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Role of MGMT Methylation Status at Time of Diagnosis and Recurrence for Patients with Glioblastoma: Clinical Implications.

Al's Comment:

 Good project, but I disagree with their conclusion.  They found that 25% of the time, the methylation status changes between the first and second surgery.   They conclude that it is insignificant and we shouldn't bother testing the second time as it provides no useful information.  They are correct for now, but  that should change very shortly as there is now a drug in clinical trials that can work on unmethylated patients. This makes the methylation status very important to determine, and for those 25% of patients with the changed status, it can be a life altering test.


Posted on: 03/10/2017

Oncologist. 2017 Mar 8. pii: theoncologist.2016-0254. doi: 10.1634/theoncologist.2016-0254. [Epub ahead of print]
Role of MGMT Methylation Status at Time of Diagnosis and Recurrence for Patients with Glioblastoma: Clinical Implications.
Brandes AA1, Franceschi E2, Paccapelo A2, Tallini G3, De Biase D3, Ghimenton C4, Danieli D5, Zunarelli E6, Lanza G7, Silini EM5, Sturiale C8, Volpin L9, Servadei F10, Talacchi A11, Fioravanti A8, Pia Foschini M3, Bartolini S2, Pession A3, Ermani M12.
 
Author information:
1
    Department of Medical Oncology, Azienda USL - IRCCS Institute of Neurological Sciences, Bologna, Italy alba.brandes@yahoo.it.
2
    Department of Medical Oncology, Azienda USL - IRCCS Institute of Neurological Sciences, Bologna, Italy.
3
    Department of Biomedical and NeuroMotor Sciences (DiBiNeM), University of Bologna, Section of Pathology, M. Malpighi, Bellaria Hospital, Bologna, Italy.
4
    Department of Pathology, Verona Hospital, Verona, Italy.
5
    Departments of Pathology.
6
    Department of Pathology, University Hospital, Modena, Italy.
7
    Department of Pathology, S. Anna University Hospital and University of Ferrara, Ferrara, Italy.
8
    Department of Neurosurgery Bellaria Hospital, Azienda USL - IRCCS Institute of Neurological Sciences, Bologna, Italy.
9
    Neuroscience and Neurosurgery, San Bortolo Hospital, Vicenza, Italy.
10
    Neurosurgery, University Hospital, Parma, Italy.
11
    Section of Neurosurgery, Department of Neurological, Neuropsychological, Morphological and Movement Sciences, University of Verona, University Hospital, Verona, Italy.
12
    Department of Neurosciences, Statistic and Informatic Unit, Azienda Ospedale-Università, Padova, Italy.
 
Abstract
BACKGROUND:
 
MGMT methylation 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 of MGMT methylation status between diagnosis and first recurrence in patients who received tumor resection for recurrent GBM.
METHODS:
 
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 the MGMT methylation status by methylation-specific polymerase chain reaction.
RESULTS:
 
From our institutional data warehouse, 295 patients with recurrent GBM who underwent second surgery were evaluated. MGMT methylation 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 second MGMT methylation assessments (K = 0.500, p < .001), MGMT methylation being stable in 75% of the cases.
CONCLUSION:
 
MGMT methylation presents relative stability during the clinical course of GBM. The Oncologist 2017;22:1-6Implications for Practice:MGMT methylation is a prognostic factor in newly diagnosed glioblastoma. In this study, we evaluated the rate of change of MGMT methylation during the clinical course of the disease, and we found a significant concordance between the first and the second MGMT methylation assessments, with MGMT methylation being stable in 75% of the cases. Thus, re-testing this biomarker at recurrence does not provide further information for clinicians. MGMT methylation 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.
 
© AlphaMed Press 2017.
PMID: 28275120 

 


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