Gastrointestinal Stromal Tumors, Version 2.2014 (original) (raw)
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NCCN Task Force report: update on the management of patients with gastrointestinal stromal tumors
Journal of the National Comprehensive Cancer Network : JNCCN, 2010
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....
Cureus
Gastrointestinal stromal tumors (GISTs) are soft-tissue sarcomas that can occur anywhere in the digestive tract, with the stomach and small intestine being the most common locations. Because no imaging modalities diagnose GIST unequivocally, histological and immunohistochemical confirmation is usually required. Most GISTs are discovered by chance; hence, determining this condition's actual frequency can be challenging. Since diagnosing the tumor could be difficult, including GIST in the differential diagnosis is crucial. The objective of this review is to explore the multiple treatment options for this tumor and provide clinicians with more information on the evolving treatment modalities, which in the future could be a possible solution to cure GIST ultimately. After exploring several studies, the authors conclude that early detection is critical since the treatment depends on the tumor size, mitotic rate, and location. Medical management using targeted therapy approved by the United States Food and Drug Administration (FDA) include tyrosine kinase inhibitors such as imatinib, sunitinib, and regorafenib. Surgical resection of the tumor is also done in cases with localized tumors. Standard chemotherapy and radiotherapy are not commonly used to treat GIST patients. However, radiotherapy may be used as a palliative therapy to ease pain (such as bone pain) or control bleeding. Additional research is needed to establish potential therapeutic targets that will result in higher and longer-term response rates.
Consensus approaches to best practice management of gastrointestinal stromal tumors
Asia-Pacific Journal of Clinical Oncology, 2008
Gastrointestinal stromal tumors are rare mesenchymal tumors of the gastrointestinal tract. Progress in diagnosis has led to increased recognition of this disease, and the availability of effective, molecularly targeted therapy has revolutionised its management. Treatment of metastatic gastrointestinal stromal tumors with imatinib has led to unprecedented improvements in progression free and overall survival and there are ongoing investigations into the optimal pre-operative and adjuvant use of imatinib. Second-line sunitinib is now available for patients who develop resistance to imatinib, and third-and fourth-line therapies are being investigated in clinical trials. In this ever-changing environment, evidence from controlled clinical trials and the authors' experience were used to comprehensively outline current best practice management of patients with gastrointestinal stromal tumors.
Controversies in the management of gastrointestinal stromal tumors
Asia-Pacific Journal of Clinical Oncology, 2014
Major advances in the medical treatment of gastrointestinal tumors (GISTs) have improved survival for both patients with advanced disease and those diagnosed with high-risk primary tumors. The Consensus approaches to best practice management of gastrointestinal stromal tumors, published in this journal in 2008, provided guidance for the management of GIST to both clinicians and regulatory authorities. Since then, clinical trials have demonstrated the benefit of adjuvant imatinib in high-risk patients, and mature data from advanced GIST studies suggest that a small but significant proportion of patients with advanced disease can achieve long-term benefit with ongoing imatinib treatment. Other evolving management strategies include the controversial use of palliative or debulking surgery to improve outcomes in advanced GIST and the development of promising new multikinase inhibitors, such as regorafenib, which has established benefit in the third-line setting. This review provides an update of recent developments in GIST management and discusses new controversies that these advances have generated. † Low case number. ‡ Two groups were combined in duodenal and rectal GIST because of small number of cases. § Dependent on whether 6-10 or >10 mitoses per 50 HPFs are detectable. AFIP, Armed Forces Institute of Pathology; HPF, high power field; NIH, National Institutes of Health.
SEOM-GEIS clinical guideline for gastrointestinal stromal tumors (2022)
Clinical and Translational Oncology
Gastrointestinal stromal tumor (GIST) is the most common malignant neoplasm of mesenchymal origin, and a paradigmatic model for a successful rational development of targeted therapies in cancer. The introduction of tyrosine kinase inhibitors with activity against KIT/PDGFRA in both localized and advanced stages has remarkably improved the survival in a disease formerly deemed resistant to all systemic therapies. These guidelines are elaborated by the conjoint effort of the Spanish Society of Medical Oncology (SEOM) and the Spanish Sarcoma Research Group (GEIS) and provide a multidisciplinary and updated consensus for the diagnosis and treatment of GIST patients. We strongly encourage that the managing of these patients should be performed within multidisciplinary teams in reference centers.
