scholarly journals Predictive Values of Programmed Cell Death-Ligand 1 Expression for Prognosis, Clinicopathological Factors, and Response to Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Inhibitors in Patients With Gynecological Cancers: A Meta-Analysis

2021 ◽  
Vol 10 ◽  
Author(s):  
Chen Zhang ◽  
Qing Yang
Keyword(s):  
Cell Death ◽  
Endometrial Cancer ◽  
Programmed Cell Death ◽  
Tumor Cells ◽  
Subgroup Analysis ◽  
Meta Analysis ◽  
Figo Stage ◽  
Infiltration Depth ◽  
Gynecological Cancers ◽  
Free Survival

BackgroundThe prognostic value of programmed cell death-ligand 1 (PD-L1) in gynecological cancers has been explored previously, but the conclusion remains controversial due to limited evidence. This study aimed to conduct an updated meta-analysis to re-investigate the predictive significance of PD-L1 expression.MethodsPubMed, EMBASE and Cochrane Library databases were searched. The associations between PD-L1 expression status and prognosis [overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), cancer-specific survival (CSS) or disease-free survival (DFS)], clinical parameters [FIGO stage, lymph node metastasis (LNM), tumor size, infiltration depth, lymphovascular space invasion (LVSI) or grade] and response to anti-PD-1/PD-L1 treatment [objective response rate (ORR)] were analyzed by hazard ratios (HR) or relative risks (RR).ResultsFifty-five studies were enrolled. Overall, high PD-L1 expression was not significantly associated with OS, PFS, RFS, CSS and DFS of gynecological cancers. However, subgroup analysis of studies with reported HR (HR = 1.27) and a cut-off value of 5% (HR = 2.10) suggested that high PD-L1 expression was correlated with a shorter OS of gynecological cancer patients. Further sub-subgroup analysis revealed that high PD-L1 expressed on tumor-infiltrating immune cells (TICs) predicted a favorable OS for ovarian (HR = 0.72), but a poor OS for cervical cancer (HR = 3.44). PD-L1 overexpression was also correlated with a lower OS rate in non-Asian endometrial cancer (HR = 1.60). High level of PD-L1 was only clinically correlated with a shorter PFS in Asian endometrial cancer (HR = 1.59). Furthermore, PD-L1-positivity was correlated with LNM (for overall, ovarian and endometrial cancer expressed on tumor cells), advanced FIGO stage (for overall, ovarian cancer expressed on tumor cells, endometrial cancer expressed on tumor cells and TICs), LVSI (for overall and endometrial cancer expressed on tumor cells and TICs), and increasing infiltration depth/high grade (only for endometrial cancer expressed on TICs). Patients with PD-L1-positivity may obtain more benefit from anti-PD-1/PD-L1 treatment than the negative group, showing a higher ORR (RR = 1.98), longer OS (HR = 0.34) and PFS (HR = 0.61).ConclusionOur findings suggest high PD-L1 expression may be a suitable biomarker for predicting the clinical outcomes in patients with gynecological cancers.

scholarly journals Comparison of Chemotherapy With PD-1/L1 or CTLA-4 Inhibitors Alone Or In Combination In Advanced Or Metastatic Non-Small Cell Lung Cancer: A Meta- Analysis

2021 ◽  
Author(s):  
Lihu Gu ◽  
Jiali Liang ◽  
Wei Dai ◽  
Jiayu Li ◽  
Yuexiu Si ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Metastatic Nsclc

