Oncology Scan: Radiation Biology and Genomic Predictors of Response.
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ABSTRACT:
SUBMITTER: Marples B
PROVIDER: S-EPMC8725062 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Radiobiology research is building the foundation for applying genomics in precision radiation oncology. Advances in high-throughput approaches will underpin increased understanding of radiosensitivity and the development of future predictive assays for clinical application. There is an established contribution of genetics as a risk factor for radiotherapy side effects. An individual's radiosensitivity is an inherited polygenic trait with an architecture that includes rare mutations in a few genes that confer large effects and common variants in many genes with small effects. Current thinking is that some will be tissue specific, and future tests will be tailored to the normal tissues at risk. The relationship between normal and tumor cell radiosensitivity is poorly understood. Data are emerging suggesting interplay between germline genetic variation and epigenetic modification with growing evidence that changes in DNA methylation regulate the radiosensitivity of cancer cells and histone acetyltransferase inhibitors have radiosensitizing effects. Changes in histone methylation can also impair DNA damage response signaling and alter radiosensitivity. An important effort to advance radiobiology in the genomic era was establishment of the Radiogenomics Consortium to enable the creation of the large radiotherapy cohorts required to exploit advances in genomics. To address challenges in harmonizing data from multiple cohorts, the consortium established the REQUITE project to collect standardized data and genotyping for ~5,000 patients. The collection of detailed dosimetric data is important to produce validated multivariable models. Continued efforts will identify new genes that impact on radiosensitivity to generate new knowledge on toxicity pathogenesis and tests to incorporate into the clinical decision-making process.
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Project description:The overall goal of radiogenomics is the identification of genomic markers that are predictive for the development of adverse effects resulting from cancer treatment with radiation. The principal rationale for a focus on toxicity in radiogenomics is that for many patients treated with radiation, especially individuals diagnosed with early-stage cancers, the survival rates are high, and therefore a substantial number of people will live for a significant period of time beyond treatment. However, many of these patients could suffer from debilitating complications resulting from radiotherapy. Work in radiogenomics has greatly benefited from creation of the Radiogenomics Consortium (RGC) that includes investigators at multiple institutions located in a variety of countries. The common goal of the RGC membership is to share biospecimens and data so as to achieve large-scale studies with increased statistical power to enable identification of relevant genomic markers. A major aim of research in radiogenomics is the development of a predictive instrument to enable identification of people who are at greatest risk for adverse effects resulting from cancer treatment using radiation. It is anticipated that creation of a predictive assay characterized by a high level of sensitivity and specificity will improve precision radiotherapy and assist patients and their physicians to select the optimal treatment for each individual.
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Project description:Future radiation oncology encompasses a broad spectrum of topics ranging from modern clinical trial design to treatment and imaging technology and biology. In more detail, the application of hybrid MRI devices in modern image-guided radiotherapy; the emerging field of radiomics; the role of molecular imaging using positron emission tomography and its integration into clinical routine; radiation biology with its future perspectives, the role of molecular signatures in prognostic modelling; as well as special treatment modalities such as brachytherapy or proton beam therapy are areas of rapid development. More clinically, radiation oncology will certainly find an important role in the management of oligometastasis. The treatment spectrum will also be widened by the rational integration of modern systemic targeted or immune therapies into multimodal treatment strategies. All these developments will require a concise rethinking of clinical trial design. This article reviews the current status and the potential developments in the field of radiation oncology as discussed by a panel of European and international experts sharing their vision during the "X-Change" symposium, held in July 2019 in Munich (Germany).
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Project description:Asthma is a complex respiratory disease considered as the most common chronic condition in children. A large genetic contribution to asthma susceptibility is predicted by the clustering of asthma and allergy symptoms among relatives and the large disease heritability estimated from twin studies, ranging from 55 to 90%. Genetic basis of asthma has been extensively investigated in the past 40 years using linkage analysis and candidate-gene association studies. However, the development of dense arrays for polymorphism genotyping has enabled the transition toward genome-wide association studies (GWAS), which have led the discovery of several unanticipated asthma genes in the last 11 years. Despite this, currently known risk variants identified using many thousand samples from distinct ethnicities only explain a small proportion of asthma heritability. This review examines the main findings of the last 2 years in genomic studies of asthma using GWAS and admixture mapping studies, as well as the direction of studies fostering integrative perspectives involving omics data. Additionally, we discuss the need for assessing the whole spectrum of genetic variation in association studies of asthma susceptibility, severity, and treatment response in order to further improve our knowledge of asthma genes and predictive biomarkers. Leveraging the individual's genetic information will allow a better understanding of asthma pathogenesis and will facilitate the transition toward a more precise diagnosis and treatment.
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Project description:Leveraging Electronic Health Records (EHR) and Oncology Information Systems (OIS) has great potential to generate hypotheses for cancer treatment, since they directly provide medical data on a large scale. In order to gather a significant amount of patients with a high level of clinical details, multicenter studies are necessary. A challenge in creating high quality Big Data studies involving several treatment centers is the lack of semantic interoperability between data sources. We present the ontology we developed to address this issue.Radiation Oncology anatomical and target volumes were categorized in anatomical and treatment planning classes. International delineation guidelines specific to radiation oncology were used for lymph nodes areas and target volumes. Hierarchical classes were created to generate The Radiation Oncology Structures (ROS) Ontology. The ROS was then applied to the data from our institution.Four hundred and seventeen classes were created with a maximum of 14 children classes (average = 5). The ontology was then converted into a Web Ontology Language (.owl) format and made available online on Bioportal and GitHub under an Apache 2.0 License. We extracted all structures delineated in our department since the opening in 2001. 20,758 structures were exported from our "record-and-verify" system, demonstrating a significant heterogeneity within a single center. All structures were matched to the ROS ontology before integration into our clinical data warehouse (CDW).In this study we describe a new ontology, specific to radiation oncology, that reports all anatomical and treatment planning structures that can be delineated. This ontology will be used to integrate dosimetric data in the Assistance Publique-Hôpitaux de Paris CDW that stores data from 6.5 million patients (as of February 2017).
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Project description:PurposeThe presence of women and people underrepresented in medicine (URiM) continues to be lower in radiation oncology (RO) than within the United States population, medical school graduates, and oncology fellowship applicants. The objective of this study was to identify demographics of matriculating medical students who are inclined to consider pursuing a residency in RO and identify barriers to entry that students may perceive before medical school training.Methods and materialsA survey of incoming medical students at New York Medical College was distributed via e-mail and assessed demographic background information, interest in and awareness of oncologic subspecialties, and perceived barriers to RO.ResultsStudents of the incoming class of 2026 had a complete response rate of 72% (155 complete responses and 8 incomplete responses of 214 class members). Two-thirds of participants had prior awareness of RO, and half have considered pursuing an oncologic subspecialty, but less than one-fourth have ever previously considered a career in RO. Students responded that they need more education, clinical exposure, and mentorship to increase their chance of choosing RO. Male participants had 3.4 times the odds of having an acquaintance in the community tell them about the specialty and also had significantly greater interest in using advanced technologies. There were no URiM participants who had personal relationships with an RO physician compared with 6 (4.5%) non-URiM participants. The average response to "What is the likelihood that you will pursue a career in RO?" showed no significant difference between genders.ConclusionsAll races and ethnicities scored a similar likelihood of pursuing a career in RO, which differs greatly from the current RO workforce. Responses emphasized the importance of education, mentorship, and exposure to RO. This study demonstrates the need for support of female and URiM students during medical school.
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