Abstract:Background: Glioblastoma (GBM) is an aggressive brain tumor with a short overall survival (OS) in general. The treatment of GBM has evolved over the last decades and is today multimodal including surgical resection followed by radiochemotherapy and adjuvant chemotherapy for patients in good performance status. The aim of this study was to evaluate the development of treatment and the outcome for GBM patients at a single regional center. Patients and methods: Survival was studied for 571 patients in our region … Show more
“…Our results showed that advancements in treatment routines, especially after 2005, led to the improvement of survival based on the Cox model estimates and improved 2-year survival for GBM patients in Germany. First, the median OS was 10 months, which is in line with results from other cancer registry studies (Fabbro-Peray et al 2019;Eriksson et al 2019;Zhu et al 2017;Johnson and O'Neill 2012;Hansen et al 2018) and the clinical trial in elderly patients by Perry et al (Perry et al 2017). Analyzing the age distribution, cases were mostly in the older age categories, which could explain the lower OS in the present study compared to the trial by Stupp et al (2005), which had an upper limit (71 years) on age when enrolling participants.…”
Introduction
Glioblastoma multiforme (GBM) is a primary malignant brain tumour characterized by a very low long-term survival. The aim of this study was to analyse the distribution of treatment modalities and their effect on survival for GBM cases diagnosed in Germany between 1999 and 2014.
Methods
Cases were pooled from the German Cancer Registries with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes for GBM or giant-cell GBM. Three periods, first (January 1999–December 2005), second (January 2006–December 2010) and a third period (January 2011–December 2014) were defined. Kaplan–Meier plots with long-rank test compared median overall survival (OS) between groups. Survival differences were assessed with Cox proportional-hazards models adjusted for available confounders.
Results
In total, 40,138 adult GBM cases were analysed, with a mean age at diagnosis 64.0 ± 12.4 years. GBM was more common in men (57.3%). The median OS was 10.0 (95% CI 9.0–10.0) months. There was an increase in 2-year survival, from 16.6% in the first to 19.3% in the third period. When stratified by age group, period and treatment modalities, there was an improved median OS after 2005 due to treatment advancements. Younger age, female sex, surgical resection, use of radiotherapy and chemotherapy, were independent factors associated with better survival.
Conclusion
The inclusion of temozolomide chemotherapy has considerably improved median OS in the older age groups but had a lesser effect in the younger age group of cases. The analysis showed survival improvements for each treatment option over time.
“…Our results showed that advancements in treatment routines, especially after 2005, led to the improvement of survival based on the Cox model estimates and improved 2-year survival for GBM patients in Germany. First, the median OS was 10 months, which is in line with results from other cancer registry studies (Fabbro-Peray et al 2019;Eriksson et al 2019;Zhu et al 2017;Johnson and O'Neill 2012;Hansen et al 2018) and the clinical trial in elderly patients by Perry et al (Perry et al 2017). Analyzing the age distribution, cases were mostly in the older age categories, which could explain the lower OS in the present study compared to the trial by Stupp et al (2005), which had an upper limit (71 years) on age when enrolling participants.…”
Introduction
Glioblastoma multiforme (GBM) is a primary malignant brain tumour characterized by a very low long-term survival. The aim of this study was to analyse the distribution of treatment modalities and their effect on survival for GBM cases diagnosed in Germany between 1999 and 2014.
Methods
Cases were pooled from the German Cancer Registries with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes for GBM or giant-cell GBM. Three periods, first (January 1999–December 2005), second (January 2006–December 2010) and a third period (January 2011–December 2014) were defined. Kaplan–Meier plots with long-rank test compared median overall survival (OS) between groups. Survival differences were assessed with Cox proportional-hazards models adjusted for available confounders.
Results
In total, 40,138 adult GBM cases were analysed, with a mean age at diagnosis 64.0 ± 12.4 years. GBM was more common in men (57.3%). The median OS was 10.0 (95% CI 9.0–10.0) months. There was an increase in 2-year survival, from 16.6% in the first to 19.3% in the third period. When stratified by age group, period and treatment modalities, there was an improved median OS after 2005 due to treatment advancements. Younger age, female sex, surgical resection, use of radiotherapy and chemotherapy, were independent factors associated with better survival.
Conclusion
The inclusion of temozolomide chemotherapy has considerably improved median OS in the older age groups but had a lesser effect in the younger age group of cases. The analysis showed survival improvements for each treatment option over time.
