A short history of the Brain Tumour Group
The Brain Tumour Group of the EORTC was formed in the early 70s by a small group of specialists, mainly neurosurgeons:
Who were soon joined by D. Afra, neurosurgeon (Budapest, Hungary)
The main aims of the group at that time were:
The group's history can be divided into two main periods: the era of the pioneers ending with the leadership of Jerzy Hildebrand and from 1996 on, the consolidation phase led by Charles Vecht and Martin van den Bent.
During this period the group also performed 2 randomized trials in patients with low-grade glioma, in conjunction with the radiotherapy group. EORTC trial 22844 compared 2 doses of radiotherapy and proved that a lower dose of radiation may be as efficacious as the higher dose, however with less cognitive toxicity with the lower dose (Karim et al. Int J Radiat Oncol Biol Phys 1996). In a second trial (EORTC 22845) we demonstrated that an expectative approach and delaying radiotherapy until tumor progression is safe and does not negatively influence survival. The trial shows however, that with early radiotherapy the time to progression increases from 3.5 years to 5.5 years, (Karim, Int J Radiat Oncol Biol Phys 2002, Van den Bent, Lancet 2005). Based on these 2 studies we also established a prognostic score for patients with low-grade glioma (Pignatti et al. J Clin Oncol 2002).
In 1996, a series of trials focusing on the most chemosensitive disease entity in neuro-oncology: the oligos (oligodendroglioma and mixed oligo-astrocytoma) were initiated. A large phase III study was launched investigating adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors (EORTC 26951). Ten years later and after randomization of 368 patients we know that adjuvant PCV chemotherapy does prolong the time to disease progression, but not overall survival. Thus chemotherapy does not need to be given at initial diagnosis and is also efficient when administered at the time of disease progression (Van den Bent et al. JCO 2006). Translational research in this study has shown that 1p/19q loss oligodendroglial tumors are a different biological entity. In addition, in two small phase II trials we demonstrated activity of temozolomide as 1 st and 2 nd line treatment in recurrent oligos (26971:Van den Bent, J Clin Oncol; 26972: Van den Bent, Annals of Oncology).
Another focus of the group is testing new chemotherapy or targeted agents in a series of early phase II trials in patients with recurrent glioblastoma. Within this program we tested XR5000, glufosfamide, RFS-2000, and imatinib (Glivec®). Current trials investigate erlotinib and there is a phase I study on lonafarnib in combination with temozolomide.
In 2001, the 1st patient was entered in a landmark study initiated by the group in collaboration with the EORTC Radiotherapy Group and with the National Cancer Institute of Canada (NCIC) Clinical Trials Group. This study accrued almost 600 patients from 15 countries and 85 centres in less than 18 months. The trial demonstrated a survival advantage of concurrent temozolomide chemotherapy and radiotherapy followed by 6 months of adjuvant temozolomide. Not only median survival was significantly prolonged, but the chances of survival at 2 years increased from 1 patient in ten to 1 patient in 4 (10% versus 26%). In addition molecular correlative studies strongly suggest that patients benefiting from the addition of chemotherapy can be identified by analysing the methylation status of the MGMT gene promoter. The impact of these studies published back to back in the prestigious New England Journal of Medicine was major. It immediately changed the standard of care worldwide, and led to formal approval of this regimen by the FDA and EMEA.. Further, the success of this trial fuelled interest in developing treatments for patients with brain tumours. Never before have there been so many treatment options and clinical trials for patients suffering from a brain tumor.
In 2006 the group has grown to around 60 active members, including neurologists and neuro-oncologists, medical oncologists, radiation oncologists, neurosurgeons, pathologists and biologists. Neurological imaging with CT and MRI has revolutionized the field and translational research, genetic and molecular, is pointing the way towards the identification of subgroups of patients who can benefit from certain treatments. At present, all our studies have major translational research side studies.