gms | German Medical Science

Objective: According to the new WHO classification lower-grade gliomas are divided into three groups: IDH1/2 mutated and 1p/19q co-deleted, IDH1/2 mutated and IDH1/2 wildtype. The better knowledge of the molecular background enabled a diagnostic classification, improving the prediction of the clinical course and oncological outcome. The aim of this study was to evaluate the impact of different therapeutic strategies for lower-grade gliomas with a particular focus on the revised WHO-classification.

Methods: This is a single-center retrospective analysis including 183 patients, who underwent treatment for lower-grade tumors. All tumors were re-classified according to the 2016 WHO classification. Comprehensive data concerning overall survival, progression free survival, different treatment modalities, functional outcome and Karnofsky Performance score have been collected and analyzed. All patients underwent a molecular profiling. Functional outcome was measured by NANO-Score (where NANO=0 means no neurological deficit).

Results: The stratification according to the molecular subtype showed that the longest OS was achieved in the IDH1/2 and 1p/19q mutated group (median OS 269 months), followed by the group of IDH mutated (median OS 167.6 months) and wildtype gliomas (median OS 32.5 months). In the IDH1/2 mutated subgroup reoperations (n>3 surgeries) for recurrent disease was significantly associated with longer OS (HR=0.3, p=0.029), while partial resection (HR=3.5, p=0.003) and chemo- or radiotherapy alone (HR=3.7, p=0.04) were significantly associated with poor clinical course. Longest OS was achieved in the group of the patients with most surgical interventions (HR=0.3, p<0.03). Insular (HR=3.9, p=0.01) and corpus callosum (HR=4.1, p=0.003) localization showed shorter OS compared to other tumor localizations. Patients with IDH wildtype gliomas, who underwent only stereotactic biopsy, had a shorter OS (HR 2.1 p=0.04) compared to those, who underwent a surgical resection. Analysis of the functional outcome in the IDH1/2 mutated group revealed that the risk for development of neurological deficits remained low during the first three surgeries (NANO mean 0.3-0.6). Any further operation increased the risk for functional impairment (NANO mean 1.6-3) significantly. In the IDH1/2 wildtype subgroup the risk for functional deficit increased significantly even after the second surgery (p<0.05).

Conclusion: The impact of different treatment modalities in lower-grade gliomas is highly dependable on the molecular subtype of the tumors. Less aggressive tumors (IDH1/2 mutated) seem to profit from more aggressive treatment like gross total resection as well as multiple resections. Reoperations in IDH1/2 wildtype tumors should be carefully discussed as the risk for neurological impairment increases rapidly, while the impact on the overall survival remains controversial.