“…2 ). Seven populations had 2-year survival available at both the earlier and later periods, enabling within-population comparisons: Surveillance, Epidemiology, and End Results (SEER) in the US 13 , 31 , Veterans Health Administration (VA) in the US 15 , Italy 26 , 35 , Switzerland 18 , 28 , France 9 , 17 , Sweden 16 , 24 and Korea 22 . The survival estimates were higher during the later period compared with the earlier period in all seven populations.…”
Section: Resultsmentioning
confidence: 99%
“…3 ) for the later period. There was at least doubling of 3-year survival in all four populations (SEER 20 , 21 , VA 15 , Italy 10 , 26 , and Sweden 16 ) that allowed a within-population comparison. Figure 3 Forest plots of 3-year overall survival stratified by recruitment period.…”
Translation of survival benefits observed in glioblastoma clinical trials to populations and to longerterm survival remains uncertain. We aimed to assess if ≥ 2-year survival has changed in relation to the trial of radiotherapy plus concomitant and adjuvant temozolomide published in 2005. We searched MEDLINE and Embase for population-based studies with ≥ 50 patients published after 2002 reporting survival at ≥ 2 years following glioblastoma diagnosis. Primary endpoints were survival at 2-, 3-and 5-years stratified by recruitment period. We meta-analysed survival estimates using a random effects model stratified according to whether recruitment ended before 2005 (earlier) or started during or after 2005 (later). PROSPERO registration number CRD42019130035. Twentythree populations from 63 potentially eligible studies contributed to the meta-analyses. Pooled 2-year overall survival estimates for the earlier and later study periods were 9% (95% confidence interval [CI] 6-12%; n/N = 1,488/17,507) and 18% (95% CI 14-22%; n/N = 5,670/32,390), respectively. Similarly, pooled 3-year survival estimates increased from 4% (95% CI 2-6%; n/N = 325/10,556) to 11% (95% CI 9-14%; n/N = 1900/16,397). One study with a within-population comparison showed similar improvement in survival among the older population. Pooled 5-year survival estimates were 3% (95% CI 1-5%; n/N = 401/14,919) and 4% (95% CI 2-5%; n/N = 1,291/28,748) for the earlier and later periods, respectively. Meta-analyses of real-world data suggested a doubling of 2-and 3-year survival in glioblastoma patients since 2005. However, 5-year survival remains poor with no apparent improvement. Detailed clinically annotated population-based data and further molecular characterization of longer-term survivors may explain the unchanged survival beyond 5 years. Glioblastoma multiforme is the most common primary malignant brain tumour in adults with an incidence rate of 3.7 per 100,000 person-years, though geographical variation exists 1. Despite an increasing understanding of the underlying pathophysiology, glioblastoma remains an incurable disease with high mortality 2. A landmark clinical trial in 2005 demonstrated that the addition of concomitant and adjuvant temozolomide to radiotherapy provided an additional survival benefit to patients diagnosed with glioblastoma 3. Multiple clinical trials had investigated novel therapies that showed promise in pre-clinical and early phase studies, but to date there have been no major additions to the treatment armamentarium for newly diagnosed patients since 2005. The median survival in the intervention arm of the 2005 trial was 14.6 months 3 , but there is uncertainty about whether survival benefit from clinical trials is translated to the population 4,5. Clinical trial participation itself is associated with better survival 6 , which may be caused by the preferential inclusion and exclusion criteria into clinical trials. In clinical practice not all patients are eligible for the trial standard of care involving maximal surgical debul...
“…The median survival in patients receiving this regimen is about 14 months [9]. However, due to that not all patients receive standard therapy, median survival for all diagnosed GBM patients is considerably less, being reported from 5.8 to 11.2 months [10][11][12][13]. Certain clinical and molecular characteristics such as younger age, good performance status and gross total surgical resection have been associated with longer survival together with O6-methylguanine methyltransferase (MGMT) promoter methylation status [14][15][16][17][18][19][20][21].…”
Background Some glioblastoma (GBM) patients survive more than five years with hitherto no clearly established epidemiological or molecular causes. Since varying rates of GBM five-year survival have been reported our aim was to assess the true prevalence of five-year survivors in Sweden from 1958 to 1999, before the introduction of concomitant temozolomide treatment.Methods After screening the Swedish Cancer Registry and the Cause of Death Register 736 out of 12765 patients with high-grade glioma were defined as five-year survivors. The full text pathology report was reviewed in 585 patients. Data on epidemiology and treatment were retrieved from the medical records of 556 patients.Results 77 five-year survivors with primary GBM were identified which corresponded to 0.60 % of the initial population. During 1990 to 1999 GBM five-year survival was 0. 90%. Younger age, Karnofsky score > 70 and non-eloquent tumour location were found in most but not all five-year survivors.Conclusion GBM five-year survival was exceedingly rare in Sweden until 2004, comprising less than 1 % of registered HGGs. Relying on registry data without reviewing the pathology report will overestimate the accurate number of five-year survivors. To our knowledge, this is the only nationwide population-based study of five-year survival in GBM patients.
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