Meta Analysis Of Early Compared With Late Radiotherapy For Limited Disease Small-cell Lung Cancer

Objective: whether more advantage in received early radiotherapy for limited stage small cell lung cancer patients is still unclear, if patients need to treated with radiation therapy earlier remains controversial, this study is mainly concentrate on comparison of beneficial between early and late radiotherapy, if more effective in improve tumor response and survival rates in patients who treated with radiotherapy earlier,as well as whether the earlier radiotherapy received more benefits in the chemotherapy toxicity for small cell lung cancer patients.Methods:Formulate search strategies for each database, search the English database MEDLINE, EMBASE, CENTRAL(the Cochrane Central Register Of Controlled Trails) and Chinese database consist of China Biology Medicine disc(CBM)Wang Fang Medical data, Chinese National Knowledge Infrastructure(CNKI).Endnote X6 was used to to manage the documents, to exclude the literatures which have less relative with research topic by reading the article title and abstract.To screened the literatures by formulate the scheme of criteria of inclusion and exclusion, search the full-text of the articles which were screened by the scheme, to create the full text filter table, read the full text carefully, and strictly enforce the criteria of exclusion and inclusion in order to decide the articles with inclusion or exclusion. Assess the risk of included studies by the table of bias risk assessment which recommended by Cochran Collaboration, to further exclude the higher-risk, lower-quality studies. Create data extraction table to extract data from the included studies. Revman5.3 systematic review software recommended by Cochran Collaboration was used to statistics and analysis, comparative analysis of complete remission rate(complete response, CR),objective response rate(objective response rate, ORR), 1 year, 2 years, 3 years,5-year survival rate, as well as leukopenia, thrombocytopenia, anemia, severe nausea or vomiting, radiation pneumonitis, esophagitis, infections and and so on meta-analysis. Relative risk(relative risk, RR) was selected to be indicator of effect magnitude, heterogeneity test was performed before summery statistic, to select effect model by the results of heterogeneity test, chose the fixed effect model while heterogeneity is low, random effect model was chose while obvious heterogeneity.Sensitivity analysis was performed to examine the reasons of heterogeneity,according to factors that may affect the prognosis,the original groupis divided into different subgroups to conduct subgroup analysis, when need. The main results are summarized in forest plots and bias summarized in funnel plots.Results:The literatures of preliminary search were1524, seven randomized controlled studies included eventually. The total number of included patients were 1463, among them 732 were divided into early radiotherapy group, 731 were divided into late radiotherapy group. Meta-analysis showed:the RR value of CR rate between the two groups is 1.05, z(u) test results showed that z = 1. 67, P = 0.09, difference of CR rate between the two groups showed no statistically significant.The difference of ORR rate and survival rate between the two groups showed not statistically significant too.The same result showed in survival.The value of RR in incidence of grade 3-4leukopenia between the two groups is 1.34, P = 0.03; RR in incidence of grade 3-4anemia is 1.42, P = 0.0002; RR in incidence of grade 3-4 esophagitis is 1.65, P =0.005; RR in incidence of infection is1.74, P = 0.01. The difference of incidence of severe leukopenia, anemia, infections and radiation esophagitis between the two groups were statistically significant. Sensitivity analysis showed that the results of the meta-analysis were stable.In subgroup analyzes, the incidence of leukopenia and esophagitis increase in early radiotherapy group while the cycles of chemotherapy up to 6. Radiation twice a day improved 2-year survival(P = 0.0007) and reduced the incidence of leukopenia(P=0.008)and esophagitis(P=0.003)in early group.Conclusion:No significant difference in tumor response rate(CR, ORR) and1,2,3,5-year survival between the two groups. Higher incidence of chemoradiotherapy toxicity in early radiotherapy group more than in late radiotherapy group. Radiation twice a day increased 2-year survival.The more cycles of chemotherapy and long interaction time of chemoradiotherapy,the higher incidence of chemoradiotherapy toxicity in LD-SCLC patients.