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European Journal of Clinical... May 2024Dabrafenib and trametinib represent targeted therapy options under investigation for treatment of gliomas harboring BRAF V600 mutations. We systematically reviewed the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dabrafenib and trametinib represent targeted therapy options under investigation for treatment of gliomas harboring BRAF V600 mutations. We systematically reviewed the literature and conducted meta-analyses to assess the efficacy and safety of these agents.
METHODS
PubMed, Embase, and Scopus were searched from inception to September 2023 for studies examining dabrafenib and/or trametinib for gliomas. Outcomes included response rates (ORR, CR, PR), progression rates (PD), 6- and 12-month PFS, adverse events, and dosing modifications. Meta-analyses were conducted using random effect models.
RESULTS
Nine studies met the inclusion criteria. Meta-analysis demonstrated overall response rates (ORR) of 50% (95% confidence interval (CI): 35-65%) for low-grade gliomas (LGG) and 40% (95% CI: 29-51%) for high-grade gliomas (HGG). Pooled ORR was 45% (95% CI: 36-54%) for both glioma grades. The complete response rate was 13% (95% CI: 05-27%) for HGG and 5% (95% CI: 1-10%) for both LGG and HGG. Six-month progression-free survival (PFS) rates reached 87% in LGG and 67% in HGG and a pooled 6-month PFS 78% (95% CI: 58-98%), declining at 12 months to 67% and 44%, respectively, with a pooled 12-month PFS 56% (95% CI: 34-79%). Grade 1-4 adverse events occurred in 100% of LGG and 63% of HGG patients.
CONCLUSIONS
Dabrafenib and trametinib demonstrate promising anti-tumor efficacy in gliomas, particularly low-grade tumors, achieving durable disease stabilization in many patients. However, toxicity significantly limited tolerability. Additional research should further examine efficacy and refine safe administration protocols across glioma subtypes.
Topics: Humans; Imidazoles; Glioma; Oximes; Pyridones; Mutation; Antineoplastic Combined Chemotherapy Protocols; Pyrimidinones
PubMed: 38345637
DOI: 10.1007/s00228-024-03635-3 -
Seminars in Ophthalmology 2014The purpose of this paper is to perform a systematic review of the published literature on complications of intra-arterial chemothrapy (IAC) for the treatment of... (Review)
Review
INTRODUCTION
The purpose of this paper is to perform a systematic review of the published literature on complications of intra-arterial chemothrapy (IAC) for the treatment of retinoblastoma.
MATERIALS AND METHODS
A literature search was performed using the Pubmed database using the terms. Complications were divided into extraocular and intraocular.
RESULTS
A total of 117 articles were found using this Pubmed search method; 35 articles were selected for review as they describe specifical complications of IAC for retinoblastoma. A variety of extraocular and intraocular complications were reported and discussed.
DISCUSSION
IAC for the treatment of retinoblastoma is a technique that has been gaining popularity in recent years, but is not without complications. Continued research is warranted to further improve current techniques and delivery of chemotherapeutic agents into the eye.
Topics: Antineoplastic Agents; Child, Preschool; Humans; Infant; Infusions, Intra-Arterial; Ophthalmic Artery; Retinal Neoplasms; Retinoblastoma
PubMed: 25325870
DOI: 10.3109/08820538.2014.959188 -
Neurosurgical Review Jan 2024High-grade gliomas (HGGs) are aggressive tumors of the central nervous system that cause significant morbidity and mortality. Despite advances in surgery and radiation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
High-grade gliomas (HGGs) are aggressive tumors of the central nervous system that cause significant morbidity and mortality. Despite advances in surgery and radiation therapy (RT), HGG still has a high incidence of recurrence and treatment failure. Intraoperative radiotherapy (IORT) has emerged as a promising therapeutic approach to achieve local tumor control while sparing normal brain tissue from radiation-induced damage.
METHODS
A systematic review and meta-analysis were conducted following PRISMA guidelines to evaluate the use of IORT for HGG. Eligible studies were included based on specific criteria, and data were independently extracted. Outcomes of interest included complications, IORT failure, survival rates at 12 and 24 months, and mortality.
RESULTS
Sixteen studies comprising 436 patients were included. The overall complication rate after IORT was 17%, with significant heterogeneity observed. The IORT failure rate was 77%, while the survival rates at 12 and 24 months were 74% and 24%, respectively. The mortality rate was 62%.
