EORTC Brain Tumour Group

Translational research associated or integrated into our clinical trials aims at identification of patient subgroups responding to the treatments tested, understanding respective underlying molecular mechanisms, and discovery of new molecular targets for future therapies. All future trial designs comprise a translational research component addressing the question asked by the trial.
Recent studies carried out by the brain tumor group have provided strong clinical evidence for the prognostic or predictive value, respectively, of molecular markers tested. The important clinical impact of these findings is reflected in the fact that the markers have been implemented in the design of the respective follow-up trials. Advances in outcome prediction will lead to individualized management of patients by means of stratifying treatments according to the individual molecular profiles of the patients’ tumors.
However, in order to perform translational research, we need adequate and correctly processed material. Please see the following links for the freezing protocols:

» Protocol snap freezing of tumour biopsies
» Protocol snap freezing of lymphocytes

The glioblastoma study 26981/22981 has demonstrated that benefit from the addition of the alkylating drug temozolomide (TMZ) was basically confined to patients whose tumours had an epigenetically inactivated MGMT repair gene. Thus, the methylation status of the MGMT gene may be considered a strong predictive factor for benefit from TMZ treatment. Furthermore, fresh frozen tumour tissue has been collected from over 10% of the patients that is currently analysed in a comprehensive molecular profiling approach supported by the TRF fund of the EORTC. The predictive value of the MGMT status will be validated in the recently opened RTOG-EORTC phase III trial that randomises newly diagnosed glioblastoma patients to a dose dense schedule of TMZ aimed at depleting the MGMT repair enzyme in the tumour tissue.

Molecular analysis of paraffin embedded tumour tissue collected from patients in study 26951 for anaplastic gliomas has shown that combined loss of chromosomes 1p and 19q was associated with a different natural history with a much better outcome that is, however, not predictive for response to adjuvant PCV treatment in this tumour. Thus 1p/19q loss is now considered to be a prognostic factor. The next trial on anaplastic glioma will require upfront testing and will only randomize the “non-deleted” patients.

Based on the same considerations, loss of heterozygosity on chromosomes 1p/19q will be assessed prospectively in low grade glioma of the study 22033/26033 that randomizes patients to RT or TMZ.

In the randomized phase II study EORTC 26034/16031 on erlotinib in glioblastoma, efforts aim at characterizing the targeted pathway, namely the EGFR receptor status and evaluation of the activation of respective downstream signalling in the tumours.

Target evaluation will be performed in the randomised 3-arm trial EORTC 26041-22041 for newly diagnosed glioblastoma testing the addition of the PTK757 to the new standard of care with combined TMZ/RT. PTK757 targets VEGFR and PDGFR. Furthermore, markers for angiogenesis will be measured in the serum of the patients.