Effect of BRAF V600E Mutation on Outcome in Pediatric Low-Grade Gliomas


Key Points

  • In pediatric low-grade gliomas treated with standard adjuvant therapy, BRAF V600E mutation was associated with poorer outcomes.
  • CDKN2A deletion and the extent of resection were independent contributors to poorer outcome in patients with BRAF V600E disease.

An analysis reported by Lassaletta et al in the Journal of Clinical Oncology showed that BRAF V600E mutation is associated with a poor outcome in pediatric low-grade gliomas treated with standard adjuvant therapy.

Study Details

The study involved patients with low-grade gliomas with long-term follow up treated at The Hospital for Sick Children. BRAF V600E mutation was detected in 69 of 405 patients (17%) with disease across a wide spectrum of histologies and sites; they included midline locations, which often are not routinely biopsied in clinical practice.

Treatment Outcomes

Patients with BRAF V600E disease had poorer outcomes after chemotherapy and radiation therapy, with 10-year progression-free survival of 27% compared with 60% in patients with wild-type disease (P < .001). CDKN2A deletion was associated with a poorer outcome in patients with BRAF V600E disease (5-year progression-free survival = 24.0% vs 68.7% for CDKN2A-balanced tumors [P = .005]), as was nontotal gross resection (5-year progression-free survival = 38.8% vs 67.8% for total resection [P = .01]). On multivariate analysis, both of these factors contributed independently to poorer outcome in BRAF V600E low-grade glioma. Similar outcomes were observed in an independent international cohort.

Quantitative imaging analysis showed that most patients with BRAF V600E exhibited progressive disease and lack of response to conventional chemotherapy. Compassionate use BRAF inhibitor treatment in 6 children with progressive BRAF V600E disease showed 49% to 80% cytoreduction, with all 6 remaining on treatment at last analysis with a median follow-up of 18.5 months.

The investigators concluded: “BRAF V600E [pediatric low-grade glioma] constitutes a distinct entity with poor prognosis when treated with current adjuvant therapy.”

The study was supported in part by grants from the Government of Canada through Genome Canada and the Ontario Genomics Institute.

Uri Tabori, MD, of the University of Toronto, The Hospital for Sick Children, is the corresponding author of the Journal of Clinical Oncology article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.