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8. Detection of H3F3A K27M or BRAF V600E in liquid biopsies of brain tumor patients as diagnostic and monitoring biomarker: impact of tumor localization and sampling method

Author

Madlener, Sibylle, Stepien, Natalia, Senfter, Daniel, Mayr, Lisa, Laemmerer, Anna, Hedrich, Cora, Baumgartner, Alicia, Lötsch-Gojo, Daniela, Sterba, Jaroslav, Pokorna, Petra, Kiesel, Barbara, Widhalm, Georg, Eckert, Franziska, Preusser, Matthias, Rössler, Karl, Azizi, Amedeo, Peyrl, Andreas, Czech, Thomas, Haberler, Christine, Slavc, Irene, Kasprian, Gregor, Dorfer, Christian, Furtner, Julia, and Gojo, Johannes

Published
2025
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10. The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location

Author

Liu, Ilon, Jiang, Li, Samuelsson, Erik R., Marco Salas, Sergio, Beck, Alexander, Hack, Olivia A., Jeong, Daeun, Shaw, McKenzie L., Englinger, Bernhard, LaBelle, Jenna, Mire, Hafsa M., Madlener, Sibylle, Mayr, Lisa, Quezada, Michael A., Trissal, Maria, Panditharatna, Eshini, Ernst, Kati J., Vogelzang, Jayne, Gatesman, Taylor A., Halbert, Matthew E., Palova, Hana, Pokorna, Petra, Sterba, Jaroslav, Slaby, Ondrej, Geyeregger, Rene, Diaz, Aaron, Findlay, Izac J., Dun, Matthew D., Resnick, Adam, Suvà, Mario L., Jones, David T. W., Agnihotri, Sameer, Svedlund, Jessica, Koschmann, Carl, Haberler, Christine, Czech, Thomas, Slavc, Irene, Cotter, Jennifer A., Ligon, Keith L., Alexandrescu, Sanda, Yung, W. K. Alfred, Arrillaga-Romany, Isabel, Gojo, Johannes, Monje, Michelle, Nilsson, Mats, and Filbin, Mariella G.

Published
2022
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11. ERN GENTURIS tumour surveillance guidelines for individuals with neurofibromatosis type 1

Author

Brunet, Joan, Van Calenbergh, Frank, Cassiman, Catherine, Czech, Thomas, Gavarrete de León, María José, Giele, Henk, Henley, Susie, Lazaro, Conxi, Lipkovskaya, Vera, Maher, Eamonn R., Martin, Vanessa, Mathijssen, Irene, Opocher, Enrico, Pires, Ana Elisabete, Pletschko, Thomas, Poupaki, Eirene, Ridola, Vita, Rietman, Andre, Rosenbaum, Thorsten, Santhouse, Alastair, Sehested, Astrid, Simmons, Ian, Taal, Walter, Wagner, Anja, Carton, Charlotte, Evans, D. Gareth, Blanco, Ignacio, Friedrich, Reinhard E., Ferner, Rosalie E., Farschtschi, Said, Salvador, Hector, Azizi, Amedeo A., Mautner, Victor, Röhl, Claas, Peltonen, Sirkku, Stivaros, Stavros, Legius, Eric, and Oostenbrink, Rianne

Published
2023
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13. Imaging response assessment for CNS germ cell tumours: consensus recommendations from the European Society for Paediatric Oncology Brain Tumour Group and North American Children's Oncology Group

Author

Morana, Giovanni, Shaw, Dennis, MacDonald, Shannon M, Alapetite, Claire, Ajithkumar, Thankamma, Bhatia, Aashim, Brisse, Hervé, Jaimes, Camilo, Czech, Thomas, Dhall, Girish, Fangusaro, Jason, Faure-Conter, Cecile, Fouladi, Maryam, Hargrave, Darren, Harreld, Julie H, Mitra, Dipayan, Nicholson, James C, Souweidane, Mark, Timmermann, Beate, Calaminus, Gabriele, Bartels, Ute, Bison, Brigitte, and Murray, Matthew J

Published
2022
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14. Cerebellar pilocytic astrocytoma: predictors of recurrence based on MRI morphology—a single-centre experience.

