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American Journal of Clinical Oncology Jun 2023Patients with recurrent or persistent ovarian cancer often have poor prognoses, and their optimal treatment regimen remains unclear. Inhibition of angiogenesis is a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with recurrent or persistent ovarian cancer often have poor prognoses, and their optimal treatment regimen remains unclear. Inhibition of angiogenesis is a valuable strategy for treating ovarian cancer, and the drug pazopanib is a potent, multitarget tyrosine kinase inhibitor. However, treatment with pazopanib in combination with chemotherapy remains controversial. We performed a systematic review and meta-analysis to clarify the efficacy and side effects of pazopanib combined with chemotherapy in the treatment of advanced ovarian cancer.
METHODS
The PubMed, Embase, and Cochrane databases were systematically searched for relevant randomized controlled trials published up to September 2, 2022. The primary outcomes of eligible studies included overall response rate (ORR), disease control rate, 1-year progression-free survival (PFS) rate, 2-year PFS rate, 1-year overall survival (OS) rate, 2-year OS rate, and adverse events.
RESULT
Outcomes from a total of 518 recurrent or persistent ovarian cancer patients from 5 studies were analyzed in this systematic review. Pooled results showed that pazopanib plus chemotherapy, when compared with chemotherapy alone, significantly improved the ORR (pooled risk ratio=1.400; 95% CI, 1.062-1.846; P = 0.017) but not the disease control rate, 1-year PFS, 2-year PFS, 1-year OS, or 2-year OS. Moreover, pazopanib increased the risk of neutropenia, hypertension, fatigue, and liver dysfunction.
CONCLUSION
Pazopanib plus chemotherapy improved patient ORR but did not improve survival; it also increased the occurrence of several adverse events. Further large-sample clinical trials are needed to verify these results to guide pazopanib use in patients with ovarian cancer.
Topics: Humans; Female; Ovarian Neoplasms; Pyrimidines; Sulfonamides; Indazoles; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36877187
DOI: 10.1097/COC.0000000000000999 -
European Review For Medical and... Feb 2023The triplet regimen based on the programmed cell death 1 (PD1)/ programmed cell death ligand 1 (PDL1) inhibitors combined radiotherapy and antiangiogenic drugs is a... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The triplet regimen based on the programmed cell death 1 (PD1)/ programmed cell death ligand 1 (PDL1) inhibitors combined radiotherapy and antiangiogenic drugs is a novel therapeutic strategy for hepatocellular carcinoma. We conducted a meta-analysis to evaluate the efficacy and safety of the triplet therapeutic regimen in the treatment of hepatocellular carcinoma.
MATERIALS AND METHODS
We searched scientific literature databases and clinical trial databases through October 31, 2022, for required studies. The pooled hazard ratio (HR) was used to analyze the overall survival (OS), progression-free survival (PFS), and the pooled relative risk (RR) was used to analyze the objective response rate (ORR), disease control rate (DCR), mortality rate (MR), and adverse events (AEs) through random or fixed effects model, 95% confidence interval (CI) was determined for all outcomes. Qualities of the included literature were assessed by MINORS Critical appraisal checklist. Funnel plot was used to assess publication bias in the included studies.
RESULTS
Five studies (3 single-arm and 2 non-randomized comparative trials), including 358 cases, were enrolled. Meta-analysis showed that the pooled ORR, DCR, and MR were 51% (95% CI: 34%-68%), 86% (95% CI: 69-102%), and 38% (95% CI: 18-59%), respectively. Compared with triplet regimen, the single or dual-combination treatments had shorter OS (HR=0.53, 95%: 0.34-0.83 via univariate analysis; HR=0.49, 95%: 0.31-0.78 via multivariable analysis) and PFS (HR=0.52, 95%: 0.35-0.77 via univariate analysis; HR=0.54, 95%: 0.36-0.80 via multivariable analysis). Common AEs to triplet regimens included skin reaction (17%), nausea/vomiting (27%), fatigue (23%), while severe AEs (10%), fever (18%), diarrhea (15%), and hypertension (5%) without statistically significant differences.
CONCLUSIONS
In the treatment of hepatocellular carcinoma, PD1/PDL1 inhibitors combined radiotherapy and antiangiogenic drugs achieved better survival benefits than alone or dual-combination regimens. In addition, the triple-combination therapy has tolerable safety.
