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International Journal of Molecular... Jul 2021Medical staff represent the largest group of workers occupationally exposed to ionizing radiation (IR). Chronic exposure to low-dose IR may result in DNA damage and... (Meta-Analysis)
Meta-Analysis
Medical staff represent the largest group of workers occupationally exposed to ionizing radiation (IR). Chronic exposure to low-dose IR may result in DNA damage and genotoxicity associated with increased risk of cancer. This review aims to identify the genotoxicity biomarkers that are the most elevated in IR-exposed vs. unexposed health workers. A systematic review of the literature was performed to retrieve relevant studies with various biomarkers of genotoxicity. Subsequent meta-analyses produced a pooled effect size for several endpoints. The search procedure yielded 65 studies. Chromosome aberrations (CA) and micronuclei (MN) frequencies were significantly different between IR-exposed and unexposed workers (θ = 3.19, 95% CI 1.46-4.93; and θ = 1.41, 95% CI 0.97-1.86, for total aberrant cells and MN frequencies, respectively), which was not the case for ring chromosomes and nucleoplasmic bridges. Although less frequently used, stable translocations, sister chromatid exchanges (SCE) and comet assay endpoints were also statistically different between IR-exposed and unexposed workers. This review confirms the relevance of CA and MN as genotoxicity biomarkers that are consistently elevated in IR-exposed vs. unexposed workers. Other endpoints are strong candidates but require further studies to validate their usefulness. The integration of the identified biomarkers in future prospective epidemiological studies is encouraged.
Topics: Biomarkers; Chromosome Aberrations; DNA Damage; Dose-Response Relationship, Radiation; Health Personnel; Humans; Occupational Exposure; Radiation, Ionizing
PubMed: 34299125
DOI: 10.3390/ijms22147504 -
Critical Reviews in Oncology/hematology Aug 2021In colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC) and gastric cancer (GC) multiple studies of inter-tumor heterogeneity have identified molecular... (Review)
Review
In colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC) and gastric cancer (GC) multiple studies of inter-tumor heterogeneity have identified molecular subtypes, which correlate with clinical features. Our aim was to investigate the attributes of molecular subtypes across three different gastrointestinal cancer types. We performed a systematic search for publications on molecular subtypes or classifications in PDAC and GC and compared the described subtypes with the established consensus molecular subtypes of CRC. Examining the characteristics of subtypes across CRC, PDAC and GC resulted in four categories of subtypes. We describe uniting and distinguishing features within a mesenchymal, an epithelial, an immunogenic and a metabolic and digestive subtype category. We conclude that molecular subtypes of CRC, PDAC and GC display relevant overlap in molecular features and clinical outcomes. This finding encourages quantitative studies on subtypes across different cancer types and could lead to a paradigm shift in future treatment strategies.
Topics: Carcinoma, Pancreatic Ductal; Gastrointestinal Neoplasms; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Recurrence, Local; Pancreatic Neoplasms
PubMed: 34284100
DOI: 10.1016/j.critrevonc.2021.103428 -
Cancers Jun 2021Radiomics supposes an alternative non-invasive tumor characterization tool, which has experienced increased interest with the advent of more powerful computers and more... (Review)
Review
Radiomics supposes an alternative non-invasive tumor characterization tool, which has experienced increased interest with the advent of more powerful computers and more sophisticated machine learning algorithms. Nonetheless, the incorporation of radiomics in cancer clinical-decision support systems still necessitates a thorough analysis of its relationship with tumor biology. Herein, we present a systematic review focusing on the clinical evidence of radiomics as a surrogate method for tumor molecular profile characterization. An extensive literature review was conducted in PubMed, including papers on radiomics and a selected set of clinically relevant and commonly used tumor molecular markers. We summarized our findings based on different cancer entities, additionally evaluating the effect of different modalities for the prediction of biomarkers at each tumor site. Results suggest the existence of an association between the studied biomarkers and radiomics from different modalities and different tumor sites, even though a larger number of multi-center studies are required to further validate the reported outcomes.
PubMed: 34208595
DOI: 10.3390/cancers13123015 -
Cancer Treatment Reviews Sep 2021Despite multimodality treatment for curatively-treated gastroesophageal adenocarcinoma (GEA), prognosis remains dismal. The benefit of adding trastuzumab to chemotherapy...
