Abstract In recent years, the focus for treating pediatric low-grade gliomas has shifted to identifying and targeting molecular drivers, particularly BRAF alterations such as BRAF V600E mutations and BRAF fusions. Little is known about the relationship between the specific BRAF alterations and clinical presentation and outcomes. Using a retrospective chart review of 70 pediatric patients at our institution, we aimed to identify differences in initial clinical presentation and long-term outcomes in patients with low-grade gliomas that had BRAF V600E (n = 27), BRAF fusion (n = 35), or other BRAF mutations (n = 8). Presenting symptoms, tumor location, age of diagnosis, and progression-free survival (PFS) were compared between the groups using ANOVA, chi-square or Fisher’s exact testing, logistic regression, and survival analysis methods. Age of diagnosis was significantly lower in patients with a BRAF fusion (KIAA) (p 0.001). Compared with BRAF fusion gliomas, BRAF V600E (p = 0.002) and other BRAF-altered gliomas (p = 0.021) were significantly more likely to occur in the cerebral hemispheres, whereas BRAF V600E gliomas were significantly less likely to occur in the cerebellum (p = 0.028), controlling for age at diagnosis. Overall PFS significantly differed between the groups (p = 0.02). 60-month restricted mean progression-free survival time was significantly higher in the V600E (45.8 (95% CI: 37.4, 54.1), p = 0.013) and other (49.4 (95% CI: 37.6, 61.2), p = 0.012) groups as compared to the fusion group (31.1 (95% CI: 23.7, 38.9)). This difference was no longer significant between the groups after accounting for age at diagnosis. Future research with a larger patient population is needed to further explore the relationship between age at diagnosis and long-term outcomes across mutation types in order to better target therapy and improve outcomes.
Williams et al. (Tue,) studied this question.