Immune-related adverse events (irAEs) and survival in solid tumors treated with immune checkpoint inhibitors (ICIs): A systematic review and meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14130-e14130
Author(s):  
Giulia Grizzi ◽  
Fausto Petrelli ◽  
Michele Ghidini ◽  
Antonio Ghidini ◽  
Margherita Ratti ◽  
...  
Keyword(s):  
Solid Tumors ◽  
T Cell Activation ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Previous History ◽  
Cochrane Library ◽  
Risk Of Death ◽  
Reduced Risk

e14130 Background: irAEs are autoimmune-toxic effects associated with ICIs used for treatment of advanced solid tumors. The correlation of these irAEs with survival is presently unknown. The objective of this meta-analysis is to assess the outcome of cancer patients treated with ICIs who develop irAEs. Methods: Two independent reviewers selected prospective or retrospective studies from PubMed, EMBASE, and the Cochrane library database from their inception to November 2018. Studies were selected if: 1) they reported correlation of irAEs (any) with outcome, 2) they included patients with solid tumors; 3) they included treatment with anti-PD-(L)1 or anti-CTLA-4 agents, 4) patients had no previous history of autoimmune disorders, 5) they were published in English language, and 6) they provided availability of adequate data to calculate hazard ratios (HRs) or odds ratios (ORs) and 95% confidence intervals (CIs). Data were pooled using HRs for overall survival (OS) or progression-free survival (PFS) or ORs for overall response rate (ORR) of irAEs vs no irAEs according to fixed or random effect model. HRs for OS (the primary outcome measure) were pooled to provide an aggregate value. Hazard ratio for PFS and ORs for ORR were secondary endpoints. Results: A total of 29 studies for a total of 4242 patients treated with ICIs were selected. Patients who developed irAEs presented a reduced risk of death (HR = 0.52, p < .001). Similarly, the occurrence of irAEs was associated with a reduced risk of progression (HR = 0.51, p < .001). The combined odds of response was 4.87 (p < .001). Conclusions: In patients treated with ICIs, irAEs predict survival and response. Although this correlation cannot be fully explained, it may be related to the strongest T cell activation. Patients showing any form of irAEs can be informed about the positive prognostic effect, and physicians can detect patients with favorable outcome to ICIs.

Novel oral anticoagulats for the treatment of left ventricle thrombosis: a systematic review and meta-analysis

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
M Serenelli ◽  
F Vitali ◽  
R Pavasini ◽  
E Tonet ◽  
G Pompei ◽  
...  
Keyword(s):  
Primary Outcome ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Left Ventricular ◽  
Left Ventricular Thrombus ◽  
Cochrane Library ◽  
Secondary Outcome ◽  
Ventricular Thrombus

Abstract Funding Acknowledgements Type of funding sources: None. Background novel oral anticoagulants (NOACs) are not guideline-recommanded treatment for left ventricular thrombus.  Purpose: the aim of this meta-analysis is to compare NOACs versus vitamin-K atagonsits (VKAs) efficacy in treating left ventricular thrombus (LVT). Methods: we systematically searched MEDLINE, Cochrane Library, Biomed Central, and Web of Science for trials comparing NOACs versus VKAs in the setting of LVT. Five studies, out of the 74 initially selected after first screening, were included in the meta-analysis. For the development of this meta-analysis, the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were followed. The shortlisted studies were retrieved as full articles and appraised independently by two unblinded reviewers. The Mantel-Haensel method with a random effect model was used for the pooled analysis. The primary outcome was the occurrence of stroke and systemic embolism. Secondary outcome was occurrence of left ventricular thrombosis resolution during treatment.  Results: 707 patients were included in the analysis for the primary outcome. Of these, 230 were treated with NOACs and 477 with VKAs. The pooled OR for the primary outcome was 0.71 (95% CI 0.18-2.86, I2 67%), thus showing similar effect in term of ischaemic protection. A total of 698 patients, 228 on NOACs and 470 on VKAs were included in the analysis of the secondary outcome. The pooled OR for the secondary outcome pooled OR 0.97, 95% CI 0.56-1.68, I2 46%. Conclusions and Relevance: NOACs seem to have a similar efficacy profile compare to VKAs and so they should be considered as an alternative treatment for left ventricular thrombosis. Large prospective randomized clinical trials are needed to confirm this exploratory finding. Abstract Figure 1

