Prognostic Molecular and Imaging Biomarkers in Primary Glioblastoma

Abstract

Purpose: Several molecular glioma markers (including isocitrate dehydrogenase 1 [IDH1] mutation, amplification of the epidermal growth factor receptor [EGFR], and methylation of the O6-methylguanine-DNA methyltransferase [MGMT] promoter) have been associated with glioblastoma survival. In this study, we examined the association between tumoral amino acid uptake, molecular markers, and overall survival in patients with IDH1 wild-type (primary) glioblastoma.

Patients and methods: Twenty-one patients with newly diagnosed IDH1 wild-type glioblastomas underwent presurgical MRI and PET scanning with alpha[C-11]-L-methyl-tryptophan (AMT). MRI characteristics (T2- and T1-contrast volume), tumoral tryptophan uptake, PET-based metabolic tumor volume, and kinetic variables were correlated with prognostic molecular markers (EGFR and MGMT) and overall survival.

Results: EGFR amplification was associated with lower T1-contrast volume (P = 0.04) as well as lower T1-contrast/T2 volume (P = 0.04) and T1-contrast/PET volume ratios (P = 0.02). Tumors with MGMT promoter methylation showed lower metabolic volume (P = 0.045) and lower tumor/cortex AMT unidirectional uptake ratios than those with unmethylated MGMT promoter (P = 0.009). While neither EGFR amplification nor MGMT promoter methylation was significantly associated with survival, high AMT tumor/cortex uptake ratios on PET were strongly prognostic for longer survival (hazards ratio, 30; P = 0.002). Estimated mean overall survival was 26 months in patients with high versus 8 months in those with low tumoral AMT uptake ratios.

Conclusions: The results demonstrate specific MRI and amino acid PET imaging characteristics associated with EGFR amplification and MGMT promoter methylation in patients with primary glioblastoma. High tryptophan uptake on PET may identify a subgroup with prolonged survival.

Conflict of interest statement

Conflict of Interest: None of the authors report any conflict of interest or disclosure.

Figures

Figure 1

Representative examples of AMT-PET in a patient with high (A) vs. low (B) uptake associated with different survival. (A) A 54 year-old male (patient #8 in Table 1) with a right frontal glioblastoma, measured with a 2.59 tumor/cortex AMT SUV-ratio, above the ROC-defined threshold of 1.94. He survived for more than 2 years after the PET scan. (B) A 68 year-old male (patient #10 in Table 1) with a right frontal glioblastoma showing a below-threshold tumor/cortex AMT SUV-ratio (1.56). He survived for only 7 months.

Figure 2

Kaplan-Meijer survival curves in patients with high (green) vs. low (blue) AMT uptake ratios (based on the cutoff threshold of 1.94 tumor/cortex SUV ratio, determined by an ROC analysis based on 1-year survival). Patients with above-threshold ratios had a substantially longer cumulative survival (hazard ratio: 30.2 [95% CI: 3.5–259]; P=.002).