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Mutation Research. Reviews in Mutation... 2024Head and neck cancer is the seventh most common malignancy globally. Head and neck squamous cell carcinoma (HNSCC) originates from squamous cells and 90% of HNC are... (Comparative Study)
Comparative Study Review
Head and neck cancer is the seventh most common malignancy globally. Head and neck squamous cell carcinoma (HNSCC) originates from squamous cells and 90% of HNC are HNSCC. The gold standard for diagnosing HNSCC is tissue biopsy. However, given tumour heterogeneity, biopsies may miss important cancer-associated molecular signatures, and more importantly, after the tumour is excised, there is no means of tracking response to treatment in patients. Captured under liquid biopsy, circulating tumour DNA (ctDNA), may identify in vivo molecular genotypes and complements tumour tissue analysis in cancer management. A systematic search was conducted in PubMed, Embase, Scopus and the Cochran Library between 2012 to early 2023 on ctDNA in HNSCC using publications written in English. We summarise 20 studies that compared mutational profiles between tumour tissue DNA (tDNA) and ctDNA, using a cohort of 631 HNSCC patients and 139 controls. Among these studies, the concordance rates varied greatly and the most mutated and the most concordant gene was TP53, followed by PIK3CA, CDKN2A, NOTCH1 and FAT1. Concordant variants were mainly found in Stage IV tumours, and the mutation type is mostly single nucleotide variants (SNV). We conclude that, as a biomarker for HNSCC, ctDNA demonstrates great promise as it recapitulates tumour genotypes, however additional multi-central trials are needed.
Topics: Humans; Circulating Tumor DNA; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Mutation; Class I Phosphatidylinositol 3-Kinases; Biomarkers, Tumor; Tumor Suppressor Protein p53; Receptor, Notch1; DNA, Neoplasm; Cyclin-Dependent Kinase Inhibitor p16; Cadherins
PubMed: 37977279
DOI: 10.1016/j.mrrev.2023.108477 -
The Oncologist Nov 2023A systematic literature review was conducted to estimate the global prevalence of Kirsten rat sarcoma virus gene (KRAS) mutations, with an emphasis on the clinically...
PURPOSE
A systematic literature review was conducted to estimate the global prevalence of Kirsten rat sarcoma virus gene (KRAS) mutations, with an emphasis on the clinically significant KRAS G12C mutation, and to estimate the prognostic significance of these mutations in patients with colorectal cancer (CRC).
DESIGN
Relevant English-language publications in the Embase, MEDLINE, and the Cochrane Library databases (from 2009 to 2021) and congress presentations (from 2016 to 2021) were reviewed. Eligible studies were those that reported the prevalence and clinical outcomes of the KRAS G12C mutation in patients with CRC.
RESULTS
A total of 137 studies (interventional [n = 8], post hoc analyses of randomized clinical trials [n = 6], observational [n = 122], and longitudinal [n =1]) were reviewed. Sixty-eight studies reported the prevalence of KRAS mutations (KRASm) in 42 810 patients with CRC. The median global prevalence of KRASm was 38% (range, 13.3%-58.9%) and that of the KRAS G12C mutation (KRAS G12C) 3.1% (range, 0.7%-14%). Available evidence suggests that KRASm are possibly more common in tumors that develop on the right side of the colon. Limited evidence suggests a lower objective response rate and inferior disease-free/relapse-free survival in patients with KRAS G12C compared with patients with KRASwt or other KRASm.
CONCLUSION
Our analysis reveals that KRAS G12C is prevalent in 3% of patients with CRC. Available evidence suggests a poor prognosis for patients with KRAS G12C. Right-sided tumors were more likely to harbor KRASm; however, their role in determining clinical outcomes needs to be investigated further.
Topics: Humans; Proto-Oncogene Proteins p21(ras); Prevalence; Colorectal Neoplasms; Neoplasm Recurrence, Local; Mutation; Lung Neoplasms
PubMed: 37432264
DOI: 10.1093/oncolo/oyad138 -
Journal of Neuromuscular Diseases 2024Despite advances in the medical management of the disease, respiratory involvement remains a significant source of morbidity and mortality in children and adults with...
