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Scientific Reports Feb 2020Anti-PD-1/PD-L1 inhibitors provide a survival advantage over conventional therapies for treatment of advanced or metastatic cancer. However, the factors determining... (Meta-Analysis)
Meta-Analysis
Anti-PD-1/PD-L1 inhibitors provide a survival advantage over conventional therapies for treatment of advanced or metastatic cancer. However, the factors determining which patients benefit the most from anti-PD-1/PD-L1 inhibitors are unknown, making treatment-related decisions difficult. We performed a systematic review and meta-analysis of acquired data to assess the efficacy and toxicity of anti-PD-1/PD-L1 inhibitors in advanced and metastatic cancer. A thorough search strategy was applied to identify randomised controlled trials (RCTs) in Pubmed, Embase, Cochrane, and major conferences. Studies meeting predefined selection criteria were selected, and two independent investigators performed data extraction; overall survival (OS), progression-free survival (PFS), and overall response rate were compared between anti-PD-1/PD-L1 inhibitors and control therapies. We calculated the pooled response rate and 95% CIs of all-grade and high-grade (≥3) adverse effects and evaluated the within-study heterogeneity using subgroup, sensitivity, and meta-regression analyses. In final, we included eligible 35 RCTs (21047 patients). The main estimated hazard ratios (HRs) for OS and PFS were 0.76 (0.71-0.82) and 0.81 (0.73-0.89) in a random-effects model. The anti-PD-1/PD-L1 inhibitor group had a significantly high risk for all-grade immune-related adverse events. Anti-PD-1/PD-L1 inhibitors were identified as a preferable treatment option for advanced or metastatic cancer patients who are male, aged < 65 years, current or former smokers, had no CNS or liver metastasis, had not EGFR mutation, and had high PD-L1 expression.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Agents; B7-H1 Antigen; Humans; Neoplasms; Programmed Cell Death 1 Receptor; Treatment Outcome
PubMed: 32034198
DOI: 10.1038/s41598-020-58674-4 -
Biomedicines Oct 2021(1) Background: Head and Neck Squamous Cell Carcinoma (HNSCC) is one of the most common malignancies globally. An early diagnosis of this disease is crucial, and the... (Review)
Review
(1) Background: Head and Neck Squamous Cell Carcinoma (HNSCC) is one of the most common malignancies globally. An early diagnosis of this disease is crucial, and the detection of gene mutations in circulating tumour DNA (ctDNA) through a liquid biopsy is a promising non-invasive diagnostic method. This review aims to provide an overview of ctDNA mutations in HNSCC patients and discuss the potential use of this tool in diagnosis and prognosis. (2) Methods: A systematic search for articles published in the English language between January 2000 and April 2021 in the Medline and Scopus databases was conducted. (3) Results: A total of 10 studies published in nine publications were selected and analysed. Altogether, 390 samples were obtained from HNSCC patients, and 79 control samples were evaluated. The most often explored gene mutation in ctDNA was . (4) Conclusions: The examination of a larger group of gene mutations and the use of a combination of multiple detection methods contribute to a higher detection rate of mutated ctDNA. More studies are necessary to verify these conclusions and to translate them into clinical practice.
PubMed: 34829777
DOI: 10.3390/biomedicines9111548 -
Hereditary Cancer in Clinical Practice Aug 2021Nearly 56% of at-risk carriers are not identified and missed as a result of the current family-history (FH) screening for genetic testing. The present study aims to... (Review)
Review
BACKGROUND
Nearly 56% of at-risk carriers are not identified and missed as a result of the current family-history (FH) screening for genetic testing. The present study aims to review the economic evaluation studies on BRCA genetic testing strategies for screening and early detection of breast cancer.
METHODS
This systematic literature review is conducted within the Cochrane Library, PubMed, Scopus, Web of Science, ProQuest, and EMBASE databases. In this paper, the relevant published economic evaluation studies are identified by following the standard Cochrane Collaboration methods and adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement reporting some recommendations for articles up to March 2020. Thereafter, the inclusion and exclusion criteria are applied to screen the articles. Disagreements are resolved through a consensus meeting. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist is used in the evaluation of quality. Finally, a narrative synthesis is performed. To compare the different levels of incremental cost-effectiveness ratio (ICER), the net present value is calculated based on a discount rate of 3% in 2019.
