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BMC Ophthalmology Nov 2023To evaluate the efficacy of anti-vascular endothelial growth factor (VEGF) in treatment of age-related macular degeneration (AMD) with retinal pigment epithelial... (Meta-Analysis)
Meta-Analysis
Comparative efficacy of aflibercept and ranibizumab in the treatment of age-related macular degeneration with retinal pigment epithelial detachment: a systematic review and network meta-analysis.
OBJECTIVES
To evaluate the efficacy of anti-vascular endothelial growth factor (VEGF) in treatment of age-related macular degeneration (AMD) with retinal pigment epithelial detachment (PED).
METHODS
Systematic review identifying studies comparing intravitreal ranibizumab (IVR), intravitreal aflibercept (IVA) and intravitreal conbercept (IVC) published before Mar 2022.
RESULTS
One randomized controlled trial and 6 observational studies were selected for meta-analysis (1,069 patients). The change of best corrected visual acuity (BCVA) in IVA 2.0 mg group was better than IVR 0.5 mg (average difference 0.07) and IVR 2.0 mg (average difference 0.10), the differences were statistically significant. The change of the height of PED in IVA 2.0 group was better than IVR 0.5 group (average difference 45.30), the difference was statistically significant. The proportion of patients without PED at last visit in IVA 2.0 group were better than those in IVR 2.0 group (hazard ratio 1.91), the difference was statistically significant. There was no significant difference compared with IVR 0.5 group (hazard ratio 1.45). IVA required fewer injections than IVR, with a mean difference of -1.58.
CONCLUSIONS
IVA appears to be superior to IVR in improvement of BCVA, height decrease of PED and regression of PED with less injections in nAMD with PED.
Topics: Humans; Ranibizumab; Angiogenesis Inhibitors; Retinal Detachment; Network Meta-Analysis; Vascular Endothelial Growth Factor A; Retinal Pigment Epithelium; Retrospective Studies; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Intravitreal Injections; Macular Degeneration
PubMed: 37990182
DOI: 10.1186/s12886-023-03214-7 -
Medicine Nov 2023This study aimed to conduct a comparative analysis of the efficacy and safety of neoadjuvant chemotherapy combined with endocrine therapy against the backdrop of single... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This study aimed to conduct a comparative analysis of the efficacy and safety of neoadjuvant chemotherapy combined with endocrine therapy against the backdrop of single neoadjuvant chemotherapy or endocrine therapy, specifically in the context of hormone receptor-positive (HR+) breast cancer treatment.
METHODS
We conducted a thorough literature search across several databases, including China National Knowledge Infrastructure, Wanfang, Weipu, Chinese Journal Full-text Database, PubMed, Web of Science, Cochrane Library, and EMBASE, adhering to the guidelines outlined in the PRISMA statement. Our specific focus was on identifying randomized controlled trials that directly compared the combined approach of neoadjuvant chemotherapy and endocrine therapy with single chemotherapy or endocrine therapy in the context of treating HR+ breast cancer. Subsequently, we utilized statistical packages implemented in R software to perform comparative analyses of key clinical indicators, encompassing the complete response, objective response rate (ORR), disease control rate, pathological complete response (pCR), and adverse reactions.
RESULTS
A total of 11 randomized controlled trials, involving 1359 patients, all of whom met our inclusion criteria and were thus included in our comprehensive analysis. Within this cohort, 688 patients (50.63%) administered neoadjuvant chemotherapy combined with endocrine therapy (NCET), 642 patients (47.24%) received neoadjuvant chemotherapy (NCT) alone, while 29 patients (2.13%) underwent neoadjuvant endocrine therapy (NET) alone. The results of our meta-analysis revealed that NCET exhibited a statistically significant enhancement in both ORR and pCR (P < .05). Nonetheless, when compared to NCT or NET, NCET did not yield a significant impact on complete response, disease control rate, and safety (P > .05). In addition, NCET demonstrated a significant improvement in ORR among patients with HR+, HER2-negative breast cancer (P < .05). However, it was also linked to a heightened incidence of serious adverse reactions within this particular patient subgroup (P < .05).
