild-type subgroup TP53 alterations had a significant negative effect on OS., Conclusions: Contrary to previous studies, our representative pediatric GC study provides evidence that GC has a strong predilection to arise on the background of specific molecular features (especially pedHGG_RTK2, pedHGG_A/B, EGFR and BCOR mutations, chromosome 6 rearrangements)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)
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- 2024
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27. Distinct relapse pattern across molecular ependymoma types.
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Obrecht-Sturm D, Schoof M, Eckhardt A, Mynarek M, Gilbert MR, Aldape K, Armstrong TS, Ramaswamy V, Bockmayr M, von Hoff K, Fleischhack G, Adolph JE, Tippelt S, Pfister SM, Pajtler K, Sturm D, Drexler R, Ricklefs FL, Stepien N, Gojo J, Pietsch T, Warmuth-Metz M, Kortmann R, Timmermann B, Haberler C, Rutkowski S, and Schüller U
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Background: Ependymoma (EPN) is not a uniform disease but represents different disease types with biological and clinical heterogeneity. However, the pattern of when and where different types of EPN relapse is not yet comprehensively described., Methods: We assembled 269 relapsed intracranial EPN from pediatric (n=233) and adult (n=36) patients from European and Northern American cohorts and correlated DNA methylation patterns and copy-number alterations with clinical information., Results: The cohort comprised the following molecular EPN types: PF-EPN-A (n=177), ST-EPN-ZFTA (n=45), PF-EPN-B (n=31), PF-EPN-SE (n=12), and ST-EPN-YAP (n=4). First relapses of PF-EPN-B (PF: posterior-fossa) and PF-EPN-SE (SE: subependymoma) occurred later than of PF-EPN-A, ST-EPN-YAP (ST: supratentorial), or ST-EPN-ZFTA (median time to relapse: 4.3 and 6.0 years vs. 1.9/1.0/2.4 years; p<0.01). Metastatic or combined recurrences in PF-EPN-B and -A more often involved the spinal cord than in ST-EPN-ZFTA (72.7% and 40.0 vs. 12.5%; p<0.01). No distant relapses were observed in ST-EPN-YAP (n=4) or PF-EPN-SE (n=12). Post-relapse survival (PRS) was poor for PF-EPN-A and ST-EPN-ZFTA (5-year PRS: 44.5±4.4/47.8±9.1%), whereas PF-EPN-B and PF-EPN-SE displayed a 5-year PRS of 89.5±7.1/90.0±9.5% (p=0.03). However, 10-year PRS for PF-EPN-B dropped to 45.8±17.3%. Neither between radiation field and relapse pattern nor between radiation field and spinal involvement at relapse an impact was identified. Notably, all patients with relapsed ST-EPN-YAP did not receive upfront radiotherapy, but were successfully salvaged using irradiation at relapse., Conclusions: Relapse patterns of specific EPN types are different. Future clinical trials, treatment adaptions, duration of surveillance and diagnostics should be planned incorporating entity-specific relapse information., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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28. Melanoma Brain Metastases Patient-Derived Organoids: An In Vitro Platform for Drug Screening.
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Abedellatif SE, Hosni R, Waha A, Gielen GH, Banat M, Hamed M, Güresir E, Fröhlich A, Sirokay J, Wulf AL, Kristiansen G, Pietsch T, Vatter H, Hölzel M, Schneider M, and Toma MI
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Background and Aims: Brain metastases are prevalent in the late stages of malignant melanoma. Multimodal therapy remains challenging. Patient-derived organoids (PDOs) represent a valuable pre-clinical model, faithfully recapitulating key aspects of the original tumor, including the heterogeneity and the mutational status. This study aimed to establish PDOs from melanoma brain metastases (MBM-PDOs) and to test the feasibility of using them as a model for in vitro targeted-therapy drug testing., Methods: Surgical resection samples from eight patients with melanoma brain metastases were used to establish MBM-PDOs. The samples were enzymatically dissociated followed by seeding into low-attachment plates to generate floating organoids. The MBM-PDOs were characterized genetically, histologically, and immunohistologically and compared with the parental tissue. The MBM-PDO cultures were exposed to dabrafenib ( BRAF inhibitor) and trametinib ( MEK inhibitor) followed by a cell viability assessment., Results: Seven out of eight cases were successfully cultivated, maintaining the histological, immunohistological phenotype, and the mutational status of the parental tumors. Five out of seven cases harbored BRAF V600E mutations and were responsive to BRAF and MEK inhibitors in vitro. Two out of seven cases were BRAF wild type: one case harboring an NRAS mutation and the other harboring a KIT mutation, and both were resistant to BRAF and MEK inhibitor therapy., Conclusions: We successfully established PDOs from melanoma brain metastases surgical specimens, which exhibited a consistent histological and mutational profile with the parental tissue. Using FDA-approved BRAF and MEK inhibitors, our data demonstrate the feasibility of employing MBM-PDOs for targeted-therapy in vitro testing.
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- 2024
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29. Comparison of mixotrophic and heterotrophic chrysomonads of similar size regarding bacterivory and growth rate.
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Pietsch T and Arndt H
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- Species Specificity, Heterotrophic Processes, Phylogeny, Chrysophyta physiology, Chrysophyta growth & development
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Small chrysomonads are important bacterivores in aquatic ecosystems with a high molecular diversity compared to low morphological differences observed by light microscopy. The high diversity of these morphologically almost indistinguishable species leads to the question to which extent their functional role in ecosystems differs and how their ecological traits can be defined. The present study investigates the prey size and population growth rate of different chrysomonad species. Eleven phylogenetically well-defined strains representing seven strains of heterotrophic and four strains of mixotrophic chrysomonads were compared. All investigated strains belonged to the same functional group of bacterivorous flagellates, feeding on the same bacteria size range, while population growth rates of chrysomonads depended on nutritional strategy and species-specific differences. We observed a high individual variability of growth rates within a population. Our results point to the necessity to consider not only differences in ecological traits among species but also among specimens within a population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)
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- 2024
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30. Imaging in malignant germ cell tumors involving the hypothalamo-neurohypophyseal axis: the evaluation of the posterior pituitary bright spot is essential.
