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

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

doi:10.1158/1078-0432.CCR-24-0581

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

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

University of Montreal
The Children's Hospital of Philadelphia
Institut Curie
Hopp Children’s Cancer Center (KiTZ)
Heidelberg University
German Cancer Research Center
University of Göttingen
Ghent University
Wrocław Medical University
Medical University of Vienna
Children's Cancer Research Institute
University of Cincinnati
Memorial Sloan-Kettering Cancer Center
Charles University
Hospices civils de Lyon
Centre Léon Bérard
University of Toronto
King Abdulaziz University
Michael Rice Centre for Hematology and Oncology
South Australian Health And Medical Research Institute
University of Adelaide
Royal Children's Hospital
Murdoch Children's Research Institute
Peter Maccallum Cancer Centre
University of Melbourne
IWK Health Centre
University of California at Irvine
Perth Children's Hospital
Telethon Kids Institute
University of Western Australia
University of Copenhagen
Kanagawa Children's Medical Center
University of New South Wales
Sydney Children's Hospital
Texas Children's Hospital Houston
Taipei Medical University
University of Michigan, Ann Arbor
Children’s National Hospital
Orlando Regional Medical Center
University of British Columbia
Western University
IRCCS Fondazione Istituto Nazionale per lo studio e la cura dei tumori - Milano
Monash Children’s Hospital
Monash University
Hudson Institute of Medical Research
Phoenix Children's Hospital
Universidade Federal de São Paulo
Hospital Infantil Universitario Nino Jesus de Madrid
Université catholique de Louvain
Vall d’Hebron Children’s Hospital
University of Zurich
Centre Georges-François Leclerc
Children's Minnesota
American University of Beirut
Aga Khan University
McGill University
University of California at San Francisco
Emory University
Children's Hospital Los Angeles
Gustave Roussy Institute
Lund University
Karolinska Institutet
University of Minnesota Twin Cities
Hygeia Hospital
Hôpital Saint-André
CHU de Brest
Institute of Cancer Research
Université Paris Cité

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

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.

Original language	English
Pages (from-to)	561-572
Number of pages	12
Journal	Clinical Cancer Research
Volume	31
Issue number	3
DOIs	https://doi.org/10.1158/1078-0432.CCR-24-0581
State	Published - 3 Feb 2025

Keywords

Adolescent
Adult
Aged
Central Nervous System Neoplasms/genetics
Child
Child, Preschool
Female
Gene Fusion
Glioma/genetics
Humans
Infant
Male
Membrane Glycoproteins
Middle Aged
Neoplasm Grading
Oncogene Proteins, Fusion/genetics
Prognosis
Protein Kinase Inhibitors/therapeutic use
Pyrazoles/therapeutic use
Pyrimidines/therapeutic use
Receptor, trkA/genetics
Receptor, trkB/genetics
Receptor, trkC/genetics
Retrospective Studies
Treatment Outcome
Young Adult

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10.1158/1078-0432.CCR-24-0581

Cite this

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., ... Perreault, S. (2025). Clinical Characteristics and Outcomes of Central Nervous System Tumors Harboring NTRK Gene Fusions. Clinical Cancer Research, 31(3), 561-572. https://doi.org/10.1158/1078-0432.CCR-24-0581

@article{6386e2f108ec4ab794e9bc1b40949561,

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.",

keywords = "Adolescent, Adult, Aged, Central Nervous System Neoplasms/genetics, Child, Child, Preschool, Female, Gene Fusion, Glioma/genetics, Humans, Infant, Male, Membrane Glycoproteins, Middle Aged, Neoplasm Grading, Oncogene Proteins, Fusion/genetics, Prognosis, Protein Kinase Inhibitors/therapeutic use, Pyrazoles/therapeutic use, Pyrimidines/therapeutic use, Receptor, trkA/genetics, Receptor, trkB/genetics, Receptor, trkC/genetics, Retrospective Studies, Treatment Outcome, Young Adult",

