Molecular diagnostic factors, prognostic implications, and long-term outcomes in pediatric pilocytic astrocytoma.

Objective: Pediatric pilocytic astrocytoma (PPA) is the most common pediatric brain tumor, accounting for more than 15% of brain tumors in children. BRAF alterations, including KIAA1549-BRAF (K-B) fusion and BRAF V600E mutation, are prevalent in pilocytic astrocytoma (PA) and have shown mixed prognostic outcomes in previous studies. In this study, the authors outline the clinical course for patients with PPA and examine factors that may aid in predicting disease trajectory.

Methods: This retrospective study included pediatric patients who underwent biopsy or resection of PA between 2009 and 2023 at the authors' institution. Clinical data, tumor genomics, and disease course outcomes were collected, and analysis included stratification by BRAF gene status.

Results: The study cohort included 112 pediatric patients, 58 of whom had the K-B fusion and 12 of whom had the BRAF V600E mutation. Significantly lower rates of recurrence/progression were noted with gross-total resection (GTR) (hazard ratio [HR] 0.27, 95% CI 0.13-0.53; p < 0.001). The K-B fusion was associated with worse progression-/recurrence-free survival (PRFS) compared to wildtype (WT) (HR 2.3, 95% CI 1.1-4.3; p = 0.03), although among patients with K-B fusion, GTR was associated with a significantly longer time to recurrence/progression (4.5 vs 0.8 years, p < 0.001). The BRAF V600E mutation was not associated with significantly different PRFS than WT (HR 1.4, 95% CI 0.4-4.5; p = 0.56). Neither the use of adjuvant therapy for incompletely resected tumors nor tumor location affected the rate of recurrence/progression.

Conclusions: Several clinical and genomic factors were identified that may affect prognostication for patients with PPA. K-B was the most common genomic alteration identified and was associated with worse PRFS, while the BRAF V600E mutation conferred no difference in PRFS when compared to the BRAF WT. GTR should be pursued when possible because it is associated with a longer time to recurrence/progression, including for tumors with the K-B fusion.