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Korean Journal of Radiology Jul 2024This study systematically reviewed the role of diffusion-weighted imaging (DWI) in the assessment of molecular prognostic biomarkers in breast cancer, focusing on the... (Meta-Analysis)
Meta-Analysis Review
This study systematically reviewed the role of diffusion-weighted imaging (DWI) in the assessment of molecular prognostic biomarkers in breast cancer, focusing on the correlation of apparent diffusion coefficient (ADC) with hormone receptor status and prognostic biomarkers. Our meta-analysis includes data from 52 studies examining ADC values in relation to estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and Ki-67 status. The results indicated significant differences in ADC values among different receptor statuses, with ER-positive, PgR-positive, HER2-negative, and Ki-67-positive tumors having lower ADC values compared to their negative counterparts. This study also highlights the potential of advanced DWI techniques such as intravoxel incoherent motion and non-Gaussian DWI to provide additional insights beyond ADC. Despite these promising findings, the high heterogeneity among the studies underscores the need for standardized DWI protocols to improve their clinical utility in breast cancer management.
Topics: Humans; Breast Neoplasms; Diffusion Magnetic Resonance Imaging; Female; Biomarkers, Tumor; Prognosis; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Ki-67 Antigen
PubMed: 38942456
DOI: 10.3348/kjr.2023.1188 -
BMC Cancer Jun 2024Novel antibody-drug conjugates (ADCs) drugs present a promising anti-cancer treatment, although survival benefits for HER2-positive advanced breast cancer (BC) remain... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Novel antibody-drug conjugates (ADCs) drugs present a promising anti-cancer treatment, although survival benefits for HER2-positive advanced breast cancer (BC) remain controversial. The aim of this meta-analysis was to evaluate the comparative effect of ADCs and other anti-HER2 therapy on progression-free survival (PFS) and overall survival (OS) for treatment of HER2-positive locally advanced or metastatic BC.
METHODS
Relevant randomized controlled trials (RCTs) were retrieved from five databases. The risk of bias was assessed with the Cochrane Collaboration's tool for RCTs by RevMan5.4 software. The hazard ratio (HR) and 95% confidence intervals (CIs) were extracted to evaluate the benefit of ADCs on PFS and OS in HER2-positive advanced BC by meta-analysis.
RESULTS
Meta-analysis of six RCTs with 3870 patients revealed that ADCs significantly improved PFS (HR: 0.63, 95% CI: 0.49-0.80, P = 0.0002) and OS (HR: 0.79, 95% CI: 0.72-0.86, P < 0.0001) of patients with HER2-positive locally advanced or metastatic BC. Subgroup analysis showed that PFS and OS were obviously prolonged for patients who previously received HER2-targeted therapy. Sensitivity analysis and publication bias suggested that the results were stable and reliable.
CONCLUSION
Statistically significant benefits for PFS and OS were observed with ADCs in HER2-positive locally advanced or metastatic BC, especially for those who received prior anti-HER2 treatment.
Topics: Humans; Breast Neoplasms; Receptor, ErbB-2; Female; Immunoconjugates; Randomized Controlled Trials as Topic; Progression-Free Survival; Treatment Outcome; Trastuzumab; Antineoplastic Agents, Immunological
PubMed: 38851684
DOI: 10.1186/s12885-024-12478-1 -
PloS One 2024Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections have emerged as the most common therapeutic approach for the management of diabetic macular... (Meta-Analysis)
Meta-Analysis Comparative Study
Comparative efficacy of anti-vascular endothelial growth factor on diabetic macular edema diagnosed with different patterns of optical coherence tomography: A network meta-analysis.
Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections have emerged as the most common therapeutic approach for the management of diabetic macular edema (DME). Despite their proven superiority over other interventions, there is a paucity of data regarding the relative effectiveness of anti-VEGF agents in treating DME diagnosed with different patterns of optical coherence tomography (OCT). In this regard, we conducted a systematic review and comparative analysis of the therapeutic efficacy of intravitreal bevacizumab, ranibizumab, aflibercept, and conbercept in the management of DME with diffuse retinal thickening (DRT), cystoid macular edema (CME), and serous retinal detachment (SRD) patterns identified using OCT. Our study encompassed a comprehensive search of PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wan Fang Data from their inception until January 25, 2023. The network meta-analysis involved the inclusion of 1606 patients from 20 retrospective studies with a moderate risk of bias but no evidence of publication bias. The DRT group had the highest increase in best-corrected visual acuity (BCVA) with anti-VEGF, while the SRD group had the greatest reduction in Central Macular Thickness (CMT). Furthermore, conbercept, ranibizumab, and bevacizumab, respectively, showed the best treatment outcomes for patients with DRT, CME, and SRD in terms of improvement in BCVA. And, conbercept exhibited the highest reduction in CMT in the DRT, CME, and SRD groups. In conclusion, our study highlights the efficacy of anti-VEGF agents in the management of DME and provides valuable insights into the selection of anti-VEGF agents tailored to the individual needs of patients.
