Systemic therapy in gastrointestinal stromal tumors

Gastrointestinal stromal tumors(GISTs)are the most common type of soft tissue sarcoma in the gastrointestinal tract.Most GISTs have been attributed to activated gain-of-function mutations in either KIT or platelet-derived growth factor receptorα,making these molecular features essential targets for therapeutic interventions.Although surgery is the standard treatment for localized GISTs,patients often experience relapse and disease progression even after surgery.In recent years,targeted therapy has significantly improved the prognosis of patients with advanced GISTs.Imatinib mesylate,a KIT inhibitor,is the first-line treatment for advanced GISTs and has revolutionized the treatment of this disease.However,drug resistance remains a major issue with imatinib treatment,as a significant majority of patients become resistant to imatinib either after initiation or after 2–3 years of treatment.Consequently,novel tyrosine kinase inhibitors such as sunitinib,regorafenib,ripretinib,and avapritinib have been introduced to address drug resistance.Immunotherapy has emerged as a potential approach for the treatment of advanced GISTs.This review comprehensively summarizes the pathogenesis of GISTs and the development of targeted therapies and immunotherapies,provides an overview of the emergence of drug resistance in advanced GISTs,and discusses the challenges and prospects associated with the treatment of GISTs.

Prognostic value of negative lymph node count in patients with jejunoileal neuroendocrine tumors

A negative lymph node(NLN)count has been shown to have a significant impact on the prognosis of many types of cancer.However,its prognostic value for jejunoileal neuroendocrine tumors(NETs)remains unclear.In this study,we investigated the prognostic value of NLN count in patients with resected jejunoileal NETs diagnosed between 1988 and 2014.The data were retrieved from the Surveillance,Epidemiology and End Results database.The X-tile program was used to determine the cutoff value of the NLN count.Univariate and multivariate Cox proportional hazards models were used to assess the prognostic value of NLN count on survival.Harrell concordance index was used to compare the prognostic validity of NLN count with 2 current prognostic systems.The optimal cutoff point of the NLN count was 8.Kaplan-Meier analysis revealed a progressively worse overall survival(OS)with an NLN count≤8 compared with an NLN count>8(P<0.001).Univariate analysis showed that the NLN count,age,tumor site,tumor size and T classification were significant prognostic factors for the OS of jejunoileal NETs,while the number of positive lymph nodes had no significant impact on OS(P=0.513).Multivariate analysis indicated that the NLN count was an independent prognostic factor for OS of jejunoileal NETs.A higher NLN count was associated with better OS(hazards ratio:0.641;95%confidence interval:0.519-0.793;P<0.001).Compared with 2 other prognostic systems,the NLN counts in this study had similar prognostic value in patients with jejunoileal NETs.Our findings suggest that the NLN count is an important independent prognostic factor for patients with jejunoileal NETs,and that it is a good adjunct for disease staging.