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BMC Cancer Dec 2023The clinical relevance of circulating tumor cell-white blood cell (CTC-WBC) clusters in cancer prognosis is a subject of ongoing debate. This study aims to unravel their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The clinical relevance of circulating tumor cell-white blood cell (CTC-WBC) clusters in cancer prognosis is a subject of ongoing debate. This study aims to unravel their contentious predictive value for patient outcomes.
METHODS
We conducted a comprehensive literature search of PubMed, Embase, and Cochrane Library up to December 2022. Eligible studies that reported survival outcomes and examined the presence of CTC-WBC clusters in solid tumor patients were included. Hazard ratios (HR) were pooled to assess the association between CTC-WBC clusters and overall survival (OS), as well as progression-free survival (PFS)/disease-free survival (DFS)/metastasis-free survival (MFS)/recurrence-free survival (RFS). Subgroup analyses were performed based on sampling time, treatment method, detection method, detection system, and cancer type.
RESULTS
A total of 1471 patients from 10 studies were included in this meta-analysis. The presence of CTC-WBCs was assessed as a prognostic factor for overall survival and PFS/DFS/MFS/RFS. The pooled analysis demonstrated that the presence of CTC-WBC clusters was significantly associated with worse OS (HR = 2.44, 95% CI: 1.74-3.40, P < 0.001) and PFS/DFS/MFS/RFS (HR = 1.83, 95% CI: 1.49-2.24, P < 0.001). Subgroup analyses based on sampling time, treatment method, detection method, detection system, cancer type, and study type consistently supported these findings. Further analyses indicated that CTC-WBC clusters were associated with larger tumor size (OR = 2.65, 95% CI: 1.58-4.44, P < 0.001) and higher alpha-fetoprotein levels (OR = 2.52, 95% CI: 1.50-4.22, P < 0.001) in hepatocellular carcinoma. However, no significant association was found between CTC-WBC clusters and TNM stage, depth of tumor invasion, or lymph node metastasis in the overall analysis.
CONCLUSIONS
CTC-WBC clusters are negative predictors for OS and PFS/DFS/MFS/RFS in patients with solid tumors. Monitoring CTC-WBC levels may provide valuable information for predicting disease progression and guiding treatment decisions.
Topics: Humans; Prognosis; Neoplastic Cells, Circulating; Disease-Free Survival; Progression-Free Survival; Liver Neoplasms
PubMed: 38087278
DOI: 10.1186/s12885-023-11711-7 -
BMC Cancer Jul 2022To describe and analyze the predictive models of the prognosis of patients with hepatocellular carcinoma (HCC) undergoing systemic treatment.
OBJECTIVE
To describe and analyze the predictive models of the prognosis of patients with hepatocellular carcinoma (HCC) undergoing systemic treatment.
DESIGN
Systematic review.
DATA SOURCES
PubMed and Embase until December 2020 and manually searched references from eligible articles.
ELIGIBILITY CRITERIA FOR STUDY SELECTION
The development, validation, or updating of prognostic models of patients with HCC after systemic treatment.
RESULTS
The systematic search yielded 42 eligible articles: 28 articles described the development of 28 prognostic models of patients with HCC treated with systemic therapy, and 14 articles described the external validation of 32 existing prognostic models of patients with HCC undergoing systemic treatment. Among the 28 prognostic models, six were developed based on genes, of which five were expressed in full equations; the other 22 prognostic models were developed based on common clinical factors. Of the 28 prognostic models, 11 were validated both internally and externally, nine were validated only internally, two were validated only externally, and the remaining six models did not undergo any type of validation. Among the 28 prognostic models, the most common systemic treatment was sorafenib (n = 19); the most prevalent endpoint was overall survival (n = 28); and the most commonly used predictors were alpha-fetoprotein (n = 15), bilirubin (n = 8), albumin (n = 8), Child-Pugh score (n = 8), extrahepatic metastasis (n = 7), and tumor size (n = 7). Further, among 32 externally validated prognostic models, 12 were externally validated > 3 times.
CONCLUSIONS
This study describes and analyzes the prognostic models developed and validated for patients with HCC who have undergone systemic treatment. The results show that there are some methodological flaws in the model development process, and that external validation is rarely performed. Future research should focus on validating and updating existing models, and evaluating the effects of these models in clinical practice.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42020200187 .