Gastrointestinal Stromal Tumours: Consensus Statement on Diagnosis and Treatment
Canadian Journal of Gastroenterology, 2006
In the multidisciplinary management of gastrointestinal stromal tumours (GISTs), there is a need to coordinate the efforts of pathology, radiology, surgery and oncology. Surgery is the mainstay for resectable nonmetastatic GISTs, but virtually all GISTs are associated with a risk of metastasis. Imatinib 400 mg/day with or without surgery is the recommended first-line treatment for recurrent or metastatic GIST; a higher dose may be considered in patients who progress, develop secondary resistance or present with specific genotypic characteristics. Adjuvant or neoadjuvant imatinib is not advised for resectable non-metastatic GISTs. Neoadjuvant imatinib may be considered when surgery would result in significant morbidity or loss of organ function. Follow-up computed tomography imaging is recommended every three to six months for at least five years. Patients with metastatic disease should be continued on imatinib due to the high risk of recurrence on discontinuation of therapy. Treatme...
Practical Aspects of Managing Gastrointestinal Stromal Tumors
Clinical Colorectal Cancer, 2006
Gastrointestinal stromal tumors (GISTs) are one of the subtypes of soft-tissue sarcomas. This group consists of > 40 different subtypes that differ considerably in terms of pathogenesis, clinical behavior, and responses to systemic therapy. Despite this great heterogeneity, patients with soft tissue sarcomas were, until recently, treated in a similar way regardless of the subtype. For patients with advanced-stage disease, single-agent doxorubicin is regarded as standard systemic treatment, because there is no other known regimen that yields a better survival benefit than doxorubicin alone. 1 Unfortunately, the prognosis of patients with metastatic disease is poor, with response rates varying between 16% and 27% and a median overall survival (OS) ranging from 7 months to 12 months with doxorubicin. For quite a while, it has been recognized that, of all subtypes, in particular, patients with metastatic GIST respond poorly to chemotherapy. Progression-free survival (PFS) rates at 3 months after first-line cytotoxic treatment for patients with GIST are considerably lower at 44%, compared with the 77% observed in patients with metastatic synovial sarcomas, another subtype. 2 Furthermore, the 2-year survival rate for metastatic GIST with doxorubicin therapy is only 10%. 3 Recently, it was revealed that, in contrast to other soft-tissue sarcoma subtypes, GIST harbors activating mutations of genes encoding the c-KIT receptor 4 or the platelet-derived growth factor receptor-(PDGFR-). 5 The mutated gene products display a ligand-independent, constitutive activation of their kinase activity, which drive the malignant behavior of GIST. This prompted the search for targeted agents inhibiting the function of these receptors. The availability of such a treatment, imatinib, that specifically targets c-KIT and PDGFR-, has dramatically changed the situation for patients with advanced GIST. With this therapy, the current median OS is approximately 5 years. 6 This review focuses on several aspects of GIST, including clinical features, pathogenesis, first-line treatment, treatment of progressive disease (PD), and novel developments. Epidemiology and Clinical Features Although GISTs are the most common mesenchymal tumors of the digestive tract, their occurrence is rare, with an incidence of roughly 1.5 per 100,000 persons annually. The most frequent age of occurrence ranges from 50 years to 70 years. The most frequent primary site is the stomach (65%), followed by the small intestine (25%). Less common primary sites include the colon, esophagus, rectum, and omentum. Dissemination predominantly occurs in the intraperitoneal space and in the liver, while other sites, such as the lungs or bones, are involved in < 5% of the cases. 7 Presenting symptoms are frequently a result of mass-related complaints, and at the time of diagnosis, these tumors can be up to 30-40 cm. Another sign can be anemia as a consequence of blood loss caused by mucosal ulceration somewhere in the digestive tract. Furthermore, GIST is sometimes incidentally diagnosed during radiologic examination or surgery for an unrelated disease condition in otherwise nonsymptomatic patients.
