Impact of Different Mediastinal Staging Modalities on Target Volume Delineation in Locally Advanced Non-Small Cell Lung Cancer: A Secondary Analysis of the Multicenter Randomized PET-Plan Trial.

Abstract

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 ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-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 ¹⁸F-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.