Author

Grin, Katherina, Azizi, Amedeo, Haberler, Christine, Peyrl, Andreas, Kasprian, Gregor, Czech, Thomas, Rössler, Karl, Gojo, Johannes, and Dorfer, Christian

Abstract

Purpose: We aimed to present our surgical experience and the impact of a solid or cystic morphology of cerebellar pilocytic astrocytoma (cPA) on surgery and the risk for a re-resection. Methods: We retrospectively analyzed all children operated at our institution between 2009 and 2023 for cPA. Tumours were categorized into 4 groups: (i) cystic PA without cyst wall enhancement, (ii) cystic PA with cyst wall enhancement, (iii) solid tumour, (iv) and solid tumour with central necrosis. Results: Forty-two children with a median age at surgery of 7.1 years (range 0.7–14 years; male to female ratio 1.5) were identified. The median follow-up time was 3.1 years (0.6–14 years). Twenty-eight patients (66.6%) presented with cystic PA (20 without and 8 with cyst wall enhancement), 9 patients (21.4%) exhibited a solid tumour with central necrosis and 5 (11.9%) had a solid tumour without central necrosis. Gross total resection could be achieved in 31 patients (73.8%), near total resection in 6 (14.3%), and subtotal resection in 5 (11.9%). Progression occurred in 11 cases with 9 patients having a 2nd resection after a mean time of 3.4 years. The highest risk for a 2nd resection was seen in the group of solid tumours with a necrotic centre (odds ratio = 2.3), progression of enhancing cyst wall remnants was seen in one out of two patients with remnants needing reoperation. Conclusion: Surgery in cerebellar PA should aim for gross total resection of the solid-enhancing tumour. [ABSTRACT FROM AUTHOR]

Published
2025
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17. Targeting fibroblast growth factor receptors to combat aggressive ependymoma

Author

Lötsch, Daniela, Kirchhofer, Dominik, Englinger, Bernhard, Jiang, Li, Okonechnikov, Konstantin, Senfter, Daniel, Laemmerer, Anna, Gabler, Lisa, Pirker, Christine, Donson, Andrew M., Bannauer, Peter, Korbel, Pia, Jaunecker, Carola N., Hübner, Jens-Martin, Mayr, Lisa, Madlener, Sibylle, Schmook, Maria T., Ricken, Gerda, Maaß, Kendra, Grusch, Michael, Holzmann, Klaus, Grasl-Kraupp, Bettina, Spiegl-Kreinecker, Sabine, Hsu, Jennifer, Dorfer, Christian, Rössler, Karl, Azizi, Amedeo A., Foreman, Nicholas K., Peyrl, Andreas, Haberler, Christine, Czech, Thomas, Slavc, Irene, Filbin, Mariella G., Pajtler, Kristian W., Kool, Marcel, Berger, Walter, and Gojo, Johannes

Published
2021
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20. Seizure outcome and use of antiepileptic drugs after epilepsy surgery according to histopathological diagnosis: a retrospective multicentre cohort study

