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Cancer Treatment Reviews Nov 2022The objective of this study was to estimate the relative efficacy and safety of targeted therapies for the treatment of metastatic melanoma using a network meta-analysis... (Meta-Analysis)
Meta-Analysis Review
Comparative efficacy and safety of targeted therapies for BRAF-mutant unresectable or metastatic melanoma: Results from a systematic literature review and a network meta-analysis.
BACKGROUND
The objective of this study was to estimate the relative efficacy and safety of targeted therapies for the treatment of metastatic melanoma using a network meta-analysis (NMA).
METHODS
A systematic literature review (SLR) identified studies in Medline, Embase and Cochrane published until November 2020. Screening used prespecified eligibility criteria. Following a transitivity assessment across included studies, Bayesian NMA was conducted.
RESULTS
A total of 43 publications reporting 15 targeted therapy trials and 42 reporting 18 immunotherapy trials were retained from the SLR and considered for the NMA. Due to substantial between-study heterogeneity with immunotherapy trials, the analysis considered a network restricted to targeted therapies. Among combination therapies, encorafenib + binimetinib was superior to dabrafenib + trametinib for overall response rate (OR = 1.86; 95 % credible interval [CrI] 1.10, 3.17), superior to vemurafenib + cobimetinib with fewer serious adverse events (SAEs) (OR = 0.51; 95 % CrI 0.29, 0.91) and fewer discontinuations due to AEs (OR = 0.45; 95 % CrI 0.21, 0.96), and superior to atezolizumab + vemurafenib + cobimetinib with fewer SAEs (OR = 0.41; 95 % CrI 0.21, 0.82). Atezolizumab + vemurafenib + cobimetinib and encorafenib + binimetinib were generally comparable for efficacy endpoints. Among double combination therapies, encorafenib + binimetinib showed high probabilities of being better for all efficacy and safety endpoints.
CONCLUSIONS
This NMA confirms that combination therapies are more efficacious than monotherapies. Encorafenib + binimetinib has a favourable efficacy profile compared to other double combination therapies and a favourable safety profile compared to both double and triple combination therapies.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Benzimidazoles; Carbamates; Humans; Melanoma; Mutation; Neoplasms, Second Primary; Network Meta-Analysis; Proto-Oncogene Proteins B-raf; Skin Neoplasms; Sulfonamides; Vemurafenib
PubMed: 36099854
DOI: 10.1016/j.ctrv.2022.102463 -
Journal of Gastrointestinal and Liver... Mar 2022Several studies have suggested that mutations in MEFV, the gene responsible for familial Mediterranean fever (FMF), are frequently detected in inflammatory bowel disease... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Several studies have suggested that mutations in MEFV, the gene responsible for familial Mediterranean fever (FMF), are frequently detected in inflammatory bowel disease (IBD) patients. We aimed to provide further evidence regarding a potential correlation between MEFV gene mutations and IBD by identifying all relevant studies and analyzing their results.
METHODS
EMBASE, PubMed/MEDLINE, and Google Scholar were used to identify all studies that published until January 2021 and reported MEFV mutation patterns in patients with ulcerative colitis (UC), Crohn's disease (CD) and indeterminate colitis (IC) with or without a control group. The Newcastle-Ottawa quality assessment scale was used to appraise the quality of the included studies.
RESULTS
Thirteen observational studies, including 937 patients and 977 controls, were analyzed. MEFV mutation rate in IBD patients was 0.238 (95%CI: 0.209-0.270; I 2 =95%); MEFV mutated alleles were more frequent in IBD patients when compared with controls (p=0.03 for UC, p=0.01 for CD and IC). Subgroup analysis indicated that MEFV mutations were increased in patients with IC when compared with UC and CD (I 2 =91%, p<0.001). Patients with extra-intestinal manifestations and pancolitis had 2.57 (95%CI 1.07-6.14; p=0.03) and 2.02 (95%CI: 1.01-4.04, P=0.049) odds ratios to carry MEFV mutant genotypes, respectively. Exon 10 mutations had the most serious impact. No source of heterogeneity was detected.
