Development And Exploration Of New Recurrence Risk-Prediction Factors And Treatment Strategies For Gastrointestinal Stromal Tumors

BackgroundGastrointestinal stromal tumor(GIST)is the most common mesenchymal tumor of the gastrointestinal tract.It typically arises from the digestive tract and rarely elsewhere in vivo.Although R0 resection remains the optimal treatment for localized GISTs,over 40% of patients will develop recurrence or metastasis after surgery.Thus,precise assessment of the recurrence of GIST patients after surgery is critical for the administration of adjuvant therapy.However,the current NIH risk category is not precise enough to predict the tumor recurrence,because the prognosis varies among patients with the same risk category.Hence,it’s increasingly important to identify additional prognostic factors in order to aid the prognostic prediction and treatment of patients,especially for intermediate and high risk GIST patients.For advanced GIST patients,imatinib was considered as first line treatment.The induction of imatinib has significantly improved the survival of patients with metastatic,recurrent and unresectable GISTs.However,the benefit of surgical resection for advanced GISTs was still under debate.Aim 1.To investigate the predictive value of preoperative fibrinogen concentration and absolute lymphocyte count in GISTs.2.To investigate the clinical benefits of surgical resection following TKIs treatment for patients with metastatic,recurrent or unresectable GISTs.Methods 1.From March 2002 to December 2017,143 intermediate and high risk GIST patients treated with R0 resection were enrolled in the present study.The optimal cut-off values of fibrinogen concentration and absolute count of lymphocyte for the prognosis of GISTs were calculated by X-tile software.The prognostic value of fibrinogen concentration and absolute lymphocyte count were analyzed.2.A systematic search of Pub Med Central,Pub Med,EMBASE and the Cochrane Library was performed with language restriction to English to identify eligible studies published from the inception dates to May 1,2019.The quality of studies was assessed by the Newcastle-Ottawa Quality Assessment Scale.The progression-free survival(PFS)and overall survival(OS)were assessed through software Stata 15.0.Results 1.There were 71 males(49.65%)and 72 females(50.35%).The median age was 56 years(19-86 years).The optimal cut off value was 4.5 g/L for fibrinogen concentration(P=0.000)and 1.0×109/L for lymphocyte count(P=0.002).The associations between the clinicopathological features and levels of fibrinogen and lymphocyte count were analyzed.No significant association was found between lymphocyte level and clinicopathological features.However,elevated fibrinogen level was correlated with tumor location,tumor size and NIH risk category.The follow up time ranged from 9 to 124 months(mean,54.33 months;median,51.73 months).Nineteen patients experienced recurrence or metastasis.Univariate analysis showed that tumor size,adjuvant therapy,fibrinogen concentration and lymphocyte count were associated with the prognosis of patients.However,only tumor size,fibrinogen concentration and lymphocyte count were independent risk factors for the prognosis of patients according to the multivariate analysis.The prognosis of patients with high fibrinogen concentration or low lymphocyte count were significantly worse than that with low fibrinogen concentration or high lymphocyte count.Further,combination of fibrinogen concentration and lymphocyte count could increase the prognostic value for GIST patients.2.A total of 36270 studies were identified using our search strategy,of which six retrospective studies were included in this meta-analysis.The pooled result revealed that surgical resection group was associated with better PFS(HR = 2.08;95% CI: 1.58 to 2.76;P<0.001)and better OS(HR = 2.13;95% CI: 1.59 to 2.85;P<0.001)compared with TKIs treatment alone group.No publication bias was identified in the six studies.Conclusions 1.Fibrinogen concentration and absolute lymphocyte count were independent prognostic factors for intermediate and high risk GIST patients.The combination of fibrinogen concentration and absolute lymphocyte count could further increase the predictive value for the prognosis of GIST patients.2.Surgical resection following TKIs treatment could significantly improve the prognosis of patients with advanced GISTs.