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CNS Neuroscience & Therapeutics Oct 2022Given that only a subset of patients with glioblastoma multiforme (GBM) responds to immuno-oncology, this study aimed to assess the impact of multiple factors on GBM... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Given that only a subset of patients with glioblastoma multiforme (GBM) responds to immuno-oncology, this study aimed to assess the impact of multiple factors on GBM immunotherapy prognosis and investigate the potential predictors.
METHODS
A quantitative meta-analysis was conducted using the random-effects model. Several potential factors were also reviewed qualitatively.
RESULTS
A total of 39 clinical trials were included after screening 1317 papers. Patients with O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation [hazard ratio (HR) for overall survival (OS) = 2.30, p < 0.0001; HR for progression-free survival (PFS) = 2.10, p < 0.0001], gross total resection (HR for OS = 0.70, p = 0.02; HR for PFS = 0.56, p = 0.004), and no baseline steroid use (HR for OS = 0.52, p = 0.0002; HR for PFS = 0.61, p = 0.02) had a relatively significant favorable OS and PFS following immunotherapy. Patients with a Karnofsky Performance Status score < 80 (HR = 1.73, p = 0.0007) and undergoing two prior relapses (HR = 2.08, p = 0.003) were associated with worse OS. Age, gender, tumor programmed death-ligand 1 expression, and history of chemotherapy were not associated with survival outcomes. Notably, immunotherapy significantly improved the OS among patients undergoing two prior recurrences (HR = 0.40, p = 0.008) but not among patients in any other subgroups, as opposed to non-immunotherapy.
CONCLUSION
Several factors were associated with prognostic outcomes of GBM patients receiving immunotherapy; multiple recurrences might be a candidate predictor. More marker-driven prospective studies are warranted.
Topics: Brain Neoplasms; DNA Methylation; DNA Modification Methylases; Glioblastoma; Humans; Immunotherapy; Neoplasm Recurrence, Local; Prognosis
PubMed: 35822692
DOI: 10.1111/cns.13915 -
Global Spine Journal Jan 2023Systematic review: Considering the infiltrative nature of intramedullary astrocytoma, the goal of surgery is to have a better patient related outcome.
STUDY DESIGN
Systematic review: Considering the infiltrative nature of intramedullary astrocytoma, the goal of surgery is to have a better patient related outcome.
OBJECTIVE
To compare the overall survival (OS) and neurologic outcomes of complete vs incomplete surgical resection for patients with intramedullary astrocytoma.
METHODS
A comprehensive search of MEDLINE, CENTRAL and EMBASE was conducted by two independent reviewers. Individual patient data (IPD) analysis and multivariate Cox Proportional Hazard Model was developed to measure the effect of surgical strategies on OS, post-operative neurological improvement (PNI), and neurological improvement in the last follow up (FNI).
RESULTS
We included 1079 patients from 35 studies. Individual patient data of 228 patients (13 articles) was incorporated into the integrative IPD analysis. Kaplan-Meier survival analysis showed complete resection (CR) significantly improved OS in comparison with the incomplete resection (IR) (log-rank test, = .004). In the multivariate IPD analysis, three prognostic factors had significant effect on the OS: (1) Extent of Resection, (2) pathology grade, and (3) adjuvant therapy. We observed an upward trend in the popularity of chemotherapy, but CR, IR, and radiotherapy had relatively stable trends during three decades.
CONCLUSION
Our study shows that CR can improve OS when compared to IR. Patients with spinal cord astrocytoma undergoing CR had similar PNI and FNI compared to IR. Therefore, CR should be the primary goal of surgery, but intraoperative decisions on the extent of resection should be relied on to prevent neurologic adverse events. Due to significant effect of adjuvant therapy on OS, PNI and FNI, it could be considered as the routine treatment strategy for spinal cord astrocytoma.
PubMed: 35486519
DOI: 10.1177/21925682221094766 -
BMC Neurology Mar 2024MGMT (O 6 -methylguanine-DNA methyltransferase) promoter methylation is a commonly assessed prognostic marker in glioblastoma (GBM). Epigenetic silencing of the MGMT...
BACKGROUND
MGMT (O 6 -methylguanine-DNA methyltransferase) promoter methylation is a commonly assessed prognostic marker in glioblastoma (GBM). Epigenetic silencing of the MGMT gene by promoter methylation is associated with greater overall and progression free survival with alkylating agent regimens. To date, there is marked heterogeneity in how MGMT promoter methylation is tested and which CpG sites are interrogated.
