分子标志物指导同步放化疗不能手术食管癌前瞻性非随机对照临床研究

Prospective non-randomized clinical study of biomarker-guided concurrent chemoradiotherapy for unrescetable esophageal squamous cell carcinoma

目的：探讨依据分子标志物筛选药物同步放化疗不能手术食管鳞癌的疗效。方法2010—2013年间54例进入研究，实验组26例，对照组28例。放疗均采用常规分割IMRT，剂量60～66 Gy，化疗在放疗第1、5周给予。实验组化疗药物根据ERCC1、TYMS、RRM1、TUBB3基因mRNA表达水平选择，对照组化疗采用顺铂＋氟尿嘧啶。主要观察两组客观有效率和OS情况。 Kaplan-Meier方法计算OS率并Logrank检验，余用χ2检验。结果实验组随访率100％，对照组随访率96％。实验组和对照组患者有效率分别为85％和86％（ P＝0.483），中位OS期分别为35.5个月和25.8个月，1、2、3年OS率分别为84％、68％、46％和71％、59％、28％（ P＝0.047），不良反应发生率相近。结论根据分子标志物筛选药物同步放化疗，可提高不能手术食管癌患者OS率，值得进一步研究。

Objective To evaluated the efficacy of biomarker-guided concurrent chemoradiotherapy in unrescetable esophageal squamous cell carcinoma patients. Methods 54 cases of unrescetable esophageal squamous cell carcinoma were enrolled in the prospective non-randomized clinical study and divided into study group and control group. All cases were treated with concurrent chemoraditherapy. Intensity-modulated radiation therapy was used with a dose of 60-66 Gy. Chemotherapy was perfromed on day 1 and d29. In the study group the selection of the chemotherapy drug was based on the excision repair cross-complementation 1 （ ERCC1） ,thymidylate synthetase （ TYMS） ,ribonucleotide reductase M1（ RRM1） ,and theβ-tubulin isotypeⅢ（ TUBB3） mRNA expression levels. In the control group,the regiment for chemotherapy was Cisplatin plus Fluorouracil. The objective response rate and overall survival （ OS ） were calculated using Kaplan-meier method and log-rank test was used for between-group comparison. The survival rate was calculated using Kaplan-Meier method and analyzed using log-rank method, other comparison was performed by χ2 test. Results The follow-up rate was 100% in the study group and 96% in the controll group. The objective response rate of the study group and the control group were 85% and 86 （ P=0. 483 ） , respectively. The median survival time （ MST） in the study group was 35. 5 months and that in the control group was 25. 8 months. The 1-,2-,and 3-year OS rates of the study group and the control group were 84%,68%,46% and 71%,59%,28% respectively （P=0. 047）.No significant differences were observed in the incidence of side-effects in the two groups. Conclusions Selecting the chemotherapy drug according to biomarker,combined with radiation therapy,could improve survival.in unrescetable esophageal squamous cell carcinoma. The value needs further investigation.