Gastrointestinal stromal tumor (GIST) is the most common malignant neoplasm of mesenchymal origin. GIST spans a wide clinical spectrum that ranges from tumors with essentially no metastatic potential to malignant and life-threatening spread diseases. Gain-of-function mutations in KIT or PDGFRA receptor tyrosine kinases are the crucial drivers of most GISTs, responsible for tumor initiation and evolution throughout the entire course of the disease. The introduction of tyrosine kinase inhibitors targeting these receptors has substantially improved the outcomes in this formerly chemoresistant cancer. As of today, five agents hold regulatory approval for the treatment of GIST: imatinib, sunitinib, regorafenib, ripretinib, and avapritinib. This, in turn, represents a success for a rare neoplasm. During the past two decades, GIST has become a paradigmatic model in cancer for multidisciplinary work, given the disease-specific particularities regarding tumor biology and tumor evolution. Herein, we review currently available evidence for the management of GIST. This clinical practice guideline has been developed by a multidisciplinary expert panel (oncologist, pathologist, surgeon, molecular biologist, radiologist, and representative of patients\' advocacy groups) from the Spanish Group for Sarcoma Research, and it is conceived to provide, from a critical perspective, the standard approach for diagnosis, treatment, and follow-up.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the gastrointestinal tract. At present, many professional academic groups and associations at home and abroad have released guidelines for the diagnosis and treatment of GIST. In 2020, Gastrointestinal Stromal Tumor Expert Committee of China Society of Clinical Oncology (CSCO) issued the first \"CSCO gastrointestinal stromal tumor diagnosis and treatment guidelines\" in China. In the same year, NCCN also released the first \"NCCN guideline for the diagnosis and treatment of gastrointestinal stromal tumors (first edition in 2021)\" by separating GIST-related content from the guideline for soft tissue sarcoma. However, there are many inconsistencies between the guidelines\' recommendation and clinical practice in China. For example, in the aspect of diagnosis, the emphasis on and implementation of molecular detection are variable, the format of molecular detection report is not unified or standardized, the selection of detection methods is inappropriate, the diagnosis of wild-type GIST is not standardized, the risk assessment is improper, and the use of EUS-FNA is relatively seldom; in the aspect of drug therapy, there are some problems, such as the lack of standardization in dose and course of targeted drugs, and off-label medication such as cross line therapy; in terms of surgical treatment, there are also some problems, such as the clinical application scenarios of laparoscopic surgery exceed the recommendations of the guidelines, and the general description of surgical intervention of advanced GIST in the guidelines cannot well guide specific clinical practice. In this context, on the one hand, clinicians need to understand the academic frontier and standardize their medical behavior with the latest guidelines; on the other hand, clinicians need to consider the scientific rationale and accessibility of treatment on some clinical problems that are not clear in the guidelines, and take whether patients can benefit the most as the criteria.
胃肠间质瘤（GIST）是胃肠道最常见的间叶来源肿瘤，当前国内外已有多个专业学术团体及行业学会针对GIST的诊断治疗推出了相应的诊疗指南。2020年，中国临床肿瘤学会（CSCO）胃肠间质瘤专家委员会发布了我国首部《CSCO胃肠间质瘤诊疗指南》；美国国家综合癌症网络（NCCN）也在同年首次把GIST相关内容从《软组织肉瘤指南》中独立出来，发布了首部NCCN《胃肠间质瘤诊疗实践指南》（2021年第1版）。但是从国内临床实践来看，在不少环节上存在指南推荐意见与临床实际操作不一致的情况，如在诊断方面，存在分子检测重视程度及普及程度参差不齐、分子检测报告格式并不统一规范、检测手段选择不合理、野生型GIST诊断不规范、危险度评估不合理以及内镜超声引导下细针穿刺活检（EUS-FNA）应用率低等问题；在药物治疗方面，存在靶向药物剂量和疗程不规范以及超适应证用药（如跨线治疗）等情况；在手术治疗方面，存在腹腔镜手术临床应用场景超过指南推荐范围以及指南对于晚期GIST外科介入相关的笼统表述不能很好地指导具体的临床工作等问题。在此背景下，临床医师一方面，需要了解学术前沿进展，以最新的指南来规范自身的医疗行为；另一方面，需要在部分指南尚未明晰的临床问题上，兼顾疗法的科学性和可及性，以患者是否能够最大程度获益为指导标准。.

