Huang Shujie, Yu Hongfan, Li Zijie, Tang Yong, Luo Liling, Wu Junhan, Li Xianglin, Shi Qiuling, Xie Songxi, Qiao Guibin
Department of Thoracic Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
State Key Laboratory of Biomedical Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, China.
J Thorac Dis. 2024 Jul 30;16(7):4719-4726. doi: 10.21037/jtd-24-274. Epub 2024 Jul 8.
Radiation-associated adverse events (ADEs) in patients with esophageal squamous cell carcinoma (ESCC) remain a problem. Recent research has focused on reducing radiation-associated ADEs while maintaining efficacy, particularly through the combination of immune checkpoint inhibitors (ICIs) with chemotherapy. Patient-reported outcomes (PROs) have also emerged as reliable measures for monitoring treatment effectiveness and quality of life (QoL). This trial aims to investigate the feasibility of using patient-reported dysphagia relief to assess pathological response following neoadjuvant immunochemotherapy, as well as the safety and efficacy of neoadjuvant immunochemotherapy combined with short-course radiotherapy for patients with locally advanced ESCC.
This study is designed as a prospective, single-arm, phase II study. Eligible ESCC patients will be invited to participate in this study. All participants will receive paclitaxel (albumin-bound) (260 mg/m, day 1), carboplatin [area under the curve (AUC) 5; 5 mg/mL/min, day 1] or cisplatin [60 mg/m, intravenous drip (ivdrip), day 1], and tislelizumab (200 mg, day 1) in the first treatment cycle. Early remission of dysphagia is defined as relief greater than 70% according to the dysphagia symptom score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire esophagus-specific questionnaire (EORTC OES-18). The early remission group (Group A) will continue with the same regimen for two treatment cycles. The latent remission group will continue with one treatment cycle followed by neoadjuvant immunochemotherapy combined with short-course radiotherapy (radiotherapy 30 Gy/10 F). The primary objective is the pathological complete response (pCR) rate. Research data collection, storage, and management will be conducted in a web-based Real-World-Data Management Platform (RWDMP). Longitudinal data will be conducted by a linear mixed model with treatment effects, baseline factors influencing the endpoint as fixed effects, and the center as a random effect.
This study will provide evidence for using patient-reported dysphagia relief to evaluate pathological response after neoadjuvant immunochemotherapy in early remission (Group A) and to evaluate the safety and efficacy of combining immunochemotherapy with short-course radiotherapy in latent remission (Group B) among patients with ESCC. Limitations include the single-arm study design, small sample size, and the need for further exploration of the specific mechanism and mediator of early dysphagia remission's effect on immunochemotherapy effectiveness.
This study is registered at Clinicaltrials.gov (NCT05596890).
食管鳞状细胞癌（ESCC）患者中与放疗相关的不良事件（ADEs）仍是一个问题。最近的研究集中在减少与放疗相关的ADEs同时维持疗效，特别是通过免疫检查点抑制剂（ICIs）与化疗联合使用。患者报告结局（PROs）也已成为监测治疗效果和生活质量（QoL）的可靠指标。本试验旨在研究使用患者报告的吞咽困难缓解情况来评估新辅助免疫化疗后的病理反应的可行性，以及新辅助免疫化疗联合短程放疗治疗局部晚期ESCC患者的安全性和疗效。
本研究设计为一项前瞻性、单臂、II期研究。符合条件的ESCC患者将被邀请参加本研究。所有参与者在第一个治疗周期将接受紫杉醇（白蛋白结合型）（260mg/m²，第1天）、卡铂[曲线下面积（AUC）5；5mg/mL/min，第1天]或顺铂[60mg/m²，静脉滴注（ivdrip），第1天]，以及替雷利珠单抗（200mg，第1天）。吞咽困难的早期缓解定义为根据欧洲癌症研究与治疗组织生活质量问卷食管特异性问卷（EORTC OES-18）中的吞咽困难症状评分缓解大于70%。早期缓解组（A组）将继续使用相同方案进行两个治疗周期。潜在缓解组将继续进行一个治疗周期，然后进行新辅助免疫化疗联合短程放疗（放疗30Gy/10F）。主要目标是病理完全缓解（pCR）率。研究数据的收集、存储和管理将在基于网络的真实世界数据管理平台（RWDMP）中进行。纵向数据将通过线性混合模型进行分析，将治疗效果、影响终点的基线因素作为固定效应，将中心作为随机效应。
本研究将为使用患者报告的吞咽困难缓解情况来评估早期缓解（A组）新辅助免疫化疗后的病理反应，以及评估潜在缓解（B组）ESCC患者免疫化疗联合短程放疗的安全性和疗效提供证据。局限性包括单臂研究设计、样本量小，以及需要进一步探索早期吞咽困难缓解对免疫化疗效果影响的具体机制和介质。
本研究已在Clinicaltrials.gov注册（NCT05596890）。
