Correlation of molecular and imaging biomarkers in primary brain tumours

Purpose: Positron emission tomography with carbon-11 labelled methionine (11C-METH PET) is a well-established imaging modality allowing to characterise tumour lesions on a metabolic and molecular level. The aim of the current study was to evaluate the relationship between 11C-METH PET semi-quantitative metrics and molecular biomarkers in patients affected by brain gliomas candidate to surgery, and determine their prognostic role with respect to disease outcome. Materials and Methods: A consecutive series of 145 patients affected by pathologically proven gliomas, who were referred to our Institution for tumour resection from March 2012 to January 2015 and submitted to pre-operative evaluation with 11C-METH PET, was retrospectively analyzed. The trial was registered at www.clinicaltrials.com (NCT02518061). Demographics, clinical-radiological features and follow up data were available for 109 patients (M:F=64:45; median age 43 years). In all cases, semi-quantitative metrics were obtained on 11C-METH PET, i.e. SUVmax, SUVratio and metabolic tumour volume (MTV). These data were correlated to disease outcome, in terms of progression-free survival (PFS), and compared to other clinical-biological information, i.e. IDH1 mutation, 1p/19q co-deletion and MGMT promoter methylation. The entire cohort was monitored for a mean period of 16.7 months (median 13). Results: According to WHO classification, we investigated 40 low grade gliomas (LGG; 36.7%) and 69 high grade gliomas (HGG; 63.3%). In all patients, tumours were identified on 11C-METH PET: median SUVmax 3.3, median SUVratio 2.3, and median MTV 9.6 cm3. We observed a statistically significant difference for SUVmax, SUVratio and MTV values based on tumour grade (p<0.001) and glioblastoma tumours (p<0.001, p<0.001 and p=0.045, respectively). According to molecular analyses, IDH1 resulted mutated in 49 patients, 1p/19q co-deleted in 58 patients and MGMT promoter methylated in 74 patients. We observed a statistically significant correlation between SUVmax and SUVratio and IDH1 mutation (p<0.001). During follow up, relapse or progression was documented in 48 cases (median PFS 8.7 months). We observed a statistically significant correlation to PFS on univariate analysis for SUVmax and SUVratio, tumour grade, IDH1 mutation, 1p/19q co-deletion and MGMT promoter methylation,. Conclusions: Metabolic characteristics on 11C-METH PET significantly correlate with histological grading and IDH1 mutation status in primary brain tumours. With respect to disease outcome, grading, molecular biomarkers, SUVmax and SUVratio resulted prognostic factors to PFS in this cohort of patients candidate to surgery.