Malignant Progression of Diffuse Low-grade Gliomas: A Systematic Review and Meta-analysis on Incidence and Related Factors

Abstract

Malignant progression of diffuse low-grade glioma (LGG) is a critical event affecting patient survival; however, the incidence and related factors have been inconsistent in literature. According to the PRISMA guidelines, we systematically reviewed articles from 2009, meta-analyzed the incidence of malignant progression, and clarified factors related to the transformation. Forty-one articles were included in this study (n = 7,122; n, number of patients). We identified two definitions of malignant progression: histologically proven (Htrans) and clinically defined (Ctrans). The malignant progression rate curves of Htrans and Ctrans were almost in parallel when constructed from the results of metaregression by the mean follow-up time. The true transformation rate was supposed to lie between the two curves, approximately 40% at the 10-year mean follow-up. Risk of malignant progression was evaluated using hazard ratio (HR). Pooled HRs were significantly higher in tumors with a larger preand postoperative tumor volume, lower degree of resection, and notable preoperative contrast enhancement on magnetic resonance imaging than in others. Oligodendroglial histology and IDH mutation (IDHm) with 1p/19q codeletion (Codel) also significantly reduced the HRs. Using Kaplan-Meier curves from eight studies with molecular data, we extracted data and calculated the 10-year malignant progression-free survival (10yMPFS). The 10yMPFS in patients with IDHm without Codel was 30.4% (95% confidence interval [95% CI]: 22.2-39.0) in Htrans and 38.3% (95% CI: 32.3-44.3) in Ctrans, and that with IDHm with Codel was 71.7% (95% CI: 61.7-79.5) in Htrans and 62.5% (95% CI: 55.9-68.5) in Ctrans. The effect of adjuvant radiotherapy or chemotherapy could not be determined.

Characterization and clinical implications of different malignant transformation patterns in diffuse low‐grade gliomas

“…For example, IDH wildtype was identified by Satar et al, 3 as a postoperative maker of MT in LGG patients. However, according to the latest WHO CNS classification scheme, 2 tumors with wildtype IDH are currently The potential predictive markers of MT in LGG have been widely investigated, 3,5 with several factors such as older age, 8,29 male sex, 4,8 tumor size, 4,10 chemotherapy, 4,6,8,30,31 radiotherapy, 31 and EOR, 8,10,26 as well as various biomarkers, including CDC20, 32 BIRC3, 33 CX3CR1, 34 FGL2. 35 However, this study identified independent predictors of MT as 1p/19q codeletion, radiotherapy, EOR, Ki-67 index, and KPS score.…”

“…Despite aggressive treatments, malignant transformation (MT) appears to be an inevitable event for patients with LGG 3,4 . Previous studies have denoted that LGG after a long‐term of follow‐up would ultimately progress to a high‐grade variant, including grade 3 and 4, both of which were defined as MT 3,5 . Early detection of indicators of MT is crucial for treatment decision‐making because of the unpredictable course of MT 3,5 .…”

“…Previous studies have denoted that LGG after a long‐term of follow‐up would ultimately progress to a high‐grade variant, including grade 3 and 4, both of which were defined as MT 3,5 . Early detection of indicators of MT is crucial for treatment decision‐making because of the unpredictable course of MT 3,5 . Therefore, many researchers have attempted to identify predictors of MT in LGG cohorts 3,4,6–9 .…”

ABCC8 is correlated with immune cell infiltration and overall survival in lower grade glioma

“…It was identified as grades II and III brain tumors by the World Health Organization. The incidence is estimated to be approximately 0.8 cases per 100,000 population (Nakasu and Nakasu, 2022).…”

Genomic profiles of IDH-mutant gliomas: MYCN-amplified IDH-mutant astrocytoma had the worst prognosis

“…Astrocytoma, isocitrate dehydrogenase (IDH)-mutant (A_IDH_mut) and oligodendroglioma, IDH-mutant and 1p/19q-codeleted (O_IDH_mut) are the 2nd and 3rd most common diffuse infiltrating gliomas in adults after glioblastoma, IDH-wildtype (GBM). According to a meta-analysis, the 10-year progression-free survival (PFS) rates of O_IDH_mut and A_IDH_mut are 62.5% ~ 71.7% and 30.4% ~ 38.3%, respectively 1 . The genomic and molecular alterations of IDH_mut oligodendroglioma and IDH_mut astrocytoma were well described by The Cancer Genome Atlas in 2015 and Ceccarelli et al in 2017 2 , 3 and introduced in neuropathological diagnosis.…”