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International Journal of Surgery... Jun 2023Available evidence shows that the incidence of toxicities associated with cancer immunotherapy, such as programmed cell death 1 (PD-1) and programmed cell death 1 ligand... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Available evidence shows that the incidence of toxicities associated with cancer immunotherapy, such as programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1)-related toxicities, is estimated to be between 0.3 and 1.3%.
OBJECTIVE
This systematic review aimed to investigate cancer patients' susceptibility to toxicities associated with PD-1/PD-L1 inhibitors and establish a clinically relevant landscape of side effects of PD-1/PD-L1 inhibitors.
DATA SOURCES
Relevant publications from PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Infrastructure (CNKI) between 2014 and 2019.
STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS
We searched randomized controlled trials (RCTs) reporting treatment-related toxicities associated with PD-1 and PD-L1 inhibitors in the treatment of cancers. The primary endpoint was to assess the difference in the incidences of toxicities between cancer patients who did and did not receive PD-1/PD-L1 inhibitors. A total of 29 RCTs, incorporating 8576 patients, met the eligibility criteria.
STUDY APPRAISAL AND SYNTHESIS METHODS
We calculated the pooled relative risks and corresponding 95% CIs using a random-effects model and assessed the heterogeneity between different groups. The subgroup analyses were conducted based on cancer type, toxicity grade (severity), system and organ, treatment regimens in the intervention arm and the control arm, PD-1/PD-L1 inhibitor drug type, and cancer type.
RESULTS
A total of 11 categories (e.g. endocrine toxicity), and 39 toxicity types (e.g. hyperthyroidism) were identified. For toxicities at any grade, those treated with PD-1/PD-L1 inhibitors were at lower risks for gastrointestinal toxicity, hematologic toxicity, and treatment event leading to discontinuation; and were at higher risks for respiratory toxicity (all P <0.05). Those treated with PD-1/PD-L1 inhibitors were at lower risks for fatigue, asthenia, and peripheral edema and were at higher risks for pyrexia, cough, dyspnea, pneumonitis, and pruritus.
LIMITATIONS
The present research is a meta-analysis at the study level rather than at the patient level; insights on risk factors associated with the development of toxicities cannot be found in our study. There was a possible overlap in Common Terminology Criteria for Adverse Events (CTCAE) definitions which prevents understanding the true rates of specific toxicities.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
For most toxicity types based on system and organ, the incidence proportions for patients in the intervention arm were lower than those in the control arm, which suggested the general safety of PD-1/PD-L1 inhibitors against conventional chemotherapy and cytotoxic t-lymphocyte-associated protein 4 (CTLA-4) inhibitors. Future research should focus on taking effective targeted measures to decrease the risks of different toxicities for different patient populations.
SYSTEMATIC REVIEW REGISTRATION NUMBER
We registered the research protocol with PROSPERO (registration number CRD42019135113).
Topics: Humans; Immune Checkpoint Inhibitors; Programmed Cell Death 1 Receptor; Neoplasms; Risk; Incidence
PubMed: 37132038
DOI: 10.1097/JS9.0000000000000368 -
Frontiers in Immunology 2023Immunotherapy has revolutionized the treatment paradigm of many cancers, however, its effectiveness in prostate cancer patients is still under question. In the present... (Meta-Analysis)
Meta-Analysis Review
Immunotherapy has revolutionized the treatment paradigm of many cancers, however, its effectiveness in prostate cancer patients is still under question. In the present systematic review and meta-analysis, we sought for assessing the efficacy and safety of Immune checkpoint inhibitors (ICIs) in patients with prostate cancer. PubMed, Scopus, Web of Science, and EMBASE databases were searched on Aguste 19, 2022. Thirty five studies met the eligibility criteria. The median overall survival (mOS) of all treatments was 14.1 months, with the longest and shortest mOS was seen among patients who received anti-CTLA-4 monotherapy and anti-PD-1/PD-L1+anti-CTLA-4 regimen at 24.9 and 9.2 months, respectively. Noteworthy, all types of adverse events had the lowest incidence in the anti-PD-1/PD-L1 monotherapy group. Considering the ICI monotherapy regimens, we found that fatigue, diarrhea, and infusion reaction had the highest incidence rates. Future studies evaluating the efficacy and safety of novel combination therapies with ICIs are warranted.