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Stock A, Calaminus G, Weisthoff M, Serfling J, Pietsch T, Bison B, Pham M, and Warmuth-Metz M
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- Humans, Male, Female, Child, Adolescent, Child, Preschool, Adult, Pituitary Neoplasms diagnostic imaging, Pituitary Neoplasms pathology, Hypothalamo-Hypophyseal System diagnostic imaging, Pituitary Gland, Posterior diagnostic imaging, Pituitary Gland, Posterior pathology, Retrospective Studies, Neoplasms, Germ Cell and Embryonal diagnostic imaging, Neoplasms, Germ Cell and Embryonal pathology, Magnetic Resonance Imaging methods
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Purpose: Malignant intracranial germ cell tumors (GCTs) are rare diseases in Western countries. They arise in midline structures and diagnosis is often delayed. We evaluated imaging characteristics and early tumor signs of suprasellar and bifocal GCT on MRI., Methods: Patients with the diagnosis of a germinoma or non-germinomatous GCT (NGGCT) who received non-contrast sagittal T1WI on MRI pre-therapy were included. Loss of the posterior pituitary bright spot (PPBS), the expansion and size of the tumor, and the expansion and infiltration of surrounding structures were evaluated. Group comparison for histologies and localizations was performed., Results: A total of 102 GCT patients (median age at diagnosis 12.3 years, range 4.4-33.8; 57 males; 67 in suprasellar localization) were enrolled in the study. In the suprasellar cohort, NGGCTs (n = 20) were noticeably larger than germinomas (n = 47; p < .001). Each tumor showed involvement of the posterior lobe or pituitary stalk. A PPBS loss (total n = 98) was observed for each localization and entity in more than 90% and was related to diabetes insipidus. Osseous infiltration was observed exclusively in suprasellar GCT (significantly more frequent in NGGCT; p = .004). Time between the first MRI and therapy start was significantly longer in the suprasellar cohort (p = .005), with an even greater delay in germinoma compared to NGGCT (p = .002). The longest interval to treatment had circumscribed suprasellar germinomas (median 312 days)., Conclusion: A loss of the PPBS is a hint of tumor origin revealing small tumors in the neurohypophysis. Using this sign in children with diabetes insipidus avoids a delay in diagnosis., (© 2024. The Author(s).)
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- 2024
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31. Radiation Therapy Plays an Important Role in the Treatment of Atypical Teratoid/Rhabdoid Tumors: Analysis of the EU-RHAB Cohorts and Their Precursors.
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Frisch S, Libuschewski H, Peters S, Gerß J, von Hoff K, Kortmann RD, Nemes K, Rutkowski S, Hasselblatt M, Pietsch T, Frühwald MC, and Timmermann B
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- Humans, Male, Female, Child, Preschool, Infant, Retrospective Studies, Child, Adolescent, Europe, Young Adult, Adult, Infant, Newborn, Prognosis, Registries, Proportional Hazards Models, Rhabdoid Tumor radiotherapy, Rhabdoid Tumor mortality, Teratoma radiotherapy, Teratoma mortality, Progression-Free Survival
- Abstract
Purpose: Atypical teratoid/rhabdoid tumor (AT/RT) is a rare malignancy of the central nervous system in young children with a dismal prognosis. Prognostic markers have been extensively investigated but have not been validated. The role of radiation therapy (RT) remains controversial. We evaluated the impact of RT as part of multimodality treatment by analyzing data of a European AT/RT cohort., Methods and Materials: We retrospectively analyzed data of the European Registry for Rhabdoid Tumors and its precursors. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Potential impact of prognostic factors was analyzed using univariable and multivariable Cox regression analyses with RT as a time-dependent factor., Results: Data of 186 children (118 male, 68 female) treated from 1990 to 2016 were evaluable. The median age at diagnosis was 1.57 years (range, 0.01-26.70 years); 47% (87/186) of the patients were under the age of 18 months. Sixty-nine percent (128/186) received RT (focal RT, n = 93; craniospinal treatment with local boost, n = 34; spinal irradiation, n = 1). The median follow-up duration of the entire cohort was 1.73 years (range, 0.06-20.11 years). The estimated PFS and OS rates were 48% (95% CI, 41%-55%) and 72% (95% CI, 65%-78%) at 1 year and 33% (95% CI, 26%-40%) and 49% (95% CI, 41%-56%) at 2 years, respectively. On multivariable analysis, RT was an independent significant prognostic factor for PFS (hazard ratio, 0.45; 95% CI, 0.27-0.75; P = .002) and OS (hazard ratio, 0.54; 95% CI, 0.32-0.93; P = .025)., Conclusions: This analysis confirms the relevance of local therapies. RT was an independent prognostic factor for outcomes in children experiencing AT/RT. However, long-term sequelae have to be carefully evaluated and considered given the young age at time of RT., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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32. Medulloblastoma in children with Fanconi anemia: Association with FA-D1/FA-N, SHH type and poor survival independent of treatment strategies.
