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Oncology Letters Jul 2024The present study compared the efficacy and safety of regorafenib plus programmed death-1 inhibitors (R-P) with regorafenib monotherapy as second-line therapies for...
Regorafenib plus programmed death‑1 inhibitors vs. regorafenib monotherapy in second‑line treatment for advanced hepatocellular carcinoma: A systematic review and meta‑analysis.
The present study compared the efficacy and safety of regorafenib plus programmed death-1 inhibitors (R-P) with regorafenib monotherapy as second-line therapies for advanced hepatocellular carcinoma (HCC). A systematic search of relevant literature published in PubMed, Embase, Web of Science and Cochrane Library databases until October 2023 was conducted. Two authors independently performed data extraction and screening using standardized protocols. Stata/MP 17.0 was used for the meta-analysis to evaluate the impact of R-P treatment on major outcome indicators, including overall survival, progression-free survival (PFS), tumor response and adverse reactions, in patients with advanced HCC. The results indicated that five cohort studies involving 444 patients with advanced HCC were included. The results revealed that R-P treatment improved overall survival [hazard ratio (HR), 0.61; 95% confidence interval (CI) 0.48-0.77; I=0.0%; P=0.663] and PFS (HR, 0.51; 95% CI 0.41-0.63; I=17.5%; P=0.303). Additionally, it increased the objective response rate (risk ratio, 2.33; 95% CI, 1.49-3.64; I=0.0%; P=0.994) and disease control rate (HR, 1.40; 95% CI, 1.20-1.63; I=0.0%; P=0.892) compared with those of regorafenib. However, R-P treatment was associated with an increased incidence of adverse events, such as hypothyroidism, thrombocytopenia and rash, compared with that in regorafenib. In conclusion, R-P is superior to regorafenib monotherapy in terms of survival benefits and tumor response.
PubMed: 38807680
DOI: 10.3892/ol.2024.14451 -
Laryngoscope Investigative... Jun 2024EGFR-tyrosine kinase inhibitor (TKI) is used to treat recurrent and metastatic nasopharyngeal carcinoma (rmNPC). This meta-analysis aims to study the efficacy and safety... (Review)
Review
OBJECTIVES
EGFR-tyrosine kinase inhibitor (TKI) is used to treat recurrent and metastatic nasopharyngeal carcinoma (rmNPC). This meta-analysis aims to study the efficacy and safety of EGFR-TKI in treating patients with rmNPC.
METHODS
We conducted a systematic search of PubMed, Embase, and Web of Science up to November 2023, and included literature that met the criteria. We extracted objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and adverse reaction-related events and performed meta-analysis using Stata 14.0.
RESULTS
A total of nine articles were included. The summary results showed that the ORR for patients treated with EGFR-TKI for rmNPC was 38% (95% CI = 27%-49%), the DCR was 71% (95% CI = 61%-80%), the mPFS was 6.29 months (95% CI = 5.22-7.35), and the mOS was 15.94 months (95% CI = 14.68-17.20). The most common grade 3-4 adverse reaction events in these patients were mucositis, nasopharyngeal necrosis, and oral ulceration. We found an incidence rate of 49% (95% CI = 38%-61%) for grade 3-4 adverse events (AEs). The anti-PD1 combined with TKI treatment method is more effective than the EGFR-TKI alone for treating rmNPC.
CONCLUSION
The study shows that EGFR-TKI has good efficacy in treating rmNPC but does not translate into survival benefits and owns a high incidence of grade 3-4 AEs. More RCT trials are needed in the future to verify the efficacy of anti-PD1 combined with TKI treatment method.
PubMed: 38803463
DOI: 10.1002/lio2.1279 -
Oncology Letters Jul 2024A meta-analysis of the clinical survival indicators, adverse reactions and safety of lenvatinib combined with programmed death-1 (PD-1) inhibitors in treating liver...
