Systematic mediastinal lymph node staging by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) improves accuracy of staging in patients with early-stage non-small-cell lung cancer (NSCLC). However, patients with locally advanced NSCLC commonly undergo only selective lymph node sampling. This study aimed to determine the proportion of patients with locally advanced NSCLC in whom systematic endoscopic mediastinal staging identified PET-occult lymph node metastases, and to describe the consequences of PET-occult disease on radiotherapy planning. This prospective, international, multicentre, single-arm, international study was conducted at seven tertiary lung cancer centres in four countries (Australia, Canada, the Netherlands, and the USA). Patients aged 18 years or older with suspected or known locally advanced NSCLC underwent systematic endoscopic mediastinal lymph node staging before combination chemoradiotherapy or high-dose palliative radiotherapy. The primary endpoint was the proportion of participants with PET-occult mediastinal lymph node metastases shown following systematic endoscopic staging. The study was prospectively registered with Australian New Zealand Clinical Trials Registry, ACTRN12617000333314. From Jan 30, 2018, to March 23, 2022, 155 patients underwent systematic endoscopic mediastinal lymph node staging and were eligible for analysis. 58 (37%) of patients were female and 97 (63%) were male. Discrepancy in extent of mediastinal disease identified by PET and EBUS-TBNA was observed in 57 (37% [95% CI 29–44]) patients. PET-occult lymph node metastases were identified in 18 (12% [7–17]) participants, including 16 (13% [7–19]) of 123 participants with clinical stage IIIA or cN2 NSCLC. Contralateral PET-occult N3 disease was identified in nine (7% [2–12]) of 128 participants staged cN0, cN1, or cN2. Identification of PET-occult disease resulted in clinically significant changes to treatment in all 18 patients. In silico dosimetry studies showed the median volume of PET-occult lymph nodes receiving the prescription dose of 60 Gy was only 10·1% (IQR 0·1–52·3). No serious adverse events following endoscopic staging were reported. Our findings suggests that systematic endoscopic mediastinal staging in patients with locally advanced or unresectable NSCLC is more accurate than PET alone in defining extent of mediastinal involvement. Standard guideline-recommended PET-based radiotherapy planning results in suboptimal tumour coverage. Our findings indicate that systematic endoscopic staging should be routinely performed in patients with locally advanced NSCLC being considered for radiotherapy to accurately inform radiation planning and treatment decision making in patients with locally advanced NSCLC. None.

中文翻译：

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纵隔系统内镜分期指导局部晚期非小细胞肺癌患者的放疗计划 (SEISMIC)：一项国际、多中心、单组临床试验


通过支气管内超声引导下经支气管针吸活检 (EBUS-TBNA) 进行系统性纵隔淋巴结分期可提高早期非小细胞肺癌 (NSCLC) 患者分期的准确性。然而，局部晚期 NSCLC 患者通常仅进行选择性淋巴结取样。本研究旨在确定系统内镜纵隔分期发现 PET 隐匿性淋巴结转移的局部晚期 NSCLC 患者的比例，并描述 PET 隐匿性疾病对放疗计划的影响。这项前瞻性、国际性、多中心、单组、国际研究是在四个国家（澳大利亚、加拿大、荷兰和美国）的七个三级肺癌中心进行的。 18 岁或以上疑似或已知局部晚期 NSCLC 患者在联合放化疗或高剂量姑息性放疗之前接受系统的内镜纵隔淋巴结分期。主要终点是系统内镜分期后显示 PET 隐匿性纵隔淋巴结转移的参与者比例。该研究已在澳大利亚新西兰临床试验注册中心前瞻性注册，ACTRN12617000333314。从2018年1月30日到2022年3月23日，155名患者接受了系统的内镜纵隔淋巴结分期，并且符合分析资格。 58 名患者（37%）为女性，97 名患者（63%）为男性。在 57 名（37% [95% CI 29-44]）患者中观察到 PET 和 EBUS-TBNA 识别的纵隔疾病程度存在差异。 18 名 (12% [7–17]) 参与者中发现 PET 隐匿性淋巴结转移，其中 123 名临床 IIIA 期或 cN2 NSCLC 参与者中有 16 名 (13% [7–19])。 128 名分期为 cN0、cN1 或 cN2 的参与者中，有 9 名（7% [2-12]）发现对侧 PET 隐匿性 N3 疾病。 PET 隐匿性疾病的识别导致所有 18 名患者的治疗发生了临床上显着的变化。计算机剂量测定研究表明，接受 60 Gy 处方剂量的 PET 隐匿淋巴结体积中值仅为 10·1% (IQR 0·1–52·3)。内镜分期后未报告严重不良事件。我们的研究结果表明，对于局部晚期或不可切除的 NSCLC 患者，系统内镜纵隔分期在确定纵隔受累程度方面比单独 PET 更准确。标准指南推荐的基于 PET 的放射治疗计划会导致肿瘤覆盖范围不理想。我们的研究结果表明，对于考虑接受放射治疗的局部晚期 NSCLC 患者，应常规进行系统内镜分期，以便准确地为局部晚期 NSCLC 患者的放射计划和治疗决策提供信息。没有任何。