title: Role ofMGMTMethylation Status at Time of Diagnosis and Recurrence for Patients with Glioblastoma: Clinical Implications.
abstract: MGMTmethylation status represents a powerful prognostic factor in newly diagnosed glioblastoma (GBM). Recently, its role in recurrent tumors has also been suggested; however, few data investigating the stability of this biomarker during the clinical course of the disease are available. In this study, we evaluated the rate of change ofMGMTmethylation status between diagnosis and first recurrence in patients who received tumor resection for recurrent GBM.
  
  
  
  We included patients who received temozolomide concurrent with and adjuvant to radiotherapy after diagnosis of GBM and had a second surgery performed at least 3 months after radiotherapy completion. Other eligibility criteria were age ≥18 years and Eastern Cooperative Oncology Group performance status 0-2. We evaluated theMGMTmethylation status by methylation-specific polymerase chain reaction.
  
  
  
  From our institutional data warehouse, 295 patients with recurrent GBM who underwent second surgery were evaluated.MGMTmethylation status at both first and second surgery was available for 108 patients. MGMT was methylated in both surgeries in 38 patients (35.2%), while it was unmethylated in 43 patients (39.8%). We found a significant concordance between the first and the secondMGMTmethylation assessments (K = 0.500,p< .001),MGMTmethylation being stable in 75% of the cases.
  
  
  
  MGMTmethylation presents relative stability during the clinical course of GBM.The Oncologist2017;22:432-437 IMPLICATIONS FOR PRACTICE:MGMTmethylation is a prognostic factor in newly diagnosed glioblastoma. In this study, we evaluated the rate of change ofMGMTmethylation during the clinical course of the disease, and we found a significant concordance between the first and the secondMGMTmethylation assessments, withMGMTmethylation being stable in 75% of the cases. Thus, re-testing this biomarker at recurrence does not provide further information for clinicians.MGMTmethylation at first surgery, extent of resection at second surgery, and time between first and second surgery are significantly correlated with overall survival. Age and extent of resection are correlated with post-progression survival.
authors.affiliation: Departments of Medical Oncology alba.brandes@yahoo.it.
authors.forename: Alba A
authors.initials: AA
authors.lastname: Brandes
authors.affiliation: Departments of Medical Oncology.
authors.forename: Enrico
authors.initials: E
authors.lastname: Franceschi
authors.affiliation: Departments of Medical Oncology.
authors.forename: Alexandro
authors.initials: A
authors.lastname: Paccapelo
authors.affiliation: Department of Biomedical and NeuroMotor Sciences (DiBiNeM), University of Bologna, Section of Pathology, M. Malpighi, Bellaria Hospital, Bologna, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tallini
authors.affiliation: Department of Biomedical and NeuroMotor Sciences (DiBiNeM), University of Bologna, Section of Pathology, M. Malpighi, Bellaria Hospital, Bologna, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: De Biase
authors.affiliation: Department of Pathology, Verona Hospital, Verona, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Ghimenton
authors.affiliation: Departments of Pathology.
authors.forename: Daniela
authors.initials: D
authors.lastname: Danieli
authors.affiliation: Department of Pathology, University Hospital, Modena, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Zunarelli
authors.affiliation: Department of Pathology, S. Anna University Hospital and University of Ferrara, Ferrara, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lanza
authors.affiliation: Departments of Pathology.
authors.forename: Enrico Maria
authors.initials: EM
authors.lastname: Silini
authors.affiliation: Neurosurgery Bellaria Hospital, Azienda USL - IRCCS Institute of Neurological Sciences, Bologna, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Sturiale
authors.affiliation: Neuroscience and Neurosurgery, San Bortolo Hospital, Vicenza, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Volpin
authors.affiliation: Neurosurgery, University Hospital, Parma, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Servadei
authors.affiliation: Section of Neurosurgery, Department of Neurological, Neuropsychological, Morphological and Movement Sciences, University of Verona, University Hospital, Verona, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Talacchi
authors.affiliation: Neurosurgery Bellaria Hospital, Azienda USL - IRCCS Institute of Neurological Sciences, Bologna, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Fioravanti
authors.affiliation: Department of Biomedical and NeuroMotor Sciences (DiBiNeM), University of Bologna, Section of Pathology, M. Malpighi, Bellaria Hospital, Bologna, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Pia Foschini
authors.affiliation: Departments of Medical Oncology.
authors.forename: Stefania
authors.initials: S
authors.lastname: Bartolini
authors.affiliation: Department of Biomedical and NeuroMotor Sciences (DiBiNeM), University of Bologna, Section of Pathology, M. Malpighi, Bellaria Hospital, Bologna, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pession
authors.affiliation: Department of Neurosciences, Statistic and Informatic Unit, Azienda Ospedale-Università, Padova, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Ermani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D011401:Promoter Regions, Genetic; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide
keywords: Glioblastoma; Heterogeneity; MGMT methylation; Recurrent glioblastoma; Surgery