-
Biomolecules Oct 2022Myocarditis and inflammatory dilated cardiomyopathy are cardiac diseases leading to heart failure. Liquid biopsy is a concept of replacing traditional biopsy with... (Review)
Review
Myocarditis and inflammatory dilated cardiomyopathy are cardiac diseases leading to heart failure. Liquid biopsy is a concept of replacing traditional biopsy with specialized blood tests. The study aim was to summarize and assess the usefulness of microRNAs and circulating free DNA as biomarkers of myocardial inflammation. For this systematic review, we searched Scopus, Embase, Web of Science, and PubMed. All studies measuring microRNAs in serum/plasma/cardiac tissue or circulating free DNA during myocarditis and non-ischemic dilated cardiomyopathy in humans in which healthy subjects or another cardiac disease served as a comparator were included. Data were extracted and miRNAs were screened and assessed using a scale created in-house. Then, highly graded miRNAs were assessed for usability as liquid biopsy biomarkers. Of 1185 records identified, 56 were eligible and 187 miRNAs were found. We did not identify any studies measuring circulating free DNA. In total, 24 of the screened miRNAs were included in the final assessment, 3 of which were selected as the best and 3 as potential candidates. We were not able to assess the risk of bias and the final inclusion decision was made by consensus. Serum levels of three miRNAs-miR-Chr8:96, miR-155, and miR-206-are the best candidates for myocardial inflammation liquid biopsy panel. Further studies are necessary to prove their role, specificity, and sensitivity.
Topics: Humans; Cardiomyopathy, Dilated; Myocarditis; MicroRNAs; Cell-Free Nucleic Acids; Biomarkers; Liquid Biopsy; Inflammation
PubMed: 36291684
DOI: 10.3390/biom12101476 -
PharmacoEconomics Oct 2023Cancer-derived material circulating in the bloodstream and other bodily fluids, referred to as liquid biopsies (LBs), has become an appealing adjunct or alternative to...
BACKGROUND
Cancer-derived material circulating in the bloodstream and other bodily fluids, referred to as liquid biopsies (LBs), has become an appealing adjunct or alternative to tissue biopsies, showing vital promise in several clinical applications.
PURPOSE
A systematic literature review was conducted to (1) summarize the current health economic evidence for LB assays and (2) identify and analyze the studies addressed or reported on the challenges of health economic modeling in precision medicine.
METHODS
Relevant studies were identified in the EMBASE, MEDLINE, Cochrane Library, EconLit, and the University of Melbourne Full Text Journal databases from 1 January 2013 to 16 September 2022. Included papers were selected if they were economic evaluations and/or budget impact analyses.
RESULTS
A total of 24 studies were included and analyzed, with the majority being full economic evaluations (n = 19, 79.2%). Four studies (16.7%) were health and budget impact analyses, and one study (4.1%) incorporated both an economic evaluation and a budget impact analysis. Cohort-level modeling techniques were the most common approach (n = 16; 80%). LB technologies were cost-effective in 15 studies (75%) considering different biomarkers, cancer types and stages, and economic analyses. These studies evaluated LBs for screening and early detection (66.7%), treatment selection (26.7%), and monitoring treatment response (6.6%). Budget impact analysis results were varied among included studies, with the majority of studies (n = 4; 80%) reporting either cost savings, minimal, or modest budget impact, while one study (20%) reported LBs as an efficient strategy. The reviewed studies often inadequately reported or addressed modeling challenges, such as patient-level processes, the combination of tests and treatments, preferences, and uncertainty.
CONCLUSION
LBs could provide a cost-effective approach for treatment selection in lung cancer and aid in the screening and early detection of other cancers, including colorectal, gastric, breast, and brain cancers. This is in comparison with various alternatives, such as the standard of care (SOC) and no screening scenario. However, it is important to mention that in some comparisons, LBs were used in combination with SOC instead of replacing it. Importantly, few studies have pointed toward LBs' cost-effectiveness for monitoring treatment response. Most health and budget impact analyses, especially those focused on lung cancer, suggest potential cost savings or a minimal-to-moderate budget impact. Nevertheless, additional research is needed to ascertain their effectiveness across various stages of lung and colorectal cancer, as well as to address potential modeling challenges.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42022307939.
