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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 -
Tomography (Ann Arbor, Mich.) Jun 2024CAR-T-cell therapy, also referred to as chimeric antigen receptor T-cell therapy, is a novel method in the field of immunotherapy for the treatment of non-Hodgkin's... (Review)
Review
CAR-T-cell therapy, also referred to as chimeric antigen receptor T-cell therapy, is a novel method in the field of immunotherapy for the treatment of non-Hodgkin's lymphoma (NHL). In patients receiving CAR-T-cell therapy, fluorodeoxyglucose Positron Emission Tomography/Computer Tomography ([F]FDG PET/CT) plays a critical role in tracking treatment response and evaluating the immunotherapy's overall efficacy. The aim of this study is to provide a systematic review of the literature on the studies aiming to assess and predict toxicity by means of [F]FDG PET/CT in patients with NHL receiving CAR-T-cell therapy. PubMed/MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL) databases were interrogated by two investigators to seek studies involving the use of [F]FDG PET/CT in patients with lymphoma undergoing CAR-T-cell therapy. The comprehensive computer literature search allowed 11 studies to be included. The risk of bias for the studies included in the systematic review was scored as low by using version 2 of the "Quality Assessment of Diagnostic Accuracy Studies" tool (QUADAS-2). The current literature emphasizes the role of [F]FDG PET/CT in assessing and predicting toxicity in patients with NHL receiving CAR-T-cell therapy, highlighting the evolving nature of research in CAR-T-cell therapy. Additional studies are warranted to increase the collected evidence in the literature.
Topics: Humans; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Lymphoma, Non-Hodgkin; Immunotherapy, Adoptive; Radiopharmaceuticals; Receptors, Chimeric Antigen; Treatment Outcome
PubMed: 38921943
DOI: 10.3390/tomography10060066 -
The Journal of Surgical Research Jun 2024Vascularized composite allotransplantation (VCA) is the transplantation of multiple tissue types as a solution for devastating injuries. Despite the highly encouraging... (Review)
Review
INTRODUCTION
Vascularized composite allotransplantation (VCA) is the transplantation of multiple tissue types as a solution for devastating injuries. Despite the highly encouraging functional outcomes of VCA, the consequences of long-term immunosuppression remain the main obstacle in its application. In this review, we provide researchers and surgeons with a summary of the latest advances in the field of cell-based therapies for VCA tolerance.
METHODS
Four electronic databases were searched: PubMed, Scopus, Cumulative Index to Nursing and Allied Health Literature , and Web of Science. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis as the basis of our organization.
RESULTS
Hematopoietic stem cells prolonged VCA survival. A combination of immature dendritic cells and tacrolimus was superior to tacrolimus alone. T cell Ig domain and mucin domain modified mature dendritic cells increased VCA tolerance. Bone marrow-derived mesenchymal stem cells prolonged survival of VCAs. A combination of adipose-derived mesenchymal stem cells, cytotoxic T-lymphocyte antigen 4 immunoglobulin, and antilymphocyte serum significantly improved VCA tolerance. Ex-vivo allotransplant perfusion with recipient's bone marrow-derived mesenchymal stem cells increased VCA survival. Recipient's adipose-derived mesenchymal stem cells and systemic immunosuppression prolonged VCA survival more than any of those agents alone. Additionally, a combination of peripheral blood mononuclear cells shortly incubated in mitomycin and cyclosporine significantly improved VCA survival. Finally, a combination of donor recipient chimeric cells, anti-αβ-T cell receptor (TCR), and cyclosporine significantly prolonged VCA tolerance.
CONCLUSIONS
Evidence from animal studies shows that cell-based therapies can prolong survival of VCAs. However, there remain many obstacles for these therapies, and they require rigorous clinical research given the rarity of the subjects and the complexity of the therapies. The major limitations of cell-based therapies include the need for conditioning with immunosuppressive drugs and radiation, causing significant toxicity. Safety concerns also persist as most research is on animal models. While completely replacing traditional immunosuppression with cell-based methods is unlikely soon, these therapies could reduce the need for high doses of immunosuppressants and improve VCA tolerance.
PubMed: 38851085
DOI: 10.1016/j.jss.2024.04.079 -
Medicine Jun 2024Moderate red wine (RW) consumption is associated with a low risk of cardiovascular disease (CVD). However, few studies have evaluated the effects of RW and white wine... (Meta-Analysis)
Meta-Analysis
Red wine alleviates atherosclerosis-related inflammatory markers in healthy subjects rather than in high cardiovascular risk subjects: A systematic review and meta-analysis.
