Extensive clinical target volume in postoperative chemoradiotherapy for esophageal squamous cell carcinoma: a phase II clinical trial (ESO-Shanghai 9).

BACKGROUND: To compare the efficacy and safety of postoperative extensive target volume irradiation with elevated radiation dose and concurrent chemotherapy with radiotherapy only for the postoperative treatment of esophageal squamous cell carcinoma.

METHODS: This trial was a single-arm phase II trial. Patients who underwent a radical transthoracic resection with negative margins within 3 months and histologically confirmed esophageal squamous cell carcinoma (pT3-4N0M0 or pTxN + M0, AJCC 7th) were eligible for this study. Postoperative radiotherapy was performed at a total dose of 45 Gy in 25 fractions with clinical target volumes of the tumor bed, anastomosis, bilateral supraclavicular, mediastinal, left gastric and celiac trunk lymph node areas. Five cycles of weekly TC (paclitaxel 50 mg/m2 , d1, carboplatin AUC = 2, d1) were given as concurrent chemotherapy. The primary endpoint was the 2-year local control rate, and the secondary endpoints were overall survival, disease free survival, local-regional recurrence free survival, distant metastasis free survival and adverse events. All endpoints were compared with those in ESO-Shanghai 8 study with postoperative radiotherapy alone (40 Gy/20Fx).

RESULTS: A total of 70 patients were enrolled from 2016 to 2018. The 2-year local control rate was 87.9% (95% CI: 83.3-92.3) in this study, which achieved the hypothesized 2-year local control rate of at least 83%. Overall survival, disease free survival, local-regional recurrence free survival and distant metastasis free survival in this study were also longer than those in previous ESO-Shanghai 8 study while most toxicities were increased and two patients in this study died of radiation pneumonitis.

CONCLUSIONS: Postoperative extensive target volume irradiation with elevated radiation dose and concurrent chemotherapy was effective. Treatment related toxicity was increased due to higher treatment intensity. Trial registration clinicaltrials.gov: NCT02916511.