Clinical characteristics and outcomes of central nervous system tumors harboring NTRK gene fusions Journal Article
| Authors: | Lamoureux, A. A.; Fisher, M. J.; Lemelle, L.; Pfaff, E.; Amir-Yazdani, P.; Kramm, C.; De Wilde, B.; Kazanowska, B.; Hutter, C.; Pfister, S. M.; Sturm, D.; Jones, D. T. W.; Orbach, D.; Pierron, G.; Raskin, S.; Drilon, A.; Diamond, E. L.; Harada, G.; Zapotocky, M.; Zamecnik, J.; Krskova, L.; Ellezam, B.; Weil, A. G.; Venne, D.; Barritault, M.; Leblond, P.; Coltin, H.; Hammad, R.; Tabori, U.; Hawkins, C.; Hansford, J. R.; Meyran, D.; Erker, C.; McFadden, K.; Sato, M.; Gottardo, N. G.; Dholaria, H.; Nørøxe, D. S.; Goto, H.; Ziegler, D. S.; Lin, F. Y.; Parsons, D. W.; Lindsay, H.; Wong, T. T.; Liu, Y. L.; Wu, K. S.; Franson, A. T.; Hwang, E.; Aguilar-Bonilla, A.; Cheng, S.; Cacciotti, C.; Massimino, M.; Schiavello, E.; Wood, P.; Hoffman, L. M.; Cappellano, A.; Lassaletta, A.; Van Damme, A.; Llort, A.; Gerber, N. U.; Ceruso, M. S.; Bendel, A. E.; Skrypek, M.; Hamideh, D.; Mushtaq, N.; Walter, A.; Jabado, N.; Alsahlawi, A.; Farmer, J. P.; Coleman, C.; Mueller, S.; Mazewski, C.; Aguilera, D.; Robison, N. J.; O’Halloran, K.; Abbou, S.; Berlanga, P.; Geoerger, B.; Øra, I.; Moertel, C. L.; Razis, E. D.; Vernadou, A.; Ducray, F.; Bronnimann, C.; Seizeur, R.; Clarke, M.; Resnick, A. C.; Alves, M.; Jones, C.; Doz, F.; Laetsch, T. W.; Perreault, S. |
| Article Title: | Clinical characteristics and outcomes of central nervous system tumors harboring NTRK gene fusions |
| 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. ©2024 The Authors. |
| Keywords: | adolescent; adult; cancer chemotherapy; child; controlled study; preschool child; treatment outcome; aged; child, preschool; middle aged; retrospective studies; young adult; unclassified drug; major clinical study; overall survival; genetics; mortality; glioma; cancer grading; metastasis; progression free survival; protein kinase inhibitor; cohort analysis; pathology; pyrimidines; retrospective study; histology; central nervous system tumor; central nervous system; central nervous system neoplasms; protein kinase inhibitors; infant; neuroblastoma; membrane glycoproteins; pyrazole derivative; pyrazoles; membrane protein; gene fusion; oncogene proteins, fusion; cancer control; pyrimidine derivative; protein kinase; therapy; brain derived neurotrophic factor receptor; receptor, trkb; pathological complete response; diagnostic test accuracy study; overall response rate; protein tyrosine kinase a; neurotrophin 3 receptor; tropomyosin; high throughput sequencing; neoplasm grading; receptor, trka; juvenile xanthogranuloma; humans; prognosis; human; male; female; article; entrectinib; tropomyosin-related kinase-b, human; receptor, trkc; larotrectinib; selitrectinib; neurotrophic tyrosine receptor kinase; oncogene fusion protein; ntrk1 protein, human; ntrk3 protein, human |
| Journal Title: | Clinical Cancer Research |
| Volume: | 31 |
| Issue: | 3 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2025-02-01 |
| Start Page: | 561 |
| End Page: | 572 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-24-0581 |
| PUBMED: | 39625867 |
| PROVIDER: | scopus |
| PMCID: | PMC11788648 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Source: Scopus |
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