The diagnosis and treatment of gastrointestinal stromal tumor (GIST) is getting more and more standardized. In the last two decades, due to the elucidation of molecular mechanism of tumorigenesis, as well as the effectiveness of tyrosine kinase inhibitors, GIST has become well-known as one of the most classical models of targeted therapy on solid tumors in the precision medicine era. The National Comprehensive Cancer Network (NCCN) issued the latest version of clinical practice guideline on soft tissue sarcoma in February 2020. Compared with previous versions, the new version of the guideline highlighted the treatment recommendations of avapritinib, which further promoted the precise targeted treatment of GIST.
胃肠间质瘤（GIST）的诊断和治疗已日趋标准化和规范化。近20年来，随着分子水平发病机制的揭示和小分子酪氨酸激酶受体抑制剂的成功应用，GIST治疗已经成为精准医疗时代最经典的实体肿瘤靶向治疗成功范例之一。2020年2月，美国国家综合癌症网络（NCCN）发布了最新版的《软组织肉瘤临床实践指南（2019年第6版）》，与既往版本相比，新版指南中的一大亮点是更新了靶向新药avapritinib的治疗推荐，进一步推动了GIST的精准靶向治疗。.

The Chicago Consensus Working Group provides multidisciplinary recommendations for the management of desmoplastic small round cell, breast, and gastrointestinal stromal tumors specifically related to peritoneal surface malignancy. These guidelines are developed with input from leading experts, including surgical oncologists, medical oncologists, pathologists, radiologists, palliative care physicians, and pharmacists. These guidelines recognize and address the emerging need for increased awareness in the appropriate management of peritoneal surface disease. They are not intended to replace the quest for higher levels of evidence.

