TY  - JOUR
A1  - Burger, Michael Christian
A1  - Ronellenfitsch, Michael Wilfried
A1  - Lorenz, Nadja Irene
A1  - Wagner, Marlies
A1  - Voß, Martin
A1  - Capper, David
A1  - Tzaridis, Theophilos
A1  - Herrlinger, Ulrich
A1  - Steinbach, Joachim Peter
A1  - Stoffels, Gabriele
A1  - Langen, Karl-Josef
A1  - Brandts, Christian Hubertus
A1  - Senft, Christian
A1  - Harter, Patrick Nikolaus
A1  - Bähr, Oliver
T1  - Dabrafenib in patients with recurrent, BRAF V600E mutated malignant glioma and leptomeningeal disease
T2  - Oncology reports
N2  - BRAF V600E mutations occur frequently in malignant melanoma, but are rare in most malignant glioma subtypes. Besides, more benign brain tumors such as ganglioglioma, dysembryoblastic neuroepithelial tumours and supratentorial pilocytic astrocytomas, only pleomorphic xanthoastrocytomas (50-78%) and epitheloid glioblastoma (50%) regularly exhibit BRAF mutations. In the present study, we report on three patients with recurrent malignant gliomas harbouring a BRAF V600E mutation. All patients presented with markedly disseminated leptomeningeal disease at recurrence and had progressed after radiotherapy and alkylating chemotherapy. Therefore, estimated life expectancy at recurrence was a few weeks. All three patients received dabrafenib as a single agent and all showed a complete or nearly complete response. Treatment is ongoing and patients are stable for 27 months, 7 months and 3 months, respectively. One patient showed a dramatic radiologic and clinical response after one week of treatment. We were able to generate an ex vivo tumor cell culture from CSF in one patient. Treatment of this cell culture with dabrafenib resulted in reduced cell density and inhibition of ERK phosphorylation in vitro. To date, this is the first series on adult patients with BRAF-mutated malignant glioma and leptomeningeal dissemination treated with dabrafenib monotherapy. All patients showed a dramatic response with one patient showing an ongoing response for more than two years.
KW  - dabrafenib
KW  - BRAF
KW  - BRAF V600E
KW  - pleomorphic xanthoastrocytoma
KW  - PXA
KW  - glioma
KW  - glioblastoma
KW  - leptomeningeal disease
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/47165
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-471650
SN  - 1791-2431
SN  - 1021-335X
N1  - Copyright: © Burger et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
VL  - 38
IS  - 6
SP  - 3291
EP  - 3296
PB  - Spandidos Publ.
CY  - Athens
ER  -