A case of gastrointestinal stromal tumor with liver and bone metastases effectively treated with radiofrequency ablation and imatinib mesylate]

A 58-year-old man was admitted because of perforation of the small intestine by a gastrointestinal stromal tumor (GIST). First, the small intestine including a GIST was resected; and then 2 month later, a part of the liver (S5) conforming to metastatic lesion was surgically removed. Twelve months later, another liver metastases was found, and surgical treatment was recommended; but the patient requested non-surgical therapy, so a radiofrequency ablation (RFA) was successfully performed. After that, recurrence of liver metastasis was not observed, but another metastasis was observed on the fifth lumbar vertebra; so administration of imatinib mesylate was started. 28 months after the initial administration the metastatic liver lesion was still invisible, and the bone metastatic lesion had not grown. The patient is alive with good performance status. This report shows that multi-modality therapy by surgery, RFA and imatinib mesylate was effective for liver and bone metastases of GIST.     

Imatinib mesylate-induced acute hepatitis in a patient treated for gastrointestinal stromal tumour

We report the first case of hepatocellular injury occurring in a patient treated for metastatic gastrointestinal stromal tumour (GIST) with imatinib mesylate, with two positive rechallenges including one with 2.5% of the current therapeutic dosage. The patient could be treated later with sunitinib without liver toxicity. Grade 3-4 liver toxicity could occur in one out of 40 treated patients with imatinib for GIST, and fatalities have been reported. Regular monitoring of liver function tests is essential in patients treated with imatinib.     

Successful resection of a giant recurrent gastrointestinal stromal tumour with imatinib mesylate as neoadjuvant therapy

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the GI tract. Although a great deal of experience has been obtained with imatinib mesylate in patients with unresectable or metastatic GISTs, its role in the neoadjuvant setting is not well established. In this paper, we describe a case of successful resection of a giant recurrent GIST with imatinib mesylate as neoadjuvant therapy.     

Successful resection of a giant recurrent gastrointestinal stromal tumour with imatinib mesylate as neoadjuvant therapy

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the GI tract. Although a great deal of experience has been obtained with imatinib mesylate in patients with unresectable or metastatic GISTs, its role in the neoadjuvant setting is not well established. In this paper, we describe a case of successful resection of a giant recurrent GIST with imatinib mesylate as neoadjuvant therapy.     

Assessment of gastrointestinal stromal tumors with computed tomography following treatment with imatinib mesylate

AIM： To evaluate and characterize the patterns of disease progression of metastatic or unresectable gastrointestinal stromal tumor （GIST） treated with imatinib mesylate, and to determine the prognostic significance associated with disease progression. METHODS： Clinical data and computed tomography （CT） images were retrospectively reviewed in 17 GIST patients who were treated with imatinib mesylate from October 2002 to October 2006. Apart from using size measurement for evaluation of tumor response [Response Evaluation Criteria in Solid Tumors （RECIST） criteria], patterns of CT changes during treatment were evaluated and correlated with clinical data. RESULTS： There were eight non-responders and nine responders. Five patterns of CT change during treatment were found： focal progression （FP）, generalized progression （GP）, generalized cystic change （GC）, new cystic lesion （NC） and new solid lesion （NS）. At the end of study, all non-responders showed GP, whereas responders showed cystic change （GC and NC） and response according to RECIST criteria. Overall survival was significantly better in patients with cystic change or response within the RECIST criteria compared with GP patients （P = 0.0271）. CONCLUSION： Various patterns of CT change in patients with GIST who responded to imatinib mesylate were demonstrated, and might determine the prognosis of the disease. A combination of RECIST criteria and pattern of CT change are proposed for response evaluation in GIST.     

A metastatic case of gastrointestinal stromal tumor (GIST) treated with imatinib mesylate (Glivec(®)) in Mali

Gastrointestinal stromal tumors (GIST) usually showing a spindle cells pattern of cell proliferation have recently benefit from a molecular definition. Indeed imatinib mesylate (Gleevec(?)) treatment has dramatically improved the management of these tumors as they frequently express the c-kit oncogene. We report the first case of a metastatic gastric GIST in a man of 45 years diagnosed and treated in Mali. The gastric tumor was particularly aggressive with a large intra-abdominal and mesenteric spreading and liver metastases. The diagnosis was done on the CD117 and CD34 expression in the tumor sample obtained by laparotomy. After a 34 months 400mg/day imatinib mesylate (Gleevec(?)) treatment a dramatic tumor regression was obtained.     