Topics: Bilirubin; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Prognosis; Sorafenib
PubMed: 35810271
DOI: 10.1186/s12885-022-09841-5 -
The Cochrane Database of Systematic... May 2022Hepatocellular carcinoma occurs mostly in people with chronic liver disease and ranks sixth in terms of global incidence of cancer, and third in terms of cancer deaths.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hepatocellular carcinoma occurs mostly in people with chronic liver disease and ranks sixth in terms of global incidence of cancer, and third in terms of cancer deaths. In clinical practice, magnetic resonance imaging (MRI) is used as a second-line diagnostic imaging modality to confirm the presence of focal liver lesions suspected as hepatocellular carcinoma on prior diagnostic test such as abdominal ultrasound or alpha-fetoprotein, or both, either in surveillance programmes or in clinical settings. According to current guidelines, a single contrast-enhanced imaging study (computed tomography (CT) or MRI) showing typical hallmarks of hepatocellular carcinoma in people with cirrhosis is considered valid to diagnose hepatocellular carcinoma. The detection of hepatocellular carcinoma amenable to surgical resection could improve the prognosis. However, a significant number of hepatocellular carcinomas do not show typical hallmarks on imaging modalities, and hepatocellular carcinoma may, therefore, be missed. There is no clear evidence of the benefit of surveillance programmes in terms of overall survival: the conflicting results can be a consequence of inaccurate detection, ineffective treatment, or both. Assessing the diagnostic accuracy of MRI may clarify whether the absence of benefit could be related to underdiagnosis. Furthermore, an assessment of the accuracy of MRI in people with chronic liver disease who are not included in surveillance programmes is needed for either ruling out or diagnosing hepatocellular carcinoma.
OBJECTIVES
Primary: to assess the diagnostic accuracy of MRI for the diagnosis of hepatocellular carcinoma of any size and at any stage in adults with chronic liver disease. Secondary: to assess the diagnostic accuracy of MRI for the diagnosis of resectable hepatocellular carcinoma in adults with chronic liver disease, and to identify potential sources of heterogeneity in the results.
SEARCH METHODS
We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Hepato-Biliary Group Diagnostic Test of Accuracy Studies Register, the Cochrane Library, MEDLINE, Embase, and three other databases to 9 November 2021. We manually searched articles retrieved, contacted experts, handsearched abstract books from meetings held during the last 10 years, and searched for literature in OpenGrey (9 November 2021). Further information was requested by e-mails, but no additional information was provided. No data was obtained through correspondence with investigators. We applied no language or document-type restrictions.
SELECTION CRITERIA
Studies assessing the diagnostic accuracy of MRI for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease, with cross-sectional designs, using one of the acceptable reference standards, such as pathology of the explanted liver and histology of resected or biopsied focal liver lesion with at least a six-month follow-up.
DATA COLLECTION AND ANALYSIS
At least two review authors independently screened studies, extracted data, and assessed the risk of bias and applicability concerns, using the QUADAS-2 checklist. We presented the results of sensitivity and specificity, using paired forest plots, and we tabulated the results. We used a hierarchical meta-analysis model where appropriate. We presented uncertainty of the accuracy estimates using 95% confidence intervals (CIs). We double-checked all data extractions and analyses.
MAIN RESULTS
We included 34 studies, with 4841 participants. We judged all studies to be at high risk of bias in at least one domain because most studies used different reference standards, often inappropriate to exclude the presence of the target condition, and the time interval between the index test and the reference standard was rarely defined. Regarding applicability, we judged 15% (5/34) of studies to be at low concern and 85% (29/34) of studies to be at high concern mostly owing to characteristics of the participants, most of whom were on waiting lists for orthotopic liver transplantation, and due to pathology of the explanted liver being the only reference standard. MRI for hepatocellular carcinoma of any size and stage: sensitivity 84.4% (95% CI 80.1% to 87.9%) and specificity 93.8% (95% CI 90.1% to 96.1%) (34 studies, 4841 participants; low-certainty evidence). MRI for resectable hepatocellular carcinoma: sensitivity 84.3% (95% CI 77.6% to 89.3%) and specificity 92.9% (95% CI 88.3% to 95.9%) (16 studies, 2150 participants; low-certainty evidence). The observed heterogeneity in the results remains mostly unexplained. The sensitivity analyses, which included only studies with clearly prespecified positivity criteria and only studies in which the reference standard results were interpreted without knowledge of the results of the index test, showed no variation in the results.