CONCLUSIONS
MEFV mutations are common in IBD and are linked with the presence of extra-intestinal manifestations and pancolitis. Further research to assess the clinical significance and evolutionary significance of MEFV mutations in IBD patients is warranted.
Topics: Chronic Disease; Colitis, Ulcerative; Crohn Disease; Familial Mediterranean Fever; Humans; Inflammatory Bowel Diseases; Mutation; Pyrin
PubMed: 35306551
DOI: 10.15403/jgld-4070 -
Seminars in Oncology 2023Available evidence suggests that in patients with advanced BRAF V600-mutant melanoma treated with the combination of BRAF and MEK inhibitors, gender could be associated... (Meta-Analysis)
Meta-Analysis Review
Available evidence suggests that in patients with advanced BRAF V600-mutant melanoma treated with the combination of BRAF and MEK inhibitors, gender could be associated with survival outcome. We performed a systematic review and meta-analysis of all randomized clinical trials (RCTs) testing the combination of BRAF and MEK inhibitors, to assess the interaction between treatment effect and patients' gender. We searched PubMed, MEDLINE, Embase, and Scopus, for phase II and III RCTs up to January 30, 2022. We included all RCTs that enrolled patients with BRAF V600-mutant advanced cutaneous melanoma and assessed combinations of BRAF and MEK inhibitors versus BRAF inhibitor monotherapy. Our aim was to assess differences if any in treatment efficacy between men and women, measured in terms of the differences in progression-free survival (PFS) and overall survival (OS) log-hazard ratios (log-HRs). We calculated the pooled PFS- and OS-HRs with 95% confidence intervals (CIs) in men and women using a random-effects model and assessed the heterogeneity between the estimates using an interaction test. Five RCTs that enrolled a total of 2,113 patients were included in the analysis. In women, the combination of BRAF and MEK inhibitors halved the risk of progression or death as compared with BRAF inhibitor monotherapy with a pooled PFS-HR of 0.50 (95%CI 0.41-0.61). In men, the benefit obtained with BRAF and MEK inhibitors was smaller with a pooled PFS-HR of 0.63 (95%CI 0.54-0.74), P-heterogeneity = .05. A similar trend was observed for OS where the pooled OS-HR was 0.62 (95%CI 0.48-0.80) in women and only 0.78, (95%CI 0.67-0.92) in men, P-heterogeneity = 0.11. These results support meaningful gender-based heterogeneity of response to combination of BRAF and MEK inhibitors targeted therapy in patients with advanced BRAF-mutant melanoma, that should be considered in future research to improve treatment effectiveness.
Topics: Male; Female; Humans; Proto-Oncogene Proteins B-raf; Randomized Controlled Trials as Topic; Melanoma; Skin Neoplasms; Protein Kinase Inhibitors; Mitogen-Activated Protein Kinase Kinases; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36967333
DOI: 10.1053/j.seminoncol.2023.03.003 -
Life (Basel, Switzerland) Mar 2023Melanoma continues to represent the most serious skin cancer worldwide. However, few attempts have been made to connect the body of research on advanced melanoma. In... (Review)
Review
Melanoma continues to represent the most serious skin cancer worldwide. However, few attempts have been made to connect the body of research on advanced melanoma. In the present review, we report on strides made in the diagnosis and treatment of intracranial metastatic melanoma. Relevant Cochrane reviews and randomized-controlled trials published by November 2022 were systematically retrieved from the Cochrane Library, EMBASE, and PubMed databases (N = 27). Search and screening methods adhered to the 2020 revision of the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Although the research surrounding the earlier detection of melanoma brain metastasis is scarce, several studies have highlighted specific markers associated with MBM. Such factors include elevated BRAFV600 mutant ctDNA, high LDH concentration, and high IGF-1R. The approach to treating MBM is moving away from surgery and toward nonsurgical management, namely, a combination of stereotactic radiosurgery (SRS) and immunotherapeutic agents. There is an abundance of emerging research seeking to identify and improve both novel and established treatment options and diagnostic approaches for MBM, however, more research is still needed to maximize the clinical efficacy, especially for new immunotherapeutics. Early detection is optimal for the efficacy of treatment and MBM prognosis. Current treatment utilizes chemotherapies and targeted therapies. Emerging approaches emphasize biomarkers and joint treatments. Further exploration toward preliminary identification, the timing of therapies, and methods to ameliorate adverse treatment effects are needed to advance MBM patient care.
