基于高频复发区改良临床靶区的术后放疗在食管鳞状细胞癌中的疗效研究

Efficacy of postoperative radiotherapy based on modified clinical target volume according to highfrequency recurrence regions in patients with esophageal squamous cell carcinoma

目的分析食管鳞状细胞癌(ESCC)患者采用基于术后高频复发区域改良的临床靶区(CTV)进行术后放疗(PORT)的生存疗效、预后影响因素及失败模式,为进一步优化PORT的CTV提供参考。方法回顾性分析2014年4月28日至2018年11月29日在南京大学医学院附属鼓楼医院肿瘤中心治疗的ESCC根治术后患者,纳入其中的pT3-4aN0或N+、并采用基于术后高频复发区域改良的CTV进行PORT的患者。Kaplan-Meier法计算总生存期(OS)、无局部区域复发生存期(LRFS),评价患者的不良反应,Cox比例风险模型行单因素和多因素生存分析,并分析PORT的失败模式。结果本研究共纳入85例患者,中位随访52.6个月,全组中位OS为74.1个月,1年、2年和3年OS率分别为97.6%、84.7%和71.7%;中位LRFS未达到,1年、2年和3年LRFS率分别为92.9%、78.6%和71.5%;3~4级不良反应发生率为17.6%(15/85),主要为淋巴细胞计数减少、骨髓抑制、消化道反应和皮肤反应。PORT后OS的单因素分析提示,分化程度(将G1+G1~2+G2分组设为对照组,G2~3+G3分组:HR=4.19,95%CI为1.91~9.17,P<0.001;NA+基底细胞样分组:HR=4.16,95%CI为1.29~13.44,P=0.017)及术后分期(HR=2.19,95%CI为1.09~4.39,P=0.030)为OS的影响因素;Cox多因素分析表明,分化程度是影响PORT后OS的独立预后因素(将G1+G1~2+G2分组设为对照组,G2~3+G3分组:HR=5.24,95%CI为2.30~11.93,P<0.001;NA+基底细胞样分组:HR=4.83,95%CI为1.33~17.62,P=0.017)。首次失败模式分析显示,39例(45.9%)出现复发,22例(25.9%)为局部区域复发,中位复发时间为术后15.2个月,19例(22.4%)出现远处转移,中位复发时间为术后14.1个月,其中2例(2.4%)为混合型失败;在局部区域复发中,16例(72.7%)为放射野内复发,部位以锁骨上、上中纵隔和上腹部胃周/腹腔动脉干淋巴引流区最常见;在远处转移中,肺、骨与肝转移最常见。结论对于根治术后高危ESCC患者,采用基于术后高频复发区域改良的CTV进行PORT,生存期佳,安全性高,值得开展多中心、大样本、前瞻性研究进一步证实。

Objective To analyze the survival efficacy,prognostic factors and failure patterns of patients with esophageal squamous cell carcinoma(ESCC)underwent postoperative radiotherapy(PORT)using modified clinical target volume(CTV)based on postoperative high-frequency recurrence regions,so as to provide reference for the further optimization of CTV of PORT.Methods The patients with ESCC underwent radical operation in Comprehensive Cancer Center of Nanjing Drum Tower Hospital,Affiliated Hospital of Nanjing University Medical School from April 28,2014 to November 29,2018 were retrospectively analyzed.Patients with stage pT3-4aN0 or N+,who underwent PORT with modified CTV based on postoperative highfrequency recurrence regions,were included in the study.Kaplan-Meier method was used to calculate overall survival(OS)and locoregional recurrence free survival(LRFS),adverse events of patients were evaluated,Cox proportional hazards model was used for univariate and multivariate survival analysis,and the failure patterns of patients after PORT were analyzed.Results A total of 85 patients were included in this study,and the median follow-up time was 52.6 months.The median OS of the whole group was 74.1 months.The 1-year,2-year and 3-year OS rates were 97.6%,84.7%and 71.7%respectively.The median LRFS was not reached,and the 1-year,2-year and 3-year LRFS rates were 92.9%,78.6%and 71.5%respectively.The incidence of grade 3-4 adverse events was 17.6%(15/85),mainly including lymphopenia,bone marrow suppression,gastrointestinal reaction and skin reaction.Univariate analysis of OS after PORT showed that the degree of differentiation(set G1+G1-2+G2 group as the control group,G2-3+G3 group HR=4.19,95%CI:1.91-9.17,P<0.001;NA+basal-like group HR=4.16,95%CI:1.29-13.44,P=0.017)and postoperative stage(HR=2.19,95%CI:1.09-4.39,P=0.030)were the influencing factors of OS.Cox multivariate analysis showed that the degree of differentiation was an independent prognostic factor for OS after PORT(set G1+G1-2+G2 group as the control group,G2-3+G3 group HR=5.24,95%CI:2.30-11.93,P<0.001;NA+basal-like group HR=4.83,95%CI:1.33-17.62,P=0.017).The first failure patterns analysis showed that 39 cases(45.9%)had recurrence,among which,22 cases(25.9%)had locoregional recurrence with the median onset time of 15.2 months after operation,19 cases(22.4%)had distant metastasis with the median onset time was 14.1 months after operation,and 2 cases(2.4%)were mixed failure mode.Among the locoregional recurrence,16 cases(72.7%)recurred in the radiation field.Among all the local recurrence sites,the lymph node drainage regions in the supraclavicular,upper middle mediastinum and upper abdominal perigastric/celiac artery trunk areas were the most common sites.Among the distant metastatic organs,lung,bone and liver metastases were the most common.Conclusion Patients of ESCC with high risk of recurrence after radical esophagectomy have long survival time and high safety after PORT with modified CTV according to the high-frequency recurrence regions.It is worthy of further confirmation by multicenter,large sample and prospective clinical trials.