Biom-24. prediction of distant recurrence in glioblastoma patients treated with standard therapy

Abstract BACKGROUND Infiltrative growth is a hallmark of glioblastoma (GBM) and is a major factor in therapeutic failure. We aimed to identify clinical and molecular factors associated with distance recurrence in glioblastoma patients treated with standard therapy (radiotherapy with concomitant and adjuvant temozolomide). METHODS Two prospective cohorts of consecutive, non-selected GBM patients administered standard therapy as primary treatment between year 2005-2016 (Cohort 1) and 2016-2021 (Cohort 2) at Rigshospitalet, Copenhagen were included. Distant recurrence was defined as a new contrast-enhancing tumor > 2 cm from the gross tumor volume. Clinical and molecular factors were screened for association with time to distant recurrence using univariate Cox regression analysis. The final model was generated employing multivariate analysis. RESULTS Cohort 1 and 2 included 628 and 395 patients, respectively. Out of the recurrence pattern evaluable patients, distant recurrence was observed in 117 patients (23%) in Cohort 1 and 73 patients (22%) in Cohort 2. PRELIMINARY RESULTS In Cohort 1, multivariate analysis showed that corticosteroid use, age, multifocal disease, ECOG performance status, and degree of tumor resection were not associated (p > 0.10) with distant recurrence. Two factors were independently associated with a higher likelihood of distant recurrence, namely non-methylated promoter of the MGMT gene (HR = 1.93; 95% CI:1.27-2.95; p = 0.002) and positive expression of Epidermal Growth Factor Receptor (EGFR) (HR = 3.70; 95% CI: 1.61-8.33; p = 0.002). In Cohort 2, the EGFR status was not available but the association of non-methylated MGMT with distant recurrence was validated (HR = 2.67; 95% CI: 1.62-4.42; p = 0.0001). CONCLUSION Non-methylated MGMT and positive EGFR expression were independent predictors of distant recurrence. Non-methylated MGMT was validated in Cohort 2 and can be used for risk stratification and to enrich clinical trials aiming at improved local or distant tumor control.