Upfront surgery versus induction chemotherapy followed by surgery in oral cavity squamous cell cancers with advanced nodal disease (SurVIC Trial): a phase 3 multicentre randomised controlled trial.

IF 2.3 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL
Dharma Ram Poonia, Amit Sehrawat, Jeewan Ram Vishnoi, Nivedita Sharma, Parmod Kumar, Bharti Devnani, Aparna Warriere, Akanksha Solanki, Puneet Pareek, Divya Aggarwal, Taruna Yadav, Prem Prakash Sharma, Ashita Gadwal, Anushka Goyal, Poonam Elhence, Pushpinder Khera, Ashish Jakhetiya, Pnahindra Swaim, Dillip Muduly, Rohit Mahajan, Pankaj Garg, Vijay Kumar, Madhabananda Kar, Sanjeev Misra
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引用次数: 0

Abstract

Introduction: Most oral cancers in India present in advanced stages and tend to have poor oncological outcomes. Chemotherapy has been associated with improved oncological outcomes in various cancers, but its role in oral cancer is still not well-defined in curative settings beyond radiosensitisation. Despite an excellent response rate, neoadjuvant chemotherapy trials have failed to show an oncological advantage. Earlier studies were limited by their heterogeneous patient population, including all head and neck subsites, and included both inoperable cancer and early-stage operable cases. Due to such patient selection, the intended results were never met. Patients with biologically aggressive diseases (advanced nodal disease) may derive greater benefit from induction chemotherapy (ICT). Therefore, we aim to determine the oncological advantage of adding ICT to oral squamous cell cancer with advanced nodal disease (N2-N3).

Methods and analysis: The study is an open-label, multicentre, randomised controlled trial, with an allocation ratio of 1:1, being conducted at seven leading cancer centres in India. The primary objective is to compare survival outcomes with and without ICT before surgery in patients with oral squamous cell carcinoma (OSCC) and advanced nodal disease, specifically focusing on 2-year disease-free survival (DFS). Secondary objectives include assessing overall survival (OS), clinical and pathological response rates, treatment compliance, treatment completion rates, adverse events, treatment-related toxicity (using Common Terminology Criteria for Adverse Events, V.5.0), quality of life (measured with Functional Assessment of Cancer Therapy-General and Functional Assessment of Cancer Therapy-Head and Neck) and postoperative complications (using the modified Clavien-Dindo classification).The study population consists of patients with operable OSCC and advanced nodal disease (N2-N3), adequate organ function, aged 18-65 years and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2. The treatment arms are the standard arm Surgery arm (SURG), which involves surgery followed by adjuvant radiotherapy with or without concurrent chemotherapy, and the experimental arm (ICT), in which patients will receive two cycles of ICT using either cisplatin, docetaxel and 5-fluorouracil or cisplatin, docetaxel and capecitabine, followed by surgery and adjuvant radiotherapy with or without concurrent chemotherapy. The sample size was calculated to detect an HR of 0.67 with 80% power. A total of 184 events are required, and with an accrual rate of 15 patients per month, 300 patients will be recruited. DFS analysis will occur 32 months after the trial begins, and follow-up will continue for 5 years. OS analysis will be conducted when 184 deaths are observed. Taking 10% of the withdrawal of consent, a total of 346 patients need to be included.

Ethics and dissemination: This trial aims to establish the potential superiority of ICT or definitively determine its futility in OSCC with advanced nodal disease. A positive outcome could provide practice-changing data, particularly for Indian patients, whereas negative results could halt the use of ICT in this setting, directing research efforts towards more effective treatment strategies.

Trial registration number: CTRI/2024/03/064586; NCT06737822; Institutional Ethics Committee (IEC) number: AIIMS/IEC/2023/4622 (lead site).

前期手术与诱导化疗后手术治疗口腔鳞状细胞癌伴晚期淋巴结疾病(SurVIC试验):一项3期多中心随机对照试验
简介:大多数口腔癌在印度出现在晚期,往往有较差的肿瘤预后。化疗与各种癌症的肿瘤预后改善有关,但其在口腔癌中的作用在放疗增敏以外的治疗环境中仍未明确定义。尽管反应率很高,但新辅助化疗试验未能显示出肿瘤学上的优势。早期的研究受限于其异质性患者人群,包括所有头颈部亚位,并且包括不可手术的癌症和早期可手术的病例。由于这样的患者选择,从未达到预期的结果。生物侵袭性疾病(晚期淋巴结疾病)患者可能从诱导化疗(ICT)中获得更大的益处。因此,我们的目标是确定在伴有晚期淋巴结疾病(N2-N3)的口腔鳞状细胞癌中加入ICT的肿瘤学优势。方法与分析:该研究是一项开放标签、多中心、随机对照试验,分配比例为1:1,在印度7家领先的癌症中心进行。主要目的是比较口腔鳞状细胞癌(OSCC)和晚期淋巴结疾病患者术前使用和不使用ICT的生存结果,特别关注2年无病生存(DFS)。次要目标包括评估总生存期(OS)、临床和病理反应率、治疗依从性、治疗完成率、不良事件、治疗相关毒性(使用不良事件通用术语标准V.5.0)、生活质量(使用癌症治疗功能评估和癌症治疗-头颈部功能评估)和术后并发症(使用改进的Clavien-Dindo分类)。研究人群包括可手术的OSCC和晚期淋巴结疾病(N2-N3),器官功能充足,年龄18-65岁,东部肿瘤合作组(ECOG)表现状态(PS)为0-2的患者。治疗组为标准组:手术组(SURG),包括手术后辅助放疗伴或不伴化疗;实验组(ICT),患者将接受两个ICT周期,使用顺铂、多西紫杉醇和5-氟尿嘧啶或顺铂、多西紫杉醇和卡培他滨,随后手术和辅助放疗伴或不伴化疗。计算样本量,在80%的功率下检测到0.67的HR。总共需要184个事件,按每月15例患者的累积率,将招募300名患者。DFS分析将在试验开始32个月后进行,随访5年。观察到184例死亡后进行OS分析。以撤回同意的10%为例,总共需要纳入346例患者。伦理和传播:本试验旨在确定ICT的潜在优势或明确其在伴有晚期淋巴结疾病的OSCC中的无用性。积极的结果可以提供改变实践的数据,特别是对印度患者而言,而消极的结果可能会阻止在这种情况下使用信息通信技术,从而将研究工作引向更有效的治疗策略。试验注册号:CTRI/2024/03/064586;NCT06737822;机构伦理委员会(IEC)编号:AIIMS/IEC/2023/4622(领导站点)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
BMJ Open
BMJ Open MEDICINE, GENERAL & INTERNAL-
CiteScore
4.40
自引率
3.40%
发文量
4510
审稿时长
2-3 weeks
期刊介绍: BMJ Open is an online, open access journal, dedicated to publishing medical research from all disciplines and therapeutic areas. The journal publishes all research study types, from study protocols to phase I trials to meta-analyses, including small or specialist studies. Publishing procedures are built around fully open peer review and continuous publication, publishing research online as soon as the article is ready.
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