颈胸上段食管鳞癌根治性同步放化疗远期预后分析及影响因素研究

Long-term Prognosis Analysis and Influencing Factors of Concurrent Chemotherapy and Radio-therapy for Cervical and Upper Thoracic Esophageal Squamous Cell Carcinoma

背景颈胸上段食管鳞癌发病率相对较低,治疗难度较大,治疗模式存在争议,缺乏便捷、准确判断预后的生物标志物,总体预后欠佳。目的探讨根治性同步放化疗模式下颈胸上段食管鳞癌患者的长期预后及其影响因素。方法选取2013年1月—2017年12月于河北医科大学第四医院放疗科行根治性同步放化疗的颈胸上段食管鳞癌患者作为研究对象。通过电子病历系统收集患者一般资料、美国东部协作肿瘤组(ECOG)评分、肿瘤部位、肿瘤长度、TNM分期、放疗剂量、照射方式、化疗方案、毒副作用等,计算衍生中性粒细胞与淋巴细胞比例(dNLR)。依据患者dNLR,将患者分为dNLR<2.15组(64例)和dNLR≥2.15组(42例)。对患者进行随访,放疗1年内每3个月复查1次,2~5年内每半年复查1次,5年后每1年复查1次,计算患者总生存期(OS)、无进展生存期(PFS)、无局部区域复发生存期(LRRFS)、无远转生存期(DMFS)。采用Kaplan-Meier法绘制患者OS、LRRFS、DMFS的生存曲线,OS、PFS、LRRFS、DMFS影响因素的单因素分析采用Log-rank检验。采用多因素Cox风险回归分析探讨患者OS、PFS、LRRFS、DMFS的影响因素。结果截至末次随访,患者3、5、7年总生存率分别为55.7%、43.0%、37.8%,中位OS为47.5〔95%CI(29.4,65.6)〕个月;3、5、7年无进展生存率分别为45.3%、37.7%、31.1%,中位PFS为30.7〔95%CI(21.1,40.3)〕个月;3、5、7年无局部区域复发生存率50.9%、41.4%、33.5%,中位LRRFS为43.5〔95%CI(21.6,65.4)〕个月;3、5、7年无远转生存率49.1%、38.6%、34.4%,中位DMFS 34.7〔95%CI(20.7,48.7)〕个月。多因素Cox风险回归分析结果显示,TNM分期、照射方式为患者OS、PFS、LRRFS及DMFS的影响因素(P<0.05),性别为LRRFS的影响因素(P<0.05),dNLR为PFS及DMFS的影响因素(P<0.05)。患者发生≥2级急性放射性肺炎、放射性食管炎、白细胞减少、贫血、血小板减少者分别为10例、25例、32例、9例、11例。结论颈胸上段食管鳞癌患者行根治性同步放化疗长期预后较为满意,且耐受良好。局部复发为主要失败模式,选择性淋巴引流区照射显著改善患者预后,可予以临床推广,dNLR对患者长期生存有一定的预测作用。

Background The incidence of cervical and upper thoracic esophageal cancer is relatively low,with difficulties and controversies of mode in treatment,lack of convenient and accurate prognostic biomarkers,and poor overall prognosis.Objective To investigate the long-term prognosis of patients with cervical and upper thoracic esophageal squamous cell carcinoma under concurrent chemotherapy and radio-therapy(CCRT).Methods Patients with cervical and thoracic upper esophageal cancer who received CCRT in the Department of Radiotherapy of the Fourth Hospital of Hebei Medical University from January 2013 to December 2017 were selected as the research subjects.General data,Eastern Cooperative Oncology Group(ECOG)score,tumor site,tumor length,TNM stage,radiotherapy dose,irradiation mode,chemotherapy regimen,toxic and side effects were collected by electronic medical record system,and neutrophil to lymphocyte ratio(dNLR)was calculated.The patients were divided into the dNLR<2.15 group(64 cases)and dNLR≥2.15 group(42 cases)according to dNLR.The patients were followed up,radiotherapy was reviewed once every 3 months for 1 year,once every 6 months for 2 to 5 years,and once every 1 year after 5 years,and overall surviva(l OS),progression-free surviva(l PFS),local relapse-free surviva(l LRRFS),and distant metastasis-free survival(DMFS)were collected.Survival curves of OS,LRRFS and DMFS were plotted by Kaplan-Meier method.The single factor analysis of OS,PFS,LRRFS and DMFS was performed by Log-rank test.Multivariate Cox proportional hazard regression model was used to explore the influencing factors of OS,PFS,LRRFS and DMFS.Results As of the last follow-up,the OS rates at 3,5 and 7 years were 55.7%,43.0%and 37.8%,with a median OS of 47.5〔95%CI(29.4,65.6)〕months;the rates of PFS at 3,5 and 7 years were 45.3%,37.7%and 31.1%,with a median PFS of 30.7〔95%CI(21.1,40.3)〕months;the LRRFS rates in 3,5 and 7 years were 50.9%,41.4%and 33.5%,with a median LRRFS of 43.5〔95%CI(21.6,65.4)〕months;the DMFS rates at 3,5 and 7 years were 49.1%,38.6%and 34.4%,with a median DMFS of 34.7〔95%CI(20.7,48.7)〕months.Multivariate Cox proportional hazard regression analysis showed that TNM stage and irradiation mode were influencing factors of OS,PFS,LRRFS and DMFS(P<0.05),gender was an influencing factor of LRRFS(P<0.05),and dNLR was an influencing factor of PFS and DMFS(P<0.05).There were 10 cases,25 cases,32 cases,9 cases and 11 cases of grade 2 and above acute radiation pneumonitis,acute radiation esophagitis,leukopenia,anemia and thrombocytopenia,respectively.Conclusion The long-term prognostic survival outcome of CCRT for cervical and upper thoracic esophageal squamous cell carcinoma was satisfactory and well tolerated.Local recurrence was the main failure pattern.Elective lymphatic drainage irradiation can significantly improve the prognosis of patients,which can be promoted clinically and dNLR has a predictive effect on long-term survival.