BACKGROUND
Despite advances in the medical management of the disease, respiratory involvement remains a significant source of morbidity and mortality in children and adults with Duchenne muscular dystrophy (DMD).
OBJECTIVE
The objective of this systematic literature review was to synthesize and grade published evidence of factors associated with respiratory health and function in DMD.
METHODS
We searched MEDLINE, Embase, and the Cochrane Library for records of studies published from January 1, 2000 (to ensure relevance to current care practices), up until and including December 31, 2022, reporting evidence of prognostic indicators and predictors of disease progression in DMD. The quality of evidence (i.e., very low to high) was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework.
RESULTS
The bibliographic search strategy resulted in the inclusion of 29 articles. In total, evidence of 10 factors associated with respiratory health and function in patients with DMD was identified: glucocorticoid exposure (high- to very low-quality evidence), DMD mutations (low-quality evidence), DMD genetic modifiers (low-quality evidence), other pharmacological interventions (i.e., ataluren, eteplirsen, idebenone, and tamoxifen) (moderate- to very low-quality evidence), body mass index and weight (low-quality evidence), and functional ability (low-quality evidence).
CONCLUSIONS
In conclusion, we identified a total of 10 factors associated with respiratory health in function in DMD, encompassing both pharmacological therapies, genetic mutations and modifiers, and patient clinical characteristics. Yet, more research is needed to further delineate sources of respiratory heterogeneity, in particular the genotype-phenotype association and the impact of novel DMD therapies in a real-world setting. Our synthesis and grading should be helpful to inform clinical practice and future research of this heavily burdened patient population.
Topics: Adult; Child; Humans; Muscular Dystrophy, Duchenne; Glucocorticoids; Activities of Daily Living; Disease Progression
PubMed: 37980679
DOI: 10.3233/JND-230094 -
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 Personalized Medicine Dec 2023Thrombosis is a detrimental sequala of COVID-19 infection; thus, prophylactic anti-coagulant therapy has been deemed mandatory in treatment unless serious... (Review)
Review
BACKGROUND
Thrombosis is a detrimental sequala of COVID-19 infection; thus, prophylactic anti-coagulant therapy has been deemed mandatory in treatment unless serious contraindications are present. Susceptibility to thromboembolic events in COVID-19, or following COVID-19 vaccination, is likely attributable to an interplay of factors, including a patient's baseline clinical status and comorbidities, alongside genetic risk factors. In Europe, 8-20% of the population are homozygous for the MTHFR (methylene tetrahydrofolate reductase) variant, which compromises folate metabolism and elevates homocysteine levels. While heightened homocysteine levels are considered a risk factor for thromboembolic events, the precise clinical significance remains a contentious issue. However, recent research suggests elevated homocysteine levels may predict the course and severity of COVID-19 infection. Given the lack of reliable biomarkers predictive of COVID-19 thrombotic risk existing in practice, and the accessibility of MTHFR screening, we established two main outcomes for this study: (1) to determine the association between hereditary MTHFR mutations and COVID-19 severity and thromboembolic events and (2) to determine the link between MTHFR variants and adverse thrombotic events following COVID-19 vaccination.
METHODS
The review was conducted in accordance with PRISMA guidelines. Medline, Scopus, and Web of Science databases were searched from pandemic inception (11 March 2020) to 30 October 2023. Eligibility criteria were applied, and data extraction performed.
RESULTS
From 63 citations identified, a total of 14 articles met the full inclusion criteria (8 of which were cross-sectional or observational studies, and 6 were case studies or reports). Among the eight observational and cross-sectional studies evaluating the relationship between MTHFR variants (C667T; A1298C) and thromboembolic events in COVID-19 infection, four studies established a connection ( = 2200), while the remaining four studies failed to demonstrate any significant association ( = 38).
CONCLUSIONS
This systematic review demonstrated a possible association between the MTHFR gene variants and COVID-19 severity, thromboembolic events, and adverse events following vaccination. However, the paucity of robust data precluded any firm conclusions being drawn. Further prospective trials are required to determine the connection between the MTHFR gene variant and COVID-19 infection and vaccination outcomes.