METHODS
To further elucidate which MGMT promoter CpG sites are of greatest interest, we performed comprehensive searches in PubMed, Web of Science, and Embase and reviewed 2,925 article abstracts. We followed the GRADE scoring system to assess risk of bias and the quality of the studies we included.
RESULTS
We included articles on adult glioblastoma that examined significant sites or regions within MGMT promoter for the outcomes: overall survival, progression free survival, and/or MGMT expression. We excluded systemic reviews and articles on lower grade glioma. fifteen articles met inclusion criteria with variable overlap in laboratory and statistical methods employed, as well as CpG sites interrogated. Pyrosequencing or BeadChip arrays were the most popular methods utilized, and CpG sites between CpG's 70-90 were most frequently investigated. Overall, there was moderate concordance between the CpG sites that the studies reported to be highly predictive of prognosis. Combinations or means of sites between CpG's 73-89 were associated with improved OS and PFS. Six studies identified CpG sites associated with prognosis that were closer to the transcription start site: CpG's 8, 19, 22, 25, 27, 32,38, and CpG sites 21-37, as well as low methylation level of the enhancer regions.
CONCLUSION
The following systematic review details a comprehensive investigation of the current literature and highlights several potential key CpG sites that demonstrate significant association with OS, PFS, and MGMT expression. However, the relationship between extent of MGMT promoter methylation and survival may be non-linear and could be influenced by potential CpG hotspots, the extent of methylation at each CpG site, and MGMT enhancer methylation status. There were several limitations within the studies such as smaller sample sizes, variance between methylation testing methods, and differences in the various statistical methods to test for association to outcome. Further studies of high impact CpG sites in MGMT methylation is warranted.
Topics: Humans; Brain Neoplasms; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Glioblastoma; Glioma; Prognosis; Tumor Suppressor Proteins
PubMed: 38521933
DOI: 10.1186/s12883-024-03605-3 -
The Cochrane Database of Systematic... May 2020This is an updated version of the original Cochrane Review published in Issue 8, 2016. High grade glioma (HGG) is a rapidly growing brain tumour in the supporting cells... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This is an updated version of the original Cochrane Review published in Issue 8, 2016. High grade glioma (HGG) is a rapidly growing brain tumour in the supporting cells of the nervous system, with several subtypes such as glioblastoma (grade IV astrocytoma), anaplastic (grade III) astrocytoma and anaplastic (grade III) oligodendroglioma. Studies have investigated the best strategy to give radiation to people with HGG. Conventional fractionated radiotherapy involves giving a daily radiation dose (called a fraction) of 180 cGy to 200 cGy. Hypofractionated radiotherapy uses higher daily doses, which reduces the overall number of fractions and treatment time. Hyperfractionated radiotherapy which uses a lower daily dose with a greater number of fractions and multiple fractions per day to deliver a total dose at least equivalent to external beam daily conventionally fractionated radiotherapy in the same time frame. The aim is to reduce the potential for late toxicity. Accelerated radiotherapy (dose escalation) refers to the delivery of multiple fractions per day using daily doses of radiation consistent with external beam daily conventionally fractionated radiotherapy doses. The aim is to reduce the overall treatment time; typically, two or three fractions per day may be delivered with a six to eight hour gap between fractions.
OBJECTIVES
To assess the effects of postoperative external beam radiation dose escalation in adults with HGG.
SEARCH METHODS
We searched CENTRAL, MEDLINE Ovid and Embase Ovid to August 2019 for relevant randomised phase III trials.
SELECTION CRITERIA
We included adults with a pathological diagnosis of HGG randomised to the following external beam radiation regimens: daily conventionally fractionated radiotherapy versus no radiotherapy; hypofractionated radiotherapy versus daily conventionally fractionated radiotherapy; hyperfractionated radiotherapy versus daily conventionally fractionated radiotherapy or accelerated radiotherapy versus daily conventionally fractionated radiotherapy.