Abstract Background: In spite of the wide use of immune-checkpoint inhibitors (ICIs) in advanced or metastatic non-small cell lung cancer (NSCLC), whether ICIs or conventional chemotherapy is more effective still remains controversial. This study was conducted to evaluate the efficacy of giving patients programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), or cytotoxic T-lymphocyte protein 4 (CTLA-4) alone or in their combination (PD-1/L1 + CTLA-4) versus simply applying chemotherapy in patients with advanced or metastatic NSCLC.Methods: This meta-analysis was conducted from PubMed, Web of Science, Medline, Embase, and the Cochrane Library up to March 2021 to identify relevant randomized controlled trials (RCTs). Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoint was adverse events (AEs). Results: The search process has identified 13 studies containing 7918 patients with advanced or metastatic NSCLC. The benefit of PD-1/L1 or CTLA-4 inhibitors alone or in combination compared with chemotherapy for advanced or metastatic NSCLC was elucidated in both overall survival (OS) [HR=0.75, 95%CI (0.70-0.80), P<0.001] and progression-free survival (PFS) [HR=0.83, 95%CI (0.73-0.95), P<0.001]. Sex is another vital factor that affects the efficacy of ICIs. Male [HR=0.71, 95%CI (0.63-0.81)] benefits more from ICIs than the female [HR 0.80, 95%CI (0.68-0.94)] in OS. Besides, ICIs were associated with fewer AEs compared to chemotherapy.Conclusion: PD-1/L1 or CTLA-4 inhibitors alone or in combination, with fewer AEs, was associated with significant improvements in terms of OS and PFS than chemotherapy in treatment of advanced or metastatic NSCLC.

scholarly journals The Prognostic Value of PD-1/PD-L1 Expression on Tumor Cells and Tumor-Infiltrating Immune Cells in Patients with Colorectal Cancer: a Systematic Review and Meta-Analysis Protocol

2021 ◽  
Author(s):  
Fateme Abedini ◽  
Saeedeh Salehi ◽  
Leila Janani ◽  
Monireh Mohsenzadegan
Keyword(s):  
Colorectal Cancer ◽  
Systematic Review ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Tumor Cells ◽  
Immune Cells ◽  
Meta Analysis ◽  
Statistical Test ◽  
Risk Of Bias ◽  
Statistical Heterogeneity

AbstractAimColorectal cancer (CRC) is one of the most common cancers in the world. However, the role of immune checkpoint molecules, especially Programmed cell death protein 1 (PD-1) and Programmed cell death-ligand 1 (PD-L1), in the progression of CRC remains unclear. This systematic review and meta-analysis will investigate the prognostic significance of PD-1/PD-L1 expression on tumor-infiltrating immune cells and tumor cells in patients with colorectal cancer.MethodsThis protocol has been prospectively registered in the PROSPERO (registration NO. CRD42020156233). A comprehensive electronic search on PubMed/MEDLINE, Scopus, Web of Science (WOS), Embase and ProQuest will be conducted using a combination of MeSH terms of “programmed cell death 1”, “programmed cell death ligand 1”, “colorectal” and “cancer” between 1 January 1990 and 31 March 2021 with no language limitation. Two independent reviewers will perform study selection, data extraction, and risk of bias assessment. The Newcastle-Ottawa Scale (NOS) for cohort studies will be used to assess the risk of bias. In the case of sufficient data, either random or fixed-effect models, will be used for meta-analysis. Statistical heterogeneity will be evaluated by 𝒳2 test with the I2 statistic. “Funnel plot”, “Begg’s statistical test”, and “Egger’s statistical test and graph” will be used to assess publication bias. Stata V.13 software will be employed for meta-analysis.Results and conclusionAccording to the meta-analysis of the aggregated data from the relevant primary studies, the relationship between expression of PD-1/PD-L1 and prognostic parameters, including progression-free survival and overall survival, will be reported. The results of the current study will be published in a peer-reviewed journal.

scholarly journals Efficacy of PD-1 or PD-L1 inhibitors and PD-L1 expression status in cancer: meta-analysis

BMJ ◽  
2018 ◽  
pp. k3529 ◽  
Author(s):  
Xian Shen ◽  
Bin Zhao
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Control Group ◽  
Controlled Trials ◽  
Clinical Benefits ◽  
American Society ◽  
Randomised Controlled ◽  
Expression Status

