| NOBRE, L., M. ZAPOTOCKY, V. RAMASWAMY, S. RYALL, J. BENNETT, D. ALDERETE, Guill J. BALAGUER, L. BARONI, U. BARTELS, A. BAVLE, M. BORNHORST, D. R. BOUE, A. CANETE, M. CHINTAGUMPALA, S. L. COVEN, O. CRUZ, S. DAHIYA, P. DIRKS, I. J. DUNKEL, D. EISENSTAT, C. F. CONTER, E. FINCH, J. L. FINLAY, D. FRAPPAZ, M. L. GARRE, K. GAUVAIN, A. G. BECHENSTEEN, J. R. HANSFORD, I. HARTING, P. HAUSER, L. N. HAZRATI, A. HUANG, S. G. INJAC, V. IURILLI, M. KARAJANNIS, G. KAUR, M. KYNCL, L. KRSKOVA, N. LAPERRIERE, V. LAROUCHE, A. LASSALETTA, S. LEARY, F. LIN, S. MASCELLI, T. MCKEOWN, T. MILDE, La Madrid A. MORALES, G. MORANA, H. MORSE, N. MUSHTAQ, D. S. OSORIO, R. PACKER, Z. PAVELKA, E. QUIROGA-CANTERO, J. RUTKA, M. SABEL, D. SALGADO, P. SOLANO, Jaroslav ŠTĚRBA, J. SU, D. SUMERAUER, M. D. TAYLOR, H. TOLEDANO, D. S. TSANG, Fernandes M. VALENTE, F. VAN LANDEGHEM, C. M. VAN TILBURG, B. WILSON, O. WITT, J. ZAMECNIK, E. BOUFFET, C. HAWKINS a U. TABORI. Outcomes of BRAF V600E Pediatric Gliomas Treated With Targeted BRAF Inhibition. JCO PRECISION ONCOLOGY. PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS, 2020, roč. 4, MAY 2020, s. 561-571. ISSN 2473-4284. Dostupné z: https://dx.doi.org/10.1200/PO.19.00298. |
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@article{1743519,
author = {Nobre, L. and Zapotocky, M. and Ramaswamy, V. and Ryall, S. and Bennett, J. and Alderete, D. and Balaguer, Guill J. and Baroni, L. and Bartels, U. and Bavle, A. and Bornhorst, M. and Boue, D. R. and Canete, A. and Chintagumpala, M. and Coven, S. L. and Cruz, O. and Dahiya, S. and Dirks, P. and Dunkel, I. J. and Eisenstat, D. and Conter, C. F. and Finch, E. and Finlay, J. L. and Frappaz, D. and Garre, M. L. and Gauvain, K. and Bechensteen, A. G. and Hansford, J. R. and Harting, I. and Hauser, P. and Hazrati, L. N. and Huang, A. and Injac, S. G. and Iurilli, V. and Karajannis, M. and Kaur, G. and Kyncl, M. and Krskova, L. and Laperriere, N. and Larouche, V. and Lassaletta, A. and Leary, S. and Lin, F. and Mascelli, S. and McKeown, T. and Milde, T. and Morales, La Madrid A. and Morana, G. and Morse, H. and Mushtaq, N. and Osorio, D. S. and Packer, R. and Pavelka, Z. and QuirogaandCantero, E. and Rutka, J. and Sabel, M. and Salgado, D. and Solano, P. and Štěrba, Jaroslav and Su, J. and Sumerauer, D. and Taylor, M. D. and Toledano, H. and Tsang, D. S. and Valente, Fernandes M. and van Landeghem, F. and van Tilburg, C. M. and Wilson, B. and Witt, O. and Zamecnik, J. and Bouffet, E. and Hawkins, C. and Tabori, U.},
article_location = {PHILADELPHIA},
article_number = {MAY 2020},
doi = {http://dx.doi.org/10.1200/PO.19.00298},
keywords = {BRAF V600E Pediatric Gliomas; BRAF Inhibition},
language = {eng},
issn = {2473-4284},
journal = {JCO PRECISION ONCOLOGY},
title = {Outcomes of BRAF V600E Pediatric Gliomas Treated With Targeted BRAF Inhibition},
url = {https://ascopubs.org/doi/10.1200/PO.19.00298},
volume = {4},
year = {2020}
}
TY - JOUR
ID - 1743519
