-
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 -
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 -
Cancer Treatment Reviews Jul 2022Despite promising results following targeted treatment with human epidermal growth factor receptor 2 (HER2)-inhibitors in HER2-positive gastric and esophageal... (Review)
Review
INTRODUCTION
Despite promising results following targeted treatment with human epidermal growth factor receptor 2 (HER2)-inhibitors in HER2-positive gastric and esophageal adenocarcinoma (GEA), prognosis remains dismal. Many patients ultimately demonstrate progression following treatment due to resistance to HER2-targeted therapy. Here, we describe the potential primary and secondary resistance mechanisms to HER2-targeted therapy in GEA.
METHODS
We systematically searched PubMed/MEDLINE, EMBASE, and CENTRAL for eligible studies describing changes that were associated with drug resistance. Study quality was assessed using an adjusted version of the OHAT risk of bias tool. Quality of proposed resistance mechanisms was assessed using predefined criteria.
RESULTS
In total, 913 records were screened, of which 73 were included that investigated mechanisms of resistance against anti-HER2 treatment in cell lines, xenograft models, patient tissue samples, and publicly available datasets. HER2-targeted therapy resistance was found to be caused by HER2 receptor changes, upregulation of compensatory receptors, (re)activation of downstream signaling pathways like PI3K/AKT and MAPK, epithelial-to-mesenchymal transition, acquirement of stem cell-like properties, alterations in cell cycle related genes, cellular metabolism, and drug pharmacokinetics.
DISCUSSION
Several different mechanisms can contribute to drug resistance to anti-HER2 treatment in GEA, mainly through loss of or mutations in the HER2 receptor and upregulation of alternative receptors such as MET, HER3, and FGFRs. Despite these preclinical results, methods to overcome the proposed resistance mechanisms in the clinical setting are lacking. Therefore, further investigation of therapy resistance in GEA patients treated with HER2 targeted therapy is essential to overcome resistance and improve treatment outcome of these patients.
Topics: Adenocarcinoma; Animals; Cell Line, Tumor; Drug Resistance, Neoplasm; Esophageal Neoplasms; Humans; Phosphatidylinositol 3-Kinases; Receptor, ErbB-2; Stomach Neoplasms
PubMed: 35689885
DOI: 10.1016/j.ctrv.2022.102418 -
Annals of Surgical Oncology Jun 2023Preoperative instead of standard postoperative partial breast irradiation (PBI) after breast-conserving surgery (BCS) has the advantage of reducing the irradiated breast... (Review)
Review
BACKGROUND
Preoperative instead of standard postoperative partial breast irradiation (PBI) after breast-conserving surgery (BCS) has the advantage of reducing the irradiated breast volume, toxicity, and number of radiotherapy sessions and can allow tumor downstaging. In this review, we assessed tumor response and clinical outcomes after preoperative PBI.
PATIENTS AND METHODS
We conducted a systematic review of studies on preoperative PBI in patients with low-risk breast cancer using the databases Ovid Medline, Embase.com, Web of Science (Core Collection), and Scopus (PROSPERO registration CRD42022301435). References of eligible manuscripts were checked for other relevant manuscripts. The primary outcome measure was pathologic complete response (pCR).
RESULTS
A total of eight prospective and one retrospective cohort study were identified (n = 359). In up to 42% of the patients, pCR was obtained and this increased after a longer interval between radiotherapy and BCS (0.5-8 months). After a maximum median follow-up of 5.0 years, three studies on external beam radiotherapy reported low local recurrence rates (0-3%) and overall survival of 97-100%. Acute toxicity consisted mainly of grade 1 skin toxicity (0-34%) and seroma (0-31%). Late toxicity was predominantly fibrosis grade 1 (46-100%) and grade 2 (10-11%). Cosmetic outcome was good to excellent in 78-100% of the patients.
CONCLUSIONS
Preoperative PBI showed a higher pCR rate after a longer interval between radiotherapy and BCS. Mild late toxicity and good oncological and cosmetic outcomes were reported. In the ongoing ABLATIVE-2 trial, BCS is performed at a longer interval of 12 months after preoperative PBI aiming to achieve a higher pCR rate.
