Survival improvements with adjuvant therapy in patients with glioblastoma

Jayamanne, Dasantha; Wheeler, Helen; Cook, Raymond; Teo, Charles; Brazier, David; Schembri, Geoffrey; Kastelan, Marina; Guo, Linxin; Back, Michael

doi:10.1111/ans.14153

Cited by 19 publications

(19 citation statements)

References 18 publications

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“…Depending of site of the tumour the inherent risks of the neurosurgical procedure may lead to morbidity which includes permanent deficits . In the population of patients with glioblastoma this may be an acceptable risk, as a complete resection not only provides better tumour control within a median survival of 18 months but also potentially less intracranial pressure during adjuvant therapy …”

Section: Discussionmentioning

confidence: 99%

Influence of molecular classification in anaplastic glioma for determining outcome and future approach to management

et al. 2019

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Introduction: Assess survival of patients with anaplastic glioma (AG) and the relationship to molecular subtype. Methods: Patients with AG managed with IMRT between 2008 and 2014 were entered into a prospective database assessing relapse-free survival (RFS) and overall survival (OS). Isocitrate dehydrogenase (IDH) mutations were assessed prospectively from 2011, and subsequent testing of historical patients allowing categorisation under WHO 2016 classification as anaplastic astrocytoma IDH wild type (AAwt), anaplastic astrocytoma IDH mutated (AAmut), anaplastic oligodendroglioma (AOD) or other glial tumour (OTH). Kaplan-Meier estimates of survival distribution were calculated for the primary endpoint of overall survival and Log-rank test used to determine associated factors. Results: One hundred and fifty-six patients were included with median followup for survivors of 4.7 years. Fifty-six per cent were managed after initial diagnosis, whilst 18% received IMRT at second or later relapse. Seventy-three per cent had temozolomide as part of initial therapy. A total of 118 or 75% of patients had IDH mutated glioma, of which 61 were AOD and 57 AAmut. There were 68 relapses and 52 deaths for a 6yrRFS of 51.2% and 6yrOS of 62.5%. AAwt was associated with worse survival (P < 0.001); and delay of RT until second or later relapse (P = 0.03). Within the 118 patients with IDH mutated tumours, 6yrOS for AOD and AAmut were 90.0% and 62.5%, respectively (P = 0.003). Also two or more craniotomies (P < 0.001), delayed RT (P = 0.006) and age <40 years (P = 0.022) were associated with worse survival on univariate analysis but only AAmut subtype and number of craniotomies on multivariate analysis. Conclusion: Within AG, molecular classification predicts for survival, and should influence current decision-making.

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Section: Discussionmentioning

confidence: 99%

Influence of molecular classification in anaplastic glioma for determining outcome and future approach to management

et al. 2019

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“…Consecutive patients managed at a regional cancer center, with adjuvant chemo-radiation therapy as per the EORTC-NCIC Protocol [2] for newly diagnosed GBM from March 2013 to December 2016 were entered into a prospective database, approved by an Institutional Ethics Review Board. Elderly patients managed with hypofractionated RT were not included in the analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Glioblastoma (GBM) is a highly malignant primary brain tumour in adults with a poor prognosis involving a median survival of 17 months [1, 2]. These tumours are highly angiogenic with elevated levels of vascular endothelial growth factor (VEGF) however two large randomised trials have failed to demonstrate an overall survival benefit of VEGF blockade by Bevacizumab (BEV) in the adjuvant therapy of patients with newly diagnosed GBM [3, 4].…”

Section: Introductionmentioning

confidence: 99%

Role of delayed salvage bevacizumab at symptomatic progression of chemorefractory glioblastoma

