临床特征与剂量学因素对局部晚期胸段食管鳞状细胞癌患者长期生存影响的分析

Analysis of clinical characteristics and dosimetric factors on long-term survival in locally advanced thoracic esophageal squamous cell carcinoma

目的:探究临床特征与剂量学因素对局部晚期胸段食管鳞状细胞癌同步放化疗后患者的生存及预后的影响。方法:选取2015年8月至2018年10月山东省肿瘤医院、河南省安阳市肿瘤医院、山东省滕州市中心人民医院及中国医科大学附属第一医院收治的158例行同步放化疗的局部晚期胸段食管鳞状细胞癌患者作为研究对象,根据放疗剂量的不同将患者分为标准剂量组(50.0~50.4 Gy,n=59)和高剂量组(>50.4 Gy,n=99)。比较两组患者治疗后的总生存期(OS)以及无进展生存期(PFS)。患者生存率的估算采用Kaplan-Meier法,组间比较采用log-rank检验;Cox比例风险回归模型分析预后不良因素;受试者工作特征(ROC)曲线分析双肺V_(30)对患者预后的预测价值。结果:158例局部晚期食管鳞状细胞癌患者同步放化疗治疗后,完全缓解19例,占12.03%;部分缓解103例,占65.19%;病情稳定27例,占17.09%;疾病进展9例,占5.70%。总有效率为77.22%。158例患者的中位OS为41个月(95%CI为25~57个月),1、3年OS率分别为76%、51%;中位PFS为24个月(95%CI为13~35个月),1、3年PFS率分别为60%、39%。其中标准剂量组患者的1、3年OS率分别为74%、56%,高剂量组分别为77%、49%,差异无统计学意义(χ^(2)=0.300,P=0.584);标准剂量组患者的1、3年PFS率分别为62%、37%,高剂量组分别为59%、40%,差异无统计学意义(χ^(2)<0.001,P=0.990)。单因素分析显示,病变长度,N分期,临床分期,同步放化疗近期疗效,计划靶体积(PTV)D max,大体肿瘤靶体积(GTV)D mean,左肺、右肺及双肺的V 5、V_(10)、V_(30)、V_(30)、D mean均是影响患者OS、PFS的预后影响因素(均P<0.05)。多因素分析显示,病变长度(HR=2.226,95%CI为1.244~3.985,P=0.007)、N分期(HR=2.819,95%CI为1.137~6.991,P=0.025)、临床分期(HR=1.897,95%CI为1.079~3.334,P=0.026)、同步放化疗近期疗效(HR=1.805,95%CI为1.250~2.606,P=0.002)、左肺V_(10)(HR=0.811,95%CI为0.668~0.986,P=0.035)、左肺V_(30)(HR=0.617,95%CI为0.408~0.933,P=0.022)、右肺V_(30)(HR=2.067,95%CI为1.010~4.231,P=0.047)、双肺V_(10)(HR=1.299,95%CI为1.016~1.662,P=0.037)及V_(30)(HR=2.368,95%CI为1.142~4.910,P=0.021)均是影响患者OS的独立预后因素;N分期(HR=2.433,95%CI为1.201~4.931,P=0.014)、同步放化疗近期疗效(HR=2.067,95%CI为1.391~3.071,P<0.001)及双肺V_(30)(HR=0.113,95%CI为0.018~0.719,P=0.021)均是影响患者PFS的独立预后因素。预测OS和PFS的ROC曲线显示,双肺V_(30)的最佳临界值均为9.5%。结论:与标准剂量组相比,提高放疗剂量未能改善局部晚期胸段食管鳞状细胞癌患者的远期生存。病变长度,N分期,临床分期,同步放化疗近期疗效,左肺的V_(10)、V_(30),右肺V_(30)及双肺的V_(10)、V_(30)均为局部晚期胸段食管鳞状细胞癌患者OS的独立预后因素,N分期、同步放化疗近期疗效及双肺V_(30)均为患者PFS的独立预后因素。当双肺V_(30)≤9.5%时,患者的OS和PFS均可从治疗中获益。