Topics: Humans; Lung Neoplasms; Liquid Biopsy; Cost-Benefit Analysis
PubMed: 37351802
DOI: 10.1007/s40273-023-01292-5 -
Cancers May 2021The potential added value of liquid biopsy (LB) is not well determined in the case of small cell lung cancer (SCLC), an aggressive tumor that can occur either de novo or... (Review)
Review
BACKGROUND
The potential added value of liquid biopsy (LB) is not well determined in the case of small cell lung cancer (SCLC), an aggressive tumor that can occur either de novo or from the histologic transformation of non-small cell lung cancer (NSCLC).
METHODS
A systematic review of studies adopting LB in patients with SCLC have been performed to assess the clinical utility of circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs).
RESULTS
After a screening of 728 records, 62 studies (32 evaluating CTCs, 27 ctDNA, and 3 both) met predetermined eligibility criteria. Only four studies evaluated LB in the diagnostic setting for SCLC, while its prognostic significance was evaluated in 38 studies and prominently supported by both ctDNA and CTCs. A meta-analysis of 11 studies as for CTCs enumeration showed an HR for overall survival of 2.63 (1.71-4.05), with a potential publication bias. The feasibility of tumor genomic profiling and the predictive role of LB in terms of response/resistance to chemotherapy was assessed in 11 and 24 studies, respectively, with greater consistency for those regarding ctDNA. Intriguingly, several case reports suggest that LB can indirectly capture the transition to SCLC in NSCLC treated with EGFR tyrosine kinase inhibitors.
CONCLUSIONS
While dedicated trials are needed, LB holds potential clinical roles in both de novo and transformed SCLC. CtDNA analysis appears the most valuable and practicable tool for both disease monitoring and genomic profiling.
PubMed: 34066817
DOI: 10.3390/cancers13092265 -
Clinical Gastroenterology and... Dec 2020Liquid biopsies, or blood samples, can be analyzed to detect circulating tumor cells (CTCs), cell-free DNA (cfDNA), and extracellular vesicles, which might identify... (Review)
Review
BACKGROUND & AIMS
Liquid biopsies, or blood samples, can be analyzed to detect circulating tumor cells (CTCs), cell-free DNA (cfDNA), and extracellular vesicles, which might identify patients with hepatocellular carcinoma (HCC) or help determine their prognoses. We performed a systematic review of studies of analyses of liquid biopsies from patients with HCC and their comparisons with other biomarkers.
METHODS
We performed a systematic review of original studies published before December 1, 2019. We included studies that compared liquid biopsies alone and in combination with other biomarkers for the detection of HCC, performed multivariate analyses of the accuracy of liquid biopsy analysis in determining patient prognoses, or evaluated the utility of liquid biopsy analysis in monitoring treatment response.
RESULTS
Our final analysis included 112 studies: 67 on detection, 46 on determining prognosis, and 25 on treatment monitoring or selection. Ten studies evaluated assays that characterized cfDNA for detection of HCC in combination with measurement of α-fetoprotein (AFP)-these studies found that the combined measurement of cfDNA and AFP more accurately identified patients with HCC than measurement of AFP alone. Six studies evaluated assays for extracellular vesicles and 2 studies evaluated assays for CTC in detection of HCC, with and without other biomarkers-most of these studies found that detection of CTCs or extracellular vesicles with AFP more accurately identified patients with HCC than measurement of AFP alone. Detection of CTCs before surgery was associated with HCC recurrence after resection in 13 of 14 studies; cfDNA and extracellular vesicles have been studied less frequently as prognostic factors. Changes in CTC numbers before vs after treatment more accurately identify patients with HCC recurrence than pretreatment counts alone, and measurements of cfDNA can identify patients with disease recurrence or progression before changes can be detected by imaging. We found little evidence that analyses of liquid biopsies can aid in the selection of treatment for HCC. Quality assessment showed risk of bias in studies of HCC detection and determination of prognosis.