Topics: Humans; Angiogenesis Inhibitors; Carcinoma, Hepatocellular; Checklist; Liver Neoplasms
PubMed: 36876689
DOI: 10.26355/eurrev_202302_31390 -
JAMA Network Open Feb 2023Although small intestinal adenocarcinomas (SIAs) are rare, they have a poor prognosis, and the optimal treatment strategies are largely unknown. Because of the lack of... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Although small intestinal adenocarcinomas (SIAs) are rare, they have a poor prognosis, and the optimal treatment strategies are largely unknown. Because of the lack of high-quality evidence, guidelines for colorectal cancer are often followed in the treatment of SIAs.
OBJECTIVE
To review the current evidence regarding survival benefit of systemic therapies, including chemotherapy, targeted agents, and immunotherapy, for patients with SIAs.
DATA SOURCES
Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses, MEDLINE and Embase were searched for articles published from January 1, 2005, until June 1, 2022.
STUDY SELECTION
Retrospective cohort studies and prospective phase 2 or 3 trials describing survival after systemic therapies for patients with SIAs were eligible for inclusion. Assessment of study eligibility was blinded and performed by 3 reviewers.
DATA EXTRACTION AND SYNTHESIS
The reviewers independently extracted data. Random effects, inverse variance, pairwise meta-analyses were performed.
MAIN OUTCOMES AND MEASURES
Primary outcomes were overall survival (OS) and progression-free survival (PFS) of patients with SIAs after systemic therapies. Measures of interest included hazard ratios for survival and median survival times.
RESULTS
Overall, 57 retrospective cohort and phase 2 studies of 35 176 patients were included. Adjuvant chemotherapy, generally fluoropyrimidine-based, was associated with increased OS in stage I to III SIAs (hazard ratio [HR], 0.60; 95% CI, 0.53-0.68), especially in stage III tumors (HR, 0.55; 95% CI, 0.48-0.64), irrespective of tumor localization. Palliative chemotherapy was also associated with an OS benefit (HR, 0.48; 95% CI, 0.40-0.58). Fluoropyrimidine-oxaliplatin combinations were superior to other regimens (OS: HR, 0.54; 95% CI, 0.30-0.99; PFS: HR, 0.46; 95% CI, 0.30-0.71). Furthermore, bevacizumab added to chemotherapy compared with chemotherapy alone was associated with significantly prolonged PFS (HR, 0.62; 95% CI, 0.43-0.89). Immunotherapy showed a 50% overall response rate in previously treated defective mismatch repair tumors.
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, adjuvant and palliative chemotherapy were both associated with improved survival of patients with SIAs, especially fluoropyrimidine-based regimens and fluoropyrimidine-oxaliplatin combinations. Adding bevacizumab to chemotherapy appears to prolong PFS and deserves further investigation. Immunotherapy seems beneficial and should be considered for patients with defective mismatch repair tumors. International collaborations should be undertaken to confirm and improve efficacy of systemic therapies for patients with SIAs.
Topics: Humans; Bevacizumab; Retrospective Studies; Oxaliplatin; Prospective Studies; Adenocarcinoma
PubMed: 36826817
DOI: 10.1001/jamanetworkopen.2023.0631 -
Frontiers in Endocrinology 2023To conduct a network meta-analysis (NMA) comparing the efficacy of anti-vascular endothelial growth factor (VEGF) therapy alone versus laser photocoagulation (LP)... (Meta-Analysis)
Meta-Analysis
Intravitreal anti-vascular endothelial growth factor, laser photocoagulation, or combined therapy for diabetic macular edema: A systematic review and network meta-analysis.
PURPOSE
To conduct a network meta-analysis (NMA) comparing the efficacy of anti-vascular endothelial growth factor (VEGF) therapy alone versus laser photocoagulation (LP) therapy alone or anti-VEGF therapy combined with LP therapy for diabetic macular edema (DME).
METHODS
PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials were systematically searched for studies comparing anti-VEGF therapy alone versus LP therapy alone or anti-VEGF therapy combined with LP therapy for DME. Primary outcomes were mean best-corrected visual acuity (BCVA) and central macular thickness (CMT) change. Relevant data were collected and pooled using NMA.
RESULTS
A total of 13 randomized controlled trials were included in our NMA. Anti-VEGF therapy significantly improved BCVA the most compared to the combined (mean difference [MD] = 1.5; 95% confidence interval [CI]: 0.084, 2.7) and LP (MD = 6.3; 95% CI: 5.1, 7.6) therapies at six months, while there was no difference in reducing CMT at six months between the anti-VEGF and combined therapies (MD = -16; 95% CI: -46, 13). At 12 months, no significant difference was found between the anti-VEGF and combined therapy in terms of BCVA (MD = 0.1; 95% CI: -1.7, 1.5) and CMT (MD = 21; 95% CI: -3.0, 44).
CONCLUSION
There was no significant difference between the anti-VEGF therapy and combined therapy. For the long-term treatment of patients with DME, combined therapy is recommended.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42022376401.
