短程放疗联合化疗和 PD-1 抑制剂治疗低位早期直肠癌：一项单臂、多中心、前瞻性、Ⅱ期试验（TORCH-E）的研究方案。

Short-course radiotherapy combined with chemotherapy and PD-1 inhibitor in low-lying early rectal cancer: study protocol for a single-arm, multicentre, prospective, phase II trial (TORCH-E).

机构信息

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China.

出版信息

BMJ Open. 2023 Oct 6;13(10):e076048. doi: 10.1136/bmjopen-2023-076048.

DOI:10.1136/bmjopen-2023-076048

PMID:37802608

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10565143/

Abstract

INTRODUCTION

Current standard treatment for patients with early rectal cancer is radical surgical resection. Although radical surgery provides effective local tumour control, it also increases the mortality risk and considerable adverse effects, including bowel, bladder, sexual dysfunction and loss of anal function, especially in patients with low-lying rectal cancer. Recent studies have shown promising synergistic effects of the combination of programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors and radiotherapy in improving tumour regression. For patients who reach a clinical complete response (cCR) after neoadjuvant therapy, a 'Watch & Wait' (W&W) approach can be adopted to preserve anorectal function and improve quality of life. Thus, this study aims to explore the efficacy and safety of radiotherapy combined with chemotherapy and PD-1 antibody in patients with low early rectal cancer.

METHODS AND ANALYSIS

TORCH-E study is designed as a multicentre, prospective, phase II trial of short-course radiotherapy (SCRT) combined with chemotherapy and PD-1 inhibitor in patients with cT1-3bN0M0 low rectal cancer. The trial was initiated in December 2022 and is currently recruiting patients, with an anticipated completion of participant enrolment by June of the following year. The enrolled 34 patients will receive SCRT (25 Gy/5 Fx), followed by four cycles of capecitabine plus oxaliplatin chemotherapy and PD-1 antibody (toripalimab) and finally receive surgery or the W&W strategy. The primary endpoint is the complete response (CR) rate, that is, the rate of pathological complete response (pCR) plus cCR. The secondary endpoints include organ preservation rate, 3-year local recurrence-free survival rate, 3-year disease-free survival rate, 3-year overall survival rate, grade 3-4 adverse effects rate and patients' quality of life.

ETHICS AND DISSEMINATION

This trial has been approved by the Ethics Committee of Fudan University Shanghai Cancer Center. Trial results will be disseminated via peer-reviewed journals and conference presentations.

TRIAL REGISTRATION NUMBER

NCT05555888 (ClinicalTrials.gov).

摘要

简介

目前，早期直肠癌患者的标准治疗方法是根治性手术切除。虽然根治性手术能有效控制局部肿瘤，但也会增加死亡率和严重的不良反应，包括肠、膀胱、性功能障碍和肛门功能丧失，特别是低位直肠癌患者。最近的研究表明，程序性细胞死亡蛋白-1（PD-1）/程序性死亡配体 1（PD-L1）抑制剂与放疗联合使用可提高肿瘤消退的协同作用。对于新辅助治疗后达到临床完全缓解（cCR）的患者，可以采用“观察等待”（W&W）方法来保留肛肠功能并提高生活质量。因此，本研究旨在探讨短程放疗（SCRT）联合化疗和 PD-1 抗体在低位早期直肠癌患者中的疗效和安全性。

方法和分析

TORCH-E 研究是一项多中心、前瞻性、Ⅱ期研究，旨在评估 SCRT 联合化疗和 PD-1 抑制剂在 cT1-3bN0M0 低位直肠癌患者中的疗效和安全性。该试验于 2022 年 12 月启动，目前正在招募患者，预计次年 6 月完成入组。入组的 34 例患者将接受 SCRT（25 Gy/5 Fx），随后接受四个周期的卡培他滨联合奥沙利铂化疗和 PD-1 抗体（替雷利珠单抗），最后接受手术或 W&W 策略。主要终点是完全缓解（CR）率，即病理完全缓解（pCR）加 cCR 的比率。次要终点包括器官保留率、3 年局部无复发生存率、3 年无病生存率、3 年总生存率、3-4 级不良事件发生率和患者的生活质量。