INTRODUCTION
Despite multimodality treatment for curatively-treated gastroesophageal adenocarcinoma (GEA), prognosis remains dismal. The benefit of adding trastuzumab to chemotherapy for advanced Human Epidermal Growth Factor 2 (HER2) positive GEA has been established in the ToGA trial. However, it remains unclear if HER2 inhibition might also be beneficial in the curative setting. Therefore, we conducted a systematic review to investigate the role of HER2 inhibitors for the curative treatment of GEA.
METHODS
A systematic literature search was performed in PubMed, EMBASE, CENTRAL, and clinicaltrials.gov to identify clinical trials investigating HER2 inhibition for the curative treatment of GEA. Study quality was assessed using the GRADE methodology.
RESULTS
From the 1825 studies retrieved, 17 were included (seven published articles; three published conference abstracts; seven ongoing studies). From the published studies, eight studies investigated single-agent HER2 inhibition. Four studies had a nonrandomized design, and two were randomized controlled trials. Two published studies were assessed as high-quality. The addition of single-agent HER2 inhibition to chemo(radio)therapy showed a pathological complete response rate (pCR) of 22.2% (range, 9.6-25%) and dual HER2 inhibition of 34.5% (34-35%). Two-year disease-free survival (DFS) was 51.0% (40-71%) with single-agent and 70.0% (70-70%) with dual HER2 therapy.
DISCUSSION
Dual-agent HER2 inhibition showed promising pCR rates and DFS. Given the limited additional toxicity of the addition of HER2 targeting agents and the potential benefit of dual-targeting, further investigation is required in a phase III randomized clinical trial. Next steps include combining checkpoint inhibitors and HER2 blockade given the suggested synergism, as well as investigating new anti-HER2 agents.
Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Esophageal Neoplasms; Humans; Protein Kinase Inhibitors; Randomized Controlled Trials as Topic; Receptor, ErbB-2; Stomach Neoplasms; Trastuzumab
PubMed: 34171733
DOI: 10.1016/j.ctrv.2021.102249 -
Journal of the National Cancer Institute Apr 2022The consensus molecular subtypes (CMSs) of colorectal cancer (CRC) capture tumor heterogeneity at the gene-expression level. Currently, a restricted number of molecular... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The consensus molecular subtypes (CMSs) of colorectal cancer (CRC) capture tumor heterogeneity at the gene-expression level. Currently, a restricted number of molecular features are used to guide treatment for CRC. We summarize the evidence on the clinical value of the CMSs.
METHODS
We systematically identified studies in Medline and Embase that evaluated the prognostic and predictive value of CMSs in CRC patients. A random-effect meta-analysis was performed on prognostic data. Predictive data were summarized.
RESULTS
In local disease, CMS4 tumors were associated with worse overall survival (OS) compared with CMS1 (hazard ratio [HR] = 3.28, 95% confidence interval = 1.27 to 8.47) and CMS2 cancers (HR = 2.60, 95% confidence interval = 1.93 to 3.50). In metastatic disease, CMS1 consistently had worse survival than CMS2-4 (OS HR range = 0.33-0.55; progression-free survival HR range = 0.53-0.89). Adjuvant chemotherapy in stage II and III CRC was most beneficial for OS in CMS2 and CMS3 (HR range = 0.16-0.45) and not effective in CMS4 tumors. In metastatic CMS4 cancers, an irinotecan-based regimen improved outcome compared with oxaliplatin (HR range = 0.31-0.72). The addition of bevacizumab seemed beneficial in CMS1, and anti-epidermal growth factor receptor therapy improved outcome for KRAS wild-type CMS2 patients.
CONCLUSIONS
The CMS classification holds clear potential for clinical use in predicting both prognosis and response to systemic therapy, which seems to be independent of the classifier used. Prospective studies are warranted to support implementation of the CMS taxonomy in clinical practice.
