MTR-09ABCB1 AS PREDICTIVE MARKER FOR POOR SURVIVAL IN PATIENTS WITH GLIOBLASTOMA TREATED WITH RADIOTHERAPY AND CONCOMITANT AND ADJUVANT TEMOZOLOMIDE

2015 
BACKGROUND: Standard treatment for newly diagnosed glioblastoma (GBM) patients is surgery followed by radiotherapy (RT) and temozolomide (TMZ) given concomitant and adjuvant. Tumor MGMT methylation status has been identified as predictive for response to TMZ. Also other factors are believed to influence TMZ effect. We examined the role of different single nucleotide variants (SNV:s) of ABCB1, a transmembrane drug transporter, for survival for GBM patients receiving RT concomitant with TMZ. PATIENTS AND METHODS: Genomic samples from patients with GBM who received RT + TMZ concomitant was analyzed for SNV:s of ABCB1, namely variants G1199A, C1236T, G2677T_A and C3435T and correlated to overall survival (OS). ABCB1 was determined using DNA from blood. RESULTS: The cohort included 101 patients, diagnosed and treated between 2004 and 2014. Median age was 60 (range 32-74). 83% of patients received RT 60 Gy, 5% 34 Gy and 12% between 40-58 Gy concomitant with TMZ. For SNV G1199A median OS for variant G/G was 18.2 months versus 11.5 months for those with G/A (p = 0.009), while the other SNV:s showed no significant correlation to survival. For 78 patients MGMT status is available. In multivariate analyses MGMT status and G1199A SNV were both independent factors for survival (p = 0.000 and 0.018 respectively). CONCLUSION: For GBM patients receiving RT concomitant with TMZ the ABCB1 SNV G1199A could be a new treatment predictive factor.
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