-
Research and Practice in Thrombosis and... Oct 2019Portal vein thrombosis (PVT) is common in cirrhosis. PVT is associated with high morbidity and mortality. Individual reports suggest that PVT occurs more frequently in...
BACKGROUND
Portal vein thrombosis (PVT) is common in cirrhosis. PVT is associated with high morbidity and mortality. Individual reports suggest that PVT occurs more frequently in patients with cirrhosis and inherited thrombophilia. The relationship between cirrhosis, PVT development, and inherited thrombophilia was explored in this study. The aim of the study was to determine whether cirrhotic patients with nontumoral PVT have an increased rate of inherited thrombophilia.
METHODS
Studies were identified by searching electronic databases up to October 2017 with English language and human subject restrictions. Two independent reviewers screened citations and extracted data. Magnitude of effect was calculated to obtain aggregate estimates of effect size and 95% confidence intervals (CIs). Between-study variability and heterogeneity were assessed.
RESULTS
Of 2893 citations identified, 9 studies composed of 1929 subjects with cirrhosis were included. The overall prevalence of PVT was 6.5% (n = 125). Both prothrombin G20210A mutation (odds ratio [OR], 2.43; 95% CI, 1.07-5.53; = 0.03) and factor V Leiden (FVL) (OR, 1.98; 95% CI, 1.06-3.68; = 0.03) were significantly associated with PVT risk. Methyltetrahydrofolate reductase C677T mutation was not associated with increased PVT risk. No heterogeneity or publication bias was observed. One important study with opposite findings could not be included due to lack of primary data.
CONCLUSIONS
FVL and PTG20210A mutation were associated with increased PVT risk in patients with cirrhosis. This finding reframes the role of inherited thrombophilia in PVT development in patients with cirrhosis. Future prospective studies investigating screening for inherited thrombophilia in all cirrhosis patients with PVT seem warranted.
PubMed: 31624785
DOI: 10.1002/rth2.12253 -
Oncotarget Feb 2016Poly (ADP-ribose) polymerase (PARP) inhibitors are a class of small-molecule drugs suppressing PARP enzymes activity, inducing the death of cells deficient in homologous... (Review)
Review
Poly (ADP-ribose) polymerase (PARP) inhibitors are a class of small-molecule drugs suppressing PARP enzymes activity, inducing the death of cells deficient in homologous recombination repair (HRR). HRR deficiency is common in tumor cells with BRCA gene mutation. Since their first clinical trial in 2003, PARP inhibitors have shown benefit in the treatment of HRR-deficient tumors. Recently, several randomized clinical trials (RCTs) have been conducted to investigate the potential benefit of administration of PARP inhibitors in cancer patients. However, the results remain controversial. To evaluate the efficiency and safety of PARP inhibitors in patients with cancer, we performed a comprehensive meta-analysis of RCTs. According to our study, PARP inhibitors could clearly improve progression-free survival (PFS), especially in patients with BRCA mutation. However, our study showed no significant difference in overall survival (OS) between the PARP inhibitors and controls, even in the BRCA mutation group. Little toxicity was reported in the rate of treatment correlated adverse events (AEs) in PARP inhibitor group compared with controls. In conclusion, PARP inhibitors do well in improving PFS with little toxicity, especially in patients with BRCA deficiency.