Is first-line immune checkpoint inhibitors (ICI) beneficial to platinum-eligible patients (pts) with advanced urothelial carcinoma (aUC)? a meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16506-e16506
Author(s):  
Ce Cheng ◽  
Iloabueke Gabriel Chineke ◽  
Ali McBride ◽  
Juan Chipollini ◽  
Edward Paul Gelmann ◽  
...  
Keyword(s):  
Publication Bias ◽  
Subgroup Analysis ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Random Effect ◽  
Fixed Effect Model ◽  
Cochrane Library ◽  
First Line ◽  
Significance Level ◽  
Line Setting

e16506 Background: ICI have proven to benefit patients diagnosed with aUC who are platinum-ineligible. The role of platinum-eligible patients, in the first-line setting is being further elucidated after single positive randomized clinical trial (RCT) with ICI. Hence, we performed a meta-analysis to interpret the association of Overall Survival (OS) and PD-1 or PD-L1 inhibitors as first-line therapies in platinum-eligible patients with aUC. Methods: Randomized controlled trials were retrieved from PubMed, Web of Science, and Cochrane Library according to established inclusion criteria. Each article was assessed by the Newcastle-Ottawa Scale. The Hazard Risk (HR) and 95% confidence intervals (CI) were calculated. Random effect or fixed-effect model was used to calculate the pooled HR, based on heterogeneity significance. Sensitivity analysis and publication bias detection were performed. All statistical analysis were performed using RevMan software (v5.4; Cochrane library) and R Core Team (2016, Vienna, Austria), and all p-values were two-tailed, and the significance level was 0.05. Results: Sixty-seven articles were obtained from the database search, and based on inclusion/exclusion criteria, five RCTs were selected involving 4063 patients. All studies were considered moderate to high quality. A statistically significant association was found between initiation of immunotherapy as first-line treatment to platinum-eligible patients and increased OS (HR 0.87; 95% CI: 0.81,0.94, p = 0.004, I2= 38%). The subgroup analysis included positive PD1 (HR 0.81; 95% CI: 0.70,0.94, p = 0.004, I2= 34%) vs. negative expression (HR 0.96; 95% CI: 0.83,1.11, p = 0.58, I2= 0%); cisplatin (HR 0.81; 95% CI: 0.69,0.96, p = 0.02, I2= 47%) vs. carboplatin administration (HR 0.87; 95% CI: 0.76,1.01, p = 0.06, I2= 21%); male (HR 0.87; 95% CI: 0.77,0.97, p = 0.01, I2= 44%) vs. female (HR 0.85; 95% CI: 0.70,1.04, p = 0.11, I2= 0%); ECOG score 0 (HR 0.77; 95% CI: 0.67,0.89, p = 0.0005, I2= 0%) vs. ≥ 1 (HR 0.90; 95% CI: 0.78,1.02, p = 0.11, I2= 6%); Caucasian (HR 0.81; 95% CI: 0.73, 0.91, p = 0.0003, I2= 39%) vs. other race (HR 0.92; 95% CI: 0.75, 1.13, p = 0.44, I2= 0%). Similar association regardless of visceral lesion or age. Funnel plot, Egger's test (p = 0.6944), and Begg's test (0.7726) found no publication bias of analysis. Conclusions: This meta-analysis showed improved OS in platinum-eligible patients receiving first-line ICI in aUC. Furthermore, a subgroup analysis yielded an increased OS and cisplatin, positive PD1 status, ECOG 0, male gender, and Caucasian race. In this rapidly evolving clinical practice changes, our meta-analysis provides support to currently recommended avelumab maintenance after platinum induction therapy in the first-line setting and further provide guidance on patient selection for aUC.

scholarly journals Clinical and Molecular Characteristics Associated with Survival in Advanced Melanoma Treated with Checkpoint Inhibitors

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Sunil Badami ◽  
Sunil Upadhaya ◽  
Ravi Kanth Velagapudi ◽  
Pushyami Mikkilineni ◽  
Ranju Kunwor ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Random Effect ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Melanoma ◽  
Cochrane Library ◽  
Molecular Characteristics ◽  
Significant Heterogeneity