DATA COLLECTION AND ANALYSIS
The primary outcomes were overall survival and adverse effects. The secondary outcomes were progression free survival and quality of life. We used the standard methodological procedures expected by Cochrane. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
Since the last version of this review, we identified no new relevant trials for inclusion. We included 11 randomised controlled trials (RCTs) with 2062 participants and 1537 in the relevant arms for this review. There was an overall survival benefit for people with HGG receiving postoperative radiotherapy compared to the participants receiving postoperative supportive care. For the four pooled RCTs (397 participants), the overall hazard ratio (HR) for survival was 2.01 favouring postoperative radiotherapy (95% confidence interval (CI) 1.58 to 2.55; P < 0.00001; moderate-certainty evidence). Although these trials may not have completely reported adverse effects, they did not note any significant toxicity attributable to radiation. Progression free survival and quality of life could not be pooled due to lack of data. Overall survival was similar between hypofractionated and conventional radiotherapy in five trials (943 participants), where the HR was 0.95 (95% CI 0.78 to 1.17; P = 0.63; very low-certainty evidence. The trials reported that hypofractionated and conventional radiotherapy were well tolerated with mild acute adverse effects. These trials only reported one participant in the hypofractionated arm developing symptomatic radiation necrosis that required surgery. Progression free survival and quality of life could not be pooled due to the lack of data. Overall survival was similar between hypofractionated and conventional radiotherapy in the subset of two trials (293 participants) which included participants aged 60 years and older with glioblastoma. For this category, the HR was 1.16 (95% CI 0.92 to 1.46; P = 0.21; high-certainty evidence). There were two trials which compared hyperfractionated radiotherapy versus conventional radiation and one trial which compared accelerated radiotherapy versus conventional radiation. However, the results could not be pooled. The conventionally fractionated radiotherapy regimens were 4500 cGy to 6000 cGy given in 180 cGy to 200 cGy daily fractions, over five to six weeks. All trials generally included participants with World Health Organization (WHO) performance status from 0 to 2 and Karnofsky performance status of 50 and higher. The risk of selection bias was generally low among these RCTs. The number of participants lost to follow-up for the outcome of overall survival was low. Attrition, performance, detection and reporting bias for the outcome of overall survival was low. There was unclear attrition, performance, detection and reporting bias relating to the outcomes of adverse effects, progression free survival and quality of life.
AUTHORS' CONCLUSIONS
Postoperative conventional daily radiotherapy probably improves survival for adults with good performance status and HGG compared to no postoperative radiotherapy. Hypofractionated radiotherapy has similar efficacy for survival compared to conventional radiotherapy, particularly for individuals aged 60 years and older with glioblastoma. There are insufficient data regarding hyperfractionation versus conventionally fractionated radiation (without chemotherapy) and for accelerated radiation versus conventionally fractionated radiation (without chemotherapy). There are HGG subsets who have poor prognosis even with treatment (e.g. glioblastoma histology, older age and poor performance status). These HGG individuals with poor prognosis have generally been excluded from randomised trials based on poor performance status. No randomised trial has compared comfort measures or best supportive care with an active intervention using radiotherapy or chemotherapy in these people with poor prognosis. Since the last version of this review, we found no new relevant studies. The search identified three new trials, but all were excluded as none had a conventionally fractionated radiotherapy arm.
Topics: Adult; Age Factors; Aged; Brain Neoplasms; Cranial Irradiation; Disease-Free Survival; Dose Fractionation, Radiation; Glioma; Humans; Middle Aged; Quality of Life; Randomized Controlled Trials as Topic; Survival Analysis
PubMed: 32437039
DOI: 10.1002/14651858.CD011475.pub3 -
European Journal of Medical Research Jan 2023Primary central nervous system (CNS) tumors are a heterogeneous group of neoplasms, including benign and malignant tumors. Since there are many heterogeneities in the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Primary central nervous system (CNS) tumors are a heterogeneous group of neoplasms, including benign and malignant tumors. Since there are many heterogeneities in the prevalence reported in previous studies on this type of tumor, this study was performed to determine the overall prevalence of different primary CNS tumors.
METHOD
The study was conducted as a systematic review and meta-analysis by searching international databases, including PubMed, Scopus, Science Direct, Web of science, and the Google Scholar search engine until August 2020. After transferring the studies to information management software (EndNote) and eliminating duplicate studies, the remaining studies were reviewed based on inclusion and exclusion criteria according to three stages of primary and secondary evaluation and qualitative evaluation. Comprehensive Meta-Analysis software, Begg, Mazumdar, and I tests were used for data analysis, publication bias analysis, and heterogeneity analysis, respectively.