Topics: Humans; Macular Edema; Diabetic Retinopathy; Ranibizumab; Bevacizumab; Endothelial Growth Factors; Vascular Endothelial Growth Factor A; Network Meta-Analysis; Laser Coagulation; Lasers; Diabetes Mellitus
PubMed: 36817588
DOI: 10.3389/fendo.2023.1096105 -
Frontiers in Immunology 2022To summarize the cytokine/chemokine levels of anti-N-methyl-Daspartate receptor encephalitis (NMDAR-E) and explore the potential role of these molecules and immune cells... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To summarize the cytokine/chemokine levels of anti-N-methyl-Daspartate receptor encephalitis (NMDAR-E) and explore the potential role of these molecules and immune cells in the pathogenic mechanism.
METHODS
The PubMed, Cochrane Library, Embase, and Web of Science databases were searched for various articles that assessed the concentrations of cytokines/chemokines in the unstimulated cerebrospinal fluid (CSF) or serum of patients with NMDAR-E in this systematic review and meta-analysis. The standardized mean difference (SMD) and 95% confidence interval (CI) were calculated by Stata17.0.
RESULTS
A total of 19 articles were included in the systematic review from 260 candidate papers, and cytokine/chemokine levels reported in the CSF/serum were examined in each article. This meta-analysis included 17 eligible studies comprising 579 patients with NMDAR-E, 367 patients with noninflammatory neurological disorders, and 42 healthy controls from China, Spain, South Korea, Australia, Czechia, and Sweden. The results indicated that the levels of different cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, IL-13, IL-1β, IL-12, and IL-17 and chemokine C-X-C motif ligand (CXCL)10 in the CSF were significantly higher in NMDAR-E patients with a large effect size. In addition, B cell activating factor (BAFF), CXCL13, and interferon (IFN)-γ levels in the CSF were higher in NMDAR-E patients with a middle effect size. In contrast, levels of IL-2 and IL-4 in the CSF and CXCL13 and BAFF in the serum did not show a significant difference between cases and controls.
CONCLUSIONS
These analyses showed that the central immune response in NMDAR-E is a process that involves multiple immune cell interactions mediated by cytokines/chemokines, and T cells play an important role in the pathogenesis of immunity.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier (CRD42022342485).
Topics: Humans; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Chemokines; Cytokines; Interleukin-12; Interleukin-6; Tumor Necrosis Factor-alpha
PubMed: 36761173
DOI: 10.3389/fimmu.2022.1064007 -
PLoS Neglected Tropical Diseases Jan 2023Few data exist on the distinct cytokine profiles of individuals with malaria coinfections and other diseases. This study focuses on data collation of distinct cytokine...
BACKGROUND
Few data exist on the distinct cytokine profiles of individuals with malaria coinfections and other diseases. This study focuses on data collation of distinct cytokine profiles between individuals with malaria coinfections and monoinfections to provide evidence for further diagnostic or prognostic studies.
METHODS
We searched five medical databases, including Embase, MEDLINE, PubMed, Ovid, and Scopus, for articles on cytokines in malaria coinfections published from January 1, 1983 to May 3, 2022, after which the distinct cytokine patterns between malaria coinfection and monoinfection were illustrated in heat maps.
RESULTS
Preliminary searches identified 2127 articles, of which 34 were included in the systematic review. Distinct cytokine profiles in malaria coinfections with bacteremia; HIV; HBV; dengue; filariasis; intestinal parasites; and schistosomiasis were tumor necrosis factor (TNF), interferon (IFN)-γ, IFN-α, interleukin (IL)-1, IL-1 receptor antagonist (Ra), IL-4, IL-7, IL-12, IL-15, IL-17; TNF, IL-1Ra, IL-4, IL-10, IL-12, IL-18, CCL3, CCL5, CXCL8, CXCL9, CXCL11, granulocyte colony-stimulating factor (G-CSF); TNF, IFN-γ, IL-4, IL-6, IL-10, IL-12, CCL2; IFN-γ, IL-1, IL-4, IL-6, IL-10, IL-12, IL-13, IL-17, CCL2, CCL3, CCL4, G-CSF; IL-1Ra, IL-10, CXCL5, CXCL8, CXCL10; TNF, IL-2, IL-4, IL-6, IL-10; and TNF, IFN-γ, IL-4, IL-5, IL-10, transforming growth factor-β, CXCL8, respectively.
CONCLUSION
This systematic review provides information on distinct cytokine profiles of malaria coinfections and malaria monoinfections. Further studies should investigate whether specific cytokines for each coinfection type could serve as essential diagnostic or prognostic biomarkers for malaria coinfections.
