Outcomes of BRAF V600E Pediatric Gliomas Treated With Targeted BRAF Inhibition
Liana Nobre
1
,
Michal Zápotocký
1, 2
,
Vijay Ramaswamy
1, 3, 4
,
Scott Ryall
1
,
Julie Bennett
1
,
Daniel Alderete
5
,
Julia Balaguer Guill
6
,
Lorena Baroni
5
,
Ute Bartels
1
,
Abhishek Bavle
7
,
Miriam Bornhorst
8
,
Daniel R. Boué
9
,
Adela Cañete
6
,
Murali Chintagumpala
10
,
Scott L Coven
11
,
Ofelia Cruz
12
,
Sonika Dahiya
13
,
Peter Dirks
14, 15
,
Ira J. Dunkel
16
,
David Eisenstat
17
,
Cecile Faure Conter
18
,
Elizabeth Finch
19
,
Jonathan L. Finlay
9
,
Didier Frappaz
18
,
Maria Luisa Garrè
20
,
Karen Gauvain
13
,
Anne Grete Bechensteen
21
,
Jordan R. Hansford
22
,
Inga Harting
23
,
Péter Hauser
24
,
Lili-Naz Hazrati
25
,
Annie Huang
1, 14
,
Sarah G Injac
10
,
Valentina Iurilli
20
,
Matthias Karajannis
16
,
Gurcharanjeet Kaur
16
,
Martin Kynčl
2
,
Lenka Krskova
2
,
Normand Laperriere
1
,
Valérie Larouche
26
,
Alvaro Lassaletta
27
,
Sarah Leary
28
,
Frank Lin
10
,
Samantha Mascelli
20
,
Tara McKeown
1
,
Till Milde
23
,
Andres Morales La Madrid
12
,
Giovanni Morana
20
,
Helena Mörse
29
,
Naureen Mushtaq
30
,
Diana S Osorio
9
,
Roger Packer
8
,
Zdenek Pavelka
31
,
Eduardo Quiroga-Cantero
32
,
James T. Rutka
14, 15
,
Magnus Sabel
33
,
Duarte Salgado
34
,
Palma Solano
32
,
Jaroslav Sterba
31
,
Jack Su
10
,
David Sumerauer
2
,
Michael D. Taylor
3, 14, 15, 25, 35
,
Helen Toledano
36
,
Derek S. Tsang
1
,
Mariana Valente Fernandes
34
,
Frank van Landeghem
17
,
Cornelis M Van Tilburg
23
,
Bev Wilson
17
,
Olaf Witt
23
,
Josef Zámečník
2
,
Eric Bouffet
1
,
Cynthia Hawkins
14, 25, 37
,
Uri Tabori
1, 14
2
9
17
18
Institute d’Hémato-Oncologie Pédiatrique, Centre Leon Berard, Lyon, France
|
22
23
Hopp Children’s Cancer Center Heidelberg, Heidelberg, Germany
|
31
33
34
Portuguese Oncology Institute, Lisbon, Portugal
|
35
Department of Surgery, University of Ontario, Toronto, ON, Canada
|
36
Schneiders Children’s Medical Center of Israel, Petah Tikva, Israel
|
Тип публикации: Journal Article
Дата публикации: 2020-11-09
scimago Q1
wos Q1
БС2
SJR: 2.409
CiteScore: 6.7
Impact factor: 5.6
ISSN: 24734284
PubMed ID:
32923898
Cancer Research
Oncology
Краткое описание
PURPOSE
Children with pediatric gliomas harboring a BRAF V600E mutation have poor outcomes with current chemoradiotherapy strategies. Our aim was to study the role of targeted BRAF inhibition in these tumors.
PATIENTS AND METHODS
We collected clinical, imaging, molecular, and outcome information from patients with BRAF V600E–mutated glioma treated with BRAF inhibition across 29 centers from multiple countries.
RESULTS
Sixty-seven patients were treated with BRAF inhibition (pediatric low-grade gliomas [PLGGs], n = 56; pediatric high-grade gliomas [PHGGs], n = 11) for up to 5.6 years. Objective responses were observed in 80% of PLGGs, compared with 28% observed with conventional chemotherapy ( P < .001). These responses were rapid (median, 4 months) and sustained in 86% of tumors up to 5 years while receiving therapy. After discontinuation of BRAF inhibition, 76.5% (13 of 17) of patients with PLGG experienced rapid progression (median, 2.3 months). However, upon rechallenge with BRAF inhibition, 90% achieved an objective response. Poor prognostic factors in conventional therapies, such as concomitant homozygous deletion of CDKN2A, were not associated with lack of response to BRAF inhibition. In contrast, only 36% of those with PHGG responded to BRAF inhibition, with all but one tumor progressing within 18 months. In PLGG, responses translated to 3-year progression-free survival of 49.6% (95% CI, 35.3% to 69.5%) versus 29.8% (95% CI, 20% to 44.4%) for BRAF inhibition versus chemotherapy, respectively ( P = .02).
CONCLUSION
Use of BRAF inhibition results in robust and durable responses in BRAF V600E–mutated PLGG. Prospective studies are required to determine long-term survival and functional outcomes with BRAF inhibitor therapy in childhood gliomas.
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(43.16%)
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ГОСТ |
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MLA
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ГОСТ
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Nobre L. et al. Outcomes of BRAF V600E Pediatric Gliomas Treated With Targeted BRAF Inhibition // JCO Precision Oncology. 2020. Vol. 4. No. 4. pp. 561-571.
