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Original article
Persisting new nodules in incidence rounds of the NELSON CT lung cancer screening study
  1. Joan E Walter1,
  2. Marjolein A Heuvelmans1,2,
  3. Kevin ten Haaf3,
  4. Rozemarijn Vliegenthart1,2,
  5. Carlijn M van der Aalst3,
  6. Uraujh Yousaf-Khan3,
  7. Peter M A van Ooijen1,2,
  8. Kristiaan Nackaerts4,
  9. Harry J M Groen5,
  10. Geertruida H De Bock6,
  11. Harry J de Koning3,
  12. Matthijs Oudkerk1
  1. 1Center for Medical Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
  2. 2Department of Radiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
  3. 3Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
  4. 4Department of Pulmonary Medicine, KU Leuven, University Hospital Leuven, Leuven, Belgium
  5. 5Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Rotterdam, The Netherlands
  6. 6Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
  1. Correspondence to Professor Matthijs Oudkerk, CMI-Center for Medical Imaging, Universitary Medical Center Groningen, University of Groningen, Groningen 9700 RB, The Netherlands; m.oudkerk{at}


Background The US guidelines recommend low-dose CT (LDCT) lung cancer screening for high-risk individuals. New solid nodules after baseline screening are common and have a high lung cancer probability. Currently, no evidence exists concerning the risk stratification of non-resolving new solid nodules at first LDCT screening after initial detection.

Methods In the Dutch-Belgian Randomized Lung Cancer Screening (NELSON) trial, 7295 participants underwent the second and 6922 participants the third screening round. We included participants with solid nodules that were registered as new or <15 mm³ (study detection limit) at previous screens and received additional screening after initial detection, thereby excluding high-risk nodules according to the NELSON management protocol (nodules ≥500 mm3).

Results Overall, 680 participants with 1020 low-risk and intermediate-risk new solid nodules were included. A total of 562 (55%) new solid nodules were resolving, leaving 356 (52%) participants with a non-resolving new solid nodule, of whom 25 (7%) were diagnosed with lung cancer. At first screening after initial detection, volume doubling time (VDT), volume, and VDT combined with a predefined ≥200 mm3 volume cut-off had high discrimination for lung cancer (VDT, area under the curve (AUC): 0.913; volume, AUC: 0.875; VDT and ≥200 mm3 combination, AUC: 0.939). Classifying a new solid nodule with either ≤590 days VDT or ≥200 mm3 volume positive provided 100% sensitivity, 84% specificity and 27% positive predictive value for lung cancer.

Conclusions More than half of new low-risk and intermediate-risk solid nodules in LDCT lung cancer screening resolve. At follow-up, growth assessment potentially combined with a volume limit can be used for risk stratification.

Trial registration number ISRCTN63545820; pre-results.

  • lung cancer

Statistics from


  • JEW and MAH contributed equally.

  • Contributors JEW, MAH, RV and MO were involved in the conception, hypotheses delineation and design of the study. JEW, MAH, KtH, RV, CMvdA, UY-K, PMAvO, KN, HJMG, GHdB, HJdK and MO acquired the data or analysed and interpreted the data. JEW, MAH, KtH, RV, CMvdA, UY-K, PMAvO, KN, HJMG, GHdB, HJdK and MO wrote the article or were substantially involved in its revision before submission.

  • Funding The NELSON trial was sponsored by the Dutch 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); GPh Verhagen Trust; Flemish League Against Cancer; Foundation Against Cancer; and Erasmus Trust Fund.

  • Competing interests KtH reports grants and non-financial support from NELSON-Netherlands-Leuven Lung Cancer Screening, during the conduct of the study, and grants from the University of Zurich, non-financial support from the International Association for the Study of Lung Cancer Strategic Screening Advisory Committee, and grants from Sunnybrook Health Sciences, outside the submitted work. CMvdA reports grants from Symposium in Thoracic Oncology, grants from the American Thoracic Society, and grants from Lancet Respiratory Medicine, outside the submitted work. KN reports grants from Flemish League against Cancer and 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 MD Anderson/Health Sciences during the 16th World Conference on Lung Cancer, outside the submitted work. All other authors declare no competing interests over the last 36 months.

  • Patient consent Obtained.

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

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

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