Genetics/Molecular diagnostics • Glioma - Center Foundation

The results of research in the field of oncological molecular diagnostics are gradually becoming more and more meaningful in the therapeutic process of patients with glioma. However, molecular analysis is still too rare and its results are not always translated into the optimization of treatment through a personalized approach. This is among other things why, within the framework of the “Learn more about tumor” project, we strive for necessary changes. The purpose of molecular diagnostics is to learn more about the tumor – genetic alterations, promoter methylation, expression profile.

Before choosing a laboratory (if it is not chosen by a hospital), it is necessary to consider whether the markers which are to be verified in the panel, can be translated into therapeutic modalities. In glioma, the number of mutations for which there are drugs studied in clinical trials is not significant. Consequently, the most important is to mark everything that can help oncologists in treatment decisions. One of the Foundation’s overarching goals is to develop, together with the medical community, recommendations describing the relationship between results that can be brought by molecular diagnostics and treatment modalities. It is not the most important to mark several hundred accidental markers that will not translate into any treatment but to mark all those that can influence decisions about therapeutic options.

Molecular diagnostics – laboratories and costs
In the attached spreadsheet we present examples of paid molecular tests.
However, before patient decides on a paid examination, it should be verified what can be done under insurance in a given country.
Polish version of our portal describes in details reimbursable options in Poland (here)
Spreadsheet
Should MGMT methylation be checked?
MGTM promoter methylation can belong to factors relevant for prognosis; it has also been for long associated with increased effectiveness of temozolomide (TMZ), which is part of standard procedures. In many countries, temozolomide is applied orally, both to children and adults, during radiotherapy and, after treatment, in few day cycles.

If MGMT methylation in the tumor is confirmed, studies demonstrate the expectation of higher effectiveness of TMZ:

(study results).

In some centers (eg. The German clinic in Heidelberg) availability of biopsy material, which makes it possible to establish methylation, is decisive as far as using or not using TMZ in child therapy is concerned. In many foreign institutions lack of methylation data means abolishing TMZ in the treatment of children with diffuse glioblastoma, as retrospective research demonstrates that a great majority of those tumors ate non-methylated, which means that the cost, i.e. side effects, would be higher than the advantage.

Summary
The recommended way of acting is to see that the following individual parameters are specified:

01

The right spectrum of genetic mutations

02

MGMT promoter methylation

03

EGFR expression

04

inhibitor receptors of t lymphocyte: CTLA-4 receptor expression on regulatory T cells and CD8+lymophocytes, CTLA4genetic variant, receptor PD-1, test showing possible production of PD1 – L protein in the tumor

05

genes of the main histocompatibility system of (MHC), in particular, HLA-A2 (blood test)

06

CMV