Secondary Glioblastoma: Molecular and Clinical Factors That Affect Outcome After Malignant Progression of a Lower Grade Tumor

Abstract Background: There is limited information on prognostic factors and associated outcomes in patients with secondary glioblastoma (sGBM). Objective: Herein we report on the outcomes of patients with sGBM and identify clinically relevant prognostic factors. Methods: We retrospectively analyzed our institutional database for patients with histological evidence of WHO grade II-III gliomas that went on to develop WHO grade IV sGBM. The assessment of the isocitrate dehydrogenase-1 (IDH1) R132H mutation was performed via immunohistochemical (IHC) staining. Results: 45 patients with sGBM were included within our analysis (median age 41 years). Mutated IDH1 (R132H) protein was present within the gliomas of 24 patients and was absent in 17; IHC assessment could not be performed for 4 patients. The median time between first diagnosis of glioma and sGBM was 158.9 weeks; median overall survival (OS) following a diagnosis of sGBM was 63.6 weeks. When assessing patient-specific (i.e. therapy-independent) factors, mutated IDH1 (R132H) protein (p = 0.01; HR: 0.54; CI: 0.33-0.87), WHO grade II tumor as precursor lesion (p = 0.05; HR: 0.49; CI: 0.25-0.97) and a frontal tumor location (p = 0.04; HR: 0.48; CI: 0.23-0.99) were found to be associated with better OS via multivariate analysis. Our data further indicate, that complete tumor removal is associated with better patient survival in sGBM patients within certain risk groups (time period to development of sGBM> 104 weeks, initial WHO grade II tumor, IDH1 mutation and time period to development of sGBM > 104 weeks, initial WHO grade II or III tumor, IDH1 wildtype, frontal lobe localization). Conclusion: Our retrospective analysis suggested that the presence of an IDH1 (R132H) mutation, frontal tumor location and WHO grade of the initial tumor are associated with OS after progression to sGBM. Moreover, some sGBM patients may benefit from complete tumor resection depending on the abovementioned patient-specific parameters, a finding which will ultimately need prospective validation.