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External quality assessment-based tumor marker harmonization simulation; insights in achievable harmonization for CA 15-3 and CEA

  • Huub H. Van Rossum EMAIL logo , Stefan Holdenrieder , Yeo-Min Yun , Dina Patel , Marc Thelen ORCID logo , Junghan Song , Nick Unsworth , Katherine Partridge , Melanie Moore , Wei Cui , Lakshmi Ramanathan , Qing H. Meng , Bart E.P.B. Ballieux , Catharine Sturgeon and Hubert Vesper
Published/Copyright: September 20, 2024
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 63 Issue 2

Abstract

Objectives

CA 15-3 and CEA are tumor markers used in routine clinical care for breast cancer and colorectal cancer, among others. Current measurement procedures (MP) for these tumor markers are considered to be insufficiently harmonized. This study investigated the achievable harmonization for CA 15-3 and CEA by using an in silico simulation of external quality assessment (EQA) data from multiple EQA programs using patient-pool based samples.

Methods

CA 15-3 and CEA data from SKML (2021), UK NEQAS (2020–2021) and KEQAS (2020–2021) were used. A harmonization protocol was defined in which MPs that were considered equivalent were used to value assign EQA samples, and recalibration was only required if the MP had a bias of >5 % with value assigned EQA. Harmonization status was assessed by determining the mean level of agreement and residual variation by CV (%).

Results

Only MPs from Abbott, Beckman, Roche and Siemens were available in all EQA programs. For CA 15-3, recalibration was proposed for Beckman MP only and for CEA, recalibration was proposed for Siemens MP only. When the harmonization procedures were applied, for CA 15-3 the pre-harmonization mean bias range per MP was reduced from −29.28 to 9.86 %, into −0.09–0.12 % after harmonization. For CEA, the mean bias range per MP was reduced from −23.78 to 2.00 % pre-harmonization to −3.13–1.42 % post-harmonization.

Conclusions

The present study suggests that a significant improvement in the harmonization status of CA 15-3 and CEA may be achieved by recalibration of a limited number of MPs.

Keywords: CEA; CA15-3; harmonization; tumor marker; standardization
Corresponding author: Huub H. Van Rossum, Department of Laboratory Medicine, Netherlands Cancer Institute, Amsterdam, Plesmanlaan 121 1066CX, The Netherlands, E-mail:

  1. Research ethics: Not applicable.

  2. Informed consent: Not applicable.

  3. Author contributions: The authors have accepted responsibility fort he entire content of this manuscript and approved ist submission.

  4. Competing interests: H. van Rossum support from Roche diagnostics, Abbott, Beckman, Siemens, Sysmex, Huvaros; employment or leadership roles: Huvaros, Director Huvaros BV., Chief Scientific Officer SelfSareSure Blood Collections BV, Honoraria: Huvaros BV; expert testimony: Abbott, Siemens; patents: PCT/NL2016/050315 Method for setting measuring equipment, computer program and measuring equipment, NL2019/ 079641 Blood collection device and method for the self-collection of blood by a user. S. Holdenrieder, employment or leadership roles: Board ISOBM, WHO-IARC Steering Committee, Associate Editor for several oncological and lab journals, SFZ BioCoDE, CEBIO; consultant or advisory roles: Instand, Roche, Thermo, Merck. L. Ramanathan, support from ADLM (formerly AACC) for travel to attend 2022Annual Scientific Meeting,support from Abbott Diagnostics, 2021–2023 for validating infectious disease markers on the i2000, support from Nova Biomedical, 2023, to study ionized Mg in critically ill patients.

  5. Research funding: H. van Rossum: Roche, Health Holland. S Holdenrieder: EU, Roche, Volition, Sysmex. L. Ramanathan: Abbott, Nova Biomedical. The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, preparation of manuscript, or final approval of manuscript.

  6. Data availability: The raw data is not available.

  7. Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry. Use of trade names is for identification only and does not imply endorsement by the Centers for Disease Control and Prevention, the Public Health Service, and the US Department of Health and Human Services.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2024-0696).

Received: 2024-06-14
Accepted: 2024-08-31
Published Online: 2024-09-20
Published in Print: 2025-01-29

© 2024 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2024-0696
Keywords for this article
CEA; CA15-3; harmonization; tumor marker; standardization

Articles in the same Issue

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