CONCLUSION
The combination of Neoadjuvant chemotherapy and endocrine therapy stands out as a significant contributor to enhancing the ORR and pCR for HR+ breast cancer patients. For breast cancer patients with HER2- status, NCET demonstrates a remarkable improvement in ORR but is also associated with the emergence of adverse reactions.
Topics: Humans; Female; Breast Neoplasms; Neoadjuvant Therapy; Receptor, ErbB-2; Antineoplastic Combined Chemotherapy Protocols; China
PubMed: 37986364
DOI: 10.1097/MD.0000000000035928 -
Eye (London, England) Apr 2024Anti-vascular endothelial growth factor (anti-VEGF) agents may occasionally need to be considered for sight-threatening macular pathology in pregnant and breastfeeding...
INTRODUCTION
Anti-vascular endothelial growth factor (anti-VEGF) agents may occasionally need to be considered for sight-threatening macular pathology in pregnant and breastfeeding women. This is controversial due to the dearth of data on systemic side effects for mother and child. We aimed to expand the evidence base to inform management.
METHODS
Retrospective case series of pregnant and breastfeeding women treated with intravitreal anti-VEGF injections at Oxford Eye Hospital between January 2015 and December 2022. In addition, we conducted a systematic review and combined eligible cases in a narrative synthesis.
RESULTS
We treated six pregnant women with anti-VEGF for diabetic macular oedema(DMO) (n = 5) or choroidal neovascularisation (CNV) (n = 1). Four received ranibizumab whilst two (not known to be pregnant) received aflibercept. Patients known to be pregnant underwent counselling by an obstetric physician. Five pregnancies resulted in live births. Combining our cases with those previously published, treatment of 41 pregnant women (42 pregnancies) are reported. Indications for treatment included CNV (n = 28/41,68%), DMO (n = 7/41,17%) and proliferative diabetic retinopathy (n = 6/41,15%). Bevacizumab (n = 22/41,54%) and ranibizumab (n = 17/41,41%) were given more frequently than aflibercept (n = 2/41,5%). Many (n = 16/41,40%) were unaware of their pregnancy when treated. Most pregnancies resulted in live births (n = 34/42,81%). First trimester miscarriages (n = 5/42,12%) and stillbirths (n = 3/42,7%) mostly occurred in women with significant risk factors.
CONCLUSION
Intravitreal anti-VEGF injections may not necessarily compromise obstetric outcomes, although clear associations cannot be drawn due to small numbers and confounders from high rates of first trimester miscarriages in general and inherently high-risk pregnancies. It may be worth considering routinely investigating pregnancy and breastfeeding status in women of childbearing age prior to each injection, as part of anti-VEGF treatment protocols.
