NIMG-41MRI FINDINGS IN THE GLARIUS TRIAL: PROGNOSTIC AND PREDICTIVE IMPLICATIONS

Abstract

BACKGROUND: The phase II GLARIUS trial assigned patients with newly diagnosed, O-6-methylguanine-DNA methyltransferase (MGMT) non-methylated glioblastoma to experimental bevacizumab/irinotecan (BEV/IRI) or standard temozolomide (TMZ). BEV/IRI prolonged progression-free survival but overall survival (OS) was similar in both arms. To identify subpopulations with a particularly favourable course, we assessed the prognostic potential of magnetic resonance imaging (MRI) markers at baseline and during the first 4 months of treatment. METHODS: MRIs at baseline, 8, and 16 weeks after therapy initiation were analyzed for T1-hyperintense and diffusion-restricted lesions, contrast-enhancing lesions qualifying for tumor progression (25% increase), and progression of Fluid-attenuated inversion recovery (FLAIR) hyperintense lesions. The MRI findings were correlated with survival. RESULTS: None of the baseline parameters was prognostic in the entire cohort or predictive in the BEV/IRI arm. The presence of diffusion-restricted lesions was neither prognostic nor predictive of BEV/IRI benefit at any timepoint. At 8 weeks of follow-up, 49 patients developing a new combined diffusion-restricted and T1-hyperintense lesion had significantly greater OS than 90 patients without such changes (median OS, 17.5 vs. 15.7 months, p = 0.003). This effect was significant in the BEV/IRI arm (median OS, 17.2 vs. 15.7 months, p = 0.026) whereas significance was narrowly missed in the TMZ arm (median, 18.0 vs. 14.8 months, p = 0.071). At 16 weeks, OS in BEV/IRI-treated patients experiencing exclusively progressive FLAIR hyperintensities (17 of 52 evaluable patients; median OS, 17.5 months) was no worse than in BEV/IRI-treated patients with no progression on FLAIR and T1-weighted contrast-enhancing images (median OS, 19.4 months). In contrast, patients with progressive contrast-enhancing lesions had significantly shorter OS (median, 14.3 months, p = 0.0003, logrank test). CONCLUSIONS: The development of combined T1-hyperintense and diffusion-restricted lesions in early follow-up MRIs is associated with improved OS, particularly in BEV/IRI-treated patients. FLAIR-only progression does not appear to be predictive of a worse outcome with BEV/IRI treatment.