A meta-analysis of the clinical survival indicators, adverse reactions and safety of lenvatinib combined with programmed death-1 (PD-1) inhibitors in treating liver cancer was conducted, providing objective and effective evidence for clinical use. The present study is anticipated to guide the clinical application of lenvatinib. In the current meta-analysis, the PubMed, Embase and Cochrane Library databases were searched from inception to September 2023. Randomized controlled trials (RCTs), non-RCTs and single-arm trial studies related to the combined treatment of lenvatinib and PD-1/PD-ligand 1 (L1) inhibitors for hepatocellular carcinoma (HCC) were included, while published and unpublished literature on other study types, literature with incomplete or inadequate information, animal experiments, literature reviews and systematic studies were excluded. Data were processed using STATA 15.1. The pooled results showed that the objective response rate [ORR; odds ratio (OR), 3.36; 95% confidence interval (CI), 2.13-5.30; P<0.001], disease control rate (DCR; OR, 1.62; 95% CI, 1.03-2.57; P=0.038) and partial response (PR; OR, 3.81; 95% CI, 2.17-6.70; P<0.001) of combined lenvatinib and PD-1/PD-L1 inhibitor therapy were significantly higher than those of lenvatinib monotherapy. Additionally, subgroup analysis results showed that the DCR of combination therapy using lenvatinib and nivolumab was significantly higher than that of lenvatinib monotherapy (OR, 2.20; 95% CI; 1.07-4.51; P=0.032). The difference between combination therapy using lenvatinib and camrelizumab, and lenvatinib monotherapy was not significant. However, the complete response, stable disease, progression disease and incidence rate of adverse events between combination therapy and lenvatinib monotherapy were not significantly different. Compared with lenvatinib alone, lenvatinib combined with PD-1/PD-L1 inhibitors significantly improved ORR, mainly PR, and DCR in patients with HCC. At present, lenvatinib is mainly combined with nivolumab to increase the DCR of lenvatinib monotherapy for HCC. In addition, the incidence rate of adverse reactions between combination therapy and lenvatinib monotherapy was not significantly different for HCC.
PubMed: 38803443
DOI: 10.3892/ol.2024.14445 -
Frontiers in Oncology 2024Newly identified as a radiological concept, interstitial lung abnormalities (ILA) is emerging as a prognostic factor for lung cancer. Yet, debates persist regarding the...
BACKGROUND
Newly identified as a radiological concept, interstitial lung abnormalities (ILA) is emerging as a prognostic factor for lung cancer. Yet, debates persist regarding the prognostic significance of ILA in lung cancer. Our inaugural meta-analysis aimed to investigate the correlation between ILA and lung cancer outcomes, offering additional insights for clinicians in predicting patient prognosis.
METHODS
Articles meeting the criteria were found through PubMed, the Cochrane Library, EMBASE, and Web of Science by February 29, 2024. The outcomes evaluated were the survival rates such as overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and cancer-specific survival (CSS).
RESULTS
A total of 12 articles with 4416 patients were included in this meta-analysis. The pooled results showed that lung cancer patients with interstitial lung abnormalities had an inferior OS (n=11; HR=2.22; 95% CI=1.68-2.95; P<0.001; I = 72.0%; Ph<0.001), PFS (n=3; HR=1.59; 95% CI=1.08-2.32; P=0.017; I = 0%; Ph=0.772), and CSS (n=2; HR=4.00; 95% CI=1.94-8.25; P<0.001; I = 0%; Ph=0.594) than those without, however, the ILA was not significantly associated with the DFS (n=2; HR=2.07; 95% CI=0.94-7.02; P=0.066; I = 90.4%; Ph=0.001). Moreover, lung cancer patients with ILA were significantly correlated with male (OR=2.43; 95% CI=1.48-3.98; P<0.001), smoking history (OR=2.11; 95% CI=1.37-3.25; P<0.001), advanced age (OR=2.50; 95% CI=1.56-4.03; P<0.001), squamous carcinoma (OR=0.42; 95% CI=0.24-0.71; P=0.01), and EGFR mutation (OR=0.50; 95% CI=0.32-0.78; P=0.002). The correlation between ILA and race, stage, ALK, however, was not significant.
CONCLUSION
ILA was a availability factors of prognosis in patients with lung cancers. These findings highlight the importance of early pulmonary fibrosis, namely ILA for prognosis in patients with lung cancer, and provide a partial rationale for future clinical work.
