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JAMA Network Open May 2022Phase 3 trials for patients with metastatic colorectal cancer (mCRC) have been conducted with varying designs and often with surrogate end points for overall survival...
Overall Survival in Phase 3 Clinical Trials and the Surveillance, Epidemiology, and End Results Database in Patients With Metastatic Colorectal Cancer, 1986-2016: A Systematic Review.
IMPORTANCE
Phase 3 trials for patients with metastatic colorectal cancer (mCRC) have been conducted with varying designs and often with surrogate end points for overall survival (OS).
OBJECTIVES
To critically examine the factors associated with clinically relevant improvement in OS (defined as ≥2 months) in these trials and to evaluate their association with outcomes reflected in Surveillance, Epidemiology, and End Results (SEER) registry data.
EVIDENCE REVIEW
Medline, EMBASE, Cochrane, Web of Science, ClinicalTrials.gov, EU Clinical Trials Register, and the International Clinical Trials Registry Platform were searched for phase 3 trials of systemic therapy for patients with mCRC by decade (1986-1996, 1997-2006, and 2007-2016), excluding early or pilot studies, studies that did not involve an anticancer drug, studies on cancer screening and prevention, reports of pooled data from multiple trials, and studies with nonpharmaceutical approaches. The association of drug development with OS outside the clinical trial setting was evaluated using data from the SEER registry, including adult patients with a primary cancer site in the colon or rectum, including adenocarcinoma, mucinous adenocarcinoma, or signet ring cell carcinoma; a distant stage; and receipt of chemotherapy as first-line therapy. Kaplan-Meier curves and log-rank tests were used to assess OS.
FINDINGS
The literature search identified 150 phase III clinical trials with 77 494 total enrollments, and 67 126 patients with mCRC were identified from the SEER database. Significant increases in survival were noted over time, best reflected in the experimental arm of first-line therapy (OS increased by 5.7 months per 10 years; 95% CI, 4.7-6.6 months; progression-free survival increased by 1.4 months per 10 years; 95% CI, 0.7-2.1 months). Although 69 of 148 trials (46.6%) met their predefined primary end point (including 20 of 44 trials [45.5%] with OS as the primary end point), only 35 of 132 trials (26.5%) resulted in improvement in OS by 2 months or more (including 13 of 42 trials [31.0%] with OS as the primary end point). Multivariable logistic regression showed that third-line therapies or later (odds ratio, 0.57; 95% CI, 0.51-0.63) and funding by pharmaceutical companies (odds ratio, 0.57; 95% CI, 0.54-0.60) were less often associated with improvement in OS. Furthermore, there was a decrease in the novelty of targets and agents over time, with trials that evaluated regimens composed entirely of previously approved drugs for mCRC increasing from 28% to 50%. Data from the SEER database showed that median OS increased from 12 months (95% CI, 12-13 months) (1986-1996) to 21 months (95% CI, 21-22 months) (2007-2015) (P < .001), but the 5-year OS continued to be low at 12.2% in 2011.
CONCLUSIONS AND RELEVANCE
In this systematic review, OS for patients with mCRC appeared to improve significantly in trials, translating into meaningful benefits outside the clinical trial setting; however, these advances, although significant cumulatively, are largely incremental individually. These data should be a call to aim for larger gains from future trials with novel drugs, building on the increasing understanding of the biology of mCRC and sophisticated translational research tools.
Topics: Adult; Antineoplastic Agents; Colorectal Neoplasms; Databases, Factual; Humans; Progression-Free Survival
PubMed: 35608860
DOI: 10.1001/jamanetworkopen.2022.13588 -
Clinical Cancer Research : An Official... Nov 2008A meta-analytic approach was used to estimate the frequency of: (a) microsatellite instability-high (MSI-H) phenotype in unselected ovarian cancers and (b) various... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
A meta-analytic approach was used to estimate the frequency of: (a) microsatellite instability-high (MSI-H) phenotype in unselected ovarian cancers and (b) various histologic subtypes of mismatch repair (MMR)-deficient epithelial ovarian cancers.
