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International Journal of Molecular... Mar 2023This systematic review aimed to assess the prognostic significance of programmed cell death-ligand 1 (PDL-1) and programmed cell death protein 1 (PD-1) in hepatocellular... (Meta-Analysis)
Meta-Analysis Review
Navigating through the PD-1/PDL-1 Landscape: A Systematic Review and Meta-Analysis of Clinical Outcomes in Hepatocellular Carcinoma and Their Influence on Immunotherapy and Tumor Microenvironment.
This systematic review aimed to assess the prognostic significance of programmed cell death-ligand 1 (PDL-1) and programmed cell death protein 1 (PD-1) in hepatocellular carcinoma (HCC). Medline, EMBASE, and Cochrane Library database searches were conducted, revealing nine relevant cohort studies (seven PDL-1 and three PD-1). Our meta-analysis showed that PD-1/PDL-1 was a marker of poor survival, regardless of the assessment method (PD-1 overall survival (OS): hazard ratio (HR) 2.40; 95% confidence interval (CI), 1.30-4.42; disease-free survival (DFS): HR 2.12; 95% CI, 1.45-3.10; PDL-1: OS: HR 3.61; 95% CI, 2.75-4.75; and DFS: HR 2.74; 95% CI, 2.09-3.59). Additionally, high level of PD-1/PDL-1 expression was associated with aging, multiple tumors, high alpha-fetoprotein levels, and advanced Barcelona Clinic Liver Cancer stage. This high level significantly predicted a poor prognosis for HCC, suggesting that anti-PD-1 therapy is plausible for patients with HCC. Furthermore, HIF-1 induces PD-1 expression, and PD1SOCS3 is associated with a better prognosis. Taken together, combination therapy may be the key to effective immunotherapy. Thus, exploring other markers, such as HIF-1 and SOCS3, along with PD-1/PDL-1 immunotherapy, may lead to improved outcomes.
Topics: Humans; B7-H1 Antigen; Biomarkers, Tumor; Carcinoma, Hepatocellular; Immunotherapy; Ligands; Liver Neoplasms; Tumor Microenvironment; Programmed Cell Death 1 Receptor
PubMed: 37047482
DOI: 10.3390/ijms24076495 -
Critical Reviews in Oncology/hematology Dec 2023The use of neoadjuvant or perioperative anti-PD(L)1 was recently tested in multiple clinical trials. We performed a systematic review and meta-analysis of randomised... (Meta-Analysis)
Meta-Analysis
Surgical and survival outcomes with perioperative or neoadjuvant immune-checkpoint inhibitors combined with platinum-based chemotherapy in resectable NSCLC: A systematic review and meta-analysis of randomised clinical trials.
The use of neoadjuvant or perioperative anti-PD(L)1 was recently tested in multiple clinical trials. We performed a systematic review and meta-analysis of randomised trials comparing neoadjuvant or perioperative chemoimmunotherapy to neoadjuvant chemotherapy in resectable NSCLC. Nine reports from 6 studies were included. Receipt of surgery was more frequent in the experimental arm (odds ratio, OR 1.39) as was pCR (OR 7.60). EFS was improved in the experimental arm (hazard ratio, HR 0.55) regardless of stage, histology, PD-L1 expression (PD-L1 negative, HR 0.74) and smoking exposure (never smokers, HR 0.67), as was OS (HR 0.67). Grade > = 3 treatment-related adverse events were more frequent in the experimental arm (OR 1.22). The experimental treatment improved surgical outcomes, pCR rates, EFS and OS in stage II-IIIB, EGFR/ALK negative resectable NSCLC; confirmatory evidence is warranted for stage IIIB tumours and with higher maturity of the OS endpoint.
Topics: Humans; B7-H1 Antigen; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Lung Neoplasms; Neoadjuvant Therapy; Platinum; Randomized Controlled Trials as Topic
PubMed: 37871779
DOI: 10.1016/j.critrevonc.2023.104190 -
Inflammation Research : Official... Mar 2024The availability of robust biomarkers of endothelial activation might enhance the identification of subclinical atherosclerosis in rheumatoid arthritis (RA). We... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The availability of robust biomarkers of endothelial activation might enhance the identification of subclinical atherosclerosis in rheumatoid arthritis (RA). We investigated this issue by conducting a systematic review and meta-analysis of cell adhesion molecules in RA patients.