CONCLUSION
This meta-analysis suggests that IORT may be a promising adjuvant treatment for selected patients with HGG. Despite the high rate of complications and treatment failures, the survival outcomes were comparable or even superior to conventional methods. However, the limitations of the study, such as the lack of a control group and small sample sizes, warrant further investigation through prospective randomized controlled trials to better understand the specific patient populations that may benefit most from IORT. However, the limitations of the study, such as the lack of a control group and small sample sizes, warrant further investigation. Notably, the ongoing RP3 trial (NCT02685605) is currently underway, with the aim of providing a more comprehensive understanding of IORT. Moreover, future research should focus on managing complications associated with IORT to improve its safety and efficacy in treating HGG.
Topics: Humans; Brain Neoplasms; Prospective Studies; Glioma; Neoplasm Recurrence, Local; Radiotherapy
PubMed: 38221545
DOI: 10.1007/s10143-024-02279-2 -
International Journal of Molecular... Feb 2022Glioblastoma (GBM) is the most common and malignant tumour of the central nervous system. Recent appreciation of the heterogeneity amongst these tumours not only changed... (Review)
Review
Glioblastoma (GBM) is the most common and malignant tumour of the central nervous system. Recent appreciation of the heterogeneity amongst these tumours not only changed the WHO classification approach, but also created the need for developing novel and personalised therapies. This systematic review aims to highlight recent advancements in understanding the molecular pathogenesis of the GBM and discuss related novel treatment targets. A systematic search of the literature in the PubMed library was performed following the PRISMA guidelines for molecular pathogenesis and therapeutic advances. Original and meta-analyses studies from the last ten years were reviewed using pre-determined search terms. The results included articles relevant to GBM development focusing on the aberrancy in cell signaling pathways and intracellular events. Theragnostic targets and vaccination to treat GBM were also explored. The molecular pathophysiology of GBM is complex. Our systematic review suggests targeting therapy at the stemness, p53 mediated pathways and immune modulation. Exciting novel immune therapy involving dendritic cell vaccines, B-cell vaccines and viral vectors may be the future of treating GBM.
Topics: Adult; Brain Neoplasms; Glioblastoma; Humans; Signal Transduction
PubMed: 35269752
DOI: 10.3390/ijms23052607 -
Neurosurgery Mar 2023Many patients with glioma and their caregivers seek complementary and alternative medicine (CAM) methods to comfort themselves, cope with cancer medication side effects,...
BACKGROUND
Many patients with glioma and their caregivers seek complementary and alternative medicine (CAM) methods to comfort themselves, cope with cancer medication side effects, and feel they are taking control of their disease.
OBJECTIVE
To summarize existing evidence on safety and efficacy of CAM treatments for gliomas.
METHODS
We performed an exhaustive electronic literature search for in vitro, animal, and clinical studies (English language, all years available) on CAM modalities for gliomas.
RESULTS
A total of 378 studies (315 unique articles) were analyzed. Distribution was as follows: in vitro-274 (73%), animal-77 (20%), and clinical-26 (7%, 2491 patients). Most studies were conducted in China (n = 135, 43%), followed by the United States (n = 62, 20%) and Spain (n = 17, 5%-6%). Resveratrol was the most commonly investigated CAM therapy in the in vitro (n = 62) and in vivo (n = 17) setting. Safety/toxicity was examined in 21% of in vitro (cytotoxic at same dose in 48%), 39% of in vivo (no evidence of organ toxicity), and 50% of clinical studies (adverse events reported in 6). Cytotoxicity was the most frequent end point among in vitro (60%) and animal studies (56%), followed by synergistic action with chemotherapy and inhibition of invasiveness and migration. Finally, 7 of 26 studies found no clinical effect, whereas 5 reported possible impact on progression-free or overall survival, 3 demonstrated decrease or arrest of tumor progression, and 2 showed positive impact on symptoms and quality of life.
CONCLUSION
These findings will hopefully educate providers and patients and stimulate further research in the field of CAM therapy for gliomas.
