Comparison of Different Methods to Test MGMT Status in Glioblastoma Patients
Condition: Glioblastoma
MeSH terms: Glioblastoma
Study type: Observational

Summary: 
      Treatment for newly diagnosed glioblastomas currently involves surgical resection followed by
      Temozolomide chemotherapy with concomitant radiotherapy, and then 6 cycles of Temozolomide in
      adjuvant. According to many studies, only those patients not expressing the enzyme repair
      MGMT benefit from the adjunction of Temozolomide. Therefore, many patients receive
      unnecessary treatment. The aim of this project is to compare different techniques for
      analysis of MGMT in order to choose the approach with the best cost/utility ratio, which will
      allow the selection of patients likely to respond to TMZ chemotherapy during the first course
      of GBM treatment.
    

Detailed description: 
      Treatment for newly diagnosed glioblastomas (GBM) currently involves surgical resection
      followed by Temozolomide (TMZ) chemotherapy with concomitant radiotherapy, and then 6 cycles
      of TMZ in adjuvant (Stupp schedule). According to many studies, only those patients not
      expressing the enzyme repair MGMT benefit from the adjunction of TMZ. Therefore, many
      patients receive unnecessary treatment at an average cost of about 15,000 euros.

      The aim of this project is to compare different techniques for analysis of MGMT in order to
      choose the approach with the best cost/utility ratio, which will allow the selection of
      patients likely to respond to TMZ chemotherapy during the first course of GBM treatment.
      Another aspect of this project is to evaluate the extra cost produced by TMZ treatment, and
      therefore the expected cost saving in the case of using a reliable predictive factor. This
      kind of evaluation is of great importance, as the MGMT test status is beginning to appear in
      the decisional care trees of high-grade gliomas The two main techniques for MGMT analysis are
      currently immunohistochemistry (IH) and molecular analysis of promoter methylation of the
      gene. Immunohistochemistry is simple and quick, but there is no consensus about labelling or
      evaluation of the staining, all of which could lead to variability in results. Studies of
      promoter methylation are currently performed by the MS-PCR technique, in particular the
      article published in the N Engl J Med in 2005 showing that only patients with a methylated
      promoter benefit from TMZ adjunction. This technique appears somewhat rudimentary compared to
      techniques avoiding subjectivity linked to eye reading of the gel after electrophoresis of
      PCR products.

      In phase one of this multicenter national study, IH, MS-PCR, MethyLight, pyrosequencing and
      MS-HRM will be compared in a retrospective study on 100 samples (frozen for molecular
      analysis and paraffin-embedded for IH), taken from patients treated according to the Stupp
      protocol and with a follow-up of 18 months at least. In phase 2, the two techniques with the
      best cost/efficacy ratio (based on predictive value, analytical quality and feasibility of
      the test) will be implemented in all the laboratories according to a standard protocol
      developed by the referral centre for the tests. The dissemination of quality controls will
      allow us to check that the same results are obtained from one laboratory to another. In phase
      3, samples will be analysed prospectively in the different centres and a medico-economic
      analysis will be undertaken on the integration of MGMT analysis into the standard care of GBM
      patients. Two types of analysis will be performed: i) on the costs of the techniques,
      allowing us in particular to estimate the possible additional clinical cost generated and its
      effect on the cost of a hospital stay, in order to adjust the charging system, and ii) on
      alternative care strategies for the patients, with or without screening, leading to improve
      the target of treatments by TMZ, with the aim of improving the definition of "options and
      recommendations" (cost-utility analysis).
    

Intervention name(s): Temozolomide; Radiation Therapy
Intervention type(s): Drug; Radiation
Intervention description(s): According to sites procedures; According to sites procedures
Other intervention name(s): Temodal (brand name).; Radiotherapy
Intervention MeSH terms: Temozolomide
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients with glioblastoma, eligible to resection and to a treatment according to the Stupp
        schedule.
      
Biospecimen description: 
      Freezed or/and parffine embedded tumor samples.
    
Keywords: Glioblastoma