Topics: Humans; Angiogenesis Inhibitors; Bevacizumab; Diabetic Retinopathy; Intravitreal Injections; Macular Edema; Network Meta-Analysis; Ranibizumab; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Tomography, Optical Coherence; Treatment Outcome; Vascular Endothelial Growth Factor A; Visual Acuity
PubMed: 38848379
DOI: 10.1371/journal.pone.0304283 -
PloS One 2024Breast cancer (BC) diagnosis and treatment rely heavily on molecular markers such as HER2, Ki67, PR, and ER. Currently, these markers are identified by invasive methods. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Breast cancer (BC) diagnosis and treatment rely heavily on molecular markers such as HER2, Ki67, PR, and ER. Currently, these markers are identified by invasive methods.
OBJECTIVE
This meta-analysis investigates the diagnostic accuracy of ultrasound-based radiomics as a novel approach to predicting these markers.
METHODS
A comprehensive search of PubMed, EMBASE, and Web of Science databases was conducted to identify studies evaluating ultrasound-based radiomics in BC. Inclusion criteria encompassed research on HER2, Ki67, PR, and ER as key molecular markers. Quality assessment using Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and Radiomics Quality Score (RQS) was performed. The data extraction step was performed systematically.
RESULTS
Our meta-analysis quantifies the diagnostic accuracy of ultrasound-based radiomics with a sensitivity and specificity of 0.76 and 0.78 for predicting HER2, 0.80, and 0.76 for Ki67 biomarkers. Studies did not provide sufficient data for quantitative PR and ER prediction analysis. The overall quality of studies based on the RQS tool was moderate. The QUADAS-2 evaluation showed that the studies had an unclear risk of bias regarding the flow and timing domain.
CONCLUSION
Our analysis indicated that AI models have a promising accuracy for predicting key molecular biomarkers' status in BC patients. We performed the quantitative analysis for HER2 and Ki67 biomarkers which yielded a moderate to high accuracy. However, studies did not provide adequate data for meta-analysis of ER and PR prediction accuracy of developed models. The overall quality of the studies was acceptable. In future research, studies need to report the results thoroughly. Also, we suggest more prospective studies from different centers.
Topics: Humans; Breast Neoplasms; Female; Biomarkers, Tumor; Artificial Intelligence; Receptor, ErbB-2; Ki-67 Antigen; Ultrasonography; Receptors, Estrogen; Receptors, Progesterone
PubMed: 38820391
DOI: 10.1371/journal.pone.0303669 -
World Journal of Stem Cells May 2024Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy. Glioma stem cells (GSCs), a subset within tumors,...
BACKGROUND
Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy. Glioma stem cells (GSCs), a subset within tumors, contribute to resistance, tumor heterogeneity, and plasticity. Recent studies reveal GSCs' role in therapeutic resistance, driven by DNA repair mechanisms and dynamic transitions between cellular states. Resistance mechanisms can involve different cellular pathways, most of which have been recently reported in the literature. Despite progress, targeted therapeutic approaches lack consensus due to GSCs' high plasticity.
AIM
To analyze targeted therapies against GSC-mediated resistance to radio- and chemotherapy in gliomas, focusing on underlying mechanisms.
METHODS
A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to September 30, 2023. The search strategy utilized relevant Medical Subject Heading terms and keywords related to including "glioma stem cells", "radiotherapy", "chemotherapy", "resistance", and "targeted therapies". Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated resistance to radiotherapy resistance (RTR).