Topics: United States; Humans; Quality of Life; Complementary Therapies; Glioma; Antineoplastic Agents; China
PubMed: 36650046
DOI: 10.1227/neu.0000000000002236 -
Journal of Neurosurgery Mar 2022The tumor characteristics and surgical outcomes of intracranial subependymomas are poorly defined. In this study the authors aimed to provide a comprehensive review of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The tumor characteristics and surgical outcomes of intracranial subependymomas are poorly defined. In this study the authors aimed to provide a comprehensive review of all clinical, pathological, radiological, and surgical aspects of this important neoplasm to inform future management strategies.
METHODS
A systematic review and meta-analysis of MEDLINE, EMBASE, Cochrane, and Google Scholar databases adherent to PRISMA guidelines was conducted.
RESULTS
Of the 1145 articles initially retrieved, 24 studies encompassing 890 cases were included. The authors identified 3 retrospective cohort studies and 21 case series, but no controlled trials. Mean age at presentation was 46.7 ± 18.1 years with a male predominance (70.2%). Common sites of tumor origin were the lateral ventricle (44.5%) and fourth ventricle (43.1%). Cumulative postoperative mortality and morbidity rates were 3.4% and 24.3% respectively. Meta-analysis revealed that male sex (HR 3.15, 95% CI 1.39-7.14, p = 0.006) was associated with poorer 5-year overall mortality rates. All-cause mortality rates were similar when performing subgroup meta-analyses for age (HR 0.50, 95% CI 0.03-7.36, p = 0.61), smaller subependymoma size (HR 1.51, 95% CI 0.78-2.92, p = 0.22), gross-total resection (HR 0.65, 95% CI 0.35-1.23, p = 0.18), and receipt of postoperative radiation therapy (HR 0.88, 95% CI 0.27-2.88, p = 0.84). Postoperative Karnofsky Performance Index scores improved by a mean difference of 1.62 ± 12.14 points (p = 0.42). The pooled overall 5-year survival rate was 89.2%, while the cumulative recurrence rate was 1.3% over a median follow-up ranging from 15.3 to 120.0 months. The pure subependymoma histopathological subtype was most prevalent (85.6%), followed by the mixed subependymoma-ependymoma tumor variant (13.7%).
CONCLUSIONS
Surgical extirpation without postoperative radiotherapy results in excellent postoperative survival and functional outcomes in the treatment of intracranial subependymomas. Aggressive tumor behavior should prompt histological reevaluation for a mixed subependymoma-ependymoma subtype. Further high-quality controlled trials are still required to investigate this rare tumor.
Topics: Female; Glioma, Subependymal; Humans; Lateral Ventricles; Male; Retrospective Studies; Survival Rate; Treatment Outcome
PubMed: 34416731
DOI: 10.3171/2021.2.JNS204052 -
American Journal of Ophthalmology Dec 2015To estimate the incidence of trilateral retinoblastoma in patients with retinoblastoma. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To estimate the incidence of trilateral retinoblastoma in patients with retinoblastoma.
DESIGN
Systematic review and meta-analysis.
METHODS
We searched Medline and Embase for scientific literature published between January 1966 and July 2015 that assessed trilateral retinoblastoma incidence. We used a random-effects model for the statistical analyses.
RESULTS
We included 23 retinoblastoma cohorts from 26 studies. For patients with bilateral retinoblastoma the unadjusted chance of developing trilateral retinoblastoma across all cohorts was 5.3% (95% confidence interval [CI]: 3.3%-7.7%); the chance of pineal trilateral retinoblastoma was 4.2% (95% CI: 2.6%-6.2%) and the chance of nonpineal trilateral retinoblastoma was 0.8% (95% CI: 0.4%-1.3%). In patients with hereditary retinoblastoma (all bilateral cases, and the unilateral cases with a family history or germline RB1 mutation) we found a trilateral retinoblastoma incidence of 4.1% (95% CI: 1.9%-7.1%) and a pineal trilateral retinoblastoma incidence of 3.7% (95% CI: 1.8%-6.2%). To reduce the risk of overestimation bias we restricted analysis to retinoblastoma cohorts with a minimum size of 100 patients, resulting in adjusted incidences of 3.8% (95% CI: 2.4%-5.4%), 2.9% (95% CI: 1.9%-4.2%), and 0.7% (95% CI: 0.3%-1.2%) for any, pineal, and nonpineal trilateral retinoblastoma, respectively, among patients with bilateral retinoblastoma. Among hereditary retinoblastoma we found an adjusted trilateral retinoblastoma incidence of 3.5% (95% CI: 1.2%-6.7%) and a pineal trilateral retinoblastoma incidence of 3.2% (95% CI: 1.4%-5.6%).
