European Radiology

, Volume 23, Issue 7, pp 1836–1845 | Cite as

Optimisation of volume-doubling time cutoff for fast-growing lung nodules in CT lung cancer screening reduces false-positive referrals

  • Marjolein A. Heuvelmans
  • Matthijs Oudkerk
  • Geertruida H. de Bock
  • Harry J. de Koning
  • Xueqian Xie
  • Peter M. A. van Ooijen
  • Marcel J. W. Greuter
  • Pim A. de Jong
  • Harry J. M. Groen
  • Rozemarijn Vliegenthart
Computed Tomography



To retrospectively investigate whether optimisation of volume-doubling time (VDT) cutoff for fast-growing nodules in lung cancer screening can reduce false-positive referrals.


Screening participants of the NELSON study underwent low-dose CT. For indeterminate nodules (volume 50–500 mm3), follow-up CT was performed 3 months after baseline. A negative baseline screen resulted in a regular second-round examination 1 year later. Subjects referred to a pulmonologist because of a fast-growing (VDT <400 days) solid nodule in the baseline or regular second round were included in this study. Histology was the reference for diagnosis, or stability on subsequent CTs, confirming benignity. Mean follow-up of non-resected nodules was 4.4 years. Optimisation of the false-positive rate was evaluated at maintained sensitivity for lung cancer diagnosis with VDT <400 days as reference.


Sixty-eight fast-growing nodules were included; 40 % were malignant. The optimal VDT cutoff for the 3-month follow-up CT after baseline was 232 days. This cutoff reduced false-positive referrals by 33 % (20 versus 30). For the regular second round, VDTs varied more among malignant nodules, precluding lowering of the VDT cutoff of 400 days.


All malignant fast-growing lung nodules referred after the 3-month follow-up CT in the baseline lung cancer screening round had VDT ≤232 days. Lowering the VDT cutoff may reduce false-positive referrals.

Key Points

Lung nodules are common in CT lung cancer screening, most being benign

Short-term follow-up CT can identify fast-growing intermediate-size lung nodules

Most fast-growing nodules on short-term follow-up CT still prove to be benign

A new volume-doubling time (VDT) cut-off is proposed for lung screening

The optimised VDT cutoff may decrease false-positive case referrals for lung cancer


Pulmonary nodule Lung neoplasms Mass screening Volumetry Computed tomography 







Computed tomography


Dutch–Belgian randomised lung cancer screening trial


National Lung Screening Trial


Positive predictive value


Volume-doubling time



The NELSON trial was sponsored by: The 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.

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


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Copyright information

© European Society of Radiology 2013

Authors and Affiliations

  • Marjolein A. Heuvelmans
    • 1
  • Matthijs Oudkerk
    • 1
  • Geertruida H. de Bock
    • 2
  • Harry J. de Koning
    • 3
  • Xueqian Xie
    • 1
  • Peter M. A. van Ooijen
    • 1
    • 4
  • Marcel J. W. Greuter
    • 4
  • Pim A. de Jong
    • 5
  • Harry J. M. Groen
    • 6
  • Rozemarijn Vliegenthart
    • 1
    • 4
  1. 1.Center for Medical Imaging-North East NetherlandsUniversity of Groningen, University Medical Center GroningenGroningenThe Netherlands
  2. 2.Department of EpidemiologyUniversity of Groningen, University Medical Center GroningenGroningenThe Netherlands
  3. 3.Department of Public HealthErasmus Medical Center RotterdamRotterdamThe Netherlands
  4. 4.Department of Radiology, EB44University of Groningen, University Medical Center GroningenGroningenThe Netherlands
  5. 5.Department of RadiologyUniversity Medical Center UtrechtUtrechtThe Netherlands
  6. 6.Department of PulmonologyUniversity of Groningen, University Medical Center GroningenGroningenThe Netherlands

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