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Journal of Neuro-oncology Sep 2023This review compares reirradiation (reRT), systemic therapy and combination therapy (reRT & systemic therapy) with regards to overall survival (OS), progression-free... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
This review compares reirradiation (reRT), systemic therapy and combination therapy (reRT & systemic therapy) with regards to overall survival (OS), progression-free survival (PFS), adverse effects (AEs) and quality of life (QoL) in patients with recurrent high-grade glioma (rHGG).
METHODS
A search was performed on PubMed, Scopus, Embase and CENTRAL. Studies reporting OS, PFS, AEs and/or QoL and encompassing the following groups were included; reirradiation vs systemic therapy, combination therapy vs systemic therapy, combination therapy vs reRT, and bevacizumab-based combination therapy vs reRT with/without non-bevacizumab-based systemic therapy. Meta-analyses were performed utilising a random effects model. Certainty of evidence was assessed using GRADE.
RESULTS
Thirty-one studies (three randomised, twenty-eight non-randomised) comprising 2084 participants were included. In the combination therapy vs systemic therapy group, combination therapy improved PFS (HR 0.57 (95% CI 0.41-0.79); low certainty) and OS (HR 0.73 (95% CI 0.56-0.95); low certainty) and there was no difference in grade 3 + AEs (RR 1.03 (95% CI 0.57-1.86); very low certainty). In the combination therapy vs reRT group, combination therapy improved PFS (HR 0.52 (95% CI 0.38-0.72); low certainty) and OS (HR 0.69 (95% CI 0.52-0.93); low certainty). In the bevacizumab-based combination therapy vs reRT with/without non-bevacizumab-based systemic therapy group, adding bevacizumab improved PFS (HR 0.46 (95% CI 0.27-0.77); low certainty) and OS (HR 0.42 (95% CI 0.24-0.72; low certainty) and reduced radionecrosis (RR 0.17 (95% CI 0.06-0.48); low certainty).
CONCLUSIONS
Combination therapy may improve OS and PFS with acceptable toxicities in patients with rHGG compared to reRT or systemic therapy alone. Particularly, combining bevacizumab with reRT prophylactically reduces radionecrosis.
REGISTRATION
CRD42022291741.
Topics: Humans; Bevacizumab; Quality of Life; Re-Irradiation; Neoplasm Recurrence, Local; Glioma; Randomized Controlled Trials as Topic
PubMed: 37733174
DOI: 10.1007/s11060-023-04441-0 -
Tomography (Ann Arbor, Mich.) Aug 2023Recent advances in tumor visualization have improved the extent of resection (EOR) of primary and secondary tumors of the central nervous system, while limiting the... (Meta-Analysis)
Meta-Analysis Review
Intraoperative Fluorophores: An Update on 5-Aminolevulinic Acid and Sodium Fluorescein in Resection of Tumors of the Central Nervous System and Metastatic Lesions-A Systematic Review and Meta-Analysis.
INTRODUCTION
Recent advances in tumor visualization have improved the extent of resection (EOR) of primary and secondary tumors of the central nervous system, while limiting the morbidity and mortality of the surgery. One area of recent interest has been the use of intraoperative fluorophores for tumor visualization such as 5-aminolevulinic acid (5-ala) and sodium fluorescein. We performed a systematic review and meta-analysis on the utility of fluorophore administration and EOR with each fluorophore to update the current literature.
METHODS
We conducted a systematic review and meta-analysis on the use of intraoperative 5-ala or fluorescein between 2021 and 2023 using the PubMed, SCOPUS, and WOS databases. The initial search yielded 8688 results. After inclusion and exclusion criteria were met, 44 studies remained for review. A meta-analysis was performed to compare the EOR between studies for each fluorophore and to compare the presence of intraoperative fluorescence by tumor type. Odds ratios (OR) were calculated for gross total resection (GTR), and two-way ANOVA tests were performed to compare rates of intraoperative fluorescence by fluorophore and tumor type.