Topics: Male; Humans; Immune Checkpoint Inhibitors; B7-H1 Antigen; Prostatic Neoplasms; Combined Modality Therapy; Databases, Factual
PubMed: 38022569
DOI: 10.3389/fimmu.2023.1181051 -
Medicine Aug 2018Published studies have reported conflicting and heterogeneous results regarding the association between human leukocyte antigen (HLA)-DRB1 polymorphisms and alopecia... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Published studies have reported conflicting and heterogeneous results regarding the association between human leukocyte antigen (HLA)-DRB1 polymorphisms and alopecia areata (AA). This study aimed to review and quantitatively analyze the association between HLA-DRB1 polymorphisms and AA.
METHODS
In this study, all relevant publications were searched through December 2016. Odds ratios (ORs) and confidence intervals (CIs) for comparisons between case and control groups were calculated. Stata 14.0 software was used to perform statistical analysis. This research does not require formal ethical approval because the data used in this analysis do not involve personal information and thus do not affect privacy.
RESULTS
Twelve articles were identified. For HLA-DRB1*04 and HLA-DRB1*16 polymorphisms, the OR (95% CIs) was 1.49 (1.24-1.78) and 1.61 (1.08-2.41), and P was <.01 and <.01, respectively. For HLA-DRB1*0301, HLA-DRB1*09, and HLA-DRB1*13 polymorphisms, the OR (95% CIs) was 0.42 (0.28-0.63), 0.74 (0.55-0.99), and 0.62 (0.40-0.98), and P was <.01, <.01, and <.01, respectively. Statistical evidence revealed no publication bias (P > .05).
CONCLUSION
The present meta-analysis suggested that HLA-DRB1*04 and HLA-DRB1*16 polymorphisms might be associated with increased AA risk, while HLA-DRB1*0301, HLA-DRB1*09, and HLA-DRB1*13 polymorphisms might decrease the AA risk. Studies with adequate methodological quality on gene-gene and gene-environment interactions are needed to validate the results in the future.
Topics: Alleles; Alopecia Areata; Case-Control Studies; Genetic Predisposition to Disease; HLA-DRB1 Chains; Humans; Odds Ratio; Polymorphism, Single Nucleotide
PubMed: 30095639
DOI: 10.1097/MD.0000000000011790 -
Frontiers in Immunology 2023The combination of nanoparticle albumin-bound paclitaxel (nab-PTX)/paclitaxel (PTX) with immune checkpoint inhibitors (ICIs) has demonstrated significant efficacy in... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The combination of nanoparticle albumin-bound paclitaxel (nab-PTX)/paclitaxel (PTX) with immune checkpoint inhibitors (ICIs) has demonstrated significant efficacy in cancer patients. However, the safety of these combination regimens remains conflicting in former researches. Therefore, in order to address this issue, we performed a systematic review and network meta-analysis (NMA) to evaluate and compare the safety profile.
METHODS
We performed a systematic review by searching randomized controlled trials (RCTs) from PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, and Web of Science up to August 15, 2022. The primary outcomes were all-grade (grade 1-5) and high-grade (grade 3-5) immune-related adverse events (irAEs). Secondary outcomes were all-grade (grade 1-5) and high-grade (grade 3-5) irAEs of subgroups of ICIs.
RESULTS
There were 22 RCTs included in the NMA, involving a total of 15 963 patients diagnosed with any type of cancer. ICIs+nab-PTX was associated with a noticeably decreased risk of grade 3-5 pneumonitis (odds ratio [OR]=0.28, 95% credible interval [CrI]: 0.09,0.90) compared to ICI monotherapy; ICIs+PTX showed a lower risk of grade 1-5 hyperthyroidism (OR=0.46, 95% CrI: 0.22-0.96) and grade 1-5 hypothyroidism (OR=0.49, 95% CrI: 0.26-0.93) than ICIs. Compared with PD-1, PD-1+PTX was associated with a statistically significantly lower risk of grade 1-5 pneumonitis (OR=0.32, 95% CrI: 0.11-0.92). PD-L1 resulted in a noticeably lower risk of grade 1-5 hypothyroidism (OR=0.34, 95% CrI: 0.12-1.00) than PD-L1+PTX. Nearly all treatment regimens containing ICIs demonstrated significantly higher risks of irAEs compared to the standard chemotherapy groups.
CONCLUSION
Nab-PTX/PTX+ICIs demonstrated an approach leading to decreased risk of irAEs compared with ICI monotherapy. This finding supports that ICIs+nab-PTX/PTX may be a safer treatment strategy. Moreover, we also found that the combination regimens containing ICIs had a higher risk of irAEs than standard chemotherapy. Additionally, ICIs+nab-PTX demonstrated a decreased risk of irAEs compared to ICIs+PTX. PD-1 inhibitors were associated with a higher risk of irAEs than PD-L1 inhibitors.