RESULTS
After performing the systematic review steps, 80 studies were included for final analysis. Based on 8 studies, the prevalence of brain tumors was 70.9%. Also, studies on 7 other studies showed that the prevalence of spinal tumors was 12.2%. A review of 14 studies showed that the prevalence of neuroepithelial tumors was 34.7%. The analysis of 27 studies reported a prevalence of glioma tumors of 42.8%. Analyses performed on other studies showed that the prevalence of pituitary adenomas was 12.2%, embryonal tumors 3.1%, ependymal tumors 3.2%, meningiomas 24.1%, glial tumors 0.8%, astrocytic 20.3%, oligodendroglial 3.9%, glioblastoma 17.7%, schwannoma 6.7%, medulloblastoma 7.7% and Polycystic astrocytomas 3.8%.
CONCLUSION
As a result, it can be stated that brain tumors are the most common type of primary CNS tumors. It was also observed that tumors involving neuroepithelial cells are more common in patients than other types of tumors.
Topics: Humans; Prevalence; Central Nervous System Neoplasms; Brain Neoplasms; Glioblastoma
PubMed: 36670466
DOI: 10.1186/s40001-023-01011-y -
Current Oncology (Toronto, Ont.) Feb 2022Dendritic cell vaccination (DCV) strategies, thanks to a complex immune response, may flare tumor regression and improve patients' long-term survival. This meta-analysis... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dendritic cell vaccination (DCV) strategies, thanks to a complex immune response, may flare tumor regression and improve patients' long-term survival. This meta-analysis aims to assess the efficacy of DCV for newly diagnosed glioblastoma patients in clinical trials.
METHODS
The study databases, including PubMed, Web of Knowledge, Google Scholar, Scopus, and Cochrane, were searched by two blinded investigators considering eligible studies based on the following keywords: "glioblastoma multiforme", "dendritic cell", "vaccination", "immunotherapy", "immune system", "immune response", "chemotherapy", "recurrence", and "temozolomide". Among the 157 screened, only 15 articles were eligible for the final analysis.
RESULTS
Regimens including DCV showed no effect on 6-month progression-free survival (PFS, HR = 1.385, 95% CI: 0.822-2.335, = 0.673) or on 6-month overall survival (OS, HR = 1.408, 95% CI: 0.882-2.248, = 0.754). In contrast, DCV led to significantly longer 1-year OS (HR = 1.936, 95% CI: 1.396-2.85, = 0.001) and longer 2-year OS (HR = 3.670, 95% CI: 2.291-5.879, = 0.001) versus control groups. Hence, introducing DCV could lead to increased 1 and 2-year survival of patients by 1.9 and 3.6 times, respectively.
CONCLUSION
Antitumor regimens including DCV can effectively improve mid-term survival in patients suffering glioblastoma multiforme (GBM), but its impact emerges only after one year from vaccination. These data indicate the need for more time to achieve an anti-GBM immune response and suggest additional therapeutics, such as checkpoint inhibitors, to empower an earlier DCV action in patients affected by a very poor prognosis.
Topics: Brain Neoplasms; Dendritic Cells; Glioblastoma; Humans; Immunotherapy; Vaccination
PubMed: 35200574
DOI: 10.3390/curroncol29020075 -
Cancer Letters Mar 2021Aberrant expression of certain genes and microRNAs (miRNAs) has been shown to drive cancer development and progression, thus the modification of aberrant gene and miRNA...
Aberrant expression of certain genes and microRNAs (miRNAs) has been shown to drive cancer development and progression, thus the modification of aberrant gene and miRNA expression presents an opportunity for therapeutic targeting. Ectopic modulation of a single dysregulated miRNA has the potential to revert therapeutically unfavorable gene expression in cancer cells by targeting multiple genes simultaneously. Although the use of noncoding RNA-based cancer therapy is a promising approach, the lack of a feasible delivery platform for small noncoding RNAs has hindered the development of this therapeutic modality. Recently, however, there has been an evolution in RNA nanotechnology, in which small noncoding RNA is loaded onto nanoparticles derived from the pRNA-3WJ viral RNA motif of the bacteriophage phi29. Preclinical studies have shown the capacity of this technology to specifically target tumor cells by conjugating these nanoparticles with ligands specific for cancer cells and resulting in the endocytic delivery of siRNA and miRNA inhibitors directly into the cell. Here we provide a systematic review of the various strategies, which have been utilized for miRNA delivery with a specific focus on the preclinical evaluation of promising RNA nanoparticles for glioblastoma (GBM) targeted therapy.
