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      A long-term follow-up of the imatinib mesylate treatment for the patients with recurrent gastrointestinal stromal tumor (GIST): the liver metastasis and the outcome

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      1 , 2 , 1 , 3 , 1 ,
      BMC Cancer
      BioMed Central

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          Abstract

          Background

          About 80% of patients with GIST would experience tumor recurrence or metastasis after radical resection. The most common site of the metastasis is the liver. Imatinib mesylate has been proved effective for advanced GIST. The present study was designed to further observe the effectiveness of the imatinib mesylate treatment on the recurrent GIST and the correlation between the liver metastasis and the outcome.

          Methods

          Forty-two patients who had recurrent GIST after the first radical resection were enrolled. According to the recurrent sites, the patients were divided into 3 groups: group LG (recurrent liver GISTs), group AG (recurrent abdominal GISTs) and group ALG (recurrent abdominal and liver GISTs). All the patients were given imatinib mesylate at an initial dose of 400 mg per day. Their clinical data was prospectively collected. A follow-up over 3 years was conducted. Tumor response, time to progression and survival were evaluated.

          Results

          The long-term Imatinib mesylate treatment was safe and well tolerated. At a median follow-up time for 39.5 months, the 3-year survival rate was 66.7%. Median TTP and OS were 37 months (95% CI: 28.2~45.8 months) and 48 months (95% CI: 37.0~58.9 months), respectively. There was no statistical difference in tumor response among the 3 groups. The similar TTP ( P = 0.291) and OS ( P = 0.160) were observed in the 3 groups.

          Conclusions

          The imatinib mesylate treatment could prolong the survival of the patients who have recurrent GIST after the radical surgery in spite of an existence of the liver metastasis. Survival was not significantly affected by liver metastasis when imatinib mesylate was warranted.

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          Most cited references14

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          Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial.

          Gastrointestinal stromal tumour is the most common sarcoma of the intestinal tract. Imatinib mesylate is a small molecule that inhibits activation of the KIT and platelet-derived growth factor receptor alpha proteins, and is effective in first-line treatment of metastatic gastrointestinal stromal tumour. We postulated that adjuvant treatment with imatinib would improve recurrence-free survival compared with placebo after resection of localised, primary gastrointestinal stromal tumour. We undertook a randomised phase III, double-blind, placebo-controlled, multicentre trial. Eligible patients had complete gross resection of a primary gastrointestinal stromal tumour at least 3 cm in size and positive for the KIT protein by immunohistochemistry. Patients were randomly assigned, by a stratified biased coin design, to imatinib 400 mg (n=359) or to placebo (n=354) daily for 1 year after surgical resection. Patients and investigators were blinded to the treatment group. Patients assigned to placebo were eligible to crossover to imatinib treatment in the event of tumour recurrence. The primary endpoint was recurrence-free survival, and analysis was by intention to treat. Accrual was stopped early because the trial results crossed the interim analysis efficacy boundary for recurrence-free survival. This study is registered with ClinicalTrials.gov, number NCT00041197. All randomised patients were included in the analysis. At median follow-up of 19.7 months (minimum-maximum 0-56.4), 30 (8%) patients in the imatinib group and 70 (20%) in the placebo group had had tumour recurrence or had died. Imatinib significantly improved recurrence-free survival compared with placebo (98% [95% CI 96-100] vs 83% [78-88] at 1 year; hazard ratio [HR] 0.35 [0.22-0.53]; one-sided p<0.0001). Adjuvant imatinib was well tolerated, with the most common serious events being dermatitis (11 [3%] vs 0), abdominal pain (12 [3%] vs six [1%]), and diarrhoea (ten [2%] vs five [1%]) in the imatinib group and hyperglycaemia (two [<1%] vs seven [2%]) in the placebo group. Adjuvant imatinib therapy is safe and seems to improve recurrence-free survival compared with placebo after the resection of primary gastrointestinal stromal tumour. US National Institutes of Health and Novartis Pharmaceuticals.
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            Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor.

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              Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal.

              The interstitial cells of Cajal (ICC) form a complex cell network within the gastrointestinal tract wall where they function as a pacemaker system. Expression of the kit proto-oncogene is essential for the development of this system. The aim of our study was to examine the hypothesis that gastrointestinal stromal tumors differentiate toward cells with an ICC phenotype. Ultrastructurally, 58 stromal tumors were characterized and found to share many features with ICC. Seventy-eight stromal tumors were immunophenotyped, particularly with regard to the kit receptor. All 78 tumors revealed strong, homogeneous immunoreactivity for the kit receptor as did ICC of adjacent and control gastrointestinal walls. Focal hyperplasia and hypertrophy of kit receptor positive cells were also observed in the gastrointestinal wall adjacent to the tumors. CD34 immunoreactivity observed in interstitial cells surrounding Auerbach's ganglia suggests that a subpopulation of ICC is CD34 positive and may explain why 56 of 78 stromal tumors were CD34 positive. Thirty control tumors, including gastrointestinal leiomyomas and leiomyosarcomas, were all negative for the kit receptor. We conclude that gastrointestinal stromal tumors show striking morphological and immunophenotypic similarities with ICC and that they may originate from stem cells that differentiate toward a pacemaker cell phenotype. We propose that the noncommittal name "gastrointestinal stromal tumor" be replaced by gastrointestinal pacemaker cell tumor.
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                Author and article information

                Journal
                BMC Cancer
                BMC Cancer
                BioMed Central
                1471-2407
                2010
                13 May 2010
                : 10
                : 199
                Affiliations
                [1 ]Department of Thoracic Oncology, Cancer Center, West China hospital, Sichuan University, Chengdu, 610041, China
                [2 ]The Second Department of Cancer Center, West China hospital, Sichuan University, Chengdu, 610041, China
                [3 ]The First Department of Cancer Center, West China hospital, Sichuan University, Chengdu, 610041, China
                Article
                1471-2407-10-199
                10.1186/1471-2407-10-199
                2876083
                20465813
                2103203d-fe5d-4157-8c5a-991834c87c10
                Copyright ©2010 Zhu et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 December 2009
                : 13 May 2010
                Categories
                Research Article

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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