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Relative change in GBM age–specific incidence rates (ASpR) averaged over two five-year periods 1995-1999 and 2011-2015 in 5-year age bands and gender.
Source publication
Objective
To investigate detailed trends in malignant brain tumour incidence over a recent time period.
Methods
UK Office of National Statistics (ONS) data covering 81,135 ICD10 C71 brain tumours diagnosed in England (1995–2015) were used to calculate incidence rates (ASR) per 100k person–years, age–standardised to the European Standard Population...
Citations
... Furthermore, the conclusions are not based on review of all literature on brain tumor incidence. Philips et al [64] reported: "a sustained and highly statistically significant ASR (age-standardized incidence rates) rise in glioblastoma multiforme (GBM) across all ages. The ASR for GBM more than doubled from 2.4 to 5.0, with annual case numbers rising from 983 to 2531." ...
Radiofrequency (RF) radiation was in 2011 classified as a possible human carcinogen by the International Agency for Research on Cancer (IARC) at the WHO. Currently the WHO undertakes a systematic review of human studies on the cancer risks. In a publication by Karipidis et al (2024), commissioned by the WHO, it was argued that based on all available studies there would be "moderate certanity evidence" that mobile phone use "likely does not increase the risk of glioma, meningioma, acoustic neuroma, pituitary tumours, and salivary gland tumours in adults, or of paediatric brain tumours." However, the authors have overlooked results showing increased risks for brain tumours in the most exposed groups, the most exposed part of the head, and longest latency time from first exposure to tumour diagnosis. The authors also claimed that there would be "moderate certainty evidence" that transmitters and mobile phone base stations do not increase the risk of pediatric leukaemia. These conclusions are based on selective inclusion of very few and low exposure studies. This WHO evaluation is contradicted by scientific results that show increased risks of cancer from exposure to RF-radiation from mobile and cordless phones, transmitters, and base stations. Other scientists have concluded, after reviewing the available evidence, that RF-radiation may increase the risk of cancer. This article analysis the Karipidis et al review and highlights several errors, omissions, and conflicts of interests that may explain the conclusions of no cancer risk. The flawed evaluation of scientific facts should lead to retraction of the article.
... As of 2018, eleven forms of PCD have been described in response to a Shawn T. Beug shawn@arc.cheo.ca [6]. While the incidence of central nervous system (CNS) tumors is low, as a whole these tumors have the third highest mortality to incidence ratio of any human cancer and the highest average treatment costs [7,8]. ...
Glioblastoma is the commonest and deadliest primary brain tumor. Glioblastoma is characterized by significant intra- and inter-tumoral heterogeneity, resistance to treatment and dismal prognoses despite decades of research in understanding its biological underpinnings. Encompassed within this heterogeneity and therapy resistance are severely dysregulated programmed cell death pathways. Glioblastomas recapitulate many neurodevelopmental and neural injury responses; in addition, glioblastoma cells are composed of multiple different transformed versions of CNS cell types. To obtain a greater understanding of the features underlying cell death regulation in glioblastoma, it is important to understand the control of cell death within the healthy CNS during homeostatic and neurodegenerative conditions. Herein, we review apoptotic control within neural stem cells, astrocytes, oligodendrocytes and neurons and compare them to glioblastoma apoptotic control. Specific focus is paid to the Inhibitor of Apoptosis proteins, which play key roles in neuroinflammation, CNS cell survival and gliomagenesis. This review will help in understanding glioblastoma as a transformed version of a heterogeneous organ composed of multiple varied cell types performing different functions and possessing different means of apoptotic control. Further, this review will help in developing more glioblastoma-specific treatment approaches and will better inform treatments looking at more direct brain delivery of therapeutic agents.
... The global prevalence data show that the annual incidence rate ranges from 0.59 to 5 per 100,000 individuals. Data are collected from multiple nations, including the United States, Australia, Britain, Korea, Greece, and Jordan, based on events specific to the age per 100,000 individuals (using the ICD-O 9450 morphological code) [4][5][6][7][8]. ...