Topics: Glioblastoma; Humans; MicroRNAs; Nanoparticles; Nanotechnology; RNA, Small Interfering; RNA, Small Untranslated; RNAi Therapeutics; Xenograft Model Antitumor Assays
PubMed: 33176185
DOI: 10.1016/j.canlet.2020.11.004 -
Radiation Oncology (London, England) Nov 2022This systematic review aims to synthesise the outcomes of different strategies of incorporating functional biological markers in the radiation therapy plans of patients... (Review)
Review
RATIONALE
This systematic review aims to synthesise the outcomes of different strategies of incorporating functional biological markers in the radiation therapy plans of patients with glioblastoma to support clinicians and further research.
METHODS
The systematic review protocol was registered on PROSPERO (CRD42021221021). A structured search for publications was performed following PRISMA guidelines. Quality assessment was performed using the Newcastle-Ottawa Scale. Study characteristics, intervention methodology and outcomes were extracted using Covidence. Data analysis focused on radiation therapy target volumes, toxicity, dose distributions, recurrence and survival mapped to functional image-guided radiotherapy interventions.
RESULTS
There were 5733 citations screened, with 53 citations (n = 32 studies) meeting review criteria. Studies compared standard radiation therapy planning volumes with functional image-derived volumes (n = 20 studies), treated radiation therapy volumes with recurrences (n = 15 studies), the impact on current standard target delineations (n = 9 studies), treated functional volumes and survival (n = 8 studies), functionally guided dose escalation (n = 8 studies), radiomics (n = 4 studies) and optimal organ at risk sparing (n = 3 studies). The approaches to target outlining and dose escalation were heterogeneous. The analysis indicated an improvement in median overall survival of over two months compared with a historical control group. Simultaneous-integrated-boost dose escalation of 72-76 Gy in 30 fractions appeared to have an acceptable toxicity profile when delivered with inverse planning to a volume smaller than 100 cm[Formula: see text].
CONCLUSION
There was significant heterogeneity between the approaches taken by different study groups when implementing functional image-guided radiotherapy. It is recommended that functional imaging data be incorporated into the gross tumour volume with appropriate technology-specific margins used to create the clinical target volume when designing radiation therapy plans for patients with glioblastoma.
Topics: Humans; Glioblastoma; Radiotherapy Dosage; Radiotherapy, Intensity-Modulated; Radiotherapy Planning, Computer-Assisted; Functional Neuroimaging
PubMed: 36371225
DOI: 10.1186/s13014-022-02146-8 -
The Cochrane Database of Systematic... May 2020Glioblastoma is an uncommon but highly aggressive type of brain tumour. Significant gains have been achieved in the molecular understanding and the pathogenesis of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Glioblastoma is an uncommon but highly aggressive type of brain tumour. Significant gains have been achieved in the molecular understanding and the pathogenesis of glioblastomas, however clinical improvements are difficult to obtain for many reasons. The current standard of care involves maximal safe surgical resection followed by chemoradiation and then adjuvant chemotherapy European Organisation for Research and Treatment of Cancer and the NCIC Clinical Trials Group (EORTC-NCIC) protocol with a median survival of 14.6 months. Successive phase III international randomised controlled studies have failed to significantly demonstrate survival advantage with newer drugs. Epidermal growth factor receptor (EGFR) is observed to be aberrant in 30% to 60% of glioblastomas. The receptor aberrancy is driven by abnormal gene amplification, receptor mutation, or both, in particular the extracellular vIII domain. EGFR abnormalities are common in solid tumours, and the advent of anti-EGFR therapies in non-small cell lung cancer and colorectal adenocarcinomas have greatly improved clinical outcomes. Anti-EGFR therapies have been investigated amongst glioblastomas, however questions remain about its ongoing role in glioblastoma management. This review aimed to report on the available evidence to date and perform a systematic analysis on the risks and benefits of use of anti-EGFR therapies in glioblastomas.
OBJECTIVES
To evaluate the efficacy and harms of anti-EGFR therapies for glioblastoma in adults.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, EBM Reviews databases, with supplementary handsearches to identify all available and relevant studies to 20 April 2020.
SELECTION CRITERIA
All randomised controlled trials (RCTs) using anti-EGFR therapies in adults with glioblastoma were eligible for inclusion. Anti-EGFR therapies included tyrosine kinase inhibitors, monoclonal antibodies, or vaccines. The comparison included investigational product added to standard of care versus standard of care or placebo, or investigational product against standard of care or placebo.
DATA COLLECTION AND ANALYSIS
The authorship team screened the search results and recorded the extracted data for analysis. We used standard Cochrane methodology to performed quantitative meta-analysis if two or more studies had appropriate and available data. Otherwise, we conducted a qualitative and descriptive analysis. We used the GRADE system to rate the certainty of the evidence. The analysis was performed along the two clinical settings: first-line (after surgery) and recurrent disease (after failure of first line treatment). Where information was available, we documented overall survival, progression-free survival, adverse events, and quality of life data from eligible studies.