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Sönksen M, Obrecht-Sturm D, Hernáiz Driever P, Sauerbrey A, Graf N, Kontny U, Reimann C, Langhein M, Kordes UR, Schwarz R, Obser T, Boschann F, Schüller U, Altendorf L, Goschzik T, Pietsch T, Mynarek M, and Rutkowski S
- Abstract
Background: Outcome of children with medulloblastoma (MB) and Fanconi Anemia (FA), an inherited DNA repair deficiency, has not been described systematically. Treatment is complicated by high vulnerability to treatment-associated side effects, yet structured data are lacking. This study aims at giving a comprehensive overview about clinical and molecular characteristics of pediatric FA MB patients., Methods: Clinical data including detailed information on treatment and toxicities of six previously unreported FA MB patients were supplemented with data of 16 published cases., Results: We identified 22 cases of children with FA and MB with clinical data available. All MBs with subgroup reporting were SHH-activated (n=9), confirmed by methylation profiling in five patients. FA MB patients exclusively belonged to complementation groups FA-D1 (n=16) or FA-N (n=3). Patients were treated with postoperative chemotherapy only (50%) or radiotherapy (RT)±chemotherapy (27%). 23% did not receive adjuvant therapy. Excessive treatment-related toxicities were frequent. Severe hematological toxicity occurred in 91% of patients treated with alkylating chemotherapy, while non-alkylating agents and RT were less toxic. Median overall survival (OS) was 1 year (95%CI 0.3-1.8). 1-year-progression-free-survival (PFS) was 26.3±10.1% and 1-year-OS was 42.1±11.3%. Adjuvant therapy prolonged survival (1y-OS/1y-PFS 0%/0% without adjuvant therapy vs. 53.3±12.9%/33.3±12.2% with adjuvant therapy, p=0.006/p=0.086)., Conclusions: MB in FA patients is strongly associated with SHH activation and FA-D1/FA-N. Despite the dismal prognosis, adjuvant therapy may prolong survival. Non-alkylating chemotherapy and RT are feasible in selected patients with careful monitoring of toxicities and dose adjustments. Curative therapy for FA MB-SHH remains an unmet medical need., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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33. Risk factors for domain-specific neurocognitive outcome in pediatric survivors of a brain tumor in the posterior fossa - Results of the HIT 2000 trial.
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Mynarek M, Rossius A, Guiard A, Ottensmeier H, von Hoff K, Obrecht-Sturm D, Bußenius L, Friedrich C, von Bueren AO, Gerber NU, Traunwieser T, Kortmann RD, Warmuth-Metz M, Bison B, Thomale UW, Krauss J, Pietsch T, Clifford SC, Pfister SM, Sturm D, Sahm F, Tischler T, and Rutkowski S
- Abstract
Background: Neurocognition can be severely affected in pediatric brain tumor survivors. We analyzed the association of cognitive functioning with radiotherapy dose, postoperative cerebellar mutism syndrome (pCMS), hydrocephalus, intraventricular methotrexate (MTX) application, tumor localization and biology in pediatric survivors of a posterior fossa tumor., Methods: Subdomain-specific neurocognitive outcome data from 279 relapse-free survivors of the HIT-2000 trial (241 medulloblastoma and 38 infratentorial ependymoma) using the Neuropsychological Basic Diagnostic (NBD) tool based on Cattell-Horn-Carroll's model for intelligence were analyzed., Results: Cognitive performance 5.14 years (mean; range=1.52-13.02) after diagnosis was significantly below normal for all subtests. Processing speed and psychomotor abilities were most affected. Influencing factors were domain-specific: CSI-dose had strong impact on most subtests. pCMS was associated with psychomotor abilities (β=-0.25 to -0.16) and processing speed (β=-0.32). Postoperative hydrocephalus correlated with crystallized intelligence (β=-0.20) and short-term memory (β=-0.15), age with crystallized intelligence (β=0.15) and psychomotor abilities (β=-0.16 and β=-0.17). Scores for fluid intelligence (β=-0.23), short-term memory (β=-0.17) and visual processing (β=-0.25) declined, and scores for selective attention improved (β=0.29) with time after diagnosis., Conclusion: Dose of CSI was strongly associated with neurocognitive outcome. Low psychomotor abilities and processing speed both in patients treated with and without CSI suggest a strong contribution of the tumor and its surgery on these functions. Future research therefore should analyze strategies to both reduce CSI-dose and toxicity caused by other treatment modalities., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
- Published
- 2024
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34. Hereditary cutaneous leiomyomatosis and low-grade glioma due to a fumarate hydratase mutation.
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Laske J, Meinhardt M, Reif S, Grossmann M, Peitzsch M, Daubner D, Schackert G, Pietsch T, Meier F, Juratli TA, and Richter S
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- 2024
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35. Preclinical evidence for the use of anti-Trop-2 antibody-drug conjugate Sacituzumab govitecan in cerebral metastasized castration-resistant prostate cancer.
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Weiten R, Niemann M, Below E, Friker LL, Ralser DJ, Toma M, Kristiansen G, Hahn O, Zechel S, Grünwald V, Bald T, Siewert J, Pietsch T, Ritter M, Hölzel M, Eckstein M, Alajati A, Krausewitz P, and Klümper N
- Subjects
- Male, Humans, Cell Line, Tumor, Nectins, Prostatic Neoplasms, Castration-Resistant drug therapy, Prostatic Neoplasms, Castration-Resistant pathology, Immunoconjugates therapeutic use, Immunoconjugates pharmacology, Cell Adhesion Molecules metabolism, Cell Adhesion Molecules genetics, Antigens, Neoplasm immunology, Brain Neoplasms secondary, Brain Neoplasms drug therapy, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized pharmacology, Camptothecin analogs & derivatives, Camptothecin therapeutic use, Camptothecin pharmacology
- Abstract
Purpose: Improved survival rates have been observed in castration-resistant prostate cancer (CRPC) due to advancements in treatment options. However, individuals with brain metastases still have limited therapeutic options and an unfavorable prognosis. Therefore, there is an urgent need to explore new therapeutic avenues, such as antibody-drug conjugates (ADCs), which have demonstrated significant clinical activity against active brain metastases in solid tumors. Our objective was to determine the expression levels of the ADC targets Trop-2 and NECTIN-4 in cerebral metastasized CRPC (mCRPC)., Methods: Immunohistochemical staining of Trop-2 and NECTIN-4 with evaluation of H-score was performed in CRPC brain metastases (n = 31). Additionally, we examined Trop-2 protein expression in prostate cancer cell lines and studied their responsiveness to the anti-Trop-2 ADC Sacituzumab govitecan (SG) in vitro., Results: Our analysis revealed that most patients exhibited moderate to strong Trop-2 expression [n = 27/31 with H-score ≥100, median H-score 220 (IQR 180-280)], while NECTIN-4 was absent in all cerebral metastases. Mechanistically, we demonstrated that the efficacy of SG depends on Trop-2 expression levels in vitro. Overexpression of Trop-2 in Trop-2-negative PC-3 cells led to sensitization to SG, whereas CRISPR-Cas9-mediated knockdown of Trop-2 in Trop-2-expressing DU-145 cells conferred resistance to SG., Conclusion: The substantial expression of Trop-2 in cerebral metastases, along with our preclinical in vitro results, supports the efficacy of SG in treating cerebral mCRPC. Thus, our results extend the understanding of the potential of ADCs in prostate cancer treatment and provide an additional treatment strategy for the challenging subset of patients with cerebral metastases., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2024
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36. Adaption of neurosurgical resection patterns for pediatric low-grade glioma spanning two decades-Report from the German LGG-studies 1996-2018.