Background. We performed meta-analysis to gather more evidence regarding clinical-molecular subgroups associated with better overall survival (OS) in advanced melanoma treated with checkpoint inhibitors. Materials and Methods. We performed a systematic search of PubMed, Scopus, Cochrane Library, and clinical trial.gov. Randomized clinical trials that compared a checkpoint inhibitor (nivolumab or pembrolizumab) with investigator choice chemotherapy or ipilimumab were included in our study. Hazard ratios (HR) and confidence interval (CI) were calculated for progression-free survival (PFS) and OS for each subgroup using generic inverse model along with the random effect method. Results. A total of 6 clinical trials were eligible for the meta-analysis. OS was prolonged in wild BRAF subgroup (HR 0.65, 95% CI 0.49-0.85, p 0.002), Programmed cell death subgroup (PD-1+) (HR 0.57, 95% CI 0.41-0.80, p 0.001), and high lactate dehydrogenase (LDH) level subgroup (HR 0.60, 95% CI 0.38-0.95, p 0.03). Similarly, we found increased OS in eastern cooperative oncology group (ECOG) 1, males and age >65 years subgroups. Conclusions. Checkpoint inhibitors significantly increased OS in patients with wild BRAF, positive PD-1, and high LDH. However, results should be interpreted keeping in mind associated significant heterogeneity. The results of this study should help in designing future clinical trials.

scholarly journals Prevalence of Human Papilloma Virus in Patients With Colorectal Cancer: A Systematic Review and Meta-analysis

2019 ◽  
Vol 7 (4) ◽  
pp. 106-112
Author(s):  
Masoud Dadashi ◽  
Shaian Tavakolian ◽  
Ebrahim Faghihloo
Keyword(s):  
Colorectal Cancer ◽  
Meta Analysis ◽  
Scientific Information ◽  
Random Effect ◽  
Random Effect Model ◽  
Hpv Infection ◽  
High Rate ◽  
Cochrane Library ◽  
High Risk Behaviors ◽  
The World

Background: Human papillomavirus (HPV) is considered as one of the most common carcinogenic viruses in humans throughout the world and is mostly associated with gynecologic malignancies. However, it is also one of the environmental factors that is involved in colorectal cancer (CRC). Objective: A meta-analysis was performed to investigate the prevalence of HPV infection in patients suffering from the CRC. Methods: The frequency of the HPV in patients with CRC was studied from 2001 to 2016. To this end, several databases were reviewed, including PubMed, Web of Science, Embase, Cochrane Library, Google Scholar, Iranmedex, and the Scientific Information Database. Then, the analysis was done by Comprehensive Meta-Analysis (V2.0, Biostat) software. Considering heterogeneity between different studies, the random effect model was used and then the results were checked with Cochran’s Q-statistic. Results: The meta-analysis revealed that the frequency of HPV infection in patients with CRC was 33.7% (a 95% CI of 28.4-39.5). The additional stratified analysis also showed that HPV infection in CRC patients was more widespread in European countries compared to Asian and American countries. Conclusion: The high rate of HPV infection is a major concern in sexually transmitted diseases around the world, therefore, controlling high-risk behaviors, vaccination, screening, and HPV subtyping can be useful in managing HPV infections.

scholarly journals Mean Platelet Volume and Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Zhongwei Zhou ◽  
Hongmei Chen ◽  
Mingzhong Sun ◽  
Huixiang Ju
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Pregnant Women ◽  
Mean Platelet Volume ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Cochrane Library ◽  
Platelet Volume

Aim. To evaluate the association between mean platelet volume (MPV) and gestational diabetes mellitus (GDM). Methods. A systematic literature search was performed in PubMed, EMBASE, Web of Science, and The Cochrane Library up to 4 September 2017. Pooled standardized mean differences (SMD) and 95% confidence interval (CI) were calculated using a random-effect model. Results. Nineteen studies comprising 1361 GDM patients and 1911 normal pregnant women were included. MPV was increased in GDM patients when compared with healthy pregnant women (SMD: 0.79; 95% CI: 0.43–1.16; P<0.001). Subgroup analyses revealed that such trend was consistent in the third-trimester (SMD: 1.35; 95% CI: 0.72–1.98), Turkish (SMD: 0.81; 95% CI: 0.43–1.19), and Italian (SMD: 2.78; 95% CI: 2.22–3.34) patients with GDM and the patients diagnosed based on Carpenter and Coustan criteria (SMD: 1.04; 95% CI: 0.42–1.65). Significantly higher MPV also were observed within cross-sectional studies (SMD: 0.99; 95% CI: 0.49–1.49). Remarkable between-study heterogeneity and potential publication bias were observed in this meta-analysis; however, sensitivity analysis indicated that the results were not unduly influenced by any single study. Conclusions. GDM patients are accompanied by increased MPV, strengthening the clinical evidence that MPV may be a predictive marker for GDM.