METHODS
A systematic search of the Medline electronic database was conducted to identify articles published between January 1, 1966, and December 31, 2007, that examined MMR deficiency in ovarian cancers. Data were extracted on the study population, sample size, MSI-H frequency, and histology of MMR-deficient ovarian tumors.
RESULTS
The pooled proportion of MSI-H ovarian cancers was 0.12 [95% confidence interval (CI), 0.08-0.17] from 18 studies with 977 cases. The proportion of histologic subtypes in the pooled analysis from 15 studies with 159 cases was serous at 0.32 (95% CI, 0.20-0.44), mucinous at 0.19 (95% CI, 0.12-0.27), endometrioid at 0.29 (95% CI, 0.22-0.36), clear cell at 0.18 (95% CI, 0.09-0.28), and mixed at 0.24 (95% CI, 0.07-0.47). There was significant heterogeneity between studies.
CONCLUSIONS
The frequency of the MSI-H phenotype in unselected ovarian cancers approximates 12%. MMR-deficient ovarian cancers also seem to be characterized by an overrepresentation of nonserous histologic subtypes. Knowledge of histologic subtype may aid clinicians in identifying the relatively large proportion of ovarian cancers due to MMR defects; such knowledge has potential implications for medical management.
Topics: DNA Mismatch Repair; Female; Humans; Microsatellite Instability; Ovarian Neoplasms; Phenotype
PubMed: 18980979
DOI: 10.1158/1078-0432.CCR-08-1387 -
Scandinavian Journal of Immunology Jun 2016Tumour-associated autoantibodies may be promising biomarkers that could facilitate breast cancer (BC) diagnosis and improve patient outcomes. This review aims to... (Meta-Analysis)
Meta-Analysis Review
Tumour-associated autoantibodies may be promising biomarkers that could facilitate breast cancer (BC) diagnosis and improve patient outcomes. This review aims to identify the tumour-associated autoantibodies with the greatest diagnostic potential. Systematic searches were conducted using PubMed and Web of Science. The most studied tumour-associated autoantibody was included in a meta-analysis, and its clinical value was determined using Fagan's nomogram. The analysis included 84 studies regarding tumour-associated autoantibodies with the diagnostic value. Anti-p53 antibody was the most frequently studied autoantibody, followed by autoantibodies against MUC1, HER2 and cyclin B1. Although individual tumour-associated autoantibodies showed low diagnostic sensitivity, combinations of autoantibodies offered relatively high sensitivity. Enzyme-linked immunosorbent assay (ELISA) was the most common detection method, and nucleic acid programmable protein microarrays appeared preferable to common protein microarrays. As the most commonly studied autoantibody, anti-p53 antibody was included in a meta-analysis. When it had been detected using ELISA and cut-off values were defined as the mean +2 or 3 standard deviations, the summary area under the receiver operating characteristic curve for the presence of BC was 0.78. Fagan's nomogram showed post-test probabilities of 32% and 6% for positive and negative results, respectively. Mammography might be supplemented by the use of tumour-associated autoantibodies as biomarkers for BC diagnosis in younger women with increased risks of BC. Even though several studies have investigated the diagnostic use of tumour-associated autoantibodies as biomarkers for BC detection, a high-quality prospective study is needed to validate their diagnostic value in practice.
