Related Experiment Videos
Serum α-fetoprotein in pediatric oncology: not a children's tale
Simona Ferraro1,2, Andrea Panzeri2, Federica Braga2
1UOC Patologia Clinica, Ospedale "Luigi Sacco", Via GB Grassi 74, Milan 20157, Italy.
Insights
Establishing reliable pediatric reference intervals for alpha-fetoprotein (AFP) is crucial for cancer diagnosis in infants. Current data variability hinders definitive interpretation, necessitating new studies and algorithmic approaches for accurate AFP assessment.
Area of Science:
- Pediatric Oncology
- Clinical Chemistry
- Biomarker Analysis
Background:
- Alpha-fetoprotein (AFP) serum concentrations are vital for managing pediatric cancers like hepatoblastoma and germ cell tumors.
- Accurate interpretation of AFP levels in infants is challenged by a lack of robust pediatric reference intervals (RI).
Purpose of the Study:
- To critically review existing literature on pediatric reference intervals for AFP.
- To assess the utility of AFP interpretation as an aid in pediatric cancer diagnosis.
Main Methods:
- Systematic literature review and critical appraisal of 3873 retrieved papers.
- Selection of six studies meeting stringent methodological and data quality criteria.
Main Results:
- Wide variability in infant AFP concentrations, particularly in the first three months, impedes defining stable reference intervals.
- Inability to establish robust RI limits the use of single AFP results for ruling out pediatric malignancies.
- An algorithm using baseline AFP, age-specific half-life (HL), and predicted concentrations may offer improved diagnostic information.
Conclusions:
- Novel studies with robust methodologies are required to establish reliable pediatric AFP reference intervals.
- Current diagnostic interpretation can be enhanced by utilizing algorithms that consider AFP concentration dynamics and half-life.
Abstract:
Background Measurement of α-fetoprotein (AFP) concentrations in the serum of infants is useful for the management of testicular germ cell tumors, hepatoblastoma and hepatocellular carcinoma. Here, we provide a critical review of the available information about pediatric reference intervals (RI), focusing on their utility in interpreting AFP as an aid for cancer diagnosis. Content Evidence sources in the available literature were critically appraised. Out of 3873 retrieved papers, 24 were finally selected and carefully inspected, and six of them overcame exclusion criteria (i.e. methodological limitations in the study design, statistical gaps, drawbacks in traceability of the AFP assay to higher order materials and/or biased reporting of AFP results). Preterm and term infants up to the 3rd month of life exhibited the highest average AFP concentrations, but the attempt of defining RI by data pooling and partitioning for age intervals was impeded by the wide variability of data. The inability of defining robust RI in the first months of life made difficult, if not impossible, using upper reference limits for ruling out malignancies with a single AFP result. Evaluating the behavior of AFP concentrations 5 days from the baseline result, if this exceeds risk thresholds partitioned for age, according to the formula Xt=X0*2-t/HL (where: t=days elapsed for AFP retest; HL=AFP half-life according to age; X0=AFP baseline concentration, and Xt=predicted AFP concentration at day 5), could give a better information. Summary Novel studies defining AFP RI in infants based on robust methodology are warranted to improve the interpretation of AFP results in pediatric oncology. In the meantime, algorithms based on both serum AFP absolute concentrations and HL may aid in cancer diagnosis.