Topics: Bevacizumab; Biomarkers, Tumor; Colorectal Neoplasms; Gene Expression Profiling; Humans; Oxaliplatin; Prognosis
PubMed: 34077519
DOI: 10.1093/jnci/djab106 -
Radiotherapy and Oncology : Journal of... Aug 2021Linear Energy Transfer (LET) is widely used to express the radiation quality of ion beams, when characterizing the biological effectiveness. However, averaged LET may be... (Review)
Review
Linear Energy Transfer (LET) is widely used to express the radiation quality of ion beams, when characterizing the biological effectiveness. However, averaged LET may be defined in multiple ways, and the chosen definition may impact the resulting reported value. We review averaged LET definitions found in the literature, and quantify which impact using these various definitions have for different reference setups. We recorded the averaged LET definitions used in 354 publications quantifying the relative biological effectiveness (RBE) of hadronic beams, and investigated how these various definitions impact the reported averaged LET using a Monte Carlo particle transport code. We find that the kind of averaged LET being applied is, generally, poorly defined. Some definitions of averaged LET may influence the reported averaged LET values up to an order of magnitude. For publications involving protons, most applied dose averaged LET when reporting RBE. The absence of what target medium is used and what secondary particles are included further contributes to an ill-defined averaged LET. We also found evidence of inconsistent usage of averaged LET definitions when deriving LET-based RBE models. To conclude, due to commonly ill-defined averaged LET and to the inherent problems of LET-based RBE models, averaged LET may only be used as a coarse indicator of radiation quality. We propose a more rigorous way of reporting LET values, and suggest that ideally the entire particle fluence spectra should be recorded and provided for future RBE studies, from which any type of averaged LET (or other quantities) may be inferred.
Topics: Humans; Linear Energy Transfer; Monte Carlo Method; Proton Therapy; Protons; Radiobiology; Relative Biological Effectiveness
PubMed: 33894298
DOI: 10.1016/j.radonc.2021.04.007 -
Frontiers in Oncology 2020Human papillomavirus (HPV) is a risk factor for squamous cell carcinoma of the head and neck (HNSCC). This study aimed to investigate the feasibility of IHC- p16INK4a...
Feasibility of Immunohistochemical p16 Staining in the Diagnosis of Human Papillomavirus Infection in Patients With Squamous Cell Carcinoma of the Head and Neck: A Systematic Review and Meta-Analysis.
Human papillomavirus (HPV) is a risk factor for squamous cell carcinoma of the head and neck (HNSCC). This study aimed to investigate the feasibility of IHC- p16INK4a (p16) as an alternative modality for diagnosing HPV infection. We searched PubMed, EMBASE, Web of Science, and Cochrane library for studies that evaluated the diagnostic accuracy of IHC-p16 staining. A total of 30 studies involving 2,963 patients were included from 2007 to 2019. The combined sensitivity was 0.94 (95% CI: 0.92-0.95); specificity, 0.90 (95% CI: 0.89-0.91); positive likelihood ratio (LR), 6.80 (95% CI: 5.63-8.21); negative LR, 0.10 (95% CI: 0.07-0.16); diagnostic odds ratio, 85.98 (95% CI: 55.57-133.03); and area under the curve value, 0.9550. Subgroup analysis showed that the IHC-p16 test was more consistent with the hybridization (ISH) test and has greater diagnostic value for oropharyngeal squamous cell carcinoma. The diagnostic efficacy of IHC-p16 varied among countries. In conclusion, IHC-p16 has high sensitivity and specificity for diagnosing HPV infection in HNSCC. The consistency of IHC-p16 findings with those of ISH indicate that their combination can be used to improve the specificity of diagnosis.
PubMed: 33324540
DOI: 10.3389/fonc.2020.524928 -
Oral Oncology Dec 2020The incidence of head and neck squamous cell carcinoma (HNSCC) is increasing worldwide, with over three quarters of cases now diagnosed in low and middle-income...
The incidence of head and neck squamous cell carcinoma (HNSCC) is increasing worldwide, with over three quarters of cases now diagnosed in low and middle-income countries (LMICs) with resource-constraints. Loco-regional recurrence remains the predominant pattern of failure mandating adequate local therapy for acceptable loco-regional control and survival. There is high-quality evidence that intensification of treatment by either by adding concurrent chemotherapy or by altering radiotherapy (RT) fractionation improves outcomes in the curative-intent management of loco-regionally advanced HNSCC. Even conservative estimates indicate that >50% of patients in LMIC are unlikely to get access to timely RT, which will only get compounded with the coronavirus disease (COVID)-19 pandemic. The radiation oncology community has been systematically testing altered fractionation schedules in several solid cancers (breast, lung, and head-neck), given the cost-effectiveness, convenience, and compliance to short-course RT regimens. Radiobiological modelling suggests that standard fractionation of 6-7 weeks in HNSCC can be compressed safely into a 4-week schedule to counter accelerated repopulation by increasing the dose per fraction and delivering 5 fractions per week which is currently being tested in the ongoing multicentric trial of hypo- vs normo-fractionated accelerated RT (HYPNO study). Herein, we discuss the radiobiological basis of curative-intent hypofractionated-accelerated RT schedule delivering 55 Gy in 20 fractions over 4 weeks in HNSCC followed by critical appraisal of the published literature on such regimens with concurrent systemic therapy and its inherent resource-sparing potential applicable across large parts of the world particularly in the context of the ongoing COVID-19 pandemic.
