Glioblastoma Clinical Trial
Official title:
Comparative Assessment of Methods to Analyze MGMT as a Predictive Factor of Response to Temozolomide in Glioblastomas.
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.
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).
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