Background: Glioblastoma, the predominant primary tumor among all central nervous systems, accounts for around 80% of cases. Prognosis in neuro-oncology involves assessing the disease’s progression in different individuals, considering the time between the initial pathological diagnosis and the time until the disease worsens. A noninvasive therapeutic approach called radiomic features (RFs), which involves the application of artificial intelligence in MRI, has been developed to address this issue. This study aims to systematically gather evidence and evaluate the prognosis significance of radiomics in glioblastoma using RFs. Methods: We conducted an extensive search across the PubMed, ScienceDirect, EMBASE, Web of Science, and Cochrane databases to identify relevant original studies examining the use of RFs to evaluate the prognosis of patients with glioblastoma. This thorough search was completed on 25 July 2024. Our search terms included glioblastoma, MRI, magnetic resonance imaging, radiomics, and survival or prognosis. We included only English-language studies involving human subjects, excluding case reports, case series, and review studies. The studies were classified into two quality categories: those rated 4–6 were considered moderate-, whereas those rated 7–9 were high-quality using the Newcastle–Ottawa Scale (NOS). Hazard ratios (HRs) and their 95% confidence intervals (CIs) for OS and PFS were combined using random effects models. Results: In total, 253 studies were found in the initial search across the five databases. After screening the articles, 40 were excluded due to not meeting the eligibility criteria, and we included only 14 studies. All twelve OS and eight PFS trials were considered, involving 1.639 and 747 patients, respectively. The random effects model was used to calculate the pooled HRs for OS and PFS. The HR for OS was 3.59 (95% confidence interval [CI], 1.80–7.17), while the HR for PFS was 4.20 (95% CI, 1.02–17.32). Conclusions: An RF-AI-based approach offers prognostic significance for OS and PFS in patients with glioblastoma.
... Glioblastoma multiforme (GBM) is known as the most devastating and incurable primary brain tumor. Patients with GBM experience a wide range of side effects and discomforts, resulting in an average life expectancy of approximately 14 months (1)(2)(3)(4). Therefore, more of them are seeking additional remedies. ...
Despite reaching enormous achievements in therapeutic approaches worldwide, GBM still remains the most incurable malignancy among various cancers. It emphasizes the necessity of adjuvant therapies from the perspectives of both patients and healthcare providers. Therefore, most emerging studies have focused on various complementary and adjuvant therapies. Among them, metabolic therapy has received special attention, and metformin has been considered as a treatment in various types of cancer, including GBM. It is clearly evident that reaching efficient approaches without a comprehensive evaluation of the key mechanisms is not possible. Among the studied mechanisms, one of the more challenging ones is the effect of metformin on apoptosis and senescence. Moreover, metformin is well known as an insulin sensitizer. However, if insulin signaling is facilitated in the tumor microenvironment, it may result in tumor growth. Therefore, to partially resolve some paradoxical issues, we conducted a narrative review of related studies to address the following questions as comprehensively as possible: 1) Does the improvement of cellular insulin function resulting from metformin have detrimental or beneficial effects on GBM cells? 2) If these effects are detrimental to GBM cells, which is more important: apoptosis or senescence? 3) What determines the cellular decision between apoptosis and senescence?
... Glioblastoma is the most aggressive and the most frequent brain neoplasia: its incidence is about 5-8 cases per 100,000 inhabitants and represents 54% of all the diagnosed gliomas (1,2). Recent data show a stable incidence in the US or Canada (3), while English and European reports indicate that the incidence is increasing (4). ...
The Stupp regimen remains the standard treatment for newly diagnosed glioblastomas, although the prognosis remains poor. Several temozolomide alternative schedules have been studied, with extended adjuvant treatment (>6 cycles of temozolomide) frequently used, although different trials have indicated contrasting results. Survival data of 87 patients who received 6 (‘6C’ group) or 12 (‘12C’ group) cycles of temozolomide were collected between 2012 and 2022. A total of 45 patients were included in the 6C group and 42 patients were included in the 12C group. Data on isocitrate dehydrogenase mutation and methylguanine-DNA-methyltransferase (MGMT) promoter methylation status were also collected. The 12C group exhibited statistically significantly improved overall survival [OS; 22.8 vs. 17.5 months; hazard ratio (HR), 0.47; 95% CI, 0.30–0.73; P=0.001] and progression-free survival (15.3 vs. 9 months; HR, 0.39; 95% CI, 0.25–0.62; P=0.001). However, in the subgroup analysis according to MGMT status, OS in the 12C group was significantly superior to OS in the 6C group only in the MGMT unmethylated tumors. The present data suggested that extended adjuvant temozolomide appeared to be more effective than the conventional six cycles.