MAIN RESULTS
The combined searches initially identified 912 records (after removal of duplicates), and further screening resulted in 19 records for full consideration. We identified nine eligible studies for inclusion in the review. There were three first-line studies and six recurrent studies. Five studies used tyrosine kinase inhibitors (TKIs); two studies used monoclonal antibodies; and two studies used targeted vaccines. More recent studies presented greater detail in the conduct of their studies and thus had a lower risk of bias. We observed no evidence benefit in overall survival with the use of anti-EGFR therapy in the first-line or recurrent setting (hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.76 to 1.04; 3 RCTs, 1000 participants, moderate-certainty evidence; and HR 0.79, 95% CI 0.51 to 1.21, 4 RCTs, 489 participants, low-certainty evidence, respectively). All the interventions were generally well tolerated with low-certainty evidence for lymphopenia (odds ratio (OR) 0.97, 95% CI 0.19 to 4.81; 4 RCTs, 1146 participants), neutropenia (OR 1.29, 95% CI 0.82 to 2.03; 4 RCTs, 1146 participants), and thrombocytopenia (OR 3.69, 95% CI 0.51 to 26.51; 4 RCTs, 1146 participants). A notable toxicity relates to ABT-414, where significant ocular issues were detected. The addition of anti-EGFR therapy showed no evidence of an increase in progression-free survival (PFS) in the first-line setting (HR 0.94, 95% CI 0.81 to 1.10; 2 RCTs, 894 participants, low-certainty evidence). In the recurrent setting, there was an increase in PFS with the use of anti-EGFR therapy (HR 0.75, 95% CI 0.58 to 0.96, 3 RCTs, 275 participants, low-certainty evidence). The available quality of life assessment data showed that anti-EGFR therapies were neither detrimental or beneficial when compared to standard care (not estimable).
AUTHORS' CONCLUSIONS
In summary, there is no evidence of a demonstrable overall survival benefit with the addition of anti-EGFR therapy in first-line and recurrent glioblastomas. Newer drugs that are specially designed for glioblastoma targets may raise the possibility of success in this population, but data are lacking at present. Future studies should be more selective in pursuing people displaying specific EGFR targets.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Antineoplastic Agents, Immunological; Brain Neoplasms; Cancer Vaccines; Disease Progression; ErbB Receptors; Glioblastoma; Humans; Lymphopenia; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Randomized Controlled Trials as Topic; Thrombocytopenia
PubMed: 32395825
DOI: 10.1002/14651858.CD013238.pub2 -
Diagnostics (Basel, Switzerland) Sep 2021The study's objective was the evaluation of the diagnostic accuracy of the T2-FLAIR mismatch sign in terms of diagnosing IDH-mutant non-codeleted (IDHmut-Noncodel) lower... (Review)
Review
The study's objective was the evaluation of the diagnostic accuracy of the T2-FLAIR mismatch sign in terms of diagnosing IDH-mutant non-codeleted (IDHmut-Noncodel) lower grade gliomas (LGG) of the brain. We searched the MEDLINE, Scopus and Cochrane Central databases. The last database search was performed on 12 April 2021. Studies that met the following were included: MRI scan assessing the presence of T2-FLAIR mismatch sign, and available IDH mutation and 1p/19q codeletion status. The quality of studies was assessed using the QUADAS-2 tool. Twelve studies involving 14 cohorts were included in the quantitative analysis. The diagnostic odds ratio [DOR (95% confidence interval; CI)] was estimated at 34.42 (20.95, 56.56), < 0.01. Pooled sensitivity and specificity (95% CI) were estimated at 40% (31-50%; = 0.05) and 97% (93-99%; < 0.01), respectively. The likelihood ratio (LR; 95% CI) for a positive test was 11.39 (6.10, 21.29; < 0.01) and the LR (95% CI) for a negative test was 0.40 (0.24, 0.65; < 0.01).The T2-FLAIR mismatch sign is a highly specific biomarker for the diagnosis of IDHmut-Noncodel LGGs. However, the test was found positive in some other tumors and had a high number of false negative results. The diagnostic accuracy of the mismatch sign might be improved when combined with further imaging parameters.
PubMed: 34573962
DOI: 10.3390/diagnostics11091620