METHODS
We searched electronic databases from inception to 31 July 2023 for case-control studies assessing the circulating concentrations of immunoglobulin-like adhesion molecules (vascular cell, VCAM-1, intercellular, ICAM-1, and platelet endothelial cell, PECAM-1, adhesion molecule-1) and selectins (E, L, and P selectin) in RA patients and healthy controls. Risk of bias and certainty of evidence were assessed using the JBI checklist and GRADE, respectively.
RESULTS
In 39 studies, compared to controls, RA patients had significantly higher concentrations of ICAM-1 (standard mean difference, SMD = 0.81, 95% CI 0.62-1.00, p < 0.001; I = 83.0%, p < 0.001), VCAM-1 (SMD = 1.17, 95% CI 0.73-1.61, p < 0.001; I = 95.8%, p < 0.001), PECAM-1 (SMD = 0.82, 95% CI 0.57-1.08, p < 0.001; I = 0.0%, p = 0.90), E-selectin (SMD = 0.64, 95% CI 0.42-0.86, p < 0.001; I = 75.0%, p < 0.001), and P-selectin (SMD = 1.06, 95% CI 0.50-1.60, p < 0.001; I = 84.8%, p < 0.001), but not L-selectin. In meta-regression and subgroup analysis, significant associations were observed between the effect size and use of glucocorticoids (ICAM-1), erythrocyte sedimentation rate (VCAM-1), study continent (VCAM-1, E-selectin, and P-selectin), and matrix assessed (P-selectin).
CONCLUSIONS
The results of our study support a significant role of cell adhesion molecules in mediating the interplay between RA and atherosclerosis. Further studies are warranted to determine whether the routine use of these biomarkers can facilitate the detection and management of early atherosclerosis in this patient group. PROSPERO Registration Number: CRD42023466662.
Topics: Humans; Intercellular Adhesion Molecule-1; Vascular Cell Adhesion Molecule-1; Platelet Endothelial Cell Adhesion Molecule-1; E-Selectin; P-Selectin; Cell Adhesion Molecules; Arthritis, Rheumatoid; Biomarkers; Atherosclerosis
PubMed: 38240792
DOI: 10.1007/s00011-023-01837-6 -
JAMA Network Open Apr 2024Randomized clinical trials (RCTs) with neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy (ICI-chemotherapy) for patients with early-stage non-small cell... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Randomized clinical trials (RCTs) with neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy (ICI-chemotherapy) for patients with early-stage non-small cell lung cancer (NSCLC) have reported consistent associations with event-free survival (EFS) and pathologic complete response (pCR) pending longer follow-up for overall survival data.
OBJECTIVE
To assess the pooled benefit of ICI-chemotherapy in 2-year EFS and pCR among patients with NSCLC and examine the impact of clinical, pathologic, and treatment-related factors.
DATA SOURCES
Full-text articles and abstracts in English were searched in EMBASE, PubMed, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews through November 1, 2023, and in oncology conference proceedings from January 1, 2008, to November 1, 2023.
STUDY SELECTION
Phase 2 or 3 RCTs with neoadjuvant ICI-chemotherapy with or without adjuvant ICIs vs neoadjuvant chemotherapy alone with or without placebo or observation in patients with previously untreated NSCLC staged IB to IIIB were included.
DATA EXTRACTION AND SYNTHESIS
Data extraction of prespecified data elements was performed by 2 reviewers using a structured data abstraction electronic form. A random-effects model was used for meta-analysis. The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline.
MAIN OUTCOMES AND MEASURES
Two-year EFS and pCR were the outcomes of interest in patients who received neoadjuvant ICI-chemotherapy (experimental arm) or neoadjuvant chemotherapy alone (control arm). Aggregated pooled hazard ratios (HRs) for time-to-event outcomes (2-year EFS) and risk ratios (RRs) for dichotomous outcomes (pCR) with their respective 95% CIs were calculated.