Topics: Humans; Immune Checkpoint Inhibitors; B7-H1 Antigen; Antineoplastic Agents, Immunological; Programmed Cell Death 1 Receptor; Network Meta-Analysis; Neoplasms; Paclitaxel; Hypothyroidism; Pneumonia
PubMed: 37520574
DOI: 10.3389/fimmu.2023.1175809 -
Frontiers in Immunology 2023Graves' disease (GD) and Graves' orbitopathy (GO) development were suspected to be HLA-related in both Asian and Caucasian populations. However, most studies were...
INTRODUCTION
Graves' disease (GD) and Graves' orbitopathy (GO) development were suspected to be HLA-related in both Asian and Caucasian populations. However, most studies were performed with application of serological methods or low resolution genetic typing, which led to inconsistent results even among the same population. The present review is intended to summarize the state-of-art knowledge on the HLA significance in GD and GO in Asians and Caucasians, as well as to find the most significant alleles for each of the populations.
METHODS
PubMed was searched for relevant articles using the following search terms: HLA plus thyroid-associated ophthalmopathy or Graves' disease or Graves' orbitopathy or thyroid eye disease or thyroid-associated orbitopathy.
RESULTS
In Asian population GD was found to be associated mostly with , , , , , and , while , , are potentially protective. can be considered associated with increased risk of GO in Asians, while may play protective role. In Caucasians, , , are associated with GD risk while , may be protective. Significance of HLA in the course of GD and novel aspects of HLA amino acid variants and potential HLA-based treatment modalities were also discussed.
Topics: Humans; Graves Ophthalmopathy; HLA-DQ Antigens; HLA-DRB1 Chains; Haplotypes; Graves Disease; HLA-B Antigens
PubMed: 37841270
DOI: 10.3389/fimmu.2023.1256922 -
Seizure Nov 2022Antiepileptic drugs (AEDs) are extensively used to manage epilepsy and other comorbidities associated with seizures. Human Leukocyte Antigen (HLA) has a strong... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Antiepileptic drugs (AEDs) are extensively used to manage epilepsy and other comorbidities associated with seizures. Human Leukocyte Antigen (HLA) has a strong association with AED-induced severe cutaneous adverse drug reactions.
OBJECTIVE
We aimed to perform a systematic review and meta-analysis to identify, critically evaluate, and synthesize the best possible evidence on HLA-associated AED-induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN).
METHODS
MEDLINE/PubMed, Scopus, and the Cochrane Library were searched for literature from inception up to July 2022. We included case control studies analyzing association between HLA and AED-induced SJS/TEN. We assessed the studies' risk of bias in using Quality of genetic studies (Q-genie) tool. Outcomes focused on association (risk) between HLA and AED-induced SJS/TEN. The estimated risk was presented in the form of odds ratio (OR).
RESULTS
We included 37 studies (51,422 participants; 7027 cases and 44,395 controls). There was a significantly higher risk of Carbamazepine-induced SJS/TEN with HLA-A (OR: 1.50; 95% CI: 1.03 to 2.17), HLA-B (OR: 1.94; 95% CI: 1.45 to 2.58), HLA-C (OR: 7.83; 95% CI: 4.72 to 12.98), and HLA-DRB1 (OR: 2.82; 95% CI: 1.94 to 4.12). Lamotrigine-induced SJS/TEN posed a higher risk with HLA-A (OR: 2.38; 95% CI: 1.26 to 4.46) and HLA-B (OR: 2.79; 95% CI: 1.75 to 4.46). Phenytoin-induced SJS/TEN showed a higher risk with HLA-A (OR: 3.47; 95% CI: 2.17 to 5.56), HLA-B (OR: 1.72; 95% CI: 1.38 to 2.15), and HLA-C (OR: 2.92; 95% CI: 1.77 to 4.83). Phenobarbital-induced SJS/TEN had a higher risk with HLA-A (OR: 6.98; 95% CI: 1.81 to 26.84), HLA-B (OR: 2.40; 95% CI: 1.39 to 4.17), and HLA-C (OR: 3.37; 95% CI: 1.03 to 11.01). Zonisamide-induced SJS/TEN was significantly associated with HLA-A*02:07 (OR: 9.77; 95% CI: 3.07 to 31.1), HLA-B*46:01 (OR: 6.73; 95% CI: 2.12 to 21.36), and HLA-DRB1×08:03 (OR: 3.78; 95% CI: 1.20 to 11.97). All other alleles of HLA were observed to have a non-significant association with AED-induced SJS/TEN. All included studies were of good quality, with a score of >50 and a mean score of 54.96 out of 77.