CONCLUSIONS
In a systematic review of 112 studies of the accuracy of liquid biopsy analysis, we found that assays for CTCs and cfDNA might aid in determining patient prognoses and monitoring HCC, and assays for cfDNA might aid in HCC detection, but there is a risk of bias in these studies. Studies must be standardized before we can assess the clinical utility of liquid biopsy analysis in the detection and management of patients with HCC.
Topics: Biomarkers, Tumor; Carcinoma, Hepatocellular; Humans; Liquid Biopsy; Liver Neoplasms; Neoplasm Recurrence, Local; Prognosis; alpha-Fetoproteins
PubMed: 32289533
DOI: 10.1016/j.cgh.2020.04.019 -
Frontiers in Oncology 2019Reports regarding liquid biopsy and gastric cancer (GC) have emerged rapidly in recent decades, yet their prognostic value still remains controversial. This study was...
Reports regarding liquid biopsy and gastric cancer (GC) have emerged rapidly in recent decades, yet their prognostic value still remains controversial. This study was aimed to assess the impact of liquid biopsy, including circulating tumor cells (CTCs) and cell-free nucleic acids, on GC patients' prognosis. PubMed, Medline, EMBASE, and ClinicalTrial.gov databases were searched for studies that report GC patient survival data stratified by CTC/circulating tumor DNA (ctDNA)/circulating miRNAs' status. The hazard ratios (HRs) and their 95% confidence intervals (CIs) for patients' overall survival (OS) and disease-free survival (DFS)/progression-free survival (PFS) were recorded or calculated depending on circulating target status. We initially identified 4,221 studies, from which 43 were eligible for further analysis, comprising 3,814 GC patients. Pooled analyses showed that detection of certain CTCs, ctDNA, and circulating miRNA was associated with poorer OS (CTCs: HR = 1.84, 95%CI 1.50-2.26, < 0.001; ctDNA: HR = 1.78, 95%CI 1.36-2.34, < 0.001; circulating miRNA: HR = 1.74, 95%CI 1.13-2.69, < 0.001) and DFS/PFS (CTCs: HR = 3.39, 95%CI 2.21-5.20, < 0.001; ctDNA: HR = 2.38, 95%CI 1.31-4.32, = 0.004; circulating miRNA: HR = 3.30, 95%CI 2.39-4.55, < 0.001) of GC patients, regardless of disease stage and time point at which sample is taken (at baseline or post-treatment). The presence of CTCs and/or cellular components identifies a group of GC with poorer prognosis. Among circulating markers, CTCs demonstrated a stronger and more stable predictive value for late-stage disease and among Mongolian populations with GC. Less data are available for ctDNA and miRNA; however, their presence may also reflect aggressive biology and warrants further prospective study.
PubMed: 31850190
DOI: 10.3389/fonc.2019.01222 -
Frontiers in Genetics 2023In the last years, liquid biopsy gained increasing clinical relevance for detecting and monitoring several cancer types, being minimally invasive, highly informative and... (Review)
Review
In the last years, liquid biopsy gained increasing clinical relevance for detecting and monitoring several cancer types, being minimally invasive, highly informative and replicable over time. This revolutionary approach can be complementary and may, in the future, replace tissue biopsy, which is still considered the gold standard for cancer diagnosis. "Classical" tissue biopsy is invasive, often cannot provide sufficient bioptic material for advanced screening, and can provide isolated information about disease evolution and heterogeneity. Recent literature highlighted how liquid biopsy is informative of proteomic, genomic, epigenetic, and metabolic alterations. These biomarkers can be detected and investigated using single-omic and, recently, in combination through multi-omic approaches. This review will provide an overview of the most suitable techniques to thoroughly characterize tumor biomarkers and their potential clinical applications, highlighting the importance of an integrated multi-omic, multi-analyte approach. Personalized medical investigations will soon allow patients to receive predictable prognostic evaluations, early disease diagnosis, and subsequent treatments.
