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      Lesion-based detection of early chemosensitivity using serial static FDG PET/CT in metastatic colorectal cancer

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          Abstract

          Purpose

          Medical oncology needs early identification of patients that are not responding to systemic therapy. 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) performed before and early during treatment has been proposed for this purpose. However, the best way to assess the change in FDG uptake between two scans has not been identified. We studied cutoff thresholds to identify responding tumours as a function of the method used to measure tumour uptake.

          Methods

          The study included 28 metastatic colorectal cancer (mCRC) patients who underwent 2 FDG PET/CT scans (baseline and at day 14 of the first course of polychemotherapy). For 78 tumour lesions, 4 standardized uptake value (SUV) indices were measured: maximum SUV (SUV max) and mean SUV in a region obtained using an isocontour (SUV 40 %), with each of these SUV normalized either by the patient body weight (BW) or body surface area (BSA). The per cent change and absolute change in tumour uptake between the baseline and the early PET scans were measured based on these four indices. These changes were correlated to the RECIST 1.0-based response using contrast-enhanced CT at baseline and at 6–8 weeks on treatment.

          Results

          The 78 tumours were classified as non-responding (NRL, n = 58) and responding lesions (RL, n = 20). Receiver-operating characteristic (ROC) curves characterizing the performance in NRL/RL classification using early FDG PET uptake had areas under the curve between 0.75 and 0.84, without significant difference between the indices. The cutoff threshold in FDG uptake per cent change to get a 95 % sensitivity of RL detection depended on the way uptake was measured: −14 % (specificity of 53 %) and −22 % (specificity of 64 %) for SUV max and SUV 40 %, respectively. Thresholds expressed as absolute SUV decrease instead of per cent change were less sensitive to the SUV definition: an SUV decline by 1.2 yielded a sensitivity of RL detection of 95 % for SUV max and SUV 40 %. For a given cutoff threshold, the sensitivity was the same whatever the normalization (by BSA or BW).

          Conclusion

          A 14 % drop of tumour FDG SUV max, 22 % drop of SUV 40 % or 1.2 drop of SUV max or SUV mean after one single course of polychemotherapy predicts objective response in mCRC lesions with a high sensitivity, potentially allowing the early identification of non-responding patients.

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          Most cited references15

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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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            Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group.

            [18F]-fluorodeoxyglucose ([18F]-FDG) uptake is enhanced in most malignant tumours which in turn can be measured using positron emission tomography (PET). A number of small clinical trials have indicated that quantification of the change in tumour [18F]-FDG uptake may provide an early, sensitive, pharmacodynamic marker of the tumoricidal effect of anticancer drugs. This may allow for the introduction of subclinical response for anticancer drug evaluation in early clinical trials and improvements in patient management. For comparison of results from smaller clinical trials and larger-scale multicentre trials a consensus is desirable for: (i) common measurement criteria; and (ii) reporting of alterations in [18F]-FDG uptake with treatment. This paper summarises the current status of the technique and recommendations on the measurement of [18F]-FDG uptake for tumour response monitoring from a consensus meeting of the European Organization for Research and Treatment of Cancer (EORTC) PET study group held in Brussels in February 1998 and confirmed at a subsequent meeting in March 1999.
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              Consensus recommendations for the use of 18F-FDG PET as an indicator of therapeutic response in patients in National Cancer Institute Trials.

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                Author and article information

                Contributors
                +33-1-69153640 , +33-1-69157196 , buvat@imnc.in2p3.fr
                Journal
                Eur J Nucl Med Mol Imaging
                Eur. J. Nucl. Med. Mol. Imaging
                European Journal of Nuclear Medicine and Molecular Imaging
                Springer-Verlag (Berlin/Heidelberg )
                1619-7070
                1619-7089
                19 June 2012
                19 June 2012
                October 2012
                : 39
                : 10
                : 1628-1634
                Affiliations
                [1 ]IMNC UMR 8165 CNRS – Paris 7 and Paris 11 Universities, Campus d’Orsay, Bâtiment 440, 91406 Orsay cedex, France
                [2 ]Nuclear Medicine Department, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium
                [3 ]Radiology Department, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium
                [4 ]Digestive Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium
                Article
                2172
                10.1007/s00259-012-2172-2
                3458195
                22710958
                d306fab1-e9a2-454f-b8e4-c9e78f11cb83
                © The Author(s) 2012
                History
                : 14 December 2011
                : 23 May 2012
                Categories
                Original Article
                Custom metadata
                © Springer-Verlag 2012

                Radiology & Imaging
                pet/ct,objective response prediction,fdg,advanced colorectal cancer,eortc criteria,suv

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