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Characteristics of new solid nodules detected in incidence screening rounds of low-dose CT lung cancer screening: the NELSON study
  1. Joan E Walter1,
  2. Marjolein A Heuvelmans1,2,
  3. Geertruida H de Bock3,
  4. Uraujh Yousaf-Khan4,
  5. Harry J M Groen5,
  6. Carlijn M van der Aalst4,
  7. Kristiaan Nackaerts6,
  8. Peter M A van Ooijen1,
  9. Harry J de Koning4,
  10. Rozemarijn Vliegenthart1,
  11. Matthijs Oudkerk1
  1. 1 Center for Medical Imaging – North East Netherlands, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
  2. 2 Department of Pulmonology, Medisch Spectrum Twente, Enschede, The Netherlands
  3. 3 Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
  4. 4 Department of Public Health, Erasmus Medical Centre Rotterdam, Rotterdam, The Netherlands
  5. 5 Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
  6. 6 Department of Pulmonary Medicine, KU Leuven – University Hospital Leuven, Leuven, Belgium
  1. Correspondence to Professor Matthijs Oudkerk, CMI-Center for Medical Imaging, University Medical Center Groningen, Groningen 9700RB, The Netherlands; m.oudkerk{at}


Purpose New nodules after baseline are regularly found in low-dose CT lung cancer screening and have a high lung cancer probability. It is unknown whether morphological and location characteristics can improve new nodule risk stratification by size.

Methods Solid non-calcified nodules detected during incidence screening rounds of the randomised controlled Dutch-Belgian lung cancer screening (NELSON) trial and registered as new or previously below detection limit (15 mm3) were included. A multivariate logistic regression analysis with lung cancer as outcome was performed, including previously established volume cut-offs (<30 mm3, 30–<200 mm3 and ≥200 mm3) and nodule characteristics (location, distribution, shape, margin and visibility <15 mm3 in retrospect).

Results Overall, 1280 new nodules were included with 73 (6%) being lung cancer. Of nodules ≥30 mm3 at detection and visible <15 mm3 in retrospect, 22% (6/27) were lung cancer. Discrimination based on volume cut-offs (area under the receiver operating characteristic curve (AUC): 0.80, 95% CI 0.75 to 0.84) and continuous volume (AUC: 0.82, 95% CI 0.77 to 0.87) was similar. After adjustment for volume cut-offs, only location in the right upper lobe (OR 2.0, P=0.012), central distribution (OR 2.4, P=0.001) and visibility <15 mm3 in retrospect (OR 4.7, P=0.003) remained significant predictors for lung cancer. The Hosmer-Lemeshow test (P=0.75) and assessment of bootstrap calibration curves indicated adequate model fit. Discrimination based on the continuous model probability (AUC: 0.85, 95% CI 0.81 to 0.89) was superior to volume cut-offs alone, but when stratified into three risk groups (AUC: 0.82, 95% CI 0.78 to 0.86), discrimination was similar.

Conclusion Contrary to morphological nodule characteristics, growth-independent characteristics may further improve volume-based new nodule lung cancer prediction, but in a three-category stratification approach, this is limited.

Trial registration number ISRCTN63545820; pre-results.

  • lung cancer
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  • Contributors JEW, MAH, RV and MO were involved in the conception, hypotheses delineation and design of the study. All authors acquired the data or analysed and interpreted the data. All authors wrote the article or were substantially involved in its revision before submission.

  • Funding The NELSON-trial was sponsored by: Netherlands Organisation for Health Research and Development (ZonMw); Dutch Cancer Society Koningin Wilhelmina Fonds (KWF); Stichting Centraal Fonds Reserves van Voormalig Vrijwillige Ziekenfondsverzekeringen (RvvZ); Siemens Germany; Rotterdam Oncologic Thoracic Steering committee (ROTS); G. Ph. Verhagen Trust; Flemish League Against Cancer; Foundation Against Cancer; and Erasmus Trust Fund.

  • Disclaimer The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

  • Competing interests CMvdA reports grants from Symposium Thoracic Oncology, grants from American Thoracic Society, grants from Lancet Respiratory Medicine, outside the submitted work. KN reports grants from Flemish League against Cancer, grants from the Belgian Foundation against Cancer, during the conduct of the study. HJMG reports grants from Eli Lilly, Roche, MSD, BMS and Novartis, outside the submitted work. HJdK took part in a 1-day advisory meeting on biomarkers organised by M.D. Anderson/Health Sciences during the 16th World Conference on Lung Cancer, outside the submitted work.

  • Patient consent Not required.

  • Ethics approval The NELSON trial (trial registration number, ISRCTN63545820) was approved by Ethics Committees of all participating centres in the Netherlands and Belgium.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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