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      Skin Metastasis of Gastrointestinal Stromal Tumors: A Case Series and Literature Review

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          Abstract

          Background

          Gastrointestinal stromal tumors (GISTs) extremely and rarely metastasize to the skin, and such metastases have not been well characterized.

          Methods

          Retrospective analysis of clinicopathological data of patients with skin metastasis of a GIST (SM-GIST) admitted to Xiangya Hospital (Changsha, Hunan, China) and literature review were conducted.

          Results

          Including our 4 cases, a total of 17 cases have been reported to date. The mean age of the patients was 55.4 years (29~70 years) and there was not sex predominance (male 10 and female 7). Primary tumors were often located in the stomach (n=9), duodenum (n=2) and small bowel (n=2). Meanwhile, SM-GIST mainly occurred in head and face (n=6), extremities (n=6), followed by abdomen wall (n=5), back (n=3) and chest (n=2). Mutation analysis revealed that the frequency of wild-type GIST (WT-GIST), exon 9, 11 and 13 mutations was 6, 1, 4 and 1, respectively. The average time to SM-GIST was 4.22 years, specifically 4.59 years in gastric and 3.8 years in non-gastric. Moreover, for the resection only group (including chemotherapy), such average time was 3.63 years, while for the combined group (resection and tyrosine kinase inhibitors (TKIs)), it was about 4.74 years. The mean survival was approximately 6.2 years. However, after the diagnosis of SM-GIST, survival was only about 1.69 years.

          Conclusion

          SM-GIST is a rare malignant condition. Non-gastric GIST, surgery without TKIs, high invasiveness and tumor burden, and molecular subtype (mutation in exon 9, 11 and wild-type) may be conducive to the development of SM-GIST. Additionally, it is also a sign of poor prognosis.

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          Most cited references36

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          Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial.

          Imatinib is approved worldwide for use in gastrointestinal stromal tumours (GIST). We aimed to assess dose dependency of response and progression-free survival with imatinib for metastatic GIST. 946 patients were randomly allocated imatinib 400 mg either once or twice a day. Those assigned the once a day regimen who had progression were offered the option of crossover. The primary endpoint was progression-free survival. Analysis was by intention to treat. At median follow-up of 760 days (IQR 644-859), 263 (56%) of 473 patients allocated imatinib once a day had progressed compared with 235 (50%) of 473 who were assigned treatment twice a day (estimated hazard ratio 0.82 [95% CI 0.69-0.98]; p=0.026). Side-effects arose in 465/470 (99%) patients allocated the once daily regimen compared with 468/472 (99%) assigned treatment twice a day. By comparison with the group treated once a day, more dose reductions (77 [16%] vs 282 [60%]) and treatment interruptions (189 [40%] vs 302 [64%]) were recorded in patients allocated the twice daily regimen, but treatment in both arms was fairly well tolerated. 52 (5%) patients achieved a complete response, 442 (47%) a partial response, and 300 (32%) stable disease, with no difference between groups. Median time to best response was 107 days (IQR 58-172). If response induction is the only aim of treatment, a daily dose of 400 mg of imatinib is sufficient; however, a dose of 400 mg twice a day achieves significantly longer progression-free survival.
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            NCCN Task Force report: update on the management of patients with gastrointestinal stromal tumors.

            The standard of care for managing patients with gastrointestinal stromal tumors (GISTs) rapidly changed after the introduction of effective molecularly targeted therapies involving tyrosine kinase inhibitors (TKIs), such as imatinib mesylate and sunitinib malate. A better understanding of the molecular characteristics of GISTs have improved the diagnostic accuracy and led to the discovery of novel immunomarkers and new mechanisms of resistance to TKI therapy, which in turn have resulted in the development of novel treatment strategies. To address these issues, the NCCN organized a task force consisting of a multidisciplinary panel of experts in the fields of medical oncology, surgical oncology, molecular diagnostics, and pathology to discuss the recent advances, identify areas of future research, and recommend an optimal approach to care for patients with GIST at all stages of disease. The task force met for the first time in October 2003 and again in December 2006 and October 2009. This supplement describes the recent developments in the field of GIST as discussed at the October 2009 meeting.
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              Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033.

              To assess potential differences in progression-free or overall survival when imatinib mesylate is administered to patients with incurable gastrointestinal stromal tumors (GIST) at a standard dose (400 mg daily) versus a high dose (400 mg twice daily). Patients with metastatic or surgically unresectable GIST were eligible for this phase III open-label clinical trial. At registration, patients were randomly assigned to either standard or high-dose imatinib, with close interval follow-up. If objective progression occurred by Response Evaluation Criteria in Solid Tumors, patients on the standard-dose arm could reregister to the trial and receive the high-dose imatinib regimen. Seven hundred forty-six patients with advanced GIST from 148 centers across the United States and Canada were enrolled onto this trial in 9 months. With a median follow-up of 4.5 years, median progression-free survival was 18 months for patients on the standard-dose arm, and 20 months for those receiving high-dose imatinib. Median overall survival was 55 and 51 months, respectively. There were no statistically significant differences in objective response rates, progression-free survival, or overall survival. After progression on standard-dose imatinib, 33% of patients who crossed over to the high-dose imatinib regimen achieved either an objective response or stable disease. There were more grade 3, 4, and 5 toxicities noted on the high-dose imatinib arm. This trial confirms the effectiveness of imatinib as primary systemic therapy for patients with incurable GIST but did not show any advantage to higher dose treatment. It appears reasonable to initiate therapy with 400 mg daily and to consider dose escalation on progression of disease.
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                Author and article information

                Journal
                Cancer Manag Res
                Cancer Manag Res
                cmar
                cancmanres
                Cancer Management and Research
                Dove
                1179-1322
                24 August 2020
                2020
                : 12
                : 7681-7690
                Affiliations
                [1 ]Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University , Changsha 410008, Hunan, People’s Republic of China
                Author notes
                Correspondence: Heli Liu Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University , Changsha410008, Hunan, People’s Republic of ChinaTel +86 13874967285 Email heliliu@csu.edu.cn
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0002-3443-6174
                http://orcid.org/0000-0002-2779-992X
                Article
                261823
                10.2147/CMAR.S261823
                7455533
                32904396
                d3a6adf4-2451-4de6-92c8-774e4f3b163b
                © 2020 Liu et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 15 May 2020
                : 04 August 2020
                Page count
                Figures: 4, Tables: 2, References: 44, Pages: 10
                Categories
                Original Research

                Oncology & Radiotherapy
                gastrointestinal stromal tumor,skin metastasis,tyrosine kinase inhibitors

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