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      Systematic Review on the Association of Radiomics with Tumor Biological Endpoints

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          Abstract

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          In this systematic review, we aim to highlight existing literature devoted to the study of an association between medical imaging radiomics and cancer biological endpoints. The use of radiomics as an ancillary tool in cancer treatment would allow for a non-invasive, inexpensive, three-dimensional characterization of the tumor phenotype, contributing to the delivery of precision medicine. Nonetheless, its clinical application remains a challenge, as extensive, multi-center validation studies of radiomic features connection with tumor biology are required. In this review, we performed a search in PubMed database for peer-reviewed studies which evaluate the association between radiomic features and the following set of clinically relevant tumor markers: anaplastic lymphoma kinase (ALK), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), epidermal growth factor (EGFR), human epidermal growth factor receptor 2 (HER-2), isocitrate dehydrogenase (IDH), antigen Ki-67, kirsten rat sarcoma viral oncogene homolog (KRAS), programmed cell death ligand 1 (PD-L1), tumor protein p53 (TP-53) and vascular endothelial growth factor (VEGF).

          Abstract

          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.

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          Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement

          Systematic reviews should build on a protocol that describes the rationale, hypothesis, and planned methods of the review; few reviews report whether a protocol exists. Detailed, well-described protocols can facilitate the understanding and appraisal of the review methods, as well as the detection of modifications to methods and selective reporting in completed reviews. We describe the development of a reporting guideline, the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015). PRISMA-P consists of a 17-item checklist intended to facilitate the preparation and reporting of a robust protocol for the systematic review. Funders and those commissioning reviews might consider mandating the use of the checklist to facilitate the submission of relevant protocol information in funding applications. Similarly, peer reviewers and editors can use the guidance to gauge the completeness and transparency of a systematic review protocol submitted for publication in a journal or other medium.
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            Radiomics: the bridge between medical imaging and personalized medicine

            Radiomics, the high-throughput mining of quantitative image features from standard-of-care medical imaging that enables data to be extracted and applied within clinical-decision support systems to improve diagnostic, prognostic, and predictive accuracy, is gaining importance in cancer research. Radiomic analysis exploits sophisticated image analysis tools and the rapid development and validation of medical imaging data that uses image-based signatures for precision diagnosis and treatment, providing a powerful tool in modern medicine. Herein, we describe the process of radiomics, its pitfalls, challenges, opportunities, and its capacity to improve clinical decision making, emphasizing the utility for patients with cancer. Currently, the field of radiomics lacks standardized evaluation of both the scientific integrity and the clinical relevance of the numerous published radiomics investigations resulting from the rapid growth of this area. Rigorous evaluation criteria and reporting guidelines need to be established in order for radiomics to mature as a discipline. Herein, we provide guidance for investigations to meet this urgent need in the field of radiomics.
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              The Ki-67 protein: from the known and the unknown.

              The expression of the human Ki-67 protein is strictly associated with cell proliferation. During interphase, the antigen can be exclusively detected within the nucleus, whereas in mitosis most of the protein is relocated to the surface of the chromosomes. The fact that the Ki-67 protein is present during all active phases of the cell cycle (G(1), S, G(2), and mitosis), but is absent from resting cells (G(0)), makes it an excellent marker for determining the so-called growth fraction of a given cell population. In the first part of this study, the term proliferation marker is discussed and examples of the applications of anti-Ki-67 protein antibodies in diagnostics of human tumors are given. The fraction of Ki-67-positive tumor cells (the Ki-67 labeling index) is often correlated with the clinical course of the disease. The best-studied examples in this context are carcinomas of the prostate and the breast. For these types of tumors, the prognostic value for survival and tumor recurrence has repeatedly been proven in uni- and multivariate analysis. The preparation of new monoclonal antibodies that react with the Ki-67 equivalent protein from rodents now extends the use of the Ki-67 protein as a proliferation marker to laboratory animals that are routinely used in basic research. The second part of this review focuses on the biology of the Ki-67 protein. Our current knowledge of the Ki-67 gene and protein structure, mRNA splicing, expression, and cellular localization during the cell-division cycle is summarized and discussed. Although the Ki-67 protein is well characterized on the molecular level and extensively used as a proliferation marker, the functional significance still remains unclear. There are indications, however, that Ki-67 protein expression is an absolute requirement for progression through the cell-division cycle. Copyright 2000 Wiley-Liss, Inc.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                16 June 2021
                June 2021
                : 13
                : 12
                : 3015
                Affiliations
                [1 ]Department of Radiation Oncology, University Hospital Zurich and University of Zurich, 8091 Zurich, Switzerland; diem.vuong@ 123456usz.ch (D.V.); Janita.vanTimmeren@ 123456usz.ch (J.E.v.T.); riccardo.dalbello@ 123456usz.ch (R.D.B.); matthias.guckenberger@ 123456usz.ch (M.G.); stephanie.tanadini-lang@ 123456usz.ch (S.T.-L.)
                [2 ]Laboratory of Applied Radiobiology, Department of Radiation Oncology, University of Zurich, 8091 Zurich, Switzerland; fabienne.tschanz@ 123456uzh.ch (F.T.); verena.waller@ 123456uzh.ch (V.W.); martin.pruschy@ 123456uzh.ch (M.P.)
                Author notes
                Author information
                https://orcid.org/0000-0003-4504-611X
                https://orcid.org/0000-0001-7153-4219
                https://orcid.org/0000-0002-8755-377X
                https://orcid.org/0000-0001-5856-1968
                https://orcid.org/0000-0002-3124-9015
                https://orcid.org/0000-0002-7146-9071
                https://orcid.org/0000-0002-4387-1522
                Article
                cancers-13-03015
                10.3390/cancers13123015
                8234501
                34208595
                63706887-e6ca-4cb6-82df-8bdf0ecd6543
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 19 May 2021
                : 11 June 2021
                Categories
                Systematic Review

                radiomics,tumor biology,cancer,imaging biomarker,tumor molecular marker

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