RESULTS
In all groups except low-grade glioma, fluorescence was present after 5-ala administration; fluorescence was present for all groups after fluorescein administration. Two-way ANOVA analysis for both fluorophores demonstrated no statistically significant difference in presence of fluorescence between type of tumor resected. Meta-analysis of EOR did show a higher, but not significant, rate of GTR in the 5-ala group compared to controls (OR = 1.29, 95% CI = 0.49; 3.37). In the fluorescein group, there were statistically significant higher odds of GTR compared to the control group (OR = 2.10, 95% CI = 1.43; 3.10, I = 0%).
CONCLUSIONS
Both 5-ala and sodium fluorescein demonstrated intraoperative fluorescence among various tumor types in both cranial and spinal tumors, as well as efficacy in improving EOR. Both fluorophores merit further investigation for use in surgery of CNS tumors.
Topics: Humans; Fluorescein; Aminolevulinic Acid; Levulinic Acids; Glioma
PubMed: 37736977
DOI: 10.3390/tomography9050124 -
Photodiagnosis and Photodynamic Therapy Dec 2014The present systematic review and meta-analysis was to analyze of the advantages of intraoperative fluorescence-guided resection of high-grade gliomas. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The present systematic review and meta-analysis was to analyze of the advantages of intraoperative fluorescence-guided resection of high-grade gliomas.
METHODS
Systematic computerized searches of the PubMed and Web of Knowledge were performed. The outcomes included diagnostic value for identification of tumor tissue, gross total resection, and prognosis. The summary receiver operating characteristic curves (SROC), the pooled sensitivities, the pooled specificities, the pooled odd ratio (OR) and the pooled hazard ratio (HR) were estimated by meta-analysis.
RESULTS
Twelve studies were included. The pooled sensitivity and the pooled specificity for identification of tumor tissue was 0.84 (95% CI: 0.81-0.87), and 0.91 (95% CI: 0.87-0.94), respectively. And the overall weighted AUC of the SROC curve was 0.9520 ± 0.0116. The summary OR of the gross total resection rate in patients with fluorescein-guided resection compared with patients with no fluorescein was 4.372 (95% CI 2.937-6.508). Fluorescein-guided resection was associated with a reduced risk of progression-free survival compared with no fluorescein, with HR 0.73 (95% CI 0.57-0.94, P = 0.01). The pooled HR of overall survival was 1.000 (95% CI 0.960-1.040) between two groups. No significant publication bias was found.
CONCLUSION
Fluorescence-guided resection of high-grade gliomas is effective for diagnosing tumor margins, increasing gross total resection, and reducing the risk of progression-free survival. But this conclusion should be confirmed by large sample randomized controlled clinical trials.
Topics: Brain Neoplasms; Fluorescent Dyes; Glioma; Humans; Microscopy, Fluorescence; Neoplasm Grading; Prevalence; Risk Factors; Surgery, Computer-Assisted; Survival Rate; Treatment Outcome
PubMed: 25131747
DOI: 10.1016/j.pdpdt.2014.08.001 -
Journal of Clinical Neuroscience :... Jan 2021Multiple glioblastoma multiforme (GBM) is classified as multifocal and multicentric GBM according to whether there is communication between the lesions. Multiple GBM is...
Multiple glioblastoma multiforme (GBM) is classified as multifocal and multicentric GBM according to whether there is communication between the lesions. Multiple GBM is more genetically heterogeneous, aggressive and resistant to chemoradiotherapy than unifocal GBM, and has a worse prognosis. There is no international consensus on the treatment of multiple GBM. This review discusses some paradigms of multiple GBM and focuses on the heterogeneity spread pathway, imaging diagnosis, pathology, molecular characterization and prognosis of multifocal and multicentric GBM. Several promising therapeutic methods of multiple GBM are also recommended.
