Lamoureux Audrey-Anne, Fisher Michael J, Lemelle Lauriane, Pfaff Elke, Amir-Yazdani Pouneh, Kramm Christof, De Wilde Bram, Kazanowska Bernarda, Hutter Caroline, Pfister Stefan M, Sturm Dominik, Jones David T W, Orbach Daniel, Pierron Gaëlle, Raskin Scott, Drilon Alexander, Diamond Eli L, Harada Guilherme, Zapotocky Michal, Zamecnik Josef, Krskova Lenka, Ellezam Benjamin, Weil Alexander G, Venne Dominic, Barritault Marc, Leblond Pierre, Coltin Hallie, Hammad Rawan, Tabori Uri, Hawkins Cynthia, Hansford Jordan R, Meyran Deborah, Erker Craig, McFadden Kathryn, Sato Mariko, Gottardo Nicholas G, Dholaria Hetal, Nørøxe Dorte Schou, Goto Hiroaki, Ziegler David S, Lin Frank Y, Parsons Donald Williams, Lindsay Holly, Wong Tai-Tong, Liu Yen-Lin, Wu Kuo-Sheng, Franson Andrea T, Hwang Eugene, Aguilar-Bonilla Ana, Cheng Sylvia, Cacciotti Chantel, Massimino Maura, Schiavello Elisabetta, Wood Paul, Hoffman Lindsey M, Cappellano Andréa, Lassaletta Alvaro, Van Damme An, Llort Anna, Gerber Nicolas U, Spalato Ceruso Mariella, Bendel Anne E, Skrypek Maggie, Hamideh Dima, Mushtaq Naureen, Walter Andrew, Jabado Nada, Alsahlawi Aysha, Farmer Jean-Pierre, Coleman Christina, Mueller Sabine, Mazewski Claire, Aguilera Dolly, Robison Nathan J, O'Halloran Katrina, Abbou Samuel, Berlanga Pablo, Geoerger Birgit, Øra Ingrid, Moertel Christopher L, Razis Evangelia D, Vernadou Anastasia, Ducray François, Bronnimann Charlotte, Seizeur Romuald, Clarke Matthew, Resnick Adam C, Alves Mélanie, Jones Chris, Doz François, Laetsch Theodore W, Perreault Sébastien
Department of Neurosciences, University of Montreal, CHU Sainte-Justine, Montreal, Quebec, Canada.
Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Clin Cancer Res. 2025 Feb 3;31(3):561-572. doi: 10.1158/1078-0432.CCR-24-0581.
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.
在不到2%的中枢神经系统肿瘤中可检测到原肌球蛋白受体激酶（TRK）融合。关于受影响患者临床病程的数据有限。
我们对TRK融合驱动的中枢神经系统肿瘤患者进行了一项国际回顾性队列研究。
共确定了119例患者。诊断时的中位年龄为4.5岁。据报告，大多数患者的组织学与高级别胶质瘤（HGG；57.1%）诊断一致，其次是低级别胶质瘤（LGG；27.7%）。儿科患者预后较好，中位总生存期为185.5个月，而成人患者为24.8个月（P<0.0001）。与HGG相比，LGG患者的预后也更好（P = 0.0012）。拉罗替尼的客观缓解率为68.8%，而非靶向治疗为38.1%。
与成人胶质瘤和HGG相比，LGG患儿预后良好。TRK抑制剂似乎能改善肿瘤控制。