Journal of the National Comprehensive Cancer Network, 2007
The NCCN Soft Tissue Sarcoma Guidelines include a subsection about treatment recommendations for gastrointestinal stromal tumors (GISTs). The standard of practice rapidly changed after the introduction of effective molecularly targeted therapy (such as imatinib and sunitinib) for GIST. Because of these changes, NCCN organized a multidisciplinary panel composed of experts in the fields of medical oncology, molecular diagnostics, pathology, radiation oncology, and surgery to discuss the optimal approach for the care of patients with GIST at all stages of the disease. The GIST Task Force is composed of NCCN faculty and other key experts from the United States, Europe, and Australia. The Task Force met for the first time in October 2003 and again in December 2006 with the purpose of expanding on the existing NCCN guidelines for gastrointestinal sarcomas and identifying areas of future research to optimize our understanding and treatment of GIST. (JNCCN 2007;5[Suppl 2]:S1–S29)
Annals of Oncology, 2005
Background: The management of gastrointestinal stromal tumors (GIST) has evolved very rapidly in the last 4 years. The objectives of this international consensus meeting were to describe the optimal management procedures for patients with GIST in localized and advanced stages, as well as research issues for the future. Materials and methods: A panel of experts from six specialties, including pathology, molecular biology, imaging, surgery, medical oncology and methodologists for clinical practice guidelines from different European and extra European sarcoma societies were invited to a 2-day workshop. Several questions were selected by the organizing committee prior to the conference. Selected panelists reviewed the current levels of evidence for each point, and presented their conclusions during the meeting. These proposals were discussed, and consensus points were identified and categorized according to the Standard Options Recommandations (SOR) of the French Federation of Cancer Centers and National Comprehensive Cancer Network (NCCN). Results: Thirty-two consensus points were identified, most from categories 2A of the NCCN and B2 of the SOR. Among these, the standard histological examination with immunohistochemical analysis using CD117, CD34, PS100, desmin and smooth muscle actin is considered standard. Molecular biology for the identification of KIT and PDGFRA mutation is an optional diagnostic procedure for GIST with negative CD117 staining, and otherwise is considered a research procedure. Complete tumor resection with negative tumor margins is the standard surgical treatment. Adjuvant imatinib after optimal tumor resection as well as neo-adjuvant imatinib remain experimental approaches to be performed within prospective clinical studies. Imatinib should be started at the date of diagnosis of metastatic relapse and given until development of intolerance or progressive disease. The optimal criteria for tumor response to imatinib remain to be delineated, and should include not only tumor size reduction or disease stabilization, but also reduction of tumor density (Hounsfield Units) on computed tomography and metabolic activity (i.e. reduction of FDG uptake on positron emission tomography). In a substantial proportion of patients, stable disease and even increase in tumor size may be associated with pathologic response to imatinib therapy, and available survival data indicate that the survival of these patients is similar to that of patients with conventional tumor response. Metastasis resection is an experimental procedure. Conclusions: Consensus points in clinical management of GIST as well as questions for future clinical trials were identified during this consensus conference on GIST management.
Current management of gastrointestinal stromal tumors – A comprehensive review
International Journal of Surgery, 2012
Background: Gastrointestinal stromal tumors (GISTs) comprise < 1% of all gastrointestinal (GI) tumors, but GISTs are the most common mesenchymal tumors of the GI tract. Dramatic changes in clinical practice have been observed in the last decade. This review highlights the overall management of GIST and its recent developments. Method: We identified literature by searching Medline and PubMed from January 1995 to December 2011 using the keywords "gastrointestinal stromal tumors", "GIST", "imatinib" and "tyrosine kinase inhibitor". Additional papers were identified by a manual search of the references from the key articles. There were no exclusion criteria for published information to the topics. Results: For localized primary GISTs, surgical resection is the mainstay of therapy. The 5-year survival rate after complete resection of GISTs is approximately 50%e65%. Many factors including tumor size, mitotic rate, tumor location, kinase mutational status and occurrence of tumor rupture have been extensively studied and proposed to be predictors of survival outcomes. Adjuvant imatinib is proposed as an option for those patients with a substantial risk of relapse. Unresectable metastatic or recurrent GIST can be treated with a tyrosine kinase inhibitor, imatinib, with a remarkable response (50%e70%) and prolonged survival (median progression-free survival: 18e20 months; median overall survival: 51e57 months). The standard approach in the case of tumor progression on 400 mg once per day is to increase the imatinib dose to 400 mg twice per day as permitted by toxicity. Use of a second-line targeted agent, sunitinib, in patients with advanced GIST who fail (or are intolerant of) imatinib therapy is advised. Conclusion: Treatment for GISTs has become increasingly complex because of the growing understanding of its biology. A multidisciplinary team that includes radiologists, medical oncologists, pathologists, and surgeons is paramount for the effective treatment of GIST.