PubMed: 36983983
DOI: 10.3390/life13030828 -
Neuro-oncology Advances 2019The introduction of the 2016 WHO Classification of Tumors of the Central Nervous System has resulted in tumor groupings with improved prognostic value for diffuse glioma... (Review)
Review
BACKGROUND
The introduction of the 2016 WHO Classification of Tumors of the Central Nervous System has resulted in tumor groupings with improved prognostic value for diffuse glioma patients. Molecular subtype, primarily based on IDH-mutational status and 1p/19q-status, is a strong predictor of survival. It is unclear to what extent this finding may be mediated by differences in anatomical location and surgical resectability among molecular subgroups. Our aim was to elucidate possible correlations between (1) molecular subtype and anatomical location and (2) molecular subtype and extent of resection.
METHODS
We performed a systematic review of literature searching for studies on molecular subtype in relation to anatomical location and extent of resection. Only original data concerning adult participants suffering from cerebral diffuse glioma were included. Studies adopting similar outcomes measures were included in our meta-analysis.
RESULTS
In the systematic analysis for research questions 1 and 2, totals of 20 and 9 studies were included, respectively. Study findings demonstrated that IDH-mutant tumors were significantly more frequently located in the frontal lobe and less often in the temporal lobe compared with IDH-wildtype gliomas. Within the IDH-mutant group, 1p/19q-codeleted tumors were associated with more frequent frontal and less frequent temporal localization compared with 1p/19q-intact tumors. In IDH-mutant gliomas, greater extent of resection was achieved than in IDH-wildtype tumors.
CONCLUSIONS
Genetic profile of diffuse cerebral glioma influences their anatomical location and seems to affect tumor resectability.
PubMed: 32642663
DOI: 10.1093/noajnl/vdz032 -
Clinical & Translational Oncology :... Feb 2024The purpose of this meta-analysis is to evaluate the efficacy and safety of TAS-102 in treating metastatic colorectal cancer (mCRC) using the most recent data available. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The purpose of this meta-analysis is to evaluate the efficacy and safety of TAS-102 in treating metastatic colorectal cancer (mCRC) using the most recent data available.
METHODS
The literature on the efficacy and safety of TAS-102 versus placebo and/or best supportive care (BSC) in mCRC was obtained through a systematic search of PubMed, Embase, and Web of Science databases through January 2023. Identify the included literature and extract pertinent data, such as the overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF), disease control rate (DCR), incidence of adverse events (AEs) and serious adverse events (SAEs).
RESULTS
There were eight eligible articles that included 2903 patients (1964 TAS-102 versus 939 Placebo and/or BSC). In this meta-analysis, TAS-102 treatment resulted in longer OS, PFS, TTF, and higher DCR in patients with mCRC versus placebo and/or BSC. TAS-102 improved OS and PFS in subgroup analyses of mCRC patients with KRAS wild-type and KRAS mutant-type. In addition, TAS-102 did not increase the incidence of serious adverse events.
CONCLUSION
TAS-102 can enhance the prognosis of mCRC patients whose standard therapy has failed, regardless of KRAS mutation status, and its safety is acceptable.
Topics: Humans; Trifluridine; Uracil; Colorectal Neoplasms; Proto-Oncogene Proteins p21(ras); Colonic Neoplasms; Rectal Neoplasms; Drug Combinations; Antineoplastic Combined Chemotherapy Protocols; Pyrrolidines; Thymine
PubMed: 37414979
DOI: 10.1007/s12094-023-03268-5 -
Journal of Neuroimmunology Dec 2023Huntington's disease (HD) is an autosomal dominant disease caused by an abnormally high number of CAG repeats at the huntingtin-encoding gene, HTT. This genetic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Huntington's disease (HD) is an autosomal dominant disease caused by an abnormally high number of CAG repeats at the huntingtin-encoding gene, HTT. This genetic alteration results in the expression of a mutant form of the protein (mHTT) and the formation of intracellular aggregates, inducing an inflammatory state within the affected areas. This dysfunction of inflammatory response leads to elevated levels of related inflammatory markers in both CNS tissue samples and body fluids. This study aims to investigate peripheral/blood concentrations of inflammatory molecules in HD.
