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Cancers Aug 2023Over the last 20 years, gliomas have made up over 89% of malignant CNS tumor cases in the American population (NIH SEER). Within this, glioblastoma is the most common... (Review)
Review
Over the last 20 years, gliomas have made up over 89% of malignant CNS tumor cases in the American population (NIH SEER). Within this, glioblastoma is the most common subtype, comprising 57% of all glioma cases. Being highly aggressive, this deadly disease is known for its high genetic and phenotypic heterogeneity, rendering a complicated disease course. The current standard of care consists of maximally safe tumor resection concurrent with chemoradiotherapy. However, despite advances in technology and therapeutic modalities, rates of disease recurrence are still high and survivability remains low. Given the delicate nature of the tumor location, remaining margins following resection often initiate disease recurrence. Photodynamic therapy (PDT) is a therapeutic modality that, following the administration of a non-toxic photosensitizer, induces tumor-specific anti-cancer effects after localized, wavelength-specific illumination. Its effect against malignant glioma has been studied extensively over the last 30 years, in pre-clinical and clinical trials. Here, we provide a comprehensive review of the three generations of photosensitizers alongside their mechanisms of action, limitations, and future directions.
PubMed: 37568734
DOI: 10.3390/cancers15153918 -
Journal of Neuro-oncology Jul 2022Glioblastoma (GBM) is a devastating disease with poor overall survival. Despite the common occurrence of GBM among primary brain tumors, metastatic disease is rare. Our... (Review)
Review
INTRODUCTION
Glioblastoma (GBM) is a devastating disease with poor overall survival. Despite the common occurrence of GBM among primary brain tumors, metastatic disease is rare. Our goal was to perform a systematic literature review on GBM with osseous metastases and understand the rate of metastasis to the vertebral column as compared to the remainder of the skeleton, and how this histology would fit into our current paradigm of treatment for bone metastases.
METHODS
A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant literature search was performed using the PubMed database from 1952 to 2021. Search terms included "GBM", "glioblastoma", "high-grade glioma", "bone metastasis", and "bone metastases".
RESULTS
Of 659 studies initially identified, 67 articles were included in the current review. From these 67 articles, a total of 92 distinct patient case presentations of metastatic glioblastoma to bone were identified. Of these cases, 58 (63%) involved the vertebral column while the remainder involved lesions within the skull, sternum, rib cage, and appendicular skeleton.
CONCLUSION
Metastatic dissemination of GBM to bone occurs. While the true incidence is unknown, workup for metastatic disease, especially involving the spinal column, is warranted in symptomatic patients. Lastly, management of patients with GBM vertebral column metastases can follow the International Spine Oncology Consortium two-step multidisciplinary algorithm for the management of spinal metastases.
Topics: Bone Neoplasms; Brain Neoplasms; Glioblastoma; Humans; Spine
PubMed: 35578056
DOI: 10.1007/s11060-022-04025-4 -
Neurosurgical Review Jun 2023Glioblastoma (GBM) is the most common and aggressive glioma histological subtype, associated with high disability and poor survival. The etiology of this condition is... (Meta-Analysis)
Meta-Analysis Review
Glioblastoma (GBM) is the most common and aggressive glioma histological subtype, associated with high disability and poor survival. The etiology of this condition is still mostly unknown, and evidence about risk factors is elusive. The aim of this study is to identify modifiable risk factors for GBM. Electronic search was performed by two reviewers independently using the keywords and MeSH terms 'glioblastoma' OR 'glioma' OR 'brain tumor' AND 'risk factor'. The inclusion criteria were (1) observational studies or experimental studies on humans, (2) studies assessing the association between glioblastoma and exposure to modifiable conditions, and (3) studies published in English or Portuguese. Studies on the pediatric population or about exposure to ionizing radiation were excluded. A total of 12 studies were included. Seven were case-control studies, and five were cohort studies. The risk factors assessed included body mass index, alcohol consumption, exposure to magnetic fields, diabetes mellitus type 2 (DM2), and use of non-steroidal anti-inflammatory drugs (NSAID). No significant link was found between GBM incidence and DM2 or magnetic field exposure. On the other hand, higher BMI, alcohol consumption, and NSAID use demonstrated a protective effect on GMB risk. However, given the limited number of studies, it is not possible to obtain a behavioral recommendation; instead, these findings are relevant to guide future basic scientific studies on GBM oncogenesis.