CONCLUSION
Our study showed a significant association between few variants of HLA alleles and AED-induced SJS/TEN. Evidences from our study could help in population-based studies and in implementation of individualized treatment regimens. These findings could be part of translational research helping in precision therapy.
Topics: Humans; Stevens-Johnson Syndrome; HLA-DRB1 Chains; HLA-C Antigens; Asian People; HLA-B Antigens; Anticonvulsants; HLA Antigens
PubMed: 36183454
DOI: 10.1016/j.seizure.2022.09.011 -
Transplant International : Official... Aug 2014Allocation of donors with regard to human leukocyte antigen (HLA) is controversial in heart transplantation. This paper is a systematic review and meta-analysis of the... (Meta-Analysis)
Meta-Analysis Review
Allocation of donors with regard to human leukocyte antigen (HLA) is controversial in heart transplantation. This paper is a systematic review and meta-analysis of the available evidence. PubMed, Embase, and the Cochrane Library were searched systematically for studies that addressed the effects of HLA matching on outcome after heart transplantation. Fifty-seven studies met the eligibility criteria. 34 studies had graft rejection as outcome, with 26 of the studies reporting a significant reduction in graft rejection with increasing degree of HLA matching. Thirteen of 18 articles that reported on graft failure found that it decreased significantly with increasing HLA match. Two multicenter studies and nine single-center studies provided sufficient data to provide summary estimates at 12 months. Pooled comparisons showed that graft survival increased with fewer HLA-DR mismatches [0-1 vs. 2 mismatches: risk ratio (RR) = 1.09 (95% confidence interval (CI): 1.01-1.19; P = 0.04)]. Having fewer HLA-DR mismatches (0-1 vs. 2) reduced the incidence of acute rejection [(RR = 0.81 (0.66-0.99; P = 0.04)]. Despite the considerable heterogeneity between studies, the short observation time, and older data, HLA matching improves graft survival in heart transplantation. Prospective HLA-DR matching is clinically feasible and should be considered as a major selection criterion.
Topics: Graft Survival; HLA-DR Antigens; Heart Transplantation; Histocompatibility Testing; Humans; Publication Bias; Transplantation, Homologous
PubMed: 24725030
DOI: 10.1111/tri.12335 -
Cancer Research Communications Oct 2022Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate below 5%. Carbohydrate antigen 19-9 (CA19-9) is the most commonly used blood-based biomarker for PDAC... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate below 5%. Carbohydrate antigen 19-9 (CA19-9) is the most commonly used blood-based biomarker for PDAC in current clinical practice, despite having been shown repeatedly to be inaccurate and have poor diagnostic performance. This review aims to assess the reported diagnostic accuracy of all blood-based biomarkers investigated to date in PDAC, by directly comparing individual biomarkers and multi-biomarker panels, both containing CA19-9 and not (novel). A systematic review was conducted in accordance with PRISMA standards in July 2020. Individualized search strategies for three academic databases identified 5,885 studies between the years 1973 and 2020. After two rounds of screening, 250 studies were included. Data were extracted and assessed for bias. A multivariate three-level meta-analysis with subgroup moderators was run in R using AUC values as effect size. On the basis of this model, the pooled AUC value for all multi-biomarker panels (AUC = 0.898; 95% confidence interval (CI): 0.88-0.91) was significantly higher than all single biomarkers (AUC = 0.803; 95% CI: 0.78-0.83; < 0.0001). The pooled AUC value for CA19-9 alone was significantly lower compared with the multi-biomarker panels containing CA19-9 ( < 0.0001). For the novel biomarkers, the pooled AUC for single biomarkers was also significantly lower compared with multi-biomarker panels ( < 0.0001). Novel biomarkers that have been repeatedly examined across the literature, such as TIMP-1, CEA, and CA125, are highlighted as promising. These results suggest that CA19-9 may be best used as an addition to a panel of biomarkers rather than alone, and that multi-biomarker panels generate the most robust results in blood-based PDAC diagnosis.