Objective To explore the effects of clinical characteristics and dosimetric factors on the survival and prognosis of patients with locally advanced thoracic esophageal squamous cell carcinoma after concurrent chemoradiotherapy(CCRT).Methods A total of 158 patients with locally advanced thoracic esophageal squamous cell carcinoma undergoing CCRT in Shandong Cancer Hospital,Anyang Cancer Hospital of Henan Province,Tengzhou Central People′s Hospital of Shandong Province and the First Affiliated Hospital of China Medical University from August 2015 to October 2018 were selected as the research subjects.These patients were divided into standard-dose group(50.0-50.4 Gy,n=59)and high-dose group(>50.4 Gy,n=99)according to the radiotherapy dose.The overall survival(OS)and progression-free survival(PFS)of the two groups after treatment were compared.Kaplan-Meier method was used to calculate survival rate and survival comparison was performed by log-rank test.Cox proportional hazard regression model was used to analyze the adverse prognostic factors.The receiver operating characteristic(ROC)curve was used to analyze the predictive value of lung V_(30) for patient prognosis.Results In 158 patients with locally advanced esophageal squamous cell carcinoma,19 cases(12.03%)had complete remission after CCRT,103 cases(65.19%)had partial remission,27 cases(17.09%)had stable disease,9 cases(5.70%)had progression disease,and the total effective rate was 77.22%.The median OS of 158 patients was 41 months(95%CI:25-57 months),and the 1-and 3-year OS rates were 76%and 51%,respectively.The median PFS was 24 months(95%CI:13-35 months),and the 1-and 3-year PFS rates were 60%and 39%,respectively.The 1-and 3-year OS rates in the standard-dose group were 74%and 56%,and those in the high-dose group were 77%and 49%,with no statistically significant difference(χ^(2)=0.300,P=0.584).The 1-and 3-year PFS rates in the standard-dose group were 62%and 37%,and those in the high-dose group were 59%and 40%,with no statistically significant difference(χ^(2)<0.001,P=0.990).Univariate analysis showed that the length of the lesion,N stage,clinical stage,short-term efficacy of CCRT,planning target volume(PTV)Dmax,gross tumor volume(GTV)Dmean,V5,V_(10),V_(30),V_(30),Dmean of the left,right and bilateral lung were all the prognostic factors for OS and PFS(all P<0.05).Multivariate analysis showed that the length of the lesion(HR=2.226,95%CI:1.244-3.985,P=0.007),N stage(HR=2.819,95%CI:1.137-6.991,P=0.025),clinical stage(HR=1.897,95%CI:1.079-3.334,P=0.026),short-term efficacy of CCRT(HR=1.805,95%CI:1.250-2.606,P=0.002),left lung V_(10)(HR=0.811,95%CI:0.668-0.986,P=0.035),left lung V_(30)(HR=0.617,95%CI:0.408-0.933,P=0.022),right lung V_(30)(HR=2.067,95%CI:1.010-4.231,P=0.047),bilateral lung V_(10)(HR=1.299,95%CI:1.016-1.662,P=0.037)and bilateral lung V_(30)(HR=2.368,95%CI:1.142-4.910,P=0.021)were independent prognostic factors affecting OS.N stage(HR=2.433,95%CI:1.201-4.931,P=0.014),short-term efficacy of CCRT(HR=2.067,95%CI:1.391-3.071,P<0.001)and bilateral lung V_(30)(HR=0.113,95%CI:0.018-0.719,P=0.021)were independent prognostic factors affecting PFS.The ROC curve for predicting OS and PFS showed that the optimal cut-off value of bilateral lung V_(30) was 9.5%.Conclusion Compared with the standard-dose group,increasing the dose of radiotherapy fails to improve the long-term survival of patients with locally advanced thoracic squamous cell carcinoma.Lesion length,N stage,clinical stage,short-term efficacy of CCRT,left lung V_(10) and V_(30),right lung V_(30),bilateral lung V_(10) and V_(30) are independent prognostic factors for OS in patients with locally advanced thoracic squamous cell carcinoma.N stage,short-term efficacy of CCRT and bilateral lung V_(30) are independent prognostic factors for PFS.When bilateral lung V_(30)≤9.5%,the patients′OS and PFS will benefit from the treatment.