PubMed: 38800393
DOI: 10.3389/fonc.2024.1397246 -
Seminars in Arthritis and Rheumatism Aug 2024The concept of treat-to-target (T2T), a treatment strategy in which treatment is directed to reach and maintain a defined goal such as remission or low disease activity... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The concept of treat-to-target (T2T), a treatment strategy in which treatment is directed to reach and maintain a defined goal such as remission or low disease activity (LDA), has been explored for several diseases including rheumatic diseases such as rheumatoid arthritis (RA). However, a comprehensive review of T2T in all rheumatic diseases has not recently been undertaken.
OBJECTIVE
To perform a systematic review and meta-analysis of the efficacy and safety of a T2T strategy in the management of adult patients with inflammatory rheumatic diseases.
METHODS
PUBMED, EMBASE and CINAHL were searched from January 1990 to December 2023 using key words related to a T2T strategy and rheumatic diseases; T2T strategy clinical trials or observational studies were included. Clinical, physical function and radiologic outcomes, cost-effectiveness, and adverse events (AEs) of the T2T strategies were investigated and a random-effect meta-analysis was conducted for the most commonly used outcomes in RA studies.
RESULTS
The search identified 7896 studies, of which 66 fit inclusion criteria, including 50 in RA, 3 in psoriatic arthritis (PsA), 1 in spondyloarthritis (SpA) and 12 in gout. For the studies comparing a T2T strategy with usual care (UC) in RA, 83.3% (20/24) showed a T2T strategy could achieve significantly better clinical outcomes, and the meta-analysis showed that patients treated with a T2T strategy were more likely to be in remission (pooled RR: 1.68 (1.47-1.92), p<0.001] and achieve DAS-28 response (pooled standardised mean difference (SMD): 0.47 (0.26-0.69), P<0.001] at 1 year than patients treated with UC. Sensitivity analyses showed that a T2T strategy with a predefined treatment protocol had better clinical efficacy than that without protocol. In terms of improving physical function and health-related quality of life (HRQoL), 11/19 (57.9%) studies found a T2T strategy was significantly more likely to achieve these than UC, with the meta-analysis for the mean change of HAQ score supporting this conclusion (pooled SMD: 1.48 (0.46-2.51), p=0.004). Five out of 9 studies (55.6%) demonstrated greater benefit regarding radiographic progression from a T2T strategy. In terms of cost-effectiveness and AEs, 2/2 studies found a T2T strategy was more cost-effective than UC and 8/8 studies showed no tendency for AEs to occur more often with a T2T strategy. For the studies in PsA and SpA, a T2T strategy was also demonstrated to be more effective than UC in clinical and functional benefits, but not in radiologic outcomes. All gout studies showed that sUA level could be controlled more effectively with a T2T strategy, and 2 studies revealed that the T2T strategy could inhibit erosion development or crystal deposition.
CONCLUSIONS
For patients with active RA, a T2T strategy has been shown in mulitple studies to increase the likelihood of achieving clinical response and improving HRQoL without increasing economic costs and AEs. Limited studies have shown clinical and functional benefits from T2T strategies in active PsA and SpA. A T2T strategy has also been found to improve clinical and radiologic outcomes in gout. T2T trials in other rheumatic diseases are lacking.
Topics: Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Remission Induction; Rheumatic Diseases; Treatment Outcome
PubMed: 38796922
DOI: 10.1016/j.semarthrit.2024.152465 -
Viruses Apr 2024This systematic review investigates the immunosuppressive environment in HBV-associated hepatocellular carcinoma (HCC), characterized by dysfunctional and exhausted... (Review)
Review
This systematic review investigates the immunosuppressive environment in HBV-associated hepatocellular carcinoma (HCC), characterized by dysfunctional and exhausted HBV-specific T cells alongside an increased infiltration of HBV-specific CD4+ T cells, particularly regulatory T cells (Tregs). Heightened expression of checkpoint inhibitors, notably PD-1, is linked with disease progression and recurrence, indicating its potential as both a prognostic indicator and a target for immunotherapy. Nevertheless, using PD-1 inhibitors has shown limited effectiveness. In a future perspective, understanding the intricate interplay between innate and adaptive immune responses holds promise for pinpointing predictive biomarkers and crafting novel treatment approaches for HBV-associated HCC.
