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

IF 10 1区医学 Q1 ONCOLOGY Clinical Cancer Research Pub Date : 2024-12-03 DOI:10.1158/1078-0432.ccr-24-0581

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, Sébastien Perreault

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Abstract

Purpose: TRK fusions are detected in less than 2% of central nervous system tumors. There are limited data on the clinical course of affected patients. Experimental design: We conducted an international retrospective cohort study of patients with TRK fusion-driven CNS tumors. Results: 119 patients were identified. The median age at 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 to 24.8 months in adults (p<.0001). Patients with LGG also had a better outcome when compared to HGG (p=0.0012). The objective response was 68.8% with larotrectinib compared to 38.1% for non-targeted treatment. Conclusions: Children with LGG glioma had a favorable outcome compared to adult and HGG. TRK inhibitors appear to improve tumor control.

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含有NTRK基因融合的中枢神经系统肿瘤的临床特点及预后

目的：在不到2%的中枢神经系统肿瘤中检测到TRK融合。受影响患者的临床病程数据有限。实验设计：我们对TRK融合驱动的CNS肿瘤患者进行了一项国际回顾性队列研究。结果：共发现119例患者。诊断时的中位年龄为4.5岁。据报道，大多数患者的组织学诊断与高级别胶质瘤（HGG）（57.1%）一致，其次是低级别胶质瘤（LGG）（27.7%）。儿童患者预后较好，中位总生存期为185.5个月，而成人为24.8个月（p<.0001）。与HGG相比，LGG患者的预后也更好（p=0.0012）。larorectinib的客观缓解率为68.8%，而非靶向治疗的客观缓解率为38.1%。结论：与成人和HGG相比，儿童LGG胶质瘤的预后较好。TRK抑制剂似乎可以改善肿瘤控制。

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来源期刊

Clinical Cancer Research 医学-肿瘤学

CiteScore

20.10

自引率

1.70%

发文量

1207

审稿时长

2.1 months

期刊介绍： Clinical Cancer Research is a journal focusing on groundbreaking research in cancer, specifically in the areas where the laboratory and the clinic intersect. Our primary interest lies in clinical trials that investigate novel treatments, accompanied by research on pharmacology, molecular alterations, and biomarkers that can predict response or resistance to these treatments. Furthermore, we prioritize laboratory and animal studies that explore new drugs and targeted agents with the potential to advance to clinical trials. We also encourage research on targetable mechanisms of cancer development, progression, and metastasis.