Cell-Free DNA at Diagnosis for Stage IV Non-Small Cell Lung Cancer: Costs, Time to Diagnosis and Clinical Relevance

Simone N. Koole, Daan C.L. Vessies, Milou M.F. Schuurbiers, Astrid Kramer, Robert D. Schouten, Koen Degeling, Linda J.W. Bosch, Michel M. van den Heuvel, Wim H. van Harten, Daan van den Broek, Kim Monkhorst, Valesca P. Retèl*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Tissue biopsies can be burdensome and are only effective in 10–30% of patients with metastasized non-small-cell lung cancer (mNSCLC). Next-generation sequencing (NGS) on cell-free DNA (cfDNA) might be an attractive alternative. We evaluated the costs, throughput time, and diagnostic yield of two diagnostic scenarios with tissue and cfDNA for mNSCLC patients, compared to diagnostics based on tissue biopsy alone. Data were retrieved from 209 stage IV NSCLC patients included in 10 hospitals in the Netherlands in the observational Lung cancer Early Molecular Assessment (LEMA) trial. Discrete event simulation was developed to compare three scenarios, using LEMA data as input where possible: (1) diagnostics with “tissue only”; (2) diagnostics with “cfDNA first”, and subsequent tissue biopsy if required (negative for EGFR, BRAF ALK, ROS1); (3) cfDNA if tissue biopsy failed (“tissue first”). Scenario-and probabilistic analyses were performed to quantify uncertainty. In scenario 1, 84% (Credibility Interval [CrI] 70–94%) of the cases had a clinically relevant test result, compared to 93% (CrI 86–98%) in scenario 2, and 93% (CrI 86–99%) in scenario 3. The mean throughput time was 20 days (CrI 17–23) pp in scenario 1, 9 days (CrI 7–11) in scenario 2, and 19 days (CrI 16–22) in scenario 3. Mean costs were €2304 pp (CrI €2067–2507) in scenario 1, compared to €3218 (CrI €3071–3396) for scenario 2, and €2448 (CrI €2382–2506) for scenario 3. Scenarios 2 and 3 led to a reduction in tissue biopsies of 16% and 9%, respectively. In this process-based simulation analysis, the implementation of cfDNA for patients with mNSCLC resulted in faster completion of molecular profiling with more identified targets, with marginal extra costs in scenario 3.

Original languageEnglish
Article number1783
Issue number7
Publication statusPublished - 1 Apr 2022


  • cfDNA
  • discrete event simulation
  • molecular diagnostics
  • non-small-cell lung cancer


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