Systematic Review-Time to Malignant Transformation in Low-grade Gliomas: Predicting a Catastrophic Event with Clinical, Neuroimaging, and Molecular Markers

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, 33 articles were included, totalling 5672 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 > 8 mm/y; 3. VDE > 4 mm/y; 4. rCBV > 1.75; 5. PTV ≥ 5 cm (65 ml); 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.