Impact of EBUS-TBNA in addition to [18F]FDG-PET/CT imaging on target volume definition for radiochemotherapy in stage III NSCLC

PURPOSE/INTRODUCTION: [!##!Materials and methods!#!All consecutive patients with primary stage III NSCLC who underwent [!##!Results!#!A total of 675 LN-stations of which 291 were positive for tumor-cells, were sampled by EBUS-TBNA in 180 patients. The rate of EBUS-positive LNs was 43% among all sampled LNs. EBUS-positivity in EBUS-probed LNs decreased from 85.8% in echelon-1 LNs to 42.4%/ 9.6% in echelon-2/ -3 LNs, respectively (p < 0.0001, Fisher's exact test). The false discovery rate of PET in comparison with EBUS results rose from 5.3% in echelon-1 to 32.9%/ 69.1% in echelon-2/ -3 LNs, respectively (p < 0.0001, Fisher's exact test). Sensitivity and specificity of FDG-PET/CT ranged from 85 to 99% and 67 to 80% for the different echelons. In 22.2% patients, EBUS-TBNA finding triggered changes of the treated CTV, compared with contouring algorithms based on FDG-avidity as the sole criterion for inclusion. CTV was enlarged in 6.7% patients due to EBUS-positivity in PET-negative LN-station and reduced in 15.5% by exclusion of an EBUS-negative but PET-positive LN-station.!##!Conclusion!#!The false discovery rate of

Patterns of nodal spread in stage III NSCLC: importance of EBUS-TBNA and 18F-FDG PET/CT for radiotherapy target volume definition

Purpose!#!The aim of this study was to compare the pattern of intra-patient spread of lymph-node (LN)-metastases within the mediastinum as assessed by !##!Methods!#!This is a single-center study based on our preceding investigation, including all consecutive patients with initial diagnosis of stage IIIA-C NSCLC, receiving concurrent radiochemotherapy (12/2011-06/2018). Inclusion criteria were curative treatment intent, !##!Results!#!In total, 180 patients were enrolled. Various patterns of LN-spread could be identified. Skip lesions with an involved echelon distal from an uninvolved one were detected in less than 10% of patients by both EBUS-TBNA and PET. The pattern with largest asymmetry was detected in cases with EBUS-TBNA- or PET-positivity at all three echelons (p < 0.0001, exact symmetry test). In a multivariable logistic model for EBUS-positivity at echelon-3, prognostic factors were PET-positivity at echelon-3 (Hazard ratio (HR) = 12.1; 95%-CI: 3.2-46.5), EBUS-TBNA positivity at echelon-2 (HR = 6.7; 95%-CI: 1.31-31.2) and left-sided tumor location (HR = 4.0; 95%-CI: 1.24-13.2). There were significantly less combined ipsilateral upper (LN-stations 2 and 4) and lower (LN-station 7) mediastinal involvements (16.8% of patients) with EBUS-TBNA than with PET (38.9%, p < 0.0001, exact symmetry test). EBUS-TBNA detected a lobe specific heterogeneity between the odds ratios of LN-positivity in the upper versus lower mediastinum (p = 0.0021, Breslow-Day test), while PET did not (p = 0.19).!##!Conclusion!#!Frequent patterns of LN-metastatic spread could be defined by EBUS-TBNA and PET and discrepancies in the pattern were seen between both methods. EBUS-TBNA showed more lobe and tumor laterality specific patterns of LN-metastases than PET and skipped lymph node stations were rare. These systematic relations offer the opportunity to further refine multi-parameter risk of LN-involvement models for target volume delineation based on pattern of spread by EBUS-TBNA and PET