Topics: Antineoplastic Agents; Humans; Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Safety
PubMed: 26399274
DOI: 10.18632/oncotarget.5367 -
Journal of Hematology Mar 2019Ibrutinib has shown to have better efficacy than standard chemoimmunotherapy in del17 positive chronic lymphocytic leukemia (CLL) patients; however its role in del17... (Review)
Review
Ibrutinib has shown to have better efficacy than standard chemoimmunotherapy in del17 positive chronic lymphocytic leukemia (CLL) patients; however its role in del17 negative patients is less clear. We aim to evaluate the efficacy of ibrutinib-based regimens in CLL. Seven databases were searched in accordance with PRISMA statement guidelines using the following keywords: chronic lymphocytic leukemia, CLL, Bruton tyrosine kinase inhibitor, BTK inhibitor, ibrutinib, and PCI-32765. Data from only prospective clinical trials was included. In a phase 3 trial (n = 136), the overall response rate (ORR) with ibrutinib was 92% whereas 18% patients had a complete response (CR). Progression free survival (PFS) and overall survival (OS) at 2 years were 89% and 95% respectively. Phase 3 trial (n = 195) with single agent ibrutinib showed ORR of 63%. PFS at 6 months and OS at 12 months were 88% and 90% respectively. In a phase 2 trial of relapsed and/or refractory (R/R) or high risk treatment naive (TN) patients, combination of ibrutinib and rituximab (n = 104) achieved an ORR of 100% (CR 28%) as compared to ORR 98% (CR 21%) with ibrutinib monotherapy (n = 102) with no significant difference in PFS. Combination of ibrutinib and ublituximab (n = 64) had an ORR of 78% (CR 7%) in a phase 3 study. In del17p negative R/R patients, combination of bendamustine/rituximab (BR) and ibrutinib (n = 289) achieved an ORR of 83% (CR/CRi 10%) and the 18 month PFS was 79%. In a phase 2 trial treated with ibrutinib (n = 145), patients with del17p R/R disease achieved an ORR of 64% and the 24 month PFS and OS was 63% and 75% respectively. In TN del17p patients (n = 35), ORR was 97% (CR-0) and the 24 month PFS and OS were 82% and 84% respectively with single agent ibrutinib. Ibrutinib is the treatment of choice for patients with del17p mutation and has good efficacy in RR/TN patients without del17p mutation. Ibrutinib is being evaluated in combination with rituximab for del17p mutations. Future prospects include combination of ibrutinib with frontline chemotherapy and other novel agents for TN and RR del17p negative patients.
PubMed: 32300434
DOI: 10.14740/jh482 -
Thoracic Cancer Feb 2023The combination of antiangiogenic agents with epidermal growth factor receptor inhibitors (EGFR-TKIs) and chemotherapy with EGFR-TKIs are the most common combination... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The combination of antiangiogenic agents with epidermal growth factor receptor inhibitors (EGFR-TKIs) and chemotherapy with EGFR-TKIs are the most common combination treatment options in epidermal growth factor receptor (EGFR) positive non-small cell lung cancer (NSCLC). This network meta-analysis was performed to evaluate the differences between them.
METHODS
We searched the PubMed, EMBASE and the Cochrane Controlled Trials Register up to August 2022. The primary outcomes were progression-free survival (PFS) and objective response rate (ORR). The secondary endpoints were overall survival (OS), disease control rate (DCR) and adverse events (AEs). The data of hazard ratio (HR) or risk ratio (RR) with their corresponding 95% confidence intervals (CIs) were extracted in the studies. A network meta-analysis (NMA) was used to indirectly compare the efficacy and safety of antiangiogenic agents plus EGFR-TKIs and chemotherapy plus EGFR-TKIs.
RESULTS
Pooled data of included studies were demonstrated that chemotherapy plus EGFR-TKIs had a benefit in ORR compared to antiangiogenic agents plus EGFR-TKIs in patients with EGFR mutated NSCLC (RR = 1.1, 95% CI: 1.0-1.2). However, there were no significant differences in PFS, OS and DCR between in the two group (PFS: HR = 1.0, 95% CI: 0.74-1.6; OS: HR = 0.78, 95% CI: 0.45-1.5; DCR: RR = 1.0, 95% CI: 0.94-1.1). The common treatment-related AEs in the two groups were relatively manageable.
CONCLUSION
Based on the efficacy and safety, the combination of chemotherapy with EGFR-TKIs is considered the best combination treatment options in advanced NSCLC with EGFR mutation.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Angiogenesis Inhibitors; Lung Neoplasms; Antineoplastic Agents; Network Meta-Analysis; ErbB Receptors; Protein Kinase Inhibitors
PubMed: 36594109
DOI: 10.1111/1759-7714.14783 -
Frontiers in Oncology 2022In non-small cell lung cancer (NSCLC) patients treated by immune checkpoint inhibitors (ICIs), tumor mutation burden (TMB) has been found to have predictive potential...