Topics: Humans; Female; Breast Neoplasms; Prospective Studies; Retrospective Studies; Breast; Mastectomy, Segmental
PubMed: 36869253
DOI: 10.1245/s10434-023-13233-9 -
Brain Sciences Jul 2022Background: High-dose ionizing radiation (IR) (>0.5 Gy) is an established risk factor for cognitive impairments, but this cannot be concluded for low-to-moderate IR... (Review)
Review
Background: High-dose ionizing radiation (IR) (>0.5 Gy) is an established risk factor for cognitive impairments, but this cannot be concluded for low-to-moderate IR exposure (<0.5 Gy) in adulthood as study results are inconsistent. The objectives are to summarize relevant epidemiological studies of low-to-moderate IR exposure in adulthood and to assess the risk of non-cancerous CNS diseases. Methods: A systematic literature search of four electronic databases was performed to retrieve relevant epidemiological studies published from 2000 to 2022. Pooled standardized mortality ratios, relative risks, and excess relative risks (ERR) were estimated with a random effect model. Results: Forty-five publications were included in the systematic review, including thirty-three in the quantitative meta-analysis. The following sources of IR-exposure were considered: atomic bomb, occupational, environmental, and medical exposure. Increased dose-risk relationships were found for cerebrovascular diseases incidence and mortality (ERRpooled per 100 mGy = 0.04; 95% CI: 0.03−0.05; ERRpooled at 100 mGy = 0.01; 95% CI: −0.00−0.02, respectively) and for Parkinson’s disease (ERRpooled at 100 mGy = 0.11; 95% CI: 0.06−0.16); Conclusions: Our findings suggest that adult low-to-moderate IR exposure may have effects on non-cancerous CNS diseases. Further research addressing inherent variation issues is encouraged.
PubMed: 35892428
DOI: 10.3390/brainsci12080984 -
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 -
Cancer Control : Journal of the Moffitt... 2021Since protein arginine methyltransferase 5 (PRMT5) is abnormally expressed in various tumors, in this study we aim to assess the association between PRMT5 and... (Meta-Analysis)
Meta-Analysis
PURPOSE
Since protein arginine methyltransferase 5 (PRMT5) is abnormally expressed in various tumors, in this study we aim to assess the association between PRMT5 and clinicopathological and prognostic features.
METHODS
Electronic databases including PubMed, Web of Science, Scopus, ScienceDirect, and the Cochrane Library were searched until July 25, 2021. The critical appraisal of the eligible studies was performed using the Newcastle-Ottawa Quality Assessment Scale. Pooled hazard ratios (HR) and pooled odds ratios (OR) were calculated to assess the effect. Engauge Digitizer version 12.1, STATA version 15.1, and R version 4.0.5 were used to obtain and analysis the data.
RESULTS
A total of 32 original studies covering 15,583 patients were included. In our data, it indicated that high level of PRMT5 was significantly correlated with advanced tumor stage (OR = 2.12, 95% CI: 1.22-3.70, =.008; = 80.7%) and positively correlated with poor overall survival (HR = 1.59, 95% CI: 1.46-1.73, < .001; = 50%) and progression-free survival (HR = 1.53, 95% CI: 1.24-1.88, < .001; = 0%). In addition, sub-group analysis showed that high level of PRMT5 was associated with poor overall survival for such 5 kinds of cancers as hepatocellular carcinoma, pancreatic cancer, breast cancer, gastric cancer, and lung cancer.
CONCLUSION
For the first time we found PRMT5 was pan-cancerous as a prognostic biomarker and high level of PRMT5 was associated with poor prognosis for certain cancers.
Topics: Humans; Neoplasm Staging; Neoplasms; Protein-Arginine N-Methyltransferases; Survival Analysis
PubMed: 34758643
DOI: 10.1177/10732748211050583 -
BMJ Open Dec 2021This study aimed to assess the accuracy of CT texture analysis (CTTA) for differentiating low-grade and high-grade renal cell carcinoma (RCC). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This study aimed to assess the accuracy of CT texture analysis (CTTA) for differentiating low-grade and high-grade renal cell carcinoma (RCC).
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
PubMed, Cochrane Library, Embase, Web of Science, OVID Medline, Science Direct and Springer were searched to identify the included studies.
ELIGIBILITY CRITERIA FOR INCLUDING STUDIES
Clinical studies that report about the accuracy of CTTA in differentiating low-grade and high-grade RCC.
METHODS
Multiple databases were searched to identify studies from their inception to 20 October 2021. Two radiologists independently extracted data from the primary studies. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic OR (DOR) were calculated to assess CTTA performance. The summary receiver operating characteristic (SROC) curve was plotted, and the area under the curve (AUC) was calculated to evaluate the accuracy of CTTA in grading RCC.
RESULTS
This meta-analysis included 11 studies, with 1603 lesions observed in 1601 patients. Values of the pooled sensitivity, specificity, PLR, NLR, DOR were 0.79 (95% CI 0.73 to 0.84), 0.84 (95% CI 0.81 to 0.87), 5.1 (95% CI 4.0 to 6.4), 0.24 (95% CI 0.19 to 0.32) and 21 (95% CI 13 to 33), respectively. The SROC curve showed that the AUC was 0.88 (95% CI 0.84 to 0.90). Deeks' test found no significant publication bias among the studies (p=0.42).