AUTHORS' CONCLUSIONS
We found that using MRI as a second-line imaging modality to diagnose hepatocellular carcinoma of any size and stage, 16% of people with hepatocellular carcinoma would be missed, and 6% of people without hepatocellular carcinoma would be unnecessarily treated. For resectable hepatocellular carcinoma, we found that 16% of people with resectable hepatocellular carcinoma would improperly not be resected, while 7% of people without hepatocellular carcinoma would undergo inappropriate surgery. The uncertainty resulting from the high risk of bias in the included studies and concerns regarding their applicability limit our ability to confidently draw conclusions based on our results.
Topics: Adult; Carcinoma, Hepatocellular; Cross-Sectional Studies; Humans; Liver Neoplasms; Magnetic Resonance Imaging; Sensitivity and Specificity; Ultrasonography
PubMed: 35521901
DOI: 10.1002/14651858.CD014798.pub2 -
Genetic Testing and Molecular Biomarkers Oct 2020Multiple studies have explored the prognostic role and clinical significance of the expression of the programmed cell death-1 () gene in hepatocellular carcinoma (HCC).... (Meta-Analysis)
Meta-Analysis
Clinicopathological and Prognostic Roles of the Expression Levels of the Programmed Cell Death-1 Gene in Patients with Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.
Multiple studies have explored the prognostic role and clinical significance of the expression of the programmed cell death-1 () gene in hepatocellular carcinoma (HCC). However, the results have been inconsistent. This study evaluated expression and its clinical significance in patients with HCC, as well as the correlation between HCC pathological features and prognoses. All related research in PubMed, Embase, and Web of Science prior to October 31, 2019, was retrieved. The Newcastle-Ottawa Scale was used to evaluate the quality of the literature. Stata 14.0 statistical software was used to analyze the data, and the correlations between expression and the clinicopathological characteristics of patients were analyzed using the odds ratio (OR) and its 95% confidence interval (CI). The hazard ratio (HR) and its 95% CI were used to analyze the correlation between high expression and patient prognosis. Begg's test was used to evaluate publication bias. A total of 581 patients were analyzed in the six studies included in the meta-analysis. Pooled analysis revealed that high levels of expression did not correlate with overall survival (HR = 0.79; 95% CI: [0.41-1.54]; = 0.493). PD-1 positivity was associated with better disease-free survival (HR = 0.52; 95% CI: [0.38-0.72]; < 0.0001). Furthermore, elevated expression corrected for age (OR = 0.62, 95% CI: [0.41-0.96]; = 0.030) and alpha-fetoprotein levels (OR = 2.27, 95% CI: [1.46-3.55]; < 0.0001), were not correlated with patient sex, tumor size, tumor multiplicity, hepatitis B virus history, tumor node metastasis stage or Barcelona Clinic Liver Cancer stage. This meta-analysis revealed that expression may be a useful prognostic marker in HCC patients. Prospective clinical studies are needed to support these findings.
Topics: Apoptosis; Biomarkers, Tumor; Carcinoma, Hepatocellular; Disease-Free Survival; Humans; Liver Neoplasms; Odds Ratio; Prognosis; Programmed Cell Death 1 Receptor; Prospective Studies
PubMed: 32990474
DOI: 10.1089/gtmb.2020.0063 -
BMC Gastroenterology Jul 2020Alpha-fetoprotein (AFP) has been widely used for many years as a serum marker for hepatocellular carcinoma (HCC). However, AFP has been recognized as having poor... (Meta-Analysis)
Meta-Analysis
The role of circulating microRNAs for the diagnosis of hepatitis B virus-associated hepatocellular carcinoma with low alpha-fetoprotein level: a systematic review and meta-analysis.
BACKGROUND
Alpha-fetoprotein (AFP) has been widely used for many years as a serum marker for hepatocellular carcinoma (HCC). However, AFP has been recognized as having poor sensitivity. More and more studies have concluded that circulating microRNAs (miRNAs) might be a promising biomarker that could complement AFP. However, the diagnostic ability of circulating miRNAs has varied among the studies. Therefore, we performed the present meta-analysis to appraise the diagnostic performance of circulating miRNAs as a biomarker for hepatitis B virus-associated HCC (HBV-HCC) patients with low AFP levels.
METHODS
We performed a systematic review and meta-analysis of the published literature to assess the diagnostic accuracy of circulating miRNAs in differentiating HBV-HCC patients with low AFP levels from non-HCC controls.