The great success of tyrosine kinase receptor inhibitor (TKI) in gastrointestinal stromal tumors(GIST) has promoted it to become a classic model of targeted cancer therapy in the era of precision medicine. Multidisciplinary diagnosis and treatment and whole-process scientific management are the key to clinical diagnosis and treatment of GIST. There are many expert consensuses or guidelines on diagnosis and treatment of GIST in the world. The English version of expert consensuses on diagnosis and treatment of GIST has been issued by the East Asian countries represented by Japan, Korea and China, respectively, in combination with their own clinical practice. In 2016, the first edition of the Asian Expert Consensus on Diagnosis and Treatment of GIST was formulated jointly by the above - mentioned countries. This paper aims to explore the similarities and differences between Chinese and Asian Consensus on the diagnosis and treatment of GIST, to improve the understanding of GIST, and to bridge the gap and explore clues for future cooperation among these countries. The overall framework of both consensuses includes the pathological diagnosis, surgery and drug treatment of GIST. The differences include the following three aspects: (1) The different focus of pathological diagnosis of GIST. The Chinese Consensus has highlighted the requirements for the management of pathological specimens of GIST and the pathological evaluation after targeted therapy. The Chinese Consensus has also tried to clarify the algorithm of diagnosis of wild-type GIST, while wild-type GIST is introduced in very few words in the Asian Consensus. (2) The difference of surgical treatment of GIST focuses on the field of minimally invasive techniques, especially the application of endoscopy in the treatment of GIST. The Asian Consensus is cautious about laparoscopic surgery and has no comments on endoscopic resection at all. At present, the Chinese Consensus does not recommend routine endoscopic treatment in GIST, but the indications have been expanded to a certain extent, reflecting the clinical needs and development trends of endoscopic therapy in China. (3) The recommendation degree of medication for GIST varies. The difference includes the indication of adjuvant therapy, the recommendation after failure of first-line treatment, and discontinuation of TKIs preoperatively, and duration of postoperative adjuvant therapy. The difference between the Chinese Consensus and the Asian Consensus reflects the gap in the practice and clinical research of GIST between China and other Asian countries (e.g. Japan and Korea). Cooperation is the main theme in the field of medical science in the 21st century. China, Japan and South Korea are all located in East Asia and have certain shared features in terms of genetic and biological background, living habits and social environment, medical system and scientific research mode. It is a good entry point to carry out international cooperation research in the field of GIST. In view of some pending problems in the diagnosis and treatment of GIST, the cooperative research between China, Japan and Korea may focus on the following aspects: (1) The value of surgery in the treatment of advanced GIST. (2) The detection of imatinib blood concentration in East Asian population and optimized rational use of targeted drugs in the oriental population. (3) Chinese researchers should optimize the strategy of endoscopic treatment of GIST, design rigorous domestic multi-center clinical trials, and provide convincing data, so as to obtain international recognition. (4) Other related studies may include the diagnosis and treatment of wild-type GIST, the value of Ki-67 in the pathological evaluation of GIST, laparoscopic surgery for gastric GIST, and the optimal duration of imatinib adjuvant therapy. Researchers in China should attach importance to the value of clinical trials, especially cooperative clinical research. Starting with improving data quality, we should welcome cooperation with an open and confident attitude and strive to promote the clinical practice and research of GIST to a new height.
酪氨酸激酶受体抑制剂在胃肠间质瘤（GIST）的治疗中取得的巨大成功，推动其成为精准医疗时代肿瘤靶向治疗的经典模型。多学科诊疗和全程化科学管理是GIST临床诊疗的关键，国际和国内相继有多个GIST诊疗专家共识推出，以日本、韩国及我国为代表的东亚国家均结合自身临床实践，推出了英文版的GIST诊疗专家共识。2016年，上述国家地区的GIST专家共同制定了第一版的《亚洲GIST诊疗专家共识》（《亚洲共识》）。本文探究了《中国GIST诊断与治疗专家共识》英文版（《中国共识》）与《亚洲共识》的\"异\"、\"同\"之处。两个共识基本一致的是在整体框架上均包括了GIST的病理诊断、外科和药物治疗；不同之处包括：（1）GIST病理诊断侧重点不同，《中国共识》增加了对GIST病理标本的处理要求及靶向药物治疗后的病理学评估；尤其是野生型GIST的诊断流程图一目了然，而《亚洲共识》对于野生型GIST仅以极少文字加以介绍。（2）GIST手术治疗的差别体现在微创领域，尤其是内镜技术在GIST治疗中的应用上。《亚洲共识》对腹腔镜手术持谨慎态度，且完全没有关于内镜治疗的内容。《中国共识》目前也不推荐在GIST中常规开展内镜治疗，但适应证较前有了一定程度的拓展，反映出GIST的内镜治疗在我国的临床需求和发展趋势。（3）GIST药物治疗推荐程度不同，包括辅助治疗适应证、晚期治疗推荐顺序、术前治疗的停药时间以及术后治疗时间。从《中国共识》与《亚洲共识》的比较看，我国在GIST诊疗实践与临床研究方面与之存在的差距，主要体现在缺乏谨慎规范的治疗理念和潜心科学的临床研究。21世纪在医学科学领域，合作共赢是主旋律。中、日、韩三国同处东亚地区，从人种的遗传学和生物学背景、到生活习惯和社会环境、再到医疗制度和科研模式，都有一定的共性，要开展GIST领域的国际化合作研究是一个很好的切入点。针对GIST诊疗领域若干悬而未决的问题，开展中、日、韩三国间的合作研究重点可以围绕这几方面：（1）手术治疗在晚期GIST治疗中的应用价值是一个值得开展合作研究的方向；（2）进行中、日、韩三国的伊马替尼血药浓度检测国际合作研究，拿出东亚人群的血药浓度数据，能够优化东方人群的靶向药物合理应用；（3）我国研究者应优化GIST内镜治疗策略，设计严谨的国内多中心临床研究，拿出令人信服的数据，从而获得国际同道对该技术的认可；（4）其他相关研究还可包括野生型GIST的诊断与治疗、ki-67在GIST病理学评估中的价值、胃GIST的腹腔镜手术以及伊马替尼辅助治疗的时限探索等问题。我国研究者应当重视临床研究、尤其是合作临床研究的价值，从提高数据质量入手，以开放和自信的姿态迎接合作，努力把我国GIST临床诊疗和研究推上一个新的高度！.

A multidisciplinary approach based on guidelines and pathological diagnosis by specialized pathologists are important for improving the prognosis and QoL of GIST patients. This study examined the adherence to the guidelines and the concordance of the pathological diagnosis of high-risk GISTs.
Among 541 patients with high-risk GISTs recruited to the prospective registry between Dec. 2012 and Dec. 2015, 534 patients were analyzed after central pathology with KIT and DOG1 IHC and genotyping of KIT and PDGFRA.
Of the 534 patients, 432 (81%) received imatinib adjuvant therapy at a starting dose of 400 or 300 mg/day. Multivariate analysis indicated that age (HR 0.71; 95% CI 0.58-0.88), tumor size (HR for > 10 cm vs < 5 cm, 3.87; 95% CI 1.72-8.74), mitosis (HR for > 10 vs < 5, 3.54; 95% CI 1.84-6.79), tumor rupture (HR 3.69; 95% CI 1.43-9.52) and performance status (HR 0.55; 95% CI 0.31-0.99) were independently related to adjuvant therapy. Among the 534 high-risk GISTs diagnosed locally, 19 tumors (3.6%) were diagnosed as non-GISTs, and the other 93 (18.1%) GISTs were reclassified into lower risk categories by central pathology. Among 10 patients with non-GISTs and 8 patients with PDGFRA D842V mutations, 4 (40%) and 3 (38%) patients, respectively, continued the therapy after receiving the central pathology results.
The adherence to guidelines and the concordance of pathological diagnoses were comparatively good for high-risk GISTs. Central pathology may contribute to improved diagnosis, but further refinements may be required.