METHODS
A search was conducted in MEDLINE, Scopus, Web of Science, and Embase databases until March 30th, 2023. Random-effect meta-analysis was used for exploring concentrations of inflammatory molecules in HD. Subgroup and sensitivity analyses were used to assess heterogeneity among the included studies. The study protocol has been registered in PROSPERO with the ID number CRD42022296078.
RESULTS
Ten studies were included in the meta-analysis. Plasma levels of Interleukin 6 (IL-6) and IL-10 were higher in HD compared to controls. Other biomarkers, namely, complement component C-reactive protein (CRP), C3, interferon-γ (IFN-γ), IL-1, IL-2, IL-8, and tumor necrosis factor-α (TNF-α), did not show any significant differences between the two groups. In addition, the subgroup analysis results established no significant differences in levels of these biomarkers in body fluids among premanifest and manifest HD patients.
CONCLUSION
The results of this study provide evidence for the presence of higher plasma levels of IL-6 and IL-10 in HD patients in comparison with healthy controls.
Topics: Humans; Huntington Disease; Interleukin-6; Interleukin-10; Biomarkers; Tumor Necrosis Factor-alpha; Huntingtin Protein
PubMed: 37984118
DOI: 10.1016/j.jneuroim.2023.578243 -
Cells Mar 2023Hereditary cerebellar ataxias (HCAs) are a heterogenous group of neurodegenerative disorders associated with severe disability. Treatment options are limited and overall... (Review)
Review
INTRODUCTION
Hereditary cerebellar ataxias (HCAs) are a heterogenous group of neurodegenerative disorders associated with severe disability. Treatment options are limited and overall restricted to symptomatic approaches, leading to poor prognoses. In recent years, there has been extensive research on gene suppression therapies (GSTs) as a new hope for disease-modifying strategies. In this article, we aim to perform a review of studies investigating the efficacy and safety profile of GSTs in HCAs.
METHODS
A structured PubMed search on GSTs in HCAs from January 1993 up to October 2020 was performed. Inclusion and exclusion criteria were defined, and the selection process was conducted accordingly. The screening process was independently carried out by two authors and was initially based on title and abstract, followed by full-text reading. The risk-of-bias assessment was performed with SYRCLE's tool. A data extraction sheet was created to collect relevant information from each selected article.
RESULTS
The initial search yielded 262 papers, of which 239 were excluded. An additional article was obtained following reference scrutiny, resulting in a total of 24 articles for final analysis. Most studies were not clear on the tools used to assess bias. In SCA1, SCA2, MJD/SCA3 and SCA7, RNA interference (iRNA) and antisense oligonucleotide (ASO) therapies proved to be well tolerated and effective in suppressing mutant proteins, improving neuropathological features and the motor phenotype. In SCA6, the phenotype was improved, but no investigation of adverse effects was performed. In FRDA, only the suppression efficacy of the electroporation of the clustered regularly interspaced short palindromic repeats associated with Cas9 enzyme system (CRISPR-Cas9) system was tested and confirmed.
CONCLUSION
The literature reviewed suggests that GSTs are well tolerated and effective in suppressing the targeted proteins, improving neuropathological features and the motor phenotype . Nonetheless, there is no guarantee that these results are free of bias. Moreover, further investigation is still needed to clarify the GST effect on HCAs such as FRDA, SCA6 and SCA2.
Topics: Animals; Cerebellar Ataxia; Trinucleotide Repeats; Spinocerebellar Degenerations; Proteins
PubMed: 37048110
DOI: 10.3390/cells12071037 -
Frontiers in Oncology 2022Pediatric and adult K27M-mutant midline gliomas have variable clinical presentations, prognoses, and molecular backgrounds. In this study, we integrated data from...