Topics: Clinical Trials, Phase III as Topic; Humans; Models, Biological; Radiation Dose Hypofractionation; Squamous Cell Carcinoma of Head and Neck; Time Factors; Treatment Outcome
PubMed: 33091846
DOI: 10.1016/j.oraloncology.2020.105045 -
Critical Reviews in Oncology/hematology Oct 2020Surgery and chemoradiotherapy can potentially cure esophageal and gastric cancer patients, although they may impact health-related quality of life (HRQoL). We aim to... (Meta-Analysis)
Meta-Analysis
Surgery and chemoradiotherapy can potentially cure esophageal and gastric cancer patients, although they may impact health-related quality of life (HRQoL). We aim to systemically review and meta-analyze literature to determine the effect of curative treatments on HRQoL in esophageal and gastric cancer.- A systematic search was performed identifying studies assessing HRQoL. Meta-analyses were performed on baseline and subsequent time-points.- From the 6067 articles retrieved, 49 studies were included (61 % low quality). Meta-analyses showed short-term HRQoL differences between esophageal cancer patients receiving definitive chemoradiotherapy (dCRT), neoadjuvant chemo(radio)therapy (nC(R)T), or surgery alone (p < 0.001), with better HRQoL with nC(R)T and surgery compared to dCRT. Over the course of 12 months, no HRQoL difference was identified between treatments in esophageal cancer (p = 0.633). Esophagectomy, but not gastrectomy, resulted in a clinically relevant decline in HRQoL. No long-term HRQoL differences were identified between curative treatments in esophageal and gastric cancer. More high-quality HRQoL studies are warranted.
Topics: Chemoradiotherapy; Esophageal Neoplasms; Esophagectomy; Humans; Quality of Life; Stomach Neoplasms
PubMed: 32818901
DOI: 10.1016/j.critrevonc.2020.103069 -
Technology in Cancer Research &... 2020It is well known that radiation damage of the pharyngeal constrictor muscles, the glottic larynx, and the supraglottic larynx may lead to dysphagia, an unwanted effect... (Meta-Analysis)
Meta-Analysis
It is well known that radiation damage of the pharyngeal constrictor muscles, the glottic larynx, and the supraglottic larynx may lead to dysphagia, an unwanted effect of head and neck radiotherapy. The reduction of radiotherapy-induced dysphagia might be achieved by adaptive radiotherapy. Although the number of studies concerning adaptive radiotherapy of head and neck cancer is continuously increasing, there are only a few studies concerning changes in dysphagia-related structures during radiotherapy.The goal of this review is to summarize the current knowledge about volumetric, dosimetric, and other changes of the pharyngeal constrictor muscles associated with head and neck radiotherapy. A literature search was performed in the MEDLINE database according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The conclusions of 8 studies that passed the criteria indicate a significant increase in the volume and the thickness of the pharyngeal constrictor muscles during radiotherapy. Moreover, the changes in magnetic resonance imaging signal intensity of the pharyngeal constrictor muscles correlate with the absorbed dose (typically higher than 50 Gy) and also with the grade of dysphagia. This systematic review presents 2 variables, which are suitable for estimation of radiotherapy-related pharyngeal constrictor muscles changes-magnetic resonance imaging signal intensity and the thickness. In the case of the thickness, there is no consensus in the level of the measurement-C2 vertebra, C3 vertebra, and the middle of the craniocaudal axis are used. It seems that reference to a position associated with a vertebral body could be more reproducible and beneficial for future research. Although late pharyngeal toxicity remains a challenge in head and neck cancer treatment, better knowledge of radiotherapy-related changes in the pharyngeal constrictor muscles contributes to adaptive radiotherapy development and thus improves the treatment results.
Topics: Deglutition Disorders; Head and Neck Neoplasms; Humans; Magnetic Resonance Imaging; Organs at Risk; Pharyngeal Muscles; Radiotherapy Dosage; Tomography, X-Ray Computed
PubMed: 32734851
DOI: 10.1177/1533033820945805