et al. 2019

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Background Assess benefit of salvage bevacizumab (BEV) at time of symptomatic progression in patients with refractory glioblastoma (GBM). Methods Patients managed with adjuvant long course chemo-radiation therapy for GBM were entered into a prospective database. At chemorefractory symptomatic progression, patients were offered BEV or best supportive care. Re-irradiation (ReRT) was used with BEV in selected patients. BEV continued indefinitely until deterioration limited hospital based infusion. The primary endpoint was median survival calculated from date of decision for BEV to proceed (BEVstart), or decision to decline BEV (BEVreject). Results Fifty-five patients were managed of which 48 patients have relapsed disease. The median survival post relapse was 6 months (95%CI: 4.6–7.4). At relapse, 28 patients received BEV with only 14% delivered at first relapse. The median number of BEV cycles was 8 (range 1–25). ReRT was subsequently used in 16 (33%) relapsed patients. BEV treated patients were associated with improved median survival post relapse with 9 months vs 3 months ( p < 0.01). The median survival from BEV related decision-making at symptomatic refractory progression to death was 4 months (95%CI: 2.0–6.0). BEVstart was associated with improved survival from this date with median survival of 6 months vs 1 month with BEVreject (p < 0.01). Median survival with ReRT from this date was 8 months vs 3 months without ReRT ( p = 0.01). In the BEV patients at eventual progression, death occurred at a median of 30 days post BEV cessation. Conclusion In this clinic managing selected patients with chemorefractory progressive glioblastoma, delayed salvage bevacizumab, often in combination with re-irradiation, may provide an increase in survival duration compared with best supportive care.

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“…Tumor cells have a strong ability for proliferation and invasion, and can invade the central nervous system (2). In 2018, patients with GBM had a poor prognosis, and the median survival time of patients was ~17 months (3). In 2019, following standard treatment, the 6-month progression-free survival rate was 25.2% in patients with recurrent glioblastoma (rGBM) (4).…”

Section: Introductionmentioning

confidence: 99%

High gene expression levels of VEGFA and CXCL8 in the peritumoral brain zone are associated with the recurrence of glioblastoma: A bioinformatics analysis

Luo

Zhong

et al. 2019

Oncol Lett

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The present study aimed to identify differentially regulated genes between the peritumoral brain zone (PBZ) and tumor core (TC) of glioblastoma (GBM), to elucidate the underlying molecular mechanisms and provide a target for the treatment of tumors. The GSE13276 and GSE116520 datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) for the PBZ and TC were obtained using the GEO2R tool. The bioinformatics and evolutionary genomics online tool Venn was used to identify common DEGs between the two datasets. The Database for Annotation, Visualization, and Integrated Discovery online tool was used to analyze enriched pathways of the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The Search Tool for the Retrieval of Interacting Genes/Proteins online tool was used to construct a protein-protein interaction (PPI) network of DEGs. Hub genes were identified using Cytohubba, a plug-in for Cytoscape. The Gene Expression Profiling Interactive Analysis (GEPIA) database was utilized to perform survival analysis. In total, 75 DEGs, including 12 upregulated and 63 downregulated genes, were identified. In the GO term analysis, these DEGs were mainly enriched in ‘regulation of angiogenesis’ and ‘central nervous system development’. Furthermore, in the KEGG pathway analysis, the DEGs were mainly enriched in ‘bladder cancer’ and ‘endocytosis’. When filtering the results of the PPI network analysis using Cytohubba, a total of 10 hub genes, including proteolipid protein 1, myelin associated oligodendrocyte basic protein, contactin 2, myelin oligodendrocyte glycoprotein, myelin basic protein, myelin associated glycoprotein, SRY-box transcription factor 10, C-X-C motif chemokine ligand 8 (CXCL8), vascular endothelial growth factor A (VEGFA) and plasmolipin, were identified. These hub genes were further subjected to GO term and KEGG pathway analysis, and were revealed to be enriched in ‘central nervous system development’, ‘bladder cancer’ and ‘rheumatoid arthritis’. These hub genes were used to perform survival analysis using the GEPIA database, and it was determined that VEGFA and CXCL8 were significantly associated with a reduction in the overall survival of patients with GBM. In conclusion, the results suggest that the recurrence of GBM is associated with high gene expression levels VEGFA and CXCL8, and the development of the central nervous system.

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Survival improvements with adjuvant therapy in patients with glioblastoma

Cited by 19 publications

References 18 publications

Influence of molecular classification in anaplastic glioma for determining outcome and future approach to management

Influence of molecular classification in anaplastic glioma for determining outcome and future approach to management

Role of delayed salvage bevacizumab at symptomatic progression of chemorefractory glioblastoma

High gene expression levels of VEGFA and CXCL8 in the peritumoral brain zone are associated with the recurrence of glioblastoma: A bioinformatics analysis

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