gms | German Medical Science

Objective: The optimal treatment of WHO grade II gliomas is still under debate. Although the extent of resection (EOR) has repeatedly been shown to improve survival, conclusions were drawn from mixed cohorts, including both astrocytic and oligodendroglial tumours in pooled survival analyses. Also, the significance of IDH1 mutations for patient outcome remains inconclusive. We therefore sought to determine the impact of EOR in an extensive and histologically well-defined cohort of WHO grade II astrocytomas (A II) eligible for resection.

Method: 46 cases with 1st resection of pure A II carried out at our department since 2004 were retrospectively identified. IDH1 mutation status at codon R132H was determined by immunohistochemistry. To objectively quantify the EOR, volumetric analysis of pre- and post-operative tumour volumes was performed on FLAIR images. Survival analysis regarding overall (OS), progression-free (PFS), and malignant progression-free survival (MPFS) as well as time to re-intervention (TTR) was conducted with uni- and multivariate regression models.

Results: This single-centre cohort analysed 46 adult patients (median age 35 years), 38 (83%) carrying IDH1 mutations. During a median follow-up of 62 months, 19 patients experienced progression, 9 malignisation and 9 died. Median pre-operative tumour volume was 44,2 cm³. Median residual volume defined on 1^st follow-up MRI was 4,3 cm³, corresponding to a median EOR of 86% (range 18-100%). No permanent deficits occurred postoperatively. Importantly, the EOR significantly influenced both PFS (p=0.038) and TTR (p=0.038) but had no impact on OS, even when restricted to IDH1-mutated patients. The resection of contrast-enhancing (CE) tumour was associated with longer MPFS (p=0.0009). In multivariate analysis, IDH1 mutation status was an independent positive prognosticator for OS (HR 0.04; p=0.002) and eloquent tumour location for PFS (HR 11.9; p=0.001).

Conclusions: The strength of this study lies in the analysis of a histologically well-defined cohort of A II, stratified for IDH1 mutation status. Maximized EOR and removal of CE tumour significantly influenced progression and malignisation. However, OS was mainly determined by tumour biology with IDH1 mutation identified as the predominant prognostic factor. These findings help to establish IDH1 as an independent prognosticator in A II and stress the importance of a histology-adjusted evaluation of the impact of EOR on patient outcome in future studies.