RESULTS
Eight trials with 3387 patients were included, with some concerns of risk of bias as assessed by the Cochrane Collaboration method, mainly related to outcomes measurements. Neoadjuvant ICI-chemotherapy was associated with improved 2-year EFS (HR, 0.57; 95% CI, 0.50-0.66; P < .001) and increased pCR rate (RR, 5.58; 95% CI, 4.27-7.29; P < .001) in the experimental vs control treatment arms. This association was not significantly modified by the main patient characteristics; tumor- or treatment-related factors, including tumor programmed cell death ligand 1 (PD-L1) status; type of platinum-compound chemotherapy; number of cycles of neoadjuvant ICI-chemotherapy; or addition of adjuvant ICIs. Patients whose tumor cells were negative for PD-L1 were at higher risk of relapse (HR, 0.75; 95% CI, 0.62-0.91) than were those with low (HR, 0.61; 95% CI, 0.37-0.71) or high PD-L1 (HR, 0.40; 95% CI, 0.27-0.58) (P = .005).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis of neoadjuvant ICI-chemotherapy RCTs in patients with early-stage NSCLC, 3 cycles of neoadjuvant platinum-based ICI-chemotherapy were associated with a meaningful improvement in 2-year EFS and pCR.
Topics: Humans; Neoadjuvant Therapy; Carcinoma, Non-Small-Cell Lung; B7-H1 Antigen; Neoplasm Recurrence, Local; Immunotherapy; Small Cell Lung Carcinoma; Adjuvants, Immunologic; Lung Neoplasms
PubMed: 38625698
DOI: 10.1001/jamanetworkopen.2024.6837 -
PloS One 2015Numerous agents targeting PD-L1/PD-1 check-point are in clinical development. However, the correlation between PD-L1 expression and prognosis of solid tumor is still in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Numerous agents targeting PD-L1/PD-1 check-point are in clinical development. However, the correlation between PD-L1 expression and prognosis of solid tumor is still in controversial. Here, we elicit a systematic review and meta-analysis to investigate the potential value of PD-L1 in the prognostic prediction in human solid tumors.
METHODS
Electronic databases were searched for studies evaluating the expression of PD-L1 and overall survival (OS) of patients with solid tumors. Odds ratios (ORs) from individual studies were calculated and pooled by using a random-effect model, and heterogeneity and publication bias analyses were also performed.
RESULTS
A total of 3107 patients with solid tumor from 28 published studies were included in the meta-analysis. The median percentage of solid tumors with PD-L1 overexpression was 52.5%. PD-L1 overexpression was associated with worse OS at both 3 years (OR = 2.43, 95% confidence interval (CI) = 1.60 to 3.70, P < 0.0001) and 5 years (OR = 2.23, 95% CI = 1.40 to 3.55, P = 0.0008) of solid tumors. Among the tumor types, PD-L1 was associated with worse 3 year-OS of esophageal cancer, gastric cancer, hepatocellular carcinoma, and urothelial cancer, and 5 year-OS of esophageal cancer, gastric cancer and colorectal cancer.
CONCLUSIONS
These results suggest that expression of PD-L1 is associated with worse survival in solid tumors. However, the correlations between PD-L1 and prognosis are variant among different tumor types. More studies are needed to investigate the clinical value of PD-L1 expression in prognostic prediction and treatment option.
Topics: B7-H1 Antigen; Disease-Free Survival; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Neoplasm Proteins; Neoplasms; Survival Rate
PubMed: 26114883
DOI: 10.1371/journal.pone.0131403 -
Current Oncology (Toronto, Ont.) May 2023Cutaneous angiosarcoma (CAS) is the most common type of angiosarcoma that predominantly affects older Caucasians. The outcomes of immunotherapy in CAS are currently... (Meta-Analysis)
Meta-Analysis Review
Cutaneous angiosarcoma (CAS) is the most common type of angiosarcoma that predominantly affects older Caucasians. The outcomes of immunotherapy in CAS are currently under investigation in relation to the expression of programmed death ligand 1 (PD-L1) and other biomarkers. We performed a systematic review and metanalysis of data from the current literature reporting on PD-L1 immunohistochemistry expression. A systematic search of publications in the electronic databases PubMed, Web of Science, and Scopus was conducted using the following terms: "PD-L1" and "angiosarcomas". A total of ten studies reporting on 279 cases were identified and included in the meta-analysis. The pooled prevalence of PD-L1 expression in CAS was 54% (95% CI 36-71%), with high heterogeneity (I = 84.81%, < 0.001). In sub-group analysis, the proportion of PD-L1 expression in CAS was significantly ( = 0.049) lower in Asian studies (ES = 35%, 95% CI 28-42%, I = 0.0%, = 0.46) than in European studies (ES = 71%, 95% CI 51-89%, I = 48.91%, = 0.12).
