AUTHOR=Cronin Christopher , McLaughlin Ronan , Lane Louise , Brett Francesca M. , Jansen Michael , Bermingham Niamh , Wyse Gerald , Grogan Liam , Morris Patrick G. , O’Reilly Seamus 

TITLE=Case report: BRAF-inhibitor therapy in BRAF-mutated primary CNS tumours including one case of BRAF-mutated Rosai-Dorfman disease

JOURNAL=Frontiers in Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.1070828

DOI=10.3389/fmed.2022.1070828

ISSN=2296-858X

ABSTRACT=BRAF V600E oncogene mutations have been reported in multiple central nervous system (CNS) tumour types, and emerging evidence supports the use of targeted therapy in BRAF-mutated gliomas. BRAF oncogene mutations have recently been identified in Rosai-Dorfman Disease (RDD) – a rare non-Langerhan’s Cell histiocytosis. This series describes 3 patients from 2 neurosurgical centres in Ireland with BRAF V600E-mutated CNS tumours. Patients include a 19-year-old male with ganglioglioma with anaplastic features, a 21-year-old male with CNS involvement of Rosai-Dorfman Disease, and a 28-year-old female with ganglioglioma with anaplastic features . 2 patients received radiation with concurrent temozolomide prior to BRAF-targeted therapy. This case series describes clinical and radiological responses to BRAF-targeted therapy in BRAF V600E-mutated gliomas across multiple tumour grades, as well as only the second published report of response to targeted therapy in BRAF-mutated RDD. Durability of disease control with BRAF-targeted therapy was generally superior to that achieved with chemoradiation; one patient has experienced ongoing disease control for 5 years.  The reported case of treatment response in BRAF-mutated RDD lends support to the strategy of genotyping and utilisation of targeted therapy in this rare disease. The optimal sequencing of BRAF-targeted therapy in BRAF-mutated gliomas/glioneuronal tumours remains unclear and further prospective studies are required to guide the use of genome-matched therapy in this patient population.