The impact of resection in IDH-mutant WHO grade 2 gliomas: a retrospective population-based parallel cohort study.

OBJECTIVE: IDH-mutant diffuse low-grade gliomas (dLGGs; WHO grade 2) are often considered to have a more indolent course. In particular, in patients with 1p19q codeleted oligodendrogliomas, survival can be very long. Therefore, extended follow-up in clinical studies of IDH-mutant dLGG is needed. The authors' primary aim was to determine results after a minimum 10-year follow-up in two hospitals advocating different surgical policies. In one center early resection was favored; in the other center an early biopsy and wait-and-scan approach was the dominant management. In addition, the authors present survival and health-related quality of life (HRQOL) in stratified groups of patients with IDH-mutant astrocytoma and oligodendroglioma. METHODS: The authors conducted a retrospective, population-based, parallel cohort study with extended long-term follow-up. The inclusion criteria were histopathological diagnosis of IDH-mutant supratentorial dLGG from 1998 through 2009 in patients aged 18 years or older. Follow-up ended January 1, 2021; therefore, all patients had primary surgery more than 10 years earlier. In region A, a biopsy and wait-and-scan approach was favored, while early resections were advocated in region B. Regional referral practice ensured population-based data, since referral to respective centers was based strictly on the patient's residential address. Previous data from EQ-5D-3L, European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, and EORTC BN20 questionnaires were reanalyzed with respect to the current selection of IDH-mutant dLGG and to molecular subgroups. The prespecified primary endpoint was long-term regional comparison of overall survival. Secondarily, between-group differences in long-term HRQOL measures were explored. RESULTS: Forty-eight patients from region A and 56 patients from region B were included. Early resection was performed in 17 patients (35.4%) from region A compared with 53 patients (94.6%) from region B (p < 0.001). Characteristics at baseline were otherwise similar between cohorts. Overall survival was 7.5 years (95% CI 4.1-10.8) in region A compared with 14.6 years (95% CI 11.5-17.7) in region B (p = 0.04). When stratified according to molecular subgroups, there was only a statistically significant survival benefit in favor of early resection for patients with astrocytomas. The were no apparent differences in the different HRQOL measures between cohorts. CONCLUSIONS: In an extended follow-up of patients with IDH-mutant dLGGs, early resection was associated with a sustained and clinically relevant survival benefit. The survival benefit was not counteracted by any detectable reduction in HRQOL.

Spatial distribution of malignant transformation in patients with low-grade glioma.

BACKGROUND: Malignant transformation represents the natural evolution of diffuse low-grade gliomas (LGG). This is a catastrophic event, causing neurocognitive symptoms, intensified treatment and premature death. However, little is known concerning the spatial distribution of malignant transformation in patients with LGG. MATERIALS AND METHODS: Patients histopathological diagnosed with LGG and subsequent radiological malignant transformation were identified from two different institutions. We evaluated the spatial distribution of malignant transformation with (1) visual inspection and (2) segmentations of longitudinal tumor volumes. In (1) a radiological transformation site < 2 cm from the tumor on preceding MRI was defined local transformation. In (2) overlap with pretreatment volume after importation into a common space was defined as local transformation. With a centroid model we explored if there were particular patterns of transformations within relevant subgroups. RESULTS: We included 43 patients in the clinical evaluation, and 36 patients had MRIs scans available for longitudinal segmentations. Prior to malignant transformation, residual radiological tumor volumes were > 10 ml in 93% of patients. The transformation site was considered local in 91% of patients by clinical assessment. Patients treated with radiotherapy prior to transformation had somewhat lower rate of local transformations (83%). Based upon the segmentations, the transformation was local in 92%. We did not observe any particular pattern of transformations in examined molecular subgroups. CONCLUSION: Malignant transformation occurs locally and within the T2w hyperintensities in most patients. Although LGG is an infiltrating disease, this data conceptually strengthens the role of loco-regional treatments in patients with LGG.

Quantitative texture analysis in the prediction of IDH status in low-grade gliomas.

OBJECTIVES: Molecular markers provide valuable information about treatment response and prognosis in patients with low-grade gliomas (LGG). In order to make this important information available prior to surgery the aim of this study was to explore if molecular status in LGG can be discriminated by preoperative magnetic resonance imaging (MRI). PATIENTS AND METHODS: All patients with histopathologically confirmed LGG with available molecular status who had undergone a preoperative standard clinical MRI protocol using a 3T Siemens Skyra scanner during 2008-2015 were retrospectively identified. Based on Haralick texture parameters and the segmented LGG FLAIR volume we explored if it was possible to predict molecular status. RESULTS: In total 25 patients (nine women, average age 44) fulfilled the inclusion parameters. The textural parameter homogeneity could discriminate between LGG patients with IDH mutation (0.12, IQR 0.10-0.15) and IDH wild type (0.07, IQR 0.06-0.09, p=0.005). None of the other four analyzed texture parameters (energy, entropy, correlation and inertia) were associated with molecular status. Using ROC curves, the area under curve for predicting IDH mutation was 0.905 for homogeneity, 0.840 for tumor volume and 0.940 for the combined parameters of tumor volume and homogeneity. We could not predict molecular status using the four other chosen texture parameters (energy, entropy, correlation and inertia). Further, we could not separate LGG with IDH mutation with or without 1p19q codeletion. CONCLUSIONS: In this preliminary study using Haralick texture parameters based on preoperative clinical FLAIR sequence, the homogeneity parameter could separate IDH mutated LGG from IDH wild type LGG. Combined with tumor volume, these diagnostic properties seem promising.

Ki-67/MIB-1 immunostaining in a cohort of human gliomas.

Histopathological malignancy grading of human gliomas is limited by subjective interpretation of the morphological criteria. Assessment of mitotic activity is a cornerstone of grading these tumours, but mitotic figures can be hard to identify in haematoxylin-eosin stained sections. Thus, determining proliferative activity by means of Ki-67/MIB-1 immunostaining has become a useful supplement. However, this method has drawbacks, so continuous testing and evaluation are required for optimization and standardization. The aim of this study was to analyse and evaluate the Ki-67/MIB-1 proliferative indices (PIs) in a series of gliomas. We found that Ki-67/MIB-1 PIs correlated well with histological malignancy grade in all glioma subtypes, but a considerable overlap of PIs was observed between the malignancy groups. Consequently, Ki-67/MIB-1 immunostaining alone is not sufficient to adequately determine the malignancy grade. Therefore, future work is necessary to clarify the role of this immunostaining in the histopathological diagnosis of human gliomas.