The Efficacy and Safety of Short-Course Radiotherapy Combined with Intracavitary Brachytherapy Followed by Pucotenlimab, Bevacizumab, Oxaliplatin, and Trifluridine/Tipiracil (TAS-102) for Total Neoadjuvant Therapy of Microsatellite Stable (MSS) Locally Advanced Low Rectal Adenocarcinoma: an Prospective, Single Arm Clinical Trial （SCRIPBOT Trial）

A Prospective Single-Arm Study of Short-Course Radiotherapy Followed by PD-1 Monoclonal Antibody, Bevacizumab, Oxaliplatin, and Trifluridine/Tipiracil for Total Neoadjuvant Therapy in MSS Locally Advanced Low Rectal Cancer. This is a Non-Randomized, Single Group Assignment, Open Label, Phase: Phase II study. The Primary Objective is to assess the organ preservation rate (clinical complete response, cCR) after total neoadjuvant therapy. Secondary Objectives are Tumor regression grade (TRG), 3-year overall survival (OS) and disease-free survival (DFS), and Safety and quality of life (QoL). In this study, the investigators will perform the multi-dimensional omics study to explore the tumors microenvironments, explore the characteristics of the treatment benefit population, and try to construct an efficacy prediction model to screen the treatment benefit population early and implement precise treatment.

开始日期2025-04-01

申办/合作机构

Sir Run Run Shaw Hospital

NCT06843434

/ Recruiting临床2期IIT

A Phase II Study of Neoadjuvant Botensilimab and Balstilimab Immunotherapy for Mismatch Repair Proficient Rectal Adenocarcinoma

The purpose of this study is to find out whether the combination of botensilimab and balstilimab (BOT/BAL) is a safe and effective treatment that causes few or mild side effects for people with mismatch repair proficient (MMRp)/microsatellite stable (MSS) locally advanced rectal adenocarcinoma. The investigators will also find out whether BOT/BAL is an effective treatment when given in combination with standard chemotherapy.

开始日期2025-02-20

申办/合作机构

Memorial Sloan Kettering Cancer Center

[+1]

NCT06281405

/ Not yet recruiting临床2期IIT

A Prospective Randomized Phase II Trial of CAPOX and PD-1 Antibody Combined With or Without Radiotherapy for Microsatellite Stable Locally Advanced Rectal Cancer (TORCH-iTNT)

TORCH-iTNT is a prospective, multicentre, randomized phase II trial. 198 LARC (T3-4/N+M0, distance from anal verge ≤12cm) patients will be treated with total neoadjuvant therapy (TNT) and assigned to Group A and Group B (1:1). Group A receives 6 cycles of Toripalimab combined with CAPOX (ToriCAPOX). Group B receives SCRT (25Gy/5Fx) followed by 6 cycles of ToriCAPOX. TME surgery is scheduled after TNT while a watch and wait (W&W) option can be applied to patients achieving clinical complete response (cCR). The primary endpoint is complete response (CR, pathological complete response [pCR] plus cCR) rate. The secondary endpoints include the grade 3-4 acute adverse effects (AE) rate, anal preservation rate, 3-year DFS rate, etc.

开始日期2024-03-01

申办/合作机构

复旦大学

100 项与微卫星稳定型直肠癌相关的临床结果

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100 项与微卫星稳定型直肠癌相关的转化医学

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0 项与微卫星稳定型直肠癌相关的专利（医药）

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项与微卫星稳定型直肠癌相关的文献（医药）

2024-04-25·Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery

[Neoadjuvant strategy for locally advanced colorectal cancer based organ preservation].

Review

作者: Hu, H B ; Deng, Y H ; Zhang, J W ; Wu, Z H ; Cheng, Y

局部进展期结直肠癌新辅助治疗在过去20年已取得较大进步，但仍存在不良反应、器官功能障碍及远期转移控制不理想等局限性。而近年来，随着手术技术的提高和肿瘤分子分型研究的进一步发展，如何进一步提高局部控制率，减少远处转移率，甚至根据临床缓解情况免除手术、保留器官是当前患者的需求所在和研究目标。随着分子分型研究的进展，结直肠癌根据微卫星状态和错配修复基因不同，有不同的治疗策略。对于微卫星不稳定局部进展期结直肠癌而言，与传统放化疗相比，免疫检查点抑制剂治疗在提高临床完全缓解率的同时，还可明显降低不良反应发生率、改善器官功能。对于微卫星稳定型局部进展期结肠癌而言，新辅助治疗目前仍处于探索阶段，标准治疗模式仍是手术结合围手术期化疗。对于微卫星稳定型局部进展期直肠癌，一方面通过加强新辅助治疗提高完全缓解率，提高器官保留率，另一方面通过选择性去放疗，保存器官功能，提高生活质量。本文针对基于器官保留策略的局部进展期结直肠癌新辅助治疗策略进行综述。.

2023-09-13·BMJ open

Neoadjuvant chemoradiation therapy combined with immunotherapy for microsatellite stable ultra-low rectal cancer (CHOICE II): study protocol of a multicentre prospective randomised clinical trial.