Predictive Efficacy of Blood-Based Tumor Mutation Burden Assay for Immune Checkpoint Inhibitors Therapy in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.
BACKGROUND
In non-small cell lung cancer (NSCLC) patients treated by immune checkpoint inhibitors (ICIs), tumor mutation burden (TMB) has been found to have predictive potential for survival. When compared to TMB detection in tissue (tTMB), detecting TMB in the blood (bTMB) has practical advantages; yet, the results of various studies are conflicting. The question of whether bTMB can be utilized as a predictive biomarker is becoming increasingly contentious. To confirm the predictive efficacy of bTMB, researchers did a systematic review and meta-analysis to look into the relationship between ICIs and bTMB.
METHOD
From the inception to March 2021, Cochrane Library, PubMed, EMBASE and other databases were systematically searched. The predictive value of bTMB in ICIs, or the efficacy of ICIs against chemotherapy, was studied. The results were presented as pooled ratio rate (RR) and hazard ratio (HR) with 95% confidence intervals for the Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Subgroup analysis, heterogeneity analyses, and sensitivity analysis were also performed.
RESULTS
A total of 2,610 NSCLC patients were studied in seven trials. There were no significant differences in OS (HR = 1.09; 95% CI: 0.62-1.91, = 0.774) or PFS (HR = 0.73; 95% CI: 0.20-2.65, = 0.629) between high and low bTMB groups in the ICIs cohort. When ICIs were compared to chemotherapy, ICIs were found to enhance OS (HR = 0.74; 95% CI: 0.59-0.92, = 0.006), but the improvement in PFS and ORR was only a numerical trend (PFS: HR = 0.83; 95% CI: 0.63-1.09, = 0.173; ORR: RR = 0.92, 95% CI: 0.77-1.10, = 0.372). NSCLC patients treated with ICIs in the high bTMB group had better survival benefits than chemotherapy patients in terms of OS (HR = 0.63; 95% CI: 0.51-0.76, 0.001), PFS (HR = 0.63; 95% CI: 0.52-0.76, 0.001), and ORR (RR = 1.86; 95% CI: 1.32-2.62, 0.001), while in the low TMB group, the results were no different or even reversed (OS: HR = 0.89; 95% CI: 0.64-1.24, = 0.485; PFS: HR = 1.21, 95% CI: 0.93-1.58, = 0.154; ORR: RR = 0.68, 95% CI: 0.54-0.85, = 0.001).
CONCLUSIONS
TMB could predict the enhanced survival benefit of NSCLC patients treated with ICIs; however the role of bTMB is limited at this stage. For NSCLC patients with high TMB, ICIc may be a better option than chemotherapy.
PubMed: 35223476
DOI: 10.3389/fonc.2022.795933 -
Critical Reviews in Oncology/hematology Mar 2016Clinical trials investigated the potential role of both KRAS and BRAF mutations, as prognostic biomarkers, in colorectal cancer (CRC) patients who underwent surgical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Clinical trials investigated the potential role of both KRAS and BRAF mutations, as prognostic biomarkers, in colorectal cancer (CRC) patients who underwent surgical treatment of CRC-related liver metastases (CLM), showing conflicting results. This meta-analysis aims to review all the studies reporting survival outcomes (recurrence free survival (RFS), and/or overall survival (OS)) of patients undergoing resection of CLM, stratified according to KRAS and/or BRAF mutation status.
MATERIALS AND METHODS
Data from all published studies reporting survival outcomes (RFS and/or OS) of CRC patients who received resection of CLM, stratified by KRAS and/or BRAF mutation status were collected, according to the PRISMA guidelines. Pooled HRs were calculated for both the OS and/or RFS.
RESULTS
Seven eligible trials (1403 patients) were included. Pooled analysis showed that KRAS mutations predicted a significantly worse both RFS (HR: 1.65; 95% CI: 1.23-2.21) and OS (HR: 1.86; 95% CI: 1.51-2.30) in patients who underwent surgical resection of CLM. BRAF mutations were also associated with a significantly worse OS (HR: 3.90; 95% CI: 1.96-7.73) in this subgroup of patients.