CONCLUSION
The estimated incidence of trilateral retinoblastoma is lower than what is reported in previous literature, especially after exclusion of small cohorts that were subject to overestimation bias in this context.
Topics: Global Health; Humans; Incidence; Retinal Neoplasms; Retinoblastoma
PubMed: 26374932
DOI: 10.1016/j.ajo.2015.09.009 -
World Neurosurgery Mar 2018Patients with brain tumors, particularly gliomas, commonly present with seizures. Higher incidence of seizure has been reported in low-grade gliomas and tumors located... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients with brain tumors, particularly gliomas, commonly present with seizures. Higher incidence of seizure has been reported in low-grade gliomas and tumors located within the temporal and insular area. The association between IDH1 and IDH2 mutations with preoperative seizures in glioma and the magnitude of this association in low-grade versus high-grade gliomas are unclear. To clarify this relationship, a systematic review and meta-analysis was performed.
METHODS
Following accepted guidelines and systematic review recommendations, electronic searches were performed in journal databases up to May 2017. Data were extracted and pooled via meta-analysis.
RESULTS
We compared 782 patients with IDH1 and IDH2 mutations with 803 patients with wild-type IDH1 and IDH2 before surgery. There was a significant difference in seizure incidence between the IDH1 mutation group (61.6%) and wild-type IDH1 group (32.1%) (odds ratio 2.76; 95% confidence interval, 1.26-6.02; I = 73%; P = 0.01). Similar findings were observed in analysis of IDH1 and IDH2 mutations (odds ratio 2.74; 95% confidence interval, 1.74-4.33; I = 58%; P < 0.0001). The difference remained in both mutation groups (IDH1, IDH1 and IDH2) with grade II gliomas but not with grade III and IV gliomas. Patients with grade II gliomas showed a higher rate of IDH1 and IDH2 mutations and seizures than patients with grade III and IV gliomas.
CONCLUSIONS
This study demonstrated a significant association of IDH1 and IDH2 mutations with incidence of preoperative seizures. This association was significant only in patients with low-grade glioma (grade II) and not in patients with higher grade gliomas (grade III and IV).
Topics: Brain Neoplasms; Gene Frequency; Glioma; Humans; Isocitrate Dehydrogenase; Mutation; Seizures
PubMed: 29288860
DOI: 10.1016/j.wneu.2017.12.112 -
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 -
Child's Nervous System : ChNS :... Sep 2020Optic pathway gliomas (OPGs), also known as Visual Pathway Gliomas, are insidious, debilitating tumours. They are most commonly WHO grade 1 pilocytic astrocytomas and... (Review)
Review
INTRODUCTION
Optic pathway gliomas (OPGs), also known as Visual Pathway Gliomas, are insidious, debilitating tumours. They are most commonly WHO grade 1 pilocytic astrocytomas and frequently occur in patients with neurofibromatosis type 1. The location of OPGs within the optic pathway typically precludes complete resection or optimal radiation dosing, hence outcomes remain poor compared to many other low-grade gliomas. The aim of this systematic review was to formulate a comprehensive list of all current ongoing clinical trials that are specifically looking at clinical care of OPGs in order to identify trends in current research and provide an overview to guide future research efforts.
METHODS
This systematic review was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The Cochrane Controlled Register of Trials (CENTRAL) and ClinicalTrials.gov were searched. Inclusion and exclusion criteria were applied and final results were reviewed.
RESULTS
501 clinical trials were identified with the search strategy. All were screened and eligible studies extracted and reviewed. This yielded 36 ongoing clinical trials, 27 of which were pharmacological agents in phase I-III. The remaining trials were a mixture of biological agents, radiation optimisation, diagnostic imaging, surgical intervention, and a social function analysis.
CONCLUSION
OPG is a complex multifaceted disease, and advances in care require ongoing research efforts across a spectrum of different research fields. This review provides an update on the current state of research in OPG and summarises ongoing trials.
Topics: Astrocytoma; Humans; Neurofibromatosis 1; Optic Nerve Glioma
PubMed: 32556546
DOI: 10.1007/s00381-020-04724-1