PubMed: 38138914
DOI: 10.3390/jpm13121687 -
Gynecologic Oncology Mar 2024POLE mutated endometrial carcinomas may represent a subspecific type of tumors harboring a more favorable prognosis. Grade 3 (G3 or high-grade) endometrioid endometrial... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
POLE mutated endometrial carcinomas may represent a subspecific type of tumors harboring a more favorable prognosis. Grade 3 (G3 or high-grade) endometrioid endometrial carcinomas remain a clinical dilemma, with some tumors behaving as the low-grade counterparts and others presenting a more aggressive behavior.
OBJECTIVES
To determine the association between POLE mutational status and the overall-survival (OS) and progression-free-survival (PFS) of patients with G3 endometrioid endometrial cancer (EC). We also aimed to determine the prevalence of POLE mutations in G3 endometrioid EC.
METHODS
We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO No: CRD4202340008). We searched the following electronic databases: PubMed/Medline, EMBASE, Cochrane Library, Scopus, and Web of Science. For time-to-event data, the effect of POLE mutation in G3 EC was described using hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Individual patient data for each study was investigated if available from the study authors. If individual patient data were not available, information regarding time-to-event outcomes was extracted using an appropriate methodology. OS and PFS were analyzed using both one-stage and two-stage approaches, the Kaplan-Meier method, and Cox-proportional hazards models.
RESULTS
This systematic review and meta-analysis included 19 studies with 3092 patients who had high-grade endometrioid EC. Patients with POLE mutations had lower risks of death (HR = 0.36, 95% CI 0.26 to 0.50, I = 0%, 10 trials) and disease progression (HR = 0.31, 95% CI 0.17 to 0.57, I = 33%, 10 trials). The pooled prevalence of POLE mutation was 11% (95% CI 9 to 13, I = 68%, 18 studies).
CONCLUSION
POLE mutations in high-grade endometrioid EC are associated with a more favorable prognosis with increased OS and PFS.
Topics: Female; Humans; Neoplasm Grading; Poly-ADP-Ribose Binding Proteins; Carcinoma, Endometrioid; Prognosis; Mutation; Endometrial Neoplasms
PubMed: 38262245
DOI: 10.1016/j.ygyno.2024.01.018 -
International Journal of Molecular... Jul 2023Assessment of the quality and current performance of computed tomography (CT) radiomics-based models in predicting epidermal growth factor receptor (EGFR) mutation... (Meta-Analysis)
Meta-Analysis Review
Systematic Review, Meta-Analysis and Radiomics Quality Score Assessment of CT Radiomics-Based Models Predicting Tumor EGFR Mutation Status in Patients with Non-Small-Cell Lung Cancer.
Assessment of the quality and current performance of computed tomography (CT) radiomics-based models in predicting epidermal growth factor receptor (EGFR) mutation status in patients with non-small-cell lung carcinoma (NSCLC). Two medical literature databases were systematically searched, and articles presenting original studies on CT radiomics-based models for predicting EGFR mutation status were retrieved. Forest plots and related statistical tests were performed to summarize the model performance and inter-study heterogeneity. The methodological quality of the selected studies was assessed via the Radiomics Quality Score (RQS). The performance of the models was evaluated using the area under the curve (ROC AUC). The range of the Risk RQS across the selected articles varied from 11 to 24, indicating a notable heterogeneity in the quality and methodology of the included studies. The average score was 15.25, which accounted for 42.34% of the maximum possible score. The pooled Area Under the Curve (AUC) value was 0.801, indicating the accuracy of CT radiomics-based models in predicting the EGFR mutation status. CT radiomics-based models show promising results as non-invasive alternatives for predicting EGFR mutation status in NSCLC patients. However, the quality of the studies using CT radiomics-based models varies widely, and further harmonization and prospective validation are needed before the generalization of these models.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Image Interpretation, Computer-Assisted; Lung Neoplasms; Mutation; Tomography, X-Ray Computed
PubMed: 37511192
DOI: 10.3390/ijms241411433 -
Chinese Medical Journal Nov 2023The brain is a common metastatic site in patients with non-small cell lung cancer (NSCLC), resulting in a relatively poor prognosis. Systemic therapy with epidermal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The brain is a common metastatic site in patients with non-small cell lung cancer (NSCLC), resulting in a relatively poor prognosis. Systemic therapy with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is recommended as the first-line treatment for EGFR -mutated, advanced NSCLC patients. However, intracranial activity varies in different drugs. Thus, brain metastasis (BM) should be considered when choosing the treatment regimens. We conducted this network meta-analysis to explore the optimal first-line therapeutic schedule for advanced EGFR -mutated NSCLC patients with different BM statuses.
