Abstract:

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 pT_3-4aN₀ or N₊, who underwent PORT with modified CTV based on postoperative high-frequency 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.

Key words: Esophageal neoplasms, Chemoradiotherapy, adjuvant, Recurrence, Prognosis