Topics: Humans; Hemangiosarcoma; Skin Neoplasms; B7-H1 Antigen
PubMed: 37232846
DOI: 10.3390/curroncol30050388 -
Frontiers in Endocrinology 2023The optimal first-line immune checkpoint inhibitor (ICI) treatment strategy for metastatic or early triple-negative breast cancer (TNBC) has not yet been determined as a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The optimal first-line immune checkpoint inhibitor (ICI) treatment strategy for metastatic or early triple-negative breast cancer (TNBC) has not yet been determined as a result of various randomized controlled trials (RCTs). The purpose of this study was to compare the efficacy and safety of ICIs in patients with metastatic or early TNBC.
METHODS
RCTs comparing the efficacy and safety of ICIs in patients with TNBC were included in the studies. Based on PRISMA guidelines, we estimated pooled hazard ratios (HRs) and odds ratios (ORs) using random-effects models of Bayesian network meta-analysis. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included pathologic complete response rate (pCR), grade ≥ 3 treatment-related adverse events (trAEs), immune-related adverse events (irAEs), and grade ≥ 3 irAEs.
RESULTS
The criteria for eligibility were met by a total of eight RCTs involving 4,589 patients with TNBC. When ICIs were used in patients without programmed death-ligand 1 (PD-L1) selection, there was a trend toward improved PFS, OS, and pCR, without significant differences. Pembrolizumab plus chemotherapy is superior to other treatment regimens in terms of survival for TNBC patients based on Bayesian ranking profiles. Subgroup analysis by PD-L1 positive population indicated similar results, and atezolizumab plus chemotherapy provided better survival outcomes. Among grade ≥ 3 trAEs and any grade irAEs, there was no statistically significant difference among different ICI agents. The combination of ICIs with chemotherapy was associated with a higher incidence of grade ≥ 3 irAEs. Based on rank probability, the ICI plus chemotherapy group was more likely to be associated with grade ≥ 3 trAEs, any grade irAEs, and grade ≥ 3 irAEs. Hypothyroidism and hyperthyroidism were the most frequent irAEs in patients receiving ICI.
CONCLUSIONS
ICI regimens had relatively greater efficacy and safety profile. Pembrolizumab plus chemotherapy and atezolizumab plus chemotherapy seem to be superior first-line treatments for intention-to-treat and PD-L1-positive TNBC patients, respectively. It may be useful for making clinical decisions to evaluate the efficacy and safety of different ICIs based on our study.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022354643.
Topics: Humans; Immune Checkpoint Inhibitors; Triple Negative Breast Neoplasms; B7-H1 Antigen; Network Meta-Analysis; Decision Making
PubMed: 37229447
DOI: 10.3389/fendo.2023.1137464 -
Medicina (Kaunas, Lithuania) Jul 2022Pancreatic cystic lesions (PCLs) are frequently incidental findings. The prevalence of PCLs is increasing, mainly due to advancements in imaging techniques, but also... (Review)
Review
Pancreatic cystic lesions (PCLs) are frequently incidental findings. The prevalence of PCLs is increasing, mainly due to advancements in imaging techniques, but also because of the aging of the population. PCLs comprise challenging clinical problems, as their manifestations vary from benign to malignant lesions. Therefore, the recognition of PCLs is achieved through a complex diagnostic and surveillance process, which in turn is usually long-term, invasive, and expensive. Despite the progress made in the identification of novel biomarkers in the cystic fluid that also support the differentiation of PCLs, their application in clinical practice is limited. We conducted a systematic review of the literature published in two databases, Pubmed and Embase, on biochemical biomarkers in PCLs that may be applied in the diagnostic algorithms of PCLs. Eleven studies on intracystic glucose, twenty studies on intracystic carcinoembryonic antigen (CEA), and eighteen studies on other biomarkers were identified. Low levels of intracystic glucose had high sensitivity and specificity in the differentiation between mucinous and non-mucinous cystic neoplasms. CEA and glucose are the most widely studied fluid biochemical markers in pancreatic cystic lesions. Glucose has better diagnostic accuracy than CEA. Other biochemical biomarkers require further research.
