Purpose BRAF V600E is a potentially highly targetable mutation detected in a subset
of pediatric low-grade gliomas (PLGGs). Its biologic and clinical effect within this
diverse group of tumors remains unknown. Patients and Methods A combined clinical
and genetic institutional study of patients with PLGGs with long-term follow-up was
performed (N = 510). Clinical and treatment data of patients with BRAF V600E mutated
PLGG (n = 99) were compared with a large international independent cohort of patients
with BRAF V600E mutated-PLGG (n = 180). Results BRAF V600E mutation was detected in
69 of 405 patients (17%) with PLGG across a broad spectrum of histologies and sites,
including midline locations, which are not often routinely biopsied in clinical practice.
Patients with BRAF V600E PLGG exhibited poor outcomes after chemotherapy and radiation
therapies that resulted in a 10-year progression-free survival of 27% (95% CI, 12.1%
to 41.9%) and 60.2% (95% CI, 53.3% to 67.1%) for BRAF V600E and wild-type PLGG, respectively
(P < .001). Additional multivariable clinical and molecular stratification revealed
that the extent of resection and CDKN2A deletion contributed independently to poor
outcome in BRAF V600E PLGG. A similar independent role for CDKN2A and resection on
outcome were observed in the independent cohort. Quantitative imaging analysis revealed
progressive disease and a lack of response to conventional chemotherapy in most patients
with BRAF V600E PLGG. Conclusion BRAF V600E PLGG constitutes a distinct entity with
poor prognosis when treated with current adjuvant therapy. (C) 2017 by American Society
of Clinical Oncology