Topics: Humans; Interleukin-10; Interleukin-17; Coinfection; Interleukin-6; Interleukin 1 Receptor Antagonist Protein; Interleukin-4; Cytokines; Interleukin-12; Tumor Necrosis Factor-alpha; Interferon-gamma; Granulocyte Colony-Stimulating Factor; Malaria
PubMed: 36716305
DOI: 10.1371/journal.pntd.0011061 -
Lung Cancer (Amsterdam, Netherlands) Feb 2023Thymic carcinoma (TC) is a rare cancer and patients failing initial chemotherapy (relapse/refractory) face limited therapeutic options given no approved options or... (Meta-Analysis)
Meta-Analysis Review
Thymic carcinoma (TC) is a rare cancer and patients failing initial chemotherapy (relapse/refractory) face limited therapeutic options given no approved options or consensus standard of care. This study aimed to identify and summarize clinical outcomes of all regimens evaluated in clinical trials of relapsed or refractory patients. Interventional trials enrolling advanced TC patients who failed first-line chemotherapy and reported outcomes in this group were eligible for inclusion in our systemic literature review (SLR). Between-study heterogeneity was assessed to determine the feasibility of pooling specific studies and treatments. Objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and duration of response (DOR) endpoints were of interest for meta-analysis. Nineteen trials were identified in the SLR. Three trials with one or two TC patients were removed from our assessment to reduce publication bias. Response rates among studies with at least ten TC patients varied from 9 % to 38 %. Pooled ORRs in patients receiving S-1 (46 patients), sunitinib (46 patients), or pembrolizumab (66 patients) were 28 %, 24 %, and 21 %, respectively. Prolonged duration of response with pembrolizumab was observed with a pooled median of 23.8 months (95 % confidence interval [CI]: 12, not reached). Median PFS of five months or greater was reported in patients treated with sunitinib, lenvatinib, pembrolizumab, capecitabine + gemcitabine, everolimus, or S-1. Median OS of 20 months or greater was reported in trials evaluating S-1 or pembrolizumab; this endpoint was not reached in trials evaluating lenvatinib, regorafenib, or sunitinib. Generalizability of treatment effects is challenging in the research of rare diseases and meta-analysis of clinical outcomes may help to increase precision and relevance of results to the larger TC population. Our study found limited treatment options upon relapse, demonstrating a need for further investigations into novel therapeutics and well-powered clinical trials to better inform on optimal treatments.
Topics: Humans; Sunitinib; Thymoma; Platinum; Neoplasm Recurrence, Local; Lung Neoplasms; Thymus Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36638588
DOI: 10.1016/j.lungcan.2023.01.003 -
Thoracic Cancer Feb 2023The combination of antiangiogenic agents with epidermal growth factor receptor inhibitors (EGFR-TKIs) and chemotherapy with EGFR-TKIs are the most common combination... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The combination of antiangiogenic agents with epidermal growth factor receptor inhibitors (EGFR-TKIs) and chemotherapy with EGFR-TKIs are the most common combination treatment options in epidermal growth factor receptor (EGFR) positive non-small cell lung cancer (NSCLC). This network meta-analysis was performed to evaluate the differences between them.
METHODS
We searched the PubMed, EMBASE and the Cochrane Controlled Trials Register up to August 2022. The primary outcomes were progression-free survival (PFS) and objective response rate (ORR). The secondary endpoints were overall survival (OS), disease control rate (DCR) and adverse events (AEs). The data of hazard ratio (HR) or risk ratio (RR) with their corresponding 95% confidence intervals (CIs) were extracted in the studies. A network meta-analysis (NMA) was used to indirectly compare the efficacy and safety of antiangiogenic agents plus EGFR-TKIs and chemotherapy plus EGFR-TKIs.
RESULTS
Pooled data of included studies were demonstrated that chemotherapy plus EGFR-TKIs had a benefit in ORR compared to antiangiogenic agents plus EGFR-TKIs in patients with EGFR mutated NSCLC (RR = 1.1, 95% CI: 1.0-1.2). However, there were no significant differences in PFS, OS and DCR between in the two group (PFS: HR = 1.0, 95% CI: 0.74-1.6; OS: HR = 0.78, 95% CI: 0.45-1.5; DCR: RR = 1.0, 95% CI: 0.94-1.1). The common treatment-related AEs in the two groups were relatively manageable.
