H3K27M Mutation and Citrate Levels
Of the 25 patients included, H3K27M mutations were identified in 7(28%) patients, while 14(56%) patients had the wild type phenotype. Four of the patients (16%) despite having a histologic diagnosis, did not have sufficient tissue to perform the H3K27M mutation studies and were excluded in the subsequent analysis. The median citrate level trended higher in patients with HGG when compared to those with LGG (1.49 vs 0.93 mmol/kg, p-value=0.16) and in the seven patients (33%) with H3K27M mutation when compared to those without (2.25 vs 0.78 mmol/kg, p-value 0.25) but this was not statistically significant (Table 2). The majority of patients with H3K27M mutation had HGGs by histological grading (6/7) with only one patient having a LGG.
On univariate analysis, the tumor histological grade (OR: 3.96, 95% confidence interval (CI): 1.32-11.94), H3K27M mutation (OR: 3.77, 95% CI: 1.05-13.61) and age (OR:1.12, 95% CI: 1.00-1.25) were statistically significant predictors for adverse prognosis (Table 3). Elevated citrate concentration >1.2mmol/kg tended to predict adverse prognosis, but this was not statistically significant (OR: 2.92, 95% CI: 0.91-2.23). The median duration of follow up was 113 months (range: 7-209 months) and the median OS for all patients was 67 months (range: 4-138 months). The median survival was significantly lower in patients with H3K27M mutations when compared to those without (24 vs 138 months, p value <0.05), in patients with elevated citrate levels >1.2 mmol/kg when compared to those without (24 vs 105 months, p-value 0.07) and in patients with HGG when compared to LGG (16 vs 138 months, p value 0.012). On multivariate analysis only the histological grade (HGG vs LGG) was statistically significant (OR: 6.02, 95% CI:1.05-34.64, p-value=0.04) (Table 3, Figure 2).