BACKGROUND
Moderate red wine (RW) consumption is associated with a low risk of cardiovascular disease (CVD). However, few studies have evaluated the effects of RW and white wine (WW) on inflammatory markers related to atherosclerosis in healthy individuals and high-risk subjects for CVD. This study aimed to assess the effect of RW on inflammatory markers in healthy individuals and high-risk subjects for CVD compared with moderate alcohol consumption.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA) was followed in this study. The PubMed, Embase, Cochrane, Web of Science, SinoMed, EbscoHost, and ScienceDirect databases were searched. The risk of bias and quality of the included trials were assessed using the Cochrane Handbook. The main results are summarized in Stata 12.
RESULTS
Twelve studies were included in the meta-analysis. The results demonstrated that RW significantly decreased circulating intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1 (VCAM-1), tumor necrosis factor-alpha (TNF-α), lymphocyte function-associated antigen-1, and Sialyl-Lewis X expression on the surface of monocytes in healthy subjects, but not in patients with CVD. Additionally, RW significantly decreased Sialyl-Lewis X but increased clusters of differentiation 40 (CD40) expressed on the surface of T lymphocytes and significantly decreased C-C chemokine receptor type 2 (CCR2) and very late activation antigen 4 (VLA-4) expressed on the surface of monocytes. Interestingly, subgroup analysis also found that RW significantly decreased circulating interleukin-6 (IL-6) in Spain but not in other countries, and significantly increased αMβ2 (Mac-1) in the group that had an intervention duration of less than 3 weeks.
CONCLUSIONS
Moderate consumption of RW is more effective than WW in alleviating atherosclerosis-related inflammatory markers in healthy people rather than high-risk subjects for CVD, but this needs to be further confirmed by studies with larger sample sizes.
Topics: Humans; Wine; Atherosclerosis; Biomarkers; Inflammation; Cardiovascular Diseases; Healthy Volunteers; Heart Disease Risk Factors
PubMed: 38847707
DOI: 10.1097/MD.0000000000038229 -
Cancer Immunology, Immunotherapy : CII Jun 2024Numerous randomized controlled trials (RCTs) have investigated PD-1/PD-L1 inhibitor-based combination therapies. The debate surrounding the potential additive clinical... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of anti-PD-1/PD-L1-based dual immunotherapies versus PD-1/PD-L1 inhibitor alone in patients with advanced solid tumor: a systematic review and meta-analysis.
INTRODUCTION
Numerous randomized controlled trials (RCTs) have investigated PD-1/PD-L1 inhibitor-based combination therapies. The debate surrounding the potential additive clinical benefits of combination of two immune-oncology (IO) therapies for cancer patients persists.
METHODS
Both published and grey sources of randomized clinical trials that compared anti-PD-1/PD-L1-based immunotherapy combinations with monotherapy in patients with advanced or metastatic solid tumors were encompassed. The primary outcome was progression-free survival (PFS), and secondary outcomes included objective response rate (ORR), overall survival (OS) and treatment-related adverse events (TRAEs).
RESULTS
Our analysis encompassed 31 studies comprising 10,341 patients, which covered 12 distinct immune-oncology combination regimens. Across all patients, the immunotherapy combinations exhibited the capability to enhance the ORR (OR = 1.23 [95% CI 1.13-1.34]) and extend PFS (HR = 0.91 [95% CI 0.87-0.95]). However, the observed enhancement in OS (HR = 0.96 [95% CI 0.91-1.01]) was of no significance. Greater benefits in terms of PFS (HR = 0.82 [95% CI 0.72 to 0.93]) and OS (HR = 0.85 [95% CI 0.73 to 0.99]) may be particularly pronounced in cases where PD-L1 expression is negative. Notably, despite a heightened risk of any-grade TRAEs (OR = 1.72 [95% CI 1.40-2.11]) and grade greater than or equal to 3 TRAEs (OR = 2.01 [95% CI 1.67-2.43]), toxicity was generally manageable.
