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000838853 1001_ $$0P:(DE-HGF)0$$aBurger, MC$$b0$$eCorresponding author
000838853 245__ $$aDabrafenib in patients with recurrent, BRAF V600E mutated malignant glioma and leptomeningeal disease
000838853 260__ $$aAthens$$bSpandidos Publ.$$c2017
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000838853 520__ $$aBRAF V600E mutations occur frequently in malignant melanoma, but are rare in most malignant glioma subtypes. Besides, more benign brain tumors such as ganglioglioma, dysembryoblastic neuroepithelial tumours and supratentorial pilocytic astrocytomas, only pleomorphic xanthoastrocytomas (50–78%) and epitheloid glioblastoma (50%) regularly exhibit BRAF mutations. In the present study, we report on three patients with recurrent malignant gliomas harbouring a BRAF V600E mutation. All patients presented with markedly disseminated leptomeningeal disease at recurrence and had progressed after radiotherapy and alkylating chemotherapy. Therefore, estimated life expectancy at recurrence was a few weeks. All three patients received dabrafenib as a single agent and all showed a complete or nearly complete response. Treatment is ongoing and patients are stable for 27 months, 7 months and 3 months, respectively. One patient showed a dramatic radiologic and clinical response after one week of treatment. We were able to generate an ex vivo tumor cell culture from CSF in one patient. Treatment of this cell culture with dabrafenib resulted in reduced cell density and inhibition of ERK phosphorylation in vitro. To date, this is the first series on adult patients with BRAF-mutated malignant glioma and leptomeningeal dissemination treated with dabrafenib monotherapy. All patients showed a dramatic response with one patient showing an ongoing response for more than two years.
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000838853 7001_ $$0P:(DE-HGF)0$$aRonellenfitsch, MW$$b1
000838853 7001_ $$0P:(DE-HGF)0$$aLorenz, NI$$b2
000838853 7001_ $$0P:(DE-HGF)0$$aWagner, M.$$b3
000838853 7001_ $$0P:(DE-HGF)0$$aVoss, M.$$b4
000838853 7001_ $$0P:(DE-HGF)0$$aCapper, D.$$b5
000838853 7001_ $$0P:(DE-HGF)0$$aTzaridis, T.$$b6
000838853 7001_ $$0P:(DE-HGF)0$$aHerrlinger, U.$$b7
000838853 7001_ $$0P:(DE-HGF)0$$aSteinbach, P.$$b8
000838853 7001_ $$0P:(DE-Juel1)131627$$aStoffels, Gabriele$$b9
000838853 7001_ $$0P:(DE-Juel1)131777$$aLangen, Karl-Josef$$b10
000838853 7001_ $$0P:(DE-HGF)0$$aBrandts, C.$$b11
000838853 7001_ $$0P:(DE-HGF)0$$aSenft, C.$$b12
000838853 7001_ $$0P:(DE-HGF)0$$aHarter, PN$$b13
000838853 7001_ $$0P:(DE-HGF)0$$aBähr, O.$$b14
000838853 773__ $$0PERI:(DE-600)2120548-6$$a10.3892/or.2017.6013$$n6$$p3291-3296$$tOncology reports$$v38$$x1021-335X$$y2017
000838853 8564_ $$uhttps://juser.fz-juelich.de/record/838853/files/or-38-06-3291.pdf$$yPublished on 2017-10-02. Available in OpenAccess from 2018-04-02.
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