ctDNA Liquid Biopsy

What It Measures

• Specific cancer driver mutations in circulating tumour DNA (e.g. KRAS, EGFR, TP53, BRCA1/2, PIK3CA)
• Tumour mutation burden (TMB) from blood — predicts immunotherapy response
• Microsatellite instability (MSI) status
• Copy number variations and chromosomal rearrangements
• Emerging resistance mutations (e.g. EGFR T790M in lung cancer)
• Methylation patterns for multi-cancer early detection (in newer platforms like Galleri)

How It Works

A standard blood draw (typically 10–20 ml) is collected in special cfDNA preservation tubes. Cell-free DNA (cfDNA) — which includes both normal and tumour-derived DNA — is extracted from plasma. Using next-generation sequencing (NGS) or targeted PCR panels, the lab identifies cancer-specific mutations at very low variant allele frequencies (often 0.1–1% of total DNA). Advanced platforms use machine learning to distinguish tumour-derived signals from normal biological variation and other non-cancer sources of cell-free DNA.

• Patients on targeted therapies — to monitor for acquired resistance mutations
• Those who cannot have a tissue biopsy (inaccessible tumour, poor health for procedure)
• Patients wanting to track treatment response without repeated scans
• People at high hereditary cancer risk wanting early detection (multi-cancer panels)
• Patients post-treatment wanting molecular remission monitoring (MRD testing)
• Those with metastatic cancer where comprehensive mutation profiling is needed

ctDNA testing has the strongest evidence base of all liquid biopsy approaches. The FDA has approved multiple ctDNA-based companion diagnostics, including Guardant360 (Roche) for lung, breast, and colorectal cancer treatment guidance, and FoundationOne Liquid CDx. Studies show ctDNA can detect cancer recurrence 6–12 months before standard imaging. The GALAXY trial (2022) in colorectal cancer showed ctDNA-guided treatment intensification improved outcomes. Multi-cancer early detection platforms (Galleri by GRAIL) have shown sensitivity of 75%+ for Stage I cancers across 50 cancer types in the PATHFINDER study. ctDNA MRD (minimal residual disease) testing is increasingly used in haematological cancers and is entering solid tumour practice.

This list is not exhaustive. Ask your oncologist or integrative physician for locally available options.

• Early-stage cancers shed very low ctDNA — false negatives are more common in Stage I/II disease
• Cannot replace tissue biopsy for initial diagnosis and pathology classification
• False positives can occur from clonal haematopoiesis (non-cancer blood cell mutations) — requires specialist interpretation
• Results must always be interpreted alongside clinical context and imaging
• Some mutations detected may be variants of uncertain significance (VUS)
• Not all ctDNA tests are equal — validated FDA-approved assays differ significantly from less regulated options