Targeted drugs has improved the overall survival of patients with gastrointestinal stromal tumor (GIST). However, there are some difficulties and controversies. Imatinib adjuvant therapy improves recurrence-free survival, but the treatment duration has not been determined. Furthermore, whether adjuvant therapy is beneficial to the GIST with c-kit exon 9 mutation and wild type is unclear. There are currently no prospective randomized controlled trials on the role of combination of surgery with tyrosine kinase inhibitor in patients with metastatic GIST. In addition, many challenging issues remain to be solved including patients education, side effect monitoring during sunitinib treatment, the influence of difference between the Eastern patients and the Western counterparts on sunitinib treatment schedule, and the choice of regimen after imatinib and sunitinib failure, etc. Difficulties exist in the discovery of new targets in the downstream of kit gene and the concurrent use of multiple targeted drugs. This article analyzes these problems in order to achieve a consensus and discuss future directions.
Gastrointestinal Stromal Tumors ; drug therapy ; Humans

For primary localized gastrointestinal stromal tumor(GIST), complete resection followed by imatinib adjuvant therapy has become a consensus among physicians for median and high risk patients. Preoperative imatinib may decrease surgical morbidity, increase resection rate, and even preserve organ function through down-staging of the tumor. For advanced GIST, the choice of treatment is targeted therapy with tyrosine kinase inhibitor. Although surgical intervention showed certain efficacy in several retrospective analyses, the role of surgery for advanced disease still needs to be proven by prospective controlled trials. Better combination of targeted therapy and surgery has become critical in multidisciplinary therapy for GIST.
Combined Modality Therapy ; Gastrointestinal Stromal Tumors ; drug therapy ; surgery ; Humans

Nowadays one of the hot research topics in gastrointestinal surgery is gastrointestinal stromal tumor (GIST). However, mechanisms of their formation and development, and the causes of recurrence following R0 resection, have not been fully understood. This article aims to investigate some important issues concerning the neoplastic essences of GIST including the genomics, bionomics, drug resistance and immunotherapy.
Gastrointestinal Stromal Tumors ; drug therapy ; genetics ; pathology ; Humans

Antineoplastic Agents ; adverse effects ; Consensus ; Gastrointestinal Neoplasms ; drug therapy ; Gastrointestinal Stromal Tumors ; drug therapy ; Humans ; Protein Kinase Inhibitors ; adverse effects

With deeper understanding of gastrointestinal stromal tumor(GIST), more and more patients are diagnosed as GIST. Although the prognosis of early GIST is satisfactory after complete surgical resection, there are still many problems in the treatment of advanced GIST. Variety of treatment options has been used in the treatment of GIST, such as surgery, targeted drug therapy, and surgery plus imatinib therapy. However, post-operative recurrence, imatinib-resistance, multi-targeted drug resistance are still challenges. Many clinical evidences show that a reasonable management strategy can improve the prognosis of patients with advanced GIST. All the doctors should have a clear mind to carry out appropriate interventions. Advanced GIST should not be simply considered to be either medical or surgical disease, but rather must be systematically managed by multidisciplinary team approach combining surgical oncology, medical oncology, pathology, and interventional medicine. This review will advocate suitable treatment strategies based on the most recent progresses in systemic treatment for advanced GIST and our clinical experience to achieve early detection, early prevention, proper management, and therefore improve the survival of these patients.
Gastrointestinal Stromal Tumors ; diagnosis ; drug therapy ; pathology ; surgery ; Humans ; Neoplasm Metastasis

Imaging study is the primary method to evaluate the efficacy of targeted therapy for gastrointestinal stromal tumor(GIST). The application of RECIST morphological criteria has limitations in the evaluation of targeted therapy, which may result in incorrect reflection of responses by conventional size-based criteria. Recent proposed Choi criteria, which combined the size and the CT value, has extended the application of radiology in the evaluation of GIST. The early change of apparent diffusion coefficient(ADC) values on diffusion-weighted imaging(DWI) can reflect the response of GIST to targeted therapy. The prominent change of ADC can be detected within one week after therapy. Through comprehensive analysis of the imaging characteristics associated with the biological behavior of GIST, new approaches may be developed in the evaluation of response of GIST to targeted therapy.
Diagnostic Imaging ; Diffusion Magnetic Resonance Imaging ; Gastrointestinal Stromal Tumors ; drug therapy ; Humans ; Prognosis ; Treatment Outcome

