Liquid Biopsies in Pediatric Medicine
Key Points
- Minimally invasive diagnostic technique using bodily fluids
- Primary sources: blood, cerebrospinal fluid, urine
- Detects circulating tumor DNA (ctDNA), cells (CTCs), and exosomes
- Enables real-time disease monitoring and treatment response assessment
- Particularly valuable in pediatric patients due to reduced invasiveness
Components Analyzed
- Circulating Tumor DNA (ctDNA)
- Cell-free DNA fragments released by tumor cells
- Contains genetic alterations specific to the tumor
- Typically comprises 0.1-10% of total cell-free DNA
- Circulating Tumor Cells (CTCs)
- Intact tumor cells in circulation
- Enables analysis of cellular properties
- Valuable for understanding metastatic processes
- Exosomes
- Membrane-bound vesicles containing tumor-derived content
- Rich source of proteins, nucleic acids, and metabolites
- Provides insights into tumor biology and progression
Clinical Applications
Cancer Diagnostics
- Early Detection
- Screening for tumor-specific mutations
- Molecular profiling for cancer classification
- Detection of minimal residual disease
- Disease Monitoring
- Treatment response assessment
- Early detection of recurrence
- Identification of resistance mechanisms
Specific Pediatric Applications
- Neuroblastoma
- MYCN amplification detection
- ALK mutation monitoring
- Treatment response tracking
- Leukemia
- Minimal residual disease detection
- Mutation profiling
- Chimerism analysis post-transplant
- Brain Tumors
- CSF analysis for tumor markers
- Monitoring tumor evolution
- Treatment response assessment
Techniques & Methods
Sample Collection
- Blood Collection Protocols
- Specific collection tubes for ctDNA preservation
- Temperature control requirements
- Processing time considerations
- CSF Collection
- Sterile technique requirements
- Volume considerations
- Storage protocols
Analysis Methods
- Digital PCR
- High sensitivity for known mutations
- Absolute quantification
- Low input DNA requirements
- Next-Generation Sequencing
- Comprehensive genomic profiling
- Detection of novel alterations
- Clonal evolution tracking
- CTC Analysis
- Immunomagnetic separation
- Microfluidic devices
- Single-cell analysis capabilities
Advantages & Limitations
Advantages
- Patient Benefits
- Minimally invasive procedure
- Reduced pain and anxiety
- Suitable for repeated sampling
- Clinical Benefits
- Real-time monitoring capability
- Comprehensive molecular profiling
- Early detection of treatment resistance
- Research Applications
- Tumor heterogeneity studies
- Clonal evolution tracking
- Drug development support
Limitations
- Technical Challenges
- Low ctDNA concentrations
- Sample quality requirements
- Standardization needs
- Clinical Limitations
- Validation requirements
- Cost considerations
- Insurance coverage challenges
Clinical Guidelines
Implementation Recommendations
- Patient Selection
- Disease-specific criteria
- Clinical scenario considerations
- Risk-benefit assessment
- Sampling Protocols
- Timing considerations
- Volume requirements
- Processing guidelines
- Result Interpretation
- Clinical context integration
- Decision-making algorithms
- Follow-up recommendations
Quality Assurance
- Laboratory Requirements
- Validation protocols
- Quality control measures
- Reporting standards
- Documentation
- Sample tracking systems
- Result documentation
- Quality metrics monitoring
Further Reading