RESULTS
In a comprehensive review of 66 studies on stem cell therapies for SCI, 452 papers were initially identified, with 203 chosen for full-text analysis. Among them, 201 were deemed eligible after excluding 168 for various reasons. The temporal breakdown of studies illustrates this trend: 2005-2010 (33.3%), 2011-2015 (36.4%), and 2016-2022 (30.3%). Key GSC models, particularly U87 (33.3%), U251 (15.2%), and T98G (15.2%), emerge as significant in research, reflecting their representativeness of glioma characteristics. Pathway analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) (27.3%) and Notch (12.1%) pathways, suggesting their crucial roles in resistance development. Targeted molecules with mTOR (18.2%), CHK1/2 (15.2%), and ATP binding cassette G2 (12.1%) as frequent targets underscore their importance in overcoming GSC-mediated resistance. Various therapeutic agents, notably RNA inhibitor/short hairpin RNA (27.3%), inhibitors ( LY294002, NVP-BEZ235) (24.2%), and monoclonal antibodies ( cetuximab) (9.1%), demonstrate versatility in targeted therapies. among 20 studies (60.6%), the most common effect on the chemotherapy resistance response is a reduction in temozolomide resistance (51.5%), followed by reductions in carmustine resistance (9.1%) and doxorubicin resistance (3.0%), while resistance to RTR is reduced in 42.4% of studies.
CONCLUSION
GSCs play a complex role in mediating radioresistance and chemoresistance, emphasizing the necessity for precision therapies that consider the heterogeneity within the GSC population and the dynamic tumor microenvironment to enhance outcomes for glioblastoma patients.
PubMed: 38817336
DOI: 10.4252/wjsc.v16.i5.604 -
Revista Peruana de Medicina... May 2024Motivation for the study. Treatment options for HER2-positive breast cancer were evaluated, focusing on the efficacy and safety of trastuzumab-emtansine (T-DM1) compared... (Meta-Analysis)
Meta-Analysis Comparative Study
OBJECTIVE.
Motivation for the study. Treatment options for HER2-positive breast cancer were evaluated, focusing on the efficacy and safety of trastuzumab-emtansine (T-DM1) compared to other anti-HER2 therapies. Main findings. Trastuzumab-deruxtecan (T-DXd) and PyroCap emerged as promising alternatives, showing substantial improvements in progression-free survival for locally advanced or metastatic breast cancer. T-DM1 showed superior efficacy to the other treatments. Implications. Our findings could inform healthcare decision-making processes to optimize strategies for HER2-positive breast cancer, and potentially improve health outcomes and quality of life. We aimed to study the efficacy and safety of trastuzumab-emtansine (T-DM1) versus other anti-HER2 therapies in HER2+ breast cancer (BC).
MATERIALS AND METHODS.
We performed a network meta-analysis (NMA) of randomized controlled trials (RCTs). Our study focused on patients undergoing treatment for unresectable locally advanced breast cancer (LABC) or metastatic breast cancer (mBC), which included regimens involving trastuzumab and taxanes. Additionally, we considered cases within the first 6 months of treatment for HER2+ early breast cancer (EBC).
RESULTS.
A total of 23 RCTs and 41 reports were included in our analysis. LABC and mBC showed no statistically significant difference in any of the comparisons of T-DM1 versus the other anti-HER2+ therapies. When assessing progression-free survival (PFS), trastuzumab-deruxtecan (T-DXd) and PyroCap demonstrated greater efficacy compared to other treatments (Hazard Ratio [HR]: 3.57; 95% confidence interval [CI]: 2.75-4.63 and HR: 1.82; 95% CI: 1.35-2.44; respectively), while T-DM1 alone exhibited superior effectiveness compared to LapCap (HR: 0.65; 95% CI: 0.55-0.77), TrasCap (HR: 0.65; 95% CI: 0.46-0.91), LapCapCitu (HR: 0.60; 95% CI: 0.33-1.10), Nera (HR: 0.55; 95% CI: 0.39-0.77), and Cap (HR: 0.37; 95% CI: 0.28-0.49).
CONCLUSIONS.
NMA allows a ranking based on the comparative efficacy and safety among the interventions available. Although superior to other schemes, T-DM1 showed a lower efficacy performance in PFS and overall response rate and a trend towards worse overall survival than T-DXd.
Topics: Humans; Breast Neoplasms; Ado-Trastuzumab Emtansine; Female; Receptor, ErbB-2; Antineoplastic Agents, Immunological; Trastuzumab; Network Meta-Analysis; Randomized Controlled Trials as Topic; Neoplasm Metastasis; Antineoplastic Combined Chemotherapy Protocols; Maytansine
PubMed: 38808848
DOI: 10.17843/rpmesp.2024.411.13351 -
BMC Cancer May 2024Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are currently recommended by the National Comprehensive Cancer Network (NCCN)...