Topics: Pregnancy; Child; Female; Humans; Ranibizumab; Angiogenesis Inhibitors; Endothelial Growth Factors; Vascular Endothelial Growth Factor A; Abortion, Spontaneous; Breast Feeding; Retrospective Studies; Bevacizumab; Receptors, Vascular Endothelial Growth Factor; Diabetic Retinopathy; Choroidal Neovascularization; Intravitreal Injections; Recombinant Fusion Proteins
PubMed: 37980398
DOI: 10.1038/s41433-023-02811-6 -
Mutation Research. Reviews in Mutation... 2024Head and neck cancer is the seventh most common malignancy globally. Head and neck squamous cell carcinoma (HNSCC) originates from squamous cells and 90% of HNC are... (Comparative Study)
Comparative Study Review
Head and neck cancer is the seventh most common malignancy globally. Head and neck squamous cell carcinoma (HNSCC) originates from squamous cells and 90% of HNC are HNSCC. The gold standard for diagnosing HNSCC is tissue biopsy. However, given tumour heterogeneity, biopsies may miss important cancer-associated molecular signatures, and more importantly, after the tumour is excised, there is no means of tracking response to treatment in patients. Captured under liquid biopsy, circulating tumour DNA (ctDNA), may identify in vivo molecular genotypes and complements tumour tissue analysis in cancer management. A systematic search was conducted in PubMed, Embase, Scopus and the Cochran Library between 2012 to early 2023 on ctDNA in HNSCC using publications written in English. We summarise 20 studies that compared mutational profiles between tumour tissue DNA (tDNA) and ctDNA, using a cohort of 631 HNSCC patients and 139 controls. Among these studies, the concordance rates varied greatly and the most mutated and the most concordant gene was TP53, followed by PIK3CA, CDKN2A, NOTCH1 and FAT1. Concordant variants were mainly found in Stage IV tumours, and the mutation type is mostly single nucleotide variants (SNV). We conclude that, as a biomarker for HNSCC, ctDNA demonstrates great promise as it recapitulates tumour genotypes, however additional multi-central trials are needed.
Topics: Humans; Circulating Tumor DNA; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Mutation; Class I Phosphatidylinositol 3-Kinases; Biomarkers, Tumor; Tumor Suppressor Protein p53; Receptor, Notch1; DNA, Neoplasm; Cyclin-Dependent Kinase Inhibitor p16; Cadherins
PubMed: 37977279
DOI: 10.1016/j.mrrev.2023.108477 -
BMC Cancer Nov 2023RAS mutations affect prognosis in patients with metastatic colorectal cancer (mCRC) and have been identified as strong negative predictive markers for anti-epidermal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
RAS mutations affect prognosis in patients with metastatic colorectal cancer (mCRC) and have been identified as strong negative predictive markers for anti-epidermal growth factor receptor monoclonal antibody (anti-EGFR mAb) therapy, but many tumors containing wild-type RAS genes still do not respond to these therapies. Some additional biomarkers may have prognostic or predictive roles, but conclusions remain controversial.
METHODS
We performed a meta-analysis and systematic review of randomized controlled trials comparing anti-EGFR mAb therapy with alternative therapy that investigated the prognostic and predictive impact of additional biomarkers in RAS wild-type (wt) mCRC patients. Hazard ratios (HRs) and 95% confidence intervals (CIs) for progression-free survival (PFS) and overall survival (OS) and odds ratios (ORs) for objective response rate (ORR) were calculated. The prognostic value of biomarkers was investigated by separately pooling HR and OR for different treatment groups in an individual study. The predictive value was assessed by pooling study interactions between treatment effects and biomarker subgroups.
RESULTS
Thirty publications reporting on eighteen trials were selected, including a total of 13,507 patients. In prognostic analysis, BRAF mutations were associated with poorer PFS [HRs = 3.76 (2.47-5.73) and 2.69 (1.82-3.98)] and OS [HRs = 2.66 (1.95-3.65) and 2.45 (1.55-3.88)] in both the experimental and control arms; low miR-31-3p expression appeared to have longer PFS and OS. In terms of predictive effect, a lack of response to anti-EGFR therapy was observed in patients with BRAF mutant tumors (P < 0.01 for PFS). Patients with tumors with any mutation in the KRAS/NRAS/BRAF/PIK3CA gene also showed similar results compared with all wild-type tumors (P for PFS, OS, and ORR were < 0.01, < 0.01 and 0.01, respectively). While low miR-31-3p expression could predict PFS (P = 0.01) and OS (P = 0.04) benefit. The prognostic and predictive value regarding PIK3CA mutations, PTEN mutations or deletions, EGFR, EREG/AREG, HER2, HER3, and HER4 expression remains uncertain.
