HGG-05. Systematic review of diffuse hemispheric glioma, H3 G34-mutant and clinical factors influencing outcomes

BACKGROUND: A comprehensive description of clinical features and factors impacting prognosis for patients with diffuse hemispheric glioma, H3 G34-mutant (DHG H3G34) is not easily accessible. Understanding survival data and prognostic features is paramount for clinical advancements and ensuring patients/families are fully informed. METHODS: To summarize clinical, basic histomolecular, and treatment variables and their impacts on survival of DHG H3G34, a systematic review was undertaken. PubMed, Embase, and Google Scholar were searched for English articles published between January 1, 2012, and June 30, 2021. Eligible studies included patient(s) of any age diagnosed with an H3 G34-mutant brain tumour with at least one measure of survival or progression. A protocol was prospectively registered in PROSPERO (CRD42021267764) and PRISMA guidelines were followed. RESULTS: 27 studies met criteria for inclusion (13 pediatric-focused, 3 adult-focused, and 11 all ages). 135 unique patients with DHG H3G34 were included (118 G34R, 8 G34V, and 9 determined via methylation alone). Median age at diagnosis was 15.8 years (IQR=13.3-22.0). At presentation, 90% had localized disease. Co-occurring alterations included ATRX mutation 93%, TP53 mutation 88%, PDGFRA mutation 46%, PDGFRA amplification 13%, and MGMT promoter methylation in 70%. 89% of patients reported progressive disease with a median time-to-progression of 10.0 months. At last follow-up, 71% had died. Median time from progression to death was 5.0 months (IQR=3.0-12.0). Median overall survival was 17.3 months (95% CI 13.5-21.1) with a 1-, 2-, 3-, 5-year survival of 75, 39, 24, and 12%, respectively. Factors found to influence survival duration were presence of MGMT promoter methylation (HR=0.48, 95% CI 0.25-0.90) and less than near-total resection upfront (HR=3.59, 95% CI 2.07-6.22). CONCLUSION: This review highlights the poor prognosis, available survival measures, important prognostic features of DHG G34, and serves as a baseline for future clinical trials, though further study to identify prognostic biomarkers is needed.