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      FDG-PET/CT for Response Monitoring in Metastatic Breast Cancer: Today, Tomorrow, and Beyond

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          Abstract

          While current international guidelines include imaging of the target lesion for response monitoring in metastatic breast cancer, they do not provide specific recommendations for choice of imaging modality or response criteria. This is important as clinical decisions may vary depending on which imaging modality is used for monitoring metastatic breast cancer. FDG-PET/CT has shown high accuracy in diagnosing metastatic breast cancer, and the Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) have shown higher predictive values than the CT-based Response Evaluation Criteria in Solid Tumors (RECIST) for prediction of progression-free survival. No studies have yet addressed the clinical impact of using different imaging modalities or response evaluation criteria for longitudinal response monitoring in metastatic breast cancer. We present a case study of a patient with metastatic breast cancer who was monitored first with conventional CT and then with FDG-PET/CT. We retrospectively applied PERCIST to evaluate the longitudinal response to treatment. We used the one-lesion PERCIST model measuring SULpeak in the hottest metastatic lesion on consecutive scans. This model provides a continuous variable that allows graphical illustration of disease fluctuation along with response categories. The one-lesion PERCIST approach seems able to reflect molecular changes and has the potential to support clinical decision-making. Prospective clinical studies addressing the clinical impact of PERCIST in metastatic breast cancer are needed to establish evidence-based recommendations for response monitoring in this disease.

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          From RECIST to PERCIST: Evolving Considerations for PET response criteria in solid tumors.

          The purpose of this article is to review the status and limitations of anatomic tumor response metrics including the World Health Organization (WHO) criteria, the Response Evaluation Criteria in Solid Tumors (RECIST), and RECIST 1.1. This article also reviews qualitative and quantitative approaches to metabolic tumor response assessment with (18)F-FDG PET and proposes a draft framework for PET Response Criteria in Solid Tumors (PERCIST), version 1.0. PubMed searches, including searches for the terms RECIST, positron, WHO, FDG, cancer (including specific types), treatment response, region of interest, and derivative references, were performed. Abstracts and articles judged most relevant to the goals of this report were reviewed with emphasis on limitations and strengths of the anatomic and PET approaches to treatment response assessment. On the basis of these data and the authors' experience, draft criteria were formulated for PET tumor response to treatment. Approximately 3,000 potentially relevant references were screened. Anatomic imaging alone using standard WHO, RECIST, and RECIST 1.1 criteria is widely applied but still has limitations in response assessments. For example, despite effective treatment, changes in tumor size can be minimal in tumors such as lymphomas, sarcoma, hepatomas, mesothelioma, and gastrointestinal stromal tumor. CT tumor density, contrast enhancement, or MRI characteristics appear more informative than size but are not yet routinely applied. RECIST criteria may show progression of tumor more slowly than WHO criteria. RECIST 1.1 criteria (assessing a maximum of 5 tumor foci, vs. 10 in RECIST) result in a higher complete response rate than the original RECIST criteria, at least in lymph nodes. Variability appears greater in assessing progression than in assessing response. Qualitative and quantitative approaches to (18)F-FDG PET response assessment have been applied and require a consistent PET methodology to allow quantitative assessments. Statistically significant changes in tumor standardized uptake value (SUV) occur in careful test-retest studies of high-SUV tumors, with a change of 20% in SUV of a region 1 cm or larger in diameter; however, medically relevant beneficial changes are often associated with a 30% or greater decline. The more extensive the therapy, the greater the decline in SUV with most effective treatments. Important components of the proposed PERCIST criteria include assessing normal reference tissue values in a 3-cm-diameter region of interest in the liver, using a consistent PET protocol, using a fixed small region of interest about 1 cm(3) in volume (1.2-cm diameter) in the most active region of metabolically active tumors to minimize statistical variability, assessing tumor size, treating SUV lean measurements in the 1 (up to 5 optional) most metabolically active tumor focus as a continuous variable, requiring a 30% decline in SUV for "response," and deferring to RECIST 1.1 in cases that do not have (18)F-FDG avidity or are technically unsuitable. Criteria to define progression of tumor-absent new lesions are uncertain but are proposed. Anatomic imaging alone using standard WHO, RECIST, and RECIST 1.1 criteria have limitations, particularly in assessing the activity of newer cancer therapies that stabilize disease, whereas (18)F-FDG PET appears particularly valuable in such cases. The proposed PERCIST 1.0 criteria should serve as a starting point for use in clinical trials and in structured quantitative clinical reporting. Undoubtedly, subsequent revisions and enhancements will be required as validation studies are undertaken in varying diseases and treatments.
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            Hallmarks of glycosylation in cancer

            Aberrant glycosylation plays a fundamental role in key pathological steps of tumour development and progression. Glycans have roles in cancer cell signalling, tumour cell dissociation and invasion, cell-matrix interactions, angiogenesis, metastasis and immune modulation. Aberrant glycosylation is often cited as a ‘hallmark of cancer’ but is notably absent from both the original hallmarks of cancer and from the next generation of emerging hallmarks. This review discusses how glycosylation is clearly an enabling characteristic that is causally associated with the acquisition of all the hallmark capabilities. Rather than aberrant glycosylation being itself a hallmark of cancer, another perspective is that glycans play a role in every recognised cancer hallmark.
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              Practical PERCIST: A Simplified Guide to PET Response Criteria in Solid Tumors 1.0.

              Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST 1.0) describes in detail methods for controlling the quality of fluorine 18 fluorodeoxyglucose PET imaging conditions to ensure the comparability of PET images from different time points to allow quantitative expression of the changes in PET measurements and assessment of overall treatment response in PET studies. The steps for actual application of PERCIST are summarized. Several issues from PERCIST 1.0 that appear to require clarification, such as measurement of size and definition of unequivocal progression, also are addressed. (©) RSNA, 2016.
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                15 August 2019
                August 2019
                : 11
                : 8
                : 1190
                Affiliations
                [1 ]Department of Nuclear Medicine, Odense University Hospital, 5000 Odense, Denmark
                [2 ]Department of Clinical Research, University of Southern Denmark, 5230 Odense, Denmark
                [3 ]Centre for Innovative Medical Technology, Odense University Hospital, 5000 Odense, Denmark
                [4 ]Department of Nuclear Medicine, Lillebaelt Hospital, 7100 Vejle, Denmark
                [5 ]Department of Oncology, Odense University Hospital, 5000 Odense, Denmark
                [6 ]Department of Clinical Genetics, Odense University Hospital, 5000 Odense, Denmark
                Author notes
                [* ]Correspondence: Malene.grubbe.hildebrandt@ 123456rsyd.dk ; Tel.: +45-3017-1888
                Author information
                https://orcid.org/0000-0003-2720-9018
                https://orcid.org/0000-0002-6124-4063
                https://orcid.org/0000-0003-4906-5422
                https://orcid.org/0000-0001-6335-3303
                https://orcid.org/0000-0001-7420-2367
                Article
                cancers-11-01190
                10.3390/cancers11081190
                6721531
                31443324
                e18cf054-0e4c-46e5-a64f-13a34cc4bd3a
                © 2019 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 ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 20 July 2019
                : 14 August 2019
                Categories
                Perspective

                precision oncology,fdg-pet/ct,percist,metastatic breast cancer

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