BACKGROUND
Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are currently recommended by the National Comprehensive Cancer Network (NCCN) guidelines and the European Society for Medical Oncology (ESMO) guidelines as the first-line (1 L) treatment for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, locally advanced/metastatic breast cancer (HR+/HER2- LABC/mBC). Although there are many treatment options, there is no clear standard of care for patients following 1 L CDK4/6i. Understanding the real-world effectiveness of subsequent therapies may help to identify an unmet need in this patient population. This systematic literature review qualitatively synthesized effectiveness and safety outcomes for treatments received in the real-world setting after 1 L CDK4/6i therapy in patients with HR+/ HER2- LABC/mBC.
METHODS
MEDLINE®, Embase, and Cochrane were searched using the Ovid® platform for real-world evidence studies published between 2015 and 2022. Grey literature was searched to identify relevant conference abstracts published from 2019 to 2022. The review was conducted in accordance with PRISMA guidelines (PROSPERO registration: CRD42023383914). Data were qualitatively synthesized and weighted average median real-world progression-free survival (rwPFS) was calculated for NCCN/ESMO-recommended post-1 L CDK4/6i treatment regimens.
RESULTS
Twenty records (9 full-text articles and 11 conference abstracts) encompassing 18 unique studies met the eligibility criteria and reported outcomes for second-line (2 L) treatments after 1 L CDK4/6i; no studies reported disaggregated outcomes in the third-line setting or beyond. Sixteen studies included NCCN/ESMO guideline-recommended treatments with the majority evaluating endocrine-based therapy; five studies on single-agent ET, six studies on mammalian target of rapamycin inhibitors (mTORi) ± ET, and three studies with a mix of ET and/or mTORi. Chemotherapy outcomes were reported in 11 studies. The most assessed outcome was median rwPFS; the weighted average median rwPFS was calculated as 3.9 months (3.3-6.0 months) for single-agent ET, 3.6 months (2.5-4.9 months) for mTORi ± ET, 3.7 months for a mix of ET and/or mTORi (3.0-4.0 months), and 6.1 months (3.7-9.7 months) for chemotherapy. Very few studies reported other effectiveness outcomes and only two studies reported safety outcomes. Most studies had heterogeneity in patient- and disease-related characteristics.
CONCLUSIONS
The real-world effectiveness of current 2 L treatments post-1 L CDK4/6i are suboptimal, highlighting an unmet need for this patient population.
Topics: Humans; Cyclin-Dependent Kinase 4; Breast Neoplasms; Receptor, ErbB-2; Cyclin-Dependent Kinase 6; Female; Protein Kinase Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Receptors, Estrogen; Receptors, Progesterone; Progression-Free Survival
PubMed: 38783218
DOI: 10.1186/s12885-024-12269-8 -
Revista Da Associacao Medica Brasileira... 2024The objective of this study was to explore the relationship between serum soluble fms-like tyrosine kinase 1 and the severity of acute pancreatitis and its diagnostic... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The objective of this study was to explore the relationship between serum soluble fms-like tyrosine kinase 1 and the severity of acute pancreatitis and its diagnostic utility.
METHODS
This study was carried out by searching Chinese and English literature from the establishment of the database to July 9, 2023, systematically, and assessing the quality and heterogeneity of the articles included.
RESULTS
Thirteen studies with a total of 986 patients were included. Patients with severe acute pancreatitis showed higher levels of soluble fms-like tyrosine kinase 1 compared with mild acute pancreatitis [weighted mean difference=76.64 pg/mL, 95% confidence interval (95%CI 50.39-102.89, p<0.001)]. Soluble fms-like tyrosine kinase 1 predicted pooled sensitivity, specificity, and area under the curve were 79%, 74%, and 0.85 for severe acute pancreatitis, with some heterogeneity (I2>50% or p<0.05). In the subgroup analysis, cutoff >150 pg/mL was found to be a heterogeneous factor.
CONCLUSION
Soluble fms-like tyrosine kinase 1 is a reliable tool for identifying acute pancreatitis severity, but only as a screening tool.
