Development and Validation of a Prognostic Molecular Phenotype and Clinical Characterization in Grade III Diffuse Gliomas Treatment with Radio-Chemotherapy.

Background: The relationship between molecular phenotype and prognosis in high-grade gliomas (WHO III and IV, HGG) treated with radiotherapy and chemotherapy is not fully understood and needs further exploration.

Methods: The HGG patients following surgery and treatment with radiotherapy and chemotherapy. Univariate and multivariate Cox analyses were used to assess the independent prognostic factors. The nomogram model was established, and its accuracy was determined via the calibration plots.

Results: A total of 215 and 88 patients had grade III glioma and grade IV glioma, respectively. Grade III oligodendroglioma (OG-G3) patients had the longest mPFS and mOS than other grade III pathology, while grade III astrocytoma (AA-G3) patients were close to IDH-1 wildtype glioblastoma (GBM) and had a poor prognosis. The IDH-1 mutant group had a better mPFS and mOS than the IDH-1 wildtype group in all grade III patients, OG-G3 and AA-G3 patients. Furthermore, 1p/19q co-deletion group had a longer mPFS and mOS than 1p/19q non-deletion group in all grade III patients. IDH-1 mutation and 1p/19q co-deletion patients had the best prognosis than other molecular types. Also, the MGMT methylation and IDH-1 mutation or 1p/19q co-deletion group had a longer mPFS and mOS than the MGMT unmethylation and IDH-1 wildtype or 1p/19q non-codeletion of grade III patients. In addition, the low Ki-67 expression group had a better prognosis than high Ki-67 expression group in grade III patients. Univariate and multivariate COX showed that 1p/19q co-deletion and MGMT methylation were the independent prognostic factors for mPFS and mOS. The calibration curve showed that the established nomogram could well predict the survival based on these covariates.

Conclusion: The AA-G3 with IDH-1 wildtype, MGMT unmethylation or 1p/19q non-codeletion patients was resistant to radiotherapy and chemotherapy, has a poor prognosis and needs a more active treatment.