Studying long-term survivors of glioblastoma may pave the way to better treatment

Brussels, May 10, 2023 – Despite major medical advances, glioblastoma remains a highly aggressive form of brain cancer, and life expectancy after diagnosis is usually very short, with a median survival time of 12 months. However, some patients survive for much longer, and studying them may provide pointers to the development of more effective treatment in the future.

The first results from the EORTC 1419 ETERNITY study, which looked at patients with glioblastoma who were still alive at least five years after diagnosis, show that freedom from progression (cancer getting worse) is a powerful predictor of overall survival. The paper¹ has just been published in the European Journal of Cancer. “Perhaps the finding seems obvious, but I don’t believe that the oncology community is wholly aware of this specific subgroup of longer-term survivors and the potential implications for treatment that understanding their survival could provide,” says lead investigator Professor Michael Weller, from the Department of Neurology, University Hospital and University of Zurich, Switzerland.

The researchers studied 280 eligible patients from 24 sites in Europe, the US, and Australia. Of these, 189 had IDH wildtype tumours (the most common form of glioblastoma), 80 were IDH mutant, and 11 were not completely characterised as one or the other.  The IDH wildtype patients had a median age of 56; 96 were female, and 139 had tumours with O⁶-methylguanine-DNA methyltransferase (MGMT) promoter methylation. Patients with MGMT promoter methylated tumours usually react better to chemotherapy.

The median overall survival was 9.9 years. The researchers found that patients without recurrence had longer median survival than patients with one or two recurrences. Surprisingly, they also had a high rate (nearly 75%) of MGMT promoter unmethylated tumours. Such patients may represent a distinct subtype of glioblastoma, the researchers believe.

“This study is the largest centrally-reviewed rigorously compiled study of long-term survival IDH wildtype glioblastoma patients in existence. Studying such survivors can help us push the boundaries of what science can explain and reveal what may be possible in terms of medical advances. We will therefore be maintaining the database and sharing it with researchers who suggest novel investigations in the future,” says Dr Vassilis Golfinopoulos, Headquarters Director at EORTC, and a co-author of the paper.

“The establishment of this group of longer-term survivors with no recurrences will enable us to look further at the biology of their tumours to see how they differ – if indeed they do, since the survival of these patients may also be due to other differences, for example, in their immune systems. Understanding this will, in turn, help us to study how we might improve outcomes for the vast majority of patients whose cancer does progress at some point, most of them very quickly (within 12 months). Once we can be sure of the differences and understand why they exist, we will be able to come a little closer to finding out whether anyone might one day be cured from this highly aggressive disease,” Prof Weller concludes.

The study was funded by The Brain Tumor Funders’ Collaborative and the EORTC Brain Tumour Group.

¹Hertler C et al. (2023). Long-term survival with IDH wildtype glioblastoma: first results from the ETERNITY Brain Tumor Funders’ Collaborative Consortium (EORTC 1419). European Journal of Cancer. https://doi.org/10.1016/j.ejca.2023.05.002