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Kelety T, Thomale UW, Kandels D, Schuhmann MU, El Damaty A, Krauss J, Frühwald MC, Driever PH, Witt O, Bison B, Warmuth-Metz M, Pietsch T, Schmidt R, and Gnekow AK
- Subjects
- Humans, Child, Female, Male, Germany, Adolescent, Child, Preschool, Infant, Neoplasm Grading, Glioma surgery, Glioma pathology, Neurosurgical Procedures methods, Brain Neoplasms surgery, Brain Neoplasms pathology
- Abstract
Introduction: Neurosurgery is considered the mainstay of treatment for pediatric low-grade glioma (LGG); the extent of resection determines subsequent stratification in current treatment protocols. Yet, surgical radicality must be balanced against the risks of complications that may affect long-term quality of life. We investigated whether this consideration impacted surgical resection patterns over time for patients of the German LGG studies., Patients and Methods: Four thousand two hundred and seventy pediatric patients from three successive LGG studies (median age at diagnosis 7.6 years, neurofibromatosis (NF1) 14.7%) were grouped into 5 consecutive time intervals (TI1-5) for date of diagnosis and analyzed for timing and extent of first surgery with respect to tumor site, histology, NF1-status, sex, and age., Results: The fraction of radiological LGG diagnoses increased over time (TI1 12.6%; TI5 21.7%), while the extent of the first neurosurgical intervention (3440/4270) showed a reduced fraction of complete/subtotal and an increase of partial resections from TI1 to TI5. Binary logistic regression analysis for the first intervention within the first year following diagnosis confirmed the temporal trends (p < 0.001) and the link with tumor site for each extent of resection (p < 0.001). Higher age is related to more complete resections in the cerebellum and cerebral hemispheres., Conclusions: The declining extent of surgical resections over time was unrelated to patient characteristics. It paralleled the evolution of comprehensive treatment algorithms; thus, it may reflect alignment of surgical practice to recommendations in respect to age, tumor site, and NF1-status integrated as such into current treatment guidelines. Further investigations are needed to understand how planning, performance, or tumor characteristics impact achieving surgical goals., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2024
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37. L-RNA aptamer-based CXCL12 inhibition combined with radiotherapy in newly-diagnosed glioblastoma: dose escalation of the phase I/II GLORIA trial.
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Giordano FA, Layer JP, Leonardelli S, Friker LL, Turiello R, Corvino D, Zeyen T, Schaub C, Müller W, Sperk E, Schmeel LC, Sahm K, Oster C, Kebir S, Hambsch P, Pietsch T, Bisdas S, Platten M, Glas M, Seidel C, Herrlinger U, and Hölzel M
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Adult, Maximum Tolerated Dose, Quality of Life, Neoplasm Recurrence, Local, Glioblastoma radiotherapy, Glioblastoma drug therapy, Aptamers, Nucleotide administration & dosage, Chemokine CXCL12 blood, Brain Neoplasms radiotherapy, Brain Neoplasms drug therapy
- Abstract
The chemokine CXCL12 promotes glioblastoma (GBM) recurrence after radiotherapy (RT) by facilitating vasculogenesis. Here we report outcomes of the dose-escalation part of GLORIA (NCT04121455), a phase I/II trial combining RT and the CXCL12-neutralizing aptamer olaptesed pegol (NOX-A12; 200/400/600 mg per week) in patients with incompletely resected, newly-diagnosed GBM lacking MGMT methylation. The primary endpoint was safety, secondary endpoints included maximum tolerable dose (MTD), recommended phase II dose (RP2D), NOX-A12 plasma levels, topography of recurrence, tumor vascularization, neurologic assessment in neuro-oncology (NANO), quality of life (QOL), median progression-free survival (PFS), 6-months PFS and overall survival (OS). Treatment was safe with no dose-limiting toxicities or treatment-related deaths. The MTD has not been reached and, thus, 600 mg per week of NOX-A12 was established as RP2D for the ongoing expansion part of the trial. With increasing NOX-A12 dose levels, a corresponding increase of NOX-A12 plasma levels was observed. Of ten patients enrolled, nine showed radiographic responses, four reached partial remission. All but one patient (90%) showed at best response reduced perfusion values in terms of relative cerebral blood volume (rCBV). The median PFS was 174 (range 58-260) days, 6-month PFS was 40.0% and the median OS 389 (144-562) days. In a post-hoc exploratory analysis of tumor tissue, higher frequency of CXCL12
+ endothelial and glioma cells was significantly associated with longer PFS under NOX-A12. Our data imply safety of NOX-A12 and its efficacy signal warrants further investigation., (© 2024. The Author(s).)- Published
- 2024
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38. Radiotherapy for Recurrent Medulloblastoma in Children and Adolescents: Survival after Re-Irradiation and First-Time Irradiation.