Gastrointestinal stromal tumor (GIST) is a mesenchymal tumor derived from Cajal cells originating from the myotonic plexus. The expression of tyrosine kinase (KIT) membrane receptors that are active on KIT is inhibited by the KIT inhibitor imatinib mesylate. GISTs are resistant to conventional chemotherapy, and radiation therapy is not significantly beneficial for GISTs. With the development of imatinib mesylate, approximately 81.6% of patients with advanced and metastatic GIST exhibit an effect above the stabilization response, thereby increasing the survival time. However, imatinib mesylate alone is unlikely to cure metastatic GISTs. Even with a partial or stable response, imatinib mesylate may be used for a longer time period. However, resection of grossly visible lesions should be considered for patients with a stable response during surgical treatment. In this study, we present a case of GIST with liver metastasis after imatinib mesylate treatment, which was followed up without recurrence after partial resection.
Drug Therapy ; Gastrointestinal Stromal Tumors ; Humans ; Imatinib Mesylate ; Liver ; Membranes ; Neoplasm Metastasis ; Protein-Tyrosine Kinases ; Recurrence

Tyrosine kinase inhibitors (TKI) significantly reduce the risk of recurrence and metastasis and prolong survival in patients with gastrointestinal stromal tumors (GIST), but drug resistance is often inevitable. Immunotherapy has been proven effective in multiple solid tumors, but the efficacy in GIST is unclear. The efficacy of immunotherapy depends on the tumor microenvironment (TME). Tumor-infiltrating immune cells and immune checkpoints are important components of TME, which not only participate in the regulation of tumor immune response but are also the key target of immunotherapy. A comprehensive analysis of them can clarify the mechanism of tumor immune escape. This review found that there are abundant tumor-infiltrating immune cells in GIST, which play an important role in tumor immune surveillance and escape. Although early clinical studies have shown that patients with GIST have a good tolerance to immunotherapy, the curative effect is not satisfactory. Therefore, how to select the responders of immunotherapy and coordinate the relationship between immunotherapy and TKIs is the key issue to be explored. At the same time, the gradual deepening of basic research and large sample prospective clinical trials will certainly provide more strategies for the application of immunotherapy in GIST.
Humans ; Gastrointestinal Stromal Tumors/drug therapy* ; Prospective Studies ; Immunotherapy/methods* ; Tumor Microenvironment ; Protein Kinase Inhibitors/pharmacology*

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Its pathogenesis is defined by mutations within the KIT and PDGFRα gene. Surgical resection is the only radical treatment at present, but recurrence is common. In recent years, targeted therapy with imatinib mesylate, which inhibits KIT kinase activity, represents the other cornerstone for the treatment of GIST. For resectable GIST, operation combined with neoadjuvant and adjuvant therapy with imatinib mesylate or other tyrosine kinase inhibitors can improve the prognosis of high-risk patients before or after complete resection. For unresectable GIST, targeted therapy with imatinib mesylate can effectively inhibit and ameliorate the progression of GIST.
Benzamides ; therapeutic use ; Gastrointestinal Neoplasms ; drug therapy ; surgery ; therapy ; Gastrointestinal Stromal Tumors ; drug therapy ; surgery ; therapy ; Humans ; Imatinib Mesylate ; Piperazines ; therapeutic use ; Pyrimidines ; therapeutic use

Gastrointestinal stromal tumor (GIST) represents the most common mesenchymal tumor of the gastrointestinal tract. With decades of development, surgical excision combined with molecular targeted agents is becoming the mode for the GIST treatment. Imatinib mesylate (IM) is the first-line therapy medicine for GIST adjuvant treatment, and it significantly reduces recurrence or metastasis and increases survival. According to the recently results of SSGXVIII/AIO study, imatinib adjuvant therapy should be administered for at least 3 years for the GIST patients with a high estimated risk of recurrence and metastasis after surgery. Nevertheless, the optimal duration of the adjuvant therapy or the follow-up policy remains unclear, and we look forward to standard assessment criteria for individualized treatment.
Benzamides ; therapeutic use ; Chemotherapy, Adjuvant ; Gastrointestinal Neoplasms ; drug therapy ; surgery ; Gastrointestinal Stromal Tumors ; drug therapy ; surgery ; Humans ; Imatinib Mesylate ; Piperazines ; therapeutic use ; Pyrimidines ; therapeutic use