Abstract
BACKGROUND
The WHO 2021 classification defines IDH wild-type (IDHw) histologically lower-grade glioma (hLGG) as molecular glioblastoma (mGBM) if TERT promotor mutation (pTERTm), EGFR amplification or chromosome 7 gain and 10 loss aberrations are indicated. However, majority of studies reported that patients with mGBM were likely to undergo biopsy rather than resection and less likely to receive adjuvant radiochemotherapy. Thus, while most studies have suggested the prognostic correspondence between hGBM and mGBM, the equivalence has not been sufficiently demonstrated. Furthermore, molecular marker frequency in IDHw hLGGs differ extensively between studies (pTERTm rates = 15% to >70%). It is unclear if such differences are caused by methodological or other factors, however, differences may affect tumor classification and prognostication.
MATERIAL AND METHODS
We systematically reviewed articles of IDHw hLGGs studies in PubMed, Ovid MEDLINE, Cochrane library and Scopus, andmeta-analyzed mGBM prevalence and overall survival (OS) according to the PRISMA statement.
RESULTS
We selected 49 studies (N = 3748) for the analyses. mGBM rates in IDHw hLGG were significantly lower in Asian regions (43.7%, 95% confidence interval [CI: 35.8-52.0]) when compared with non-Asian regions (65.0%, [CI: 52.9-75.4]) (P = 0.005). IDHw hLGGs without pTERTm rarely expressed other molecular markers in Asian studies when compared with non-Asian studies. We compared OS rates of IDHw hLGG tumors between Asian and non-Asian studies using individual patients’ data. The median OS rate in Asian mGBM tumors (21.1 months [CI: 16.1-24.7]) was similar to in non-Asian tumors (20.8 months [CI: 17.9-22.7]) (P = 0.45). Patients with mGBM had significantly longer OS times when compared with histological GBM (hGBM) (pooled hazard ratio (pHR) in univariate analyses 0.824, [CI: 0.694-0.98], P = 0.028, I2 = 46%)). Moderate heterogeneity improved in the pooled HR in multivariate analyses, which showed a significantly better OS in mGBM (HR 0.61 [CI: 0.50-0.74], I2 = 0%) (P < 0.0001). In patients with mGBM, histological grade was a significant prognostic factor (P = 0.018), as was age (P = 0.001) and surgical extent (P = 0.018).
CONCLUSION
Patients with mGBM have better OS when compared with patients with hGBM, especially when grade II histology is indicated. We identified differences between Asian and non-Asian regions in terms of molecular marker frequency pattern for mGBM in IDHw hLGG. However, OS rates in patients with mGBM were concordant between Asian and non-Asian cohorts.