Patients with lower grade gliomas (LGGs), including WHO grade 2 and 3 tumours, face almost inevitable progression despite multi-modality therapy. Survival is influenced by multiple factors such as extent of resection, tumour grade, and genetic alterations. Tumours may recur at the same grade (recurrence) or undergo malignant transformation (progression)to high grade glioma (HGG). Early recurrence or progression is characterised as manifesting within the first 24 months following the diagnosis, while late recurrence or progression occurs after this period. Our current understanding is impacted by prior studies which are based on the previous WHO grading system (WHO 2016) and now have limited clinical relevance. Thus, there is a need for new cohorts that consider updated molecular classification.
To identify a cohort of patients for comparison we have leveraged the BRAIN registry (Brain tumour Registry Australia INnovation). BRAIN is a database designed to capture comprehensive clinical information about patients diagnosed with brain tumours. Preliminary survival analysis of the cohort using the WHO 2016 grading was investigated by performing a Kaplan-Meier analysis. Reclassification of samples to WHO 2021 requires the investigation of IDH, ATRX, 1p19q and CDKN2A/B mutation statuses, through immunohistochemistry and genetic sequencing.
Ongoing data collection has identified 378 patients with WHO Grade 2 and 3 IDH mutant LGG, with ages ranging from 15 to 89 years. Among these cohorts, 140 patients underwent at least one additional surgery due to tumour regrowth, categorised as either recurrence (62 cases, 44%) or progression (29 cases, 21%), while 49 cases (35%) are currently under evaluation. The proportion of patients experiencing early recurrence or progression is nearly equivalent to those encountering late events. Evaluation of the survival analysis based on time to recurrence or progression revealed that patients with early recurrence or rapid progression had worse clinical outcomes compared to patients with late events.
Our preliminary findings have identified a cohort of patients with poor survival for further analysis, with time to progression significantly impacting the long-term survival outcomes for patients with LGG. Using the updated WHO grading system is critical to reflect the current fact-based survival status in patients with LGG.