P16.26 * MINIMUM APPARENT DIFFUSION COEFFICIENT MEASUREDBY 3T MR IMAGES IN GLIOBLASTOMA AND O6-METHYLGUANINE-DNA-METHYTRANSFERASE GENE PROMOTER METHYLATED STATUS

Abstract

INTRODUCTION: Glioblastoma (GBM) is the most aggressive type of primary brain tumour. O6-methylguanine-DNA-methytransferase (MGMT) gene promoter methylation status has proven to be a predictive prognostic marker for longer survival in patients with newly diagnosed GBM treated with surgery, radiotherapy and chemotherapy. Patients showing a methylation of the MGMT promoter have a longer overall survival. We used Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) to obtain data about brain tumor structure. It is know that an increased perilesional swelling and tumor cellularity affect DW MRI and the Apparent Diffusion Coefficient (ADC). So far, few studies have analyzed the association between ADC values and MGMT methylation status with conflicting results. More trials are needed to assess the predictive value of DWI MRI as a non-invasive assessment of MGMT promoter methylation status that could add helpful information for clinical management. OBJECTIVE: To assess the correlation between ADC values and MGMT promoter methylation status in patients with GBM. MATERIAL AND METHODS: A retrospective analysis of 3 Tesla MR preoperative studies was perfomed in 13 patients with newly diagnosed GBM (7 M,6 F, mean age 60 years). The analysis of ADC value within the tumor was conducted using automatic co-registration between ADC maps and T1 contrast enhanced weighed images, with MathLab®-based SPM8® dedicated software, and semiautomatic quantitative analysis with 3D Slicer®. MGMT status was evaluated with polymerase chain reaction (PCR) real time (Pyromark Q96 ID System®) in the tumor tissue. RESULTS: The relationship between minimum ADC and percentage of MGMT methylation status was tested with Pearson's linear correlation coefficient, showing moderate correlation (r = 0,48). Observing the high variability of the minimum ADC data, the population has been divided into 4 classes, to reduce this problem. Plotted data revealed a strong correlation between minimum ADC plotted groups and MGMT(r = 0,94). Furthermore, minimum ADC values in tumors presenting under the threshold of 20% of MGMT methylation status were significantly different compared to minimum ACD values measured in tumors over 20% of MGMT methylation status (non parametric Mann-Whitney test, p = 0,04). DISCUSSION: DW-MRI may provide important insight into subtypes of GBM with different gene expressions. Recent studies found an association between the ADC values and the MGMT promoter methylation status. Our findings, even if limited by a relatively small population, showed that minimum ADC value measured within tumor was statistically different between GBM showing MGMT status methylation respectively below and above 20%. CONCLUSION: ADC values may be considered as a noninvasive biomarker of GBM MGMT promoter methylation status and furthermore as an index of patients prognosis.