Topics: Animals; Biomarkers, Tumor; Breast Neoplasms; Cyclin B1; Enzyme-Linked Immunosorbent Assay; Female; Humans; Mammography; Mucin-1; Predictive Value of Tests; Protein Array Analysis; Receptor, ErbB-2; Reference Standards; Sensitivity and Specificity; Tumor Suppressor Protein p53
PubMed: 26991924
DOI: 10.1111/sji.12430 -
European Journal of Radiology Jul 2009Ovarian cancer is the commonest tumor in female patients with a propensity for recurrence even after primary chemotherapy in early stage. The accuracy of CA 125, PET... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND AND PURPOSE
Ovarian cancer is the commonest tumor in female patients with a propensity for recurrence even after primary chemotherapy in early stage. The accuracy of CA 125, PET alone, PET-CT, CT and MRI in diagnosing the recurrent ovarian carcinoma has never been systematically assessed, and present systematic review was aimed at this issue.
METHODS
We searched for articles published from January 1995 to November 2007, inclusion criteria including: articles were reported in English or Chinese; CA 125, PET whether interpreted with or without the use of CT, CT or MRI was used to detect recurrent ovarian carcinoma; Histopathologic analysis and/or close clinical and imaging follow-up for at least 6 months. We extracted data to calculate sensitivity, specificity, SROC curves and AUC and to test for heterogeneity.
RESULT
In 34 included studies, CA 125 had the highest pooled specificity, 0.93 (95% CI: 0.89-0.95); PET-CT had highest pooled sensitivity, 0.91 (95% CI: 0.88-0.94). The AUC of CA 125, PET alone, PET-CT, CT and MRI were 0.9219, 0.9297, 0.9555, 0.8845 and 0.7955, respectively. Results of pairwise comparison between each modality demonstrated AUC of PET, whether interpreted with or without the use of CT, was higher than that of CT or MR, p<0.05. The pooled sensitivity, pooled specificity and AUC showed no statistical significance between PET alone and PET-CT. There was heterogeneity among studies and evidence of publication bias.
CONCLUSION
PET-CT might be a useful supplement to current surveillance techniques, particularly for those patients with an increasing CA 125 level and negative CT or MR imaging. However, regarding to diagnostic accuracy, interpreted CT images may have limited additional value on PET in detecting recurrent ovarian cancer.
Topics: Biomarkers, Tumor; CA-125 Antigen; Female; Humans; Magnetic Resonance Imaging; Neoplasm Proteins; Neoplasm Recurrence, Local; Ovarian Neoplasms; Positron-Emission Tomography; Prevalence; Reproducibility of Results; Sensitivity and Specificity; Subtraction Technique; Tomography, X-Ray Computed
PubMed: 18378417
DOI: 10.1016/j.ejrad.2008.02.019 -
PloS One 2015To evaluate the predicting value of MUC1 expression in lymph node and distant metastasis of colorectal cancer (CRC). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the predicting value of MUC1 expression in lymph node and distant metastasis of colorectal cancer (CRC).
METHODS
Pubmed/ MEDLINE and EMBASE were searched to identify eligible studies that evaluated the correlation between MUC1 and CRC. A meta-analysis was conducted to evaluate the impact of MUC1 expression on CRC metastasis.
RESULTS
A total of 18 studies (n = 3271) met inclusion criteria and the mean Newcastle-Ottawa Scale (NOS) score was 6.3 with a range from 4 to 8. The pooled OR in the meta-analysis of 15 studies indicated that positive MUC1 expression correlated with more CRC node metastasis (OR = 2.32, 95% CI = 1.63-3.29). The data synthesis of 6 studies suggested that MUC1 expression predicted more possibility of CRC distant metastasis (OR = 2.22, 95% CI = 1.23-4.00). In addition, the combined OR of 7 studies showed that MUC1 expression indicated higher Duke's stage (OR = 3.02, 95% CI = 2.11-4.33). No publication bias was found in the mate-analysis by Begg's test or Egger's test with the exception of the meta-analysis of MUC1 with CRC node metastasis (Begg's test p = 0.729, Egger's test p = 0.000).
CONCLUSIONS
Despite of some modest bias, the pooled evidence suggested that MUC1 expression was significantly correlated with CRC metastasis.