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Adolph JE, Fleischhack G, Tschirner S, Rink L, Dittes C, Mikasch R, Dammann P, Mynarek M, Obrecht-Sturm D, Rutkowski S, Bison B, Warmuth-Metz M, Pietsch T, Pfister SM, Pajtler KW, Milde T, Kortmann RD, Dietzsch S, Timmermann B, and Tippelt S
- Abstract
Background: Radiotherapy (RT) involving craniospinal irradiation (CSI) is important in the initial treatment of medulloblastoma. At recurrence, the re-irradiation options are limited and associated with severe side-effects., Methods: For pre-irradiated patients, patients with re-irradiation (RT2) were matched by sex, histology, time to recurrence, disease status and treatment at recurrence to patients without RT2., Results: A total of 42 pre-irradiated patients with RT2 were matched to 42 pre-irradiated controls without RT2. RT2 improved the median PFS [21.0 (CI: 15.7-28.7) vs. 12.0 (CI: 8.1-21.0) months] and OS [31.5 (CI: 27.6-64.8) vs. 20.0 (CI: 14.0-36.7) months]. Concerning long-term survival after ten years, RT2 only lead to small improvements in OS [8% (CI: 1.4-45.3) vs. 0%]. RT2 improved survival most without (re)-resection [PFS: 17.5 (CI: 9.7-41.5) vs. 8.0 (CI: 6.6-12.2)/OS: 31.5 (CI: 27.6-NA) vs. 13.3 (CI: 8.1-20.1) months]. In the RT-naïve patients, CSI at recurrence improved their median PFS [25.0 (CI: 16.8-60.6) vs. 6.6 (CI: 1.5-NA) months] and OS [40.2 (CI: 18.7-NA) vs. 12.4 (CI: 4.4-NA) months]., Conclusions: RT2 could improve the median survival in a matched cohort but offered little benefit regarding long-term survival. In RT-naïve patients, CSI greatly improved their median and long-term survival.
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- 2024
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39. BCOR::CREBBP fusion in malignant neuroepithelial tumor of CNS expands the spectrum of methylation class CNS tumor with BCOR/BCOR(L1)-fusion.
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Ebrahimi A, Waha A, Schittenhelm J, Gohla G, Schuhmann MU, and Pietsch T
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- Adult, Humans, Methylation, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins metabolism, Repressor Proteins genetics, CREB-Binding Protein genetics, Central Nervous System Neoplasms diagnostic imaging, Central Nervous System Neoplasms genetics, Neoplasms, Neuroepithelial diagnostic imaging, Neoplasms, Neuroepithelial genetics, Neoplasms, Neuroepithelial pathology, Brain Neoplasms diagnostic imaging, Brain Neoplasms genetics, Brain Neoplasms pathology, Glioma genetics
- Abstract
Methylation class "CNS tumor with BCOR/BCOR(L1)-fusion" was recently defined based on methylation profiling and tSNE analysis of a series of 21 neuroepithelial tumors with predominant presence of a BCOR fusion and/or characteristic CNV breakpoints at chromosome 22q12.31 and chromosome Xp11.4. Clear diagnostic criteria are still missing for this tumor type, specially that BCOR/BCOR(L1)-fusion is not a consistent finding in these tumors despite being frequent and that none of the Heidelberger classifier versions is able to clearly identify these cases, in particular tumors with alternative fusions other than those involving BCOR, BCORL1, EP300 and CREBBP. In this study, we introduce a BCOR::CREBBP fusion in an adult patient with a right temporomediobasal tumor, for the first time in association with methylation class "CNS tumor with BCOR/BCOR(L1)-fusion" in addition to 35 cases of CNS neuroepithelial tumors with molecular and histopathological characteristics compatible with "CNS tumor with BCOR/BCOR(L1)-fusion" based on a comprehensive literature review and data mining in the repository of 23 published studies on neuroepithelial brain Tumors including 7207 samples of 6761 patients. Based on our index case and the 35 cases found in the literature, we suggest the archetypical histological and molecular features of "CNS tumor with BCOR/BCOR(L1)-fusion". We also present four adult diffuse glioma cases including GBM, IDH-Wildtype and Astrocytoma, IDH-Mutant with CREBBP fusions and describe the necessity of complementary molecular analysis in "CNS tumor with BCOR/BCOR(L1)-alterations for securing a final diagnosis., (© 2024. The Author(s).)
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- 2024
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40. Modulated critical currents of spin-transfer torque-induced resistance changes in NiCu/Cu multilayered nanowires.
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Fu M, Hartmann R, Braun J, Andreev S, Pietsch T, and Scheer E
- Abstract
We present a novel method combining anodic aluminum oxide template synthesis and nanolithography to selectively deposit vertically patterned magnetic nanowires on a Si substrate. With this approach we fabricated three-dimensional nanowire-based spin valve devices without the need of complex etching processes or additional spacer coating. Through this method, we successfully obtained NiCu/Cu multilayered nanowire arrays with a controlled sequence along the long axis of the nanowires. Both magnetic switching and excitation phenomena driven by spin-polarized currents were clearly demonstrated in our NiCu/Cu multilayered nanowires. Moreover, the critical currents for switching and excitation were observed to be modulated in an oscillatory manner by the magnetic field in the nanowire-based devices. We present a toy model to qualitatively explain these observations., (Copyright © 2024, Fu et al.)
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- 2024
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41. Clinically relevant molecular hallmarks of PFA ependymomas display intratumoral heterogeneity and correlate with tumor morphology.
