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. Results Pathological 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. Trial registration This clinical trial was registered in the United States Trial, ID: NCT01551641 Key words: Esophageal carcinoma; Radiotherapy; Pathological response; Vascular endothelial growth factor; Prognosis