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Outcomes of BRAF V6...
Outcomes of BRAF V600E pediatric gliomas treated with targeted BRAF inhibition
- Article/chapterEnglish2020
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LIBRIS-ID:oai:gup.ub.gu.se/299017
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https://gup.ub.gu.se/publication/299017URI
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https://doi.org/10.1200/PO.19.00298DOI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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© 2020 by American Society of Clinical Oncology 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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Zapotocky, Michal
(author)
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Ramaswamy, Vijay
(author)
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Ryall, Scott
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Bennett, Julie
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Alderete, Daniel
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Guill, Julia Balaguer
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Baroni, Lorena
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Bartels, Ute
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Bavle, Abhishek
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Bornhorst, Miriam
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Boue, Daniel R.
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Canete, Adela
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Chintagumpala, Murali
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Coven, Scott L.
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Cruz, Ofelia
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Dahiya, Sonika
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Dirks, Peter
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Dunkel, Ira J.
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Eisenstat, David
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Conter, Cecile Faure
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Finch, Elizabeth
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Finlay, Jonathan L.
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Frappaz, Didier
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Garre, Maria Luisa
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Gauvain, Karen
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Bechensteen, Anne Grete
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Hansford, Jordan R.
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Harting, Inga
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Hauser, Peter
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Hazrati, Lili Naz
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Huang, Annie
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Injac, Sarah G.
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Iurilli, Valentina
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Karajannis, Matthias
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Kaur, Gurcharanjeet
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Kyncl, Martin
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Krskova, Lenka
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Laperriere, Normand
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Larouche, Valerie
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Lassaletta, Alvaro
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Leary, Sarah
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Lin, Frank
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Mascelli, Samantha
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McKeown, Tara
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Milde, Till
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la Madrid, Andres Morales
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Morana, Giovanni
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Morse, Helena
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Mushtaq, Naureen
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Osorio, Diana S.
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Packer, Roger
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Pavelka, Zdenek
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Quiroga-Cantero, Eduardo
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Rutka, James
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Sabel, Magnus,1966Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Clinical Sciences, Department of Pediatrics(Swepub:gu)xsabma
(author)
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Salgado, Duarte
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Solano, Palma
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Sterba, Jaroslav
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Su, Jack
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Sumerauer, David
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Taylor, Michael D.
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Toledano, Helen
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Tsang, Derek S.
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Fernandes, Mariana Valente
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van Landeghem, Frank
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van Tilburg, Cornelis M.
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Wilson, Bev
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Witt, Olaf
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Zamecnik, Josef
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Bouffet, Eric
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Hawkins, Cynthia
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Tabori, Uri
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Göteborgs universitetInstitutionen för kliniska vetenskaper, Avdelningen för pediatrik
(creator_code:org_t)
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In:JCO Precision Oncology3, s. 561-5712473-4284
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Nobre, Liana
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Zapotocky, Micha ...
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Ramaswamy, Vijay
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Ryall, Scott
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Bennett, Julie
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Alderete, Daniel
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Guill, Julia Bal ...
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Baroni, Lorena
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Bartels, Ute
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Bavle, Abhishek
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Bornhorst, Miria ...
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Boue, Daniel R.
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Canete, Adela
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Chintagumpala, M ...
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Coven, Scott L.
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Cruz, Ofelia
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Dahiya, Sonika
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Dirks, Peter
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Dunkel, Ira J.
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Eisenstat, David
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Conter, Cecile F ...
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Finch, Elizabeth
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Finlay, Jonathan ...
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Frappaz, Didier
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Garre, Maria Lui ...
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Gauvain, Karen
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Bechensteen, Ann ...
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Hansford, Jordan ...
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Harting, Inga
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Hauser, Peter
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Hazrati, Lili Na ...
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Huang, Annie
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Injac, Sarah G.
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Iurilli, Valenti ...
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Karajannis, Matt ...
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Kaur, Gurcharanj ...
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Kyncl, Martin
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Krskova, Lenka
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Laperriere, Norm ...
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Larouche, Valeri ...
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Lassaletta, Alva ...
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Leary, Sarah
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Lin, Frank
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Mascelli, Samant ...
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McKeown, Tara
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Milde, Till
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la Madrid, Andre ...
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Morana, Giovanni
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Morse, Helena
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Mushtaq, Naureen
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Osorio, Diana S.
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Packer, Roger
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Pavelka, Zdenek
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Quiroga-Cantero, ...
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Rutka, James
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Sabel, Magnus, 1 ...
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Salgado, Duarte
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Solano, Palma
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Sterba, Jaroslav
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Su, Jack
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Sumerauer, David
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Taylor, Michael ...
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Toledano, Helen
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Tsang, Derek S.
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Fernandes, Maria ...
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van Landeghem, F ...
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van Tilburg, Cor ...
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Wilson, Bev
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Witt, Olaf
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Zamecnik, Josef
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Bouffet, Eric
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Hawkins, Cynthia
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Tabori, Uri
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Pediatrics
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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JCO Precision On ...
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University of Gothenburg