P01.12 Stability of actionable mutations in primary and recurrent glioblastomas

Abstract

Introduction: Current efforts to improve patient survival in glioblastomas (GBMs) is often based on a personalized medicine approach where individual patients are treated based on their acquired genetic changes. For ethical reasons, this approach is mainly carried out at tumor recurrence. However, all molecular data is derived from the initial tumor: resections of recurrent GBMs are seldom performed. This study aims to assess whether genetic tumor changes of initial GBMs are still present at recurrence. This establishes whether repeated tumor biopsies are necessary prior to patient inclusion in targeted therapy trials for relapsing GBM. Materials and methods: Patients aged > 18, diagnosed with GBM both at presentation and at recurrence were included in the analysis. All patients were treated according to the current standard of care (temozomolide and radiotherapy). DNA was isolated from pairs of initial and recurrent GBM (FFPE) tumor and samples were sequenced on a panel of ~350 oncogenes and tumor suppressor genes. Results: To date, 255 patients were identified from twelve centers in six countries. Complete clinical data is available from 197 patients with median age of 54.3 years. 98% and 91% of patients had performance score (KPS) >70 at first surgery and second surgery respectively. Our cohort contained relatively few biopsies (3.2% and 4.3% at initial and recurrent surgery respectively). Median survival was 20.9 months, and median time to second surgery 11.2 months. Higher age, greater lesion size at second surgery and steroid treatment were associated with poorer survival in this patient cohort. Preliminary data showed that 6 out of 16 sequenced recurrent GBM samples (37.5%) either gained or lost point mutations in TP53, EGFR, PTEN, TERT, MTOR and MSH6 genes among others. Sequencing analysis of additional tumors is ongoing. CONCLUSION: This preliminary data warrants caution when extrapolating genetic profiling data from initial to recurrent GBM tumors.