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Variations in tumor growth, intra-individual biological variability, and the interpretation of changes

  • Jaume Trapé EMAIL logo , Silvia Bérgamo , Carolina González-Fernández , José Rives and Laura González-García
Published/Copyright: February 19, 2024
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 62 Issue 8

Abstract

Objectives

The identification of changes in tumor markers (TMs) in cancer patients that indicate response to treatment, stabilization or disease progression is a challenge for laboratory medicine. Several approaches have been proposed: assessing percentage increases, applying discriminant values, and estimating half-life (t1/2) or doubling time (DT). In all of them it is assumed that the TM is a surrogate of the variation in tumor size. In general this variation is time-dependent, but this is not the case of intraindividual biological variability (CVi), which can range from 6 % in CA15-3 to 22 % in CA125. When decisions are made on the basis of DT or t1/2, these values can be affected by the CVi; if it is very large, the growth rate very slow and the period of time between determinations very short, the result obtained for DT may be due mainly to the CVi. The aim of this study is to establish the relationship between the CVi and temporal variables.

Methods

We related equations for calculating DT and t1/2 to the reference change values in tumor markers.

Results

The application of the formula obtained allows the calculation of the optimal time between measurements to ensure that the influence of the CVi is minimal in different types of tumors and different scenarios.

Conclusions

Intraindividual variation affects the calculation of DT and t1/2. It is necessary to establish the minimum time between two measurements to ensure that the CVi does not affect their calculation or lead to misinterpretation.

Keywords: cancer; doubling time; half-lives; biological variation; tumor markers interpretation
Corresponding author: Jaume Trapé, Laboratory Medicine Department, Althaia Xarxa Assistencial Universitària de Manresa, Dr Joan Soler 1–3 08243, Manresa, Catalonia, Spain; Tissue Repair and Regeneration Laboratory (TR2Lab), Centre for Health and Social Care Research (CESS), University of Vic – Central University of Catalonia, Institut de Recerca i Innovació en Ciències de la Vida i de la Salut a la Catalunya Central (IRIS-CC), Vic, Spain; and Faculty of Medicine, University of Vic – Central University of Catalonia, Vic, Spain, E-mail:

  1. Research ethics: Not applicable.

  2. Informed consent: Not applicable.

  3. Author contributions: JT designed the study and wrote the paper. SB, CG-F, LG-G, JR-J revised the manuscript critically for important intellectual content and approved its submission. JT accept responsibility for the entire content of this manuscript. The authors have accepted responsibility for the entire content of this manuscript and approved its submission.

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

  5. Research funding: None declared.

  6. Data availability: Not applicable.

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Received: 2023-07-24
Accepted: 2024-02-02
Published Online: 2024-02-19
Published in Print: 2024-07-26

© 2024 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Analytical performance specifications – moving from models to practical recommendations
  4. Opinion Papers
  5. What the Milan conference has taught us about analytical performance specification model definition and measurand allocation
  6. The role of analytical performance specifications in international guidelines and standards dealing with metrological traceability in laboratory medicine
  7. How clinical laboratories select and use Analytical Performance Specifications (APS) in Italy
  8. Outcome-based analytical performance specifications: current status and future challenges
  9. Analytical performance specifications based on biological variation data – considerations, strengths and limitations
  10. State-of-the-art model for derivation of analytical performance specifications: how to define the highest level of analytical performance technically achievable
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  12. When bias becomes part of imprecision: how to use analytical performance specifications to determine acceptability of lot-lot variation and other sources of possibly unacceptable bias
  13. Using analytical performance specifications in a medical laboratory
  14. Issues in assessing analytical performance specifications in healthcare systems assembling multiple laboratories and measuring systems
  15. Applying the Milan models to setting analytical performance specifications – considering all the information
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  35. AWMF statement on medical services in laboratory diagnostics and pathology with regard to the IVDR
  36. An outline of measurement uncertainty of total protein in urine estimated according to the ISO Technical Specification 20914
  37. Early diagnosis of severe illness in an outpatient – the Sysmex XN’s neutrophil reactivity parameter
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https://doi.org/10.1515/cclm-2023-0780
Keywords for this article
cancer; doubling time; half-lives; biological variation; tumor markers interpretation