Topics: Humans; Child; Glioblastoma; Risk Factors; Glioma; Brain Neoplasms; Diabetes Mellitus, Type 2; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 37340151
DOI: 10.1007/s10143-023-02051-y -
Discover Oncology Oct 2023In the past decade, there has been little progress in the treatment of malignant glioma. Recently, oncolytic virus has made great progress in glioma treatment, and a... (Review)
Review
PURPOSE
In the past decade, there has been little progress in the treatment of malignant glioma. Recently, oncolytic virus has made great progress in glioma treatment, and a number of clinical trials have shown their potential of prolonging the survival time of glioma patients. Our objective is to evaluate effectiveness and safety of oncolytic virus (OV) in malignant glioma treatment.
METHODOLOGY
Based upon PRISMA, we collected relevant published clinical trials by searching medical databases up to January 16, 2023, applying the language restrictions in English and Chinese. We cross-searched the terms: 'glioma', 'glioblastoma', 'oncolytic viruses', 'oncolytic virotherapy' with filter 'clinical trial'. Two researchers independently extracted the data regarding case definitions, published years, trial phase, characteristics of patients, administration of drug, overall survival (OS), and adverse events.
RESULTS
19 published clinical trials in OV treatment of malignant glioma were included in the further systematic review analysis. None of them induced irresistible adverse effects attributing to OV treatment, median overall survival varied from 3.25 to 20.2 months after treatments. According to trials providing patient's detailed molecular diagnosis, we find that the effectiveness of OV treatment has no significant difference in patients with different IDH or MGMT status.
CONCLUSIONS
Current clinical trials have initially shown the potential of oncolytic virotherapy as a new treatment for malignant glioma. Besides development of virus types, the strategy of OV use is an urgent problem to be solved in future clinical application, such as repeated administrations, innovative drug delivery systems, and biomarkers.
PubMed: 37845388
DOI: 10.1007/s12672-023-00769-1 -
Reviews in the Neurosciences Feb 2021Vascular endothelial growth factor (VEGF) has a crucial role in the angiogenesis of various tumors, including glioma. As the levels of VEGF would change in patients with... (Meta-Analysis)
Meta-Analysis Review
Vascular endothelial growth factor (VEGF) has a crucial role in the angiogenesis of various tumors, including glioma. As the levels of VEGF would change in patients with glioma, we conducted the current systematic review and meta-analysis to more clearly determine the VEGF level alterations in different grades of glioma. PubMed and Scopus databases were sensitively searched for all the possible keywords addressing glioma and VEGF. Case-control and cohort studies on human subjects, which measured VEGF levels were eligible to be included in the study. Out of a total number of 3,612 studies, 22 studies were included and 12 studies entered the meta-analysis. This review revealed that serum levels of VEGF in glioma patients were 1.56 pg/dL higher compared to healthy controls ( = 0.05). Besides, immunohistochemistry (IHC) measurement of VEGF in surgical biopsies indicated significant difference in these two groups as well ( = 0.02). Yet, there was not a significant difference between patients with low-grade gliomas (World Health Organization (WHO) grades I-II, LGG) and those with high-grade gliomas (WHO grades III-IV, HGG) ( = 0.43). The results of this systematic review and meta-analysis demonstrate that VEGF levels would significantly increase in glioma, and therefore, could be potentially considered as a biomarker for this cancer.