SIGNIFICANCE
In a systematic review and three-level multivariate meta-analysis, it is shown for the first time that blood-based multi-biomarker panels for the diagnosis of PDAC exhibit superior performance in comparison with single biomarkers. CA19-9 is demonstrated to have limited utility alone, and to perform poorly in patient control cohorts of both healthy and benign individuals. Multi-biomarker panels containing CA19-9 produce the best diagnostic performance overall.
Topics: Humans; CA-19-9 Antigen; Biomarkers, Tumor; Case-Control Studies; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal
PubMed: 36969742
DOI: 10.1158/2767-9764.CRC-22-0190 -
Oncotarget Apr 2017Ovarian reserve reflects a woman's fertility potential. The ABO blood group system is a very stable genetic marker. Although many recent studies have explored the... (Meta-Analysis)
Meta-Analysis Review
Ovarian reserve reflects a woman's fertility potential. The ABO blood group system is a very stable genetic marker. Although many recent studies have explored the relationship between ABO blood group and ovarian reserve, a consensus has not yet been reached. This paper is the first meta-analysis and systematic review of the relationship between ABO blood type and ovarian reserve. We analyzed seven cross-sectional studies evaluating follicle stimulating hormone (FSH) or anti-Mullerian hormone (AMH) levels in 55,113 participants to determine ovarian reserve. This study found no relationship between ABO blood type and ovarian reserve when FSH was used as an indicator of ovarian reserve (A vs non-A:OR=1.03, 95% CI:0.96-1.11; B vs non-B: OR=0.98, 95% CI:0.75-1.29; AB vs non-AB:OR=0.96, 95% CI:0.71-1.30; O vs non-O:OR=1.03, 95%CI:0.74-1.43).There was also no relationship between ABO blood type and ovarian reserve when AMH was used as an indicator (A vs non-A:OR=0.89, 95% CI:0.76-1.03; B vs non-B:OR=1.02, 95% CI:0.80-1.30; AB vs non-AB:OR=1.14, 95% CI:0.80-1.64, O vs non-O:OR=1.07, 95% CI:0.86-1.34). Overall, the current study found no relationship between ABO blood group and ovarian reserve. However, additional rigorous, high-quality and multi-indicator studies with large sample sizes are required for further verification.
Topics: ABO Blood-Group System; Cross-Sectional Studies; Female; Genetic Association Studies; Genetic Heterogeneity; Humans; Odds Ratio; Ovarian Reserve
PubMed: 28445964
DOI: 10.18632/oncotarget.15759 -
Radiotherapy and Oncology : Journal of... Sep 2023In recent years, the treatment landscape for breast cancer has undergone significant advancements, with the introduction of several new anticancer agents. One such agent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
In recent years, the treatment landscape for breast cancer has undergone significant advancements, with the introduction of several new anticancer agents. One such agent is trastuzumab emtansine (T-DM1), an antibody drug conjugate that has shown improved outcomes in both early and advanced breast cancer. However, there is currently a lack of comprehensive evidence regarding the safety profile of combining T-DM1 with radiation therapy (RT). In this study, we aim to provide a summary of the available data on the safety of combining RT with T-DM1 in both early and metastatic breast cancer settings.
MATERIALS AND METHODS
This systematic review and meta-analysis project is part of the consensus recommendations by the European Society for Radiotherapy and Oncology (ESTRO) Guidelines Committee on integrating RT with targeted treatments for breast cancer. A thorough literature search was conducted using the PUBMED/MedLine, Embase, and Cochrane databases to identify original studies focusing on the safety profile of combining T-DM1 with RT.
RESULTS
After applying eligibility criteria, nine articles were included in the meta-analysis. Pooled data from these studies revealed a high incidence of grade 3 + radionecrosis (17%), while the rates of grade 3 + radiation-related pneumonitis (<1%) and skin toxicity (1%) were found to be very low.
CONCLUSION
Although there is some concern regarding a slight increase in pneumonitis when combining T-DM1 with postoperative RT, the safety profile of this combination was deemed acceptable for locoregional treatment in non-metastatic breast cancer. However, caution is advised when irradiating intracranial sites concurrently with T-DM1. There is a pressing need for international consensus guidelines regarding the safety considerations of combining T-DM1 and RT for breast cancer.
Topics: Humans; Female; Ado-Trastuzumab Emtansine; Trastuzumab; Receptor, ErbB-2; Antibodies, Monoclonal, Humanized; Maytansine; Treatment Outcome; Breast Neoplasms
PubMed: 37437610
DOI: 10.1016/j.radonc.2023.109805