Author

Aichholzer, Martin, Amorim, Isabel, Aparicio, Javier, Aronica, Eleonora, Arzimanoglou, Alexis, Barba, Carmen, Beck, Jürgen, Becker, Albert, Beckervordersandforth, Jan C, Bien, Christian G, Blümcke, Ingmar, Bodi, Istvan, Braun, Kees PJ, Catenoix, Helene, Chassoux, Francine, Chipaux, Mathilde, Cloppenborg, Thomas, Coras, Roland, Cross, J Helen, De Palma, Luca, De Tisi, Jane, Deleo, Francesco, Devaux, Bertrand, Di Gennaro, Giancarlo, Dorfmüller, Georg, Duncan, John S, Elger, Christian, Ernst, Katharina, Esposito, Vincenzo, Feucht, Martha, Gadze, Zeljka Petelin, Garbelli, Rita, Geleijns, Karin, Gil-Nagel, Antonio, Grote, Alexander, Grunwald, Thomas, Guerrini, Renzo, Hamer, Hajo, Honavar, Mrinalini, Jacques, Thomas S, Jakovcevic, Antonia, Jutila, Leena, Kalina, Adam, Kälviäinen, Reetta, Klein, Karl Martin, Koenig, Kristina, Krsek, Pavel, Kudernatsch, Manfred, Kudr, Martin, Lamberink, Herm J, Malmgren, Kristina, Marusic, Petr, Melikyan, Armen, Menzler, Katja, Noachtar, Soheyl, Otte, Willem M, Özkara, Çiğdem, Pieper, Tom, Pimentel, Jose, Raicevic, Savo, Rheims, Sylvain, Ribeiro, Joana, Rosenow, Felix, Rössler, Karl, Rydenhag, Bertil, Sales, Francisco, San Antonio-Arce, Victoria, Schaller, Karl Lothar, Schijns, Olaf, Scholl, Theresa, Schramm, Johannes, Schulze-Bonhage, Andreas, Sciot, Raf, Seeck, Margitta, Shishkina, Lyudmila, Sokic, Dragoslav, Specchio, Nicola, Theys, Tom, Thom, Maria, Delgado, Rafael Toledano, Toulouse, Joseph, Uzan, Mustafa, van Loon, Johannes, Van Paesschen, Wim, von Oertzen, Tim J, Jansen, Floor, Leijten, Frans, van Rijen, Peter, Spliet, Wim GM, Mühlebner, Angelika, Kasper, Burkhard S, Fauser, Susanne, Polster, Tilman, Kalbhenn, Thilo, Delev, Daniel, McEvoy, Andrew, Miserocchi, Anna, Landré, Elisabeth, Turak, Bares, Varlet, Pascale, Ferrand-Sorbets, Sarah, Fohlen, Martine, Bulteau, Christine, Edelvik, Anna, Shah, Mukesch J, Scheiwe, Christian, Delicado, Eva Gutierrez, Tisdall, Martin, Eltze, Christin, Akkol, Serdar, Deniz, Kaancan, Oz, Buge, Holthausen, Hans, Hartlieb, Till, Staudt, Martin, Casciato, Sara, Quarato, Pier P, Giangaspero, Felice, Streichenberger, Nathalie, Guenot, Marc, Isnard, Jean, Valentijn, Antonio, Chang, Amanda, Mullatti, Nandini, Zamecnik, Josef, Zarubova, Jana, Tomasek, Martin, Immonen, Arto, Saarela, Anni, Rauramaa, Tuomas, Lobrinus, Johannes A, Egervari, Kristof, Momjian, Shahan, Harti, Elisabeth, Lohr, Hannah, Kroell, Judith, Vermeulen, Lynn, Cleeren, Evy, Vlasov, Pavel, Kozlova, Antonia, Vorobyev, Alexey, Goeppel, Gudrun, Samueli, Sharon, Czech, Thomas, Hainfellner, Johannes, Puttinger, Gertraud, Schwarz, Gabriele, Stefanits, Harald, Weis, Serge, Spreafico, Roberto, Villani, Flavio, Rossini, Laura, Hermsen, Anke, Knake, Susanne, Nimsky, Christopher, Carl, Barbara, Belohlavkova, Anezka, Benova, Barbora, Bisschop, Jeroen, Colon, Albert, van Kranen-Mastenbroek, Vivianne, Rouhl, Rob PW, Hoogland, Govert, Rumiá, Jordi, Ramírez-Camacho, Alia, Candela-Cantó, Santiago, Ostrowsky-Coste, Karine, Panagiotakaki, Eleni, Montavont, Alexandra, Kosal, Pascale Keo, Gokce-Samar, Zeynep, Milleret, Clara, Buccoliero, Anna M, Giordano, Flavio, Sulentic, Vlatko, Mrak, Goran, Desnica, Andrej, CarfíPavia, Giusy, De Benedictis, Alessandro, Marras, Carlo E, Bascarevic, Vladimir, Vojvodic, Nikola, Ristic, Aleksandar, Rebelo, Olinda, Aledo-Serrano, Angel, Garcia-Morales, Irene, Anciones, Carla, and Braun, Kees P J

Published
2020
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21. Single-Cell RNA-Seq Reveals Cellular Hierarchies and Impaired Developmental Trajectories in Pediatric Ependymoma

