Neoadjuvant Chemoimmunotherapy Combined With Node-Sparing Radiotherapy for Clinical T3N+ Locally Advanced Esophageal Squamous Cell Carcinoma: A Prospective Single-Arm, Phase II Study (CINSREC Trial).

INTRODUCTION: The promising therapeutic outcomes of neoadjuvant chemoimmunotherapy (NCIT) in locally advanced esophageal squamous cell carcinoma (ESCC) have been confirmed by multiple phase II clinical trials and are widely used in clinical practice. However, there are some cases, such as clinical T3N+ stage, that achieve poor tumor regression after receiving NCIT, reflecting the insufficient efficacy of NCIT for advanced T-type tumors. It may be necessary to add concurrent radiotherapy to further improve the local control effect of tumor, but it also means higher adverse events and immune suppression when irradiating tumor-draining lymph nodes. Nevertheless, node-sparing radiotherapy can enhance the effect of NCIT with fewer adverse effects, which has been applied to other solid tumors. The aim of this study was to evaluate the safety and efficacy of NCIT combined with node-sparing radiotherapy for clinical T3N+ locally advanced ESCC (CINSREC trial).

METHODS: Forty eligible patients with pathologically confirmed ESCC of clinical T3N + M0 stage were allocated to receive neoadjuvant immunotherapy (tislelizumab, q3w × 2 cycles) plus chemotherapy (nad-paclitaxel + carboplatin, q3w × 2 cycles) and node-sparing radiotherapy (41.4 Gy/23 times) treatment. The primary end point of this study is the pathological complete response rate. The secondary end points include major pathological response rate, adverse events, 2-year overall survival, and disease-free survival.

DISCUSSION: This is the first prospective clinical trial to investigate the safety and efficacy of NCIT combined with node-sparing radiotherapy for clinical T3N+ locally advanced ESCC. We hypothesize that this promising strategy can provide a better pCR rate and acceptable safety.

TRIAL REGISTRATION: ClinicalTrial.gov: NCT06965829.