... The appendix in this paper and future follow-up studies should report brain tumor incidence by type and location. For future follow-up studies, prior research (e.g., Hardell et al., 2015b;Schüz et al., 2011;Philips et al., 2018) indicates that COSMOS should report the effects of cumulative exposure to wireless phone use (cordless phones and mobile phones) on glioma and glioblastoma incidence and by the location of tumors, especially in the frontal and temporal lobes, and the risk for ipsilateral versus contralateral tumors. The authors should also compare their annual tumor incidence rates to age-adjusted rates from the cancer registries of the countries participating in the study. ...
... Glioblastoma multiforme (GBM) constitutes a significant part (54.7%) and stands out as the most aggressive form, and is associated with high invasiveness, rapid growth, rapid spread in brain tissue, high recurrence rate, resistance to apoptosis, and an unfavorable poor prognosis. Although current treatment involves surgery, radiation therapy, and chemotherapy, the prognosis remains poor, with a median survival of approximately 12 to 18 months and a five-year survival rate of approximately 4.7% [23][24][25][26][27]. ...
The metabolism of glucose and lipids plays a crucial role in the normal homeostasis of the body. Although glucose is the main energy substrate, in its absence, lipid metabolism becomes the primary source of energy. The main means of fatty acid oxidation (FAO) takes place in the mitochondrial matrix through β-oxidation. Glioblastoma (GBM) is the most common form of primary malignant brain tumor (45.6%), with an incidence of 3.1 per 100,000. The metabolic changes found in GBM cells and in the surrounding microenvironment are associated with proliferation, migration, and resistance to treatment. Tumor cells show a remodeling of metabolism with the use of glycolysis at the expense of oxidative phosphorylation (OXPHOS), known as the Warburg effect. Specialized fatty acids (FAs) transporters such as FAT, FABP, or FATP from the tumor microenvironment are overexpressed in GBM and contribute to the absorption and storage of an increased amount of lipids that will provide sufficient energy used for tumor growth and invasion. This review provides an overview of the key enzymes, transporters, and main regulatory pathways of FAs and ketone bodies (KBs) in normal versus GBM cells, highlighting the need to develop new therapeutic strategies to improve treatment efficacy in patients with GBM.
... Les radiations ionisantes constituent aujourd'hui le seul facteur de risque extrinsèque avéré du sousgroupe des gliomes et des glioblastomes [1,2,[9][10][11]. Le rôle de l'exposition aux radiations thérapeutiques (radiothérapie) dans l'enfance dans le développement du sous-groupe des gliomes, est questionné par certains auteurs [8,10]. ...
... Les radiations ionisantes constituent aujourd'hui le seul facteur de risque extrinsèque avéré du sousgroupe des gliomes et des glioblastomes [1,2,[9][10][11]. Le rôle de l'exposition aux radiations thérapeutiques (radiothérapie) dans l'enfance dans le développement du sous-groupe des gliomes, est questionné par certains auteurs [8,10]. Le rôle d'autres facteurs de risque suspectés (pesticides, champs électromagnétiques) est également questionné mais les études restent jusqu'à présent non conclusives [1, 9,[11][12][13][14][15][16][17][18]. ...
... [43]. La plupart des études et revues internationales mentionnées ci-dessus utilisent ou rapportent des données issues de registres de cancers en population générale [10,12,41,43,44,50], sauf l'étude australienne dont les données n'incluent que les glioblastomes histologiquement confirmés [42]. ...
... 2 Registry studies have found that the incidence of GBM is comparable in the US, England, and Canada, and has been increasing in recent decades across all age groups. 3,4 GBM is a grade IV, diffusely infiltrating, highly cellular, and pleomorphic glioma arising from the astrocyte glial cells. 5 In the 2021 WHO classification of central nervous system tumours, 6 4 types of glioblastoma were recognized, of which GBM with IDH wild type accounted for about 90% of the cases. 1 Most GBM tumours occur in parts of the brain above the brainstem (supratentorial), namely the hemispheres and corpus callosum. ...