CONCLUSIONS
In RAS wt mCRC patients receiving EGFR-targeted therapy, BRAF mutation is a powerful prognostic and therapy-predictive biomarker, with no effect found for PIK3CA mutation, PTEN mutation or deletion, but the combined biomarker KRAS/NRAS/BRAF/PIK3CA mutations predict resistance to anti-EGFR therapy. Low miR-31-3p expression may have positive prognostic and therapy predictive effects. Evidence on the prognostic and predictive roles of EGFR and its ligands, and HER2/3/4 is insufficient.
Topics: Humans; Prognosis; Proto-Oncogene Proteins B-raf; Colorectal Neoplasms; Proto-Oncogene Proteins p21(ras); ErbB Receptors; Antibodies, Monoclonal; Colonic Neoplasms; Rectal Neoplasms; Biomarkers; Class I Phosphatidylinositol 3-Kinases; Mutation; MicroRNAs; Biomarkers, Tumor
PubMed: 37974093
DOI: 10.1186/s12885-023-11600-z -
American Journal of Cardiovascular... Jan 2024Pulmonary arterial hypertension (PAH) is a progressive, cureless disease, characterized by increased pulmonary vascular resistance and remodeling, with subsequent... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pulmonary arterial hypertension (PAH) is a progressive, cureless disease, characterized by increased pulmonary vascular resistance and remodeling, with subsequent ventricular dilatation and failure. New therapeutic targets are being investigated for their potential roles in improving PAH patients' symptoms and reversing pulmonary vascular pathology.
METHOD
We aimed to address the available knowledge from the published randomized controlled trials (RCTs) regarding the role of Rho-kinase (ROCK) inhibitors, bone morphogenetic protein 2 (BMP2) inhibitors, estrogen inhibitors, and AMP-activated protein kinase (AMPK) activators on the PAH evaluation parameters. This systematic review (SR) was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CDR42022340658) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
Overall, 5092 records were screened from different database and registries; 8 RCTs that met our inclusion criteria were included. The marked difference in the study designs and the variability of the selected outcome measurement tools among the studies made performing a meta-analysis impossible. However, the main findings of this SR relate to the powerful potential of the AMPK activator and the imminent antidiabetic drug metformin, and the BMP2 inhibitor sotatercept as promising PAH-modifying therapies. There is a need for long-term studies to evaluate the effect of the ROCK inhibitor fasudil and the estrogen aromatase inhibitor anastrozole in PAH patients. The role of tacrolimus in PAH is questionable. The discrepancy in the hemodynamic and clinical parameters necessitates defining cut values to predict improvement. The differences in the PAH etiologies render the judgment of the therapeutic potential of the tested drugs challenging.
CONCLUSION
Metformin and sotatercept appear as promising therapeutic drugs for PAH.
CLINICAL TRIALS REGISTRATION
This work was registered in PROSPERO (CDR42022340658).
Topics: Humans; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; AMP-Activated Protein Kinases; Familial Primary Pulmonary Hypertension; Estrogens; Metformin
PubMed: 37945977
DOI: 10.1007/s40256-023-00613-5 -
BMC Urology Nov 2023Telomerase reverse transcriptase (TERT) mutation represents the most prevalent genetic mutation found in urothelial carcinoma (UC) and holds potential as a prognostic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Telomerase reverse transcriptase (TERT) mutation represents the most prevalent genetic mutation found in urothelial carcinoma (UC) and holds potential as a prognostic indicator for tumor outcomes. However, the association between TERT mutation and prognosis in UC patients remains poorly elucidated due to conflicting findings in existing literature. Therefore, this study aimed to investigate the effect of the TERT mutation on the survival of UC patients.
METHODS
We systematically searched the PubMed, Embase, and Cochrane Library databases for studies that investigated the relationship between the TERT mutation and the prognosis of UC patients. Endpoints included the 2-year and 5-year recurrence-free survival (RFS) and overall survival (OS). The Newcastle-Ottawa Scale (NOS) tool was used to assess the risk of bias in the included studies. Review Manager 5.3 was used for the meta-analysis.