Topics: Brain Neoplasms; Glioma; Humans; Neovascularization, Pathologic; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
PubMed: 33125340
DOI: 10.1515/revneuro-2020-0062 -
Current Oncology (Toronto, Ont.) Feb 2023Outcomes for patients with high-grade glioma remain poor. Temozolomide (TMZ) is the only drug approved for first-line treatment of glioblastoma multiforme, the most... (Review)
Review
Outcomes for patients with high-grade glioma remain poor. Temozolomide (TMZ) is the only drug approved for first-line treatment of glioblastoma multiforme, the most aggressive form of glioma. Chronotherapy highlights the potential benefit of timed TMZ administration. This is based on pre-clinical studies of enhanced TMZ-induced glioma cytotoxicity dependent on circadian, oscillating expression of key genes involved in apoptosis, DNA damage repair, and cell-cycle mediated cell death. The current systematic review's primary aim was to evaluate the efficacy and toxicity of TMZ chronotherapy. A systemic review of literature following PRISMA guidelines looking at clinical outcomes on TMZ chronotherapy on gliomas was performed. The search in the English language included three databases (PubMed, EMBASE, and Cochrane) and five conferences from 1946 to April 2022. Two independent reviewers undertook screening, data extraction, and risk-of-bias assessment. A descriptive analysis was conducted due to limited data. Of the 269 articles screened, two unique studies were eligible and underwent abstraction for survival and toxicity findings. Both studies-one a retrospective cohort study (n = 166) and the other a prospective randomized feasibility study (n = 35)-were conducted by the same academic group and suggested a trend for improved overall survival, but possibly increased toxicity when TMZ was administered in the morning (vs. evening). There was limited evidence suggesting possible therapeutic value from administering TMZ in the morning, which may be consistent with the pre-clinical observations of the importance of the timing of TMZ administration in vitro. Larger, pragmatic, prospective randomized controlled trials are needed to ascertain the value of TMZ chronotherapy to provide optimized and equitable care for this population.
Topics: Humans; Temozolomide; Retrospective Studies; Prospective Studies; Brain Neoplasms; Glioma; Chronotherapy; Randomized Controlled Trials as Topic
PubMed: 36826108
DOI: 10.3390/curroncol30020147 -
World Neurosurgery Oct 2023Sonodynamic therapy (SDT) has emerged as an encouraging noninvasive technique that uses ultrasound to activate targeted agents to induce antitumor effects for the... (Review)
Review
Sonodynamic therapy (SDT) has emerged as an encouraging noninvasive technique that uses ultrasound to activate targeted agents to induce antitumor effects for the treatment of glioma. With extensive variation in the types of sonosensitizers, protocols for sonication, and model systems, a comprehensive overview of existing preclinical data on the efficacy of SDT in glioma treatment is warranted. Here, we conduct a systematic review of preclinical and early clinical literature on implementing SDT to treat in vitro and in vivo models of glioma. Our findings suggest that coupling sonosensitizers such as 5-aminolevulinic acid, hematoporphyrin monomethyl ether, and sinoporphyrin sodium with focused ultrasound induces robust cytotoxic activity in tumor cells (in vitro and in vivo). These effects are likely mediated by the oxidative stress induced by reactive oxygen species production, apoptotic signaling cascades, and intracellular calcium overload. Future research is needed to better understand the biochemical and mechanistic properties of SDT, and ongoing trials may help elucidate the clinical feasibility of glioma treatment with optimized sonically activated treatments.
Topics: Humans; Ultrasonic Therapy; Glioma; Aminolevulinic Acid; Apoptosis; Reactive Oxygen Species; Antineoplastic Agents; Cell Line, Tumor
PubMed: 37454909
DOI: 10.1016/j.wneu.2023.07.030 -
Journal of Neuro-oncology Dec 2023Glioma is a challenging malignant tumor with a low survival rate and no effective treatment. Recently, ganciclovir, an antiviral drug, combined with gene therapy and its... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Glioma is a challenging malignant tumor with a low survival rate and no effective treatment. Recently, ganciclovir, an antiviral drug, combined with gene therapy and its own antiviral ability, has been proposed as a potential treatment for glioma. However, there are differences in the results of various clinical trials. In this study, we conducted a systematic review and meta-analysis to evaluate the efficacy of ganciclovir in treating glioma.
METHODS
We searched databases such as PubMed, EMBASE, and Cochrane Library before March 30, 2023. The search terms included glioma, ganciclovir, valganciclovir and treatment. Calculated 1, 2 and 4-year survival rate by risk difference (RD), and overall survival (OS) by odds ratio (OR).
RESULTS
Five randomized controlled trials (RCTs) with a total of 606 high-grade glioma patients were included. The results showed that ganciclovir can improve 2-yeaer (RD = 0.179, 95% CI 0.012-0.346, P = 0.036) and 4-year survival rate (RD = 0.185, 95% CI 0.069-0.3, P = 0.002) and OS (OR 2.393, 95% CI 1.212-4.728, P = 0.012) compared with the control group.