author = "Lamoureux, \{Audrey Anne\} and Fisher, \{Michael J.\} and Lauriane Lemelle and Elke Pfaff and Pouneh Amir-Yazdani and Christof Kramm and \{De Wilde\}, Bram and Bernarda Kazanowska and Caroline Hutter and Pfister, \{Stefan M.\} and Dominik Sturm and Jones, \{David T.W.\} and Daniel Orbach and Ga{\"e}lle Pierron and Scott Raskin and Alexander Drilon and Diamond, \{Eli L.\} and Guilherme Harada and Michal Zapotocky and Josef Zamecnik and Lenka Krskova and Benjamin Ellezam and Weil, \{Alexander G.\} and Dominic Venne and Marc Barritault and Pierre Leblond and Hallie Coltin and Rawan Hammad and Uri Tabori and Cynthia Hawkins and Hansford, \{Jordan R.\} and Deborah Meyran and Craig Erker and Kathryn McFadden and Mariko Sato and Gottardo, \{Nicholas G.\} and Hetal Dholaria and N{\o}r{\o}xe, \{Dorte Schou\} and Hiroaki Goto and Ziegler, \{David S.\} and Lin, \{Frank Y.\} and Parsons, \{Donald Williams\} and Holly Lindsay and Wong, \{Tai Tong\} and Liu, \{Yen Lin\} and Wu, \{Kuo Sheng\} and Franson, \{Andrea T.\} and Eugene Hwang and Ana Aguilar-Bonilla and Sylvia Cheng and Chantel Cacciotti and Maura Massimino and Elisabetta Schiavello and Paul Wood and Hoffman, \{Lindsey M.\} and Andr{\'e}a Cappellano and Alvaro Lassaletta and \{Van Damme\}, An and Anna Llort and Gerber, \{Nicolas U.\} and Ceruso, \{Mariella Spalato\} and Bendel, \{Anne E.\} and Maggie Skrypek and Dima Hamideh and Naureen Mushtaq and Andrew Walter and Nada Jabado and Aysha Alsahlawi and Farmer, \{Jean Pierre\} and Christina Coleman and Sabine Mueller and Claire Mazewski and Dolly Aguilera and Robison, \{Nathan J.\} and Katrina O{\textquoteright}Halloran and Samuel Abbou and Pablo Berlanga and Birgit Geoerger and Ingrid {\O}ra and Moertel, \{Christopher L.\} and Razis, \{Evangelia D.\} and Anastasia Vernadou and Fran{\c c}ois Ducray and Charlotte Bronnimann and Romuald Seizeur and Matthew Clarke and Resnick, \{Adam C.\} and M{\'e}lanie Alves and Chris Jones and Fran{\c c}ois Doz and Laetsch, \{Theodore W.\} and S{\'e}bastien Perreault",

note = "{\textcopyright}2024 The Authors; Published by the American Association for Cancer Research.",

year = "2025",

month = feb,

day = "3",

doi = "10.1158/1078-0432.CCR-24-0581",

language = "English",

volume = "31",

pages = "561--572",

journal = "Clinical Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research Inc.",

number = "3",

}

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, Ceruso, MS, 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 2025, 'Clinical Characteristics and Outcomes of Central Nervous System Tumors Harboring NTRK Gene Fusions', Clinical Cancer Research, vol. 31, no. 3, pp. 561-572. https://doi.org/10.1158/1078-0432.CCR-24-0581

TY - JOUR

T1 - Clinical Characteristics and Outcomes of Central Nervous System Tumors Harboring NTRK Gene Fusions

AU - Lamoureux, Audrey Anne

AU - Fisher, Michael J.

AU - Lemelle, Lauriane

AU - Pfaff, Elke

AU - Amir-Yazdani, Pouneh

AU - Kramm, Christof

AU - De Wilde, Bram

AU - Kazanowska, Bernarda

AU - Hutter, Caroline

AU - Pfister, Stefan M.

AU - Sturm, Dominik

AU - Jones, David T.W.

