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Scientific Reports Mar 2023NTRK gene fusions are rare somatic mutations found across cancer types with promising targeted therapies emerging. Healthcare systems face significant challenges in...
NTRK gene fusions are rare somatic mutations found across cancer types with promising targeted therapies emerging. Healthcare systems face significant challenges in integrating these treatments, with uncertainty in prevalence and optimal testing methods to identify eligible patients. We performed a systematic review of NTRK fusion prevalence to inform efficient diagnostic screening and scale of therapeutic uptake. We searched Medline, Embase and Cochrane databases on 31/03/2021. Inclusion criteria were studies reporting fusion rates in solid tumours, English language, post-2010 publication and minimum sample size. Critical appraisal was performed using a custom 11-item checklist. Rates were collated by cancer type and pooled if additional synthesis criteria were met. 160 studies were included, with estimates for 15 pan-cancer and 429 specific cancer types (63 paediatric). Adult pan-cancer estimates ranged 0.03-0.70%, with higher rates found in RNA-based assays. In common cancers, rates were consistently below 0.5%. Rare morphological subtypes, colorectal microsatellite instability, and driver mutation exclusion cancers had higher rates. Only 35.6% of extracted estimates used appropriate methods and sample size to identify NTRK fusions. NTRK fusion-positive cancers are rare and widely distributed across solid tumours. Small-scale, heterogeneous data confound prevalence prediction. Further large-scale, standardised genomic data are needed to characterise NTRK fusion epidemiology.
Topics: Adult; Humans; Child; Receptor, trkA; Prevalence; Neoplasms; Genomics; Oncogene Proteins, Fusion; Gene Fusion
PubMed: 36914665
DOI: 10.1038/s41598-023-31055-3 -
Scientific Reports Sep 2016Over-expression of TROP2 (the trophoblast cell surface antigen 2) was reported to predict poor prognosis in various solid tumors in number of studies. However, the... (Meta-Analysis)
Meta-Analysis Review
Over-expression of TROP2 (the trophoblast cell surface antigen 2) was reported to predict poor prognosis in various solid tumors in number of studies. However, the results remained not comprehensive. Therefore, we here carried out this meta-analysis of relevant studies published on this topic to quantitatively evaluate the clinicopathological significance of TROP2 in solid tumors. Relevant articles were identified through searching the PubMed, Web of Science and Embase database. The primary outcomes were overall survival (OS) and disease-free survival (DFS). In this meta-analysis, 16 studies involving 2,569 participants were included, and we drew the conclusion that TROP2 overexpression was significantly associated with poor OS (pooled HR = 1.896, 95% CI = 1.599-2.247, P < 0.001) and short DFS (pooled HR = 2.336, 95% CI = 1.596-3.419, P < 0.001). Furthermore, the subgroup analysis revealed that the associations between TROP2 overexpression and the outcome endpoints (OS or DFS) were significant in in patients with female genital system neoplasms, as well in gastrointestine neoplasms. In addition, subgroup analysis found no difference HR across populations of different descent.Taken together, TROP2 overexpression was associated with poor survival in human solid tumors. TROP2 may be a valuable prognosis predictive biomarker and a potential therapeutic target in human solid tumors.
Topics: Antigens, Neoplasm; Biomarkers, Tumor; Cell Adhesion Molecules; Gene Expression; Humans; Neoplasms; Prognosis; Publication Bias; Survival Analysis
PubMed: 27645103
DOI: 10.1038/srep33658 -
Oncotarget Jan 2017Karyopherin α2 (KPNA2), a member of the Karyopherin α family, has recently been reported to play an important role in tumor progression. However, the association... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Karyopherin α2 (KPNA2), a member of the Karyopherin α family, has recently been reported to play an important role in tumor progression. However, the association between KPNA2 expression and prognosis in cancer remains controversial. So we performed this meta-analysis to evaluate whether expression of KPNA2 was associated with prognosis in patients with solid tumor.
METHODS/FINDINGS
24 published eligible studies, including 6164 cases, were identified and included in this meta-analysis through searching of PubMed, EMBASE and Web of Science. We found that KPNA2 expression was an independent predictor for the prognosis of solid tumor with primary outcome (overall survival [OS]: pooled HR=1.767, 95% CI=1.503-2.077, P<0.001) and secondary outcomes (time to recurrence [TTR], recurrence free survival [RFS] and progression free survival [PFS]). However, the association between KPNA2 overexpression and disease free survival [DFS] in solid tumors was not significant (pooled HR=1.653, 95% CI=0.903-3.029, P=0.104). Furthermore, the subgroup analysis revealed that KPNA2 overexpression was associated with poor OS in East-Asian patients and European patients, as well as patients with gastric and colorectal cancer.
