Rimner Andreas, Dejonckheere Cas Stefaan, Sahlmann Jörg, Barth Simeon Ari, Schimek-Jasch Tanja, Adebahr Sonja, Hecht Markus, Waller Cornelius F, Schmid Severin, Stolz Daiana, Miederer Matthias, Brose Alexander, Binder Harald, König Jochem, Grosu Anca-Ligia, Nestle Ursula, Gkika Eleni
Department of Radiation Oncology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Department of Radiation Oncology, University Hospital Bonn, Bonn, Germany.
Int J Radiat Oncol Biol Phys. 2025 Aug 1;122(5):1217-1226. doi: 10.1016/j.ijrobp.2025.02.041. Epub 2025 Mar 5.
To evaluate the role of different invasive and noninvasive mediastinal staging methods in patients with locally advanced non-small cell lung cancer treated with definitive chemoradiation therapy in the prospective PET-Plan trial (ARO-2009-09; NCT00697333) and to evaluate the impact of endobronchial ultrasound-guided transbronchial needle aspiration and mediastinoscopy on target volume definition.
Patients treated per protocol (n = 172), all receiving isotoxically dose-escalated chemoradiation therapy, were included in this unplanned secondary analysis. Radiation treatment planning was based on an F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) targeting all CT-positive lymph nodes (ie, short-axis diameter > 10 mm), even if PET-negative, plus elective nodal irradiation (arm A) or targeting only PET-positive nodes (arm B). The concordance rate between different staging modalities and their impact on target volume delineation was calculated.
The median follow-up time (95% confidence interval) was 41.1 (33.8-50.4) months. A total of 2752 lymph node stations were evaluated noninvasively, whereas 330 were examined invasively. Of 172 patients, 87 (50.6%) underwent ≥1 invasive staging modality. The number of different staging procedures per patient did not correlate with any of the primary endpoints (overall survival, progression-free survival, or freedom from local progression). The sensitivity of F-FDG PET/CT was 89.7% (78/87) and the specificity was 67.5% (112/166) based on histology as assessed by endobronchial ultrasound. When using the results from mediastinoscopy, the sensitivity of PET was 82.6% (19/23) and the specificity was 66.7% (36/54). On the basis of invasive staging methods, 13 lymph node stations in 9 patients (10.3%) were PET-negative while positive on invasive staging, thus leading to a significant adjustment in the target volume.
In this unplanned secondary analysis of the PET-Plan trial, the additional use of invasive staging resulted in relevant changes to the target volume in a tenth of patients. Invasive staging did not, however, have an effect on outcome in this trial, with a low rate of isolated out-of-field recurrences (6 in arm A vs 3 in arm B). Radiation treatment planning can thus be based on invasive staging in addition to noninvasive PET in patients undergoing definitive chemoradiation therapy for locally advanced non-small cell lung cancer. Prospective randomized data are required to confirm these findings.
在前瞻性PET-Plan试验（ARO-2009-09；NCT00697333）中，评估不同的有创和无创纵隔分期方法在接受根治性放化疗的局部晚期非小细胞肺癌患者中的作用，并评估支气管内超声引导下经支气管针吸活检术和纵隔镜检查对靶体积定义的影响。
本非计划的二次分析纳入了按照方案治疗的患者（n = 172），所有患者均接受了等剂量递增的放化疗。放射治疗计划基于F-氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描（F-FDG PET/CT），针对所有CT阳性淋巴结（即短轴直径> 10 mm），即使PET为阴性，再加上选择性淋巴结照射（A组），或仅针对PET阳性淋巴结（B组）。计算了不同分期方式之间的一致性率及其对靶体积勾画的影响。
中位随访时间（95%置信区间）为41.1（33.8 - 50.4）个月。共对2752个淋巴结站进行了无创评估，而330个进行了有创检查。172例患者中，87例（50.6%）接受了≥1种有创分期方式。每位患者不同分期程序的数量与任何主要终点（总生存期、无进展生存期或无局部进展生存期）均无相关性。根据支气管内超声评估的组织学结果，F-FDG PET/CT的敏感性为89.7%（78/87），特异性为67.5%（112/166）。使用纵隔镜检查结果时，PET的敏感性为82.6%（19/23），特异性为66.7%（36/54）。基于有创分期方法，9例患者（10.3%）的13个淋巴结站PET为阴性，但有创分期为阳性，从而导致靶体积有显著调整。
在PET-Plan试验的本次非计划二次分析中，额外使用有创分期使十分之一的患者靶体积发生了相关变化。然而，在本试验中，有创分期对结局没有影响，野外孤立复发率较低（A组6例 vs B组3例）。因此，对于接受局部晚期非小细胞肺癌根治性放化疗的患者，放射治疗计划除了基于无创PET外，还可基于有创分期。需要前瞻性随机数据来证实这些发现。
