Discussion
toxicity
ESOPHAGEAL CANCER, RECURRENCE, METASTASIS
In this phase II clinical trial, we explored the efficacy and safety of postoperative extensive target volume irradiation with elevated radiation dose and concurrent chemotherapy. Compared with the ESO-Shanghai 8 study, the survival results of this study showed a significant improvement in the 2-year local control rate and met the hypothesized 2-year local control rate of at least 83%. Treatment related toxicity was increased due to higher treatment intensity.Data were conflicting about the role of postoperative radiotherapy. In the clinical trials from Ténière et al. and Fok et al., no overall survival improvement was shown in the results [In our previous study (ESO-Shanghai 8), an extensive target volume to cover all high-risk recurrence areas and a total dose of 40 Gy were used in postoperative radiotherapy. The extensive target volume irradiation was feasible in dose distribution and the toxicity was tolerable, but the in-field recurrence rate remained high [In the ESO-Shanghai 8 study, we found that the distant metastasis rate was relatively high [In this study, the toxicity was more frequent and severe than that in ESO-Shanghai 8 study, which was partly due to the addition of chemotherapy [Compared with the surgery data of our center, the rate of recurrence of supraclavicular and mediastinal lymph nodes was reduced in the chemoradiotherapy group in this study (Supraclavicular: 6.5% vs. 2.9%; Mediastinal: 12.3% vs. 5.7%) while no difference was observed in the rate of recurrence of abdominal lymph nodes. (Abdominal: 5.0% vs. 4.3%) [Therefore, based on the results of this study, we designed another phase II clinical study (ESO-Shanghai 17, NCT 04764227), using targeted high-risk regional areas (supraclavicular, upper and middle mediastinal lymph node areas) as clinical target volume for radiotherapy and also concurrent with weekly TC chemotherapy in patients after radical resection of T3-4NxM0 or TxN + M0 esophageal cancer, which was expected to reduce the occurrence of treatment-related toxicity without reducing the local control rate and lowering the disease-free survival.As a single-arm study, there were limitations in study design. We could only compare the results of this study with historical studies, which may be potentially biased by different accrual time/sites and patient characteristics across studies. Besides, many studies applied immune checkpoint inhibitors to neoadjuvant therapy followed by surgery in recent years, and the pathological complete response rates reported in various studies were inspiring. For these patients, whether postoperative chemoradiotherapy is still meaningful and what is the most suitable target volume for radiation needed further research.In all, postoperative extensive target volume irradiation with elevated radiation dose and concurrent chemotherapy was effective. Treatment related toxicity was increased due to higher treatment intensity. We hope postoperative chemoradiotherapy with high-risk regional target volumes in future clinical trials could decrease the treatment-related toxicity rate without reducing the efficacy.