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Gödicke S, Kresbach C, Ehlert M, Obrecht D, Altendorf L, Hack K, von Hoff K, Carén H, Melcher V, Kerl K, Englinger B, Filbin M, Pajtler KW, Gojo J, Pietsch T, Rutkowski S, and Schüller U
- Subjects
- Child, Humans, In Situ Hybridization, Fluorescence, Histones, Gene Expression Profiling, Neoplasm Recurrence, Local, Ependymoma
- Abstract
Posterior fossa type A (PF-EPN-A, PFA) ependymoma are aggressive tumors that mainly affect children and have a poor prognosis. Histopathology shows significant intratumoral heterogeneity, ranging from loose tissue to often sharply demarcated, extremely cell-dense tumor areas. To determine molecular differences in morphologically different areas and to understand their clinical significance, we analyzed 113 PF-EPN-A samples, including 40 corresponding relapse samples. Cell-dense areas ranged from 0 to 100% of the tumor area and displayed a higher proportion of proliferating tumor cells (p < 0.01). Clinically, cell density was associated with poor progression-free and overall survival (p
PFS = 0.0026, pOS < 0.01). Molecularly, tumor areas with low and high cell density showed diverging DNA methylation profiles regarding their similarity to distinct previously discovered PF-EPN-A subtypes in 9/21 cases. Prognostically relevant chromosomal changes at 1q and 6q showed spatial heterogeneity within single tumors and were significantly enriched in cell-dense tumor areas as shown by single-cell RNA (scRNA)-sequencing as well as copy number profiling and fluorescence in situ hybridization (FISH) analyses of different tumor areas. Finally, spatial transcriptomics revealed cell-dense areas of different tumors to be more similar than various different areas of the same tumor. High-density areas distinctly overexpressed genes encoding histone proteins, WNT5A, TGFB1, or IGF2. Relapsing tumors displayed a higher proportion of cell-dense areas (p = 0.036), a change in PF-EPN-A methylation subtypes (13/32 patients), and novel chromosome 1q gains and 6q losses (12/32 cases) compared to corresponding primary tumors. Our data suggest that PF-EPN-A ependymomas habor a previously unrecognized intratumoral heterogeneity with clinical implications, which has to be accounted for when selecting diagnostic material, inter alia, by histological evaluation of the proportion of cell-dense areas., (© 2024. The Author(s).)- Published
- 2024
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42. Facile Synthesis of Anhydrous Rare-Earth Trichlorides from their Oxides in Chloridoaluminate Ionic Liquids.
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Shah S, Pietsch T, and Ruck M
- Abstract
Wide applications of anhydrous rare-earth (RE) trichlorides RECl
3 in organometallic chemistry, for the synthesis of optical and magnetic materials, and as catalysts require a facile approach for their synthesis. The known methods use or produce toxic substances, are complicated and have limited reliability and upscaling. It has been shown that task-specific ionic liquids (ILs) can dissolve many metal oxides without special reaction conditions at moderate temperature, making the metals accessible to downstream chemistry. Using imidazolium chloridoaluminate ILs, pure crystalline anhydrous RECl3 (RE=La-Nd, Sm-Dy) can be synthesized in one step from RE oxides in high yield. The Lewis acidic IL acts as solvent and reaction partner. The by-product [Al4 O2 Cl10 ]2- , which was detected spectroscopically, remains in solution. The reacted IL can be removed quantitatively by washing. ILs with various imidazolium cations and AlCl3 content and the effect of temperature and reaction time were tested., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)- Published
- 2024
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43. Improved prognostic stratification of patients with isocitrate dehydrogenase-mutant astrocytoma.
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Weller M, Felsberg J, Hentschel B, Gramatzki D, Kubon N, Wolter M, Reusche M, Roth P, Krex D, Herrlinger U, Westphal M, Tonn JC, Regli L, Maurage CA, von Deimling A, Pietsch T, Le Rhun E, and Reifenberger G
- Subjects
- Humans, Cohort Studies, Homozygote, Prognosis, Retrospective Studies, Sequence Deletion, Astrocytoma genetics, Astrocytoma therapy, Isocitrate Dehydrogenase genetics
- Abstract
Prognostic factors and standards of care for astrocytoma, isocitrate dehydrogenase (IDH)-mutant, CNS WHO grade 4, remain poorly defined. Here we sought to explore disease characteristics, prognostic markers, and outcome in patients with this newly defined tumor type. We determined molecular biomarkers and assembled clinical and outcome data in patients with IDH-mutant astrocytomas confirmed by central pathology review. Patients were identified in the German Glioma Network cohort study; additional cohorts of patients with CNS WHO grade 4 tumors were identified retrospectively at two sites. In total, 258 patients with IDH-mutant astrocytomas (114 CNS WHO grade 2, 73 CNS WHO grade 3, 71 CNS WHO grade 4) were studied. The median age at diagnosis was similar for all grades. Karnofsky performance status at diagnosis inversely correlated with CNS WHO grade (p < 0.001). Despite more intensive treatment upfront with higher grade, CNS WHO grade was strongly prognostic: median overall survival was not reached for grade 2 (median follow-up 10.4 years), 8.1 years (95% CI 5.4-10.8) for grade 3, and 4.7 years (95% CI 3.4-6.0) for grade 4. Among patients with CNS WHO grade 4 astrocytoma, median overall survival was 5.5 years (95% CI 4.3-6.7) without (n = 58) versus 1.8 years (95% CI 0-4.1) with (n = 12) homozygous CDKN2A deletion. Lower levels of global DNA methylation as detected by LINE-1 methylation analysis were strongly associated with CNS WHO grade 4 (p < 0.001) and poor outcome. MGMT promoter methylation status was not prognostic for overall survival. Histomolecular stratification based on CNS WHO grade, LINE-1 methylation level, and CDKN2A status revealed four subgroups of patients with significantly different outcomes. In conclusion, CNS WHO grade, global DNA methylation status, and CDKN2A homozygous deletion are prognostic in patients with IDH-mutant astrocytoma. Combination of these parameters allows for improved prediction of outcome. These data aid in designing upcoming trials using IDH inhibitors., (© 2024. The Author(s).)
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- 2024
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44. p16 Immunohistochemistry as a Screening Tool for Homozygous CDKN2A Deletions in CNS Tumors.
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Zschernack V, Andreiuolo F, Dörner E, Wiedey A, Jünger ST, Friker LL, Maruccia R, and Pietsch T
- Subjects
- Humans, Immunohistochemistry, Homozygote, Sequence Deletion, Cyclin-Dependent Kinase Inhibitor p16 genetics, Cyclin-Dependent Kinase Inhibitor p16 metabolism, Gene Deletion, Meningioma genetics, Glioma genetics, Meningeal Neoplasms genetics, Ependymoma genetics
- Abstract
The 2021 World Health Organization classification of tumors of the central nervous system emphasizes the significance of molecular parameters for an integrated diagnosis. Homozygous deletion of cyclin-dependent kinase inhibitor 2a (CDKN2A) has been associated with an adverse prognosis in IDH -mutant gliomas, supratentorial ependymomas, meningiomas, and MPNST. In this study, we examined the value of p16 protein immunohistochemistry as a rapid and cost-effective screening tool for a homozygous CDKN2A deletion. Genetic analyses for CDKN2A in 30 pleomorphic xanthoastrocytomas, 32 IDH -wild-type high-grade gliomas, 40 supratentorial ependymomas with ZFTA-RELA gene fusion, 21 IDH-mutant astrocytomas, and 24 meningiomas were performed mainly by a molecular inversion probe assay, a high-resolution, quantitative technology for the assessment of chromosomal copy number alterations. Immunohistochemistry for p16 proved to have a high positive predictive value (range 90% to 100%) and an overall low negative predictive value (range 22% to 93%) for a homozygous CDKN2A deletion. In a setting where molecular testing is limited for cost and time reasons, p16 immunohistochemistry serves as a useful and rapid screening tool for identifying cases that should be subjected to further molecular testing for CDKN2A deletions., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationship with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2024
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45. Pineal anlage tumor: clinical and diagnostic features, and rationales for treatment.
