Department of Surgery, Máxima MC, Veldhoven, PO BOX 7777, 5500 MB, Veldhoven, The Netherlands.
Department of Respiratory Medicine, Amsterdam University Medical Centre, University of Amsterdam, PO BOX 22700, 1100 DE, Amsterdam, The Netherlands.
Trials. 2021 Feb 27;22(1):168. doi: 10.1186/s13063-021-05127-6.
Invasive mediastinal nodal staging is recommended by guidelines in selected patients with resectable non-small cell lung cancer (NSCLC). Endosonography is recommended as initial staging technique, followed by confirmatory mediastinoscopy in case of negative N2 or N3 cytology after endosonography. Confirmatory mediastinoscopy however is under debate owing its limited additional diagnostic value, its associated morbidity and its delay in the start of lung cancer treatment. The MEDIASTrial examines whether confirmatory mediastinoscopy can be safely omitted after negative endosonography in mediastinal nodal staging of NSCLC. The present work is the proposed statistical analysis plan of the clinical consequences of omitting mediastinoscopy, which is submitted before closure of the MEDIASTrial and before knowledge of any results was done to enhance transparency of scientific behaviour.
The primary outcome measure of this non-inferiority trial will be unforeseen N2 disease resulting from lobe-specific mediastinal lymph node dissection. For non-inferiority, the upper limit of the 95% confidence interval of the unforeseen N2 rate in the group without mediastinoscopy should not exceed 14.3% in order to probably have no negative impact on survival. Since this is a non-inferiority trial, both an intention to treat (ITT) and a per protocol (PP) analyses will be done. The ITT and the PP analyses should both indicate non-inferiority before the diagnostic strategy omitting mediastinoscopy will be interpreted as non-inferior to the strategy with mediastinoscopy. Secondary outcome measures include 30-day major morbidity and mortality, the total number of days of hospital care, overall and disease free 2-year survival, generic and disease-specific health related quality of life and cost-effectiveness and cost-utility of staging strategies with and without mediastinoscopy.
The MEDIASTrial will determine if confirmatory mediastinoscopy can be omitted after tumour negative systematic endosonography in invasive mediastinal staging of patients with resectable NSCLC.
Netherlands Trial Register NL6344/NTR6528 . Registered on 2017 July 06.
在可切除的非小细胞肺癌（NSCLC）患者中，指南推荐进行侵袭性纵隔淋巴结分期。超声内镜检查被推荐作为初始分期技术，如果超声内镜检查后纵隔 N2 或 N3 细胞学检查为阴性，则建议进行确认性纵隔镜检查。然而，由于其有限的附加诊断价值、相关发病率以及对肺癌治疗开始时间的延迟，确认性纵隔镜检查仍存在争议。MEDIASTrial 研究旨在评估在 NSCLC 的纵隔淋巴结分期中，阴性超声内镜检查后是否可以安全地省略确认性纵隔镜检查。本研究是在 MEDIASTrial 关闭之前提交的，并且在获得任何结果之前进行了省略纵隔镜检查的临床后果的统计分析计划，以提高科学行为的透明度。
该非劣效性试验的主要结局指标将是由于肺叶特异性纵隔淋巴结清扫术导致的意外 N2 疾病。为了非劣效性，不进行纵隔镜检查组的意外 N2 率的 95%置信区间上限不应超过 14.3%，以可能对生存没有负面影响。由于这是一项非劣效性试验，将同时进行意向治疗（ITT）和方案（PP）分析。在诊断策略省略纵隔镜检查被解释为不劣于纵隔镜检查策略之前，ITT 和 PP 分析均应表明非劣效性。次要结局指标包括 30 天主要发病率和死亡率、总住院天数、总 2 年生存率、一般和疾病特异性健康相关生活质量以及有无纵隔镜检查的分期策略的成本效益和成本效用。
MEDIASTrial 将确定在可切除 NSCLC 患者的侵袭性纵隔分期中，肿瘤阴性系统性超声内镜检查后是否可以省略确认性纵隔镜检查。
荷兰试验注册 NL6344/NTR6528。于 2017 年 7 月 6 日注册。
