Objective: To observe the pathological response in the tumor tissue and the changes of serum level of vascular endothelial growth factor (VEGF) in esophageal cancer patients receiving concurrent chemoradiotherapy, in order to study the impacts of these two factors on the prognosis of patients.
Methods: One hundred pathologically confirmed esophageal cancer patients were treated with radiotherapy including 72 patients with concurrent chemoradiotherapy. After 4 weeks, gastroscopy was performed to collect tumor biopsies for examination of pathological changes. The responses to radiotherapy were classified into three degrees: mild, moderate and intensive. Moreover, serum samples were collected from the patients prior to, at the fourth week during radiotherapy, and one week after radiotherapy, and serum VEGF level was determined. The changes of serum VEGF were classified as increased, unchanged and decreased. Serum samples from 30 healthy subjects were collected and represented as VEGF healthy control.
Results: Among the eighty-nine patients evaluable, the 1- and 3-year overall survival (OS) rates were 70.8% and 33.3%, respectively; 1-year and 3-year progression-free survival (PFS) rates were 61.8% and 28.2%, respectively; and 1-year and 3-year local control (LC) rates were 76.9% and 50.0%, respectively. The 1-year OS rates in the patients with mild, moderate and intensive pathological responses were 50.0%, 76.9% and 78.0%, respectively. The 1-year OS rate in the mild response group was significantly lower than that in the intensive response group (P<0.05). The 1-year and 3-year PFS rates in the three groups were 36.4%, 73.1%, 68.3%, and 0.0%, 40.0% and 38.9%, respectively, showing that the rate in the mild response group was significantly lower than that in the moderate and intensive response groups (P<0.05 for both). The PFS rate in the mild response group was significantly lower than that in the moderate and intensive response groups(P<0.05 for both). Moreover, the 1-year local control (LC) rates in the three groups were 52.9%, 83.3% and 83.8%, and the three-year LC rates were 0.0%, 64.3% and 64.0%, respectively, showing that the lowest LC rates in the mild response group were significantly lower than that in the moderate and intensive response groups (P<0.05 for both). The average serum VEGF levels in the patients prior to, during and after radiotherapy were (109.6±33.7) ng/L, (101.2±24.3) ng/L and (99.5±22.9) ng/L, respectively, all significantly higher than that in the healthy subjects [(79.6±39.2) ng/L, P<0.05 for both]. The level of serum VEGF was decreased during and after radiotherapy compared with that before radiotherapy (F=6.124, P=0.004). The 1-year OS rates in the VEGF-increased, unchanged and decreased groups were 50.0%, 67.4% and 86.7%, respectively, and the 3-year OS rates in these three groups were 15.4%, 27.0% and 50.0%, respectively. The OS rates in the increased group were significantly lower than that in the VEGF-decreased group (P<0.05). Moreover, the 3-year PFS rates in the three groups were 7.7%, 21.6% and 46.4%, respectively, and the rate in the VEGF-increased group was significantly lower than that in the VEGF-decreased group (P<0.05). The multi-variate analysis showed that TNM stage, pathological response and serum VEGF were independent factors affecting the survival in the non-surgical patients with esophageal cancer (P<0.05 for all).
Conclusions: Tumor tissue pathological response and variation of serum VEGF level in response to chemoradiotherapy can be used to predict the efficacy of chemoradiotherapy in non-surgical patients with esophageal cancer. Hence, monitoring the pathological response and VEGF changes during the course of therapy is of utmost importance to evaluate and perform an individualized therapy in clinical practice.