Author

Gojo, Johannes, Englinger, Bernhard, Jiang, Li, Hübner, Jens M., Shaw, McKenzie L., Hack, Olivia A., Madlener, Sibylle, Kirchhofer, Dominik, Liu, Ilon, Pyrdol, Jason, Hovestadt, Volker, Mazzola, Emanuele, Mathewson, Nathan D., Trissal, Maria, Lötsch, Daniela, Dorfer, Christian, Haberler, Christine, Halfmann, Angela, Mayr, Lisa, Peyrl, Andreas, Geyeregger, Rene, Schwalm, Benjamin, Mauermann, Monica, Pajtler, Kristian W., Milde, Till, Shore, Marni E., Geduldig, Jack E., Pelton, Kristine, Czech, Thomas, Ashenberg, Orr, Wucherpfennig, Kai W., Rozenblatt-Rosen, Orit, Alexandrescu, Sanda, Ligon, Keith L., Pfister, Stefan M., Regev, Aviv, Slavc, Irene, Berger, Walter, Suvà, Mario L., Kool, Marcel, and Filbin, Mariella G.

Published
2020
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22. An Integrative Model of Cellular States, Plasticity, and Genetics for Glioblastoma

Author

Neftel, Cyril, Laffy, Julie, Filbin, Mariella G., Hara, Toshiro, Shore, Marni E., Rahme, Gilbert J., Richman, Alyssa R., Silverbush, Dana, Shaw, McKenzie L., Hebert, Christine M., Dewitt, John, Gritsch, Simon, Perez, Elizabeth M., Gonzalez Castro, L. Nicolas, Lan, Xiaoyang, Druck, Nicholas, Rodman, Christopher, Dionne, Danielle, Kaplan, Alexander, Bertalan, Mia S., Small, Julia, Pelton, Kristine, Becker, Sarah, Bonal, Dennis, Nguyen, Quang-De, Servis, Rachel L., Fung, Jeremy M., Mylvaganam, Ravindra, Mayr, Lisa, Gojo, Johannes, Haberler, Christine, Geyeregger, Rene, Czech, Thomas, Slavc, Irene, Nahed, Brian V., Curry, William T., Carter, Bob S., Wakimoto, Hiroaki, Brastianos, Priscilla K., Batchelor, Tracy T., Stemmer-Rachamimov, Anat, Martinez-Lage, Maria, Frosch, Matthew P., Stamenkovic, Ivan, Riggi, Nicolo, Rheinbay, Esther, Monje, Michelle, Rozenblatt-Rosen, Orit, Cahill, Daniel P., Patel, Anoop P., Hunter, Tony, Verma, Inder M., Ligon, Keith L., Louis, David N., Regev, Aviv, Bernstein, Bradley E., Tirosh, Itay, and Suvà, Mario L.

Published
2019
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24. Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq

Author

Filbin, Mariella G., Tirosh, Itay, Hovestadt, Volker, Shaw, McKenzie L., Escalante, Leah E., Mathewson, Nathan D., Neftel, Cyril, Frank, Nelli, Pelton, Kristine, Hebert, Christine M., Haberler, Christine, Yizhak, Keren, Gojo, Johannes, Egervari, Kristof, Mount, Christopher, van Galen, Peter, Bonal, Dennis M., Nguyen, Quang-De, Beck, Alexander, Sinai, Claire, Czech, Thomas, Dorfer, Christian, Goumnerova, Liliana, Lavarino, Cinzia, Carcaboso, Angel M., Mora, Jaume, Mylvaganam, Ravindra, Luo, Christina C., Peyr, Andreas, Popović, Mara, Azizi, Amedeo, Batchelor, Tracy. T., Frosch, Matthew P., Martinez-Lage, Maria, Kieran, Mark W., Bandopadhayay, Pratiti, Beroukhim, Rameen, Fritsch, Gerhard, Getz, Gad, Rozenblatt-Rosen, Orit, Wucherpfennig, Kai W., Louis, David N., Monje, Michelle, Slavc, Irene, Ligon, Keith L., Golub, Todd R., Regev, Aviv, Bernstein, Bradley E., and Suvà, Mario L.