Treatment of pulmonary fibrosis for twenty weeks with imatinib mesylate in a patient with mixed connective tissue disease

Interstitial lung disease, which is common in patients with mixed connective tissue disease (MCTD), can progress to severe pulmonary fibrosis. The tyrosine kinase inhibitor imatinib mesylate has recently been shown to prevent experimental pulmonary, dermal, and renal fibrosis. Our patient, a 64-year-old woman with MCTD and rapidly progressive pulmonary fibrosis, presented with rapid deterioration despite treatment with immunosuppressants. During 20 weeks of treatment with imatinib mesylate at 400 mg/day, our patient improved significantly according to several outcome measures, including New York Heart Association classification, diffusing capacity for carbon monoxide, 6-minute walking distance, arterial oxygen pressure, and reduction of ground-glass opacities seen on high-resolution computed tomography. No adverse effects of imatinib mesylate were observed. These findings suggest that imatinib mesylate might be effective in patients with fibrotic diseases and warrant the initiation of larger clinical studies on the safety and efficacy of imatinib mesylate in connective tissue diseases.     

Imatinib for the treatment of patients with unresectable or metastatic malignant KIT-positive gastrointestinal stromal tumours: an open-label Belgian trial

BACKGROUND: Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumours of the gastrointestinal tract. They are defined immunohistologically as KIT positive tumours. The only effective treatment for malignant GIST was surgery until 2000. Imatinib mesylate (STI571, Glivec) has shown substantial anticancer activity in patients with metastatic or unresectable GIST. PATIENTS AND METHODS: 57 patients who were diagnosed with unresectable or metastatic malignant GIST were entered into this study. The patients were given 400 mg Glivec orally once daily. The dose could be increased to 600 mg orally once daily and then to 400 mg twice daily if tumour progression was noticed. Daily treatment was interrupted or dose was decreased only in the case of limiting toxicities. We evaluated the tumour response and the safety of the drug. RESULTS: 85% of GIST patients showed a partial response or stable disease after 8 weeks of treatment with imatinib. The main side effects were nausea, vomiting, anorexia, skin rash, periorbital oedema and diarrhea. CONCLUSION: This study confirms that imatinib is an active agent against malignant GIST with manageable toxicities.     

Gastrointestinal stromal tumors

Introduction

The gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the intestinal tract, known to be refractory to conventional chemotherapy or radiation. Its pathogenesis is defined by mutations within the KIT and PDGFRA gene, which constitutively activate KIT and PDGFRA oncoproteins, and serve as crucial diagnostic and therapeutic targets.

Discussion

Besides surgery, therapy with imatinib mesylate, which inhibits KIT kinase activity, represents the other cornerstone for the treatment of GIST. Still, the only curative option for GIST is given after complete surgical removal even in a metastatic setting, but recurrence is common, and the risk can be defined by surgical factors like incomplete resection, intraperitoneal rupture, or bleeding and tumor associated factors like tumor size, mitotic index, or localization.

Conclusion

Consequently, adjuvant therapy with imatinib mesylate or other tyrosine kinase inhibitors is recommended for high-risk patients after complete resection. For unresectable and advanced GIST, a partial response or stable disease can be achieved in about 80% of patients with imatinib mesylate.     

Pathologic complete response confirmed by surgical resection for liver metastases of gastrointestinal stromal tumor after treatment with imatinib mesylate

A 39-year-old male underwent distal gastrectomy for a high grade gastrointestinal stromal tumor （GIST）. Computed tomography （CT） and magnetic resonance imaging （MRI） 107 mo after the operation, revealed a cystic mass （14 cm in diameter） and a solid mass （9 cm in diameter） in the right and left lobes of the liver, respectively. A biopsy specimen of the solid mass showed a liver metastasis of GIST. The patient received imatinib mesylate （IM） treatment, 400 mg/day orally. Following the IM treatment for a period of 35 mo, the patient underwent partial hepatectomy （S4 ＋ S5）. The effect of IM on the metastatic lesions was interpreted as pathologic complete response （CR）. Pathologically verified cases showing therapeutic efficacy of IM have been rarely reported.     

