新辅助化疗或放化疗联合信迪利单抗对比新辅助放化疗治疗局部晚期食管鳞状细胞癌：一项多中心、随机、对照、III期试验的研究方案（SCIENCE研究）

Neoadjuvant chemotherapy or chemoradiotherapy plus sintilimab versus neoadjuvant chemoradiotherapy for locally advanced oesophageal squamous cell carcinoma: a study protocol of a multicentre, randomised, controlled, phase III trial (SCIENCE study).

作者信息

He Wenwu, Bai Hansong, Lv Jiahua, Tang Peng, Hu Tongchen, Zhou Haining, Xiao Wenguang, Peng Lin, Liu Guangyuan, Wang Kangning, Fang Qiang, Qi Yunxiang, Liang Long, Zheng Xiumei, Qing Haomiao, Chen Yungchang, Zhou Yehan, Xie Wenjing, Han Yongtao, Leng Xuefeng

机构信息

Department of Thoracic Surgery, Sichuan Cancer Hospital and Institute, Chengdu, Sichuan, China.

Department of Radiotherapy, Sichuan Cancer Hospital and Institute, Chengdu, Sichuan, China.

出版信息

BMJ Open. 2025 Jun 4;15(6):e095828. doi: 10.1136/bmjopen-2024-095828.

DOI:10.1136/bmjopen-2024-095828

PMID:40467307

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12142158/

Abstract

INTRODUCTION

Oesophageal squamous cell carcinoma (ESCC) is a globally challenging digestive tract malignancy with poor prognosis and limited treatment options. Early-stage ESCC is often asymptomatic, leading to a late-stage diagnosis in many cases. Neoadjuvant therapy combined with surgery is the standard treatment approach for locally advanced ESCC. In recent years, immunotherapy has shown significant efficacy in ESCC. However, various neoadjuvant treatment regimens, including chemotherapy, radiotherapy and immunotherapy, have produced inconsistent outcomes. This study aims to evaluate the efficacy and safety of neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) combined with immunotherapy compared with nCRT alone.

METHODS AND ANALYSIS

This is a prospective, multicentre, randomised, controlled phase III trial enrolling 420 patients with locally advanced thoracic ESCC. Patients will be randomly assigned (1:1:1) into three groups: (A) nCT plus sintilimab, (B) nCRT plus sintilimab or (C) nCRT alone. The primary endpoints are pathological complete response and event-free survival. Secondary endpoints include the objective remission rate, disease control rate, R0 resection rate, major pathological remission rate, disease-free survival, overall survival, patient quality of life and patient-reported outcomes. Data will be analysed using both the intention-to-treat and per-protocol approaches, with multiple imputation methods for handling missing data.

ETHICS AND DISSEMINATION

The study has been approved by the Ethics Committee for Medical Research and New Medical Technology of Sichuan Cancer Hospital (approval number: SCCHEC-02-2022-108). Written informed consent will be obtained from all participants. The findings will be disseminated through peer-reviewed journals and conference presentations.

TRIAL REGISTRATION NUMBER

NCT05244798.

摘要

引言

食管鳞状细胞癌（ESCC）是一种在全球范围内具有挑战性的消化道恶性肿瘤，预后较差且治疗选择有限。早期ESCC通常无症状，导致许多病例在晚期才被诊断出来。新辅助治疗联合手术是局部晚期ESCC的标准治疗方法。近年来，免疫疗法在ESCC中显示出显著疗效。然而，包括化疗、放疗和免疫疗法在内的各种新辅助治疗方案产生的结果并不一致。本研究旨在评估新辅助化疗（nCT）或新辅助放化疗（nCRT）联合免疫疗法与单纯nCRT相比的疗效和安全性。

方法与分析

这是一项前瞻性、多中心、随机对照III期试验，招募420例局部晚期胸段ESCC患者。患者将被随机分配（1:1:1）为三组：（A）nCT加信迪利单抗，（B）nCRT加信迪利单抗或（C）单纯nCRT。主要终点是病理完全缓解和无事件生存期。次要终点包括客观缓解率、疾病控制率、R0切除率、主要病理缓解率、无病生存期、总生存期、患者生活质量和患者报告的结果。将使用意向性分析和符合方案分析方法对数据进行分析，并采用多重填补方法处理缺失数据。