PD-1/L1 inhibitors may increase the risk of pericardial disease in non-small-cell lung cancer patients: a meta-analysis and systematic review.

Background: The advent of PD-1/L1 inhibitors has changed the landscape for patients with non-small-cell lung cancer (NSCLC). Meanwhile, the adverse events of PD-1/L1 inhibitors have been focused. Methods: The Cochrane Central Register of Controlled Trials, PubMed and Embase databases and ClinicalTrials.gov were searched from inception to February 2021. Results: 18 studies involving 11,394 patients with NSCLC were included. PD-1/L1 inhibitor monotherapy was associated (relative risk, 95% confidence interval) with an increased risk of pericardial effusion (2.72 [1.45-5.12]; p = 0.002) and cardiac tamponade (2.76 [1.15-6.62]; p = 0.023), whereas PD-1/L1 inhibitors combined with chemotherapy did not increase the risk of pericardial effusion and cardiac tamponade (3.08 [0.93-10.21]; p = 0.066 and 3.27 [0.37-28.94]; p = 0.288, respectively). Conclusion: For patients with NSCLC, treatment with PD-1/L1 inhibitor monotherapy increases the risk of pericardial effusion and cardiac tamponade, but PD-1/L1 inhibitors combined with chemotherapy do not.

In this study, the authors found that the incidence of pericardial effusion and cardiac tamponade in non-small-cell lung cancer patients treated with PD-1/L1 inhibitors was 0.63% and 0.35%, respectively, and in chemotherapy was 0.07% and less than 0.01%, respectively. The authors found that PD-1/L1 inhibitors combined with chemotherapy did not increase the risk of cardiac adverse events (AEs); however, the risk of cardiac AEs with PD-1/L1 inhibitor monotherapy should be considered, and the damage of pembrolizumab to the pericardium needs further attention. The mechanism of pericardial effusion and cardiac tamponade is not well understood, and pseudoprogression cannot be ruled out. Although the incidence of cardiac AEs is low, the prevention and management of immunotherapy should be paid attention to.

Efficacy and safety of sirolimus in the treatment of vascular malformations: A protocol for systematic review and meta-analysis.

BACKGROUND: The pathophysiologic of vascular malformations is still unclear, and the treatment of vascular malformations is a challenge. With improvement in the understanding of pathogenesis of vascular malformations, sirolimus has been a promising and effective treatment. As so far, there is absent convincing evidence to confirm the efficacy of sirolimus for vascular malformations. The purpose of this study was to evaluate the effectiveness and safety of sirolimus in the treatment of vascular malformations. METHODS: The literatures about the management of vascular malformations with sirolimus would be searched from databases of MEDLINE, EMBASE, PubMed, Web of Science, Clinicaltrials.org., Cochrane Library, China Biology Medicine Database (CBM), Wan Fang Database, China National Knowledge Infrastructure Database (CNKI), and VIP Science Technology Periodical Database. We will search each database from inception or 1995 to August 20, 2020. Two researchers worked independently on literature selection, data extraction and quality assessment. The efficacy and safety of sirolimus in the treatment of vascular malformations were the main outcomes. Adverse events after sirolimus were evaluated as the secondary outcomes. The included studies will be analyzed by Review Manager 5.3. If the results are applicable, meta-analysis would also be performed. RESULTS: The study will evaluate the efficacy and safety of sirolimus in the treatment of vascular malformations based on current evidence. CONCLUSION: The conclusion of this study will provide more reliable, evidence-based data for the use of sirolimus in the treatment of vascular malformations. PROSPERO REGISTRATION NUMBER: CRD42020167881.

Adverse cardiac events in the treatment of non-small cell lung cancer with programmed death-1and programmed death-ligand 1 inhibitors: A protocol for systematic review and meta-analysis.

BACKGROUND: Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) inhibitors are immune therapies that have shown great promise in the treatment of multiple cancers. However, immune-related adverse events of PD-1 and PD-L1 inhibitors may limit their use in non-small cell lung cancer (NSCLC). Given the rising number of clinical trials in recent years, it is essential to perform a meta-analysis to provide assess the cardiotoxicity of PD-1/ PD-L1 inhibitors in NSCLC therapy. METHOD AND ANALYSIS: The ClinicalTrials.gov, Embase, PubMed, and Cochrane Central Register of Controlled Trials repositories will be searched from their inception to December 2019. The bibliography of the searching process will be imported into Endnote X9 software. Two reviewers independently will screen the literature, extract data, and conduct the risk of bias for every added study. The data analysis will be analyzed using Stata15.0 software. Specific adverse cardiac events will be identified, with particular attention on atrial fibrillation, cardiac arrest, cardiac failure, and pericarditis. This review will be performed as per the Preferred Reporting Item for Systematic Review and meta-analysis statement recommendations. ETHICS AND DISSEMINATION: This study will provide support for the cardiotoxicity linked to the treatment of NSCLC using PD-1/PD-L1 inhibitors. The data in the meta-analysis will be retrieved from completed and published clinical trials; therefore, ethical review and patient informed consent will not be required. PROSPERO NUMBER: CRD42020156397.

Cardiac adverse events of PD-1 and PD-L1 inhibitors in cancer protocol for a systematic review and network meta-analysis: A protocol for systematic review.

INTRODUCTION: Programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have been increasingly used in the treatment of cancer. Immunosuppressive therapy can control the cancer well and is suitable for the moderate to severe diseases. However, according to clinical observation, immune-related cardiac adverse events against PD-1or/and PD-L1 are inevitable, but generally reversible. Understanding the cardiac adverse events of PD-1 or/and PD-L1 inhibitors is crucial to improve the anti-cancer efficacy and ensure the life safety of patients. The variability of cardiac adverse events between different immunosuppressants and different cancers is not clear. METHODS AND ANALYSIS: This protocol established in this study has been reported following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. We will search the following electronic bibliographic databases: PubMed, Cochrane Library, EMBASE databases and ClinicalTrials.gov from their inception to December 2019. We will use a combination of Medical Subject Heading, and free-text terms with various synonyms to search based on the Eligibility criteria. We will include RCTs on PD-1 or/and PD-L1 inhibitors therapy to analyze. In addition, our study will include some clinical trials. All relevant RCTs will be included, such as early phase I/II, phase III experimental trials, prospective and retrospective observational studies. According to the inclusion and exclusion criteria outlined above, the full texts of each eligible study will be retrieved for further identification by one reviewer. Two authors will screen the titles and abstracts of all records retrieved in above electronic databases independently to find potentially eligible reviews. Data will be extracted by 2 reviewers independently using a pre-designed data extraction form. The other reviewer will validate data. I-square (I) test, substantial heterogeneity, sensitivity analysis and publication bias assessment will be performed accordingly. For our network meta-analysis, we will use Stata 15.0 and WinBUGS 1.4.3. ETHICS AND DISSEMINATION: Ethics approval and patient consent would be not required because the data of this network meta-analysis mainly are obtained from existing resources. This network meta-analysis will be published in a peer-reviewed journal. PROSPERO NUMBER: CRD42019142865.