Treatment of gastrointestinal stromal tumor with imatinib mesylate: a retrospective single-center experience in Heidelberg

BACKGROUND: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. Surgery has been the only effective therapy. However, many patients still eventually die of disease recurrence. Chemotherapy and radiation therapy have been of limited value. Imatinib mesylate (Glivec) is an orally administered competitive inhibitor of tyrosine kinases associated with the KIT, ABL protein, licensed for the treatment of metastatic GIST since 2002 in Germany. METHODS: We summarized the data of 16 patients with advanced or metastatic GIST treated with imatinib mesylate in palliative and neoadjuvant settings. RESULTS: Overall response was 81%, with no evidence of disease (NED) in 3/16 (19%), partial response (PR) in 9/16 (56%) and stable disease (SD) in 1/16 (6%), whereas 3/16 patients (19%) suffered from progressive disease (PD). Mean follow-up was 18.6 months [range: 4-30]. Mean progression-free survival (PFS) was 17.6 months [range: 0-30], mean overall survival (OS) from initial diagnosis was 32.3 months [range: 5-122]. Most common side effects were periorbital edema and skin rash. CONCLUSION: Imatinib mesylate is well tolerated in a dose of up to 800 mg/day and has significant activity during long- term treatment of patients with advanced or metastatic GIST.     

Diagnosis and satisfactory surgical treatment of a jejunal stromal tumor

GIST is the most common mesenchymal tumor of the gastrointestinal tract. The discovery of KIT proto-oncogene mutations in the pathogenesis of this tumor, and the development of imatinib mesylate, a specific inhibitor of KIT tyrosine kinase function have revolutionized the treatment of GIST. We present the clinical case of a patient with an upper digestive bleeding secondary to a jejunal GIST. Therapeutic options are highlighted.     

Imatinib‐associated neutropenia may not be overcome by filgrastim treatment in patients with blastic phase of chronic myeloid leukaemia

Imatinib mesylate is a very effective treatment in patients with Philadelphia (Ph)‐positive chronic myeloid leukaemia (CML). However, in patients with advanced phase CML, it is still unclear whether, in the presence of myelosuppression, therapy with imatinib should be continued. It has been reported that intermittent filgrastim treatment may overcome imatinib‐associated neutropenia and allow improved delivery of imatinib. Such combined sequential treatment is theoretically attractive as it may lead to better disease response. Here, we report a patient with blastic phase CML who developed severe and prolonged myelosuppression during imatinib treatment. Despite cessation of imatinib and 2 months of filgrastim therapy neither recurrence of Ph‐positive or Ph‐negative cells occurred. We conclude that filgrastim treatment may not always reverse imatinib‐associated neutropenia therefore the decision of continued imatinib therapy in patients with advanced CML should be taken with caution.     

甲磺酸伊马替尼致间质性肺炎1例并文献复习

目的 提高对甲磺酸伊马替尼所致间质性肺炎的认识,做到早期诊断和治疗,改善患者预后.方法 对北京大学首钢医院呼吸内科诊治的1例甲磺酸伊马替尼致间质性肺炎患者的临床资料进行回顾性分析,并进行相关文献复习.结果 患者女性,小肠间质瘤术后服用甲磺酸伊马替尼3个半月后出现水肿、呼吸困难,入院后胸部CT提示双肺弥漫分布的斑片影,BALF显示细胞总数升高(0.54×109/L),其中淋巴细胞56％.除外感染、自身免疫性疾病和其他药物因素,诊断甲磺酸伊马替尼导致的间质性肺炎,停止服用伊马替尼3周后患者呼吸困难无改善,后加用糖皮质激素治疗,激素治疗约2周后患者呼吸困难明显减轻,胸部CT双肺斑片影较前部分吸收,激素治疗4个月后复查胸部CT病变较前明显吸收,但遗留肺间质纤维化改变,停用激素治疗.随访患者未再服用甲磺酸伊马替尼,2年及5年后胸部CT较前无明显变化,3年后患者因小肠间质瘤复发再次手术切除.结论 服用甲磺酸伊马替尼后出现呼吸困难症状应考虑间质性肺炎可能,早期诊断、停药和应用糖皮质激素治疗可获得显著效果,停药后应长期随访患者基础疾病及肺部情况.通过这此例报道并进行文献复习有助于提高对甲磺酸伊马替尼所致间质性肺炎的认识.     

Metachronous Primary Adenocarcinoma of Lung During Adjuvant Imatinib Mesylate Therapy for Gastrointestinal Stromal Tumor of Stomach: A Case Report

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in gastrointestinal tracts; however, the synchronous or metachronous coexistence of GIST with additional primary malignancy is not common.Here, we present an unusual case of gastric GIST with metachronous primary lung adenocarcinoma diagnosed during his adjuvant treatment with oral receptor tyrosine kinase inhibitor imatinib mesylate (400 mg daily). After 6-month use of imatinib, the patient suffered from dry cough and dyspnea. Subsequent lung biopsy demonstrated adenocarcinoma with diffuse interstitial changes.Our research emphasizes the possibility of an additional primary tumor with GIST, and reminds the clinicians to strengthen the surveillance of the additional cancer during the follow-up of GIST patients.     

