title: Prognostic value of molecular and imaging biomarkers in patients with supratentorial glioma.
abstract: OBJECTIVE
  We evaluated the relationship between11C-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 preoperative11C-METH PET were analysed. Semiquantitative evaluation of the11C-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 on11C-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.
  
  
  CONCLUSIONS
  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).
authors.affiliation: Nuclear Medicine, Humanitas Cancer Center, Humanitas Clinical and Research Hospital, Via Manzoni 56, 20089, Rozzano, MI, Italy. egesta.lopci@cancercenter.humanitas.it.
authors.forename: Egesta
authors.identifier: http://orcid.org/0000-0001-9732-1094
authors.initials: E
authors.lastname: Lopci
authors.affiliation: Neurosurgery, Humanitas Clinical and Research Hospital, Rozzano, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Riva
authors.affiliation: Università degli Studi di Milano, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Olivari
authors.affiliation: Neurosurgery, Humanitas Clinical and Research Hospital, Rozzano, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Raneri
authors.affiliation: Neuro-Oncology, University & City of Health and Science Hospital, Turin, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Soffietti
authors.affiliation: Nuclear Medicine, Galliera Hospital, Genova, Italy.
authors.forename: Arnoldo
authors.initials: A
authors.lastname: Piccardo
authors.affiliation: Neuroradiology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bizzi
authors.affiliation: Radiosurgery and Radiotherapy, Humanitas Clinical and Research Hospital, Rozzano, Milan, Italy.
authors.forename: Pierina
authors.initials: P
authors.lastname: Navarria
authors.affiliation: Radiosurgery and Radiotherapy, Humanitas Clinical and Research Hospital, Rozzano, Milan, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Ascolese
authors.affiliation: Neuro-Oncology, University & City of Health and Science Hospital, Turin, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Rudà
authors.affiliation: Pathology, Humanitas Clinical and Research Hospital, Rozzano, Milan, Italy.
authors.forename: Bethania
authors.initials: B
authors.lastname: Fernandes
authors.affiliation: Neurosurgery, Humanitas Clinical and Research Hospital, Rozzano, Milan, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Pessina
authors.affiliation: Medical Oncology, Humanitas Clinical and Research Hospital, Rozzano, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Grimaldi
authors.affiliation: Radiology Department, Humanitas Clinical and Research Hospital, Rozzano, Milan, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Simonelli
authors.affiliation: Università degli Studi di Milano, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Rossi
authors.affiliation: Università degli Studi di Milano, Milan, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Alfieri
authors.affiliation: Radiology Department, Humanitas Clinical and Research Hospital, Rozzano, Milan, Italy.
authors.forename: Paolo Andrea
authors.initials: PA
authors.lastname: Zucali
authors.affiliation: Pathology, Humanitas Clinical and Research Hospital, Rozzano, Milan, Italy.|Humanitas University, Rozzano, Milan, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Scorsetti
authors.affiliation: Neurosurgery, Humanitas Clinical and Research Hospital, Rozzano, Milan, Italy.|Università degli Studi di Milano, Milan, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Bello
authors.affiliation: Nuclear Medicine, Humanitas Cancer Center, Humanitas Clinical and Research Hospital, Via Manzoni 56, 20089, Rozzano, MI, Italy.|Humanitas University, Rozzano, Milan, Italy.
authors.forename: Arturo
authors.initials: A
authors.lastname: Chiti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D012008:Recurrence; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor
keywords: 11C-methionine PET; 1p/19q codeletion; Glioma prognosis; IDH1 mutation; MGMT promoter methylation; WHO classification