CONCLUSION
KPNA2 expression may be a useful prognostic biomarker to monitor cancer prognosis. Further prospective studies with larger sample sizes are required to confirm our findings.
Topics: Asian People; Biomarkers, Tumor; Colorectal Neoplasms; Disease-Free Survival; Humans; Neoplasm Recurrence, Local; Prognosis; Stomach Neoplasms; Up-Regulation; White People; alpha Karyopherins
PubMed: 27974678
DOI: 10.18632/oncotarget.13863 -
British Journal of Clinical Pharmacology Sep 2014The objective of this systematic review was to characterize the pharmacokinetics and pharmacodynamics of denosumab (XGEVA®), a fully human IgG2 monoclonal antibody... (Review)
Review
AIM
The objective of this systematic review was to characterize the pharmacokinetics and pharmacodynamics of denosumab (XGEVA®), a fully human IgG2 monoclonal antibody which binds to receptor activator of nuclear factor kappa-B ligand (RANKL), for the treatment of skeletal-related events (SREs) in patients with advanced cancer and bone metastases.
METHODS
A total of 708 patients (116 healthy patients and 592 patients with solid tumours or multiple myeloma and bone metastases) included in seven clinical studies were evaluated for denosumab pharmacokinetics. Denosumab was administered as a single subcutaneous (s.c.) dose or multiple s.c. doses, ranging from 0.1 to 3.0 mg kg(-1) or 30 mg to 180 mg fixed dosing, every 1 or 3 months for up to 45 months.
RESULTS
Consistent with the results in healthy adults, single s.c. doses of denosumab demonstrated dose-dependent, non-linear pharmacokinetics in advanced cancer patients with bone metastases across a wide dose range (0.1-3.0 mg kg(-1) ). Reductions in levels of the bone turnover marker, uNTx/Cr, were observed within 1 day. The duration of reductions generally increased with dose and dosing frequency. In patients with solid tumours and bone metastases, pharmacokinetics and pharmacodynamic comparisons across tumour types and concomitant cancer therapies (chemotherapies and/or hormone therapies) suggest that neither tumour type nor type of concomitant therapy markedly affects denosumab pharmacokinetics or pharmacodynamics.
CONCLUSIONS
Denosumab displayed non-linear pharmacokinetics at doses below 60 mg but at higher doses, denosumab exposure increased approximately dose-proportionally in advanced cancer patients with bone metastases. Following a 120 mg, every 4 weeks dosing schedule, similar denosumab pharmacokinetics and pharmacodynamics were observed across tumour types and were independent of concomitant cancer therapies.
Topics: Adult; Antibodies, Monoclonal, Humanized; Bone Neoplasms; Denosumab; Dose-Response Relationship, Drug; Humans; Neoplasms; RANK Ligand
PubMed: 24548274
DOI: 10.1111/bcp.12355 -
Medicine Oct 2018The prognostic role of targeting protein for Xklp2 (TPX2) in solid tumors has been investigated in several researches, but the results remain controversial. Here we... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The prognostic role of targeting protein for Xklp2 (TPX2) in solid tumors has been investigated in several researches, but the results remain controversial. Here we present a meta-analysis to systematically review the association between TPX2 expression levels and prognosis of human solid tumors.
METHODS
Studies published until December 2017 were searched in PubMed, Web of Science, and EBSCO, 13 studies (2134 patients) were collected for analysis. Odds ratios (ORs) for overall survival (OS) and disease-free survival (DFS) from individual studies were calculated by the application of Mantel-Haenszel random effect model. Pooled ORs were estimated by Z test. Publication bias and interstudy heterogeneity analyses were also performed.