Tyrosine kinase inhibitors (TKIs) have improved the overall survival of patients with gastrointestinal stromal tumors (GISTs), but their side effects can impact dose intensity and, consequently, the clinical benefit. To date, no guideline or consensus has been published on the TKI-associated adverse reactions. Therefore, the Chinese Society of Surgeons for Gastrointestinal Stromal Tumor of the Chinese Medical Doctor Association organized an expert panel discussion involving representatives from gastrointestinal surgery, medical oncology, cardiology, dermatology, nephrology, endocrinology, and ophthalmology to consider the systemic clinical symptoms, molecular and cellular mechanisms, and treatment recommendations of GISTs. Here, we present the resultant evidence- and experience-based consensus to guide the management of TKI-associated side events in clinical practice.

In order to further promote the standardization of diagnosis and treatment of gastrointestinal stromal tumor (GIST) in China, the members of Chinese Society of Clinical Oncology (CSCO) Expert Committee on GIST thoroughly discussed the key contents of the consensus guidelines, and voted on the controversial issue. In final, the Chinese consensus guidelines for the diagnosis and management of GIST (2017 edition) was formed on the basis of 2013 edition consensus guidelines, which is hereby announced. The consensus included the pathological diagnosis, recurrence risk classification evaluation, targeted agent therapy, surgery and principles of surveillance of GIST.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the digestive tract, with an incidence of 1.1 cases/100,000 inhabitants/year. A group of experts from the Spanish Society of Pathology and the Spanish Society of Oncology met to discuss a brief update on GISTs and agree on aspects relating to the pathological and molecular diagnosis of these tumors. GISTs are generally solitary, well-circumscribed lesions of variable size (<10 mm-35 cm) that may present with intra- or extra-luminal parietal growth or a mixed-type (hourglass) growth pattern. Histologically, they are unencapsulated neoplasms displaying expansive growth and spindle-shaped (70%), epithelioid (20%), or mixed cellularity (10%). Mitotic activity is generally moderate or low and should be evaluated only in areas with high cellularity or higher mitotic frequency. The great majority of GISTs harbour mutually exclusive activating mutations in genes coding for the type III receptor tyrosine kinases KIT and PDGFRA; less commonly, GISTs have also been reported to display mutations elsewhere, including BRAF and NF1 and SDH-complex genes. The method most widely used to detect KIT and PDGFRA mutations is amplification of the exons involved by polymerase chain reaction followed by direct sequencing (Sanger method) of these amplification products. Molecular analyses should always specify the type of analysis performed, the region or mutations evaluated, and the sensitivity of the detection method employed.

Although gastrointestinal stromal tumors (GISTs) are a rare type of cancer, they are the commonest sarcoma in the gastrointestinal tract. Molecularly targeted therapy, such as imatinib therapy, has revolutionized the treatment of advanced GIST and facilitates scientific research on GIST. Nevertheless, surgery remains a mainstay of treatment to obtain a permanent cure for GIST even in the era of targeted therapy. Many GIST guidelines have been published to guide the diagnosis and treatment of the disease. We review current versions of GIST guidelines published by the National Comprehensive Cancer Network, by the European Society for Medical Oncology, and in Japan. All clinical practice guidelines for GIST include recommendations based on evidence as well as on expert consensus. Most of the content is very similar, as represented by the following examples: GIST is a heterogeneous disease that may have mutations in KIT, PDGFRA, HRAS, NRAS, BRAF, NF1, or the succinate dehydrogenase complex, and these subsets of tumors have several distinctive features. Although there are some minor differences among the guidelines--for example, in the dose of imatinib recommended for exon 9-mutated GIST or the efficacy of antigen retrieval via immunohistochemistry--their common objectives regarding diagnosis and treatment are not only to improve the diagnosis of GIST and the prognosis of patients but also to control medical costs. This review describes the current standard diagnosis, treatment, and follow-up of GISTs based on the recommendations of several guidelines and expert consensus.