49 Clinical Outcomes and Survival Analysis of IDH1-Mutant Grade 4 Astrocytoma: A Retrospective Review in NHS Tayside (2018-2025)

Abstract Introduction IDH1-mutant Grade 4 astrocytoma’s are associated with younger age and superior prognosis compared to IDH wildtype glioblastoma. However long-term outcomes remain variable. We evaluate outcomes, treatment tolerance, and survival within NHS Tayside. Methods Retrospective review of IDH1-mutant grade 4 astrocytoma between 2018 and 2025. Data extracted from NHS database, including demographics, surgery (biopsy vs debulking), MGMT methylation status, adjuvant treatment (Radiotherapy (XRT) and Temozolomide), overall survival, progression free survival, grade 3 or 4 toxicities, recurrence and treatment after recurrence. Results Eight patients identified. Median age 36 years (range 20-59, M:F 3:1). Surgical intervention: gross total debulking (50%), partial debulking (25%) and biopsy alone (25%). All patients (100%) had adjuvant therapy; TMZ alone (12.5%), combination XRT and TMZ (87.5%). No toxicities grade 3 or above from XRT and TMZ. 87.5% suffered disease recurrence and underwent further treatment. Overall, median progression free survival (PFS) was 16 months, and median overall survival (OS)was 38 months. 50% of the cohort remains alive. Conclusion IDH1 mutant grade 4 astrocytoma’s affect a young demographic in NHS Tayside. Adjuvant therapy was well tolerated; high recurrence rate and 16-month PFS underscore aggressive nature of this tumour. Median OS (38 months) surpasses 14.6 median OS in Stupp trial, where IDH1 status was unknown. A study of IDHI1mut Grade 4 astrocytoma by Lasica et al, 2025 reports median OS of 71 months. Age > 50 and CDKN2A/B deletion are significant negative prognosticators for OS. Going forward, review of high-risk molecular markers such as CDKN2A/B homozygous deletion, will better risk-stratify our patients and help tailor treatment.