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Obrecht-Sturm D, Pfaff E, Mynarek M, Bison B, Rodehüser M, Becker M, Kietz S, Pfister SM, Jones DT, Sturm D, von Deimling A, Sahm F, Kortmann RD, Schwarz R, Pietsch T, Fleischhack G, and Rutkowski S
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Humans, Infant, Young Adult, Neoplasm Recurrence, Local pathology, Recurrence, Treatment Outcome, Brain Neoplasms diagnosis, Brain Neoplasms surgery, Pineal Gland surgery, Pineal Gland pathology, Pinealoma diagnosis, Pinealoma surgery, Supratentorial Neoplasms pathology
- Abstract
Purpose: To provide a treatment-focused review and develop basic treatment guidelines for patients diagnosed with pineal anlage tumor (PAT)., Methods: Prospectively collected data of three patients with pineal anlage tumor from Germany was combined with clinical details and treatment information from 17 published cases., Results: Overall, 20 cases of PAT were identified (3 not previously reported German cases, 17 cases from published reports). Age at diagnosis ranged from 0.3 to 35.0 (median: 3.2 ± 7.8) years. All but three cases were diagnosed before the age of three years. For three cases, metastatic disease at initial staging was described. All patients underwent tumor surgery (gross-total resection: 9, subtotal resection/biopsy: 9, extent of resection unknown: 2). 15/20 patients were alive at last follow-up. Median follow-up for 10/15 surviving patients with available follow-up and treatment data was 2.4 years (0.3-6.5). Relapse was reported for 3 patients within 0.8 years after diagnosis. Five patients died, 3 after relapse and 2 from early postoperative complications. Two-year-progression-free- and -overall survival were 65.2 ± 12.7% and 49.2 ± 18.2%, respectively. All 4 patients who received intensive chemotherapy including high-dose chemotherapy combined with radiotherapy (2 focal, 2 craniospinal [CSI]) had no recurrence. Focal radiotherapy- and CSI-free survival rates in 13 evaluable patients were 46.2% (6/13) and 61.5% (8/13), respectively., Conclusion: PAT is an aggressive disease mostly affecting young children. Therefore, adjuvant therapy using intensive chemotherapy and considering radiotherapy appears to comprise an appropriate treatment strategy. Reporting further cases is crucial to evaluate distinct treatment strategies., (© 2024. The Author(s).)
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- 2024
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46. Ependymoma from Benign to Highly Aggressive Diseases: A Review.
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Jünger ST, Zschernack V, Messing-Jünger M, Timmermann B, and Pietsch T
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- Humans, Age Distribution, Combined Modality Therapy, Ependymoma genetics, Brain Neoplasms genetics
- Abstract
Ependymomas comprise biologically distinct tumor types with respect to age distribution, (epi)genetics, localization, and prognosis. Multimodal risk-stratification, including histopathological and molecular features, is essential in these biologically defined tumor types. Gross total resection (GTR), achieved with intraoperative monitoring and neuronavigation, and if necessary, second-look surgery, is the most effective treatment. Adjuvant radiation therapy is mandatory in high-risk tumors and in case of residual tumor. There is yet growing evidence that some ependymal tumors may be cured by surgery alone. To date, the role of chemotherapy is unclear and subject of current studies.Even though standard therapy can achieve reasonable survival rates for the majority of ependymoma patients, long-term follow-up still reveals a high probability of relapse in certain biological entities.With increasing knowledge of biologically distinct tumor types, risk-adapted adjuvant therapy gains importance. Beyond initial tumor control, and avoidance of therapy-induced morbidity for low-risk patients, intensified treatment for high-risk patients comprises another challenge. With identification of specific risk features regarding molecular alterations, targeted therapy may represent an option for individualized treatment modalities in the future., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)
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- 2024
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47. Author Correction: Multiomic neuropathology improves diagnostic accuracy in pediatric neuro-oncology.
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Sturm D, Capper D, Andreiuolo F, Gessi M, Kölsche C, Reinhardt A, Sievers P, Wefers AK, Ebrahimi A, Suwala AK, Gielen GH, Sill M, Schrimpf D, Stichel D, Hovestadt V, Daenekas B, Rode A, Hamelmann S, Previti C, Jäger N, Buchhalter I, Blattner-Johnson M, Jones BC, Warmuth-Metz M, Bison B, Grund K, Sutter C, Hirsch S, Dikow N, Hasselblatt M, Schüller U, Koch A, Gerber NU, White CL, Buntine MK, Kinross K, Algar EM, Hansford JR, Gottardo NG, Schuhmann MU, Thomale UW, Hernáiz Driever P, Gnekow A, Witt O, Müller HL, Calaminus G, Fleischhack G, Kordes U, Mynarek M, Rutkowski S, Frühwald MC, Kramm CM, von Deimling A, Pietsch T, Sahm F, Pfister SM, and Jones DTW
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- 2024
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48. Clinical outcome of pediatric medulloblastoma patients with Li-Fraumeni syndrome.