AU - Nobre, L. - Zapotocky, M. - Ramaswamy, V. - Ryall, S. - Bennett, J. - Alderete, D. - Balaguer, Guill J. - Baroni, L. - Bartels, U. - Bavle, A. - Bornhorst, M. - Boue, D. R. - Canete, A. - Chintagumpala, M. - Coven, S. L. - Cruz, O. - Dahiya, S. - Dirks, P. - Dunkel, I. J. - Eisenstat, D. - Conter, C. F. - Finch, E. - Finlay, J. L. - Frappaz, D. - Garre, M. L. - Gauvain, K. - Bechensteen, A. G. - Hansford, J. R. - Harting, I. - Hauser, P. - Hazrati, L. N. - Huang, A. - Injac, S. G. - Iurilli, V. - Karajannis, M. - Kaur, G. - Kyncl, M. - Krskova, L. - Laperriere, N. - Larouche, V. - Lassaletta, A. - Leary, S. - Lin, F. - Mascelli, S. - McKeown, T. - Milde, T. - Morales, La Madrid A. - Morana, G. - Morse, H. - Mushtaq, N. - Osorio, D. S. - Packer, R. - Pavelka, Z. - Quiroga-Cantero, E. - Rutka, J. - Sabel, M. - Salgado, D. - Solano, P. - Štěrba, Jaroslav - Su, J. - Sumerauer, D. - Taylor, M. D. - Toledano, H. - Tsang, D. S. - Valente, Fernandes M. - van Landeghem, F. - van Tilburg, C. M. - Wilson, B. - Witt, O. - Zamecnik, J. - Bouffet, E. - Hawkins, C. - Tabori, U.
PY - 2020
TI - Outcomes of BRAF V600E Pediatric Gliomas Treated With Targeted BRAF Inhibition
JF - JCO PRECISION ONCOLOGY
VL - 4
IS - MAY 2020
SP - 561-571
EP - 561-571
PB - LIPPINCOTT WILLIAMS & WILKINS
SN - 24734284
KW - BRAF V600E Pediatric Gliomas
KW - BRAF Inhibition
UR - https://ascopubs.org/doi/10.1200/PO.19.00298
L2 - https://ascopubs.org/doi/10.1200/PO.19.00298
N2 - PURPOSEChildren 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 METHODSWe collected clinical, imaging, molecular, and outcome information from patients with BRAF V600E-mutated glioma treated with BRAF inhibition across 29 centers from multiple countries.RESULTSSixty-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).CONCLUSIONUse 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.
ER -
NOBRE, L., M. ZAPOTOCKY, V. RAMASWAMY, S. RYALL, J. BENNETT, D. ALDERETE, Guill J. BALAGUER, L. BARONI, U. BARTELS, A. BAVLE, M. BORNHORST, D. R. BOUE, A. CANETE, M. CHINTAGUMPALA, S. L. COVEN, O. CRUZ, S. DAHIYA, P. DIRKS, I. J. DUNKEL, D. EISENSTAT, C. F. CONTER, E. FINCH, J. L. FINLAY, D. FRAPPAZ, M. L. GARRE, K. GAUVAIN, A. G. BECHENSTEEN, J. R. HANSFORD, I. HARTING, P. HAUSER, L. N. HAZRATI, A. HUANG, S. G. INJAC, V. IURILLI, M. KARAJANNIS, G. KAUR, M. KYNCL, L. KRSKOVA, N. LAPERRIERE, V. LAROUCHE, A. LASSALETTA, S. LEARY, F. LIN, S. MASCELLI, T. MCKEOWN, T. MILDE, La Madrid A. MORALES, G. MORANA, H. MORSE, N. MUSHTAQ, D. S. OSORIO, R. PACKER, Z. PAVELKA, E. QUIROGA-CANTERO, J. RUTKA, M. SABEL, D. SALGADO, P. SOLANO, Jaroslav ŠTĚRBA, J. SU, D. SUMERAUER, M. D. TAYLOR, H. TOLEDANO, D. S. TSANG, Fernandes M. VALENTE, F. VAN LANDEGHEM, C. M. VAN TILBURG, B. WILSON, O. WITT, J. ZAMECNIK, E. BOUFFET, C. HAWKINS a U. TABORI. Outcomes of BRAF V600E Pediatric Gliomas Treated With Targeted BRAF Inhibition. \textit{JCO PRECISION ONCOLOGY}. PHILADELPHIA: LIPPINCOTT WILLIAMS \&{} WILKINS, 2020, roč.~4, MAY 2020, s.~561-571. ISSN~2473-4284. Dostupné z: https://dx.doi.org/10.1200/PO.19.00298.
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