Topics: Brain Neoplasms; Glioblastoma; Humans
PubMed: 33358091
DOI: 10.1016/j.jocn.2020.11.025 -
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 -
Neurosurgical Review Jun 2019Multiple high-grade gliomas (M-HGGs) are well--separated tumors, differentiated as multifocal (MF) and multicentric (MC) by their MRI features. The authors performed a... (Meta-Analysis)
Meta-Analysis
Multiple high-grade gliomas (M-HGGs) are well--separated tumors, differentiated as multifocal (MF) and multicentric (MC) by their MRI features. The authors performed a systematic review and meta-analysis of literature examining epidemiology, clinical and radiological characteristics, management, and the overall survival from M-HGGs. According to PRISMA guidelines, a comprehensive review of studies published between January 1990 and January 2017 was carried out. The authors identified studies that examined the prevalence rate, clinical and radiological characteristics, treatment, and overall survival from M-HGGs in patients with HGG. Data were analyzed using a random-effects meta-analysis model. Finally, we systematically reviewed demographic characteristics, lesion location, and surgical and adjuvant treatments. Twenty-three studies were included in this systematic review. The M-HGGs prevalence rate was 19% (95% CI 13-26%) and the hazard ratio of death from M-HGGs in the HGGs population was 1.71 (95% CI 1.49-1.95, p < 0.0001). The MC prevalence rate was 6% (CI 95% 4-10%), whereas MF prevalence rate was 11% (CI 95% 6-20%) (p < 0.0001). There were no statistically significant differences between MF and MC HGGs in gender, lesion location, histological type, and surgical treatment. Survival analysis of MC tumors showed that surgical resection (gross total resection or subtotal resection) is an independent predictor of improved outcome (HR 7.61 for biopsy subgroup, 95% CI 1.94-29.78, p = 0.004). The prevalence of M-HGGs is approximately 20% of HGGs. The clinical relevance of separating M-HGGs in MF and MC tumors remains questionable and its prognostic significance is unclear. When patient status and lesion characteristics make it safe and feasible, cytoreduction should be attempted in patients with M-HGGs because it improves overall survival.
Topics: Biopsy; Brain Neoplasms; Glioma; Humans; Magnetic Resonance Imaging; Prognosis; Survival Analysis
PubMed: 29138949
DOI: 10.1007/s10143-017-0928-7 -
British Journal of Cancer Feb 2002A rapid and systematic review of the effectiveness and cost-effectiveness of temozolomide in the treatment of recurrent malignant glioma was commissioned by the NHS HTA... (Review)
Review
A rapid and systematic review of the effectiveness and cost-effectiveness of temozolomide in the treatment of recurrent malignant glioma was commissioned by the NHS HTA Programme on behalf of NICE. The full report has been published elsewhere. This paper summarizes the results for the effectiveness of temozolomide in people with recurrent glioblastoma multiforme and anaplastic astrocytoma. The review was conducted using standard systematic review methodology involving a systematic literature search, quality assessment of included studies with systematic data extraction and data synthesis. One randomized controlled trial and four uncontrolled studies were identified for inclusion. The key results were that temozolomide may increase progression-free survival but has no significant impact on overall length of survival. The main effect from temozolomide may have been in those patients who had not received any prior chemotherapy regimens, however further randomized controlled trials are required to confirm this suggestion. Temozolomide appears to produce few serious adverse effects and may also have a positive impact on health-related quality of life. Overall the evidence-base is weak and few strong conclusions can be drawn regarding the effectiveness of temozolomide. Large, well-designed randomized controlled trails conducted in a wider patient population are needed.