Topics: Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Hepatitis B virus; Adaptive Immunity; T-Lymphocytes, Regulatory; Programmed Cell Death 1 Receptor; Immune Checkpoint Inhibitors; Hepatitis B; Hepatitis B, Chronic; CD4-Positive T-Lymphocytes; T-Lymphocytes; Immunotherapy
PubMed: 38793588
DOI: 10.3390/v16050707 -
International Journal of Molecular... May 2024Sickle cell nephropathy (SCN) is a common complication of sickle cell disease (SCD) that significantly contributes to morbidity and mortality. In addition to clinical... (Review)
Review
Sickle cell nephropathy (SCN) is a common complication of sickle cell disease (SCD) that significantly contributes to morbidity and mortality. In addition to clinical and life-style factors, genetic variants influence this risk. We performed a systematic review, searching five databases. Studies evaluating the effect of genetic modifiers on SCN were eligible. Twenty-eight studies (fair-to-good quality) were included: one genome-wide association study, twenty-six case-control studies, and one article combining both approaches. was significantly associated with albuminuria and hyperfiltration in children and with worse glomerular filtration in adults. On the other hand, alpha-thalassemia protected patients against albuminuria and hyperfiltration, while variants were protective against albuminuria alone. The long GT-tandem repeat polymorphism led to a lower glomerular filtration rate. No modifiers for the risk of hyposthenuria were identified. A genome-wide association approach identified three new loci for proteinuria (, , and ) and nine loci were linked with eGFR (, , , , , , , , and ). In conclusion, this systematic review supports the role of genetic modifiers in influencing the risk and progression of SCN. Incorporating and expanding this knowledge is crucial to improving the management and clinical outcomes of patients at risk.
Topics: Humans; Anemia, Sickle Cell; Genome-Wide Association Study; Genetic Predisposition to Disease; Kidney Diseases; Apolipoprotein L1; Disease Progression; Genes, Modifier; Glomerular Filtration Rate
PubMed: 38791464
DOI: 10.3390/ijms25105427 -
International Journal of Molecular... May 2024Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Given its prevalence, reliable biomarkers for early diagnosis are required.... (Meta-Analysis)
Meta-Analysis Review
Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Given its prevalence, reliable biomarkers for early diagnosis are required. Exosomal proteins within extracellular nanovesicles are promising candidates for diagnostic, screening, prognostic, and disease monitoring purposes in neurological diseases such as PD. This review aims to evaluate the potential of extracellular vesicle proteins or miRNAs as biomarkers for PD. A comprehensive literature search until January 2024 was conducted across multiple databases, including PubMed, EMBASE, Web of Science, and Cochrane Library, to identify relevant studies reporting exosome biomarkers in blood samples from PD patients. Out of 417 articles screened, 47 studies were selected for analysis. Among exosomal protein biomarkers, α-synuclein, tau, Amyloid β 1-42, and C-X-C motif chemokine ligand 12 (CXCL12) were identified as significant markers for PD. Concerning miRNA biomarkers, miRNA-24, miR-23b-3p, miR-195-3p, miR-29c, and mir-331-5p are promising across studies. α-synuclein exhibited increased levels in PD patients compared to control groups in twenty-one studies, while a decrease was observed in three studies. Our meta-analysis revealed a significant difference in total exosomal α-synuclein levels between PD patients and healthy controls (standardized mean difference [SMD] = 1.369, 95% confidence interval [CI] = 0.893 to 1.846, < 0.001), although these results are limited by data availability. Furthermore, α-synuclein levels significantly differ between PD patients and healthy controls (SMD = 1.471, 95% CI = 0.941 to 2.002, < 0.001). In conclusion, certain exosomal proteins and multiple miRNAs could serve as potential biomarkers for diagnosis, prognosis prediction, and assessment of disease progression in PD.