RESULTS
Circulating miRNAs showed promising potential in the diagnosis of HBV-HCC patients with low AFP levels. In the low-AFP HBV-HCC patients, the area under the curve (AUC) was 0.88 (95% confidence interval [CI]: 0.84-0.90). The pooled sensitivity and specificity were 0.84 (95% CI: 0.78-0.88) and 0.76 (95% CI: 0.69-0.83), respectively.
CONCLUSIONS
The detection of circulating miRNAs provides a valuable method for the diagnosis of HBV-HCC in patients with low AFP levels.
Topics: Biomarkers, Tumor; Carcinoma, Hepatocellular; Circulating MicroRNA; Hepatitis B virus; Humans; Liver Neoplasms; MicroRNAs; ROC Curve; alpha-Fetoproteins
PubMed: 32736604
DOI: 10.1186/s12876-020-01345-5 -
Diagnostics (Basel, Switzerland) Feb 2023the early diagnosis of hepatocellular carcinoma (HCC) benefits from the use of alpha-fetoprotein (AFP) together with imaging diagnosis using abdominal ultrasonography,...
BACKGROUND AND OBJECTIVES
the early diagnosis of hepatocellular carcinoma (HCC) benefits from the use of alpha-fetoprotein (AFP) together with imaging diagnosis using abdominal ultrasonography, CT, and MRI, leading to improved early detection of HCC. A lot of progress has been made in the field, but some cases are missed or late diagnosed in advanced stages of the disease. Therefore, new tools (serum markers, imagistic technics) are continually being reconsidered. Serum alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist II (PIVKA II) diagnostic accuracy for HCC (global and early disease) has been investigated (in a separate or cumulative way). The purpose of the present study was to determine the performance of PIVKA II compared to AFP.
MATERIALS AND METHODS
systematic research was conducted in PubMed, Web of Science, Embase, Medline and the Cochrane Central Register of Controlled Trials, taking into consideration articles published between 2018 and 2022.
RESULTS
a total number of 37 studies (5037 patients with HCC vs. 8199 patients-control group) have been included in the meta-analysis. PIVKA II presented a better diagnostic accuracy in HCC diagnostic vs. alpha-fetoprotein (global PIVKA II AUROC 0.851 vs. AFP AUROC 0.808, respectively, 0.790 vs. 0.740 in early HCC cases). The conclusion from a clinical point of view, concomitant use of PIVKA II and AFP can bring useful information, added to that brought by ultrasound examination.
PubMed: 36899960
DOI: 10.3390/diagnostics13050816 -
Journal of Clinical Medicine Jan 2023Background GALAD score, comprising five clinical parameters, is a predictive model developed for hepatocellular carcinoma (HCC) detection. Since its emergence, its... (Review)
Review
Background GALAD score, comprising five clinical parameters, is a predictive model developed for hepatocellular carcinoma (HCC) detection. Since its emergence, its diagnostic ability has been validated in different populations with a wide variation. Therefore, we conducted a meta-analysis to investigate its overall diagnostic performance in differentiating HCC in chronic liver diseases. Methods Eligible studies were searched in the , , , , , and databases by 29 May 2022. Pooled sensitivity, pooled specificity, and area under the receiver operating characteristic curve (AUC) with the corresponding 95% confidence intervals (CI) were estimated. Results Fifteen original studies (comprising 19,021 patients) were included. For detecting any-stage HCC, GALAD score yielded an excellent ability, with pooled sensitivity, specificity, and AUC of 0.82 (95%CI: 0.78-0.85), 0.89 (95%CI: 0.85-0.91), and 0.92 (95%CI: 0.89-0.94), respectively. Notably, further analyses demonstrated a good diagnostic accuracy of GALAD score for identifying Barcelona Clinic Liver Cancer staging (BCLC) 0/A HCC, with a moderate sensitivity (0.73 (95%CI: 0.66-0.79)) and a high specificity (0.87 (95%CI: 0.81-0.91)); by contrast, only 38% of early-stage patients can be identified by alpha-fetoprotein, with an AUC value of 0.70 (95%CI: 0.66-0.74). Following subgroup analyses based on different HCC etiologies, higher sensitivities and AUC values were observed in subgroups with hepatitis C or non-viral liver diseases. For detecting BCLC 0/A HCC in the cirrhotic population, GALAD score had a pooled sensitivity, specificity, and AUC of 0.78 (95%CI: 0.66-0.87), 0.80 (95%CI: 0.72-0.87), and 0.86 (95%CI: 0.83-0.89). Conclusions We highlighted the superior diagnostic accuracy of GALAD score for detecting any-stage HCC with a high sensitivity and specificity, especially for early-stage HCC, with a relatively stable diagnostic performance. The addition of GALAD score into ultrasound surveillance may identify more HCC patients. Our findings imply the robust power of the GALAD score as a HCC screening or diagnostic tool, and it should be further validated by more studies with high quality.
