Egesta Lopci1, Marco Riva2, Laura Olivari3, Fabio Raneri2, Riccardo Soffietti4, Arnoldo Piccardo5, Alberto Bizzi6, Pierina Navarria7, Anna Maria Ascolese7, Roberta Rudà4, Bethania Fernandes8, Federico Pessina2, Marco Grimaldi9, Matteo Simonelli10, Marco Rossi3, Tommaso Alfieri3, Paolo Andrea Zucali10, Marta Scorsetti8,11, Lorenzo Bello2,3, Arturo Chiti12,11. 1. Nuclear Medicine, Humanitas Cancer Center, Humanitas Clinical and Research Hospital, Via Manzoni 56, 20089, Rozzano, MI, Italy. egesta.lopci@cancercenter.humanitas.it. 2. Neurosurgery, Humanitas Clinical and Research Hospital, Rozzano, Milan, Italy. 3. Università degli Studi di Milano, Milan, Italy. 4. Neuro-Oncology, University & City of Health and Science Hospital, Turin, Italy. 5. Nuclear Medicine, Galliera Hospital, Genova, Italy. 6. Neuroradiology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. 7. Radiosurgery and Radiotherapy, Humanitas Clinical and Research Hospital, Rozzano, Milan, Italy. 8. Pathology, Humanitas Clinical and Research Hospital, Rozzano, Milan, Italy. 9. Medical Oncology, Humanitas Clinical and Research Hospital, Rozzano, Milan, Italy. 10. Radiology Department, Humanitas Clinical and Research Hospital, Rozzano, Milan, Italy. 11. Humanitas University, Rozzano, Milan, Italy. 12. Nuclear Medicine, Humanitas Cancer Center, Humanitas Clinical and Research Hospital, Via Manzoni 56, 20089, Rozzano, MI, Italy.
Abstract
PURPOSE: We evaluated the relationship between 11C-methionine PET (11C-METH PET) findings and molecular biomarkers in patients with supratentorial glioma who underwent surgery. METHODS: A consecutive series of 109 patients with pathologically proven glioma (64 men, 45 women; median age 43 years) referred to our Institution from March 2012 to January 2015 for tumour resection and who underwent preoperative 11C-METH PET were analysed. Semiquantitative evaluation of the 11C-METH PET images included SUVmax, region of interest-to-normal brain SUV ratio (SUVratio) and metabolic tumour volume (MTV). Imaging findings were correlated with disease outcome in terms of progression-free survival (PFS), and compared with other clinical biological data, including IDH1 mutation status, 1p/19q codeletion and MGMT promoter methylation. The patients were monitored for a mean period of 16.7 months (median 13 months). RESULTS: In all patients, the tumour was identified on 11C-METH PET. Significant differences in SUVmax, SUVratio and MTV were observed in relation to tumour grade (p < 0.001). IDH1 mutation was found in 49 patients, 1p/19q codeletion in 58 patients and MGMT promoter methylation in 74 patients. SUVmax and SUVratio were significantly inversely correlated with the presence of IDH1 mutation (p < 0.001). Using the 2016 WHO classification, SUVmax and SUVratio were significantly higher in patients with primary glioblastoma (IDH1-negative) than in those with other diffuse gliomas (p < 0.001). Relapse or progression was documented in 48 patients (median PFS 8.7 months). Cox regression analysis showed that SUVmax and SUVratio, tumour grade, tumour type on 2016 WHO classification, IDH1 mutation status, 1p/19q codeletion and MGMT promoter methylation were significantly associated with PFS. None of these factors was found to be an independent prognostic factor in multivariate analysis. CONCLUSION: 11C-METH PET parameters are significantly correlated with histological grade and IDH1 mutation status in patients with glioma. Grade, pathological classification, molecular biomarkers, SUVmax and SUVratio were prognostic factors for PFS in this cohort of patients. The trial was registered with ClinicalTrials.gov (registration: NCT02518061).
PURPOSE: We evaluated the relationship between 11C-methionine PET (11C-METH PET) findings and molecular biomarkers in patients with supratentorial glioma who underwent surgery. METHODS: A consecutive series of 109 patients with pathologically proven glioma (64 men, 45 women; median age 43 years) referred to our Institution from March 2012 to January 2015 for tumour resection and who underwent preoperative 11C-METH PET were analysed. Semiquantitative evaluation of the 11C-METH PET images included SUVmax, region of interest-to-normal brain SUV ratio (SUVratio) and metabolic tumour volume (MTV). Imaging findings were correlated with disease outcome in terms of progression-free survival (PFS), and compared with other clinical biological data, including IDH1 mutation status, 1p/19q codeletion and MGMT promoter methylation. The patients were monitored for a mean period of 16.7 months (median 13 months). RESULTS: In all patients, the tumour was identified on 11C-METH PET. Significant differences in SUVmax, SUVratio and MTV were observed in relation to tumour grade (p < 0.001). IDH1 mutation was found in 49 patients, 1p/19q codeletion in 58 patients and MGMT promoter methylation in 74 patients. SUVmax and SUVratio were significantly inversely correlated with the presence of IDH1 mutation (p < 0.001). Using the 2016 WHO classification, SUVmax and SUVratio were significantly higher in patients with primary glioblastoma (IDH1-negative) than in those with other diffuse gliomas (p < 0.001). Relapse or progression was documented in 48 patients (median PFS 8.7 months). Cox regression analysis showed that SUVmax and SUVratio, tumour grade, tumour type on 2016 WHO classification, IDH1 mutation status, 1p/19q codeletion and MGMT promoter methylation were significantly associated with PFS. None of these factors was found to be an independent prognostic factor in multivariate analysis. CONCLUSION:11C-METH PET parameters are significantly correlated with histological grade and IDH1 mutation status in patients with glioma. Grade, pathological classification, molecular biomarkers, SUVmax and SUVratio were prognostic factors for PFS in this cohort of patients. The trial was registered with ClinicalTrials.gov (registration: NCT02518061).
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