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Analytical performance specifications – moving from models to practical recommendations
  4. Opinion Papers
  5. What the Milan conference has taught us about analytical performance specification model definition and measurand allocation
  6. The role of analytical performance specifications in international guidelines and standards dealing with metrological traceability in laboratory medicine
  7. How clinical laboratories select and use Analytical Performance Specifications (APS) in Italy
  8. Outcome-based analytical performance specifications: current status and future challenges
  9. Analytical performance specifications based on biological variation data – considerations, strengths and limitations
  10. State-of-the-art model for derivation of analytical performance specifications: how to define the highest level of analytical performance technically achievable
  11. Analytical performance specifications for combined uncertainty budget in the implementation of metrological traceability
  12. When bias becomes part of imprecision: how to use analytical performance specifications to determine acceptability of lot-lot variation and other sources of possibly unacceptable bias
  13. Using analytical performance specifications in a medical laboratory
  14. Issues in assessing analytical performance specifications in healthcare systems assembling multiple laboratories and measuring systems
  15. Applying the Milan models to setting analytical performance specifications – considering all the information
  16. Guidelines and Recommendations
  17. Recommendations for blood sampling in emergency departments from the European Society for Emergency Medicine (EUSEM), European Society for Emergency Nursing (EuSEN), and European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for the Preanalytical Phase. Executive summary
  18. General Clinical Chemistry and Laboratory Medicine
  19. Assessment of accuracy of laboratory testing results, relative to peer group consensus values in external quality control, by bivariate z-score analysis: the example of D-Dimer
  20. The stability of 65 biochemistry analytes in plasma, serum, and whole blood
  21. Assessment of the 2023 European Kidney Function Consortium (EKFC) equations in a Chinese adult population
  22. In vitro, in vivo metabolism and quantification of the novel synthetic opioid N-piperidinyl etonitazene (etonitazepipne)
  23. Quantification of blood glial fibrillary acidic protein using a second-generation microfluidic assay. Validation and comparative analysis with two established assays
  24. Association of prehospital lactate levels with base excess in various emergencies – a retrospective study
  25. Reference Values and Biological Variations
  26. Stability of ten serum tumor markers after one year of storage at −18°C
  27. Variations in tumor growth, intra-individual biological variability, and the interpretation of changes
  28. Cancer Diagnostics
  29. N-linked glycosylation of the M-protein variable region: glycoproteogenomics reveals a new layer of personalized complexity in multiple myeloma
  30. Cardiovascular Diseases
  31. Reference intervals for high sensitivity cardiac troponin I and N-terminal pro-B-type natriuretic peptide in children and adolescents on the Siemens Atellica
  32. Infectious Diseases
  33. Fetal chronic hypoxia does not affect urinary presepsin levels in newborns at birth
  34. Letters to the Editor
  35. AWMF statement on medical services in laboratory diagnostics and pathology with regard to the IVDR
  36. An outline of measurement uncertainty of total protein in urine estimated according to the ISO Technical Specification 20914
  37. Early diagnosis of severe illness in an outpatient – the Sysmex XN’s neutrophil reactivity parameter
  38. Analytical and diagnostic performance of Theradiag i-Tracker assays on IDS-iSYS for infliximab and adalimumab therapeutic drug monitoring
  39. Improving the diagnosis of AATD with aid of serum protein electrophoresis: a prospective, multicentre, validation study
  40. Cerebrospinal fluid kappa free light chains in patients with tumefactive demyelination
  41. Diagnostic value of quantitative chemiluminescence immunoassay for anti-gp210 and anti-sp100 antibodies in primary biliary cholangitis
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