Article

作者: Gao, Xianhua ; Peng, Zhiying ; Jia, Hang ; Gong, Haifeng ; Yu, Guanyu ; Wen, Rongbo ; Zhang, Wei ; Yu, Yue ; Lou, Zheng ; Zhang, Tianshuai ; Fan, Hao ; Zhou, Leqi ; Pan, Anfu ; Zhu, Xiaoming

INTRODUCTIONNeoadjuvant chemoradiotherapy (nCRT) could bring tumour shrinking and downstaging and increase the probability of organ preservation for patients with low rectal cancer. But for ultra-low rectal cancer, there is little possibility for organ preservation. Immunotherapy has been shown to have significant survival benefits in microsatellite instability-high patients but poor response in microsatellite stable (MSS) patients. Studies have demonstrated that radiotherapy and immunotherapy have synergistic effects in cancer treatment. There is no existing evidence about the clinical efficacy of immunotherapy combined with nCRT for patients with MSS ultra-low rectal cancer.METHOD AND ANALYSISThis trial is an open-labelled multicentre prospective randomised controlled trial (NCT05215379) with two parallel groups and allocation ratio 1:1 (nCRT+immunotherapy vs nCRT group). Eligible participants will be aged 18-75 years, with a desire for anus preservation, confirmed cT_1-3aN_0-1M₀ rectal adenocarcinoma, confirmed MSS type, inferior margin of ≤5 cm from the anal verge. The primary endpoint of this trial is complete clinical response (cCR) rate. Immunotherapy is added after 1 week of chemoradiotherapy for two cycles, and then the patients will be administered two cycles of immunotherapy and CAPOX. The evaluations will be carried out after the completion of the whole neoadjuvant therapy. We expect the programme to improve the cCR rate and the quality of life for patients with ultra-low rectal cancer.ETHICS AND DISSEMINATIONThis trial was approved by the Ethics committee of Changhai Hospital and other medical centres (Grant number:CHEC2022-118). The results of this study will provide further insight into the clinical efficacy of immunotherapy in combination with nCRT in patients with MSS ultra-low rectal cancer.TRIAL REGISTRATION NUMBERNCT05215379.

2023-04-03·Expert Review of Anticancer Therapy

Neutrophil-to-lymphocyte ratio predicts survival of patients with rectal cancer receiving neo-adjuvant chemoradiation followed by radical resection: a meta-analysis

Review

作者: Colloca, Giuseppe ; Venturino, Antonella ; Guarneri, Domenico

BACKGROUNDNeutrophil-to-lymphocyte ratio is suggested as a prognostic and predictive factor for patients with rectal cancer. The purpose of the current meta-analysis is to evaluate the relationship between neutrophil-lymphocyte ratio (NLR) and the outcome of patients, with rectal cancer receiving chemoradiation and surgery.METHODSA systematic review on two databases and a selection of studies were done. Thereafter, two meta-analyses were performed, evaluating the relationship of baseline NLR with overall survival (OS) and disease-free survival (DFS).RESULTSThirty-one retrospective studies were selected. Twenty-six studies have documented a significant relationship of NLR to OS (HR 2.05, CI 1.66-2.53), whereas 23 studies have reported a weaker but significant relationship of NLR to DFS (HR 1.78, CI 1.49-2.12). Among the moderator variables, a possible effect for age and sex on the relationship of NLR with DFS is suggested.CONCLUSIONSBaseline NLR >3 is a simple and reproducible prognostic factor, with a more consistent effect in the elderly. It could be a reliable variable to support clinicians in defining personalized treatment strategies, even though a standardization of the cutoff and a better characterization among microsatellite unstable rectal tumors are necessary.

