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Clinical utility of personalized reference intervals for CEA in the early detection of oncologic disease

  • Débora Martínez-Espartosa ORCID logo , Estíbaliz Alegre , Hugo Casero-Ramírez , Jorge Díaz-Garzón ORCID logo , Pilar Fernández-Calle , Patricia Fuentes-Bullejos ORCID logo , Nerea Varo and Álvaro González EMAIL logo
Published/Copyright: August 6, 2024
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 63 Issue 2

Abstract

Objectives

Personalized reference intervals (prRI) have been proposed as a diagnostic tool for assessing measurands with high individuality. Here, we evaluate clinical performance of prRI using carcinoembryonic antigen (CEA) for cancer detection and compare it with that of reference change values (RCV) and other criteria recommended by clinical guidelines (e.g. 25 % of change between consecutive CEA results (RV25) and the cut-off point of 5 μg/L (CP5)).

Methods

Clinical and analytical data from 2,638 patients collected over 19 years were retrospectively evaluated. A total 15,485 CEA results were studied. For each patient, we calculated prRI and RCV using computer algorithms based on the combination of different strategies to assess the number of CEA results needed, consideration of one or two limits of reference interval and the intraindividual biological variation estimate (CVI) used: (a) publicly available (CVI-EU), (b) CVI calculated using an indirect method (CVI-NOO) and (c) within-person BV (CVP). For each new result identified falling outside the prRI, exceeding the RCV interval, RV25 or CP5, we searched for records identifying the presence of tumour at 3 and 12 months after the test. The sensitivity, specificity and predictive power of each strategy were calculated.

Results

PrRI approaches derived using CVI-EU, and both limits of reference interval achieve the best sensitivity (87.5 %) and NPV (99.3 %) at 3 and 12 months of all evaluated criteria. Only 3 results per patients are enough to calculate prRIs that reach this diagnostic performance.

Conclusions

PrRI approaches could be an effective tool to rule out new oncological findings during the active surveillance of patients.

Keywords: biological variation; cancer; CEA; personalized reference intervals; reference change value; reference intervals
Corresponding author: Álvaro González, Biochemistry Department, Clínica Universidad de Navarra, Pamplona, Spain; and Navarra Institute for Health Research (IDISNA), 31008 Pamplona, Spain, E-mail:
Nerea Varo and Álvaro González contributed equally to this work.

Acknowledgments

We would like to thank Dra. María Romero for her support in the preparation of the manuscript.

  1. Research ethics: This study was approved by the Research Ethics Committee of the University of Navarra (2023-041) in agreement with the World Medical Association Declaration of Helsinki and the Spanish law.

  2. Informed consent: Not applicable.

  3. Author contributions: A.E and V.N collected the data, M-E.D, A.E, V.N and G.A concieved and designed the analysis, M-E.D and F-B.P performed the analysis, C-R.H contributed analysis tools, M-E.D, A.E, V.N, G.A D-G.J and F-C.P wrote the paper and revised the article for intellectual content. All authors discussed the results and contributed to the final manuscript.

  4. Competing interests: The authors state no conflict of interest.

  5. Research funding: None declared.

  6. Data availability: The datasets generated during the current study are available from the corresponding author on reasonable request.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2024-0546).

Received: 2024-04-30
Accepted: 2024-07-02
Published Online: 2024-08-06
Published in Print: 2025-01-29

© 2024 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2024-0546
Keywords for this article
biological variation; cancer; CEA; personalized reference intervals; reference change value; reference intervals

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  1. Frontmatter
  2. Editorial
  3. CD34+ progenitor cells meet metrology
  4. Reviews
  5. Venous blood collection systems using evacuated tubes: a systematic review focusing on safety, efficacy and economic implications of integrated vs. combined systems
  6. The correlation between serum angiopoietin-2 levels and acute kidney injury (AKI): a meta-analysis
  7. Opinion Papers
  8. Advancing value-based laboratory medicine
  9. Clostebol and sport: about controversies involving contamination vs. doping offence
  10. Direct-to-consumer testing as consumer initiated testing: compromises to the testing process and opportunities for quality improvement
  11. Perspectives
  12. An improved implementation of metrological traceability concepts is needed to benefit from standardization of laboratory results
  13. Genetics and Molecular Diagnostics
  14. Comparative analysis of BCR::ABL1 p210 mRNA transcript quantification and ratio to ABL1 control gene converted to the International Scale by chip digital PCR and droplet digital PCR for monitoring patients with chronic myeloid leukemia
  15. General Clinical Chemistry and Laboratory Medicine
  16. IVDCheckR – simplifying documentation for laboratory developed tests according to IVDR requirements by introducing a new digital tool
  17. Analytical performance specifications for trace elements in biological fluids derived from six countries federated external quality assessment schemes over 10 years
  18. The effects of drone transportation on routine laboratory, immunohematology, flow cytometry and molecular analyses
  19. Accurate non-ceruloplasmin bound copper: a new biomarker for the assessment and monitoring of Wilson disease patients using HPLC coupled to ICP-MS/MS
  20. Construction of platelet count-optical method reflex test rules using Micro-RBC#, Macro-RBC%, “PLT clumps?” flag, and “PLT abnormal histogram” flag on the Mindray BC-6800plus hematology analyzer in clinical practice
  21. Evaluation of serum NFL, T-tau, p-tau181, p-tau217, Aβ40 and Aβ42 for the diagnosis of neurodegenerative diseases
  22. An immuno-DOT diagnostic assay for autoimmune nodopathy
  23. Evaluation of biochemical algorithms to screen dysbetalipoproteinemia in ε2ε2 and rare APOE variants carriers
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  25. Allowable total error in CD34 cell analysis by flow cytometry based on state of the art using Spanish EQAS data
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