Radiation Oncology (Sep 2021)

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

  • Maja Guberina,
  • Kaid Darwiche,
  • Hubertus Hautzel,
  • Christoph Pöttgen,
  • Nika Guberina,
  • Thomas Gauler,
  • Till Ploenes,
  • Lale Umutlu,
  • Dirk Theegarten,
  • Clemens Aigner,
  • Wilfried E. E. Eberhardt,
  • Martin Metzenmacher,
  • Marcel Wiesweg,
  • Rüdiger Karpf-Wissel,
  • Martin Schuler,
  • Ken Herrmann,
  • Martin Stuschke

DOI
https://doi.org/10.1186/s13014-021-01904-4
Journal volume & issue
Vol. 16, no. 1
pp. 1 – 12

Abstract

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Abstract 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 18F-FDG PET/CT and systematic endobronchial ultrasound-guided transbronchial-needle aspiration (EBUS-TBNA) for precise target volume definition in stage III NSCLC. 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, 18F-FDG PET/CT and EBUS-TBNA prior to start of treatment. The lymphatic drainage was classified into echelon-1 (ipsilateral hilum), echelon-2 (ipsilateral LN-stations 4 and 7) and echelon-3 (rest of the mediastinum, contralateral hilum). The pattern of spread was classified according to all permutations of echelon-1, echelon-2, and echelon-3 EBUS-TBNA findings. 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.

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