Introduction: Glioblastoma (GBM) remains an aggressive tumor despite modern treatment. Recent investigations show that isocitrate dehydrogenase 1 and 2 (IDH1/2) mutations play a critical role in GBM pathogenesis and clinical prognosis. IDH1/2 converts alpha-ketoglutarate to isocitrate in the Krebs cycle, while IDH1/2 mutation can generate the oncometabolite 2-hydroxyglutarate, which may alter GBM epigenetic signaling. While mutated IDH1/2 has been widely observed in low-grade glioma, its prevalence and clinical understanding in GBM remains more limited. This study presents, to our knowledge, the first metaanalysis of IDH1/2 mutations in GBM.
Methods: A Medline search of studies since 2008 with key words, “isocitrate dehydrogenase”, “IDH”, “GBM”, “glioblastoma”, and “prognosis” was performed and yielded 16 studies. Thirteen studies reporting overall survival were selected. Mean variables with standard error were analyzed by T-test. Cochran’s Q test and I2 test for study heterogeneity were performed.
Results: This metaanalysis included 2459 GBM patients, with an expected lower number of IDH-mut samples identified (1898 vs. 255, p<0.0005). Between IDH-wt and IDH-mut samples, mean age was not significantly different (53.3±4.5 vs. 44.0±3.9 years, p=0.16) and no correlation between mean age and overall survival was seen in either group (p=0.738). Median overall survival was significantly better in IDH-mut samples (12.3±1.4 vs. 41.8±11.8 months, p=0.03). Hazard ratios were analyzed by Forest plot and showed a central tendency of 0.37±0.07 (95% CI: 0.21, 0.81). Cochran’s Q test (99.5) and I2 (90.0) signified heterogeneity between studies.
Conclusions: This study reaffirms the improved prognosis of patients with IDH1/2 mutation. While the correlation between younger age and IDH1/2 mutations did not reach significance, these results may be complicated by the heterogeneity of the retrospective studies. Nonetheless, both median overall survival and survival hazard ratios remain better with IDH1/2 mutation suggesting an independent association with improved prognosis.
Patient Care: This research will elucidate the current impact of isocitrate dehydrogenase 1/2 mutation on glioblastoma prognosis in order to identify future areas for investigation.
Learning Objectives: 1. Understand the impact of IDH1/2 mutations on GBM prognosis, 2. Evaluate the available literature on IDH1/2 mutations in GBM, 3.Understand the effect of IDH1/2 mutations on presenting age at time of GBM diagnosis