Analysis Of The Efficacy Of Chemoradiotherapy For The Patients With Locally Advanced Rectal Cancer

Objective:To explore the prognosticfactors of chemoradiotherapy（CRT）±total mesorectal resection（TME）for patients with locally advanced rectal cancer（LARC）by retrospective analysis,and to analyze the efficacy and influence factors of LARC with neoadjuvant chemoradiotherapy（n CRT）and TME.Methods:Patients who were newly diagnosed and pathology confirmed as rectal adenocarcinoma with clinical stage cT_3-4/N₊M₀,distance from anus≤12cm,complete radiotherapy in our department,with complete case and follow-up data,were collected in Fourth Hospital of Hebei Medical University from January 2015 to August 2020.Results:A total of 209 patients with LARC were enrolled in the study group,respectively,142 males and 67 females,with a median age of 61 years（from 27-88 years）.Besides,56 cases were complicated with anemia,CEA>5ng/m L in 113cases,CA19-9>27U/m L in 60 cases.Pro-treatment,the median hemoglobin level was 130.20g/L（range of 52.90-167.00g/L）.According to the AJCC seventh edition clinical staging criteria of rectal cancer,there were 3cases of cT₂,136cases of cT₃,70 cases of cT₄,6 cases of cN₀,33 cases of cN₁,72 cases of cN_2a,98 cases of cN_2b,6 cases of cII,1 case of cIIIA,94 cases of cIIIB and 108 cases of cIIIC.145 patients underwent TME after neoadjuvant chemoradiotherapy,while 64 patients did not receive surgical treatment because of their advanced age,disease progression,refusal of operation and so on.55 patients died（26.3%）by the end of clinical follow-up in the December 1,2020,among them,27 cases died of distant metastasis,8 cases died of local progression,7 cases died of nutrition consumption,and 6 cases died of non-tumor causes（such as respiratory failure,cerebral infarction,pulmonary embolism,etc.）.Besides,the cause of death in 7 cases is unknown.In the whole group,49 patients developed disease progression（23.4%）,of which 7cases（3.3%）had local progression,38 cases（18.2%）with distant metastasis,and 4 cases（1.9%）with local progression and distant metastasis.1、3、5-year survival rates of the whole group were 92.9%and 66.7%respectively.Univariate survival analysis showed that the factors,age,whether there were anemia before treatment,neutrophil/lymphocyte ratio（NLR）,CEA,CA19-9,cT stage and whether combined operation were related to overall survival（Overall Survival,OS）.The results of multivariate analysis showed that age,pre-treatment CEA,CA19-9,NLR and where combined with operation were independent risk factors for OS in patients with LARC.1、3、5-year disease-free survival（Disease-Free Survial,DFS）of the whole group was89.1%,69.3%and 60.2%,respectively.Univariate and multivariate analysis all showed that surgical treatment was an independent risk factor on DFS for patients with LARC（P<0.05）.Among the 134 patients who underwent TME operation in our hospital after n CRT,83 patients underwent total neoadjuvant therapy（TNT）.The sphincter preservation rate was 78.4%（105/134）,in which the sphincter preservation rate was 66.2%（5/77）in patients with distance from anal margin≤5cm,and 94.7%（54/57）in patients with distance from anal margin>5cm.The total p T downstaging rate was 43.3%（58/134）,while p N downstaging rate was 84.3%（113/134）,and the total pathologically downstaging rate was80.6%（108/134）.Univariate analysis showed that CEA level and cT stage before treatment was related to the rate of downstaging（P<0.05）,while multivariate analysis showed that CEA level was an independent risk factor affecting the rate of downstaging after n CRT in patients with LARC（P<0.05）.The rate of pathologically complete response（p CR）in all patients was 14.2%（19/134）.Univariate and multivariate analysis showed that whether TNT was used or not was an independent risk factor affecting the rate of p CR（P<0.05）.The 1、3、5-year OS of the group were 94.5%、76.6%and 67.1%.The cumulative local recurrence（LR）rate and distant metastasis（DM）rate were5.4%and 30.2%,respectively,and 1、3、5-year DFS of the group were 94.5%,76.6%and 67.1%,respectively.Univariate analysis showed that CEA level before treatment,postoperative pathological downstaging and yp TNM was related to OS（P<0.05）,while multivariate analysis showed that postoperative pathological downstaging was an independent influencing factor of OS（P<0.05）.No risk factors affecting DFS were found in univariate survival and multivariate analysis.Postoperative complications occurred in 24 cases（17.9%）.And there was no death related to postoperative complications.The incidence of grade 3-4 adverse reactions in the n CRT+TME group during n CRT was 9.7%,mainly characterized by hematological system-related adverse reactions.Conclusion:1.Compared with chemoradiotherapy alone,TME surgery combined with chemoradiotherapy can significantly prolong OS in patients with locally advanced rectal cancer.The patients with higher levels of CEA,CA19-9 and NLR before treatment of locally advanced rectal cancer have a poor prognosis after chemoradiotherapy.2.Neoadjuvant chemoradiotherapy combined with TME surgery,most patients can achieve the purpose of downstaging,while portions of patients can achieve the purpose of sphincter preservation in low LARC patients and p CR,and about 2 to 3 low LARC patients can achieve sphincter preservation,besides,the treatment-related side effects can be well tolerated.The patients with lower levels of CEA before treatment,the descending rate was higher after neoadjuvant chemoradiotherapy,and the p CR rate was higher in patients with TNT.3.The rate of OS was higher in patients with locally advanced rectal cancer who got the downstaging after n CRT.