On February 9, 2015, the NCCN released the latest version of the Clinical Practice Guidelines for Soft Tissue Sarcomas (hereinafter referred to as “the Guidelines”) – the 1st edition of 2015, and many tumors have been updated accordingly based on previous research results. “Gastrointestinal mesenchymal tumor, the star of sarcoma, has also been changed in terms of genetic testing and prediction of biological behavior. Compared with the 2014 edition of the guidelines, there are not many updates, however, the weight of the updated sections is not light. It can be said that the concept of individualized treatment of gastrointestinal mesenchymal tumors is better reflected in the new edition of the guidelines, and in modern medicine with advanced molecular pathology, gastrointestinal mesenchymal tumors deserve to continue to act as the pioneer of individualized treatment of targeted therapy for solid tumors. (A) The value of genetic testing Gastrointestinal mesenchymal tumor can be the benchmark of targeted therapy because the pathogenesis of the vast majority of tumors is clear, and according to the pathogenesis, a number of columns of drugs are designed, including those of imatinib, sunitinib and regorafenib, which are successfully used in the clinic and have greatly improved the survival of patients. Molecularly, GIST occurs in approximately 86% of patients due to mutations in c-KIT and PDGFRA, and patients with mutations in these two genes are referred to as wild-type GIST, and many of these patients, especially pediatric GIST, are due to mutations in the succinate dehydrogenase gene (SDH), and therefore, in the 2014 edition of the guidelines, the NCCN used the term In the 2014 edition of the guidelines, the NCCN used the term “highly recommended” and recommended testing for c-KIT, PDGFRA, and wild-type GIST followed by testing for SDH gene mutation status. The 2015 edition adds to this by adding “test for mutation type when planning drug therapy”, further demonstrating the value of genetic testing in clinical use. Gastrointestinal mesenchymal tumors are one of the few tumors for which the dose of targeted therapy is selected according to the status of different mutations at different loci. Patients with exon 9 mutations required increased doses of imatinib to achieve good efficacy, while certain specific loci, such as PDGFRA D842V, were insensitive to both imatinib and sunitinib treatment. Based on these findings, it is recommended to routinely test the mutation status of c-KIT and PDGFRA in patients who are scheduled for drug therapy and to select the appropriate drug dose based on the results. The significance of genetic testing is not limited to this, as there are differences in the benefit of different types of genetic mutations in patients treated with adjuvant therapy. c-KIT exon 11 mutations can significantly benefit from adjuvant therapy with imatinib, while exon 9 mutations and those with no mutations were found to have a trend of benefit, without statistically significant differences, and further studies are needed. In contrast, the majority of patients who progressed on imatinib therapy developed a secondary mutation, i.e., another mutation on top of the primary mutation, resulting in tumor cells that are no longer sensitive to drug therapy. Therefore, detection of the type of secondary mutation in drug-resistant patients is also valuable for guiding clinical treatment, if conditions permit. (B) Biological behavior prediction The prognosis of gastrointestinal mesenchymal tumor patients after surgical resection and the prediction of biological behavior has been a hot topic of research. From the beginning, in 2002, Professor Fletcher of pathology at Harvard Medical School proposed to classify patients into different risk levels based on parameters such as site, size and number of nuclear divisions, which was adopted by NIH as the official risk level staging and widely used in clinical practice. On this basis, Prof. Joensuu from Finland improved the NIH staging in 2008, i.e., tumor rupture was included in the grading system to further improve the prognosis judgment. Currently, Europe and some Asian countries (including China) have adopted the modified version of NIH staging to make prognosis judgment for patients after surgical resection and to give relevant postoperative adjuvant treatment measures. However, in the United States, the country where the NCCN guidelines are published, the most common system used clinically to determine the risk of recurrence is a different system: the AFIP (Armed Forces Institute of Pathology) criteria proposed by Miettinen in 2006, which classifies the risk of recurrence for each category of patients into The table allows for the clinical estimation of the specific risk of recurrence for each patient in general. The 2015 edition of the NCCN guidelines is clearly in sync with US clinical care, removing the judgments of benign, very low risk, low risk, intermediate risk, and high risk for GIST mesenchymal stromal tumors from the page on predicting biological behavior of GIST, and making more refined judgments about patients’ risk of recurrence, more precisely predicting patients’ risk of recurrence after surgery for gastrointestinal mesenchymal tumors in a more concise and clear form of data. However, what confuses us is that the description of intermediate and high risk is still retained on the decision diagram for treatment (GIST-6), and postoperative imatinib treatment is recommended based on this. The footnote to this description cites data from the Z9001 clinical trial that patients with tumors larger than 3 cm benefited from adjuvant targeted therapy with imatinib, significantly prolonging recurrence-free survival (RFS) despite no significant improvement in overall survival (OS), and that the criteria for adjuvant therapy in this clinical trial were not based on risk staging, although, of course, the Z9001 study was initiated in The Z9001 study was initiated in 2002, when the risk level was not widely used. It can be seen that the NCCN guidelines are not perfect, and the prediction of malignant potential of GIST is a clinical challenge that needs to be overcome. We believe that in subsequent editions, the NCCN will gradually improve the results of the study and introduce more accurate and widely used clinical criteria.