PubMed: 37077538
DOI: 10.3389/fgene.2023.1152470 -
Frontiers in Genetics 2023To date, tissue biopsy represents the gold standard for characterizing non-small-cell lung cancer (NSCLC), however, the complex architecture of the disease has...
To date, tissue biopsy represents the gold standard for characterizing non-small-cell lung cancer (NSCLC), however, the complex architecture of the disease has introduced the need for new investigative approaches, such as liquid biopsy. Indeed, DNA analyzed in liquid biopsy is much more representative of tumour heterogeneity. We performed a meta-analysis of 17 selected papers, to attest to the diagnostic performance of liquid biopsy in identifying EGFR mutations in NSCLC. In the overall studies, we found a sensitivity of 0.59, specificity of 0.96 and diagnostic odds ratio of 24,69. Since we noticed a high heterogeneity among different papers, we also performed the meta-analysis in separate subsets of papers, divided by 1) stage of disease, 2) experimental design and 3) method of mutation detection. Liquid biopsy has the highest sensitivity/specificity in high-stage tumours, and prospective studies are more reliable than retrospective ones in terms of sensitivity and specificity, both NGS and PCR-based techniques can be used to detect tumour DNA in liquid biopsy. Overall, liquid biopsy has the potential to help the management of NSCLC, but at present the non-homogeneous literature data, lack of optimal detection methods, together with relatively high costs make its applicability in routine diagnostics still challenging.
PubMed: 38116291
DOI: 10.3389/fgene.2023.1254839 -
Journal of Clinical and Experimental... Oct 2022The identification of non-invasive biomarkers from biological fluids collected by liquid biopsy provides new horizons for individualized therapeutic strategies and... (Review)
Review
BACKGROUND
The identification of non-invasive biomarkers from biological fluids collected by liquid biopsy provides new horizons for individualized therapeutic strategies and improves clinical decision-making in OSCC patients. Circulating microRNAs have emerged as biomarkers that may reflect not only the existence of cancer, but also the dynamic, malignant potential, and drug resistance of tumors. The aim of the systematic review is to evaluate and summarize the results of the published studies regarding the use of microRNAs as biomarkers for OSCC.
MATERIAL AND METHODS
A literature search was conducted on PubMed, Scopus, Web of Science, and Cochrane databases till November 2020. A total of 34 studies met the inclusion criteria and were therefore subjected to quality assessment. Each study was subjected to data extraction including; patient characteristics, type of fluid sample (whole blood, plasma, serum, or saliva), molecular analysis method, specific dysregulated microRNA, and microRNA expression pattern.
RESULTS
The analysis showed that 57 microRNAs of liquid biopsy samples of four different fluids (whole blood, serum, plasma, and saliva) were analyzed. The prognostic and therapeutic significance of these microRNAs were suggested by several studies; where 41 microRNAs were upregulated while 16 were downregulated.
CONCLUSIONS
Scientific evidence supports the interest in the use of microRNAs in the diagnosis and prognosis in OSCC patients; however, further studies in a larger cohort of patients are mandatory to introduce liquid biopsy in the routine clinical practice for the OSCC management. Biomarkers, liquid biopsy, microRNA, oral squamous cell carcinoma, systematic review.
PubMed: 36320672
DOI: 10.4317/jced.59736 -
Translational Gastroenterology and... 2021Blood-borne tumour markers in the form of circulating tumour cells (CTCs) are of intense research interest in the diagnostic and prognostic work-up of hepatocellular...
BACKGROUND
Blood-borne tumour markers in the form of circulating tumour cells (CTCs) are of intense research interest in the diagnostic and prognostic work-up of hepatocellular carcinoma (HCC).