Topics: Antineoplastic Agents, Alkylating; Astrocytoma; Brain Neoplasms; Clinical Trials as Topic; Dacarbazine; Disease-Free Survival; Evidence-Based Medicine; Glioblastoma; Humans; Neoplasm Recurrence, Local; Survival Rate; Temozolomide; Treatment Outcome
PubMed: 11870527
DOI: 10.1038/sj.bjc.6600135 -
Journal of Neurosurgery. Pediatrics Dec 2023Diffuse intrinsic pontine gliomas (DIPGs) are aggressive and malignant tumors of the brainstem. Stereotactic biopsy can obtain molecular and genetic information for...
OBJECTIVE
Diffuse intrinsic pontine gliomas (DIPGs) are aggressive and malignant tumors of the brainstem. Stereotactic biopsy can obtain molecular and genetic information for diagnostic and potentially therapeutic purposes. However, there is no consensus on the safety of biopsy or effect on survival. The authors aimed to characterize neurological risk associated with and the effect of stereotactic biopsy on survival among patients with DIPGs.
METHODS
A systematic review was performed in accordance with PRISMA guidelines to identify all studies examining pediatric patients with DIPG who underwent stereotactic biopsy. The search strategy was deployed in PubMed, Embase, and Scopus. The quality of studies was assessed using the Grading of Recommendations, Assessment, Development and Evaluation system, and risk of bias was evaluated with the Cochrane Risk of Bias in Nonrandomized Studies-of Interventions tool. Bibliographic, demographic, clinical, and outcome data were extracted from studies meeting inclusion criteria.
RESULTS
Of 2634 resultant articles, 13 were included, representing 192 patients undergoing biopsy. The weighted mean age at diagnosis was 7.5 years (range 0.5-17 years). There was an overall neurosurgical complication rate of 13.02% (25/192). The most common neurosurgical complication was cranial nerve palsy (4.2%, 8/192), of which cranial nerve VII was the most common (37.5%, 3/8). The second most common complication was perioperative hemorrhage (3.6%, 7/192), followed by hemiparesis (2.1%, 4/192), speech disorders (1.6%, 3/192) such as dysarthria and dysphasia, and movement disorders (1.0%, 2/192). Hydrocephalus was less commonly reported (0.5%, 1/192), and there were no complications relating to wound infection/dehiscence (0%, 0/192) or CSF leak (0%, 0/192). No mortality was specifically attributed to biopsy. Diagnostic yield of biopsy revealed a weighted mean of 97.4% (range 91%-100%). Of the studies reporting survival data, 37.6% (32/85) of patients died within the study follow-up period (range 2 weeks-48 months). The mean overall survival in patients undergoing biopsy was 9.73 months (SD 0.68, median 10 months, range 6-13 months).
CONCLUSIONS
Children with DIPGs undergoing biopsy have mild to moderate rates of neurosurgical complications and no excessive morbidity. With reasonably acceptable surgical risk and high diagnostic yield, stereotactic biopsy of DIPGs can allow for characterization of patient-specific molecular and genetic features that may influence prognosis and the development of future therapeutic strategies.
Topics: Humans; Child; Infant; Child, Preschool; Adolescent; Glioma; Diffuse Intrinsic Pontine Glioma; Brain Stem Neoplasms; Biopsy
PubMed: 37724839
DOI: 10.3171/2023.7.PEDS22462 -
Gene Aug 2018An increasing number of studies have shown that long noncoding RNAs (lncRNAs) play important roles in the development of glioma. However, a systematic review and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
An increasing number of studies have shown that long noncoding RNAs (lncRNAs) play important roles in the development of glioma. However, a systematic review and meta-analysis to evaluate the clinical value of lncRNA expression in glioma patients is lacking. We performed this study to assess the relationship between the expression of various lncRNAs and the clinicopathological features, diagnosis and prognosis of glioma.
MATERIALS AND METHODS
Eligible studies were identified through a comprehensive literature search. We conducted a subgroup analysis to assess the clinicopathological value of urothelial carcinoma associated 1 (UCA1). Pooled hazard ratios (HRs) of lncRNAs for survival were calculated to analyze the prognostic performance of lncRNAs.
