Difference Of Strategies On Adjuvant Chemotherapy For Resected Gastric Cancer Between Domestic And Foreign Studies:a Systematic Review

Objective:Gastric cancer (GC) is one of the most common cancers in China, and it is mainly treated with surgery now. Though the eligible evidence from evidence based medicine (EBM) is limited, adjuvant chemotherapy (AC) is a routine auxiliary treatment for resected GC for reduction of death and relapse in China, according to the guidelines issued in2011by the Ministry of Health of the People’s Republic of China. We aimed to clarify the different strategies on AC for resected GC between domestic and foreign studies and characterised the status quo among Chinese patients.Methods:Data sources:A series of databases were retrieved up to March2012, including English databases such as Cochrane Library, Medline, and Embase; Chinese databases such as the Chinese database of the National Knowledge Infrastructure (CNKI), and VIP Chinese Peridical Database. Eligibility criteria:The patients were diagnosed pathologically as gastric cancer. The treatment group was treated with AC, while the control group was treated with surgery alone. Randomized control trial (RCT) was main study design. The included studies provided hazard ratio (HR) of death or relevant data enough for HRs’calculation. Language limitation was English and Chinese. Study appraisal method:The methodological quality was assessed according to the "Risk of Bias" in Cochrane Handbook. The quality of the evidence from meta-analysis was evaluated with GRADE assessment.Results:Two reviewers extracted the data from the retrieved literatures, independently. HR of death was taken as primary endpoint outcome and HR of relapse as secondary endpoint outcomes. Review Manager5.1was applied for meta-analysis and quality assessment for individual studies. Stata11.0was used to detect publication bias. GRADE profiler3.6was employed to rate the quality of the evidence.Results:A total of35RCTs were subjected to the final analysis, including4043patients in treatment group and3884in the control group, as well as4clinical control trials (CCTs), which accessed the final analysis with238and252patients, respectively.Good heterogeneity (P=1.00, I2=0%) was calculated within the3subgroups, containing subgroup of anti-metabolites plus others with antibiotics, subgroup of anti-metabolites plus others without antibiotics, and subgroup without anti-metabolites, a test for the pooled HR of death yielded0.91(95%confident interval [CI]:[0.85,0.97], Z=3.06, P=0.002). The HRs of death in the3subgroups were0.93,0.90and0.84, respectively, with corresponding95%CIs of [0.86,1.01],[0.78,1.03] and [0.73,0.97]. A significant difference was only displayed in the without-anti-metabolites subgroup (P=0.02). The prognosis was improved by AC after surgery in a month significantly (PO.05).In the4subgroups stratified with geographic area, the HR of death was0.93(95%CI:[0.86,1.01]) in Europe,0.94(95%CI:[0.77,1.15]) in the United States,0.85(95%CI:[0.74,0.98]) in Asian countries other than China, and0.82(95%CI:[0.66,1.02]) in China. It indicated that patients in Asian countries could benefit more from AC than patients in non-Asian countries.Though there was no statistical significance (P>0.05) in each region, the pooled data indicated that D2lymphadenectomy-based AC was effective (HR=0.89,95%CI:[0.80,0.99], Z=2.10, P=0.04).After analysis of relapse after surgery-based AC, the pooled data in European and Asian countries other than China was statistically different (P<0.05). It suggested AC could reduce the risk of relapse in the European and the Asian except Chinese.The GRADE assessment on HR of death indicated the quality of Chinese studies was low quality. It was moderate in European studies, while in other regions studies recommendation strength was high quality.Conclusion:AC was an effective treatment for resected patients with GC in general. When given to the patients after surgery within a month, AC could improve the prognosis and reduce the risk of death effectively. Asian except Chinese patients could gain more survival benefit from AC than European and American patients could. Because the related domestic researches were still inadequate and poor quality, it was hard to determine whether the effect was exaggerated or not when the foreign evidence was applied directly among Chinese patients. Based on present treatment status quo, further reseaches focus in type of patients, dose of schemes, route of administration as well as other factors should be conducted.