Abstract Objective To evaluate the relative efficacy of programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitors versus conventional drugs in patients with cancer that were PD-L1 positive and PD-L1 negative. Design Meta-analysis of randomised controlled trials. Data sources PubMed, Embase, Cochrane database, and conference abstracts presented at the American Society of Clinical Oncology and European Society of Medical Oncology up to March 2018. Review methods Studies of PD-1 or PD-L1 inhibitors (avelumab, atezolizumab, durvalumab, nivolumab, and pembrolizumab) that had available hazard ratios for death based on PD-L1 positivity or negativity were included. The threshold for PD-L1 positivity or negativity was that PD-L1 stained cell accounted for 1% of tumour cells, or tumour and immune cells, assayed by immunohistochemistry staining methods. Results 4174 patients with advanced or metastatic cancers from eight randomised controlled trials were included in this study. Compared with conventional agents, PD-1 or PD-L1 inhibitors were associated with significantly prolonged overall survival in both patients that were PD-L1 positive (n=2254, hazard ratio 0.66, 95% confidence interval 0.59 to 0.74) and PD-L1 negative (1920, 0.80, 0.71 to 0.90). However, the efficacies of PD-1 or PD-L1 blockade treatment in patients that were PD-L1 positive and PD-L1 negative were significantly different (P=0.02 for interaction). Additionally, in both patients that were PD-L1 positive and PD-L1 negative, the long term clinical benefits from PD-1 or PD-L1 blockade were observed consistently across interventional agent, cancer histotype, method of randomisation stratification, type of immunohistochemical scoring system, drug target, type of control group, and median follow-up time. Conclusions PD-1 or PD-L1 blockade therapy is a preferable treatment option over conventional therapy for both patients that are PD-L1 positive and PD-L1 negative. This finding suggests that PD-L1 expression status alone is insufficient in determining which patients should be offered PD-1 or PD-L1 blockade therapy.

scholarly journals Prognostic Value of Lactate Dehydrogenase in Patients with Hepatocellular Carcinoma: A Meta-Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Weihao Kong ◽  
Xiaomin Zuo ◽  
Hao Liang ◽  
Jingxiong Hu ◽  
Huabing Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Sensitivity Analysis ◽  
Lactate Dehydrogenase ◽  
Publication Bias ◽  
Subgroup Analysis ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Free Survival

Background. Previous studies have shown the prognostic value of lactate dehydrogenase (LDH) in hepatocellular carcinoma (HCC), but the results are not persuasive. Therefore, the purpose of our study was to quantitatively explore the prognostic value of LDH in hepatocellular carcinoma.Methods. We searched the Web of Science, Embase, PubMed, and the Cochrane Library for literature published before October 2018 on the prognostic value of LDH in patients with hepatocellular carcinoma. The combined hazard ratios (HRs) and 95% confidence intervals (CIs) were utilized to assess the prognostic value of LDH in overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS) of HCC. Subgroup analysis, sensitivity analysis, and metaregression were used to explore the source of heterogeneity. Funnel plots with Begg’s test and Egger’s test were used to detect potential publication biases. Furthermore, combined odds ratios (ORs) were utilized to assess the correlation between LDH and clinicopathological features.Results. A total of 10 nonrandomized controlled studies were included in this meta-analysis. The combined effects of LDH on HCC patients’ OS, RFS/DFS, and PFS were HR = 2.07, 95% CI: 1.63-2.62, P < 0.001; HR = 1.62, 95% CI: 1.37-1.90, P < 0.001; and HR = 1.96, 95% CI: 1.14-3.36, P = 0.014, respectively. Subgroup analysis and sensitivity analysis showed that the outcome was stable, and the results of the metaregression also identified statistical models as an important source of heterogeneity. Potential publication bias was detected in the OS studies, so the trim-and-fill method was used to explore publication bias, and the results showed stability. Furthermore, the combined OR suggests that LDH was significantly correlated with gender, Child-Pugh grade, alpha-fetoprotein, vascular invasion, and tumor size.Conclusions. Preoperative LDH elevation is significantly associated with poor prognosis in patients with HCC, which may be a promising factor in assessing the prognosis of patients with HCC.

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