Introduction: In the post-genomic era of glioma biology, an emerging paradigm is that the molecular and genomic features of gliomas may be more important than tumor grade in determining prognosis. Here, we analyze The Cancer Genome Atlas (TCGA) to assess whether isocitrate dehydrogenase mutation (IDHm) and mutated methylguanine methyltransferase (mMGMT) are better prognostic indicators than tumor grade.
Methods: We identified 1,115 astrocytic gliomas of all grades. We assessed survival using univariate and multivariate Cox proportional hazards models. Multivariate models were adjusted for tumor grade, age, Karnofsky’s Performance Score (KPS), mMGMT, and IDHm.
Results: Pearson’s correlation analysis indicated significant pairwise associations between mMGMT and age (r=-0.22), KPS (r=0.14), and tumor grade (r=-0.32) (all p<0.05). Similarly, there were significant pairwise associations between IDHm and age (r=-0.60), KPS (r=0.34), and tumor grade (r=-0.70) (all p<0.05). Multivariate analysis showed that age, KPS, tumor grade, mMGMT, and IDHm independently contributed to survival prognosis. For mMGMT tumors, the median survival for grade II, III, and IV tumors was 17.10, 12.70, and 8.55 months; and for MGMT unmethylated tumors, was 13.25, 13.75, and 9.30 months, respectively. For IDHm tumors, two distinct survival distributions were observed for each tumor grade. The first distribution with survival < 60 months, exhibited median survival for grades II, III, and IV patients of 14.3, 12.5, and 16.6 months, while patients surviving >= 60 months demonstrated median survivals of 88.10, 75.15, and 91.10 months, respectively. These survival distributions in IDHm survival did not significantly differ. Wild type IDH tumors fell into a single distribution, with median survival of 7.40, 10.40, and 9.70 months for grade II, III, and IV tumors, respectively. Similar survival patterns were observed in the CGGA.
Conclusions: Survival prognostication requires synthesis of molecular features of tumors with patient characteristics and tumor grade. For IDHm gliomas, however, tumor grade is a pertinent prognostic factor.
Patient Care: This research will improve patient care because it will help us understand the relevance of tumor grade in the post-genomic era of medicine. As we learn more about the molecular features of gliomas and how they associate with survival, we can begin to synthesize this information with existing clinical, patient, and tumor characteristics to provide better prognostic information.
Learning Objectives: 1) Understand whether tumor grade still holds prognostic importance in the post-genomic era
2) Assess the importance of molecular features and how they correspond to prognosis in conjunction with tumor grade
3) Synthesize molecular features with tumor grade to provide more robust prognostic information for gliomas