RESULTS
Among 788 initially retrieved citations, 12 studies were included. More than 60% of the studies were originated from high-income countries and were published after 2016. It is noteworthy that most of the studies evaluated the payer perspective. Moreover, the robustness of the results were analyzed through one-way and probabilistic sensitivity analyses in nearly 66% of these studies. Nearly, 25% of the studies are focused and defined population-based and family history BRCA tests as comparators; afterwards, the cost-effectiveness of the former was confirmed. The highest and lowest absolute values for the ICERs were $65,661 and $9 per quality adjusted life years, respectively. All studies met over 70% of the CHEERs criteria checklist, which was considered as 93% of high quality on average as well.
CONCLUSIONS
The genetic BRCA tests for the general population as well as unselected breast cancer patients were cost-effective in high and upper-middle income countries and those with prevalence of gene mutation while population-based genetic tests for low-middle income countries are depended on the price of the tests.
PubMed: 34454549
DOI: 10.1186/s13053-021-00191-0 -
Pharmacology 2023Non-small cell lung cancer (NSCLC) accounts for about 85% of generally reported lung cancer patients. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Non-small cell lung cancer (NSCLC) accounts for about 85% of generally reported lung cancer patients.
OBJECTIVES
This is a systematic review of the clinical efficacy and safety of osimertinib in treating epidermal growth factor receptor (EGFR) mutation-positive advanced NSCLC.
METHODS
A network search was completed for clinical research literature (from inception of each database to May 30, 2020) on osimertinib for EGFR mutation-positive advanced NSCLC. Strict inclusion and exclusion criteria were formulated to screen the literature. After data extraction, RevMan 5.3 software was utilized for quality evaluation and meta-analysis. The primary endpoints were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events of grades 3 and 4.
RESULTS
Finally, 6 eligible articles and a total of 1,848 patients containing 1,123 in experimental groups and 725 in control groups were included. Meta-analysis indicated that ORR (odds ratio [OR] = 3.40, 95% CI 1.64∼7.01, p = 0.0009), DCR (OR = 4.36, 95% CI 3.09∼6.15, p < 0.00001), PFS (HR = 0.36, 95% CI 0.27∼0.47, p < 0.00001), and OS (OR = 0.58, 95% CI 0.46∼0.72, p < 0.00001) of the experimental group were prominently better than the control group. Adverse events of grades 3 and 4 mainly incorporated decreased nausea, rash, stomatitis, and vomiting, which were dramatically relieved compared with the control group.
CONCLUSION
Osimertinib is currently an appreciably effective and well-tolerated therapeutic avenue for EGFR mutation-positive advanced NSCLC.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Antineoplastic Agents; Protein Kinase Inhibitors; Aniline Compounds; ErbB Receptors; Mutation
PubMed: 36470213
DOI: 10.1159/000527321 -
Annals of Palliative Medicine Feb 2021Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has been approved by the U.S. Food and Drug Administration in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has been approved by the U.S. Food and Drug Administration in treating T790M mutationpositive advanced non-small cell lung cancer (NSCLC). A systematic review and meta-analysis was conducted to assess the efficacy and safety of osimertinib in treating advanced NSCLC patients with acquired T790M mutation.
METHODS
PubMed, EMBASE, Cochrane Library and Web of Science were searched to obtain the eligible studies following the "population, interventions, comparisons, outcomes, study design" (PICOS) criteria. The pooled analysis of objective response rate (ORR), disease controlled rate (DCR), progressionfree survival (PFS), overall survival (OS) and adverse events (AEs) were performed using STATA12.0 and RevMan5.0.
RESULTS
A total of 1,050 patients were included in the meta-analysis. The combined osimertinib ORR was 0.64 (95% CI, 0.60-0.69), the ORR of central nervous system (CNS) was 0.54 (95% CI, 0.37-0.71), DCR was 0.89 (95% CI, 0.86-0.92), PFS at six months (PFS-6m) rate was 0.69 (95% CI, 0.58-0.79), PFS at one year (PFS-1y) rate was 0.33 (95% CI, 0.20-0.46), OS at one year (OS-1y) rate was 0.69 (95% CI, 0.55-0.84). The pooled incidence rate of the AEs of grade ≥ III was 0.25 (95% CI, 0.09-0.40). The results from Begg's and Egger's tests presented no publication bias in the included studies.