METHODS
Randomized controlled trials focusing on EGFR-TKIs (alone or in combination) in advanced and EGFR -mutant NSCLC patients, who have not received systematic treatment, were systematically searched up to December 2021. We extracted and analyzed progression-free survival (PFS) and overall survival (OS). A network meta-analysis was performed with the Bayesian statistical model to determine the survival outcomes of all included therapy regimens using the R software. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to compare intervention measures, and overall rankings of therapies were estimated under the Bayesian framework.
RESULTS
This analysis included 17 RCTs with 5077 patients and 12 therapies, including osimertinib + bevacizumab, aumolertinib, osimertinib, afatinib, dacomitinib, standards of care (SoC, including gefitinib, erlotinib, or icotinib), SoC + apatinib, SoC + bevacizumab, SoC + ramucirumab, SoC + pemetrexed based chemotherapy (PbCT), PbCT, and pemetrexed free chemotherapy (PfCT). For patients with BM, SoC + PbCT improved PFS compared with SoC (HR = 0.40, 95% CI: 0.17-0.95), and osimertinib + bevacizumab was most likely to rank first in PFS, with a cumulative probability of 34.5%, followed by aumolertinib, with a cumulative probability of 28.3%. For patients without BM, osimertinib + bevacizumab, osimertinib, aumolertinib, SoC + PbCT, dacomitinib, SoC + ramucirumab, SoC + bevacizumab, and afatinib showed superior efficacy compared with SoC (HR = 0.43, 95% CI: 0.20-0.90; HR = 0.46, 95% CI: 0.31-0.68; HR = 0.51, 95% CI: 0.34-0.77; HR = 0.50, 95% CI: 0.38-0.66; HR = 0.62, 95% CI: 0.43-0.89; HR = 0.64, 95% CI: 0.44-0.94; HR = 0.61, 95% CI: 0.48-0.76; HR = 0.71, 95% CI: 0.50-1.00), PbCT (HR = 0.29, 95% CI: 0.11-0.74; HR = 0.31, 95% CI: 0.15-0.62; HR = 0.34, 95% CI: 0.17-0.69; HR = 0.34, 95% CI: 0.18-0.64; HR = 0.42, 95% CI: 0.21-0.82; HR = 0.43, 95% CI: 0.22-0.87; HR = 0.41, 95% CI: 0.22-0.74; HR = 0.48, 95% CI: 0.31-0.75), and PfCT (HR = 0.14, 95% CI: 0.06-0.32; HR = 0.15, 95% CI: 0.09-0.26; HR = 0.17, 95% CI: 0.09-0.29; HR = 0.16, 95% CI: 0.10-0.26; HR = 0.20, 95% CI: 0.12-0.35; HR = 0.21, 95% CI: 0.12-0.39; HR = 0.20, 95% CI: 0.12-0.31; HR = 0.23, 95% CI: 0.16-0.34) in terms of PFS. And, SoC + apatinib showed relatively superior PFS when compared with PbCT (HR = 0.44, 95% CI: 0.22-0.92) and PfCT (HR = 0.21, 95% CI: 0.12-0.39), but similar PFS to SoC (HR = 0.65, 95% CI: 0.42-1.03). No statistical differences were observed for PFS in patients without BM between PbCT and SoC (HR = 1.49, 95% CI: 0.84-2.64), but both showed favorable PFS when compared with PfCT (PfCT vs. SoC, HR = 3.09, 95% CI: 2.06-4.55; PbCT vs. PfCT, HR = 0.14, 95% CI: 0.06-0.32). For patients without BM, osimertinib + bevacizumab was most likely to rank the first, with cumulative probabilities of 47.1%. For OS, SoC + PbCT was most likely to rank first in patients with and without BM, with cumulative probabilities of 46.8%, and 37.3%, respectively.
