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      Imaging therapy response of gastrointestinal stromal tumors (GIST) with FDG PET, CT and MRI: a systematic review

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          Abstract

          Purpose

          Improvement of the therapeutic approaches in gastrointestinal stromal tumors (GIST) by the introduction of targeted therapies requires appropriate diagnostic tools, which allow sufficient assessment of therapeutic response, including differentiation of true progression from pseudoprogression due to myxoid degeneration or intratumoral hemorrhage. In this literature review the impact and limitations of different imaging modalities used in GIST therapy monitoring are discussed.

          Methods

          PubMed and Cochrane library search were performed using appropriate keywords. Overall, 39 original papers fulfilled the defined criteria and were included in this systematic review.

          Results

          Morphological imaging modalities like computed tomography (CT) are primarily used for both diagnosis and therapy monitoring. However, therapy with tyrosine kinase inhibitors and other targeted therapies in GIST may lead only to a minor tumor volume reduction even in cases of response. Therefore, the use of Response Evaluation Criteria in Solid Tumors (RECIST) has limitations. To overcome those limitations, modified response criteria have been introduced for the CT-based therapy assessment, like the Choi criteria as well as criteria based on dual energy CT studies. Functional imaging techniques, mostly based on FDG PET-CT are in use, in particular for the assessment of early treatment response.

          Conclusions

          The impact and the limitations of PET-based therapy monitoring, as well as its comparison with CT, MRI and survival data are discussed in this review. CT is still the standard method for the evaluation of therapy response despite its several limitations. FDG PET-CT is helpful for the assessment of early therapy response; however, more prospective data are needed to define its role as well as the appropriate time intervals for therapy monitoring. A multiparametric evaluation based on changes in both morphological and functional data has to be assessed in further prospective studies.

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

          Richard L. Wahl, Heather Jacene, Yvette Kasamon … (2009)
          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.

            H. Young, R. Baum, U Cremerius … (1999)
            [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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              Biology of gastrointestinal stromal tumors.

              Christopher L Corless, Jonathan A. Fletcher, Michael Heinrich (2004)
              Once a poorly defined pathologic oddity, in recent years, gastrointestinal stromal tumor (GIST) has emerged as a distinct oncogenetic entity that is now center stage in clinical trials of kinase-targeted therapies. This review charts the rapid progress that has established GIST as a model for understanding the role of oncogenic kinase mutations in human tumorigenesis. Approximately 80% to 85% of GISTs harbor activating mutations of the KIT tyrosine kinase. In a series of 322 GISTs (including 140 previously published cases) studied by the authors in detail, mutations in the KIT gene occurred with decreasing frequency in exons 11 (66.1%), 9 (13%), 13 (1.2%), and 17 (0.6%). In the same series, a subset of tumors had mutations in the KIT-related kinase gene PDGF receptor alpha (PDGFRA), which occurred in either exon 18 (5.6%) or 12 (1.5%). The remainder of GISTs (12%) were wild type for both KIT and PDGFRA. Comparative studies of KIT-mutant, PDGFRA-mutant, and wild-type GISTs indicate that there are many similarities between these groups of tumors but also important differences. In particular, the responsiveness of GISTs to treatment with the kinase inhibitor imatinib varies substantially depending on the exonic location of the KIT or PDGFRA mutation. Given these differences, which have implications both for the diagnosis and treatment of GISTs, we propose a molecular-based classification of GIST. Recent studies of familial GIST, pediatric GIST, and variant forms of GIST related to Carney's triad and neurofibromatosis type 1 are discussed in relationship to this molecular classification. In addition, the role of mutation screening in KIT and PDGFRA as a diagnostic and prognostic aid is emphasized in this review.
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                Author and article information

                Contributors
                Antonia Dimitrakopoulou-Strauss:
                ORCID: http://orcid.org/0000-0003-0338-9472
                ++49 6221 422500 , ads@ads-lgs.de , a.dimitrakopoulou-strauss@dkfz.de
                Journal
                Journal ID (nlm-ta): Clin Transl Imaging
                Journal ID (iso-abbrev): Clin Transl Imaging
                Title: Clinical and Translational Imaging
                Publisher: Springer Milan (Milan )
                ISSN (Print): 2281-5872
                ISSN (Electronic): 2281-7565
                Publication date (Electronic): 3 May 2017
                Publication date PMC-release: 3 May 2017
                Publication date (Print): 2017
                Volume: 5
                Issue: 3
                Pages: 183-197
                Affiliations
                [1 ]ISNI 0000 0004 0492 0584, GRID grid.7497.d, Clinical Cooperation Unit Nuclear Medicine, , German Cancer Research Center, ; Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
                [2 ]ISNI 0000 0001 2190 4373, GRID grid.7700.0, Division of Surgical Oncology and Thoracic Surgery, Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, , Heidelberg University, ; Mannheim, Germany
                [3 ]ISNI 0000 0001 2190 4373, GRID grid.7700.0, Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, , Heidelberg University, ; Mannheim, Germany
                Author information
                http://orcid.org/0000-0003-0338-9472
                Article
                Publisher ID: 229
                DOI: 10.1007/s40336-017-0229-8
                PMC ID: 5658474
                PubMed ID: 29104864
                SO-VID: 8a91c46e-f542-49b6-be5f-b8374e4ae2d6
                Copyright © © Italian Association of Nuclear Medicine and Molecular Imaging 2017
                History
                Date received : 2 February 2017
                Date accepted : 17 April 2017
                Categories
                Subject: Systematic Review
                Custom metadata
                issue-copyright-statement © Italian Association of Nuclear Medicine and Molecular Imaging 2017

                Keywords: molecular imaging,pet,gist,oncology,therapy monitoring,personalized medicine
                Data availability:
                Keywords: molecular imaging, pet, gist, oncology, therapy monitoring, personalized medicine

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