Long-term survival of a case with multiple liver metastases from duodenal gastrointestinal stromal tumor drastically reduced by the treatment with imatinib and hepatectomy

Constitutive activation of KIT receptor tyrosine kinase is a critical factor in the pathogenesis of gastrointestinal stromal tumors (GISTs). But there is little information on whether combination of imatinib mesylate (IM) and surgical treatment can prolong survival in the cases with unresectable multiple liver metastases. We report a case of postoperative recurrence of GIST treated by the tyrosine kinase inhibitor IM and surgical treatment. The initial complete response (CR) to treatment continued for 18 mo, but single liver metastasis showed regrowth in the left hepatic lobe during IM treatment. After partial resection of the recurrent tumor, postoperative course was uneventful and the patient has survived without recurrence for 24 mo. Currently, imatinib is the first-line therapy for non-resectable GISTs, but a single agent therapy often leads to tumor resistance. Even if tolerance to imatinib occurs, a combination of imatinib and surgical treatment can prolong survival in some cases as reported here. However, further studies on a large number of cases of recurrent GIST are necessary to evaluate the effectiveness of IM treatment combined with surgery.     

Control of aggressive fibromatosis by treatment with imatinib mesylate. A case report and review of the literature

Objective There has been only one report available that focuses on the treatment with imatinib mesylate of two individual persons with aggressive fibromatosis. The authors concluded that after long-term treatment, for 9 and 11 months, with imatinib mesylate, both patients demonstrated radiographic and clinical responses. The novel therapy should be considered as salvage in patients with aggressive fibromatosis expressed platelet-derived growth factor receptor—alfa, beta (PDGFR-alfa, PDGFR-beta), and/or c-kit, whose tumors are uncontrollable by the standard management. On the other hand, the number of kinases blocked by imatinib mesylate is notching up, for instance the tyrosine kinase, which is associated with macrophage-colony stimulating factor receptor (M-CSFR). Methods The patient was suffering from aggressive fibromatosis after prior therapy including surgery (R2), radiotherapy, and systemic treatment with combination of tamoxifen and sulindac. The tumor specimen was immunostained for PDGFR-beta and c-kit (CD117), and PDGFR-alfa and cytokines platelet-derived growth factor-alfa and beta were not assessed. The tests for both assessed molecules revealed negative results. In spite of this, the patient underwent a unique treatment with imatinib mesylate at the dose of 400 mg orally once daily for 3 years and 2 months. Results After three months of the therapy, radiographic (met criteria of SD but small decrease of the tumor was noted) and clinical responses were recorded for the first time. The same was seen after 6 and 13 months of therapy continuation with imatinib mesylate. Currently, the patient is treated with imatinib mesylate (400 mg orally once daily) without any toxicity effects. The last MRI revealed readily a smaller tumor (35 × 20 mm) after such a therapy lasted more than 3 years. Conclusions Treatment with imatinib mesyalte has been a well-accepted therapy for chronic myelagenous leukemia (CML) and gastrointestinal stromal tumors (GIST). There have been established four kinases (p210^bcr/abl, c-kit, PDGFR-alfa, PDGFR-beta) suggested as the target for imatinib mesylate. Other potential targets will be discovered as it has lately been determined that M-CSFR kinase activity was blocked by imatinib mesylate. The salvage therapy for aggressive fibromatosis with imatinib mesylate seems to be an attractive opportunity for patients with the advanced disease, whose prior therapy failed.     

Imatinib-associated neutropenia may not be overcome by filgrastim treatment in patients with blastic phase of chronic myeloid leukaemia

Imatinib mesylate is a very effective treatment in patients with Philadelphia (Ph)-positive chronic myeloid leukaemia (CML). However, in patients with advanced phase CML, it is still unclear whether, in the presence of myelosuppression, therapy with imatinib should be continued. It has been reported that intermittent filgrastim treatment may overcome imatinib-associated neutropenia and allow improved delivery of imatinib. Such combined sequential treatment is theoretically attractive as it may lead to better disease response. Here, we report a patient with blastic phase CML who developed severe and prolonged myelosuppression during imatinib treatment. Despite cessation of imatinib and 2 months of filgrastim therapy neither recurrence of Ph-positive or Ph-negative cells occurred. We conclude that filgrastim treatment may not always reverse imatinib-associated neutropenia therefore the decision of continued imatinib therapy in patients with advanced CML should be taken with caution.