Clinical Characteristics and Outcomes of Central Nervous System Tumors Harboring NTRK Gene Fusions

Lamoureux, AA; Fisher, MJ; Lemelle, L; Pfaff, E; Amir-Yazdani, P; Kramm, C; De Wilde, B; Kazanowska, B; Hutter, C; Pfister, SM; Sturm, D; Jones, DTW; Orbach, D; Pierron, G; Raskin, S; Drilon, A; Diamond, EL; Harada, G; Zapotocky, M; Zamecnik, J; Krskova, L; Ellezam, B; Weil, AG; Venne, D; Barritault, M; Leblond, P; Coltin, H; Hammad, R; Tabori, U; Hawkins, C; Hansford, JR; Meyran, D; Erker, C; McFadden, K; Sato, M; Gottardo, NG; Dholaria, H; N&#248;r&#248;xe, DS; Goto, H; Ziegler, DS; Lin, FY; Parsons, DW; Lindsay, H; Wong, TT; Liu, YL; Wu, KS; Franson, AT; Hwang, E; Aguilar-Bonilla, A; Cheng, S; Cacciotti, C; Massimino, M; Schiavello, E; Wood, P; Hoffman, LM; Cappellano, A; Lassaletta, A; Van Damme, A; Llort, A; Gerber, NU; Spalato Ceruso, M; Bendel, AE; Skrypek, M; Hamideh, D; Mushtaq, N; Walter, A; Jabado, N; Alsahlawi, A; Farmer, JP; Coleman, C; Mueller, S; Mazewski, C; Aguilera, D; Robison, NJ; O&#39;Halloran, K; Abbou, S; Berlanga, P; Geoerger, B; &#216;ra, I; Moertel, CL; Razis, ED; Vernadou, A; Ducray, F; Bronnimann, C; Seizeur, R; Clarke, M; Resnick, AC; Alves, M; Jones, C; Doz, F; Laetsch, TW; Perreault, S

Author(s): Lamoureux, AA; Fisher, MJ; Lemelle, L; Pfaff, E; Amir-Yazdani, P; Kramm, C; De Wilde, B; Kazanowska, B; Hutter, C; Pfister, SM; Sturm, D; Jones, DTW; Orbach, D; Pierron, G; Raskin, S; Drilon, A; Diamond, EL; Harada, G; Zapotocky, M; Zamecnik, J; Krskova, L; Ellezam, B; Weil, AG; Venne, D; Barritault, M; Leblond, P; Coltin, H; Hammad, R; Tabori, U; Hawkins, C; Hansford, JR; Meyran, D; Erker, C; McFadden, K; Sato, M; Gottardo, NG; Dholaria, H; Nørøxe, DS; Goto, H; Ziegler, DS; Lin, FY; Parsons, DW; Lindsay, H; Wong, TT; Liu, YL; Wu, KS; Franson, AT; Hwang, E; Aguilar-Bonilla, A; Cheng, S; Cacciotti, C; Massimino, M; Schiavello, E; Wood, P; Hoffman, LM; Cappellano, A; Lassaletta, A; Van Damme, A; Llort, A; Gerber, NU; Spalato Ceruso, M; Bendel, AE; Skrypek, M; Hamideh, D; Mushtaq, N; Walter, A; Jabado, N; Alsahlawi, A; Farmer, JP; Coleman, C; Mueller, S; Mazewski, C; Aguilera, D; Robison, NJ; O'Halloran, K; Abbou, S; Berlanga, P; Geoerger, B; Øra, I; Moertel, CL; Razis, ED; Vernadou, A; Ducray, F; Bronnimann, C; Seizeur, R; Clarke, M; Resnick, AC; Alves, M; Jones, C; Doz, F; Laetsch, TW; Perreault, S;
Details: Publication Year 2025-02-03,Volume 31,Issue #3,Page 561-572
Journal Title: Clinical Cancer Research
Publication Type: Research article
Abstract: PURPOSE: 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. EXPERIMENTAL DESIGN: We conducted an international retrospective cohort study of patients with TRK fusion-driven central nervous system tumors. RESULTS: 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. CONCLUSIONS: Children with LGG had a favorable outcome compared with adult glioma and HGG. TRK inhibitors seem to improve tumor control.
Publisher: American Association for Cancer Research
Keywords: Humans; Female; Male; Child; Child, Preschool; Adult; Adolescent; *Central Nervous System Neoplasms/genetics/therapy/mortality/pathology; *Receptor, trkA/genetics/antagonists & inhibitors; *Glioma/genetics/pathology/mortality/therapy; Prognosis; *Oncogene Proteins, Fusion/genetics; Young Adult; Retrospective Studies; Infant; Middle Aged; Receptor, trkB/genetics/antagonists & inhibitors; Protein Kinase Inhibitors/therapeutic use; Pyrazoles/therapeutic use; Pyrimidines/therapeutic use; Treatment Outcome; Receptor, trkC/genetics/antagonists & inhibitors; Neoplasm Grading; Gene Fusion; Aged; Membrane Glycoproteins
Department(s): Laboratory Research
Publisher's Version: https://doi.org/10.1158/1078-0432.Ccr-24-0581
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-02-04 07:05:29

Last Modified: 2025-02-04 07:05:55