Introduction
The last decades have witnessed a progressive paradigm shift in the
non-surgical management of pediatric low-grade gliomas (PLGG). While
radiation was historically the standard treatment, its use has
progressively decreased with the development of chemotherapy strategies
that have shown the possibility to delay or avoid radiotherapy in most
patients1. A new shift
is currently happening with evidence that alterations within the
mitogen-activated protein kinase (MAPK) pathway affect most PLGGs and
represent potential therapeutic
targets2. Phase I and II
trials have shown the efficacy of BRAF and MEK inhibitors in recurrent
and/or refractory PLGG34. Response rates to
these agents are promising and appear to be superior to those observed
with chemotherapy, and clinical trials are ongoing to compare the
efficacy of the new agents with standard chemotherapy in treatment naïve
patients 5. However, a
number of questions remain unanswered regarding these new compounds, and
in particular with regard to the management of patients who fail to
respond or progress while treated with MEK or BRAF inhibitors. Herein we
describe a patient with BRAFV600E mutated PLGG who progressed on a
combination of dabrafenib and tramatenib. This patient eventually
responded to a chemotherapeutic regimen consisting of thioguanine,
procarbazine, lomustine and vincristine (TPCV) resulting in reversal of
life-threatening symptoms.