Published
2018

25. Biological material collection to advance translational research and treatment of children with CNS tumours: position paper from the SIOPE Brain Tumour Group

Author

Rutkowski, Stefan, Modena, Piergiorgio, Williamson, Daniel, Kerl, Kornelius, Nysom, Karsten, Pizer, Barry, Bartels, Ute, Puget, Stephanie, Doz, François, Michalski, Antony, von Hoff, Katja, Chevignard, Mathilde, Avula, Shivaram, Murray, Matthew J, Schönberger, Stefan, Czech, Thomas, Schouten-van Meeteren, Antoinette Y N, Kordes, Uwe, Kramm, Christof M, van Vuurden, Dannis G, Hulleman, Esther, Janssens, Geert O, Solanki, Guirish A, van Veelen, Marie-Luise C, Thomale, Ulrich, Schuhmann, Martin U, Jones, Chris, Giangaspero, Felice, Figarella-Branger, Dominique, Pietsch, Torsten, Clifford, Steve C, Pfister, Stefan M, and Van Gool, Stefaan W

Published
2018
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27. A European randomised controlled trial of the addition of etoposide to standard vincristine and carboplatin induction as part of an 18-month treatment programme for childhood (≤16 years) low grade glioma – A final report

Author

Gnekow, Astrid K., Slavc, Irene, Perilongo, Giorgio, Picton, Sue, Walker, David, Stokland, Tore, Sandstrom, Per Erik, Clausen, Niels, Arola, Mikko, Jonsson, Olafur Gisli, Cruz, Ofelia, Navajas, Aurora, Teijeiro, Anna, Grill, Jacques, Kalifa, Chantal, Raquin, Marie-Anne, Verlooy, Joris, Hans, Volkmar, Pietsch, Torsten, Scheurlen, Wolfram, Hainfellner, Johannes, Giangaspero, Felice, Ironside, James, Robson, Keith, Skullerud, Kari, Scheie, David, NN, Ruchoux, Marie-Madeleine, Jouvet, Anne, Figarella-Branger, Dominique, Lellouch-Toubiana, Arielle, Warmuth-Metz, Monika, Prayer, Daniela, Calderone, Milena, Jaspan, Tim, Bakke, Soren Jacob, Vazquez, Eli, Couanet, Dominique, Kortmann, Rolf D., Diekmann, Karin, Scarzello, Giovanni, Taylor, Roger, Lote, Knut, Giralt, Jordi, Carrie, Christian, Habrand, Jean Louis, Soerensen, Niels, Czech, Thomas, Chumas, Paul, Gustavson, Bengt, Zerah, Michel, Wabbels, Bettina, Pinello, Maria Luisa, Fielder, Alistair, Simmons, Ian, Christoffersen, Terje, Calaminus, Gabriele, Brockmann, Knut, Straeter, Ronald, Ebinger, Friedrich, Hernaiz-Driever, Pablo, Lackner, Herwig, Kennedy, Colin, Glaser, Adam, Stromberg, Bo, Indiano, Jose Ma, Rodary, Chantal, Bouffet, Eric, Frappaz, Didier, Faldum, Andreas, Emser, Angela, De Salvo, Gian Luca, Stephens, Suzanne, Machin, David, Le Deley, Marie-Cécile, Egeland, Thore, Freemann, Carolyn, Schrappe, Martin, Sposto, Richard, Walker, David A., Kandels, Daniela, Picton, Susan, Giorgio Perilongo, Sandstrom, Per Eric, Schmidt, René, Kilmartin, Denise, and De Paoli, Angela

Published
2017
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33. TERT expression is susceptible to BRAF and ETS-factor inhibition in BRAFV600E/TERT promoter double-mutated glioma

Author

Gabler, Lisa, Lötsch, Daniela, Kirchhofer, Dominik, van Schoonhoven, Sushilla, Schmidt, Hannah M., Mayr, Lisa, Pirker, Christine, Neumayer, Katharina, Dinhof, Carina, Kastler, Lucia, Azizi, Amedeo A., Dorfer, Christian, Czech, Thomas, Haberler, Christine, Peyrl, Andreas, Kumar, Rajiv, Slavc, Irene, Spiegl-Kreinecker, Sabine, Gojo, Johannes, and Berger, Walter

Published
2019
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37. The Site of Origin of Medulloblastoma: Surgical Observations Correlated to Molecular Groups.