CONCLUSIONS
The findings of this meta-analysis suggest that CTTA has a high accuracy in differentiating low-grade and high-grade RCC. A standardised methodology and large sample-based study are necessary to certain the diagnostic accuracy of CTTA in RCC grading for clinical decision making.
Topics: Carcinoma, Renal Cell; Humans; Kidney Neoplasms; ROC Curve; Sensitivity and Specificity; Tomography, X-Ray Computed
PubMed: 34937716
DOI: 10.1136/bmjopen-2021-051470 -
International Journal of Radiation... 2022Brain development during embryogenesis and in early postnatal life is particularly complex and involves the interplay of many cellular processes and molecular...
BACKGROUND
Brain development during embryogenesis and in early postnatal life is particularly complex and involves the interplay of many cellular processes and molecular mechanisms, making it extremely vulnerable to exogenous insults, including ionizing radiation (IR). Microcephaly is one of the most frequent neurodevelopmental abnormalities that is characterized by small brain size, and is often associated with intellectual deficiency. Decades of research span from epidemiological data on exposure of the A-bomb survivors, to studies on animal and cellular models that allowed deciphering the most prominent molecular mechanisms leading to microcephaly. The Adverse Outcome Pathway (AOP) framework is used to organize, evaluate and portray the scientific knowledge of toxicological effects spanning different biological levels of organizations, from the initial interaction with molecular targets to the occurrence of a disease or adversity. In the present study, the framework was used in an attempt to organize the current scientific knowledge on microcephaly progression in the context of ionizing radiation (IR) exposure. This work was performed by a group of experts formed during a recent workshop organized jointly by the Multidisciplinary European Low Dose Initiative (MELODI) and the European Radioecology Alliance (ALLIANCE) associations to present the AOP approach and tools. Here we report on the development of a putative AOP for congenital microcephaly resulting from IR exposure based on discussions of the working group and we emphasize the use of a novel machine-learning approach to assist in the screening of the available literature to develop AOPs.
CONCLUSION
The expert consultation led to the identification of crucial biological events for the progression of microcephaly upon exposure to IR, and highlighted current knowledge gaps. The machine learning approach was successfully used to screen the existing knowledge and helped to rapidly screen the body of evidence and in particular the epidemiological data. This systematic review approach also ensured that the analysis was sufficiently comprehensive to identify the most relevant data and facilitate rapid and consistent AOP development. We anticipate that as machine learning approaches become more user-friendly through easy-to-use web interface, this would allow AOP development to become more efficient and less time consuming.
Topics: Animals; Adverse Outcome Pathways; Microcephaly; Risk Assessment; Machine Learning; Referral and Consultation
PubMed: 35947014
DOI: 10.1080/09553002.2022.2110312 -
Frontiers in Immunology 2021Head and neck cancer (HNC) is the sixth most common malignancy worldwide; head and neck squamous cell carcinoma (HNSCC) account for the most cases of HNC. Past smoking...
Head and neck cancer (HNC) is the sixth most common malignancy worldwide; head and neck squamous cell carcinoma (HNSCC) account for the most cases of HNC. Past smoking and alcohol consumption are common risk factors of HNSCC; however, an increasing number of cases associated with human papillomavirus (HPV) infection have been reported in recent years. The treatment of HNSCC is integrated and multimodal including traditional surgery, radiotherapy, chemotherapy, and targeted therapy. Since pembrolizumab was approved in 2016, an increasing number of studies have focused on immunotherapy. However, not all of HNSCC patients have a better outcome on immunotherapy. Immunotherapy has been reported to be more effective in HPV-positive patients, but its molecular mechanism is still unclear. Some researchers have proposed that the high proportion of infiltrating immune cells in HPV-positive tumors and the difference in immune checkpoint expression level may be the reasons for their better response. As a result, a series of individualized immunotherapy trials have also been conducted in HPV-positive patients. This paper summarizes the current status of HNSCC immunotherapy, individualized immunotherapy in HPV-positive patients, and immune differences in HPV-positive tumors to provide new insights into HNSCC immunotherapy and try to identify patients who may benefit from immunotherapy.
Topics: Alphapapillomavirus; Antineoplastic Agents, Immunological; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Head and Neck Neoplasms; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Papillomavirus Infections; Progression-Free Survival; Randomized Controlled Trials as Topic; Squamous Cell Carcinoma of Head and Neck
PubMed: 34305889
DOI: 10.3389/fimmu.2021.652054