Topics: Humans; Parkinson Disease; Exosomes; Biomarkers; MicroRNAs; alpha-Synuclein; Amyloid beta-Peptides
PubMed: 38791346
DOI: 10.3390/ijms25105307 -
Biomedicines May 2024This systematic review evaluates the clinical outcomes and molecular predictors of response to pembrolizumab in patients with advanced and metastatic cervical cancer. We... (Review)
Review
Clinical Outcomes and Molecular Predictors of Pembrolizumab (Keytruda) as a PD-1 Immune Checkpoint Inhibitor in Advanced and Metastatic Cervical Cancer: A Systematic Review and Meta-Analysis.
This systematic review evaluates the clinical outcomes and molecular predictors of response to pembrolizumab in patients with advanced and metastatic cervical cancer. We adhered to the PRISMA guidelines for systematic reviews, conducting a database search in PubMed, Scopus, and Embase. The eligibility criteria centered on clinical outcomes, including the overall survival (OS), progression-free survival (PFS), and immune-related biomarkers post-pembrolizumab therapy. We included both prospective and retrospective studies that detailed clinical outcomes and molecular characteristics predictive of therapeutic response. Our search yielded six studies involving 846 patients treated with pembrolizumab from 2017 to 2022. The meta-analysis of these studies showed that pembrolizumab, used as monotherapy or in combination with chemotherapy, extended the OS by a weighted median of 10.35 months and the PFS by 8.50 months. The treatment demonstrated a pooled objective response rate (ORR) of 22.39%, although the I test result of 67.49% showed a high heterogeneity among the studies. Notably, patients with high PD-L1 expression (CPS ≥ 10) experienced improved outcomes in terms of the PFS and OS. The most common complications were fatigue, diarrhea, and immune-related adverse events. Pembrolizumab significantly enhances clinical outcomes in metastatic cervical cancer, particularly among patients with high PD-L1 expression. The drug maintains a good safety profile, reinforcing its treatment potential for patients with advanced and metastatic cervical cancer. Future studies should explore long-term effects and strategies to integrate pembrolizumab optimally into current treatment regimens, aiming to maximize patient benefits and effectively manage side effects.
PubMed: 38791070
DOI: 10.3390/biomedicines12051109 -
Medicine May 2024The aim of this study is to examine the impact of the Orlistat on glucose levels and glucose tolerance in individuals with prediabetes, as well as assess its efficacy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The aim of this study is to examine the impact of the Orlistat on glucose levels and glucose tolerance in individuals with prediabetes, as well as assess its efficacy and safety in preventing the progression to diabetes.
METHODS
For achieving the appropriate randomized controlled trials, we enrolled the public datas from the following electronic databases: The Cochrane library, Embase, China National Knowledge Infrastructure, VIP, Wan-Fang, and China Biology Medicine disc. The article focused on the orlistat intervention of glucose tolerance and glycemic status in prediabetic patients. We restricted the publication time from the creation to May 2023.
RESULTS
Six subjects were included in the study, with a total of 1076 participants (532 in the control group vs 544 in the experimental group). The results indicated that the orlistat can reduce the fasting blood glucose [relative risk (RR) = -2.18, 95% confidence intervals (CI) (-2.471, -1.886)], as well as the 2 hour postprandial blood glucose [RR = -1.497, 95% CI (-1.811, -1.183)]. Furthermore, it can prevent the impaired glucose tolerance patients to type 2 diabetes mellitus [RR = 0.605, 95% CI (0.462, 0.791)], and reversal the impaired glucose tolerance [RR = 2.092, 95% CI (1.249, 3.503)].
CONCLUSIONS
In prediabetic people, the orlistat can control weight, reduce the fasting blood glucose and the 2 hour postprandial blood glucose, and then delay the progression of diabetes. However, due to the quantitative restrictions, additional high-quality study needs to be conducted to improve the reliability of the results.
Topics: Humans; Orlistat; Prediabetic State; Diabetes Mellitus, Type 2; Blood Glucose; Disease Progression; Anti-Obesity Agents; Randomized Controlled Trials as Topic; Lactones
PubMed: 38787971
DOI: 10.1097/MD.0000000000038354