CONCLUSION
Based on the efficacy and safety, the combination of chemotherapy with EGFR-TKIs is considered the best combination treatment options in advanced NSCLC with EGFR mutation.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Angiogenesis Inhibitors; Lung Neoplasms; Antineoplastic Agents; Network Meta-Analysis; ErbB Receptors; Protein Kinase Inhibitors
PubMed: 36594109
DOI: 10.1111/1759-7714.14783 -
European Urology Open Science Jan 2023The advent of immune check inhibitors (ICIs) has tremendously changed the prognosis of metastatic renal cell carcinoma (mRCC), adding an unseen substantial overall... (Review)
Review
CONTEXT
The advent of immune check inhibitors (ICIs) has tremendously changed the prognosis of metastatic renal cell carcinoma (mRCC), adding an unseen substantial overall survival benefit. These agents could be administered alone or in combination with anti-vascular endothelial growth factor (anti-VEGF) therapies. So far, treatment allocation is based only on clinical stratification risk models.
OBJECTIVE
Herein, we aimed to report the different molecular classifications reported in the first-line treatment of mRCC and discuss the awaited clinical implications in terms of treatment selection.
EVIDENCE ACQUISITION
Medline database as well as European Society for Medical Oncology (ESMO)/American Society of Clinical Oncology (ASCO) conference proceedings were searched to identify biomarker studies. Inclusion criteria comprised randomized and nonrandomized clinical trials that included patients treated in the first line of mRCC setting, patients treated with anti-VEGF therapies or ICIs, biological modeling, and available survival outcomes.
EVIDENCE SYNTHESIS
Four classification models were identified with subsequent clinical implications: Beuselinck model (34 gene signatures), IMmotion150, Hakimi, and JAVELIN 101 model. Tumor profiling shows distinct outcomes when treated with one or other combination. Patients are clustered into two gene signatures: angiogenic and proinflammatory (as per JAVELIN). The first is more likely to respond to therapy that includes anti-VEGF agents, while the best outcomes are obtained with an ICI combination with the second.
CONCLUSIONS
The findings presented here were mostly derived from ancillary registered studies of new drugs in the setting of mRCC. Further validation is needed, which sets new paradigms for investigation in clinical research based on tumor biology for treatment allocation and not only on clinical stratification tools.
PATIENT SUMMARY
First-line treatment of metastatic kidney includes immunotherapy alone or in combination with antiangiogenic therapy. However, clinical practice demonstrated that the "one treatment fits all" strategy might not be the best approach. In fact, recent studies showed that the addition of immunotherapy agents will not benefit all patients equally, and some still respond either equally to or better than anti-vascular endothelial growth factor alone. This review revealed biomarker modeling that impacts treatment selection. Recent tumor profiling into "angiogenic signature" more sensitive to angiogenic agents versus "immune signature" more likely to achieve the best response with immunotherapy should be validated. Tumor biology features might be more powerful than clinical classification for a tailored treatment approach.
PubMed: 36573246
DOI: 10.1016/j.euros.2022.11.006 -
Medicine Dec 2022Previous studies have reported controversial results on levels of inflammatory cytokines in patients with arsenic exposure. This study aims to evaluate the associations... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous studies have reported controversial results on levels of inflammatory cytokines in patients with arsenic exposure. This study aims to evaluate the associations between arsenic exposure and inflammatory cytokines and C-reaction protein (CRP).
METHODS
We searched the databases including PubMed, Embase, Web of Science, and China national knowledge infrastructure (CNKI) for studies reporting levels of cytokines and CRP in patients with arsenic exposure compared to the controls. The retrieval time was from January 2000 to September 2022.
RESULTS
13 observational studies involving 1665 arsenic exposed and 1091 unexposed individuals were included. Among these studies, 6 from China, 4 from India, 2 from Bangladesh and 1 from Turkey. Our result showed that interleukin (IL)-6, IL-8, and IL-12 levels were significantly higher in arsenic-exposed individuals compared to the control group, IL-2 level was significantly lower, and Tumor necrosis factor-α, Interferon-γ, CRP, and IL-10 levels were not changed. After sensitivity analyses, tumor necrosis factor-α and Interferon-γ levels were significantly higher in arsenic-exposed individuals compared to the control group. High heterogeneity was detected in most studies.
CONCLUSION
Many cytokines (such as IL-6, IL-8, and IL-12) have altered in individuals with arsenic exposure, this indicates arsenic exposure could trigger the cell-mediated inflammatory response. Regular examining immune function (such as inflammatory cytokines) in individuals with the risk of arsenic exposure is important to human health.
Topics: Humans; Cytokines; Arsenic; Tumor Necrosis Factor-alpha; Interferon-gamma; Interleukin-8; Interleukin-6; Inflammation; Interleukin-12
PubMed: 36550845
DOI: 10.1097/MD.0000000000032352