Author

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

Subjects
*BRAIN, *SURGICAL therapeutics, *SEQUENCE analysis, *CONFIDENCE intervals, *NEUROSURGERY, *IMMUNOHISTOCHEMISTRY, *GLIOMAS, *MOLECULAR pathology, *ACQUISITION of data, *FISHER exact test, *GENE expression, *BRAIN tumors, *RISK assessment, *CHI-squared test, *MEDICAL records, *DESCRIPTIVE statistics, *CASE studies, *CHILDREN
Abstract

Simple Summary: Medulloblastoma is one of the most common malignant brain tumor types and comprises the molecular groups WNT-MB, SHH-MB TP53-wildtype, SHH-MB TP53-mutant and non-WNT/non-SHH MB. Developmental gene expression data suggest that these molecular groups arise from different sites of origin in the developing brain. Therefore, we hypothesized that intraoperative observation could enable the neurosurgeon to predict the molecular group during surgery and opt for a less aggressive resection in molecular groups with favorable prognosis to preserve neurological function. We reviewed the intraoperative reports, surgical videos and information on the molecular group of 58 patients who were operated at our institution from 1996 to 2020. Our data demonstrate that the correct prediction of the molecular group based on the intraoperatively observed site of origin was limited. Based on our results, we conclude that maximal safe resection should remain the aim of surgery irrespective of the observed site of origin. Developmental gene expression data from medulloblastoma (MB) suggest that WNT-MB originates from the region of the embryonic lower rhombic lip (LRL), whereas SHH-MB and non-WNT/non-SHH MB arise from cerebellar precursor matrix regions. This study aimed to analyze detailed intraoperative data with regard to the site of origin (STO) and compare these findings with the hypothesized regions of origin associated with the molecular group. A review of the institutional database identified 58 out of 72 pediatric patients who were operated for an MB at our department between 1996 and 2020 that had a detailed operative report and a surgical video as well as clinical and genetic classification data available for analysis. The STO was assessed based on intraoperative findings. Using the intraoperatively defined STO, "correct" prediction of molecular groups was feasible in 20% of WNT-MB, 60% of SHH-MB and 71% of non-WNT/non-SHH MB. The positive predictive values of the neurosurgical inspection to detect the molecular group were 0.21 (95% CI 0.08–0.48) for WNT-MB, 0.86 (95% CI 0.49–0.97) for SHH-MB and 0.73 (95% CI 0.57–0.85) for non-WNT/non-SHH MB. The present study demonstrated a limited predictive value of the intraoperatively observed STO for the prediction of the molecular group of MB. [ABSTRACT FROM AUTHOR]

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

Author

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

Subjects
GENE expression, CEREBROSPINAL fluid examination, DRIED blood spot testing
Abstract

To develop a robust and easily applicable miRNA detection method, we established a qRT-PCR method to detect miR517a and validated its expression across 11 ETMR tumor tissues as well as controls (Fig. MiR517a was significantly higher in blood of ETMR patients as compared to samples of non-tumor bearing controls and of medulloblastoma patients (MB) (Fig. To develop liquid biopsy tools for ETMR, we performed a comprehensive analysis of cell-free DNA as well as miRNA in cerebrospinal fluid and blood of ETMR patients (Fig. CNV of miR517a detected in tumor DNA and cfDNA from CSF for case#5 and case#9. d Swimmer plot of 5 ETMR patients, including all dates of surgery, liquid biopsies, and MRIs. e Illustration of experimental workflow (created with BioRender). [Extracted from the article]

Published
2023
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43. Proof-of-Concept for Liquid Biopsy Disease Monitoring of MYC -Amplified Group 3 Medulloblastoma by Droplet Digital PCR.

Author

Stepien, Natalia, Senfter, Daniel, Furtner, Julia, Haberler, Christine, Dorfer, Christian, Czech, Thomas, Lötsch-Gojo, Daniela, Mayr, Lisa, Hedrich, Cora, Baumgartner, Alicia, Aliotti-Lippolis, Maria, Schned, Hannah, Holler, Johannes, Bruckner, Katharina, Slavc, Irene, Azizi, Amedeo A., Peyrl, Andreas, Müllauer, Leonhard, Madlener, Sibylle, and Gojo, Johannes

Subjects
PUBLIC health surveillance, DISEASE progression, GLIOMAS, FLUORESCENCE in situ hybridization, RESEARCH funding, BODY fluid examination, POLYMERASE chain reaction, SENSITIVITY & specificity (Statistics), DATA analysis software, LONGITUDINAL method
Abstract