INTRODUCTION
Pediatric and adult K27M-mutant midline gliomas have variable clinical presentations, prognoses, and molecular backgrounds. In this study, we integrated data from published studies to investigate the differences between these two groups.
METHODS
PubMed and Web of Science were searched for potential data. Studies were included if they had available individual participant data on patients age of K27M-mutant midline gliomas. For time-to-event analyses, Kaplan-Meier analysis and Cox regression models were carried out; corresponding hazard ratios (HR) and 95% confidence intervals (CI) were computed to analyze the impact of age and clinical covariates on progression-free survival (PFS) and overall survival (OS).
RESULTS
We included 43 studies comprising 272 adults and 657 pediatric midline gliomas with K27M mutation for analyses. In adults, there was a male predilection whereas females were slightly more common than males in the pediatric group. Spinal cord tumors were more frequent in adults. The prevalence of K27M mutation was significantly higher in the pediatric cohort. Compared to adult patients, pediatric K27M-mutant midline gliomas exhibited more aggressive features including higher rates of pathologic features of high-grade tumors and Ki67 proliferation index, and had a shorter PFS and OS. Genetically, mutations were more common whereas methylation, , and mutations were less prevalent in the pediatric cohort.
CONCLUSION
Pediatric K27M-mutant midline gliomas were demographically, clinically, and molecularly distinct from adult patients, highlighting an opportunity to refine the risk stratification for these neoplasms.
PubMed: 35371982
DOI: 10.3389/fonc.2022.858148 -
Cytokine Mar 2020Owing to involvement of host genetic factors in susceptibility to brucellosis infection and its outcome, this study aimed to carry out a comprehensive systematic review... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Owing to involvement of host genetic factors in susceptibility to brucellosis infection and its outcome, this study aimed to carry out a comprehensive systematic review and meta-analysis to derive a precise evaluation of the association between the risk of brucellosis and its focal complication and all cytokines examined in case-control studies, including Interferon gamma (IFN-γ), Tumor Necrosis Factor (TNF)-α, TNF-β, Transforming Growth Factor(TGF)-β, IL-2, IL-4, IL-6, IL-10, IL-12B, IL-15, and IL-18 polymorphisms.
METHODS
A systematic literature search in PubMed, Web of Science, Google Scholar, and Scopus was performed to identify the relevant studies, and related information was extracted. The effect size (ES) and corresponding 95% confidence intervals (CIs) were calculated to estimate the association.
RESULTS
From 158 initial results, twenty-five eligible studies were included in the meta-analysis. Overall, the pooled results showed that the dominant models of IFN-γ UTR5644, TGF-β rs1800470 and rs1800471, TNF-α rs1800629, and IL-10 rs1800872 were significantly less frequent in brucellosis patients than the controls. Also, the pooled analysis of the mutant allele vs. wild allele of TGF-β rs1800471 and IL-10 rs1800872 showed negative association with brucellosis risk. On the other hand, our pooled analysis demonstrated that the mutant allele of IL-4 rs2243250 and IL-18 rs1946519 were associated with increased susceptibility to brucellosis. In addition, the IFN-γ UTR5644 and TGF-β rs1800470 were more frequent in the patients without focal forms.
CONCLUSIONS
IL-4 rs2243250 and IL-18 rs1946519 have a positive correlation with brucellosis whereas the IFN-γ UTR5644, TGF-β rs1800470 and rs1800471, TNF-α rs1800629, and IL-10 rs1800872 showed a negative association with this disease. The association between the other single nucleotide polymorphisms (SNP) and brucellosis risk was not confirmed in the current meta-analysis. PROSPERO Registration: CRD42018117203.
Topics: Animals; Brucellosis; Cytokines; Genetic Predisposition to Disease; Genotype; Humans; Polymorphism, Single Nucleotide
PubMed: 31816580
DOI: 10.1016/j.cyto.2019.154949