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International Journal of Radiation... Mar 2023The Lyman model is one of the most used radiobiological models for calculation of normal-tissue complication probability (NTCP). Since its introduction in 1985, many...
PURPOSE
The Lyman model is one of the most used radiobiological models for calculation of normal-tissue complication probability (NTCP). Since its introduction in 1985, many authors have published parameter values for the model based on clinical data of different radiotherapeutic situations. This study attempted to collect the entirety of radiobiological parameter sets published to date and provide an overview of the data basis for different variations of the model. Furthermore, it sought to compare the parameter values and calculated NTCPs for selected endpoints with sufficient data available.
METHODS AND MATERIALS
A systematic literature analysis was performed, searching for publications that provided parameters for the different variations of the Lyman model in the Medline database using PubMed. Parameter sets were grouped into 13 toxicity-related endpoint groups. For 3 selected endpoint groups (≤25% reduction of saliva 12 months after irradiation of the parotid, symptomatic pneumonitis after irradiation of the lung, and bleeding of grade 2 or less after irradiation of the rectum), parameter values were compared and differences in calculated NTCP values were analyzed.
RESULTS
A total of 509 parameter sets from 130 publications were identified. Considerable heterogeneities were detected regarding the number of parameters available for different radio-oncological situations. Furthermore, for the 3 selected endpoints, large differences in published parameter values were found. These translated into great variations of calculated NTCPs, with maximum ranges of 35.2% to 93.4% for the saliva endpoint, of 39.4% to 90.4% for the pneumonitis endpoint, and of 5.4% to 99.3% for the rectal bleeding endpoint.
CONCLUSIONS
The detected heterogeneity of the data as well as the large variations of published radiobiological parameters underline the necessity for careful interpretation when using such parameters for NTCP calculations. Appropriate selection of parameters and validation of values are essential when using the Lyman model.
Topics: Humans; Probability; Radiotherapy Planning, Computer-Assisted; Rectum; Radiobiology
PubMed: 36029911
DOI: 10.1016/j.ijrobp.2022.08.039 -
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 -
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 -
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 -
Radiography (London, England : 1995) Aug 2022Advances in Radiotherapy (RT) technology and increase of complexity in cancer care have enabled the implementation of new treatment techniques. Subsequently, a greater... (Review)
Review
INTRODUCTION
Advances in Radiotherapy (RT) technology and increase of complexity in cancer care have enabled the implementation of new treatment techniques. Subsequently, a greater level of autonomy, responsibility, and accountability in the practice of Therapeutic Radiographers/Radiation Therapists (TR/RTTs) has led to Advanced Practice (AP) roles. The published evidence of this role is scattered with confusing terminology and divergence regarding the perception of whether a specific role represents AP internationally. This study aims to establish an international baseline of evidence on AP roles in RT to identify roles and activities performed by TR/RTTs at advanced level practice and to summarise the impact.
METHODS
A systematic PRISMA review of the literature was undertaken. Thematic analysis was used to synthesise the roles and associated activities. Six RT external experts validated the list. The impact was scrutinised in terms of clinical, organisational, and professional outcomes.
RESULTS
Studies (n = 87) were included and categorised into four groups. AP roles were listed by clinical area, site-specific, and scope of practice, and advanced activities were organised into seven dimensions and 27 sub-dimensions. Three most-reported outcomes were: enhanced service capacity, higher patient satisfaction, and safety maintenance.
CONCLUSION
Evidence-based AP amongst TR/RTTs show how AP roles were conceptualised, implemented, and evaluated. Congruence studies have shown that TR/RTTs are at par with the gold-standard across the various AP roles.
IMPLICATIONS FOR PRACTICE
This is the first systematic literature review synthetisising AP roles and activities of TR/RTTs. This study also identified the main areas of AP that can be used to develop professional frameworks and education guiding policy by professional bodies, educators and other stakeholders.
Topics: Allied Health Personnel; Humans; Radiation Oncology
PubMed: 35550932
DOI: 10.1016/j.radi.2022.04.009 -
Clinical Oncology (Royal College of... Oct 2022Patient factors affect the risk of radiotherapy toxicity, but many are poorly defined. Studies have shown that race affects cancer incidence, survival, drug response,...
AIMS
Patient factors affect the risk of radiotherapy toxicity, but many are poorly defined. Studies have shown that race affects cancer incidence, survival, drug response, molecular pathways and epigenetics. Effects on radiosensitivity and radiotherapy toxicity are not well studied. The aim of the present study was to identify the effects of race and ethnicity on the risk of radiotherapy toxicity.
MATERIALS AND METHODS
A systematic review was carried out of PubMed, Ovid Medline and Ovid Embase with no year limit. PRISMA 2020 guidelines were followed. Two independent assessors reviewed papers.
RESULTS
Of 607 papers screened, 46 fulfilled the inclusion criteria. Papers were published between 1996 and 2021 and involved 30-28,354 individuals (median 433). Most involved patients with prostate (33%), breast (26%) and lung (9%) cancer. Both early and late toxicities were studied. Some studies reported a higher risk of toxicity in White men with prostate cancer compared with other races and ethnicities. For breast cancer patients, some reported an increased risk of toxicity in White women compared with other race and ethnic groups. In general, it was difficult to draw conclusions due to insufficient reporting and analysis of race and ethnicity in published literature.
CONCLUSIONS
Reporting of race and ethnicity in radiotherapy studies must be harmonised and improved and frameworks are needed to improve the quality of reporting. Further research is needed to understand how ancestral heritage might affect radiosensitivity and risk of radiotherapy toxicity.
Topics: Ethnicity; Humans; Incidence; Male; Prostatic Neoplasms; Radiation Injuries
PubMed: 35431121
DOI: 10.1016/j.clon.2022.03.013 -
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 -
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 -
Cancer Treatment Reviews Nov 2021Esophageal and gastric malignancies are associated with poor prognosis, in part due to development of recurrences or metastases after curative treatment. The...
Esophageal and gastric malignancies are associated with poor prognosis, in part due to development of recurrences or metastases after curative treatment. The transforming growth factor β (TGF-β) pathway might play a role in the development of treatment resistance. In this systematic review, we provide an overview of preclinical studies investigating the role of TGF-β in esophageal and gastric malignancies. We systematically searched MEDLINE/PubMed and EMBASE for eligible preclinical studies describing the effect of TGF-β or TGF-β inhibition on hallmarks of cancer, such as proliferation, migration, invasion, angiogenesis and immune evasion. In total, 2107 records were screened and 45 articles were included, using mouse models and 45 different cell lines. TGF-β failed to induce apoptosis in twelve of sixteen tested cell lines. TGF-β could either decrease (five cell lines) or increase proliferation (seven cell lines) in gastric cancer cells, but had no effect in esophageal cancer cells. In all esophageal and all but two gastric cancer cell lines, TGF-β increased migratory, adhesive and invasive capacities. In vivo studies showed increased metastasis in response to TGF-β treatment. Additionally, TGF-β was shown to induce vascular endothelial growth factor production and differentiation of cancer-associated fibroblasts and regulatory T-cells. In conclusion, we found that TGF-β enhances hallmarks of cancer in most gastric and esophageal cancer cell lines, but not in all. Therefore, targeting the TGF-β pathway could be an attractive strategy in patients with gastric or esophageal cancer, but additional clinical trials are needed to define patient groups who would benefit most.
Topics: Animals; Esophageal Neoplasms; Humans; Mice; Stomach Neoplasms; Transforming Growth Factor beta
PubMed: 34536730
DOI: 10.1016/j.ctrv.2021.102285 -
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