Which glioblastoma multiforme patient will become a long‐term survivor? A population‐based study

Abstract

In this clinical and histopathological study, the frequency of long-term glioblastoma multiforme (GBM) survivors (LTGBMSs) was determined in a population-based study. The Alberta Cancer Registry was used to identify all patients diagnosed with GBM in Alberta between January 1, 1975, and December 31, 1991. Patient charts were reviewed and histology reexamined. LTGBMSs were defined as GBM patients surviving 3 years after diagnosis. Each LTGBMS was compared with 3 age-, sex-, and year of diagnosis-matched controls, and patient/treatment or tumor characteristics that predicted long-term survival were determined. There were 689 GBMs diagnosed in the study period; 15 (2.2%) of these patients survived 3 years. LTGBMSs (average age, 43.5 +/- 3.3 years) were significantly younger when compared with all GBM patients (average age, 53.0 +/- 0.56 years). LTGBMSs had a higher Karnofsky Performance Status score at diagnosis compared with controls. LTGBMSs were much more likely to have had a gross total resection and adjuvant chemotherapy than control GBM patients. Tumors from LTGBMSs tended to have fewer mitoses and a significantly lower Ki-67 cellular proliferation index compared with controls. Radiation-induced dementia was common and disabling in LTG-BMSs. In conclusion, conventionally treated GBM patients in an unselected population have a very small chance of long-term survival. The use of aggressive surgical resection and adjuvant chemotherapy may make long-term survival more likely in GBM patients if their performance status is high at diagnosis.

Independent Molecular Development of Metachronous Glioblastomas with Extended Intervening Recurrence‐free Interval

“…Its prognosis is dismal with a median survival time of 12 months after diagnosis, despite aggressive therapy (20). Nevertheless, up to 2% of all GBM patients show a long-term survival of more than 3 years (29). The genetic factors, which are responsible for the long recurrence-free time are still unknown (4).…”

ENvironmental Dynamics Underlying Responsive Extreme Survivors (ENDURES) of Glioblastoma: a Multi-disciplinary Team-based, Multifactorial Analytical Approach

“…These predictors could be present at any stage of the patient treatment process and could be based on factors like patient demographics or molecular and genetic features. With small sample sizes of less than 15 ES, two studies found that a majority of ES patients presented with seizures 6,16 . Previous literature has also established that long-term survivors (3+ years) tend to be younger than the average GBM patient 16 .…”

“…With small sample sizes of less than 15 ES, two studies found that a majority of ES patients presented with seizures 6,16 . Previous literature has also established that long-term survivors (3+ years) tend to be younger than the average GBM patient 16 . Multiple studies found that ES cohorts have an average age of 40 years at time of diagnosis 7,8,13,17 , while the average age of primary GBM patients tends to be above 60 years 18,19 .…”

Integrative analysis of DNA methylation suggests down-regulation of oncogenic pathways and reduced de-novo mutation in survival outliers of glioblastoma

“…While the majority of GBM patients live no longer than 2 years, there is a subset of patients who live longer than 3 years and are classified as long-term survivors (LTS). This group of patients remains a puzzle to researchers in the field, as studies on clinical, radiological, histological, and molecular characteristics have yet to yield consensus regarding determinants of durable response to the current treatment (Scott et al 1999;Burton et al 2002a;Burton et al 2002b;Shinojima et al 2004;Krex et al 2007;Martinez et al 2007;Shinawi et al 2013;Ma et al 2015;Lu et al 2016;Mock et al 2016;Prasanna et al 2016;Nakagawa et al 2017;Peng et al 2017). Classic genetic markers of favorable prognosis such as O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation or isocitrate dehydrogenase (IDH) mutation do not fully account for LTS-GBM (Hartmann et al 2013;Gerber et al 2014;Amelot et al 2015;Millward et al 2016;Sarmiento et al 2016;Smrdel et al 2016).…”