CONCLUSIONS
This study suggests that incorporating an additional immunotherapy agent with PD-1/PD-L1 inhibitors can elevate the response rate and reduce the risk of disease progression, all while maintaining manageable toxicity. However, there remains a challenge in translating these primary clinical benefits into extended overall survival.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; B7-H1 Antigen; Immune Checkpoint Inhibitors; Immunotherapy; Neoplasms; Programmed Cell Death 1 Receptor; Randomized Controlled Trials as Topic
PubMed: 38834888
DOI: 10.1007/s00262-024-03734-1 -
European Urology Oncology May 2024Metastatic prostate cancer (mPCa) harbors genomic alterations that may predict targeted therapy efficacy. These alterations can be identified not only in tissue but also... (Review)
Review
BACKGROUND AND OBJECTIVE
Metastatic prostate cancer (mPCa) harbors genomic alterations that may predict targeted therapy efficacy. These alterations can be identified not only in tissue but also directly in biologic fluids (ie, liquid biopsies), mainly blood. Liquid biopsies may represent a safer and less invasive alternative for monitoring patients treated for mPCa. Current research focuses on the description and validation of novel predictive biomarkers to improve precision medicine in mPCa. Our aim was to systematically review the current evidence on liquid biopsy biomarkers for predicting treatment response in mPCa.
METHODS
We systematically searched Medline, Web of Science, and evidence-based websites for publications on circulating biomarkers in mPCa between March 2013 and February 2024 for review. Endpoints were: prediction of overall survival, biochemical or radiographic progression-free survival after treatment (chemotherapy, androgen deprivation therapy, androgen receptor pathway inhibitors [ARPIs], immunotherapy, or PARP inhibitors [PARPIs]). For each biomarker, the level of evidence (LOE) for clinical validity was attributed: LOE IA and IB, high level of evidence; LOE IIB and IIC, intermediate level; and LOE IIIC and LOE IV-VD, weak level.
KEY FINDINGS AND LIMITATIONS
The predictive value of each biomarker for the response to several therapies was evaluated in both metastatic hormone-sensitive (mHSPC) and castration-resistant prostate cancer (mCRPC). In patients with mCRPC, BRCA1/2 or ATM mutations predicted response to ARPIs (LOE IB) and PARPIs (LOE IIB), while AR-V7 transcripts or AR-V7 protein levels in circulating tumor cells (CTCs) predicted response to ARPIs and taxanes (LOE IB). CTC quantification predicted response to cabazitaxel, abiraterone, and radium-223 (LOE IIB), while TP53 alterations predicted response to Lu prostate-specific membrane antigen radioligand treatment (LOE IIB). AR copy number in circulating tumor DNA before the first treatment line and before subsequent lines predicted response to docetaxel, cabazitaxel, and ARPIs (LOE IIB). In mHSPC, DNA damage in lymphocytes was predictive of the response to radium-223 (LOE IIB).
CONCLUSIONS AND CLINICAL IMPLICATIONS
BRCA1/2, ATM, and AR alterations detected in liquid biopsies may help clinicians in management of patients with mPCa. The other circulating biomarkers did not reach the LOE required for routine clinical use and should be validated in prospective independent studies.
PATIENT SUMMARY
We reviewed studies assessing the value of biomarkers in blood or urine for management of metastatic prostate cancer. The evidence indicates that some biomarkers could help in selecting patients eligible for specific treatments.
PubMed: 38824003
DOI: 10.1016/j.euo.2024.05.003 -
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 -
Frontiers in Immunology 2024Currently, therapies such as chimeric antigen receptor-T Cell (CAR-T) and immune checkpoint inhibitors like programmed cell death protein-1 (PD-1) blockers are showing...
Currently, therapies such as chimeric antigen receptor-T Cell (CAR-T) and immune checkpoint inhibitors like programmed cell death protein-1 (PD-1) blockers are showing promising results for numerous cancer patients. However, significant advancements are required before CAR-T therapies become readily available as off-the-shelf treatments, particularly for solid tumors and lymphomas. In this review, we have systematically analyzed the combination therapy involving engineered CAR-T cells and anti PD-1 agents. This approach aims at overcoming the limitations of current treatments and offers potential advantages such as enhanced tumor inhibition, alleviated T-cell exhaustion, heightened T-cell activation, and minimized toxicity. The integration of CAR-T therapy, which targets tumor-associated antigens, with PD-1 blockade augments T-cell function and mitigates immune suppression within the tumor microenvironment. To assess the impact of combination therapy on various tumors and lymphomas, we categorized them based on six major tumor-associated antigens: mesothelin, disialoganglioside GD-2, CD-19, CD-22, CD-133, and CD-30, which are present in different tumor types. We evaluated the efficacy, complete and partial responses, and progression-free survival in both pre-clinical and clinical models. Additionally, we discussed potential implications, including the feasibility of combination immunotherapies, emphasizing the importance of ongoing research to optimize treatment strategies and improve outcomes for cancer patients. Overall, we believe combining CAR-T therapy with PD-1 blockade holds promise for the next generation of cancer immunotherapy.