RESULTS
In total, 40 studies, including 30 investigating clinicopathological features, 3 investigating diagnoses and 32 investigating prognoses, were analyzed in this study. UCA1 expression was positively associated with tumor size (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.06-4.15; P < 0.001) and World Health Organization (WHO) grade (OR, 3.84, [95% CI 1.84-8.01], P < 0.001). In the prognostic meta-analysis, high metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression could predict poor overall survival (OS) in patients with glioma, with a pooled HR of 2.32 (95% CI: 1.64-3.27, P < 0.001).
CONCLUSIONS
This systematic review and meta-analysis demonstrated that lncRNAs are associated with tumor size, WHO grade, and prognosis in glioma patients. lncRNAs could function as potential molecular biomarkers of the clinicopathology and prognosis of glioma.
Topics: Biomarkers, Tumor; Brain Neoplasms; Glioma; Humans; Prognosis; RNA, Long Noncoding
PubMed: 29777909
DOI: 10.1016/j.gene.2018.05.054 -
International Journal of Molecular... Jun 2023Gliomas are the most common brain tumor in adults, and molecularly targeted therapies to treat gliomas are becoming a frequent topic of investigation. The current state... (Review)
Review
Gliomas are the most common brain tumor in adults, and molecularly targeted therapies to treat gliomas are becoming a frequent topic of investigation. The current state of molecular targeted therapy research for adult-type diffuse gliomas has yet to be characterized, particularly following the 2021 WHO guideline changes for classifying gliomas using molecular subtypes. This systematic review sought to characterize the current state of molecular target therapy research for adult-type diffuse glioma to better inform scientific progress and guide next steps in this field of study. A systematic review was conducted in accordance with PRISMA guidelines. Studies meeting inclusion criteria were queried for study design, subject (patients, human cell lines, mice, etc.), type of tumor studied, molecular target, respective molecular pathway, and details pertaining to the molecular targeted therapy-namely the modality, dose, and duration of treatment. A total of 350 studies met the inclusion criteria. A total of 52 of these were clinical studies, 190 were laboratory studies investigating existing molecular therapies, and 108 were laboratory studies investigating new molecular targets. Further, a total of 119 ongoing clinical trials are also underway, per a detailed query on clinicaltrials.gov. GBM was the predominant tumor studied in both ongoing and published clinical studies as well as in laboratory analyses. A few studies mentioned IDH-mutant astrocytomas or oligodendrogliomas. The most common molecular targets in published clinical studies and clinical trials were protein kinase pathways, followed by microenvironmental targets, immunotherapy, and cell cycle/apoptosis pathways. The most common molecular targets in laboratory studies were also protein kinase pathways; however, cell cycle/apoptosis pathways were the next most frequent target, followed by microenvironmental targets, then immunotherapy pathways, with the wnt/β-catenin pathway arising in the cohort of novel targets. In this systematic review, we examined the current evidence on molecular targeted therapy for adult-type diffuse glioma and discussed its implications for clinical practice and future research. Ultimately, published research falls broadly into three categories-clinical studies, laboratory testing of existing therapies, and laboratory identification of novel targets-and heavily centers on GBM rather than IDH-mutant astrocytoma or oligodendroglioma. Ongoing clinical trials are numerous in this area of research as well and follow a similar pattern in tumor type and targeted pathways as published clinical studies. The most common molecular targets in all study types were protein kinase pathways. Microenvironmental targets were more numerous in clinical studies, whereas cell cycle/apoptosis were more numerous in laboratory studies. Immunotherapy pathways are on the rise in all study types, and the wnt/β-catenin pathway is increasingly identified as a novel target.
Topics: Adult; Humans; Animals; Mice; Molecular Targeted Therapy; beta Catenin; Mutation; Glioma; Brain Neoplasms; Oligodendroglioma; Isocitrate Dehydrogenase
PubMed: 37445633
DOI: 10.3390/ijms241310456