Topics: Biomarkers, Tumor; Colorectal Neoplasms; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Mucin-1; Neoplasm Metastasis; Predictive Value of Tests
PubMed: 26367866
DOI: 10.1371/journal.pone.0138049 -
Journal of Magnetic Resonance Imaging :... Oct 2021Differentiation of benign and malignant pancreatic cystic lesions on MRI, computed tomography (CT), and endoscopic ultrasound (EUS) is critical for determining... (Meta-Analysis)
Meta-Analysis
Diagnostic Accuracy of MRI for Differentiation of Benign and Malignant Pancreatic Cystic Lesions Compared to CT and Endoscopic Ultrasound: Systematic Review and Meta-analysis.
BACKGROUND
Differentiation of benign and malignant pancreatic cystic lesions on MRI, computed tomography (CT), and endoscopic ultrasound (EUS) is critical for determining management.
PURPOSE
To perform a systematic review evaluating the diagnostic accuracy of MRI for diagnosing malignant pancreatic cystic lesions, and to compare the accuracy of MRI to CT and EUS.
STUDY TYPE
Systematic review and meta-analysis.
DATA SOURCES
MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus were searched until February 2020 for studies reporting MRI accuracy for assessing pancreatic cystic lesions.
FIELD STRENGTH
1.5T or 3.0T.
ASSESSMENT
Methodologic and outcome data were extracted by two reviewers (AU and MA, 2 years of experience each). All studies of pancreatic cystic lesions on MRI were identified. Studies with incomplete MRI technique were excluded. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool.
STATISTICAL TESTS
Sensitivity/specificity was pooled using bivariate random-effects meta-analysis with 95% confidence intervals (95%CI). Pairwise-comparison of MRI to CT and EUS was performed. The impact of gadolinium-based contrast agents, mucinous lesions, and risk of bias were explored using meta-regression.
RESULTS
MRI pooled sensitivity was 76% (95%CI 67% to 84%) and specificity was 80% (95%CI 74% to 85%) for distinguishing benign and malignant lesions. MRI and CT had similar sensitivity (P = 0.822) and specificity (P = 0.096), but MRI was more specific than EUS (80% vs. 75%, P < 0.05). Studies including only contrast-enhanced MRI were more sensitive than those including unenhanced exams (P < 0.05). MRI sensitivity and specificity did not differ for mucinous lesions (P = 0.537 and P = 0.384, respectively) or for studies at risk of bias (P = 0.789 and P = 0.791, respectively).
DATA CONCLUSION
MRI and CT demonstrate comparable accuracy for diagnosing malignant pancreatic cystic lesions. EUS is less specific than MRI, which suggests that, in some cases, management should be guided by MRI findings rather than EUS.
LEVEL OF EVIDENCE
3 TECHNICAL EFFICACY STAGE: 2.
Topics: Endosonography; Humans; Magnetic Resonance Imaging; Pancreatic Cyst; Pancreatic Neoplasms; Sensitivity and Specificity; Tomography, X-Ray Computed
PubMed: 33847435
DOI: 10.1002/jmri.27606 -
Clinical Gastroenterology and... Sep 2021Endoscopic remission is a recognized therapeutic endpoint in inflammatory bowel disease (IBD; Crohn's disease (CD), ulcerative colitis (UC)). The impact of persistent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Endoscopic remission is a recognized therapeutic endpoint in inflammatory bowel disease (IBD; Crohn's disease (CD), ulcerative colitis (UC)). The impact of persistent histologic activity on long-term outcomes is less clear and limited by small studies.
METHODS
We performed a systematic search of PubMed and Embase to identify eligible studies examining the association between histologic activity and relapse in patients with CD or UC in endoscopic remission. Studies were pooled together using random effects meta-analysis per the DerSimonian and Laird inverse variance method. The impact of different histologic scales, cut-offs, and individual features were examined.