PubMed: 36769597
DOI: 10.3390/jcm12030949 -
Cancer Medicine Feb 2020A meta-analysis was formulated to appraise the diagnostic accuracy of circulating tumor DNA (ctDNA) in hepatocellular carcinoma (HCC). (Meta-Analysis)
Meta-Analysis
PURPOSE
A meta-analysis was formulated to appraise the diagnostic accuracy of circulating tumor DNA (ctDNA) in hepatocellular carcinoma (HCC).
MATERIALS AND METHODS
We enrolled all relevant studies published until September 2019. Four primary subgroups were investigated: the subgroup of quantitative or qualitative analysis of ctDNA, the subgroup of Ras association domain family 1 isoform A (RASSF1A) methylation in ctDNA and the subgroup of the combined alpha-fetoprotein (AFP) and ctDNA assay. We analyzed the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) as well as the area under the curve (AUC).
RESULTS
A total of 33 qualified articles with 4113 subjects were incorporated into our meta-analysis. The combined SEN, SPE, and DOR in quantitative studies were 0.722 (95% confidence interval (95% CI): 0.686-0.756), 0.823 (95% CI: 0.789-0.854), 18.532 (95% CI: 8.245-41.657), respectively, yielding an AUC of 0.880. For qualitative studies, the corresponding value was 0.568 (95% CI: 0.548-0.587), 0.882 (95% CI: 0.867-0.897), 10.457 (95% CI: 7.270-15.040) and 0.787, respectively. Detection of RASSF1A methylation yielded an AUC of 0.841, with a SEN of 0.644 (95% CI: 0.608-0.678) and a SPE of 0.875 (95% CI: 0.847-0.900). AFP combined with ctDNA assay achieved an AUC of 0.944, with a SEN of 0.760 (95% CI: 0.728-00.790) and a SPE of 0.920 (95% CI: 0.893-00.942).
CONCLUSION
Circulating tumor DNA displays a promising diagnostic potential in HCC. However, it is not independently sufficient and can serve as an assistant tool combined with AFP for HCC screening and detection.
Topics: Carcinoma, Hepatocellular; Circulating Tumor DNA; DNA Methylation; Humans; Liver Neoplasms; Mass Screening; Predictive Value of Tests; ROC Curve; Tumor Suppressor Proteins; alpha-Fetoproteins
PubMed: 31876977
DOI: 10.1002/cam4.2799 -
Medicine Aug 2019Post-treatment alpha-fetoprotein (AFP) response has been reported to be associated with prognosis of hepatocellular carcinoma (HCC) patients, but the results were not... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Post-treatment alpha-fetoprotein (AFP) response has been reported to be associated with prognosis of hepatocellular carcinoma (HCC) patients, but the results were not consistent. This meta-analysis aimed to explore the relationship between AFP response and clinical outcomes of HCC.
METHODS
PubMed, Embase, Medline and Cochrane library were searched for relevant articles published before March 20, 2019. The data were analyzed using RevMan5.3 software.
RESULTS
Twenty-nine articles with 4726 HCC patients were finally included for analysis. The pooled results showed that post-treatment AFP response was significantly associated with overall survival (OS) (hazard ratio (HR) = 0.41, 95% confidence interval (CI): 0.35-0.47, P <.001), progression free survival (PFS) (HR = 0.46, 95% CI: 0.39-0.54, P <.001) and recurrence free survival (RFS) (HR = 0.41, 95% CI: 0.29-0.56, P <.001) of HCC patients.
CONCLUSION
post-treatment AFP response might be a useful prognostic marker for HCC patients.
Topics: Humans; Liver Neoplasms; Prognosis; alpha-Fetoproteins
PubMed: 31374020
DOI: 10.1097/MD.0000000000016557 -
Gut Jan 2022
Meta-Analysis
Topics: Carcinoma, Hepatocellular; Early Detection of Cancer; Humans; Liver Neoplasms; Ultrasonography; alpha-Fetoproteins
PubMed: 33649047
DOI: 10.1136/gutjnl-2020-323615