METHODS
This is a meta-analysis. Using a PICO strategy, adults with HCC was the population, with the individual CTCs as the intervention and comparators. The primary outcome was the sensitivity and specificity of HCC detection with tumour specific single gene methylation alteration. Secondary outcomes were the comparison using specific assay methods and the effect of early late stages on CTC positivity. We included patients with HCC who had samples taken from peripheral blood and had sufficient data to assess the outcome data. ASSIA, Cochrane library, EMbase, Medline, PubMed and the knowledge network Scotland were systematically searched with appropriate Mesh terms employed. The quality assessment of diagnostic accuracy studies (QUADAS) was used to ensure quality of data. Statistical analysis was performed using the 'Rev Man' meta-analysis soft ward for Windows.
RESULTS
The review included 36 studies, with a total of 5,853 patients. Here, we found that AFP has the highest overall diagnostic performance. The average Youden index amongst all CTC was 0.46 with a mode and median of 0.5 with highest of 0.87 and lowest of 0.01.
CONCLUSIONS
The available literature provides weak evidence that there is potential in the use of CTC, however the lack of a standardised procedure in the study of CTC contribute to the lack of consensus of use. Future research should include large scaled, standardized studies for the diagnostic accuracy of CTCs.
PubMed: 34805576
DOI: 10.21037/tgh.2020.01.11 -
Medicine Jan 2020Liquid biopsy is a novel method for cancer diagnosis, which has been applied in lung and breast cancers, demonstrating high diagnostic value. However, clinical value of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Liquid biopsy is a novel method for cancer diagnosis, which has been applied in lung and breast cancers, demonstrating high diagnostic value. However, clinical value of it in pancreatic cancer (PC) remains to be verified. The aim of this meta-analysis was to evaluate overall diagnostic value of various liquid biopsy methods (circulating tumor DNA, circulating tumor cells and exosomes) in detecting PC.
METHODS
We comprehensively searched relevant studies in PubMed, Medline, Embase, and Web of Science without time limitation according to PRISMA. Data necessary for reconstructing a 2 × 2 table was calculated from the original articles. The methodological quality of included studies was evaluated by QUADAS-2. Statistical analysis including was performed by the software Meta-Disc version 1.4, and STATA 14.2.
RESULTS
A total of 19 studies including 1872 individuals were included in this meta-analysis. In which, 7 were studies about ctDNA, 7 were on CTCs and 6 were about exosomes (Sefrioui D, studied diagnostic accuracy of both ctDNA and CTCs, with no common patients in these 2 groups). The pooled sensitivity estimates for ctDNA, CTCs and exosomes in detecting PC with their 95% confidential intervals (95% CI) were 0.64 (95%CI 0.58-0.70), 0.74 (95%CI 0.68-0.79) and 0.93 (95%CI 0.90-0.95), respectively. The pooled specificity estimates were 0.92(95%CI 0.88-0.95), 0.83 (95%CI 0.78-0.88) and 0.92 (95%CI 0.88-0.95), respectively. The area under curve (AUC) of the sROC for ctDNA, CTCs and exosomes in detecting PC were 0.9478, 0.8166, and 0.9819, respectively. The overall sensitivity, specificity and AUC of the sROC curve for overall liquid biopsy in detecting PC were 0.80 (95%CI 0.77-0.82), 0.89 (95%CI 0.87-0.91) and 0.9478, respectively.
CONCLUSION
This meta-analysis confirmed that liquid biopsy had high diagnostic value in detecting PC. In ctDNA, CTCs and exosomes these 3 subgroups, exosomes showed highest sensitivity and specificity.
Topics: Biomarkers, Tumor; DNA, Neoplasm; Exosomes; Humans; Liquid Biopsy; Pancreatic Neoplasms; Sensitivity and Specificity
PubMed: 32011436
DOI: 10.1097/MD.0000000000018581