Systematic review—Time to malignant transformation in low-grade gliomas: Predicting a catastrophic event with clinical, neuroimaging, and molecular markers

Abstract

Background Despite an initially indolent course, all WHO grade II, LGGs inevitably transform to malignant, WHO grades III and IV, without current curative options. Malignant transformation (MT) remains unpredictable with limited prognostic markers to steer timing of interventions. The aim of this study was to review and assign predictive value to specific clinical, molecular and radiological markers impacting MT, thereby justifying timely therapeutic interventions. Methods Searches of MEDLINE, Embase and Cochrane databases were conducted from inception to April 28, 2021 and outputs were analysed in accordance with PRISMA protocol. Results From an initial 5,032 articles, 31 articles were included, totalling 5,193 patients. Forty-three prognostic factors were registered to significantly impact MT. These were categorised as 7 clinical; 14 neuroimaging; 8 biological/molecular; 3 volumetric; 5 topological; 3 histological; and 3 treatment-related. Following analysis, 10 factors were highlighted: the pre-operative prognosticators were 1. presentation with epileptic seizures; 2. VDE >8mm/year; 3. VDE >4mm/year; 4. rCBV >1.75; 5. PTV ≥5 cm (65ml); 6. PTV ≥100 ml; and 7. cortical involvement. The post-operative prognosticators were 1.IDH-wt; 2. TP53 mutation; and 3. temozolomide monotherapy. Conclusions The management of LGGs remains controversial, as conservative and invasive treatment may be associated with MT and impaired quality of life, respectively. Our review indicates that MT can be predicted by specific metrics in VDE, PTV and rCBV, alongside cortical involvement. Additionally, patients with IDH-wt tumours TP53 mutations, or receiving TMZ monotherapy are more likely to undergo MT. Our data may form the basis of a predictive scoring system.

Analysis of Clinical Characteristics and Risk Factors of Postoperative Recurrence and Malignant Transformation of Low-Grade Glioma

“…It was found that the mechanism of epilepsy induced by glioma may be that the invasive tumor cells change the excitability of the surrounding normal neurons, making them the pacemakers of seizures. However, the destructive effect of malignant tumors on peripheral neurons and their axons obstructs the occurrence and transmission of epilepsy [ 26 , 27 ]. In addition, patients with tumor over 5 cm accounted for 27.45% in the control group and 52.63% in the observation group, which was larger in the observation group than that in the control group.…”

High Expression of Glycolytic Genes in Clinical Glioblastoma Patients Correlates With Lower Survival

“…GBM tumors are known to either develop de novo or from LGG tumors. In fact, without treatment, LGGs almost always develop into high grade gliomas (Satar et al, 2021). Recent classification of metabolic properties of LGG tumors has been used to identify important genes in the progression of GBM from LGG, including alterations in lipid metabolism (Wu et al, 2019) and glutamate-and calcium-signaling (Pei et al, 2020).…”

Brain Gliomas and Ollier Disease: Molecular Findings as Predictive Risk Factors?

“…The rate of malignant transformation of LGG ranges from 25% to 72% [ 46 ] and it is influenced by several risk factors, such as preoperative tumor size, velocity of diametric expansion, astrocytoma histology, extent of resection, and treatment with chemotherapy, radiotherapy, and adjuvant chemo-radiotherapy [ 46 ].…”