What Is the Indication Under Review? The indication under review is for the treatment of adults with newly diagnosed glioblastoma multiforme (ndGBM) following maximal debulking surgery and completion of radiotherapy together with and after standard of care maintenance chemotherapy. Glioblastoma is the development of cancer among glial cells in the central nervous system and is the most common form of brain cancer in Canada. What Is Optune? Optune is a medical device that produces alternating electrical fields called tumour-treating fields to target the growth of cancerous cells in addition to chemotherapy. Current treatment for glioblastoma consists of a combination of surgery, radiotherapy, and chemotherapy. How Did CADTH Evaluate This Device? To examine the value of Optune for the treatment of ndGBM, CADTH: reviewed and critically appraised the clinical and economic evidence submitted by the sponsor reviewed the literature to identify and describe ethical considerations relevant to the use of Optune, as well as to assess the validity of the sponsor’s modelling approaches, assumptions, and estimates regarding Optune sought input from patient and clinician groups and consulted an expert panel. What Did CADTH Find? Clinical Evidence This review included the EF-14 trial, a pivotal, multicentre, open-label randomized controlled trial that assessed the efficacy and safety of Optune plus temozolomide in adults with ndGBM following maximal debulking surgery and completion of radiotherapy, together with and after standard of care maintenance chemotherapy. Based on the single trial, there is evidence of low to moderate certainty that Optune plus temozolomide likely increases progression-free survival at 6 months of treatment and overall survival at 24 months of treatment compared to temozolomide alone. The treatment effect of Optune plus temozolomide on progression-free survival and overall survival may be dose-dependent, with at least 18 hours of daily use required for the most benefit. Overall, the evidence was of very low to moderate certainty due to concerns regarding selection bias and low generalizability of the results to real-world settings. Economic Evidence The submitted fee for Optune is 899,470 per quality-adjusted life-year (QALY) gained (incremental costs = 50,000 per QALY gained and 50,000 and 75,795,323 to cover 232 patients over the initial 3 years of funding. Ethical Considerations The extent to which Optune meets patients’ needs for an effective, accessible, and easily usable treatment may depend on an individual patient’s values and caregiver support network, especially as Optune requires managing an additional treatment modality and may require additional caregiver support. Further study on how — or if — factors such as functional status, race, sex, age, socioeconomic status, and availability of caregiver support have implications for device uptake and ability to adhere to treatment would be helpful to inform patient-centred and equitable use, given the diverse patient population in Canada. Careful attention must be paid to the quality of clinical consent conversations, including considerations of disease progression potentially impairing capacity to consent and requiring a substitute decision-maker. Equity-enhancing strategies for implementation will need to be explored to ensure that Optune is accessible in an equitable and effective manner for all eligible patients in Canada.
... Although this is still low, they are constantly increasing. Since the 1990s, when incidence rates were about 2.5 per 100,000 people-years, they have almost doubled (18). Although the incidence is low compared to other tumors, GBM is the most common malignant brain tumor, accounting for 54-57% of all gliomas (19). ...
Background/aim:
Fisetin is a yellow-coloring flavonoid that can be found in a wide variety of plants, vegetables, and fruits, such as strawberries, apples, and grapes. It has been shown to have biological activity by targeting different pathways regulating survival and death and to bear antioxidant and anti-inflammatory activity. Fisetin was shown to be cytotoxic on different cancer cell lines and has the ability to kill therapy-induced senescent cancer cells. The aim of the study was to investigate the DNA damaging and cytotoxic potential of fisetin and its ability to enhance the killing effect of temozolomide on glioblastoma cells.
Materials and methods:
We used LN229 glioblastoma cells and measured survival and apoptosis by flow cytometry, DNA strand breaks by the alkaline comet and γH2AX assay, and the DNA damage response by western blot analysis.
Results:
Fisetin was cytotoxic on glioblastoma cells, inducing apoptosis. In the dose range of 40-80 μM it also induced DNA damage, as measured by the alkaline comet and γH2AX assay, and triggered DNA damage response, as revealed by p53 activation. Furthermore, fisetin enhanced the genotoxic effect of methyl methanesulfonate, presumably due to inhibition of DNA repair processes. When administered together with temozolomide, the first-line therapeutic for glioblastoma, it enhanced cell death, reduced the yield of senescent cells following treatment and exhibited senolytic activity on glioblastoma cells.
Conclusion:
Data show that high-dose fisetin has a genotoxic potential and suggest that, harnessing the cytotoxic and senolytic activity of the flavonoid, it may enhance the effect of anticancer drugs and eliminate therapy-induced senescent cells. Therefore, it may be useful for adjuvant cancer therapy, including glioblastoma, which is worth to be studied in clinical trials.