Predictors of benefits to chemoimmunotherapy (CIT) in stage IV non-small-cell lung cancer (NSCLC): A meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20595-e20595
Author(s):  
Hazem Edmond El-Osta ◽  
Anita Lyn Sabichi
Keyword(s):  
Liver Metastasis ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Performance Status ◽  
Random Effect ◽  
Single Agent ◽  
Random Effect Model ◽  
Phase Iii ◽  
Smoking History ◽  
Metastatic Nsclc

e20595 Background: Immune checkpoint inhibitors (ICIs) have changed the landscape of NSCLC therapy. In previous study, gender, smoking history, and PD-L1 status were found to influence the efficacy of ICI monotherapy in NSCLC. This meta-analysis evaluated the clinical and molecular factors predictive of benefit from the addition of ICIs to first-line (1L) chemotherapy in metastatic NSCLC. Methods: Using the random effect model, we computed and compared the pooled hazard ratio (HR) of progression-free survival (PFS) and overall survival (OS) among the selected subgroups. The correlation between PD-L1 expression level and outcome was analyzed by meta-regression. Results: 7 phase III randomized trials comparing CIT vs. chemo in the 1L treatment of stage 4 NSCLC were included. CIT evenly improved the PFS irrespective of age, gender, histology, smoking history and ECOG performance status (PS). While patients (pts) with liver metastasis or ALK/EGFR aberration had greater PFS with the addition of ICI to Bevacizumab (BEV) based chemo regimen, the derived benefit was no longer statistically significant among pts treated with non-BEV-based regimens. Whereas the PFS superiority conferred by CIT was noticed across all PD-L1 expression subgroups, the benefit correlated with PD-L1 level and was more pronounced in the “PD-L1 high” subset. Except for pts with EGFR/ALK abnormalities, squamous histology or liver metastasis, CIT yielded a consistent amelioration of OS across the other selected subgroups. Conclusions: Survival advantage associated with 1L CIT in metastatic NSCLC was observed in different pts population including those for which single-agent ICI has limited therapeutic benefit. Our findings support the role of chemo +/- VEGF blockade as enhancer of ICIs activity even in “less immunogenic” context. [Table: see text]

scholarly journals The Associations between VEGF Gene Polymorphisms and Diabetic Retinopathy Susceptibility: A Meta-Analysis of 11 Case-Control Studies

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Liyuan Han ◽  
Lina Zhang ◽  
Wenhua Xing ◽  
Renjie Zhuo ◽  
XiaLu Lin ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Recessive Model ◽  
Cochrane Library ◽  
Published Data ◽  
Case Control Studies ◽  
Asian Populations ◽  
Effect Model

Aims. Published data on the associations of VEGF polymorphisms with diabetic retinopathy (DR) susceptibility are inconclusive. A systematic meta-analysis was undertaken to clarify this topic.Methods. Data were collected from the following electronic databases: PubMed, Embase, OVID, Web of Science, Elsevier Science Direct, Excerpta Medica Database (EMBASE), and Cochrane Library with the last report up to January 10, 2014. ORs and 95% CIs were calculated for VEGF–2578C/A (rs699947), –1154G/A (rs1570360), –460T/C (rs833061), −634G>C (rs2010963), and +936C/T (rs3025039) in at least two published studies. Meta-analysis was performed in a fixed/random effect model by using the software STATA 12.0.Results. A total of 11 studies fulfilling the inclusion criteria were included in this meta-analysis. A significant relationship between VEGF+936C/T (rs3025039) polymorphism and DR was found in a recessive model (OR = 3.19, 95% CI = 1.20–8.41, andP(z)=0.01) in Asian and overall populations, while a significant association was also found between –460T/C (rs833061) polymorphism and DR risk under a recessive model (OR = 2.12, 95% CI = 1.12–4.01, andP(z)=0.02).Conclusions. Our meta-analysis demonstrates that +936C/T (rs3025039) is likely to be associated with susceptibility to DR in Asian populations, and the recessive model of –460T/C (rs833061) is associated with elevated DR susceptibility.

scholarly journals β lactam monotherapy versus β lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials

BMJ ◽  
2004 ◽  
Vol 328 (7441) ◽  
pp. 668 ◽  
Author(s):  
Mical Paul ◽  
Ishay Benuri-Silbiger ◽  
Karla Soares-Weiser ◽  
Leonard Leibovici
Keyword(s):  
Relative Risk ◽  
Combination Therapy ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Cochrane Library ◽  
Randomised Trials ◽  
Intention To Treat ◽  
Relative Risks ◽  
Development Of Resistance