Simple Summary: MYC is a well-described oncogene across multiple cancer types. In medulloblastoma (MB), significance is subtype-dependent and associated with a particularly dismal outcome in MYC-amplified group 3 MBs. In our study, we established a highly sensitive and specific method for the detection of MYC amplification in cerebrospinal fluid (CSF) enabling its use as a liquid biopsy biomarker. We show preliminary results of its potential as a marker for early diagnosis, disease staging and monitoring. The fast and cost-effective method could substantially improve means of diagnosis and therapy monitoring in high-risk MBs. Background: Liquid biopsy diagnostic methods are an emerging complementary tool to imaging and pathology techniques across various cancer types. However, there is still no established method for the detection of molecular alterations and disease monitoring in MB, the most common malignant CNS tumor in the pediatric population. In the presented study, we investigated droplet digital polymerase chain reaction (ddPCR) as a highly sensitive method for the detection of MYC amplification in bodily fluids of group 3 MB patients. Methods: We identified a cohort of five MYC-amplified MBs by methylation array and FISH. Predesigned and wet-lab validated probes for ddPCR were used to establish the detection method and were validated in two MYC-amplified MB cell lines as well as tumor tissue of the MYC-amplified cohort. Finally, a total of 49 longitudinal CSF samples were analyzed at multiple timepoints during the course of the disease. Results: Detection of MYC amplification by ddPCR in CSF showed a sensitivity and specificity of 90% and 100%, respectively. We observed a steep increase in amplification rate (AR) at disease progression in 3/5 cases. ddPCR was proven to be more sensitive than cytology for the detection of residual disease. In contrast to CSF, MYC amplification was not detectable by ddPCR in blood samples. Conclusions: ddPCR proves to be a sensitive and specific method for the detection of MYC amplification in the CSF of MB patients. These results warrant implementation of liquid biopsy in future prospective clinical trials to validate the potential for improved diagnosis, disease staging and monitoring. [ABSTRACT FROM AUTHOR]

Published
2023
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45. Mild Malformation of Cortical Development with Oligodendroglial Hyperplasia in Frontal Lobe Epilepsy: A New Clinico‐Pathological Entity

Author

Schurr, Johannes, Coras, Roland, Rössler, Karl, Pieper, Tom, Kudernatsch, Manfred, Holthausen, Hans, Winkler, Peter, Woermann, Friedrich, Bien, Christian G., Polster, Tilman, Schulz, Reinhard, Kalbhenn, Thilo, Urbach, Horst, Becker, Albert, Grunwald, Thomas, Huppertz, Hans‐Juergen, Gil‐Nagel, Antonio, Toledano, Rafael, Feucht, Martha, Mühlebner, Angelika, Czech, Thomas, and Blümcke, Ingmar

Published
2017
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47. Visual outcomes after anterior temporal lobectomy and transsylvian selective amygdalohippocampectomy: A quantitative comparison of clinical and diffusion data.

Author

Pruckner, Philip, Nenning, Karl‐Heinz, Fischmeister, Florian Ph.S, Yildirim, Mehmet‐Salih, Schwarz, Michelle, Reitner, Andreas, Aull‐Watschinger, Susanne, Koren, Johannes, Baumgartner, Christoph, Prayer, Daniela, Rössler, Karl, Dorfer, Christian, Czech, Thomas, Pataraia, Ekaterina, Kasprian, Gregor, and Bonelli, Silvia

Subjects
TEMPORAL lobectomy, TEMPORAL lobe epilepsy, EPILEPSY surgery, VISUAL fields, VISUAL pathways, PERIMETRY
Abstract

