Why do some glioblastoma patients live longer than others? Alice Laurenge (Institut du Cerveau et de la Moelle épinière, Sorbonne Université and Hôspitaux universitaire La Pitié Salpêtrière – Charles Foix, France) tried to answer this question with an analysis that she presented virtually at EAN 2020.
The median survival for glioblastoma patients currently lies between 12 and 15 months.1 However, a small proportion of patients survive more than 5 years after their diagnosis. While some clinical parameters, like performance status or age, are well-known survival predictors, only a few molecular features have been correlated with the survival outcomes of glioblastoma patients.1 “Therefore,” Prof. Laurenge said, “we wanted to clarify the clinical and molecular characteristics associated with long- or short-term survival.”
To this end, the team retrospectively identified glioblastoma patients who survived more than 5 years (n=74) or less than 1 year (n=376) from the Paris database collected between 1996 and 2017. Various clinical and molecular data of identified cases were available.
Favourable parameters consistent with previous findings
In the analysed cohort, Prof. Laurenge and her colleagues found longer survival correlated with young age (P<0.0001) and a high Karnofsky performance score (KPS) (P<0.0001). Additionally, long-term surviving patients underwent surgical resection more often than patients with shorter survival (P<0.0001). Isocitrate dehydrogenase (IDH) 1 or 2 mutations were also found to be significantly correlated with long-term survival (P<0.0001). Taken together, these results confirmed previously available data from similar studies.2,3
Other molecular features identified
However, Prof. Laurenge and her team also identified other molecular features that were correlated with longer survival in glioblastoma patients. Patients who lived more than 5 years after the time of diagnosis were more likely to have a methyl guanine methyl transferase (MGMT) promoter methylation (P=0.0032), and more frequently harboured gains in chromosomes 19p (P=0.029) and 19q (P=0.049). Interestingly, none of the typical hallmark features of glioblastomas, such as loss of chromosome 10, epidermal growth factor receptor (EGFR) gene amplification, or telomerase reverse transcriptase (TERT) mutations, were associated with short-term survival.
A long way to go
At the end of the presentation, the chair of the session, Andreas Hottinger (Département d’oncologie, Lausanne University Hospital, Switzerland), pointed out that “the highlight of the findings is that the classical molecular markers that we see in glioblastoma do not seem to predict outcome”. And indeed, after this initial analysis, Prof. Laurenge and her team are now looking into the biological basis and mechanisms behind their unexpected findings. She concluded that her data “confirmed previous findings, but also raised new questions.” Researchers are not sure yet why some glioblastoma patients live longer than others – but they are on the right track to find out.
For more coverage from EAN 2020, click here.