项与微卫星稳定型直肠癌相关的新闻（医药）

2024-09-09

·思路迪医药 3D Medicines

戴胜教授：新辅助短程放疗序贯恩沃利单抗联合CAPEOX能够给MSS局部晚期直肠癌带来革命性的pCR结果

摘要自从免疫治疗被批准用于晚期错配修复缺失（dMMR）/高度微卫星不稳定（MSI-H）的实体瘤治疗之后。免疫治疗就从晚期后线治疗到早期的新辅助治疗均展现了出色的疗效。然而，大多数直肠癌患者为微卫星稳定性（MSS），对于免疫治疗无应答。这就导致MSS型局部晚期直肠癌的新辅助治疗一直采取的是传统的治疗手段，疗效乏善可陈。为了破解这个困境，浙江大学邵逸夫医院戴胜教授团队开展了针对MSS型局部晚期直肠癌的PRECAM研究，旨在明确短程放疗序贯恩沃利单抗联合CAPEOX的新辅助治疗方案的疗效。该研究全文近期正式发表于《International journal of surgery》（IF 12.5）杂志。在此，我们特邀请戴胜教授针对该研究进行解读，希望能够给各位同道带来启发和借鉴。戴胜教授采访视频 MSS/pMMR局部晚期直肠癌的新辅助治疗挑战重重如今，局部晚期直肠癌的主要治疗模式包括：长程同步放化疗（CRT）或短程放疗（SRT）序贯全直肠系统膜切除术（TME）。随着新药的不断研发，局部晚期直肠癌的治疗格局发生了改变，出现了同步放化疗序贯免疫、诱导化疗、巩固治疗等新模式。截至目前，对于局部晚期直肠癌新辅助治疗最大的挑战是单纯的新辅助同步放化疗给局部晚期直肠癌患者所带来的病理完全缓解率（pCR）和客观缓解率（ORR）仍差强人意。其中，该治疗模式所带给患者的pCR仅有20%左右，这意味着80%的患者通过单纯的新辅助同步放化疗治疗之后，仍存在肿瘤残留，这给患者的预后和生存带来了不利的影响。因为在既往的研究就进行过达到pCR患者和未达到pCR患者的远期总生存（OS）的比较，发现两者存在着差异。因此，如何通过不同治疗手段的组合，以提升局部晚期直肠癌患者治疗应答率成为大家关注的话题。除此之外，局部晚期直肠癌新辅助治疗的挑战，还包括：其一，由于新辅助的放疗、化疗对于患者术后的功能仍然会有一定的影响，因此，如何能让更多的局部晚期直肠癌患者免于手术，从而达到保肛的目的，亦是目前的治疗挑战之一；其二对于高度微卫星不稳定（MSI-H）的直肠癌，单用免疫检查点抑制剂可以让患者获得不错的疗效，然而，90%以上的直肠癌患者均为微卫星稳定型（MSS）直肠癌。MSS型直肠癌难以从免疫单药治疗中获益，因此，通常被称为“冷肿瘤“。如何提升此类患者的新辅助免疫治疗疗效，亦是临床治疗的一个巨大挑战。短程放疗序贯后续治疗更具性价比戴胜教授在直肠癌的新辅助放化疗中，有长程和短程两种放疗模式。相比标准的长程同步放化疗，短程放疗序贯化疗的优势主要包括：其一，短程放疗治疗周期较短。短程放疗采取的是每天进行1次5Gy的照射，共5次。短周期极大的提升了患者治疗的便利性，也减轻了患者的心理负担；其二，短程放疗序贯化疗的局部并发症相比标准长程同步放化疗更少；其三，短程放疗给患者带来的经济负担也更轻。短程放化疗联合免疫更能给局部晚期直肠癌带来pCR提升戴胜教授我们在进行PRECAM研究设计时，也参考了国内外专家学者的临床研究，例如：STELLAR研究、TORCH研究等。总体而言，在研的新辅助免疫联合治疗的治疗模式，一共有两大类：一类是长程同步放化疗联合免疫，另一类是短程放化疗联合免疫。从现有的研究结果中可以看到，似乎短程放化疗联合免疫能够给局部晚期直肠癌患者带来更高的pCR。因此，在PRECAM研究中，我们采取了短程放化疗联合免疫治疗。彼时，恰逢恩沃利单抗上市，所以，我们发起了短程放化疗联合恩沃利单抗用于局部晚期直肠癌新辅助治疗的临床研究。从PRECAM研究结果可知，短程放化疗联合恩沃利单抗能够给局部晚期直肠癌患者带来不错的疗效，并且，未给患者带来严重的毒副反应。短程放化疗联合恩沃利单抗可以给MSS局部晚期直肠癌带来更高器官保留率戴胜教授根据PRECAM研究初步结果可知，短程放化疗联合恩沃利单抗给MSS局部晚期直肠癌患者带来了高达62.5%的pCR，即32例入组的患者中，有20例患者达到了pCR。这意味着，对于MSS局部晚期直肠癌可以通过新辅助短程放化疗联合免疫治疗达到更高的pCR，以实现更高的器官保留率，从而获得更高的生活质量。高器官保留率和高生活质量是局部晚期直肠癌，或者说低位直肠癌治疗努力的方向。 MSS型局部晚期直肠癌的新辅助治疗研究方兴未艾，期待进行更多探索戴胜教授 MSS型局部晚期直肠癌，或者说低位直肠癌未来治疗的发展方向，主要包括：其一，在保留功能的前提下，尽量追求更高的pCR，甚至是免手术、保器官的比例，从而获得更长的生存时间；其二，希望能够有更多的新药，纳入MSS型局部晚期直肠癌的新辅助治疗探索之中，如此有利于发现更优的治疗模式，实现更为个性化的新辅助治疗；其三，希望能够有更多的多中心的随机对照研究，证实MSS型局部晚期直肠癌患者可以从短程放化疗联合免疫的新辅助治疗中获益。如今，在PRECAM研究结果揭晓之后，我们团队也进行了多中心的临床研究，目前该研究的初步结果令人鼓舞；其四，希望能够开展更多的机制性研究，帮助发掘MSS型局部晚期直肠癌免疫治疗的生物标志物和靶点，这有利于帮助我们筛选优势治疗人群，从而为患者追求更大程度的获益。仅供医疗卫生专业人士阅读作者：MED24；审校：汪珊珊、高加索、张莉娟颜爱竹；

免疫疗法放射疗法临床结果