RESULTS
TPX2 overexpression was associated with poor OS at 3 and 5 years [OR = 4.63, 95% confidence interval (CI): 3.27-6.56, P < .00001; OR = 4.05, 95% CI: 2.32-7.07, P < .00001, respectively] of solid tumors. Similar results were observed with DFS at 3 and 5 years (OR = 3.35, 95% CI: 1.83-6.14, P < .0001; OR = 2.94, 95% CI: 1.74-4.98, P < .0001, respectively). Subgroup analysis revealed that increased TPX2 expression was related to worse prognosis of gastric cancer and hepatocellular cancer, while irrelevant to esophageal squamous cell cancer at 5-year survival rate.
CONCLUSIONS
Overexpression of TPX2 is related to poor survival rate in most solid tumors, which indicates that the expression level of TPX2 is a significant prognostic parameter and potential therapeutic target in various solid tumors.
Topics: Biomarkers, Tumor; Cell Cycle Proteins; Humans; Microtubule-Associated Proteins; Neoplasms; Nuclear Proteins; Prognosis
PubMed: 30412141
DOI: 10.1097/MD.0000000000013018 -
International Immunopharmacology Sep 2022Cancer patients particularly those with hematological malignancies are at higher risk of affecting by severe coronavirus disease 2019 (COVID-19). Due to the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cancer patients particularly those with hematological malignancies are at higher risk of affecting by severe coronavirus disease 2019 (COVID-19). Due to the immunocompromised nature of the disease and the immunosuppressive treatments, they are more likely to develop less antibody protection; therefore, we aimed to evaluate the immunogenicity of COVID-19 vaccines in patients with hematological malignancies.
METHODS
A comprehensive systematic search was conducted in PubMed, Scopus, and Web of Science databases, as well as Google scholar search engine as of December 10, 2021. Our primary outcomes of interest comprised of estimating the antibody seropositive rate following COVID-19 vaccination in patients with hematological malignancies and to compare it with those who were affected by solid tumors or healthy subjects. The secondary outcomes were to assess the vaccine's immunogenicity based on different treatments, status of the disease, and type of vaccine. After the two-step screening, the data were extracted and the summary measures were calculated using a random-effect model.
RESULTS
A total of 82 articles recording 13,804 patients with a diagnosis of malignancy were included in the present review. The seropositive rates in patients with hematological malignancies after first and second vaccine doses were 30.0% (95% confidence interval (95%CI): 11.9-52.0) and 62.3% (95%CI 56.0-68.5), respectively. These patients were less likely to develop antibody response as compared to cases with solid tumors (RR 0.73, 95%CI 0.67-0.79) and healthy subjects (RR 0.62, 95%CI 0.54-0.71) following complete immunization. Chronic lymphocytic leukemia (CLL) patients had the lowest response rate among all subtypes of hematological malignancies (first dose: 22.0%, 95%CI 13.5-31.8 and second dose: 47.8%, 95%CI 41.2-54.4). Besides, anti-CD20 therapies (5.7%, 95%CI 2.0-10.6) and bruton's tyrosine kinase inhibitors (26.8%, 95%CI 16.9-37.8) represented the lowest seropositiveness post first and second doses, respectively. Notably, patients who were in active status of disease showed lower antibody detection rate compared to those on remission status (RR 0.87, 95%CI 0.76-0.99). Furthermore, lower rate of seropositivity was found in patients received BNT162.b2 compared to ones who received mRNA-1273 (RR 0.89, 95%CI 0.79-0.99).
CONCLUSION
Our findings highlight the substantially low rate of seroprotection in patients with hematological malignancies with a wide range of rates among disease subgroups and different treatments; further highlighting the fact that booster doses might be acquired for these patients to improve immunity against SARS-CoV-2.
Topics: Adult; Antibodies, Viral; COVID-19; COVID-19 Vaccines; Hematologic Neoplasms; Humans; Immunity; Leukemia, Lymphocytic, Chronic, B-Cell; SARS-CoV-2; Vaccines
PubMed: 35843148
DOI: 10.1016/j.intimp.2022.109046 -
Diagnostic and Interventional Imaging 2020The purpose of this study was to perform a systematic review of current literature describing the efficacy and technical outcomes of transarterial liver therapies using... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The purpose of this study was to perform a systematic review of current literature describing the efficacy and technical outcomes of transarterial liver therapies using automated feeder detection (AFD) software.
MATERIALS AND METHODS
This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. A structured search was performed in the PubMed, SCOPUS, and Embase databases of patients undergoing locoregional therapy of liver tumors utilizing AFD software. Demographic data, procedure data (including radiometrics) and tumor response rate were recorded. Where available, performance of AFD was compared to conventional digital subtraction angiography (DSA) and cone-beam CT (CBCT) without AFD.