CONCLUSIONS
Osimertinib demonstrated a superior therapeutic benefit with high efficacy and low toxicity for T790M-positive advanced NSCLC patients who were treated with early-generation EGFR-TKIs. Meanwhile, osimertinib showed promising for the treatment of advanced patients with CNS metastases.
Topics: Acrylamides; Aniline Compounds; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Humans; Lung Neoplasms; Mutation; Protein Kinase Inhibitors
PubMed: 33474947
DOI: 10.21037/apm-20-1357 -
Diagnostics (Basel, Switzerland) Jan 2023Methodological advancements, such as relative haplotype and relative mutation dosage analyses, have enabled non-invasive prenatal diagnosis of autosomal recessive and... (Review)
Review
BACKGROUND
Methodological advancements, such as relative haplotype and relative mutation dosage analyses, have enabled non-invasive prenatal diagnosis of autosomal recessive and X-linked diseases. Duchenne muscular dystrophy (DMD) is an X-linked recessive disease characterized by progressive proximal muscular dystrophy and a high mortality rate before the age of twenty. We aimed to systematically present obtainable data regarding a non-invasive prenatal diagnosis of DMD and provide a comprehensive resume on the topic. The emphasis was given to the comparison of different available protocols and molecular methods used for fetal inheritance deduction, as well as their correlation with prognostic accuracy.
METHODS
We searched the Scopus and PubMed databases on 11 November 2022 and included articles reporting a non-invasive prenatal diagnosis of DMD in families at risk using relative dosage analysis methods.
RESULTS
Of the 342 articles identified, 7 met the criteria. The reported accuracy of NIPT for DMD was 100% in all of the studies except one, which demonstrated an accuracy of 86.67%. The combined accuracy for studies applying indirect RHDO, direct RHDO, and RMD approaches were 94.74%, 100%, and 100%, respectively. Confirmatory results by invasive testing were available in all the cases. Regardless of the technological complexity and low prevalence of the disease that reduces the opportunity for systematic research, the presented work demonstrates substantial accuracy of NIPT for DMD.
CONCLUSIONS
Attempts for its implementation into everyday clinical practice raise many ethical and social concerns. It is essential to provide detailed guidelines and arrange genetic counseling in order to ensure the proper indications for testing and obtain informed parental consent.
PubMed: 36672993
DOI: 10.3390/diagnostics13020183 -
Frontiers in Immunology 2021genes are mutated in approximately 8% of melanoma patients; however, the impact of gene alterations on the efficiency of immunotherapy has not been clarified. This...
BACKGROUND
genes are mutated in approximately 8% of melanoma patients; however, the impact of gene alterations on the efficiency of immunotherapy has not been clarified. This study focused on the correlation between gene mutations and the treatment response.
METHODS
Six metastatic melanoma clinical cohorts treated with immune checkpoint inhibitors [anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) or anti-programmed cell death-1 (PD-1)] were recruited in this study. RNA expression profiling results from each of these six cohorts and the Cancer Genome Atlas (TCGA) melanoma cohort were analysed to explore the mechanism related to immune activation.
RESULTS
Compared to patients with wild-type , those with mutations in an independent anti-CTLA-4-treated cohort had higher objective response rates, longer progression-free survival, and longer overall survival (OS). These findings were further validated in a pooled anti-CTLA-4-treated cohort in terms of the OS. However, there was no correlation between mutations and OS in the anti-PD-1-treated cohort. Subgroup Cox regression analysis suggested that patients with mutations received fewer benefits from anti-PD-1 monotherapy than from anti-CTLA-4 treatment. Furthermore, transcriptome profiling analysis revealed that melanoma tumours with mutation was enriched in CD8 T cells, B cells, and neutrophil cells, also expressed high levels of CD33 and IL10, implying a potential mechanism underlying the benefit of melanoma patients with mutations from anti-CTLA-4 treatment.
CONCLUSIONS
mutations were identified as an independent predictive factor for anti-CTLA-4 therapy in melanoma patients. Anti-CTLA-4 treatment might be more effective than anti-PD-1 therapy for patients with mutated melanoma.
Topics: Humans; Immunotherapy; MAP Kinase Kinase 1; MAP Kinase Kinase 2; Melanoma; Mutation; Progression-Free Survival; Survival Rate
PubMed: 35069558
DOI: 10.3389/fimmu.2021.785526 -
Investigative Ophthalmology & Visual... Jul 2023The aim of this systematic review was to investigate the available data on the epidemiology of oculocutaneous albinism (OCA) around the world, and to determine whether a...
