化疗剂量强度对晚期结肠癌患者近期疗效的影响:基于真实世界数据研究

Effects of chemotherapy dose intensity on short-term efficacy in patients with advanced colon cancer:a study based on real-world data

目的探讨不同化疗剂量强度对晚期结肠癌患者的近期疗效和不良反应的影响。方法建立2017年1月至2020年12月中国中医科学院望京医院和中日友好医院晚期结肠癌患者真实世界数据库,纳入连续两周期接受相同化疗方案治疗的病例,共105例。根据化疗平均相对剂量强度(ARDI)进行分组,评估不同化疗剂量强度的人群差异、治疗方案、近期疗效和不良反应发生情况。采用受试者工作特征(ROC)曲线分析ARDI对近期疗效的预测价值。结果高剂量强度组31例(ARDI≥80%),中剂量强度组34例(80%<ARDI<60%),低剂量强度组40例(ARDI≤60%)。高剂量强度组、中剂量强度组和低剂量强度组间年龄(χ^(2)=13.20,P=0.010)和Karnofsky功能状态(KPS)评分(χ^(2)=7.99,P=0.008)差异均具有统计学意义;与低剂量强度组比较,高剂量强度组青中年人占比高,老年人占比低(χ^(2)=12.63,P=0.002);与中剂量强度组比较,低剂量强度组KPS评分≥60分患者占比低,KPS评分<60分患者占比高(P=0.013)。3组间化疗方案的应用情况差异具有统计学意义(χ^(2)=22.88,P=0.027),高剂量强度组与低剂量强度组的化疗方案应用情况差异具有统计学意义(χ^(2)=16.25,P=0.009)。高、中、低剂量强度组接受联合化疗方案的占比分别为96.77%(30/31)、82.35%(28/34)、80.00%(32/40)。高、中、低剂量强度组化疗药物减量的发生率分别为93.55%(29/31)、100%(34/34)、100%(40/40),化疗延迟的发生率分别为41.94%(13/31)、79.41%(27/34)、87.50%(35/40)。高、中、低剂量强度组客观缓解率分别为22.58%(7/31)、14.71%(5/34)、2.50%(1/40),差异具有统计学意义(χ^(2)=7.11,P=0.027);高、中、低剂量强度组疾病控制率分别为93.55%(29/31)、91.18%(31/34)、87.50%(35/40),差异无统计学意义(χ^(2)=0.75,P=0.714)。高、中、低剂量强度组治疗前后癌胚抗原差值分别为2.09、0.47、-0.72 ng/ml,差异具有统计学意义(χ^(2)=10.09,P=0.006),与低剂量强度组比较,高剂量强度组治疗前后癌胚抗原的差值更大(χ^(2)=23.12,P=0.005);高、中、低剂量强度组治疗前后糖类抗原199差值分别为2.30、0.00、-0.21 U/ml,差异具有统计学意义(χ^(2)=8.85,P=0.012),与低剂量强度组比较,高剂量强度组治疗前后糖类抗原199的差值更大(χ^(2)=21.40,P=0.010)。3组患者均未发生3级以上不良反应,安全性良好,最常见的不良反应为贫血(61.90%,65/105)、白细胞减少(39.05%,41/105)、中性粒细胞减少(29.52%,31/105)、恶心(36.19%,38/105)。高、中、低剂量强度组间不良反应发生率差异均无统计学意义(均P>0.05)。ROC曲线分析发现,化疗ARDI阈值为64%时预测客观缓解的曲线下面积为0.70,敏感性为92.30%,特异性为52.10%。结论真实世界中接受高剂量强度化疗的结肠癌患者具有较好的客观缓解率,肿瘤标志物下降明显;接受低剂量强度化疗的结肠癌患者基线状态较差,但在疾病控制率方面与高剂量强度化疗患者无明显差异,且不良反应可控。