RESULTS
A total of 14 full-text manuscripts met inclusion criteria, comprising 1042 tumors in 604 patients (305 men, 156 women; mean age, 68.6±6.0 [SD] years), including 537 patients with hepatocellular carcinoma, 8 with metastases from neuroendocrine tumors, and 59 patients without reported etiology. Reported sensitivity of AFD ranged between 86% and 98.5%, compared to DSA alone (38% - 64%) or DSA in combination with CBCT (69% - 81%). Three studies reported tumor response by modified response evaluation criteria in solid tumors (mRECIST) guidelines, with complete response in the range of 60% - 69%.
CONCLUSION
AFD is a promising new technology for the identification of intrahepatic and extrahepatic tumor-feeding arteries and should be considered a useful adjunct to conventional DSA and CBCT in the treatment of liver tumors.
Topics: Aged; Angiography, Digital Subtraction; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Cone-Beam Computed Tomography; Female; Humans; Liver Neoplasms; Male; Middle Aged; Software
PubMed: 32035822
DOI: 10.1016/j.diii.2020.01.011 -
British Journal of Clinical Pharmacology Feb 2022Mycophenolic acid (MPA) is an immunosuppressive drug commonly used for prophylaxis of graft rejection in solid organ transplant recipients. The main concern with the... (Meta-Analysis)
Meta-Analysis Review
AIM
Mycophenolic acid (MPA) is an immunosuppressive drug commonly used for prophylaxis of graft rejection in solid organ transplant recipients. The main concern with the prolonged use of immunosuppressive drugs is the risk of developing cancer. However, it remains unclear whether the immunosuppressive regimens containing MPA confer an increased degree of cancer risk. The present study aimed to determine the association between MPA exposure and the incidence of cancer in solid organ transplant recipients.
METHODS
A systematic search was performed on the PubMed, EMBASE and Cochrane Library databases. Relevant articles that had findings on the incidence (or event) of cancer in cohorts with and without MPA exposure were retrieved for data extraction. A meta-analysis was conducted by means of the random-effects model, and the relative risk (RR) and its 95% confidence interval (95% CI) were used as a summary effect measure.
RESULTS
A total of 39 studies were eligible for inclusion, with 32 studies that enabled meta-analysis. MPA exposure was significantly associated with a lower risk of cancer when compared to azathioprine exposure (RR = 0.66, 95% CI = 0.53-0.81, P < .001) or no exposure to any additional treatments (RR = 0.85, 95% CI = 0.73-0.99, P = .04). There was no significant difference in cancer risk for the comparison between MPA exposure and mammalian target of rapamycin (mTOR) inhibitor exposure (RR = 1.54, 95% CI = 0.96-2.46, P = .07).
CONCLUSIONS
MPA exposure was not associated with an increased risk of cancer and may even be associated with a lower risk of cancer when compared to azathioprine or no treatment.
Topics: Azathioprine; Graft Rejection; Humans; Immunosuppressive Agents; Mycophenolic Acid; Neoplasms; Organ Transplantation; Risk
PubMed: 34240462
DOI: 10.1111/bcp.14979 -
JCO Precision Oncology Jun 2023Evidence suggests that neurotrophic tyrosine receptor kinase () gene fusions in solid tumors are predictive biomarkers for targeted inhibition across a number of adult... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Evidence suggests that neurotrophic tyrosine receptor kinase () gene fusions in solid tumors are predictive biomarkers for targeted inhibition across a number of adult and pediatric tumor types. However, despite robust clinical response to tyrosine receptor kinase (TRK) inhibitors, the natural history and prognostic implications of fusions in solid tumors are poorly understood. It is important to evaluate their prognostic significance on survival to provide some context to the clinical effectiveness observed in clinical trials of TRK-targeted therapies.
METHODS
A systematic literature review was conducted in Medline, Embase, Cochrane, and PubMed to identify studies comparing the overall survival (OS) of patients with fusion-positive (+) versus fusion-negative (-) tumors. Five retrospective matched case-control studies published before 11 August 2022 were assessed for inclusion, and three were selected for the meta-analysis (sample size: 69 +, 444 -). Risk of bias was assessed using the Risk of Bias Assessment tool for Non-randomized Studies tool. The pooled hazard ratio (HR) was estimated using a Bayesian random-effects model.
