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Clinical characteristics and outcomes of central nervous system tumors harboring NTRK gene fusions

Tropomyosin receptor kinase (TRK) fusions are detected in less than 2% of central nervous system tumors. There are limited data on the clinical course of affected patients.We conducted an international retrospective cohort study of patients with TRK fusion-driven central nervous system tumors.A tota...

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Main Authors: Lamoureux, Audrey-Anne (Author) , Fisher, Michael J. (Author) , Lemelle, Lauriane (Author) , Pfaff, Elke (Author) , Amir-Yazdani, Pouneh (Author) , Kramm, Christof (Author) , De Wilde, Bram (Author) , Kazanowska, Bernarda (Author) , Hutter, Caroline (Author) , Pfister, Stefan (Author) , Sturm, Dominik (Author) , Jones, David T. W. (Author) , Orbach, Daniel (Author) , Pierron, Gaëlle (Author) , Raskin, Scott (Author) , Drilon, Alexander (Author) , Diamond, Eli L. (Author) , Harada, Guilherme (Author) , Zapotocky, Michal (Author) , Zamecnik, Josef (Author) , Krskova, Lenka (Author) , Ellezam, Benjamin (Author) , Weil, Alexander G. (Author) , Venne, Dominic (Author) , Barritault, Marc (Author) , Leblond, Pierre (Author) , Coltin, Hallie (Author) , Hammad, Rawan (Author) , Tabori, Uri (Author) , Hawkins, Cynthia (Author) , Hansford, Jordan R. (Author) , Meyran, Deborah (Author) , Erker, Craig (Author) , McFadden, Kathryn (Author) , Sato, Mariko (Author) , Gottardo, Nicholas G. (Author) , Dholaria, Hetal (Author) , Nørøxe, Dorte Schou (Author) , Goto, Hiroaki (Author) , Ziegler, David S. (Author) , Lin, Frank Y. (Author) , Parsons, Donald Williams (Author) , Lindsay, Holly (Author) , Wong, Tai-Tong (Author) , Liu, Yen-Lin (Author) , Wu, Kuo-Sheng (Author) , Franson, Andrea T. (Author) , Hwang, Eugene (Author) , Aguilar-Bonilla, Ana (Author) , Cheng, Sylvia (Author) , Cacciotti, Chantel (Author) , Massimino, Maura (Author) , Schiavello, Elisabetta (Author) , Wood, Paul (Author) , Hoffman, Lindsey M. (Author) , Cappellano, Andréa (Author) , Lassaletta, Alvaro (Author) , Van Damme, An (Author) , Llort, Anna (Author) , Gerber, Nicolas U. (Author) , Spalato Ceruso, Mariella (Author) , Bendel, Anne E. (Author) , Skrypek, Maggie (Author) , Hamideh, Dima (Author) , Mushtaq, Naureen (Author) , Walter, Andrew (Author) , Jabado, Nada (Author) , Alsahlawi, Aysha (Author) , Farmer, Jean-Pierre (Author) , Coleman, Christina (Author) , Mueller, Sabine (Author) , Mazewski, Claire (Author) , Aguilera, Dolly (Author) , Robison, Nathan J. (Author) , O’Halloran, Katrina (Author) , Abbou, Samuel (Author) , Berlanga, Pablo (Author) , Geoerger, Birgit (Author) , Øra, Ingrid (Author) , Moertel, Christopher L. (Author) , Razis, Evangelia D. (Author) , Vernadou, Anastasia (Author) , Ducray, François (Author) , Bronnimann, Charlotte (Author) , Seizeur, Romuald (Author) , Clarke, Matthew (Author) , Resnick, Adam C. (Author) , Alves, Mélanie (Author) , Jones, Chris (Author) , Doz, François (Author) , Laetsch, Theodore W. (Author) , Perreault, Sébastien (Author)
Format: Article (Journal)
Language:English
Published: 1 February 2025
In: Clinical cancer research
Year: 2025, Volume: 31, Issue: 3, Pages: 561-572
ISSN:1557-3265
DOI:10.1158/1078-0432.CCR-24-0581
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1158/1078-0432.CCR-24-0581
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Author Notes:Audrey-Anne Lamoureux, Michael J. Fisher, Lauriane Lemelle, Elke Pfaff, Pouneh Amir-Yazdani, Christof Kramm, Bram De Wilde, Bernarda Kazanowska, Caroline Hutter, Stefan M. Pfister, Dominik Sturm, David T.W. Jones, Daniel Orbach, Gaëlle Pierron, Scott Raskin, Alexander Drilon, Eli L. Diamond, Guilherme Harada, Michal Zapotocky, Josef Zamecnik, Lenka Krskova, Benjamin Ellezam, Alexander G. Weil, Dominic Venne, Marc Barritault, Pierre Leblond, Hallie Coltin, Rawan Hammad, Uri Tabori, Cynthia Hawkins, Jordan R. Hansford, Deborah Meyran, Craig Erker, Kathryn McFadden, Mariko Sato, Nicholas G. Gottardo, Hetal Dholaria, Dorte Schou Nørøxe, Hiroaki Goto, David S. Ziegler, Frank Y. Lin, Donald Williams Parsons, Holly Lindsay, Tai-Tong Wong, Yen-Lin Liu, Kuo-Sheng Wu, Andrea T. Franson, Eugene Hwang, Ana Aguilar-Bonilla, Sylvia Cheng, Chantel Cacciotti, Maura Massimino, Elisabetta Schiavello, Paul Wood, Lindsey M. Hoffman, Andréa Cappellano, Alvaro Lassaletta, An Van Damme, Anna Llort, Nicolas U. Gerber, Mariella Spalato Ceruso, Anne E. Bendel, Maggie Skrypek, Dima Hamideh, Naureen Mushtaq, Andrew Walter, Nada Jabado, Aysha Alsahlawi, Jean-Pierre Farmer, Christina Coleman, Sabine Mueller, Claire Mazewski, Dolly Aguilera, Nathan J. Robison, Katrina O’Halloran, Samuel Abbou, Pablo Berlanga, Birgit Geoerger, Ingrid Øra, Christopher L. Moertel, Evangelia D. Razis, Anastasia Vernadou, François Ducray, Charlotte Bronnimann, Romuald Seizeur, Matthew Clarke, Adam C. Resnick, Mélanie Alves, Chris Jones, François Doz, Theodore W. Laetsch, and Sébastien Perreault
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Summary:Tropomyosin receptor kinase (TRK) fusions are detected in less than 2% of central nervous system tumors. There are limited data on the clinical course of affected patients.We conducted an international retrospective cohort study of patients with TRK fusion-driven central nervous system tumors.A total of 119 patients were identified. The median age at the time of diagnosis was 4.5 years. The majority were reported to have a histology consistent with a diagnosis of high-grade glioma (HGG; 57.1%) followed by low-grade glioma (LGG; 27.7%). Pediatric patients had a better prognosis, with a median overall survival of 185.5 months compared with 24.8 months in adults (P < 0.0001). Patients with LGG also had a better outcome when compared with HGG (P = 0.0012). The objective response was 68.8% with larotrectinib compared with 38.1% for nontargeted treatment.Children with LGG had a favorable outcome compared with adult glioma and HGG. TRK inhibitors seem to improve tumor control.
Item Description:Gesehen am 06.08.2025
Physical Description:Online Resource
ISSN:1557-3265
DOI:10.1158/1078-0432.CCR-24-0581

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