Neoadjuvant Short-Course Radiotherapy Followed By Consolidation Chemotherapy For Treatment With Locally Advanced Rectal Cancer:A Meta-Analysis

Background:There are two general approaches to preoperative neoadjuvant therapy for locally advanced rectal cancer(LARC),Conventionally long-course chemoradiotherapy(LCCRT),consisting of long-course radiotherapy with concomitant fluoropyrimidine chemotherapy and short-course radiotherapy(SCRT).Both preoperative neoadjuvant treatments have similar safety and efficacy profiles,but SCRT is inferior to conventional LCCRT in terms of pathologic complete response(p CR)rate and tumor downstaging.The Stockholm III trial suggest that extending the interval between SCRT and surgery can improve p CR rates.Other trials suggest that the upfront systemic chemotherapy,which is delivered in the waiting period between SCRT and resection,is well-tolerated,the cooperation regimen of consolidation chemotherapy and delayed surgery after SCRT had high p CR rates and tumor downstaging,shortening the treatment time and thus improving patient compliance.Purpose:We performed this meta-analysis to compare neoadjuvant short-course radiotherapy combined with consolidation chemotherapy(SCRT/CCT)and standard LCCRT for LARC.Methods:Pub Med,Cochrane Library,Embase,China Knowledge Network(CNKI),China Biomedical Literature Database(CBM),Wanfang database and Veep.com were searched to collect all literature comparing SCRT/CCT with LCCRT published since the establishment of the database until October 1,2022,and the qualified literature was screened for quality assessment,and extracted relevant data information,and Meta-analysis was performed using Rev Man 5.4 software.There were 12 study endpoints,including p CR,R0 resection,tumor downstaging,sphincter preservation,DFS,OS,acute grade 3～4 toxicity,overall postoperative complications,anastomotic leakage,wound infection,local recurrence,and distant metastasis.Data from the literature were tested for heterogeneity,and potential sources of heterogeneity were explored by sensitivity analysis or subgroup analysis.The included studies were tested for publication bias by drawing funnel plots with Rev Man 5.4 software.Result:A total of 12 papers were included in the Meta-analysis,with a cumulative total of 3242 patients,including 1620 in the trial group and 1622 in the control group.Compared with the LCCRT group,the SCRT/CCT group had a higher p CR rate(RR:1.60,95% CI: 1.36 ～ 1.89,P<0.05),a higher sphincter preservation rate(RR: 1.09,95% CI: 1.02 ～ 1.15,P<0.05),and a higher incidence of acute grade 3～4 toxicity(RR=1.94,95% CI.1.65 ～ 2.29,P<0.05).The differences were not statistically significant when comparing disease-free survival(DFS),overall survival(OS),R0 resection rate,tumor downstaging rate,local recurrence rate,distant metastasis rate,overall postoperative complication rate,anastomotic leakage and wound infection rate between the two groups.Conclusion:1.Neoadjuvant SCRT combined with consolidation chemotherapy has a higher p CR rate and sphincter preservation rate compared with standard LCCRT.2.Neoadjuvant SCRT combined with consolidation chemotherapy has a higher incidence of acute grade 3～4 toxicity compared with standard LCCRT.3.SCRT combined with consolidation chemotherapy is safe and effective as a neoadjuvant alternative treatment option for LARC,and can shorten treatment time,reduce treatment costs,and enhance patient compliance with treatment.