Outcomes of BRAF V600E pediatric gliomas treated with targeted BRAF inhibition

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Fältnamn	Indikatorer	Metadata
000		06016naa a2201153 4500
001		oai:gup.ub.gu.se/299017
003		SwePub
008		240528s2020 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://gup.ub.gu.se/publication/2990172 URI
024	7	a https://doi.org/10.1200/PO.19.002982 DOI
040		a (SwePub)gu
041		a eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Nobre, Liana4 aut
245	1 0	a Outcomes of BRAF V600E pediatric gliomas treated with targeted BRAF inhibition
264	1	c 2020
520		a © 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.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Pediatrik0 (SwePub)302212 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Pediatrics0 (SwePub)302212 hsv//eng
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology0 (SwePub)302032 hsv//eng
700	1	a Zapotocky, Michal4 aut
700	1	a Ramaswamy, Vijay4 aut
700	1	a Ryall, Scott4 aut
700	1	a Bennett, Julie4 aut
700	1	a Alderete, Daniel4 aut
700	1	a Guill, Julia Balaguer4 aut
700	1	a Baroni, Lorena4 aut
700	1	a Bartels, Ute4 aut
700	1	a Bavle, Abhishek4 aut
700	1	a Bornhorst, Miriam4 aut
700	1	a Boue, Daniel R.4 aut
700	1	a Canete, Adela4 aut
700	1	a Chintagumpala, Murali4 aut
700	1	a Coven, Scott L.4 aut
700	1	a Cruz, Ofelia4 aut
700	1	a Dahiya, Sonika4 aut
700	1	a Dirks, Peter4 aut
700	1	a Dunkel, Ira J.4 aut
700	1	a Eisenstat, David4 aut
700	1	a Conter, Cecile Faure4 aut
700	1	a Finch, Elizabeth4 aut
700	1	a Finlay, Jonathan L.4 aut
700	1	a Frappaz, Didier4 aut
700	1	a Garre, Maria Luisa4 aut
700	1	a Gauvain, Karen4 aut
700	1	a Bechensteen, Anne Grete4 aut
700	1	a Hansford, Jordan R.4 aut
700	1	a Harting, Inga4 aut
700	1	a Hauser, Peter4 aut
700	1	a Hazrati, Lili Naz4 aut
700	1	a Huang, Annie4 aut
700	1	a Injac, Sarah G.4 aut
700	1	a Iurilli, Valentina4 aut
700	1	a Karajannis, Matthias4 aut
700	1	a Kaur, Gurcharanjeet4 aut
700	1	a Kyncl, Martin4 aut
700	1	a Krskova, Lenka4 aut
700	1	a Laperriere, Normand4 aut
700	1	a Larouche, Valerie4 aut
700	1	a Lassaletta, Alvaro4 aut
700	1	a Leary, Sarah4 aut
700	1	a Lin, Frank4 aut
700	1	a Mascelli, Samantha4 aut
700	1	a McKeown, Tara4 aut
700	1	a Milde, Till4 aut
700	1	a la Madrid, Andres Morales4 aut
700	1	a Morana, Giovanni4 aut
700	1	a Morse, Helena4 aut
700	1	a Mushtaq, Naureen4 aut
700	1	a Osorio, Diana S.4 aut
700	1	a Packer, Roger4 aut
700	1	a Pavelka, Zdenek4 aut
700	1	a Quiroga-Cantero, Eduardo4 aut
700	1	a Rutka, James4 aut
700	1	a Sabel, Magnus,d 1966u Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Clinical Sciences, Department of Pediatrics4 aut0 (Swepub:gu)xsabma
700	1	a Salgado, Duarte4 aut
700	1	a Solano, Palma4 aut
700	1	a Sterba, Jaroslav4 aut
700	1	a Su, Jack4 aut
700	1	a Sumerauer, David4 aut
700	1	a Taylor, Michael D.4 aut
700	1	a Toledano, Helen4 aut
700	1	a Tsang, Derek S.4 aut
700	1	a Fernandes, Mariana Valente4 aut
700	1	a van Landeghem, Frank4 aut
700	1	a van Tilburg, Cornelis M.4 aut
700	1	a Wilson, Bev4 aut
700	1	a Witt, Olaf4 aut
700	1	a Zamecnik, Josef4 aut
700	1	a Bouffet, Eric4 aut
700	1	a Hawkins, Cynthia4 aut
700	1	a Tabori, Uri4 aut
710	2	a Göteborgs universitetb Institutionen för kliniska vetenskaper, Avdelningen för pediatrik4 org
773	0	t JCO Precision Oncologyg 3, s. 561-571q 3<561-571x 2473-4284
856	4 8	u https://gup.ub.gu.se/publication/299017
856	4 8	u https://doi.org/10.1200/PO.19.00298

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Av författaren/redakt...: Nobre, Liana; Zapotocky, Micha ...; Ramaswamy, Vijay; Ryall, Scott; Bennett, Julie; Alderete, Daniel; visa fler...; Guill, Julia Bal ...; Baroni, Lorena; Bartels, Ute; Bavle, Abhishek; Bornhorst, Miria ...; Boue, Daniel R.; Canete, Adela; Chintagumpala, M ...; Coven, Scott L.; Cruz, Ofelia; Dahiya, Sonika; Dirks, Peter; Dunkel, Ira J.; Eisenstat, David; Conter, Cecile F ...; Finch, Elizabeth; Finlay, Jonathan ...; Frappaz, Didier; Garre, Maria Lui ...; Gauvain, Karen; Bechensteen, Ann ...; Hansford, Jordan ...; Harting, Inga; Hauser, Peter; Hazrati, Lili Na ...; Huang, Annie; Injac, Sarah G.; Iurilli, Valenti ...; Karajannis, Matt ...; Kaur, Gurcharanj ...; Kyncl, Martin; Krskova, Lenka; Laperriere, Norm ...; Larouche, Valeri ...; Lassaletta, Alva ...; Leary, Sarah; Lin, Frank; Mascelli, Samant ...; McKeown, Tara; Milde, Till; la Madrid, Andre ...; Morana, Giovanni; Morse, Helena; Mushtaq, Naureen; Osorio, Diana S.; Packer, Roger; Pavelka, Zdenek; Quiroga-Cantero, ...; Rutka, James; Sabel, Magnus, 1 ...; Salgado, Duarte; Solano, Palma; Sterba, Jaroslav; Su, Jack; Sumerauer, David; Taylor, Michael ...; Toledano, Helen; Tsang, Derek S.; Fernandes, Maria ...; van Landeghem, F ...; van Tilburg, Cor ...; Wilson, Bev; Witt, Olaf; Zamecnik, Josef; Bouffet, Eric; Hawkins, Cynthia; Tabori, Uri; visa färre...

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