AbstractObjective To compare β lactam monotherapy with β lactam-aminoglycoside combination therapy for severe infections.Data sources Medline, Embase, Lilacs, Cochrane Library, and conference proceedings, to 2003; references of included studies; contact with all authors. No restrictions, such as language, year of publication, or publication status.Study selection All randomised trials of β lactam monotherapy compared with β lactam-aminoglycoside combination therapy for patients without neutropenia who fulfilled criteria for sepsis.Data selection Two reviewers independently applied selection criteria, performed quality assessment, and extracted the data. The primary outcome assessed was all cause fatality by intention to treat. Relative risks were pooled with the random effect model (relative risk < 1 favours monotherapy).Results 64 trials with 7586 patients were included. There was no difference in all cause fatality (relative risk 0.90, 95% confidence interval 0.77 to 1.06). 12 studies compared the same β lactam (1.02, 0.76 to 1.38), and 31 studies compared different β lactams (0.85, 0.69 to 1.05). Clinical failure was more common with combination treatment overall (0.87, 0.78 to 0.97) and among studies comparing different β lactams (0.76, 0.68 to 0.86). There was no advantage to combination therapy among patients with Gram negative infections (1835 patients) or Pseudomonas aeruginosa infections (426 patients). There was no difference in the rate of development of resistance. Nephrotoxicity was significantly more common with combination therapy (0.36, 0.28 to 0.47). Heterogeneity was not significant for these comparisons.Conclusions In the treatment of sepsis the addition of an aminoglycoside to β lactams should be discouraged. Fatality remains unchanged, while the risk for adverse events is increased.

scholarly journals Breast Cancer Risk in Rheumatoid Arthritis: An Update Meta-Analysis

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Guo Tian ◽  
Jia-Ning Liang ◽  
Zhuo-Yun Wang ◽  
Dian Zhou
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Subgroup Analysis ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Cochrane Library ◽  
Number Of Patients ◽  
The Impact

Background. The incidence of breast cancer in RA patients remains controversial. Thus we performed a meta-analysis to investigate the impact of RA on breast cancer.Methods. Published literature was available from PubMed, Embase, and Cochrane Library. Pooled standardized incidence rate (SIR) was computed by random-effect model analysis.Results. We identified 16 separate studies in the present study, in which the number of patients ranged from 458 to 84,475. We did not find the increased cancer risk in RA patients (SIR=0.86, 95%CI=0.72–1.02). However, subgroup analysis showed that breast cancer risk in RA patients was positively different in Caucasians (SIR=0.82, 95%CI=0.73–0.93) and non-Caucasians (SIR=1.21, 95%CI=1.19–1.23), respectively. In subgroup analysis by style, a reduced incidence was found in hospital-based case subjects (SIR=0.82, 95%CI=0.69–0.97). Similarly, subgroup analysis for adjusted factors indicated that in A3 (age and sex) and A4 (age, sex, and race/ethnicity) the risk was decreased (SIR=0.87, 95%CI=0.76–0.99;SIR=0.63, 95%CI=0.59–0.67).Conclusions. The meta-analysis revealed no increased breast cancer risk in RA patients. However, in the subgroup analysis, the risk of breast cancer is increased in non-Caucasians patients with RA while it decreased in Caucasian population, hospital-based case subjects, and A3 group. Such relationship may provide preference for risk of breast cancer in different population.

scholarly journals Detecting Melanoma Antigen Family A3 Expression in Solid/Non-Solid Human Tumor

2020 ◽  
Author(s):  
Haoran Jiang ◽  
Lihao Zhao ◽  
Han Yang ◽  
Mengjing Zhao ◽  
Yuxia Duan ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Human Tumor ◽  
Squamous Carcinoma ◽  
Cochrane Library ◽  
Published Data ◽  
Melanoma Antigen ◽  
Effect Model ◽  
Positive Rate

Abstract Background: MAGEA3 is a member of melanoma antigen family and has been recognized to express in many types of human cancers recently. In spite of the development of cancer vaccine, the prognostic value of MAGEA3 has not been well evaluated, due to the variability of clinical data and lack of clinical trials on the prognostic values.Method: Studies that evaluated MAGEA3 expression with a follow-up for at least 36 months were selected by searching in PubMed, WOS, Cochrane library, Embase. Published data was recorded and calculated into odds ratios (OR) for mortality in three or five years with Mantel-Haenszel random-effect model. Results: 11 studies were selected. The median positive rate was 45%. MAGEA3 always combines with worse survival on three or five years survival. The correlation between MAGEA3 and squamous carcinoma seemed stronger than adenocarcinoma on three-year OS while things got a reverse when it came to five-year OS. Most importantly, we found that all solid tumors originated from endoderm seemed to enjoy a strongest correlation among all the three germ layers.Conclusion: In this meta-analysis, we found that the expression of MAGEA3 can connect with worse outcome, and it probably can be a predictor for patients’ prognosis in clinical practice.

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