CONCLUSIONS
This meta-analysis suggests both KRAS and BRAF mutations as poor, prognostic biomarkers, associated with worse survival outcomes, in patients undergoing hepatic resection of CLM.
Topics: Biomarkers, Tumor; Colorectal Neoplasms; Hepatectomy; Humans; Liver Neoplasms; Mutation; Prognosis; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Survival Rate
PubMed: 26775732
DOI: 10.1016/j.critrevonc.2015.12.015 -
Journal of Translational Medicine Feb 2024Tumor mutational burden (TMB) has been demonstrated to predict the response to immune checkpoint inhibitors (ICIs) in various cancers. However, the role of TMB in head... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tumor mutational burden (TMB) has been demonstrated to predict the response to immune checkpoint inhibitors (ICIs) in various cancers. However, the role of TMB in head and neck squamous cell carcinoma (HNSCC) has not yet been specifically addressed. Since HNSCC patients exhibit a rather limited response to ICIs, there is an unmet need to develop predictive biomarkers to improve patient selection criteria and the clinical benefit of ICI treatment.
METHODS
We conducted a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. HNSCC cohort studies were selected when TMB prior to ICI treatment was evaluated, TMB cutoff value was available, and the prognostic value of TMB was evaluated by time-to-event survival analysis. A total of 11 out of 1960 articles were analyzed, including 1200 HNSCC patients.
RESULTS
The results showed that those patients harboring high TMB exhibited a significantly superior overall response rate (OR = 2.62; 95% CI 1.74-3.94; p < 0.0001) and a survival advantage (HR = 0.53; 95% CI 0.39-0.71; p < 0.0001) after ICI treatment.
CONCLUSION
This is the first meta-analysis to demonstrate a higher response and clinical benefit from ICI therapy in HNSCC patients with high TMB.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Prognosis; Immunotherapy; Survival Analysis; Biomarkers, Tumor; Head and Neck Neoplasms; Mutation
PubMed: 38311741
DOI: 10.1186/s12967-024-04937-x -
Vaccine Mar 2015Vaccine-derived polioviruses (VDPVs), strains of poliovirus mutated from the oral polio vaccine, pose a challenge to global polio eradication. Immunodeficiency-related... (Review)
Review
BACKGROUND
Vaccine-derived polioviruses (VDPVs), strains of poliovirus mutated from the oral polio vaccine, pose a challenge to global polio eradication. Immunodeficiency-related vaccine-derived polioviruses (iVDPVs) are a type of VDPV which may serve as sources of poliovirus reintroduction after the eradication of wild-type poliovirus. This review is a comprehensive update of confirmed iVDPV cases published in the scientific literature from 1962 to 2012, and describes clinically relevant trends in reported iVDPV cases worldwide.
METHODS
We conducted a systematic review of published iVDPV case reports from January 1960 to November 2012 from four databases. We included cases in which the patient had a primary immunodeficiency, and the vaccine virus isolated from the patient either met the sequencing definition of VDPV (>1% divergence for serotypes 1 and 3 and >0.6% for serotype 2) and/or was previously reported as an iVDPV by the World Health Organization.
RESULTS
We identified 68 iVDPV cases in 49 manuscripts reported from 25 countries and the Palestinian territories. 62% of case patients were male, 78% presented clinically with acute flaccid paralysis, and 65% were iVDPV2. 57% of cases occurred in patients with predominantly antibody immunodeficiencies, and the overall all-cause mortality rate was greater than 60%. The median age at case detection was 1.4 years [IQR: 0.8, 4.5] and the median duration of shedding was 1.3 years [IQR: 0.7, 2.2]. We identified a poliovirus genome VP1 region mutation rate of 0.72% per year and a higher median percent divergence for iVDPV1 cases. More cases were reported from high income countries, which also had a larger age variation and different distribution of immunodeficiencies compared to upper and lower middle-income countries.
CONCLUSION
Our study describes the incidence and characteristics of global iVDPV cases reported in the literature in the past five decades. It also highlights the regional and economic disparities of reported iVDPV cases.