AU - Orbach, Daniel

AU - Pierron, Gaëlle

AU - Raskin, Scott

AU - Drilon, Alexander

AU - Diamond, Eli L.

AU - Harada, Guilherme

AU - Zapotocky, Michal

AU - Zamecnik, Josef

AU - Krskova, Lenka

AU - Ellezam, Benjamin

AU - Weil, Alexander G.

AU - Venne, Dominic

AU - Barritault, Marc

AU - Leblond, Pierre

AU - Coltin, Hallie

AU - Hammad, Rawan

AU - Tabori, Uri

AU - Hawkins, Cynthia

AU - Hansford, Jordan R.

AU - Meyran, Deborah

AU - Erker, Craig

AU - McFadden, Kathryn

AU - Sato, Mariko

AU - Gottardo, Nicholas G.

AU - Dholaria, Hetal

AU - Nørøxe, Dorte Schou

AU - Goto, Hiroaki

AU - Ziegler, David S.

AU - Lin, Frank Y.

AU - Parsons, Donald Williams

AU - Lindsay, Holly

AU - Wong, Tai Tong

AU - Liu, Yen Lin

AU - Wu, Kuo Sheng

AU - Franson, Andrea T.

AU - Hwang, Eugene

AU - Aguilar-Bonilla, Ana

AU - Cheng, Sylvia

AU - Cacciotti, Chantel

AU - Massimino, Maura

AU - Schiavello, Elisabetta

AU - Wood, Paul

AU - Hoffman, Lindsey M.

AU - Cappellano, Andréa

AU - Lassaletta, Alvaro

AU - Van Damme, An

AU - Llort, Anna

AU - Gerber, Nicolas U.

AU - Ceruso, Mariella Spalato

AU - Bendel, Anne E.

AU - Skrypek, Maggie

AU - Hamideh, Dima

AU - Mushtaq, Naureen

AU - Walter, Andrew

AU - Jabado, Nada

AU - Alsahlawi, Aysha

AU - Farmer, Jean Pierre

AU - Coleman, Christina

AU - Mueller, Sabine

AU - Mazewski, Claire

AU - Aguilera, Dolly

AU - Robison, Nathan J.

AU - O’Halloran, Katrina

AU - Abbou, Samuel

AU - Berlanga, Pablo

AU - Geoerger, Birgit

AU - Øra, Ingrid

AU - Moertel, Christopher L.

AU - Razis, Evangelia D.

AU - Vernadou, Anastasia

AU - Ducray, François

AU - Bronnimann, Charlotte

AU - Seizeur, Romuald

AU - Clarke, Matthew

AU - Resnick, Adam C.

AU - Alves, Mélanie

AU - Jones, Chris

AU - Doz, François

AU - Laetsch, Theodore W.

AU - Perreault, Sébastien

PY - 2025/2/3

Y1 - 2025/2/3

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Aged

KW - Central Nervous System Neoplasms/genetics

KW - Child

KW - Child, Preschool

KW - Female

KW - Gene Fusion

KW - Glioma/genetics

KW - Humans

KW - Infant

KW - Male

KW - Membrane Glycoproteins

KW - Middle Aged

KW - Neoplasm Grading

KW - Oncogene Proteins, Fusion/genetics

KW - Prognosis

KW - Protein Kinase Inhibitors/therapeutic use

KW - Pyrazoles/therapeutic use

KW - Pyrimidines/therapeutic use

KW - Receptor, trkA/genetics

KW - Receptor, trkB/genetics

KW - Receptor, trkC/genetics

KW - Retrospective Studies

KW - Treatment Outcome

KW - Young Adult

UR - https://www.scopus.com/pages/publications/85217005317

U2 - 10.1158/1078-0432.CCR-24-0581

DO - 10.1158/1078-0432.CCR-24-0581

M3 - Article

C2 - 39625867

AN - SCOPUS:85217005317

SN - 1078-0432

VL - 31

SP - 561

EP - 572

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 3

ER -

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

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Keywords

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