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      Asian Consensus Guidelines for the Diagnosis and Management of Gastrointestinal Stromal Tumor

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          Abstract

          Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors originating in the gastrointestinal tract. With the introduction of molecular-targeted therapy for GISTs which has yielded remarkable outcomes, these tumors have become a model of multidisciplinary oncological treatment. Although Western clinical guidelines are available for GISTs, such as those published by the National Comprehensive Cancer Network (NCCN) and the European Society of Medical Oncology (ESMO), the clinical situations in Asian countries are different from those in Western countries in terms of diagnostic methods, surgical approach, and availability of new targeted agents. Accordingly, we have reviewed current versions of several GIST guidelines published by Asian countries (Japan, Korea, China, and Taiwan) and the NCCN and ESMO and discussed the areas of dissensus. We here present the first version of the Asian GIST consensus guidelines that were prepared through a series of meetings involving multidisciplinary experts in the four countries. These guidelines provide an optimal approach to the diagnosis and management of GIST patients in Asian countries.

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          Most cited references 75

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          Diagnosis of gastrointestinal stromal tumors: A consensus approach.

          As a result of major recent advances in understanding the biology of gastrointestinal stromal tumors (GISTs), specifically recognition of the central role of activating KIT mutations and associated KIT protein expression in these lesions, and the development of novel and effective therapy for GISTs using the receptor tyrosine kinase inhibitor STI-571, these tumors have become the focus of considerable attention by pathologists, clinicians, and patients. Stromal/mesenchymal tumors of the gastrointestinal tract have long been a source of confusion and controversy with regard to classification, line(s) of differentiation, and prognostication. Characterization of the KIT pathway and its phenotypic implications has helped to resolve some but not all of these issues. Given the now critical role of accurate and reproducible pathologic diagnosis in ensuring appropriate treatment for patients with GIST, the National Institutes of Health convened a GIST workshop in April 2001 with the goal of developing a consensus approach to diagnosis and morphologic prognostication. Key elements of the consensus, as described herein, are the defining role of KIT immunopositivity in diagnosis and a proposed scheme for estimating metastatic risk in these lesions, based on tumor size and mitotic count, recognizing that it is probably unwise to use the definitive term "benign" for any GIST, at least at the present time. Copyright 2002, Elsevier Science (USA). All rights reserved.
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            Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial.

            No effective therapeutic options for patients with unresectable imatinib-resistant gastrointestinal stromal tumour are available. We did a randomised, double-blind, placebo-controlled, multicentre, international trial to assess tolerability and anticancer efficacy of sunitinib, a multitargeted tyrosine kinase inhibitor, in patients with advanced gastrointestinal stromal tumour who were resistant to or intolerant of previous treatment with imatinib. Blinded sunitinib or placebo was given orally once daily at a 50-mg starting dose in 6-week cycles with 4 weeks on and 2 weeks off treatment. The primary endpoint was time to tumour progression. Intention-to-treat, modified intention-to-treat, and per-protocol analyses were done. This study is registered at ClinicalTrials.gov, number NCT00075218. 312 patients were randomised in a 2:1 ratio to receive sunitinib (n=207) or placebo (n=105); the trial was unblinded early when a planned interim analysis showed significantly longer time to tumour progression with sunitinib. Median time to tumour progression was 27.3 weeks (95% CI 16.0-32.1) in patients receiving sunitinib and 6.4 weeks (4.4-10.0) in those on placebo (hazard ratio 0.33; p<0.0001). Therapy was reasonably well tolerated; the most common treatment-related adverse events were fatigue, diarrhoea, skin discolouration, and nausea. We noted significant clinical benefit, including disease control and superior survival, with sunitinib compared with placebo in patients with advanced gastrointestinal stromal tumour after failure and discontinuation of imatinab. Tolerability was acceptable.
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              Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival.

              To analyze the outcome of 200 patients with gastrointestinal stromal tumor (GIST) who were treated at a single institution and followed up prospectively. A GIST is a visceral sarcoma that arises from the gastrointestinal tract. Surgical resection is the mainstay of treatment because adjuvant therapy is unproven. Two hundred patients with malignant GIST were admitted and treated at Memorial Hospital during the past 16 years. Patient, tumor, and treatment variables were analyzed to identify patterns of tumor recurrence and factors that predict survival. Of the 200 patients, 46% had primary disease without metastasis, 47% had metastasis, and 7% had isolated local recurrence. In patients with primary disease who underwent complete resection of gross disease (n = 80), the 5-year actuarial survival rate was 54%, and survival was predicted by tumor size but not microscopic margins of resection. Recurrence of disease after resection was predominantly intraabdominal and involved the original tumor site, peritoneum, and liver. GISTs are uncommon sarcomas. Tumor size predicts disease-specific survival in patients with primary disease who undergo complete gross resection. Tumor recurrence tends to be intraabdominal. Investigational protocols are indicated to reduce the rate of recurrence after resection and to improve the outcome for patients with GIST.
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                Author and article information

                Affiliations
                [1 ]Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
                [2 ]Korean GIST Study Group, Seoul, Korea
                [3 ]Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
                [4 ]Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
                [5 ]Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
                [6 ]Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan
                [7 ]Japanese GIST Subcommittee, Nishinomiya, Japan
                [8 ]Department of Pathology, Hyogo College of Medicine, Nishinomiya, Japan
                [9 ]Department of Pathology, Peking University Third Hospital, Beijing, China
                [10 ]Chinese Expert Committee on GIST, Sichuan, China
                [11 ]Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Sichuan, China
                [12 ]Department of Pathology and Laboratory Medicine, Cathay General Hospital, Taipei, Taiwan
                [13 ]Department of Surgery, Chang Gung Memorial Hospital and University, Taoyuan, Taiwan
                [14 ]Department of Surgery, National Cancer Center Hospital East, Chiba, Japan
                [15 ]Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China
                [16 ]National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
                [17 ]Department of Internal Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
                Author notes
                Correspondence: Yoon-Koo Kang  Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea  Tel: 82-2-3010-3210 Fax: 82-2-3010-8772 E-mail: ykkang@ 123456amc.seoul.kr
                Co-Correspondence: Toshirou Nishida  Department of Surgery, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan  Tel: 81-4-7133-1111 Fax: 81-4-7134-8676 E-mail: tnishida@ 123456east.ncc.go.jp
                Co-Correspondence: Lin Shen  Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Fu-Cheng Road 52, Hai-Dian District, Beijing 100142, China  Tel: 86-10-8819-6561 Fax: 86-10-8819-6561 E-mail: lin100@ 123456medmail.com.cn
                Co-Correspondence: Li-Tzong Chen  National Institute of Cancer Research, National Health Research Institutes, and Department of Internal Medicine, National Cheng Kung University Hospital, National Cheng Kung University, No.367, Sheng-Li Road, Tainan 70456, Taiwan  Tel: 886-6-700-0123 Fax: 886-6-208-3427 E-mail: leochen@ 123456nhri.org.tw
                [*]

                Dong-Hoe Koo and Min-Hee Ryu contributed equally to this work.

                Journal
                Cancer Res Treat
                Cancer Res Treat
                CRT
                Cancer Research and Treatment : Official Journal of Korean Cancer Association
                Korean Cancer Association
                1598-2998
                2005-9256
                October 2016
                24 June 2016
                : 48
                : 4
                : 1155-1166
                27384163 5080813 10.4143/crt.2016.187 crt-2016-187
                Copyright © 2016 by the Korean Cancer Association

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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