Topics: Capsid Proteins; Disease Eradication; Female; Humans; Immunologic Deficiency Syndromes; Male; Mutation Rate; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Vaccination
PubMed: 25600519
DOI: 10.1016/j.vaccine.2015.01.018 -
In Vivo (Athens, Greece) Jan 2017Mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase domain (TKD) are associated with response and resistance to targeted therapy. The EGFR mutation... (Review)
Review
BACKGROUND
Mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase domain (TKD) are associated with response and resistance to targeted therapy. The EGFR mutation status in patients with advanced oral and oropharyngeal squamous cell carcinoma (OOSCC) was evaluated. A systematic literature review was undertaken to summarize current evidence and estimate the overall prevalence of EGFR TKD mutations in patients with head and neck squamous cell carcinoma (HNSCC).
MATERIALS AND METHODS
Genomic DNA was extracted from formalin-fixed, paraffin-embedded tumor samples of 113 patients with OOSCC. Pyrosequencing was performed to investigate mutations in EGFR exons 18 to 21. Medline databases were searched for relevant studies. Studies reporting mutations in the EGFR TKD in HNSCC were eligible for inclusion in the systematic review.
RESULTS
No mutations in the EGFR TKD were observed in 113 samples of OOSCC. A total of 53 eligible studies were included in the systematic review. In total, from the review, 117 patients harboring a total of 159 EGFR TKD mutations were reported among 4122 patients with HNSCC. The overall prevalence of EGFR TKD mutations in HNSCC was 2.8%.
CONCLUSION
Large-scale studies are warranted to provide further evidence regarding the mutation status of EGFR in patients with HNSCC.
Topics: Carcinoma, Squamous Cell; ErbB Receptors; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Mutation; Neoplasm Staging; Polymerase Chain Reaction; Prognosis; Retrospective Studies; Survival Rate
PubMed: 28064216
DOI: 10.21873/invivo.11020 -
Gland Surgery Oct 2020Papillary thyroid carcinoma (PTC), the most common malignancy of the endocrine system, is frequently driven by mutation, which was reported in 35-60% cases in Western... (Review)
Review
Papillary thyroid carcinoma (PTC), the most common malignancy of the endocrine system, is frequently driven by mutation, which was reported in 35-60% cases in Western series. Numerous studies have recently emerged from Asian countries and regions; however sufficient summary is lacking to date. mutation serves as a diagnostic and prognostic tool in thyroid cancer, therefore establishing a rate of on the national scale could be of practical significance. We performed systematic reviews of available literature to investigate the prevalence of mutation in series of PTC from various Asian countries and regions. Out of the total 3,966 reports identified via initial screening, 138 studies encompassing over 40,000 PTCs were included for the final analysis. A vast majority (90.2%) of PTCs with known status were from East Asia, including China, South Korea, and Japan, with mutation rates of 71.2%, 75.5%, and 70.6%, respectively. Less abundant Indian and Saudi Arabian series found 45.6% and 46.3% prevalence of in PTC, respectively. Much limited evidence was available from Thailand, Iran, Kazakhstan, Taiwan, Singapore, Indonesia, Hong Kong, Philippines, Vietnam, Iraq, and Myanmar. No relevant publications were found from other highly populated countries, such as Pakistan, Bangladesh, and Malaysia. After grouping by geographic region, we found that the highest rate of was reported in the PTC series from East Asia (76.4%). Much lower rate (45-48%) was seen in PTC cohorts from South Asia, Central Asia, and the Middle East while the Southeast Asian series were in between (57%). Further subgroup analysis revealed that studies employing fresh frozen tissue and fine-needle aspirates showed higher rates of compared to those used formalin-fixed paraffin-embedded tissues. We found that the PTC series enrolled patients' cohorts after 2010 demonstrated a higher rate of compared to the earlier series. Finally, pediatric PTCs had lower prevalence compared to the baseline rate for the country. In conclusion, despite considerable among and within countries heterogeneity, the Asian PTC series showed a higher prevalence of mutation than that in Western series. Causes of geographic heterogeneity, whether genuine (etiology, genetics) or methodology-related should be further investigated.
PubMed: 33224863
DOI: 10.21037/gs-20-430