Objective: Anterior temporal lobectomy (ATL) and transsylvian selective amygdalohippocampectomy (tsSAHE) are effective treatment strategies for intractable temporal lobe epilepsy but may cause visual field deficits (VFDs) by damaging the optic radiation (OpR). Due to the OpR's considerable variability and because it is indistinguishable from surrounding tissue without further technical guidance, it is highly vulnerable to iatrogenic injury. This imaging study uses a multimodal approach to assess visual outcomes after epilepsy surgery. Methods: We studied 62 patients who underwent ATL (n = 32) or tsSAHE (n = 30). Analysis of visual outcomes was conducted in four steps, including the assessment of (1) perimetry outcome (VFD incidence/extent, n = 44/40), (2) volumetric OpR tractography damage (n = 55), and the (3) relation of volumetric OpR tractography damage and perimetry outcome (n = 35). Furthermore, (4) fixel‐based analysis (FBA) was performed to assess micro‐ and macrostructural changes within the OpR following surgery (n = 36). Results: Altogether, 56% of all patients had postoperative VFDs (78.9% after ATL, 36.36% after tsSAHE, p =.011). VFDs and OpR tractography damage tended to be more severe within the ATL group (ATL vs. tsSAHE, integrity of contralateral upper quadrant: 65% vs. 97%, p =.002; OpR tractography damage: 69.2 mm3 vs. 3.8 mm3, p =.002). Volumetric OpR tractography damage could reliably predict VFD incidence (86% sensitivity, 78% specificity) and could significantly explain VFD extent (R2 =.47, p =.0001). FBA revealed a more widespread decline of fibre cross‐section within the ATL group. Significance: In the context of controversial visual outcomes following epilepsy surgery, this study provides clinical as well as neuroimaging evidence for a higher risk and greater severity of postoperative VFDs after ATL compared to tsSAHE. Volumetric OpR tractography damage is a feasible parameter to reliably predict this morbidity in both treatment groups and may ultimately support personalized planning of surgical candidates. Advanced diffusion analysis tools such as FBA offer a structural explanation of surgically induced visual pathway damage, allowing noninvasive quantification and visualization of micro‐ and macrostructural tract affection. [ABSTRACT FROM AUTHOR]

Published
2023
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48. Sociocultural variables have a major impact on participation in patients treated for paediatric posterior fossa tumours.

Author

Hoffmann‐Lamplmair, Doris, Gram, Alexandra, Krottendorfer, Kerstin, Peyrl, Andreas, Leiss, Ulrike, Czech, Thomas, Slavc, Irene, and Pletschko, Thomas

Subjects
SOCIAL participation, STATISTICS, KRUSKAL-Wallis Test, HYDROCEPHALUS, ECONOMIC status, MANN Whitney U Test, CANCER relapse, CANCER patients, RISK assessment, ACADEMIC achievement, SOCIAL context, DESCRIPTIVE statistics, QUESTIONNAIRES, EXERCISE, DATA analysis, ODDS ratio, VALUES (Ethics), SEIZURES (Medicine), INFRATENTORIAL brain tumors, EDUCATIONAL attainment, PARENTS, RELIGION, CHILDREN, ADOLESCENCE
Abstract

Background: This study investigates the severeness of participation barriers in patients surviving paediatric posterior fossa tumours (PFT) many years after treatment. In the past, aetiological studies on adverse outcome have primarily focused on pathobiological risk factors. The current analysis aims to investigate the importance of environmental variables. Methods: On average, 10 years after diagnosis, educational and social difficulties of 42 patients surviving paediatric PFT (mean age 17 years) were inquired using a self‐constructed questionnaire following the Psychosocial Resource‐Orientated Assessment (PREDI). Educational or social participation barriers were defined by self‐ and/or proxy‐reported difficulties in school or in peer relationships. Accordingly, the children and adolescents were categorized into groups of adequate and limited participation. Subsequently, the study identified potential pathobiological (treatment type, hydrocephalus, tumour relapse, gender, age at diagnosis, seizures and cerebellar mutism) and environmental (parental and maternal education, siblings, main language, discrepancies between personal and environmental values, regular physical activity and private living space) risk factors and investigated whether patients with adequate and limited participation differed in the number of risk factors. Results: Almost one decade after treatment, two thirds of patients experienced educational and/or social difficulties. Patients with limited participation were more frequently associated with environmental factors such as low maternal education degree, siblings, main language other than German, discrepancies between societal and personal values and irregular physical activity, as well as the pathobiological risk factors treatment type, hydrocephalus, tumour relapse, cerebellar mutism and seizures. These variables significantly discriminated between patients with and without limited participation. Conclusions: Limited participation in patients treated for paediatric PFT is common. Next to pathobiological, also environmental risk factors play a major role in educational and social participation barriers. This highlights the fact that solely considering pathobiology is not sufficient when investigating risk factors for the emergence of late sequelae. Future aetiological studies must adopt a biopsychosocial perspective. [ABSTRACT FROM AUTHOR]

Published
2023
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