Topics: Humans; Pancreatitis; Severity of Illness Index; Acute Disease; Biomarkers; Vascular Endothelial Growth Factor Receptor-1; Sensitivity and Specificity; Predictive Value of Tests
PubMed: 38775515
DOI: 10.1590/1806-9282.20231694 -
American Journal of Physiology. Heart... Jul 2024The reduced uterine perfusion pressure (RUPP) model is frequently used to study preeclampsia and fetal growth restriction. An improved understanding of influential... (Meta-Analysis)
Meta-Analysis Review
The reduced uterine perfusion pressure (RUPP) model is frequently used to study preeclampsia and fetal growth restriction. An improved understanding of influential factors might improve reproducibility and reduce animal use considering the variability in RUPP phenotype. We performed a systematic review and meta-analysis by searching Medline and Embase (until 28 March, 2023) for RUPP studies in murine. Primary outcomes included maternal blood pressure (BP) or proteinuria, fetal weight or crown-rump length, fetal reabsorptions, or antiangiogenic factors. We aimed to identify influential factors by meta-regression analysis. We included 155 studies. Our meta-analysis showed that the RUPP procedure results in significantly higher BP (MD = 24.1 mmHg; [22.6; 25.7]; = 148), proteinuria (SMD = 2.3; [0.9; 3.8]; = 28), fetal reabsorptions (MD = 50.4%; [45.5; 55.2]; = 42), circulating soluble FMS-like tyrosine kinase-1 (sFlt-1) (SMD = 2.6; [1.7; 3.4]; = 34), and lower fetal weight (MD = -0.4 g; [-0.47; -0.34]; = 113. The heterogeneity (variability between studies) in primary outcomes appeared ≥90%. Our meta-regression identified influential factors in the method and time point of BP measurement, randomization in fetal weight, and type of control group in sFlt-1. The RUPP is a robust model considering the evident differences in maternal and fetal outcomes. The high heterogeneity reflects the observed variability in phenotype. Because of underreporting, we observed reporting bias and a high risk of bias. We recommend standardizing study design by optimal time point and method chosen for readout measures to limit the variability. This contributes to improved reproducibility and thereby eventually improves the translational value of the RUPP model.
Topics: Fetal Growth Retardation; Female; Pregnancy; Pre-Eclampsia; Animals; Disease Models, Animal; Mice; Uterus; Blood Pressure; Vascular Endothelial Growth Factor Receptor-1; Fetal Weight
PubMed: 38758122
DOI: 10.1152/ajpheart.00056.2024 -
Lung Cancer (Amsterdam, Netherlands) Jun 2024Crizotinib was approved to treat patients with advanced non-small cell lung cancer (aNSCLC) with ROS proto-oncogene 1 (ROS1) gene fusion in 2016. We conducted a... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of crizotinib in the treatment of advanced non-small cell lung cancer with ROS1 gene fusion: a systematic literature review and meta-analysis of real-world evidence.
BACKGROUND
Crizotinib was approved to treat patients with advanced non-small cell lung cancer (aNSCLC) with ROS proto-oncogene 1 (ROS1) gene fusion in 2016. We conducted a systematic literature review to identify real-world evidence (RWE) studies and estimated the efficacy and safety of crizotinib using meta-analyses (MA) for objective response rate (ORR), real-world progression-free survival (PFS), and overall survival (OS).
METHODS
We searched MEDLINE®, Embase, and Cochrane CENTRAL from January 2016 to March 2023 using Ovid® for published single-arm or comparative RWE studies evaluating patients (N ≥ 20) receiving crizotinib monotherapy for aNSCLC with ROS1 gene fusion. Pooled estimates for ORR and grade 3/4 adverse events (AEs) were derived using the metafor package in R while pooled estimates for median real-world PFS (rwPFS) and OS were derived using reconstructed individual patient data from published Kaplan-Meier curves. The primary analysis included all studies regardless of crizotinib line of therapy; a subgroup analysis (SA) was conducted using studies evaluating patients receiving first-line crizotinib.
RESULTS
Fourteen studies met the eligibility criteria and were considered feasible for MA. For the primary analysis, the pooled ORR (N = 9 studies) was 70.6 % (95 % confidence interval [CI]: 57.0, 81.3), median rwPFS was 14.5 months (N = 11 studies), and OS was 40.2 months (N = 9 studies). In the SA, the pooled ORR (N = 4 studies) was 81.1 % (95 % CI: 76.1, 85.2) and the median rwPFS (N = 4 studies) and OS (N = 2 studies) were 18.1 and 60 months, respectively. All MAs were associated with significant heterogeneity (I > 25 %). Grade 3/4 AEs occurred in 18.7 % of patients (pooled estimate).
CONCLUSION
The results from this study are consistent with clinical trial data and, taken collectively, supports crizotinib as a safe and effective treatment across different lines of therapy in patients with ROS1 aNSCLC in the real-world setting.
Topics: Crizotinib; Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Proto-Oncogene Mas; Proto-Oncogene Proteins; Protein-Tyrosine Kinases; Protein Kinase Inhibitors; Oncogene Proteins, Fusion; Treatment Outcome; Antineoplastic Agents; Gene Fusion
PubMed: 38749072
DOI: 10.1016/j.lungcan.2024.107816