RESULTS
Nine studies with a total of 1,552 patients were included in the analysis. Two studies were prospective, and seven were retrospective. The TERT promoter mutation was associated with a lower 2-year OS (relative risk [RR] = 0.92, 95% confidence interval [CI] 0.86-0.98; P = 0.007) and a lower 5-year OS (RR = 0.80, 95% CI 0.68-0.94; P = 0.008) compared with the TERT wild type. However, no significantly differences were found between two groups in terms of HR for OS (hazard ratio [HR] = 1.29, 95% CI 0.80-2.08; P = 0.29). Furthermore, we investigated the differences in RFS and disease-specific survival (DSS) between the two groups.
CONCLUSION
The TERT mutation increases the risk of death and decreases the survival time of UC patients. TERT may be a valuable marker with individual prognostic value.
Topics: Humans; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Prospective Studies; Retrospective Studies; Prognosis; Mutation; Telomerase
PubMed: 37915019
DOI: 10.1186/s12894-023-01349-9 -
Scientific Reports Oct 2023Molecular biomarkers have the potential to predict the recurrence risk of early-stage lung adenocarcinoma (LUAD) after complete resection, but the study results are... (Meta-Analysis)
Meta-Analysis
Molecular biomarkers have the potential to predict the recurrence risk of early-stage lung adenocarcinoma (LUAD) after complete resection, but the study results are controversial. We aimed to clarify the association of molecular alterations with disease-free survival (DFS) and recurrence-free survival (RFS) in early-stage LUAD with R0 resection. Comprehensive searches were conducted in PubMed/MEDLINE, Web of Science, and Cochrane Library for this systematic review and meta-analysis with date restrictions from 2012 to 2022. In the 18 included studies, data from a total of 7417 participants in 11 studies and 4167 participants in 9 studies were collected for the EGFR and KRAS meta-analyses, respectively. Two studies were assessed as having a moderate risk of bias, and the others were all assessed as having a high individual risk of bias. The molecular alterations in KRAS rather than EGFR, were associated with a high risk of recurrence for early-stage LUAD patients suffering from R0 resection, especially for those in pStage I, the pooled hazard ratios (HRs) of KRAS were 2.71 (95% CI, 1.81-4.06; I = 22%; P < 0.00001) and 1.95 (95% CI, 1.25-3.20; I = 57%; P = 0.003) with small interstudy heterogeneity in univariate and multivariate analyses, respectively. This finding suggests that molecular alterations in KRAS that could be detected by polymerase chain reaction techniques would provide new insight into stratifying risk and personalizing patient postoperative follow-up.
Topics: Humans; Proto-Oncogene Proteins p21(ras); Adenocarcinoma of Lung; Prognosis; Lung Neoplasms; ErbB Receptors
PubMed: 37907475
DOI: 10.1038/s41598-023-42851-2 -
BMC Cancer Oct 2023It remains uncertain whether first-line treatment with upfront brain radiotherapy (RT) in combined with epidermal growth factor receptor tyrosine kinase inhibitors... (Meta-Analysis)
Meta-Analysis
First-line treatment with TKI plus brain radiotherapy versus TKI alone in EGFR-mutated non-small cell Lung cancer with brain metastases: a systematic review and meta-analysis.
BACKGROUND
It remains uncertain whether first-line treatment with upfront brain radiotherapy (RT) in combined with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is superior to EGFR-TKIs alone for EGFR-mutated non-small cell lung cancer with newly diagnosed brain metastases (BMs). Therefore, we performed a meta-analysis to address this issue.
METHODS
We searched PubMed, Embase, Cochrane Library, and Web of Science databases for eligible studies published until February 28, 2023. The primary outcomes of interest were overall survival (OS) and intracranial progression-free survival (iPFS), reported as hazard ratios (HRs) and 95% confidence intervals (CIs).