CONCLUSIONS
This meta-analysis showed that ganciclovir significantly improved the prognosis of glioma patients. Therefore, we suggest that more cases of ganciclovir as a glioma treatment can be conducted, or a large clinical trial can be designed.
Topics: Humans; Ganciclovir; Glioma; Prognosis; Randomized Controlled Trials as Topic
PubMed: 38066255
DOI: 10.1007/s11060-023-04503-3 -
Neurosurgical Review Apr 2021Given the median survival of 15 months after diagnosis, novel treatment strategies are needed for glioblastoma. Beta-blockers have been demonstrated to inhibit...
Given the median survival of 15 months after diagnosis, novel treatment strategies are needed for glioblastoma. Beta-blockers have been demonstrated to inhibit angiogenesis and tumor cell proliferation in various cancer types. The aim of this study was to systematically review the evidence on the effect of beta-blockers on glioma growth. A systematic literature search was performed in the PubMed, Embase, Google Scholar, Web of Science, and Cochrane Central to identify all relevant studies. Preclinical studies concerning the pharmacodynamic effects of beta-blockers on glioma growth and proliferation were included, as well as clinical studies that studied the effect of beta-blockers on patient outcomes according to PRISMA guidelines. Among the 980 citations, 10 preclinical studies and 1 clinical study were included after title/abstract and full-text screening. The following potential mechanisms were identified: reduction of glioma cell proliferation (n = 9), decrease of glioma cell migration (n = 2), increase of drug sensitivity (n = 1), induction of glioma cell death (n = 1). Beta-blockers affect glioma proliferation by inducing a brief reduction of cAMP and a temporary cell cycle arrest in vitro. Contrasting results were observed concerning glioma cell migration. The identified clinical study did not find an association between beta-blockers and survival in glioma patients. Although preclinical studies provide scarce evidence for the use of beta-blockers in glioma, they identified potential pathways for targeting glioma. Future studies are needed to clarify the effect of beta-blockers on clinical endpoints including survival outcomes in glioma patients to scrutinize the value of beta-blockers in glioma care.
Topics: Adrenergic beta-Antagonists; Brain Neoplasms; Cell Death; Cell Proliferation; Clinical Trials as Topic; Drug Evaluation, Preclinical; Glioblastoma; Glioma; Humans; Neovascularization, Pathologic
PubMed: 32172480
DOI: 10.1007/s10143-020-01277-4 -
Journal of Oncology Pharmacy Practice :... Oct 2023We conducted a systematic review and meta-analysis aiming to assess the efficacy and safety of Nivolumab treatment in patients with newly diagnosed and recurrent... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
We conducted a systematic review and meta-analysis aiming to assess the efficacy and safety of Nivolumab treatment in patients with newly diagnosed and recurrent glioblastoma multiforme (GBM).
DATA SOURCES
Our study followed the guidelines outlined in the preferred reporting items for systematic reviews and meta-analyses (PRISMA) recommendations. The protocol for this review can be found in the International Prospective Register of Systematic Reviews Database (CRD42022340071). We performed searches on the Medline, PubMed, Embase, Scopus, and Web of Science databases.
DATA SUMMARY
A total of 545 studies were identified through our comprehensive search across the five databases (PubMed: 78, Embase: 82, Medline: 173, Scopus: 138, Web of Science: 74). After conducting a thorough analysis, our meta-analysis indicated that treatment with Nivolumab led to improved overall survival (OS) outcomes in newly diagnosed glioblastoma patients, as evidenced by a prolonged median OS based on trial data. However, there was no significant beneficial effect observed in terms of median progression-free survival (PFS), as well as OS at 6, 12, and 24 months. Furthermore, our results demonstrated no efficacy of Nivolumab in the treatment of recurrent GBM patients.
CONCLUSIONS
In conclusion, Nivolumab demonstrated promising results that warrant further investigation for its use in newly diagnosed glioblastoma patients. However, its effectiveness was not observed in the context of recurrent GBM.
Topics: Humans; Glioblastoma; Nivolumab; Neoplasm Recurrence, Local; Progression-Free Survival; Brain Neoplasms
PubMed: 37503551
DOI: 10.1177/10781552231190104