数据库辅助研究：结直肠癌新辅助治疗的应用——基于DACCA的华西真实世界数据报道

Application of neoadjuvant therapy for colorectal cancer-a study on DACCA——based real world data from West China Hospital

目的通过研究华西肠癌数据库(Database from Colorectal Cancer,DACCA),在真实数据背景下分析该医疗中心结直肠癌的新辅助治疗情况。方法数据选用DACCA版本为2019年8月15日更新版。删重后提取全部肿瘤部位为结直肠及肿瘤性质为腺癌、黏液腺癌和印戒细胞癌的患者。结果T分期、N分期、M分期、临床分期、肿瘤部位、肿瘤到肛门齿状线距离、肿瘤病理学性质、肿瘤分化程度、新辅助方案及患者依从性的有效数据分别为2783、2789、2790、2811、4148、3824、4191、3676、4090和499条。肿瘤病理学性质不为空且新辅助方案为单纯化疗、单纯放疗或放化疗的有效数据共1839条,其中印戒细胞癌50条(2.7%),黏液腺癌299条(16.3%),腺癌1490条(81.0%)。各种病理学特征选用的新辅助治疗方案的差异有统计学意义(χ2=9.138,P=0.041)。除去手术日期一栏为空值的数据行,推荐和不推荐使用新辅助治疗的有效数据行分别为2234条(82.1%)和486条(17.9%)。在数据量较多的年份中,即完成新辅助治疗的患者中,符合推荐指征的患者占比为27.4%~67.6%,平均47.4%;不符合推荐指征却推荐的患者(超适应证应用)占比为7.3%~70.0%,平均39.8%。通过回归分析,符合推荐(y=–0.0325x 66.0032,P=0.020)的比例随年份变化整体呈逐渐下降的趋势;超适应证应用(y=–0.0545x+110.1746,P=0.002)的比例随年份变化整体呈现下降的趋势。新辅助治疗方案及是否推荐不为空值的有效数据为1161条,不同推荐意见组患者的新辅助治疗使用率的差异有统计学意义(χ2=9.244,P=0.002)。患者依从性显示为积极配合和被动接受,且新辅助治理方案显示为单纯放疗、单纯化疗和放化疗的有效数据为470条。积极配合与被动接受患者采用的新辅助治疗方案的差异无统计学意义(χ2=0.537,P=0.841)。临床缓解程度符合研究条件的有效数据为388条,其中完全缓解121条(31.2%),部分缓解180条(46.4%),疾病稳定79条(20.4%),疾病进展8条(2.1%),不同新辅助治疗方案患者的临床缓解程度比较差异无统计学意义(H=0.435,P=0.783)。肿瘤病理缓解等级(TRG)符合研究条件的有效数据为346条,其中TRG047条(13.6%),TRG139条(11.3%),TRG2180条(52.0%)和TRG380条(23.1%),不同新辅助治疗方案患者的肿瘤TRG比较差异无统计学意义(H=1.816,P=0.518)。结论真实世界反映出西部区域性医疗中心所覆盖的结直肠癌患者中,对于新辅助治疗的需求是巨大的。尽管新辅助治疗的实施受到医生推荐行为的影响很大,但是仍没完全达到按照一些特定的临床应用指南进行新辅助治疗的选择和推荐。更多的行为因素带来的影响,还需要进一步的深入分析和研究。

Objective To analyze the neoadjuvant therapy of colorectal cancer in this center in the background of real world data by studying Database from Colorectal Cancer(DACCA)in West China Hospital of Sichuan University.Methods Data was selected from DACCA who was updated on August 15,2019.After deleting duplicate value,patients whose tumor location and tumor pathologic characteristic showed colon or rectum,as well as adenocarcinoma,mucinous adenocarcinoma,and signet ring cell carcinoma were enrolled.Results There were 2783,2789,2790,2811,4148,3824,4191,3676,4090,and 499 valid data of T,N,and M stages,clinical stages,tumor site,distance from tumor to anal dentate line,tumor pathologic characteristics,degree of tumor differentiation,neoadjuvant therapy,and compliance,respectively.There were 1839 lines that“nature of the tumor pathology”was not empty and neoadjuvant scheme for the pure chemotherapy,radiotherapy alone or radiation,and chemotherapy,including 50 lines of signet ring cell carcinoma(2.7%),299 lines of mucous adenocarcinoma(16.3%),1490 lines of adenocarcinoma(81.0%),various kinds of pathology in selection of neoadjuvant therapy difference was statistically significant(χ2=9.138,P=0.041).Except for the data lines with null value in the column of“operation date”,there were 2234(82.1%)and 486(17.9%)effective data lines of“recommended”and“not recommended”for the use of neoadjuvant therapy,respectively.In the years with a large amount of data,among the patients who completed neoadjuvant therapy,the proportion of patients meeting the recommended indications was 27.4%–67.6%,with an average of 47.4%.Patients who did not meet the recommended indications but were recommended(off-label use)accounted for 7.3%–70.0%,with an average of 39.8%.According to regression analysis,the proportion in line with the recommendation(y=–0.0325x+66.0032,P=0.020)varies with the year,and the overall trend shows a gradual decline.The proportion of the use of super indications(y=–0.0545x+110.1746,P=0.002)changed with the year,and the overall trend showed a decline.A total of 1161 valid data with non-null values of“eoadjuvant therapy regimen”and“recommended or not recommended”showed statistically significant difference in the use rate of neoadjuvant therapy among patients with different recommendation groups(χ2=9.244,P=0.002).“Patient compliance”was shown as“active cooperation”and“passive acceptance”,and“neoadjuvant therapy”was shown as“radiotherapy alone”“chemotherapy alone”,and“chemoradiotherapy”were 470 lines.There was no statistically significant difference in neoadjuvant therapy between patients receiving active and passive treatment(χ2=0.537,P=0.841).The effective data of clinical remission degree meeting the research conditions were 388 lines,including 121 lines of complete response(31.2%),180 lines of partial response(46.4%),79 lines of stable disease(20.4%),and 8 lines of progressive disease(2.1%).There was no statistically significant difference in clinical response degree among patients with different neoadjuvant therapy(H=0.435,P=0.783).There were 346 lines with effective data of pathologic tumor regression grade(TRG)meeting the study conditions,including 47 lines with TRG0(13.6%),39 lines with TRG1(11.3%),180 lines with TRG2(52.0%),and 80 lines with TRG3(23.1%).There was no statistical difference in the degree of TRG among patients with different neoadjuvant therapy(H=1.816,P=0.518).Conclusions The real world study reflects that in the western regional medical center,the demand for neoadjuvant therapy among the patients with colorectal cancer covered is huge.Although the implementation of neoadjuvant therapy is greatly influenced by the doctor’s recommendation behavior,the selection and recommendation of neoadjuvant therapy according to some specific clinical application guidelines are not fully met.The impact of more behavioral factors requires further in-depth analysis and research.