Postoperative chemoradiotherapy for esophageal squamous cell Carcinoma: Results from ESO-Shanghai 17 and joint analyses for phase II clinical trials

To explore efficacy and safety of postoperative chemoradiotherapy in esophageal squamous cell carcinoma.

Two single-arm, phase II trials (ESO-Shanghai 9 and 17) were conducted with the same inclusion criteria: 1) age 18-75, 2) ECOG 0-1, 3) within 3 months after surgery, 4) pathologically confirmed esophageal squamous cell carcinoma(pT3-4orN+,M0), with R0 margins, 5) no preoperative therapy. Both were postoperative concurrent chemoradiotherapy with weekly paclitaxel and carboplatin, and extended-field or small T-shaped field radiotherapy at dose of 45 Gy/25Fx or 50.4 Gy/28Fx in ESO-Shanghai 9 or 17. The primary endpoint was 2-year local control rate, secondary endpoints including overall survival, treatment-related toxicities, and failure patterns.

ESO-Shanghai 17 enrolled 70 patients from 2020 to 2023. 2-year local control rate was 83.8 %, and 1, 2, 3-year overall survival rates were 95.7 %, 84.0 %, 67.1 %. Local recurrence occurred in 24.3 % and distant metastasis in 21.4 %. There were no significant differences in local recurrence and metastasis. Both studies exhibited similar local recurrence-free survival and overall survival, disease free survival, and distant metastasis-free survival (P = 0.178, 0.224, 0.358, 0.440). No patients experienced grade Ⅳ or higher adverse events (except for leukopenia and neutropenia) in ESO-Shanghai 17. While ESO-Shanghai 9 reported two cases of grade V pneumonia, and grade Ⅲ or higher leukopenia and neutropenia incidences were higher than ESO-Shanghai 17.

Postoperative chemoradiotherapy (50.4 Gy/28Fx with small T-shaped field) yielded local control and survival comparable to ESO-Shanghai 9, with no radiation pneumonitis-related deaths in esophageal squamous cell carcinoma.(Clinicaltrial: ESO-Shanghai 9, NCT02916511; ESO-Shanghai 17, NCT04764227).