FINDINGS
Our meta-analysis included 28 studies contributing 2,806 patients (2677 UC; 129 CD). In UC, histologically active disease was associated with an overall increased risk of relapse (OR, 2.41; 95% CI, 1.91-3.04), with a similar effect noted in the subgroup with endoscopic Mayo endoscopic score of 0 vs 0 or 1. More rigorous Geboes cut-offs demonstrated numerically stronger impact on relapse rates-Geboes <3.1 (OR, 2.40; 95% CI, 1.57-3.65), Geboes <2.1 (OR, 3.91; 95% CI, 2.21-6.91) and Geboes 0 (OR, 7.40; 95% CI, 2.00-18.27). Among individual histologic features, basal plasmacytosis (OR, 1.94), neutrophilic infiltrations (OR, 2.30), mucin depletion (OR, 2.05), and crypt architectural irregularities (OR, 2.22) predicted relapse. There was no association between histologic activity and relapse in CD.
CONCLUSIONS
In patients with UC in endoscopic remission, persistent histologic activity is associated with higher rates of relapse. Greater degree of normalization may have a stronger impact.
Topics: Colitis; Colitis, Ulcerative; Crohn Disease; Humans; Inflammatory Bowel Diseases; Remission Induction
PubMed: 33010406
DOI: 10.1016/j.cgh.2020.09.046 -
World Journal of Surgical Oncology Feb 2024Invasive mucinous adenocarcinoma of the lung (IMA) is a unique and rare subtype of lung adenocarcinoma with poorly defined prognostic factors and highly controversial... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Invasive mucinous adenocarcinoma of the lung (IMA) is a unique and rare subtype of lung adenocarcinoma with poorly defined prognostic factors and highly controversial studies. Hence, this study aimed to comprehensively identify and summarize the prognostic factors associated with IMA.
METHODS
A comprehensive search of relevant literature was conducted in the PubMed, Embase, Cochrane, and Web of Science databases from their inception until June 2023. The pooled hazard ratio (HR) and corresponding 95% confidence intervals (CI) of overall survival (OS) and/or disease-free survival (DFS) were obtained to evaluate potential prognostic factors.
RESULTS
A total of 1062 patients from 11 studies were included. In univariate analysis, we found that gender, age, TNM stage, smoking history, lymph node metastasis, pleural metastasis, spread through air spaces (STAS), tumor size, pathological grade, computed tomography (CT) findings of consolidative-type morphology, pneumonia type, and well-defined heterogeneous ground-glass opacity (GGO) were risk factors for IMA, and spiculated margin sign was a protective factor. In multivariate analysis, smoking history, lymph node metastasis, pathological grade, STAS, tumor size, and pneumonia type sign were found to be risk factors. There was not enough evidence that epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) mutations, CT signs of lobulated margin, and air bronchogram were related to the prognosis for IMA.
CONCLUSION
In this study, we comprehensively analyzed prognostic factors for invasive mucinous adenocarcinoma of the lung in univariate and multivariate analyses of OS and/or DFS. Finally, 12 risk factors and 1 protective factor were identified. These findings may help guide the clinical management of patients with invasive mucinous adenocarcinoma of the lung.
Topics: Humans; Adenocarcinoma of Lung; Adenocarcinoma, Mucinous; Lung; Lung Neoplasms; Lymphatic Metastasis; Neoplasm Staging; Pneumonia; Prognosis; Retrospective Studies; Male; Female
PubMed: 38303008
DOI: 10.1186/s12957-024-03326-4 -
Journal of Cardiovascular Medicine... Dec 2014An increasing number of clinical studies have explored the possibility of using tumor biomarker carbohydrate antigen 125 (CA 125) in the management of patients with... (Meta-Analysis)
Meta-Analysis Review
AIMS
An increasing number of clinical studies have explored the possibility of using tumor biomarker carbohydrate antigen 125 (CA 125) in the management of patients with heart failure. This systematic review and meta-analysis was performed to comprehensively summarize the available evidence and evaluate the applicability of CA 125 in heart failure.