Topics: Humans; Programmed Cell Death 1 Receptor; Immunotherapy, Adoptive; Lymphoma; Immune Checkpoint Inhibitors; Receptors, Chimeric Antigen; Animals; Neoplasms; Combined Modality Therapy; Tumor Microenvironment; Antigens, Neoplasm; T-Lymphocytes
PubMed: 38799440
DOI: 10.3389/fimmu.2024.1389971 -
The Journal of Heart and Lung... May 2024Current monitoring after heart transplantation (HT) employs repeated invasive endomyocardial biopsies (EMB). Although positive EMB confirms rejection, EMB fails to...
BACKGROUND
Current monitoring after heart transplantation (HT) employs repeated invasive endomyocardial biopsies (EMB). Although positive EMB confirms rejection, EMB fails to predict impending, subclinical, or EMB-negative rejection events. While non-human leukocyte antigen (non-HLA) antibodies have emerged as important risk factors for antibody-mediated rejection after HT, their use in clinical risk stratification has been limited. A systematic review of the role of non-HLA antibodies in rejection pathologies has the potential to guide efforts to overcome deficiencies of EMB in rejection monitoring.
METHODS
Databases were searched to include studies on non-HLA antibodies in HT recipients. Data collected included the number of patients, type of rejection, non-HLA antigen studied, association of non-HLA antibodies with rejection, and evidence for synergistic interaction between non-HLA antibodies and donor-specific anti-human leukocyte antigen antibody (HLA-DSA) responses.
RESULTS
A total of 56 studies met the inclusion criteria. Strength of evidence for each non-HLA antibody was evaluated based on the number of articles and patients in support versus against their role in mediating rejection. Importantly, despite previous intense focus on the role of anti-major histocompatibility complex class I chain-related gene A (MICA) and anti-angiotensin II type I receptor antibodies (AT1R) in HT rejection, evidence for their involvement was equivocal. Conversely, the strength of evidence for other non-HLA antibodies supports that differing rejection pathologies are driven by differing non-HLA antibodies.
CONCLUSIONS
This systematic review underscores the importance of identifying peri-HT non-HLA antibodies. Current evidence supports the role of non-HLA antibodies in all forms of HT rejection. Further investigations are required to define the mechanisms of action of non-HLA antibodies in HT rejection.
PubMed: 38796046
DOI: 10.1016/j.healun.2024.05.012 -
Breast Cancer : Basic and Clinical... 2024Oncotype-Dx (ODx) is a 21-gene assay used as a prognostic and predictive tool for hormone receptor (HR)-positive and human epidermal growth factor receptor 2... (Review)
Review
Association Between Ki-67 Proliferative Index and Oncotype-Dx Recurrence Score in Hormone Receptor-Positive, HER2-Negative Early Breast Cancers. A Systematic Review of the Literature.
BACKGROUND
Oncotype-Dx (ODx) is a 21-gene assay used as a prognostic and predictive tool for hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative, node-negative, or 1 to 3 lymph node-positive early breast cancers (EBCs). The cost of the test, which is not available in low-middle income countries (LMICs), is not within the means of most individuals. The Ki-67 index is a marker of tumor proliferation that is cost-effective and easily performed and has been substituted in many cases to obtain prognostic information.
OBJECTIVE
We aimed to identify the correlation between the ODx recurrence score (RS) and the Ki-67 index in HR-positive EBCs and to determine whether Ki-67, like the ODx, can help facilitate clinical decision-making.
DESIGN
Systematic review correlating Ki-67 index and ODx in HR-positive and HER2-negative EBCs as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
DATA SOURCES AND METHODS
We searched different databases between January 2010 and May 2023 and included retrospective/prospective cohorts, clinical trials, case-control, and cross-sectional studies involving HR-positive and HER2-negative EBCs correlating the Ki-67 index and ODx RS categories.
RESULTS
Of the 18 studies included, 16 indicated a positive or weakly positive correlation between ODx and the Ki-67 index. The combined value of the included studies is <0.05 ( = .000), which shows a statistical significance between the 2. Our review also discusses the potential of machine learning and artificial intelligence (AI) in Ki-67 assessment, offering a cost-effective and reproducible alternative.
CONCLUSION
Even although there are limitations, studies indicate a favorable association between ODx and the Ki-67 index in specific situations. This implies that Ki-67 can offer important predictive details, especially regarding the likelihood of relapse in HR-positive EBC. This is particularly significant in LMICs where financial constraints often hinder the availability of costly diagnostic tests.
PubMed: 38779417
DOI: 10.1177/11782234241255211