ГОСТ со всеми авторами (до 50)
Скопировать
Nobre L. et al. Outcomes of BRAF V600E Pediatric Gliomas Treated With Targeted BRAF Inhibition // JCO Precision Oncology. 2020. Vol. 4. No. 4. pp. 561-571.
Цитировать
RIS
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TY - JOUR
DO - 10.1200/po.19.00298
UR - https://doi.org/10.1200/po.19.00298
TI - Outcomes of BRAF V600E Pediatric Gliomas Treated With Targeted BRAF Inhibition
T2 - JCO Precision Oncology
AU - Nobre, Liana
AU - Zápotocký, Michal
AU - Ramaswamy, Vijay
AU - Ryall, Scott
AU - Bennett, Julie
AU - Alderete, Daniel
AU - Balaguer Guill, Julia
AU - Baroni, Lorena
AU - Bartels, Ute
AU - Bavle, Abhishek
AU - Bornhorst, Miriam
AU - Boué, Daniel R.
AU - Cañete, Adela
AU - Chintagumpala, Murali
AU - Coven, Scott L
AU - Cruz, Ofelia
AU - Dahiya, Sonika
AU - Dirks, Peter
AU - Dunkel, Ira J.
AU - Eisenstat, David
AU - Faure Conter, Cecile
AU - Finch, Elizabeth
AU - Finlay, Jonathan L.
AU - Frappaz, Didier
AU - Garrè, Maria Luisa
AU - Gauvain, Karen
AU - Bechensteen, Anne Grete
AU - Hansford, Jordan R.
AU - Harting, Inga
AU - Hauser, Péter
AU - Hazrati, Lili-Naz
AU - Huang, Annie
AU - Injac, Sarah G
AU - Iurilli, Valentina
AU - Karajannis, Matthias
AU - Kaur, Gurcharanjeet
AU - Kynčl, Martin
AU - Krskova, Lenka
AU - Laperriere, Normand
AU - Larouche, Valérie
AU - Lassaletta, Alvaro
AU - Leary, Sarah
AU - Lin, Frank
AU - Mascelli, Samantha
AU - McKeown, Tara
AU - Milde, Till
AU - Morales La Madrid, Andres
AU - Morana, Giovanni
AU - Mörse, Helena
AU - Mushtaq, Naureen
AU - Osorio, Diana S
AU - Packer, Roger
AU - Pavelka, Zdenek
AU - Quiroga-Cantero, Eduardo
AU - Rutka, James T.
AU - Sabel, Magnus
AU - Salgado, Duarte
AU - Solano, Palma
AU - Sterba, Jaroslav
AU - Su, Jack
AU - Sumerauer, David
AU - Taylor, Michael D.
AU - Toledano, Helen
AU - Tsang, Derek S.
AU - Valente Fernandes, Mariana
AU - van Landeghem, Frank
AU - Van Tilburg, Cornelis M
AU - Wilson, Bev
AU - Witt, Olaf
AU - Zámečník, Josef
AU - Bouffet, Eric
AU - Hawkins, Cynthia
AU - Tabori, Uri
PY - 2020
DA - 2020/11/09
PB - American Society of Clinical Oncology (ASCO)
SP - 561-571
IS - 4
VL - 4
PMID - 32923898
SN - 2473-4284
ER -
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BibTex (до 50 авторов)
Скопировать
@article{2020_Nobre,
author = {Liana Nobre and Michal Zápotocký and Vijay Ramaswamy and Scott Ryall and Julie Bennett and Daniel Alderete and Julia Balaguer Guill and Lorena Baroni and Ute Bartels and Abhishek Bavle and Miriam Bornhorst and Daniel R. Boué and Adela Cañete and Murali Chintagumpala and Scott L Coven and Ofelia Cruz and Sonika Dahiya and Peter Dirks and Ira J. Dunkel and David Eisenstat and Cecile Faure Conter and Elizabeth Finch and Jonathan L. Finlay and Didier Frappaz and Maria Luisa Garrè and Karen Gauvain and Anne Grete Bechensteen and Jordan R. Hansford and Inga Harting and Péter Hauser and Lili-Naz Hazrati and Annie Huang and Sarah G Injac and Valentina Iurilli and Matthias Karajannis and Gurcharanjeet Kaur and Martin Kynčl and Lenka Krskova and Normand Laperriere and Valérie Larouche and Alvaro Lassaletta and Sarah Leary and Frank Lin and Samantha Mascelli and Tara McKeown and Till Milde and Andres Morales La Madrid and Giovanni Morana and Helena Mörse and Naureen Mushtaq and others},
title = {Outcomes of BRAF V600E Pediatric Gliomas Treated With Targeted BRAF Inhibition},
journal = {JCO Precision Oncology},
year = {2020},
volume = {4},
publisher = {American Society of Clinical Oncology (ASCO)},
month = {nov},
url = {https://doi.org/10.1200/po.19.00298},
number = {4},
pages = {561--571},
doi = {10.1200/po.19.00298}
}
Цитировать
MLA
Скопировать
Nobre, Liana, et al. “Outcomes of BRAF V600E Pediatric Gliomas Treated With Targeted BRAF Inhibition.” JCO Precision Oncology, vol. 4, no. 4, Nov. 2020, pp. 561-571. https://doi.org/10.1200/po.19.00298.