METHODS
We searched PubMed, Embase, and Cochrane Central Register of controlled trials. Of the 253 studies identified, 23 studies investigating the application of CA 125 in the clinical management of heart failure were included for meta-analyses and systematic review.
RESULTS
The serum levels of CA 125 increased significantly in heart failure patients compared with healthy controls (standardized mean difference of 1.49 U/ml, P < 0.001). The fluctuation of CA 125 was closely associated with echocardiographic parameters. Likewise, the CA 125 levels were positively correlated with brain natriuretic peptide and N-terminal pro-BNP. Further investigation found that CA 125 levels increased accordingly as cardiac function declined from the New York Heart Association class I/II to class III and further from class III to IV [1.58, 95% confidence interval (0.75-2.41) and 1.37, 95% confidence interval (0.76-1.98) U/ml, respectively]. Heart failure patients with poor outcomes showed higher CA 125 level relative to those without adverse effects in short-term or long-term follow-up.
CONCLUSION
CA 125 is a promising biomarker in the diagnosis, stratification, and outcome evaluation of heart failure patients. CA 125 may be regarded as a surrogate marker of echocardiographic variables, N-terminal pro-BNP and brain natriuretic peptide.
Topics: Biomarkers; CA-125 Antigen; Heart Failure; Humans; Membrane Proteins; Predictive Value of Tests; Prognosis; Risk Factors; Severity of Illness Index
PubMed: 25353973
DOI: 10.2459/JCM.0000000000000051 -
Langenbeck's Archives of Surgery Nov 2023Studies evaluating the rate and histology of appendiceal neoplasms between complicated and uncomplicated appendicitis include a small number of patients. Therefore, we... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Studies evaluating the rate and histology of appendiceal neoplasms between complicated and uncomplicated appendicitis include a small number of patients. Therefore, we sought a meta-analysis and systematic review comparing the rates and types of appendiceal neoplasm between complicated and uncomplicated appendicitis.
METHODS
We included articles published from the time of inception of the datasets to September 30, 2022. The electronic databases included English publications in Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, and Scopus.
RESULTS
A total of 4962 patients with appendicitis enrolled in 4 comparative studies were included. The mean age was 43.55 years (16- 94), and half were male (51%). Based on intra-operative findings, 1394 (38%) had complicated appendicitis, and 3558 (62%) had uncomplicated appendicitis. The overall incidence rate of neoplasm was 1.98%. No significant difference was found in the incidence rate of appendiceal neoplasm between complicated (3.29%) and uncomplicated (1.49%) appendicitis (OR 0.44, 95% CI 0.16- 1.23; p < 0.087; I2 = 54.9%). The most common appendiceal neoplasms were Neuroendocrine Tumors (NET) (49.21%), Nonmucinous Adenocarcinoma (24.24%), Mixed Adeno-Neuroendocrine Tumor (MANEC) (11.40%), Mucinous Adenocarcinoma (4.44%). There was a significant difference between complicated and uncomplicated appendicitis in rates of adenocarcinoma (50% vs. 13%), NET (31% vs. 74%), MANEC (19% vs. 13%) (P < 0.001).
CONCLUSION
While there was no significant difference in the overall neoplasm rate between complicated and uncomplicated appendicitis, the NET rate was significantly higher in uncomplicated appendicitis. In comparison, the Adenocarcinoma rate was considerably higher in Complicated appendicitis. These findings emphasize the importance of evaluating risk factors for neoplasm when considering appendectomy in patients with appendicitis.
Topics: Humans; Male; Adult; Female; Appendiceal Neoplasms; Appendicitis; Incidence; Risk Factors; Appendectomy; Neuroendocrine Tumors; Adenocarcinoma; Retrospective Studies
PubMed: 37940770
DOI: 10.1007/s00423-023-03164-0