RESULTS
In the meta-analysis, the median follow-up ranged from 2 to 14 years and the median OS was between 10.1 and 12.7 months (where reported). Comparing patients with tumors + and -, the pooled HR estimate for OS was 1.51 (95% credible interval, 1.01 to 2.29). The patients analyzed had no previous or current exposure to TRK inhibitors.
CONCLUSION
In patients not treated with TRK inhibitor therapies, those with + solid tumors have a 50% increased risk of mortality within 10 years from diagnosis or the start of standard therapy compared with those with - status. Although this is the most robust estimate of the comparative survival rate to date, further studies are required to reduce uncertainty.
Topics: Adult; Child; Humans; Prognosis; Bayes Theorem; Retrospective Studies; Neoplasms; Gene Fusion
PubMed: 37384865
DOI: 10.1200/PO.22.00651 -
Health Technology Assessment... Jul 2013Denosumab offers an alternative, or additional, treatment for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumours. (Review)
Review
BACKGROUND
Denosumab offers an alternative, or additional, treatment for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumours.
OBJECTIVES
The aim of this review was to assess the clinical effectiveness and cost-effectiveness of denosumab, within its licensed indication, for the prevention of SREs in patients with bone metastases from solid tumours.
DATA SOURCES
Databases searched were MEDLINE (1948 to April 2011), EMBASE (1980 to March 2011), The Cochrane Library (all sections; Issue 1, 2011) and Web of Science with Conference Proceedings (1970 to May 2011).
REVIEW METHODS
Only randomised controlled trials (RCTs) assessing denosumab, bisphosphonates (BPs) or best supportive care (BSC) in patients with bone metastases were included. Systematic reviews and observational studies were used for safety and quality-of-life assessments. Study quality was assessed using the Cochrane risk of bias tool. Studies suitable for meta-analysis were synthesised using network meta-analysis (NMA). A systematic review was conducted for cost, quality-of-life and cost-effectiveness studies. The results of this informed the cost-utility modelling. This principally estimated the cost-effectiveness of denosumab relative to zoledronic acid for when BPs are currently recommended and relative to BSC when BPs are not recommended or are contraindicated.
RESULTS
A literature search identified 39 studies (eight suitable for NMA). Denosumab was effective in delaying time to first SRE and reducing the risk of multiple SREs compared with zoledronic acid. Generally speaking, denosumab was similar to zoledronic acid for quality of life, pain, overall survival and safety. The NMA demonstrated that denosumab was more effective in delaying SREs than placebo, but was limited by numerous uncertainties. Cost-utility modelling results for denosumab relative to zoledronic acid were driven by the availability of the patient access scheme (PAS) for denosumab. Without this, denosumab was not estimated to be cost-effective compared with zoledronic acid. With it, the cost-effectiveness ranged between dominance for breast and prostate cancer, to between £5400 and £15,300 per quality-adjusted life-year (QALY) for other solid tumours (OSTs) including non-small cell lung cancer (NSCLC) and £12,700 per QALY for NSCLC. Owing to small patient gains estimated, the cost-effectiveness of denosumab was very sensitive to the zoledronic acid price. Denosumab was not estimated to be cost-effective compared with BSC.
LIMITATIONS
Only subgroup data were available for denosumab for NSCLC, and OSTs excluding NSCLC. The NMA was subject to numerous uncertainties. Owing to small patient gains estimated, the cost-effectiveness of denosumab was very sensitive to the zoledronic acid price.
CONCLUSION
Denosumab, compared with zoledronic acid and placebo, is effective in delaying SREs, but is similar with regard to quality of life and pain. Cost-effectiveness showed that without the PAS denosumab was not estimated to be cost-effective relative to either zoledronic acid or BSC. With the PAS, denosumab was estimated to be cost-effective relative to zoledronic acid but not BSC.
STUDY REGISTRATION
PROSPERO number CRD42011001418.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Antibodies, Monoclonal, Humanized; Bone Density Conservation Agents; Bone Neoplasms; Breast Neoplasms; Cost-Benefit Analysis; Denosumab; Female; Humans; Lung Neoplasms; Male; Models, Economic; Prostatic Neoplasms; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic
PubMed: 23870108
DOI: 10.3310/hta17290