Disease	Esophageal cancer
Stage of Disease/Treatment	Metastatic/advanced
Prior Therapy	1 prior regimen
Type of study	Phase II, single arm
Primary Endpoint	Overall response rate
Secondary Endpoint	Toxicity
Secondary Endpoint	Disease control rate
Secondary Endpoint	Progression‐free survival
Secondary Endpoint	Overall survival
Additional Details of Endpoints or Study Design
This study was conducted according to a protocol approved by the Sun Yat‐Sen University Cancer Center Human Research Ethical Committee. Informed consent was obtained from each enrolled patients prior to enrollment in the study.
Eligibility Criteria:
All enrolled patients had histopathologically confirmed ESCC. The inclusion criteria were as following: (a) Eastern Cooperative Oncology Group (ECOG) performance status scores from 0–2; (b) age from 18 to 75 years; (c) R0 resection for primary cancer with two‐incision esophagectomy or three‐incision esophagectomy; and (d) local postoperative recurrence comprehensively confirmed by endoscopy, ultrasonography, computed tomography (CT), physical examination, and/or biopsy. Local recurrence was defined as recurrence at anastomosis with or without regional lymph nodes or regional lymph nodes alone; (a) no distant metastasis; (b) no previous radiotheraphy (RT); and (c) no serious cardiac, liver, pulmonary, or renal disease.
Study Design:
Radiotherapy regimen: All patients received three‐dimensional conformal radiation therapy, intensity‐modulated radiation therapy, or Tomo treatment plan conducted by Pinnacle or Monacle planning system. A linear accelerator (6MV) was used as the X‐ray source. The prescribed total dose was from 50.4 to 60 Gy and the daily fractional dose was 2.0 Gy administered 5 days per week. Modification of the total dose was allowed according to individuals' target volume planning. The immobilization and simulation were performed according to the standard protocol established in our department. For treatment planning, briefly, the gross tumor volume (GTV) included the recurrent tumor or lymph nodes present in previous CT scans, positron emission tomography‐CT, or endoscopy. The clinical target volume (CTV) comprised the anastomosis, supraclavicular, and regional lymph nodes. PTV1 was defined as the GTV plus a 0.5‐cm margin, and PTV2 was defined as the CTV plus a 0.5‐cm margin in all directions, respectively. The spinal cord dose was not to exceed 46.0 Gy. Doses to normal lung tissue were calculated by dose‐volume histograms,with a mean lung dose less than 17 Gy and V20 less than 30%.
Concurrent chemotherapy regimen: Continuous infusion cisplatin 25mg/m2 over 2h on day 1 and 5‐FU 1176/m2 over 72h on days 1–3 repeated weekly for 4 weeks. If grade 3 or greater toxicities occurred, the discontinuation or dose‐reduced chemotherapy will be considered. The treatment protocol schedule is shown in Figure 2. The primary endpoint was tumor response, and the secondary endpoints were survival rate and toxicity.
Response, Toxicity, and Survival: During concurrent chemoradiotherapy, complete blood count and serum chemistry profile were examined each week to monitor for adverse events. Barium‐swallow examination and contrast‐enhanced CT scan with or without endoscopy were performed for response assessment at two months after the CCRT. RECIST criteria were used to determine response. A senior radiologist and a radiation oncologist independently evaluated the tumor response by a comprehensive review of the CT scan and endoscopy. The clinical response rate was defined as the proportion of patients with a complete response (CR) or partial response (PR). All patients were monitored regularly for acute and chronic toxicities during treatment and during follow‐up, which were graded according to the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE 3.0). After the CCRT, patients were first followed up at 2 months, then every 3 months for the first year, every 6 months for 2 years, and then annually to record the progression of the disease and survival. PFS was defined as the date from treatment to tumor progression or death. OS was measured from treatment to date of death by any cause.
Statistical analysis: The SPSS 22.0 software program was used for analyses. The Kaplan‐Meier method was used to analyze the PFS and OS rate. The quantitative results are expressed as medians and ranges. Statistical comparisons between the two groups were performed with χ2 statistics. A value of p < .05 was considered to be significant.
Investigator's Analysis	Active and should be pursued further