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Kolodziejczak AS, Guerrini-Rousseau L, Planchon JM, Ecker J, Selt F, Mynarek M, Obrecht D, Sill M, Autry RJ, Stutheit-Zhao E, Hirsch S, Amouyal E, Dufour C, Ayrault O, Torrejon J, Waszak SM, Ramaswamy V, Pentikainen V, Demir HA, Clifford SC, Schwalbe EC, Massimi L, Snuderl M, Galbraith K, Karajannis MA, Hill K, Li BK, Walsh M, White CL, Redmond S, Loizos L, Jakob M, Kordes UR, Schmid I, Hauer J, Blattmann C, Filippidou M, Piccolo G, Scheurlen W, Farrag A, Grund K, Sutter C, Pietsch T, Frank S, Schewe DM, Malkin D, Ben-Arush M, Sehested A, Wong TT, Wu KS, Liu YL, Carceller F, Mueller S, Stoller S, Taylor MD, Tabori U, Bouffet E, Kool M, Sahm F, von Deimling A, Korshunov A, von Hoff K, Kratz CP, Sturm D, Jones DTW, Rutkowski S, van Tilburg CM, Witt O, Bougeard G, Pajtler KW, Pfister SM, Bourdeaut F, and Milde T
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- Child, Humans, Retrospective Studies, Prospective Studies, Germ-Line Mutation, Tumor Suppressor Protein p53 genetics, Li-Fraumeni Syndrome complications, Li-Fraumeni Syndrome genetics, Li-Fraumeni Syndrome therapy, Medulloblastoma therapy, Medulloblastoma drug therapy, Cerebellar Neoplasms therapy, Cerebellar Neoplasms drug therapy
- Abstract
Background: The prognosis for Li-Fraumeni syndrome (LFS) patients with medulloblastoma (MB) is poor. Comprehensive clinical data for this patient group is lacking, challenging the development of novel therapeutic strategies. Here, we present clinical and molecular data on a retrospective cohort of pediatric LFS MB patients., Methods: In this multinational, multicenter retrospective cohort study, LFS patients under 21 years with MB and class 5 or class 4 constitutional TP53 variants were included. TP53 mutation status, methylation subgroup, treatment, progression free- (PFS) and overall survival (OS), recurrence patterns, and incidence of subsequent neoplasms were evaluated., Results: The study evaluated 47 LFS individuals diagnosed with MB, mainly classified as DNA methylation subgroup "SHH_3" (86%). The majority (74%) of constitutional TP53 variants represented missense variants. The 2- and 5-year (y-) PFS were 36% and 20%, and 2- and 5y-OS were 53% and 23%, respectively. Patients who received postoperative radiotherapy (RT) (2y-PFS: 44%, 2y-OS: 60%) or chemotherapy before RT (2y-PFS: 32%, 2y-OS: 48%) had significantly better clinical outcome then patients who were not treated with RT (2y-PFS: 0%, 2y-OS: 25%). Patients treated according to protocols including high-intensity chemotherapy and patients who received only maintenance-type chemotherapy showed similar outcomes (2y-PFS: 42% and 35%, 2y-OS: 68% and 53%, respectively)., Conclusions: LFS MB patients have a dismal prognosis. In the presented cohort use of RT significantly increased survival rates, whereas chemotherapy intensity did not influence their clinical outcome. Prospective collection of clinical data and development of novel treatments are required to improve the outcome of LFS MB patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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49. Embryonal tumor with multilayered rosettes located in the brainstem: Promising results after multimodal treatment including interstitial brachytherapy.
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Jünger ST, Rueß D, Kabbasch C, Gielen GH, Pietsch T, Johann P, Landgraf P, Kocher M, Goldbrunner R, Simon T, and Ruge MI
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- 2023
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50. Perinatally diagnosed congenital craniopharyngiomas in the KRANIOPHARYNGEOM trials.
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Beckhaus J, Boekhoff S, Scheinemann K, Schilling FH, Fleischhack G, Binder G, Bison B, Pietsch T, Friedrich C, and Müller HL
- Abstract
Background: Craniopharyngiomas (CPs) are rare embryonic tumors. Clinical presentation and outcome of patients perinatally diagnosed with congenital CP (cCP) are not clear and refer mainly to a few case reports in the literature. The aim of this study was to analyze clinical presentation and outcome in patients with cCP., Study Design: Three hundred and sixty-one patients diagnosed with adamantinomatous CP were recruited 2007-2022 in KRANIOPHARYNGEOM 2007/Registry 2019 and prospectively observed. In two cases, cCP was diagnosed prenatally and in one case on the second day of life. Pre- and perinatal diagnostic findings, postnatal evaluation, and therapeutic interventions and outcome in these three cases of cCP were analyzed., Results: All patients survived. One patient developed psychomotor retardation and a mild hemiparesis. Prenatal routine ultrasound examination led to the diagnosis of cCP. Tumor resection was performed during the early postnatal period (range: 11-51 days of age). Functional capacity, measured by Fertigkeitenskala-Münster-Heidelberg (FMH) was reduced in three and behavioral parameters, measured by the Strength and Difficulties Questionnaire (SDQ) were abnormal in two cases., Conclusion: cCP is a rare diagnosis with a prevalence of 0.83% in our study group. Compared to cases reported in the literature, the presented cases were treated immediately and had a better prognosis. Based on improvements of diagnostic and therapeutic techniques, prenatal diagnosis of cCP should lead to transfer prior to delivery of cCP patients to a specialized center for delivery and postnatal treatment of newborns with sellar masses by a multidisciplinary team to secure the improved prognosis of these patients., Significance Statement: We previously reported that lower event-free survival rates after craniopharyngioma are associated with younger age at diagnosis. Perinatally diagnosed congenital craniopharyngiomas are very rare. This article presents three unique cases with congenital craniopharyngioma, comparing their diagnostics, therapy, and development. All three cases had surgery during the early postnatal period with sparing of the posterior hypothalamus. In each case, endocrinopathy was present at follow-up. Low functional capacity was reported in all cases and an abnormal total difficulties score in two cases. Compared to the literature, the presented cases had better prognosis in morbidity and mortality. This report and the review of the literature confirm the importance of a multidisciplinary approach in the diagnostic and treatment of the very rare condition of congenital craniopharyngioma.
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- 2023
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