Camrelizumab and Low-Dose Radiotherapy With Concurrent Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma (Nice-Rt Study): Preliminary Results

Abstract Background Combining immunotherapy with chemoradiotherapy offers a promising neoadjuvant approach for locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, large irradiation fields required for extensive lymph node involvement may reduce treatment tolerance. Recent studies suggest that low-dose radiotherapy (LDRT) can enhance the tumor microenvironment and improve the efficacy of immunotherapy. The NICE-RT study utilized LDRT to distant lymph nodes, aiming to reduce side effects while optimizing treatment outcomes. Methods The NICE-RT study was a prospective, phase I trial enrolling patients aged 18–75 with treatment-naïve LA-ESCC and at least one positive lymph node ≥5 cm from the primary tumor. Patients received radiotherapy, chemotherapy (nab-paclitaxel 80 mg/m2, carboplatin AUC = 2 qw), and immunotherapy (Camrelizumab 200 mg/m2 q3w). Target volume of radiotherapy included the primary tumor and nearby lymph nodes (standard-dose area, 41.4Gy/23Fx), and distant lymph nodes (low-dose area, 2Gy/4Fx before each immunotherapy). Surgery occurred 4–8 weeks later, followed by adjuvant immunotherapy (Camrelizumab 200 mg/m2 q3w, up to one year). The primary endpoints were safety and pCR rate. Results From December 2022 to April 2024, 11 patients were enrolled. Six completed all neoadjuvant treatments, while 5 discontinued chemotherapy after 4 weeks due to intolerance. Five patients experienced grade 3 adverse events, with no grade 4 or 5 events. One patient with a clinical complete response declined surgery. Among the 10 who had surgery, 60% achieved pCR in the primary tumor, 40% reached ypN0, with an overall pCR of 20% and MPR of 80%. LDRT-treated distant lymph nodes were pathologically negative in 70% of patients. Of the 3 patients with positive nodes, 2 also had positives in the standard-dose area. Conclusion This study designed a neoadjuvant treatment combining LDRT, immunotherapy and CCRT for LA-ESCC. Preliminary results suggest it is safe and effective, with long-term survival benefits requiring further follow-up.