Topics: Biomarkers, Tumor; Carcinoembryonic Antigen; Diagnosis, Differential; Glucose; Humans; Pancreatic Cyst; Pancreatic Neoplasms
PubMed: 35893110
DOI: 10.3390/medicina58080994 -
Annals of Surgical Oncology Jan 2023Almost one-third of colorectal cancer (CRC) patients experience recurrence after resection; nevertheless, follow-up strategies remain controversial. We sought to... (Meta-Analysis)
Meta-Analysis Review
Circulating Tumor DNA, Imaging, and Carcinoembryonic Antigen: Comparison of Surveillance Strategies Among Patients Who Underwent Resection of Colorectal Cancer-A Systematic Review and Meta-analysis.
BACKGROUND
Almost one-third of colorectal cancer (CRC) patients experience recurrence after resection; nevertheless, follow-up strategies remain controversial. We sought to systematically assess and compare the accuracy of carcinoembryonic antigen (CEA), imaging [positron emission tomography (PET) and computed tomography (CT) scans], and circulating tumor DNA (CtDNA) as surveillance strategies.
PATIENTS AND METHODS
PubMed, Medline, Embase, Scopus, Cochrane, Web of Science, and CINAHL were systematically searched. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used to assess methodological quality. We performed a bivariate random-effects meta-analysis and reported pooled sensitivity, specificity, and diagnostic odds ratio (DOR) values for each surveillance strategy.
RESULTS
Thirty studies were included in the analysis. PET scans had the highest sensitivity to detect recurrence (0.95; 95%CI 0.91-0.97), followed by CT scans (0.77; 95%CI 0.67-0.85). CtDNA positivity had the highest specificity to detect recurrence (0.95; 95%CI 0.91-0.97), followed by increased CEA levels (0.88; 95%CI 0.82-0.92). Furthermore, PET scans had the highest DOR to detect recurrence (DOR 120.7; 95%CI 48.9-297.9) followed by CtDNA (DOR 37.6; 95%CI 20.8-68.0).
CONCLUSION
PET scans had the highest sensitivity and DOR to detect recurrence, while CtDNA had the highest specificity and second highest DOR. Combinations of traditional cross-sectional/functional imaging and newer platforms such as CtDNA may result in optimized surveillance of patients following resection of CRC.
Topics: Humans; Carcinoembryonic Antigen; Circulating Tumor DNA; Cross-Sectional Studies; Colorectal Neoplasms
PubMed: 36219278
DOI: 10.1245/s10434-022-12641-7 -
Medicine Feb 2018The aim of this study was to evaluate the association of human leukocyte antigen (HLA)-DQ and HLA-DQA1/DQB1 alleles with Vogt-Koyanagi-Harada (VKH), providing further... (Review)
Review
OBJECTIVE
The aim of this study was to evaluate the association of human leukocyte antigen (HLA)-DQ and HLA-DQA1/DQB1 alleles with Vogt-Koyanagi-Harada (VKH), providing further evidences on the genetic background of this disease.
METHODS
A comprehensive literature search was conducted on the relationship of HLA-DQ and/or HLA-DQA1/DQB1 alleles with VKH through PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, VIP, and databases for grey literature. The last search was in October 2017. Pooled odds ratio (OR) with 95% confidence interval (95% CI) was calculated from extracted data to access the strength of the association between a genotype and VKH.
RESULTS
HLA-DQ4 was confirmed to increase the risk of VKH significantly (OR = 4.63, 95% CI: 1.74-12.31, P = .002), while HLA-DQ1 seemed to reduce VKH occurrence with OR = 0.32 (95% CI: 0.22-0.47, P < .00001). HLA-DQA1*0301-(OR = 4.52, 95% CI: 1.42-14.35, P = .01) and HLA-DQB1*0401-(OR = 23.12, 95% CI: 11.54-46.31, P < .00001) positive patients probably had a rising tendency to suffer from VKH. Alleles including HLA-DQA1*0103, 0401, 0501 and HLA-DQB1*0301, 0402, 0601, 0603 were significant protective genetic factors.
CONCLUSION
We concluded that HLA-DQ4 carriers had a higher risk of VKH and HLA-DQ1 seemed to be protective. People with positive HLA-DQA1*0301 and HLA-DQB1*0401 demonstrated to be more susceptible to VKH. HLA-DQA1*0103, 0401, 0501 and HLA-DQB1*0301, 0402, 0601, 0603 could be potential protectors.
Topics: Genetic Predisposition to Disease; HLA-DQ Antigens; HLA-DQ alpha-Chains; HLA-DQ beta-Chains; Humans; Protective Factors; Uveomeningoencephalitic Syndrome
PubMed: 29443768
DOI: 10.1097/MD.0000000000009914