CONCLUSION
Osimertinib + bevacizumab is most likely to rank first in PFS in advanced EGFR -mutated NSCLC patients with or without BM, and SoC + PbCT is most likely to rank first in OS.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Afatinib; Lung Neoplasms; Bevacizumab; Bayes Theorem; Network Meta-Analysis; Protein Kinase Inhibitors; Pemetrexed; ErbB Receptors; Brain Neoplasms; Mutation
PubMed: 37160733
DOI: 10.1097/CM9.0000000000002468 -
Critical Reviews in Oncology/hematology Apr 2024We conducted a systematic review and meta-analysis to evaluate outcomes after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in TP53-mutated... (Meta-Analysis)
Meta-Analysis Review
We conducted a systematic review and meta-analysis to evaluate outcomes after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in TP53-mutated myelodysplastic syndromes (MDS). A literature search was performed on PubMed, Cochrane, Embase, and Clinicaltrials.gov. After screening 626 articles, eight studies were included. Data were extracted following the PRISMA guidelines and analyzed using the meta-package by Schwarzer et al. We analyzed 540 patients. The pooled median 3 (1-5) year overall survival was 21% (95% CI 0.08-0.37, I2=91%, n=540). The pooled relapse rate was 58.9% (95% CI 0.38-0.77, I2=93%, n=487) at a median of 1.75 (1-3) years. The pooled 4-year progression- free survival was 34.8% (95% CI 0.15-0.57, I2=72%, n=105). Outcomes of Allo-HSCT for TP53-mutated MDS patients remain poor, with 21% OS at three years; however, Allo-HSCT confers a survival advantage as compared to non-transplant palliative therapies. Our findings suggest the need to explore novel therapeutic agents in prospective clinical trials.
Topics: Humans; Prospective Studies; Myelodysplastic Syndromes; Hematopoietic Stem Cell Transplantation; Progression-Free Survival; Transplantation Conditioning; Tumor Suppressor Protein p53
PubMed: 38423375
DOI: 10.1016/j.critrevonc.2024.104310 -
Cancers Nov 2023Survival in oesophago-gastric cancer (OGC) is poor due to early diagnostic challenges. Non-invasive risk stratification may identify susceptible patients with... (Review)
Review
Survival in oesophago-gastric cancer (OGC) is poor due to early diagnostic challenges. Non-invasive risk stratification may identify susceptible patients with pre-malignant or benign disease. Following diagnostic confirmation with endoscopic biopsy, early OGC may be treated sooner. Mucins are transmembrane glycoproteins implicated in OGC with potential use as biomarkers of malignant transformation. This systematic review defines the role of mucins in OGC diagnosis. A literature search of MEDLINE, Web of Science, Embase and Cochrane databases was performed following PRISMA protocols for studies published January 1960-December 2022. Demographic data and data on mucin sampling and analysis methods were extracted. The review included 124 studies ( = 11,386 patients). Gastric adenocarcinoma (GAc) was the commonest OG malignancy ( = 101) followed by oesophageal adenocarcinoma (OAc, = 24) and squamous cell carcinoma (OSqCc, = 10). Mucins MUC1, MUC2, MUC5AC and MUC6 were the most frequently implicated. High MUC1 expression correlated with poorer prognosis and metastases in OSqCc. MUC2 expression decreases during progression from healthy mucosa to OAc, causing reduced protection from gastric acid. MUC5AC was upregulated, and MUC6 downregulated in GAc. Mucin expression varies in OGC; changes may be epigenetic or mutational. Profiling upper GI mucin expression in OGC, with pre-malignant, benign and healthy controls may identify potential early diagnostic biomarkers.
PubMed: 37958425
DOI: 10.3390/cancers15215252