食管癌放疗肿瘤病理缓解程度及血管内皮生长因子变化与预后的相关性分析

目的 探讨食管癌放疗或同步放化疗中肿瘤组织的病理缓解和血管内皮生长因子（VEGF）血清浓度变化与预后的关系。方法 前瞻性对89例食管癌患者进行放疗或同步放化疗，于放疗第4周行胃镜下活检评估病理缓解情况；并分别于放疗前、放疗第4周以及放疗结束后1周内采集患者外周血，采用双抗体夹心亲和素-生物素酶联免疫吸附法检测血清VEGF水平。分析病理缓解程度和VEGF动态变化与患者预后的关系。运用Kaplan-Meier法计算生存率和绘制生存曲线，Log-rank检验进行生存分析，采用Cox比例风险模型进行多因素生存分析。结果 病理完全缓解组（CR组）和未完全缓解组（非CR组）患者分别为67例和22例。CR组1年、3年和5年总生存（OS）率分别为77.6%、46.3%和35.2%，中位OS为30.0个月（95%CI 14.3~45.6个月）；非CR组1年、3年和5年OS率分别50%、0%和0%，中位OS为11.4个月（95%CI 4.2~18.6个月），CR组OS显著好于非CR组（P<0.001）。CR组1年、3年和5年无进展生存（PFS）率分别为69.7%、40.9%和34.3%，中位PFS为21.7个月（95%CI 13.1~30.3个月）；非CR组1年、3年和5年PFS率分别为36.4%、0%和0%，中位PFS为7.4个月（95%CI 2.1~12.4个月）。CR组PFS明显好于非CR组（P<0.001）。血清VEGF增高组、稳定组和降低组患者分别为16例、43例和30例。增高组1年、3年和5年OS率分别为50%、18.8%和12.5%，中位OS为9.2个月（95%CI 2.2~17.9个月）；稳定组1年、3年和5年OS率分别为67.4%、30.2%和19.9%，中位OS为19.9个月（95%CI 14.9~24.9个月）；降低组1年、3年和5年OS率分别为86.7%、50%和42.9%，中位OS为28.7个月（95%CI 5.4~51.2个月），血清VEGF降低组OS显著好于增高组（P<0.05）。增高组1年、3年和5年PFS率分别为43.8%、12.5%和0%，中位PFS为8.0个月（95%CI 2.5~15.9个月）；稳定组1年、3年和5年PFS率分别为57.1%、26.2%和20.8%，中位PFS为15.5个月（95%CI 10.7~20.4个月）；降低组1年、3年和5年PFS率分别为76.7%、46.7%和39.7%，中位PFS为20.1个月（95%CI 2.4~40.1个月）；血清VEGF降低组PFS显著好于增高组（P=0.013）。结论放疗中肿瘤组织病理缓解状况和血清VEGF变化趋势与食管癌预后密切相关。

Association between pathological response or VEGF serum changes during radiotherapy and prognosis in patients with esophageal carcinoma

Objective To observe the pathological response in tumor tissues and the vascular endothelial growth factor (VEGF) changes in serum of patients with esophageal carcinoma receiving radiotherapy or concurrent chemoradiotherapy, and to investigate the relationship between these two factors and the prognosis of these patients. Methods A total of eighty-nine patients with esophageal carcinoma treating with radiotherapy or concurrent chemo-radiotherapy were prospective included. Gastroscopy and biopsy were performed at 4 week of radiotherapy to assess pathologicalresponse. VEGF serum levels were measured by double antibody sandwich avidin-biotin ELISA prior to, at 4 week of, and 1 week after radiotherapy. The relationship between pathological response in tumor tissues and VEGF serum changes and the prognosis of the patients were analyzed. The survival curve and survival rate were respectively drawn and calculated by the Kaplan-Meier method, and the Log-rank test was used for survival analysis. Multivariate Cox proportional hazard model was used to analyze the prognostic factors. ResultsPathological responses were classified into two degrees:Non-CR responses (22 cases), and CR responses (67 cases). The 1-, 3- and 5-year OS rates in CR group and non-CR group were 77.6%, 46.3%, 35.2% (median OS:30.0 months, 95%CI 14.3-45.6 months) and 50.0%, 0.0%, 0.0% (median OS:11.4 months, 95%CI 4.2-18.6 months), respectively, showing that the OS in CR group were significantly higher than that in non-CR group (P<0.001). Meanwhile, the 1-, 3- and 5-year PFS rates in CR group and non-group were 69.7%, 40.9%, 34.3% (median PFS:21.7 months, 95%CI 13.1-30.3 months) and 36.4%, 0.0%, 0.0% (median PFS:7.4 months, 95%CI 2.1-12.4 months), respectively, showing that the PFS in CR group was significantly higher than that in non-CR group (P<0.001). VEGF serum changes were classified into three degrees:increased group (16 cases), stable group (43 cases) and decreased group (30 cases). The 1-, 3- and 5-year OS rates in VEGF increased group were 50.0%, 18.8%, 12.5% (median OS:9.2 months, 95%CI 2.2-17.9 months), respectively, while the 1-, 3- and 5-year OS rates in VEGF stable group were 67.4%, 30.2%, 19.9% (median OS:19.9 months, 95%CI 14.9-24.9 months), respectively, and the 1-, 3- and 5-year OS rates in VEGF-decreased group were 86.7%, 50.0%, 42.9% (median OS:28.7 months, 95%CI 5.4-51.2 months), respectively, showing that the OS in VEGF-decreased group was significantly the highest among the three groups (P<0.05). The 1-, 3- and 5-year PFS rates in VEGF-increased group were 43.8%, 12.5%, 0 (median PFS:8.0 months, 95%CI 2.5-15.9 months), respectively, while the 1-, 3- and 5-year PFS rates in VEGF stable group were 57.1%, 26.2%, 20.8% (median PFS:15.5 months, 95%CI 10.7-20.4 months), respectively, and the 1-, 3- and 5-year PFS rates in VEGF decreased group were 76.7%, 46.7%, 39.7% (median PFS:20.1 months, 95%CI 2.4-40.1 months), respectively, showing that the PFS in VEGF decreased group was significantly the highest among the three groups (P=0.013). Conclusions Pathological response and VEGF changing trend during radiotherapy were both closely related to prognosis of patients with esophageal carcinoma.