PURPOSE
The aim of this systematic review was to investigate the available data on the epidemiology of oculocutaneous albinism (OCA) around the world, and to determine whether a generalizable, worldwide prevalence figure could be proposed.
METHODS
Extensive literature search strategies were conducted, interrogating PubMed, Scopus, and Web of Science, to locate relevant literature. Ultimately 34 studies reporting original data were included for analysis.
RESULTS
Findings showed that most data were outdated, and only 6 of 34 articles (18%) were published after 2010. There were few good studies with sound methodology and large, clearly defined population samples. Only a small proportion of countries worldwide (26/193 [13%]) have produced prevalence figures for OCA. By continent, African studies were disproportionately represented (15/34 [44%]). The highest prevalence rates (range, 1 in 22 to 1 in 1300; mean, 1 in 464) were reported in population isolates. The mean prevalence from four African countries was 1 in 4264 (range, 1 in 1755 to 1 in 7900). Prevalence for three countries in Europe (mean, 1 in 12,000; range, 1 in 10,000 to 1 in 15,000) may be underestimated, as the phenotype, in fair-skinned populations, may be missed or misdiagnosed as ocular albinism or isolated visual impairment. Population rates may vary depending on local cultural factors (e.g., consanguineous matings) and may change over time.
CONCLUSIONS
The prevalence of OCA varies widely between continents and population groups, and it is often influenced by local factors. It was not possible, therefore, to determine a single, generalizable worldwide prevalence rate for OCA, although continental rates for Africa and Europe are useful.
Topics: Humans; Mutation; Prevalence; Albinism, Oculocutaneous; Phenotype; Albinism, Ocular
PubMed: 37440261
DOI: 10.1167/iovs.64.10.14 -
Journal of Comparative Effectiveness... Jun 2022To conduct a systematic literature review of real-world evidence on the burden of tyrosine kinase inhibitor (TKI) failure in Chinese patients with chronic myeloid... (Review)
Review
To conduct a systematic literature review of real-world evidence on the burden of tyrosine kinase inhibitor (TKI) failure in Chinese patients with chronic myeloid leukemia (CML). We identified 155 references in Chinese- and English-language journals from 2001 to 2021. The age-adjusted mortality rate in Chinese CML patients was decreasing. Imatinib treatment had a higher annual treatment failure risk than nilotinib (0.199 vs 0.041). Patients with TKI treatment failure tended to be young (median: 38.6 years), have progressive disease (44.3%) and harbor mutations (51.6%). The disease burden of TKI treatment failure included reduced health outcomes and increased health resource utilization and costs. CML relapse cases could continuously rise in China due to increasing TKI treatment failure over extended survival.
Topics: Asian People; Humans; Imatinib Mesylate; Language; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Protein Kinase Inhibitors
PubMed: 35411807
DOI: 10.2217/cer-2022-0032 -
Frontiers in Oncology 2022In light of the development of RAS inhibitors, a reliable assessment of the prevalence of RAS mutations and their correlation with the clinical features of patients with...
In light of the development of RAS inhibitors, a reliable assessment of the prevalence of RAS mutations and their correlation with the clinical features of patients with HNC is crucially needed. This meta-analysis compiles the findings of 149 studies with over 8500 HNC patients and assesses the global prevalence of mutations in the HRAS, KRAS and NRAS genes. The available data were stratified according to geographical region, clinical features, and tumor characteristics, including human papillomavirus (HPV) infection status and tumor stage. In addition, the distribution of codon substitutions in each RAS gene was assessed. The estimated mutation rate is highest for HRAS (7%), followed by KRAS (2.89%) and NRAS (2.20%). HRAS prevalence in South Asia (15.28%) is twice as high as the global estimate. HRAS mutations are more prevalent in oral cavity and salivary gland tumors. In contrast, KRAS mutations are found more frequently in sinonasal tumors, and NRAS mutations are found chiefly in tumors of the nasopharynx. OR analyses show a significant association between HRAS mutations and a high tumor stage (OR=3.63). In addition, there is a significant association between HPV-positive status and KRAS mutations (OR=2.09). This study highlights RAS as a potential therapeutic target in certain subsets of HNC patients.
PubMed: 35600380
DOI: 10.3389/fonc.2022.838911