Objective To investigate the effects of different chemotherapy dose intensity on the shortterm efficacy and adverse reactions of patients with advanced colon cancer.Methods A real-world database of patients with advanced colon cancer in Wangjing Hospital of China Academy of Chinese Medical Sciences and China-Japan Friendship Hospital from January 2017 to December 2020 was established,including 105 patients treated with the same chemotherapy regimen for two consecutive cycles.The patients were grouped according to the average relative dose intensity(ARDI)of chemotherapy,and the population differences,treatment regimens,short-term efficacy and adverse reactions of different chemotherapy dose intensities were evaluated.The receiver operating characteristic(ROC)curve was used to analyze the predictive value of ARDI for shortterm efficacy.Results There were 31 patients in the high dose intensity group(ARDI≥80%),34 patients in the medium dose intensity group(80%<ARDI<60%),and 40 patients in the low dose intensity group(ARDI≤60%).There were statistically significant differences in age(χ^(2)=13.20,P=0.010)and Karnofsky functional status(KPS)score(χ^(2)=7.99,P=0.008)among the high dose intensity group,medium dose intensity group and low dose intensity group.Compared with the low dose intensity group,the proportion of young and middleaged patients in the high dose intensity group was higher,and the proportion of elderly patients was lower(χ^(2)=12.63,P=0.002).Compared with the medium dose intensity group,the proportion of patients with KPS score≥60 was lower and the proportion of patients with KPS score<60 was higher in the low dose intensity group(P=0.013).There was a statistically significant difference in the application of chemotherapy regimen among the three groups(χ^(2)=22.88,P=0.027),and there was a statistically significant difference in the application of chemotherapy regimen between the high dose intensity group and low dose intensity group(χ^(2)=16.25,P=0.009).The proportions of the high,medium and low dose intensity groups receiving combined chemotherapy were 96.77%(30/31),82.35%(28/34)and 80.00%(32/40)respectively.The incidences of chemotherapy drug reduction in the high,medium and low dose intensity groups were 93.55%(29/31),100%(34/34)and 100%(40/40)respectively,and the incidences of chemotherapy delay were 41.94%(13/31),79.41%(27/34)and 87.50%(35/40)respectively.The objective response rates of the high,medium and low dose intensity groups were 22.58%(7/31),14.71%(5/34)and 2.50%(1/40)respectively,with a statistically significant difference(χ^(2)=7.11,P=0.027).The disease control rates of the high,medium and low dose intensity groups were 93.55%(29/31),91.18%(31/34)and 87.50%(35/40)respectively,with no statistically significant difference(χ^(2)=0.75,P=0.714).The differences of carcinoembryonic antigen before and after treatment in the high,medium and low dose intensity groups were 2.09,0.47 and-0.72 ng/ml respectively,with a statistically significant difference(χ^(2)=10.09,P=0.006).Compared with the low dose intensity group,the difference of carcinoembryonic antigen before and after treatment in the high dose intensity group was greater(χ^(2)=23.12,P=0.005).The differences of carbohydrate antigen 199 before and after treatment in the high,medium and low dose intensity groups were 2.30,0.00 and-0.21 U/ml respectively,with a statistically significant different(χ^(2)=8.85,P=0.012).Compared with the low dose intensity group,the difference of carbohydrate antigen 199 before and after treatment in the high dose intensity group was greater(χ^(2)=21.40,P=0.010).No adverse reactions above grade 3 occurred in the three groups,and the safety was good.The most common adverse reactions were anemia(61.90%,65/105),leucopenia(39.05%,41/105),neutropenia(29.52%,31/105)and nausea(36.19%,38/105).There were no statistically significant differences in the incidences of adverse reactions among the high,medium and low dose intensity groups(all P>0.05).ROC curve analysis found that the area under the curve predicting objective response was 0.70,the sensitivity was 92.30%,and the specificity was 52.10%when the chemotherapy ARDI threshold was 64%.Conclusion In the real world,colon cancer patients receiving high dose intensive chemotherapy have better objective response rate,and tumor markers decreased significantly.The baseline status of colon cancer patients receiving low dose intensive chemotherapy is poor,but there is no statistically significant difference in disease control rate between patients receiving low dose intensive chemotherapy and patients receiving high dose intensive chemotherapy,and the adverse reactions are controllable.