RESULTS
Twenty-four retrospective studies with 3184 patients were included. First- or second-generation EGFR-TKIs were used in each study. Upfront brain RT plus EGFR-TKIs significantly prolonged OS (HR = 0.75, 95% CI: 0.64-0.88) and iPFS (HR = 0.61, 95% CI: 0.52-0.72) compared to EGFR-TKIs alone. There were no significant differences in OS and iPFS benefits from the combination therapy between asymptomatic and symptomatic patients, patients with exon 19 and 21 mutations, patients with 1-3 and > 3 BMs, and males and females, respectively (HRs interaction, P > 0.05 for each subgroup comparison).
CONCLUSIONS
First-line treatment with upfront brain RT plus EGFR-TKIs is likely to be more effective than EGFR-TKIs alone. The benefits of combination therapy did not appear to be significantly affected by BM-related symptoms, EGFR mutation subtype, number of BMs, or sex.
Topics: Female; Humans; Male; Brain; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Lung Neoplasms; Mutation; Protein Kinase Inhibitors; Retrospective Studies
PubMed: 37904083
DOI: 10.1186/s12885-023-11548-0 -
BMC Cancer Oct 2023N-myc downstream-regulated gene-1 (NDRG1) is well-described as a potent metastasis suppressor, but its role in human breast cancer remains controversial and unclear.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
N-myc downstream-regulated gene-1 (NDRG1) is well-described as a potent metastasis suppressor, but its role in human breast cancer remains controversial and unclear. Therefore, the present study utilized a systematic review and meta-analysis approach to synthesize the association between NDRG1 protein expression and the aggressive characteristics of breast cancer.
METHODS
The protocol for the systematic review and meta-analysis was registered on the PROSPERO website (CRD42023414814). Relevant articles were searched for in PubMed, Scopus, Embase, MEDLINE, and Ovid between March 30, 2023, and May 5, 2023. The included studies were critically evaluated using the Joanna Briggs Institute critical appraisal tools. The results from individual studies were qualitatively synthesized using textual narrative synthesis. Using a random-effects model, the pooled log odds ratio of effect estimate was used to look at the link between NDRG1 protein expression and aggressive features of breast cancer, such as tumor grade, tumor stage, metastasis to the axillary lymph nodes, and hormonal receptor status.
RESULTS
A total of 1423 articles were retrieved from the electronic database search, and six studies that met the eligibility criteria were included for synthesis. There was an association between the expression of NDRG1 protein and the status of the axillary lymph nodes (P = 0.01, log Odds Ratio (OR): 0.59, 95% Confidence Interval (CI): 0.13-1.05, I: 24.24%, 292 breast cancer cases with positive axillary lymph nodes and 229 breast cancer cases with negative axillary lymph nodes, 4 studies). NDRG1 protein expression and human epidermal growth factor receptor 2 (Her2) status were found to have a negative relationship (P = 0.01, log OR: -0.76, 95% CI: -1.32-(-0.20), I: 32.42%, 197 breast cancer cases with Her2 positive and 272 breast cancer cases with Her2 negative, 3 studies). No correlation was found between NDRG1 protein expression and tumor grade (P = 0.10), estrogen receptor (ER) status (P = 0.57), or progesterone receptor (PR) status (P = 0.41).
CONCLUSION
The study concluded that increased NDRG1 protein expression was associated with increased metastasis of the tumor to the axillary lymph node. Additionally, increased NDRG1 protein expression was observed in Her2-negative breast cancer, suggesting its role in both less aggressive and more aggressive behavior depending on breast cancer subtypes. Based on the findings of the meta-analysis, an increase in NDRG1 protein expression was associated with aggressive characteristics of breast cancer.
Topics: Female; Humans; Axilla; Breast Neoplasms; Cell Cycle Proteins; Intracellular Signaling Peptides and Proteins; Lymph Nodes; Receptor, ErbB-2; Receptors, Progesterone
PubMed: 37858101
DOI: 10.1186/s12885-023-11517-7